JP2008273924A - 2-thienylcarbapenem derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a carbapenem derivative for parenteral injection or oral use effective against pneumococci including PRSP (penicillin-resistant Streptococcus pneumoniae), influenza bacteria including BLNAR (β-lactamase non-producing ampicillin-resistant) influenza bacteria, Branhamella catarrhalis etc., clinically causing problems. <P>SOLUTION: The compound which is the carbapenem derivative having a thienyl subjected to ring condensation in the 2-position on the carbapenem ring and represented by formula (I) or a pharmaceutically acceptable salt thereof is provided. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a carbapenem compound having excellent antibacterial activity and a broad antibacterial spectrum. Specifically, the present invention relates to a novel carbapenem derivative having a condensed bicyclic thiophene ring at the 2-position on the carbapenem ring.

  Carbapenem derivatives exhibit strong antibacterial activity and a wide range of excellent antibacterial spectrum, and therefore are being actively studied as highly useful β-lactam agents, and imipenem, panipenem, meropenem, biapenem, and doripenem are already in clinical use. It is used in the field. However, methicillin-resistant Staphylococcus aureus (hereinafter abbreviated as “MRSA”), penicillin-resistant Streptococcus pneumoniae (hereinafter abbreviated as “PRSP”), resistant Pseudomonas aeruginosa and intestines which are still clinically problematic in antibacterial activity. Drugs that are more effective against cocci, cataracts, and the like, and also effective against H. influenzae including non-β-lactamase-producing ampicillin-resistant Haemophilus influenzae (hereinafter sometimes referred to as “BLNAR”) are demanded. Yes. In addition, not only injections but also drugs that can be administered orally are required for administration forms.

Non-Patent Document 1 reports a group of compounds using various bonding modes at the 2-position of the carbapenem ring, and reports of compounds having a direct heterocyclic ring at the 2-position of the carbapenem ring are as follows.
Patent Document 1 reports a compound group having imidazo [5,1-b] thiazole at the 2-position of the carbapenem ring. Although these were effective against Haemophilus influenzae, they were not satisfactory in terms of pharmacokinetics.
In Patent Document 2, a compound group having imidazo [5,1-b] thiazole at the 2-position of the carbapenem ring is described, but these compound groups were excellent compound groups as injections.
Further, compounds having a thiophene ring at the 2-position of the carbapenem ring are reported in Patent Document 3 and Patent Document 4. However, these are structurally free of a β-methyl group at the 1-position and the thiophene ring is monocyclic, and there is no disclosure or suggestion of a bicyclic thiophene ring as in the present invention. Furthermore, there is no disclosure of specific antibacterial activity and stability to DHP-1.

Patent Documents 5 to 8 describe compounds having a thienopyridinium ring. However, they are a group of compounds suitable for injection because the bonding mode with the 2-position on the carbapenem ring is thioethylene and the like, and the structure is different and the thienopyridinium ring takes a quaternary ammonium salt. In Patent Document 9, a compound having a thienopyridinium ring is reported, but the structure is different through a biphenyl group, and for antibacterial activity, methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), methicillin resistant Although it is reported to be effective by limiting to clotting enzyme negative staphylococci (MRCNS), there is no report of specific activity data.
Expert Opinion Therapeutic Patents, (UK), 2001, 11 (8), p1267-1276 WO2000 / 066581 Patent 3878131 WO2003 / 40146 WO2002 / 53566 JP-A 61-63679 JP 61-63678 A JP 61-83183 A JP 61-83184 A JP 05-92976

  As described above, pneumoniae, including penicillin-resistant pneumococci (PRSP), which is a clinical problem today, β-lactamase non-producing ampicillin-resistant Haemophilus influenzae (BLNAR), and Carbapenem derivatives used in the field are not necessarily satisfactory antibacterial activity, and at the same time, it is clinically possible to provide compounds with pharmacokinetics that can be applied not only to injections but also to oral preparations. Still desired.

  The compound according to the present invention is represented by the following formula (I), and according to the present invention, a pharmaceutically acceptable salt thereof is also provided:

[式中、Ｒ^１は水素原子またはメチル基を表し、Ｒ^２は水素原子、置換されていてもよい
Ｃ１−６アルキル基、ホルミル基、置換されていてもよいアルキルカルボニル基、置換されていてもよいアリールカルボニル基、置換されていてもよい複素環カルボニル基、置換されていてもよいアルキルオキシカルボニル基、置換されていてもよいアミノオキソアセチル基、置換されていてもよいアミド基、置換されていてもよいチオアミド基、置換されていてもよいスルホニル基、または、置換されていてもよい複素環を表し、Ｒ^３は、水素原子、または、生体内で加水分解されうる基を表し、Ｒ^４は、Ｃ１−６アルキル基、ハロゲン原子、ホルミル基、置換されていてもよいアミド基、Ｃ１−６アルキルカルボニル基、または、アリールカルボニル基を表し、Ｒ^５は、ＸまたはＹの炭素原子上に０〜６個有していてもよく、Ｃ１−６アルキル基、ハロゲン原子、ホルミル基、カルバモイル基、Ｃ１−６アルキルカルボニル基、または、アリールカルボニル基を表し、Ｘは、Ｃ１−２アルキレン、または、Ｃ＝Ｏを表し、Ｙは、Ｃ１−２アルキレン、または、Ｃ＝Ｏを表す。]

[Wherein, R ¹ represents a hydrogen atom or a methyl group, R ² represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, a formyl group, an optionally substituted alkylcarbonyl group, An optionally substituted arylcarbonyl group, an optionally substituted heterocyclic carbonyl group, an optionally substituted alkyloxycarbonyl group, an optionally substituted aminooxoacetyl group, an optionally substituted amide group, a substituted R ³ represents an optionally substituted thioamide group, an optionally substituted sulfonyl group, or an optionally substituted heterocycle, R ³ represents a hydrogen atom or a group that can be hydrolyzed in vivo, and R 3 ^4, C1-6 alkyl group, a halogen atom, a formyl group, an optionally substituted amide group, C1-6 alkylcarbonyl group, or an aryl carbonium Represents Le group, ^{R 5} may have 0-6 on a carbon atom of X or Y, C1-6 alkyl group, a halogen atom, a formyl group, a carbamoyl group, C1-6 alkylcarbonyl group, Alternatively, it represents an arylcarbonyl group, X represents C1-2 alkylene or C═O, and Y represents C1-2 alkylene or C═O. ]

  According to a preferred embodiment of the present invention is a compound of the following formula (II) or a pharmaceutically acceptable salt thereof:

[式中、Ｒ^１は水素原子またはメチル基を表し、Ｒ^２は水素原子、置換されていてもよい
Ｃ１−６アルキル基、ホルミル基、置換されていてもよいアルキルカルボニル基、置換されていてもよいアリールカルボニル基、置換されていてもよい複素環カルボニル基、置換されていてもよいアルキルオキシカルボニル基、置換されていてもよいアミノオキソアセチル基、置換されていてもよいアミド基、置換されていてもよいチオアミド基、置換され
ていてもよいスルホニル基、または、置換されていてもよい複素環を表し、Ｒ^３は、水素原子、または、生体内で加水分解されうる基を表し、Ｒ^４は、Ｃ１−６アルキル基、ハロゲン原子、ホルミル基、カルバモイル基、Ｃ１−６アルキルカルボニル基、または、アリールカルボニル基を表し、Ｒ^５は、ＸまたはＹの炭素原子上に０〜６個有していてもよく、Ｃ１−６アルキル基、ハロゲン原子、ホルミル基、カルバモイル基、Ｃ１−６アルキルカルボニル基、または、アリールカルボニル基を表し、Ｘは、Ｃ１−２アルキレン、または、Ｃ＝Ｏを表し、Ｙは、Ｃ１−２アルキレン、または、Ｃ＝Ｏを表す。]

[Wherein, R ¹ represents a hydrogen atom or a methyl group, R ² represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, a formyl group, an optionally substituted alkylcarbonyl group, An optionally substituted arylcarbonyl group, an optionally substituted heterocyclic carbonyl group, an optionally substituted alkyloxycarbonyl group, an optionally substituted aminooxoacetyl group, an optionally substituted amide group, a substituted R ³ represents an optionally substituted thioamide group, an optionally substituted sulfonyl group, or an optionally substituted heterocycle, R ³ represents a hydrogen atom or a group that can be hydrolyzed in vivo, and R 3 ^4, C1-6 alkyl group, a halogen atom, a formyl group, a carbamoyl group, C1-6 alkylcarbonyl group, or an aryl carbonyl group, ⁵ may have 0-6 on a carbon atom of X or Y, C1-6 alkyl group, a halogen atom, a formyl group, a carbamoyl group, C1-6 alkylcarbonyl group, or an arylcarbonyl group And X represents C1-2 alkylene or C = O, and Y represents C1-2 alkylene or C = O. ]

  According to another aspect of the present invention, there is provided a compound of the following formula (III) or a pharmaceutically acceptable salt thereof as a synthetic intermediate of the compound of formula (I):

[式中、Ｘａは、Ｃ１−２アルキレンを表し、Ｙａは、Ｃ１−２アルキレンを表し、Ｒ^２
ａが水素原子またアミノ基の保護基を表し、ＰＧがカルボキシル基の保護基を表す。]

[Wherein, Xa represents C1-2 alkylene, Ya represents C1-2 alkylene, R ^2
a represents a protecting group for ^a hydrogen atom or an amino group, and PG represents a protecting group for a carboxyl group. ]

  A pharmaceutical composition according to the present invention comprises a compound of formula (I) according to the present invention or a pharmaceutically acceptable salt thereof. Preferably, the pharmaceutical composition comprises a compound of formula (I) according to the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. More preferably, this pharmaceutical composition is used as an antibacterial agent.

  According to another aspect of the present invention, a bacterial infection comprising administering to a patient in need thereof an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to the present invention. Or a method of treating or preventing a symptom associated therewith is provided.

  According to yet another aspect of the present invention, use of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to the present invention for the manufacture of a medicament for the treatment or prevention of bacterial infections or symptoms associated therewith. Is provided.

The carbapenem derivative of the formula (I) according to the present invention has a wide and strong antibacterial activity against gram positive bacteria and gram negative bacteria. In particular, it has a strong antibacterial activity against pneumococci including PRSP, Haemophilus influenzae including BLNAR, catalucocci, and various pathogens including β-lactamase producing bacteria. Of the compounds of formula (I) according to the present invention, the carbapenem derivative of (I), wherein R ³ is a group that can be hydrolyzed in vivo, exhibits oral absorption and is metabolically deesterified in vivo. To produce an active body having antibacterial activity (in the compound of formula (I) R ³ is a hydrogen atom or a pharmaceutically acceptable salt). For this reason, the compound of the formula (I) of the present invention is useful not only as an injection but also as an ester. Furthermore, the carbapenem derivative according to the present invention is excellent in pharmacokinetics, has low toxicity, and is highly safe.

Definitions In this specification, the term “C 1-6 alkyl group”, “C 1-7 alkyl group” or “C 1-6 alkyloxy group” as a group or part of a group means that the group is linear or branched, Or a cyclic | annular C1-C6 or 1-7 alkyl group or alkyloxy group is each meant. The terms “C 3-6 cycloalkyl” and “C 3-6 cycloalkyloxy group” represent a cyclic alkyl group or alkyloxy group having 3 to 6 carbon atoms. Alkyloxy and alkoxy are synonymous.
Examples of “C 1-6 alkyl group” and “C 1-7 alkyl group” as a group or part of a group include methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl. Tert-butyl, cyclobutyl, n-pentyl, neopentyl,
Examples include isopentyl, tert-pentyl, cyclopentyl, n-hexyl, isohexyl, cyclohexyl, n-heptyl and the like.
Examples of the “C 1-6 alkyloxy group” as a group or a part of the group include methoxy, ethoxy, n-propoxy, isopropoxy, cyclopropoxy, n-butoxy, sec-butoxy, tert-butoxy, cyclo Examples include butoxy, n-pentyloxy, neopentyloxy, isopentyloxy, tert-pentyloxy, cyclopentyloxy, n-hexyloxy, isohexyloxy, cyclohexyloxy and the like.
Further, “C1-2 alkylene” represents alkylene having 1 to 2 carbon atoms, such as methylene and ethylene.
In addition, the “C2-6 alkenyl group” as a group or a part of the group is a linear or branched group having 2 to 6 carbon atoms, and examples thereof include a vinyl group, an allyl group, a 1-propenyl group, Isopropenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 2-methyl-1-propenyl group, 2-methylallyl group, 1-methyl-1-propenyl group, 1-methylallyl group, 1,1 -Dimethylvinyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-
Examples include a pentenyl group, 3-methyl-1-butenyl group, 1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, and 5-hexenyl group.

In the present specification, the “halogen atom” represents an atom such as fluorine, chlorine, bromine or iodine. Preferably, the halogen atom is a chlorine atom, a bromine atom or an iodine atom.
In the present specification, the “aryl group” as a group or a part of the group means a phenyl group or a naphthyl group.
In the present specification, the term “heterocycle” as a group or a part of the group is the same or different and has 4 to 7 having one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. A membered ring (preferably 5 to 7 membered) aromatic heterocyclic ring and an aliphatic heterocyclic ring are meant. Preferably, the heterocyclic ring includes furan, pyrrole, imidazole, pyrazole, thiazole, triazole, thiadiazole, pyridine, pyrazine, pyridazine, pyrimidine, oxazole, isoxazole, thiophene, azetidine, pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, Represents thiazoline, oxazoline, imidazoline and the like, more preferably, furan, thiophene, imidazole, thiazole, pyridine, pyrimidine, oxazole, azetidine, pyrrolidine, piperidine, piperazine, morpholine, thiazoline and the like.

Examples of the “acyl group” as a group or a part of the group include formyl group, “C 1-6 alkylcarbonyl group”, “arylcarbonyl group”, “heterocyclic carbonyl group” and the like.
Examples of the “C 1-6 alkylcarbonyl group” include acetyl group, propionyl group, butyryl group, isobutyryl group, cyclopropanecarbonyl group, valeryl group, isovaleryl group, pivaloyl group, cyclobutanecarbonyl group, cyclopentanecarbonyl group and the like. Examples of the “arylcarbonyl group” include a benzoyl group and a phthaloyl group. The “heterocyclic carbonyl group” is a group having a carbonyl group in the heterocyclic ring. Examples thereof include a thiazole carbonyl group, an oxazole carbonyl group, a pyridine carbonyl group, a furan carbonyl group, a thiophene carbonyl group, an imidazole carbonyl group, and a pyrrolidine carbonyl group.
The “group that can be hydrolyzed in vivo” means that it can be hydrolyzed in vivo and easily decomposed to cause deesterification, and can be a free carboxylic acid that is an active substance, or a salt thereof. An example will be described later.

Compound The present invention is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof.
According to one preferred embodiment of the present invention, there is provided a compound represented by the formula (II) or a pharmaceutically acceptable salt thereof.

In the formula, R ¹ represents a hydrogen atom or a methyl group. According to one preferred embodiment of the invention, R ¹ is a methyl group.
X represents C1-2 alkylene or C═O. According to a preferred embodiment of the present invention, methylene, ethylene and C═O are represented.
Y represents C1-2 alkylene or C═O. According to a preferred embodiment of the present invention, methylene, ethylene and C═O are represented.
X or Y may have 0 to 6 R ⁵ on the carbon atom.
In the formula (I) or (II), a compound in which either X or Y is C═O and the other is not C═O is preferable.
Specifically, a compound in which X is methylene and Y is methylene, a compound in which X is methylene and Y is ethylene, a compound in which X is methylene and Y is C═O, a compound in which X is ethylene and Y is methylene, A compound in which X represents ethylene and Y represents ethylene, a compound in which X represents ethylene and Y represents C═O, a compound in which X represents C═O and Y represents methylene, a compound in which X represents C═O and Y represents ethylene .
More preferably, a compound in which X is methylene and Y is methylene, a compound in which X is methylene and Y is ethylene, a compound in which X is methylene and Y is C═O, a compound in which X is ethylene and Y is methylene, X A compound represented by the above formula (I) or (II) wherein X represents C═O and X represents C═O and Y represents methylene, X represents C═O and Y represents ethylene is there.

R ² represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, a formyl group, an optionally substituted alkylcarbonyl group, an optionally substituted arylcarbonyl group, or an optionally substituted heterocyclic carbonyl Group, alkyloxycarbonyl group which may be substituted, aminooxoacetyl group which may be substituted, amide group which may be substituted, thioamide group which may be substituted, sulfonyl group which may be substituted Or represents an optionally substituted heterocyclic ring.
According to one preferred embodiment of the present invention, R ² may be substituted with a hydrogen atom, a C 1-6 alkyl group optionally substituted with the following substituent group A, a formyl group, or the following substituent group B. C1-6 alkylcarbonyl group, benzoyl group, heterocyclic carbonyl group optionally substituted with the following substituent group C, C1-6 alkyloxycarbonyl group optionally substituted with C1-6 alkyloxy group, the following substitution An aminooxoacetyl group which may be substituted with the group D, an amide group which may be substituted with the following substituent group D, a thioamide group which may be substituted with the following substituent group D, a C1-6 alkyl group Represents a sulfonyl group which may be substituted with a C1-6 alkylamino group, or a heterocyclic ring which may be substituted with the following substituent group C.
The substituent group A represents a hydroxyl group, a carbamoyl group, a cyano group, a C1-6 alkyloxy group, an aryl group, a heterocyclic ring, an amino group, a mono C1-6 alkylamide group, or a diC1-6 alkylamide group. Group B represents a hydroxyl group, a cyano group, a C1-6 alkyloxy group, an acetamide group, an acetyloxy group, an amino group, a mono C1-6 alkylamino group, a diC1-6 alkylamino group, a heterocyclic ring, The group C represents a C1-6 alkyl group, an acetyl group, a benzoyl group, a hydroxyl group, and an amino group, and the substituent group D represents a C1-6 alkyl group and an aryl group.

R ² is more preferably a hydrogen atom, “C 1-6 optionally substituted with the following substituent group A.
Examples of the “alkyl group” include methyl group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, n-butyl group, tert-butyl group, carbamoylmethyl group, carbamoylethyl group, carbamoylpropyl group, cyanomethyl group, cyanoethyl. Group, cyanopropyl group, benzyl group, methoxymethyl group, ethoxymethyl group, methoxyethyl group, ethoxyethyl group, hydroxymethyl group, hydroxyethyl group, pyridin-2-ylmethyl group, pyridin-3-ylmethyl group, pyridine-4 -Ylmethyl group, N-methylamidomethyl group, N, N-dimethylamidomethyl group, aminomethyl group, and the like. Formyl group, “C1-6 alkylcarbonyl group optionally substituted by the following substituent group B” As acetyl group, propionyl group, isobutyryl group , Cyclopropanecarbonyl group, cyanoacetyl group, methoxyacetyl group, ethoxyacetyl group, 2- (2-oxopyrrolidin-1-yl) acetyl group, methoxypropionyl group, ethoxypropionyl group, acetamide acetyl group, 3-a Cetamide propionyl group, (S) -2-acetamidopropionyl group, (R) -2-acetamidopropionyl group, (S) -2-acetamido-3-methylbutanoyl group, hydroxyacetyl group, 3- Hydroxypropionyl group, (S) -2-hydroxypropionyl group, (R) -2-hydroxypropionyl group, hydroxyisobutyryl group, acetyloxyacetyl group, aminoacetyl group, N-methylaminoacetyl group, N-acetyl- N-methylaminoacetyl group, N, N-dimethylaminoacetyl group, etc. Examples of the benzoyl group and “heterocyclic carbonyl group optionally substituted with the following substituent group C” include thiazole-2-carbonyl group, thiazole-4-carbonyl group, thiazole-5-carbonyl group, 4- Methylthiazole-5-carbonyl group, oxazole-2-carbonyl group, oxazole-4-carbonyl group, oxazole-5-carbonyl group, pyridine-2-carbonyl group, pyridine-3-carbonyl group, pyridine-4-carbonyl group, Furan-2-carbonyl group, furan-3-carbonyl group, thiophene-2-carbonyl group, thiophene-3-carbonyl group, 1-methyl-1H-imidazole-2-carbonyl group, 1-methyl-1H-imidazole-4 -Carbonyl group, pyrrolidine-1-carbonyl group, (R) -1-acetyl Examples include a loridine-2-carbonyl group, and examples of the “C 1-6 alkyloxycarbonyl group optionally substituted with a C 1-6 alkyloxy group” include a methoxycarbonyl group, an ethoxycarbonyl group, and a methoxyethoxycarbonyl group. Examples of the “aminooxoacetyl group optionally substituted with the following substituent group D” include aminooxoacetyl group, N-methylaminooxoacetyl group, N, N-dimethylaminooxoacetyl group, phenylaminooxo Examples of the amide group optionally substituted with the following substituent group D include carbamoyl group, N-methylamide group, N-ethylamide group, N, N-dimethylamide group, phenylamide group. And “a thioamido group optionally substituted with the following substituent group D” and Examples thereof include a thioamide group, an N-methylthioamide group, an N, N-dimethylthioamide group, a phenylthioamide group, and the like, “a sulfonyl optionally substituted with a C1-6 alkyl group or a C1-6 alkylamino group”. Examples of the “group” include a methanesulfonyl group, a sulfamoyl group, an N-methylsulfonamide group, an N, N-dimethylsulfonamide group and the like, and “a heterocyclic ring optionally substituted by the following substituent group C” Pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, oxazol-2-yl group, 4,5-dihydrooxazol-2-yl group, imidazol-2-yl group, 1-acetyl -4,5-dihydro-1H-imidazol-2-yl group, 1-benzoyl-4,5-dihydro-1H-imidazol-2-yl group, Chill dihydro -1H- imidazol-2-yl group, thiazol-2-yl group, 4,5-dihydro-2-yl group, and the like.

R ³ represents a hydrogen atom or a group that can be hydrolyzed in vivo. According to one preferred embodiment of the present invention, R ³ is a hydrogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, an optionally substituted C 1-6 alkylcarbonyloxy C 1-6 alkyl group, C 3 -6 cycloalkylcarbonyloxy C1-6 alkyl group, C3-6 cycloalkylmethylcarbonyloxy C1-6 alkyl group, C2-6 alkenylcarbonyloxy C1-6 alkyl group, arylcarbonyloxy C1-6 alkyl group, tetrahydrofuranylcarbonyl Oxymethyl group, C1-6 alkyloxy C1-6 alkyl group, C1-6 alkyloxy C1-6 alkyloxy C1-6 alkyl group, arylmethyloxy C1-6 alkyl group, arylmethyloxy C1-6 alkyloxy C1- 6 alkyl group, optionally substituted C1- 7 alkyloxycarbonyloxy C1-6 alkyl group, C1-6 alkyloxycarbonyloxy C1-6 alkyloxy group, C3-6 cycloalkyloxycarbonyloxy C1-6 alkyl group which may have a substituent, C3-6 Cycloalkylmethoxycarbonyloxy C1-6 alkyl group, aryloxycarbonyloxy C1-6 alkyl group, 3-phthalidyl group which may have a substituent on the aromatic ring, may have a substituent on the aromatic ring 2- (3-phthalidylidene) ethyl group, 2-oxotetrahydrofuran-5-yl group, mono C1-6 alkylaminocarbonyloxymethyl group, diC1-6 alkylaminocarbonyloxymethyl group, 2-oxo-5-C1- 6 alkyl-1,3-dioxolen-4-ylmethyl group, may have a substituent Piperidinylcarbonyloxy C1-6 alkyl group, diC1-6 alkylaminocarbonylmethyl group, 1,3-dioxoisoindolyl-C1-6 alkyl group, arylcarbonylaminocarbonyl C1 which may have a substituent -6 alkyl group, optionally substituted arylcarbonylamino C1-6 alkyl group, diC3-6 cycloalkylaminocarbonyl C1-6 alkyl group, tetrahydropyranyloxycarbonyloxymethyl group, 1,3-di An oxanyloxycarbonyloxymethyl group, a C1-6 alkyl C3-6 cycloalkylaminocarbonyloxy C1-6 alkyl group, or the like.

Further preferred embodiments are as follows.
Examples of R ³ include a hydrogen atom, a “C 1-6 alkyl group” such as a methyl group, an ethyl group, an n-hexyl group, a 2-ethylbutyl group, and a “C 2-6 alkenyl group” such as a vinyl group and an allyl group.
The substituent of the “optionally substituted C 1-6 alkylcarbonyloxy C 1-6 alkyl group” is one or more, preferably 1 to 6 substituted, C 1-6 alkyl groups, A C1-6 alkyloxy group, a C2-6 alkenyl group, a tetrahydropyran group and the like can be mentioned. As the “optionally substituted C 1-6 alkylcarbonyloxy C 1-6 alkyl group”, pivaloyloxymethyl group, isobutyryloxymethyl group, (3-methylbutanoyloxy) methyl group, acetoxymethyl group , (3,3-dimethylbutanoyloxy) methyl group, (3-methoxypropanoyloxy) methyl group, (2- (tetrahydro-2H-pyran-4-yl) acetoxy) methyl group, (3-ethylpentanoyl) And oxy) methyl) groups.
Examples of the “C 3-6 cycloalkylcarbonyloxy C 1-6 alkyl group” include a (2-cyclohexylcarbonyloxy) methyl group, a (2-cyclopentylcarbonyloxy) methyl group, and the like.
Examples of the “C 3-6 cycloalkylmethylcarbonyloxy C 1-6 alkyl group” include (2-cyclohexylacetoxy) methyl group, (2-cyclopentylacetoxy) methyl group and the like.
“C 2-6 alkenylcarbonyloxy C 1-6 alkyl group includes an allylcarbonyloxymethyl group.
Examples of the “arylcarbonyloxy C 1-6 alkyl group” include a benzoyloxymethyl group.
A tetrahydrofuranylcarbonyloxymethyl group may be mentioned.
Examples of the “C 1-6 alkyloxy C 1-6 alkyl group” include (propan-1-yl) oxymethyl group, methoxycarbonyloxymethyl group, ethoxycarbonyloxymethyl group and the like.
“C1-6 alkyloxy C1-6 alkyloxy C1-6 alkyl group” includes methoxymethoxymethyl group, “arylmethyloxy C1-6 alkyl group” includes benzylmethoxymethyl group, “arylmethyloxy C1-6 alkyl group” Examples of the “oxy C 1-6 alkyl group” include a benzyloxymethoxymethyl group.
The substituent of the “optionally substituted C 1-7 alkyloxycarbonyloxy C 1-6 alkyl group” is one or more, preferably 1 to 6 substituted, C 1-6 alkyl groups , C1-6 alkyloxy group, C2-6 alkenyl group, mono C1-6 alkylamino group, diC1-6 alkylamino group, mono C1-6 alkylaminocarbonyl group, diC1-6 alkylaminocarbonyl group, piperidy Examples include a nylcarbonyl group, an acetamido group, and a hydroxy group. As the “optionally substituted C 1-7 alkyloxycarbonyloxy C 1-6 alkyl group”, a neopentyloxycarbonyloxymethyl group, (n-pentyloxycarbonyloxy) methyl group, (pentan-3-yl) Oxycarbonyloxymethyl group, (tert-butyloxycarbonyloxy) methyl group, isopropyloxycarbonyloxymethyl group, isobutyloxycarbonyloxymethyl group, isopentyloxycarbonyloxymethyl group, n-butoxycarbonyloxymethyl group, (heptane- 4-yloxycarbonyloxy) methyl group, (4-methylpentyloxycarbonyloxy) methyl group, (1,3-dimethoxypropan-2-yloxycarbonyloxy) methyl group, (2-diethylamino-2-oxoethoxy) (Carbonyloxy) methyl group, (2-oxo-2- (piperidin-1-yl) ethoxycarbonyloxy) methyl group, (2-acetamidoethoxycarbonyloxy) methyl group, (2-diisopropylaminoethoxycarbonyloxy) methyl group, (3-hydroxypropoxycarbonyloxy) methyl group, (3-methoxypropoxycarbonyloxy) methyl group, (2-ethylbutoxycarbonyloxy) methyl group, (3,3-dimethylbutoxycarbonyloxy) methyl group, (3-methyl 2-ptenyloxycarbonyloxy) methyl group, 1- (methoxycarbonyloxy) ethyl group, 1- (ethoxycarbonyloxy) ethyl group, 1- (isopropyloxycarbonyloxy) ethyl group, 1- (isobutyloxycarbonyloxy) ) Examples include an ethyl group, 1- (tert-butoxycarbonyloxy) ethyl group, 1- (neopentyloxycarbonyloxy) ethyl group, and the like.
Examples of the “C 1-6 alkyloxycarbonyloxy C 1-6 alkyl group” include a methoxycarbonyloxymethoxy group, an ethoxycarbonyloxymethoxy group, an ethoxycarbonyloxyethoxy group, and the like.
The substituent of the “optionally substituted C 3-6 cycloalkyloxycarbonyloxy C 1-6 alkyl group” is one or more, preferably 1 to 6 substituted, C 1-6 alkyl Group, C1-6 alkyloxy group, etc., and "C3-6 cycloalkyloxycarbonyloxy C1-6 alkyl group which may have a substituent" includes 1- (cyclohexyloxycarbonyloxy) ethyl group, cyclopentyl Oxycarbonyloxymethyl group, cyclohexyloxycarbonyloxymethyl group, (3,3,5,5-tetramethylcyclohexyloxycarbonyloxy) methyl group, 1- (cyclohexyloxycarbonyloxy) -2-methylpropan-1-yl group 1- (cyclopentyloxycarbonyloxy) ethyl group and the like. It is.
Examples of the “C 3-6 cycloalkylmethyloxycarbonyloxy C 1-6 alkyl group” include a (cyclohexylmethyloxycarbonyloxy) methyl group.
“Aryloxycarbonyloxy C 1-6 alkyl group” is a phenyloxycarbonyloxymethyl group, “optionally substituted 3-phthalidyl group on an aromatic ring” is a phthalidyl group, etc. Examples of the “2- (3-phthalidylidene) ethyl group which may have a group” include 2- (3-phthalidylidene) ethyl group.
Examples of the 2-oxotetrahydrofuran-5-yl group and “mono C 1-6 alkylaminocarbonyloxymethyl group” include a methylaminocarbonyloxymethyl group.
N, N-diisobutylaminocarbonyloxymethyl group, N, N-diisopropylaminocarbonyloxymethyl group, N, N-di-n-propylaminocarbonyloxymethyl group as “diC 1-6 alkylaminocarbonyloxymethyl group”, N-cyclohexyl-N-methylaminocarbonyloxymethyl group, N-pentan-1-ylaminocarbonyloxymethyl group, N-isobutyl-N-isopropylaminocarbonyloxymethyl group, N-tert-butyl-N-ethylaminocarbonyl Oxymethyl group, N-ethyl-N-isoamylaminocarbonyloxymethyl group, N, N-di- (butan-1-yl) aminocarbonyloxymethyl group, N- (hexane-1-yl) -N-methylamino Carbonyloxymethyl group, N-cyclohexyl Examples include a ru-N-ethylaminocarbonyloxymethyl group, a 1- (N, N-diisopropylaminocarbonyloxy) ethyl group, and the like.
Examples of “2-oxo-5-C 1-6 alkyl-1,3-dioxolen-4-ylmethyl group” include (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl group and the like. .
The substituent of the “optionally substituted piperidinylcarbonyloxy C 1-6 alkyl group” is 1 or more, preferably 1 to 6 substituted, C 1-6 alkyl group, C 1 -6 alkyloxy group, etc., and (cis-2,6-dimethylpiperidin-1-yl) carbonyloxymethyl group as “optionally substituted piperidinylcarbonyloxy C1-6 alkyl group”, Examples include 1-[(cis-2,6-dimethylpiperidin-1-yl) carbonyloxy] ethyl group, (piperidin-1-yl) carbonyloxymethyl group, and the like.
Examples of the “C 1-6 alkyl C 3-6 cycloalkylaminocarbonyloxy C 1-6 alkyl group” include a methylcyclohexylaminocarbonyloxymethyl group and the like, and the “di C 1-6 alkylaminocarbonylmethyl group” includes N, N-diisobutyl. Examples of the aminocarbonylmethyl group and “1,3-dioxoisoindolyl-C1-6 alkyl group” include a (1,3-dioxoisoindoline-2-yl) methyl group.
The substituent of the “arylcarbonylaminocarbonyl C1-6 alkyl group optionally having substituent (s)” may be substituted by 1 or more, preferably 1 to 6, and may be a C1-6 alkyl group, C1- 6 alkyloxy groups and the like, and as the “arylcarbonylaminocarbonyl C1-6 alkyl group optionally having substituent (s)”, (N-methylbenzamido) carbonylmethyl group and the like can be mentioned.
The substituent of the “arylcarbonylamino C1-6 alkyl group optionally having substituent (s)” may be substituted with 1 or more, preferably 1 to 6, may be substituted with a C1-6 alkyl group, C1-6 Examples thereof include an alkyloxy group, and examples of the “arylcarbonylamino C 1-6 alkyl group which may have a substituent” include a (N-methylbenzamido) methyl group.
As “diC 3-6 cycloalkylaminocarbonyl C 1-6 alkyl group”, (2- (N, N-dicyclohexylamino) -2-oxo) ethyl group, “tetrahydropyranyloxycarbonyloxymethyl group” as (tetrahydro -2H-pyran-4-yloxycarbonyloxy) methyl group and “1,3-dioxanyloxycarbonyloxymethyl group” include (1,3-dioxan-5-yloxycarbonyloxy) methyl group and the like. .

R ⁴ represents a C 1-6 alkyl group, a halogen atom, a formyl group, a carbamoyl group, a C 1-6 alkylcarbonyl group, or an arylcarbonyl group. Preferably a C1-6 alkyl group etc. are mentioned.
R ⁵ may have 0 to 6 carbon atoms on X or Y, and is a C 1-6 alkyl group, a halogen atom, a formyl group, a carbamoyl group, a C 1-6 alkylcarbonyl group, or an arylcarbonyl group. Represents. Preferably, a C1-6 alkyl group etc. are mentioned.

According to another aspect of the present invention, the synthetic intermediate of the compound of formula (I) is the compound of the above formula (III), or a pharmaceutically acceptable salt thereof, wherein Xa is C1-2. Alkylene is represented, Ya represents C1-2 alkylene, R ^2a represents a protecting group for a hydrogen atom or an amino group, and PG represents a protecting group for a carboxyl group.
Xa represents C1-2 alkylene, preferably methylene or ethylene.
Ya represents C1-2 alkylene, preferably methylene or ethylene.
R ^2a represents a hydrogen atom or an amino-protecting group. The amino-protecting group represents one protected by a normal protecting group. Here, the normal protecting group is ProtectiveGr.
This is the one described in oops in Organic Synthesis (Theodora W. Greene, Peter GM Wuts, published by John Wiley & Sons, Inc.) and is well known to those skilled in the art. More preferably, R ^2a is a hydrogen atom, tert-butyloxycarbonyl group, 4-nitrobenzyloxycarbonyl group, 9-fluorenylmethyloxycarbonyl group, trifluoroacetyl group, 4-methoxybenzyl group, 2,4- Examples include dimethoxybenzyl group, 3,4-dimethoxybenzyl group, 4-toluenesulfonyl group, 2-nitrobenzenesulfonyl group, 4-nitrobenzenesulfonyl group and the like.
PG represents a protecting group for a carboxyl group. The carboxyl-protecting group represents one protected by a normal protecting group. Here, the normal protecting group is ProtectiveGr.
This is the one described in oops in Organic Synthesis (Theodora W. Greene, Peter GM Wuts, published by John Wiley & Sons, Inc.) and is well known to those skilled in the art. More preferably, PG
Includes 4-nitrobenzyl group, 4-methoxybenzyl group, diphenylmethyl group, tert-butyldimethylsilyl group, allyl group and the like.

Next, specific examples of the compound of formula (I) and the intermediate (III) thereof according to the present invention are illustrated, but the present invention is not limited thereto.
1. (1S, 5R, 6S) -2- (5- (3,4-Dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6 1-((R) -1-triethylsiloxyethyl) -1-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl (1S, 5R, 6S) -2- (5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl ) -1-Carbapen-2-em-3-carboxylic acid 4-nitrobenzyl (1S, 5R, 6S) -1-Methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1-triethylsiloxy Ethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 4. (1S, 5R, 6S) -1-Methyl-2- (4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-triethylsiloxy 4. Ethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) Sodium -1-methyl-1-carbapene-2-em-3-carboxylate (1S, 5R, 6S) -2- (5-acetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl ) Sodium 1-methyl-1-carbapene-2-em-3-carboxylate (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c]
8. pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate (1S, 5R, 6S) -2- (5- (4,5-Dihydrooxazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 9.-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1S, 5R, 6S) -2- (5-Formyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) Sodium -1-methyl-1-carbapene-2-em-3-carboxylate11. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (N-methylcarbamothioyl) -5,6-dihydro-4H-thieno [2 , 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate12. (1S, 5R, 6S) -2- (5- (1-acetyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole -2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid13. (1S, 5R, 6S) -2- (5- (1-Benzoyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-
Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid14. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl ) -1-Carbapen-2-em-3-carboxylic acid15. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-methyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine 2-yl) -1-carbapene-2-em-3-carboxylic acid16. (1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-propionyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-yl) -1-carbapene-2-em-3-carboxylate sodium 18. (1S, 5R, 6S) -2- (5- (2-Ethoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 18. 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isobutyryl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) Sodium -1-methyl-1-carbapene-2-em-3-carboxylate20. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-methylsulfonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole 2-yl) -1-carbapene-2-em-3-carboxylate 21. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (5- (2-methoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole 2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate 22. (1S, 5R, 6S) -2- (5- (2-Acetamidoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate 23. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-hydroxy-2-methylpropanoyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 24. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-methoxypropanoyl) -5,6-dihydro-4H-thieno [2,3-c] Pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate 25. (1S, 5R, 6S) -2- (5-Cyclopropanecarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxy Ethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 26. (1S, 5R, 6S) -2- (5-((S) -2-Acetamidepropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate27. (1S, 5R, 6S) -2- (5-((R) -2-acetamidopropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate 28. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (4-methylthiazole-5-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 29. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5- (thiazole-2-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid30. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (thiazole-4-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 31. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5- (oxazole-4-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 32. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-4-carbonyl) -5,6-dihydro- 4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylic acid (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-2-carbonyl) -5,6-dihydro- 4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylic acid 34. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 35. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-4-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 36. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-2-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 37. (1S, 5R, 6S) -2- (5- (furan-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate 38. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (thiophene-2-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 39. (1S, 5R, 6S) -2- (5- (3-Acetamidepropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 40. (1S, 5R, 6S) -2- (5-((S) -1-acetylpyrrolidin-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) Sodium 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate41. (1S, 5R, 6S) -2- (5-((S) -2-Acetamido-3-methylbutanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
Sodium M-3-carboxylate42. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-methyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-yl) -1-carbapene-2-em-3-carboxylic acid; (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (5-methoxycarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) Sodium 1-methyl-1-carbapene-2-em-3-carboxylate 44. (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 45. (1S, 5R, 6S) -2- (5-Cyclopropyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole-2-
Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1S, 5R, 6S) -2- (5-Cyanomethyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Carboxylic acid 48. (1S, 5R, 6S) -2- (5- (N, N-dimethylsulfamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 49. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-hydroxypropanoyl) -5,6-dihydro-4H-thieno- [2,3-c ] Sodium pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate

51. (1S, 5R, 6S) -2- (5- (2-Cyanoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (5- (2-methoxy) ethoxycarbonyl-5,6-dihydro-4H-thieno [2,3-c] Pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 53. (1S, 5R, 6S) -2- (5- (2-N, N-dimethylamino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate 54. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5- (2-N-phenylamino-2-oxoacetyl) -5,6-dihydro- 4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-
Sodium M-3-carboxylate55. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-((S) -2-hydroxypropanoyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate 56. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2-N-methylamino-2-oxoacetyl) -5,6-dihydro- 4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylate sodium (1S, 5R, 6S) -2- (5- (2-acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c]
Pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid 58. (1S, 5R, 6S) -2- (5- (2-Acetamidoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 59. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] Pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 60. (1S, 5R, 6S) -2- (5- (3-Acetamidepropanoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate 61. (1S, 5R, 6S) -2- (5- (2-Ethoxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate 62. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate (1S, 5R, 6S) -2- (5- (4,5-Dihydrooxazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
M-3-carboxylic acid 64. (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate 65. (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 66. (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6- 67. ((R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium (1S, 5R, 6S) -2- (6-Acetyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl ) Sodium 1-methyl-1-carbapene-2-em-3-carboxylate 68. (1S, 5R, 6S) -2- (6- (2-Hydroxyacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate 69. (1S, 5R, 6S) -2- (6- (4,5-Dihydrooxazol-2-yl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
M-3-carboxylic acid 70. (1S, 5R, 6S) -2- (6- (2-N, N-dimethylaminoacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 71. (1S, 5R, 6S) -2- (6- (2-Amino-2-oxoacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6- ((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium (1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl)- 4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-
Carbapen-2-em-3-carboxylic acid 74. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl)- 5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylic acid (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 76. (1S, 5R, 6S) -2- (5-tert-Butyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate 77. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-6-oxo-5,6-dihydro-4H-thieno [2,3- c) pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 78. (1S, 5R, 6S) -2- (5-Isopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1 79-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 80. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 81. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-2-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 82. (1S, 5R, 6S) -2- (5-Benzyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1 83-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (5- (2-methoxyethyl) -6-oxo-5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 84. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-hydroxyethyl) -6-oxo-5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 85. (1S, 5R, 6S) -2- (5-Cyclopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-5,6-dihydro-4H-thieno [2,3- c) Sodium pyrrol-2-yl) -1-carbapen-2-em-3-carboxylate (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-3-yl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 88. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 89. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 90. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-2-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 91. (1S, 5R, 6S) -2- (5-Benzyl-4-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1 2-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 92. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-4,5,6,7-tetrahydrothieno [3,2 -c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate 93. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethyl) -4-oxo-4,5,6,7-tetrahydrothieno [3, 2-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 94. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-2-ylmethyl) -4,5,6,7- 96. Tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate sodium (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4-oxo-4,5,6,7-tetrahydrothieno [3,2-c] pyridine 2-yl) -1-carbapene-2-em-3-carboxylate sodium 96. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-methyl-7-oxo-4,5,6,7-tetrahydrothieno [2,3 -c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate sodium (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (6-isopropyl-7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridine 2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 98. (1S, 5R, 6S) -2- (6- (2-Dimethylamino-2-oxoethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 99. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (6- (2-methoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2, 3-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate 100. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6- (2-hydroxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2, 3-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate

101. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (7-oxo-6- (pyridin-3-yl) -4,5,6,7- Sodium tetrahydrothieno [2,3-c] pyridin-2-yl) -1-carbapen-2-em-3-carboxylate102. (1S, 5R, 6S) -2- (6- (2-Ethoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6- ((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 103. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1- (Cyclohexyloxycarbonyloxy) ethyl 1-methyl-1-carbapene-2-em-3-carboxylate (mixture of diastereomers)
104. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) Pivaloyloxymethyl-1-methyl-1-carbapen-2-em-3-carboxylate 105. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (neopentyloxycarbonyloxy) methyl 106. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (n-pentyloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclopentyloxycarbonyloxy) methyl 108. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (pentan-3-yloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (2-cyclohexylacetoxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methylbutanoyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (tert-butyloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (isobutyloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (N, N-diisopropylaminocarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl 115. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) Acetoxymethyl-1-methyl-1-carbapene-2-em-3-carboxylate 116. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclohexyloxycarbonyloxy) methyl 117. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (isopropyloxycarbonyloxy) methyl 118. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid n-hexyl; (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (N, N-diisobutylaminocarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (N, N-diisobutylaminocarbonyl) methyl 121. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (phenyloxycarbonyloxy) methyl 122. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 2-ethylbutyl-1-methyl-1-carbapene-2-em-3-carboxylate 123. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-Methyl-1-carbapene-2-em-3-carboxylic acid (cis-2,6 dimethylpiperidin-1-ylcarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (isopentyloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 126. Methyl -1-methyl-1-carbapene-2-em-3-carboxylic acid (isobutyryloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclohexylmethyloxycarbonyloxy) methyl 127. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (n-butoxycarbonyloxy) methyl 128. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (heptan-4-yloxycarbonyloxy) methyl129. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) Benzoyloxymethyl-1-methyl-1-carbapene-2-em-3-carboxylate130. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (1,3-dioxoisoindoline-2-yl) methyl 131. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (N-methylbenzamido) methyl132. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (2- (N, N-dicyclohexylamino) -2-oxo) ethyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3,3-dimethylbutanoyloxy) methyl134. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Methyl-1-carbapene-2-em-3-carboxylic acid (tetrahydro-2H-pyran-4-yloxycarbonyloxy) methyl135. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Methyl-1-carbapen-2-em-3-carboxylic acid (1,3-dioxane-5-yloxycarbonyloxy) methyl 136. (1S, 5R, 6S) -2- (5-acetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2-
Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
137. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
138. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (N, N-diisopropylaminocarbonyloxy) methyl (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (neopentyloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno- [2,3-c]
141 pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid (cyclohexyloxycarbonyloxy) methyl. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 142-acetoxymethyl 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (tetrahydro-2H-pyran-4-yloxycarbonyloxy) methyl 143. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1,3-dioxane-5-yloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
145. (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (neopentyloxycarbonyloxy) methyl 146. (1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
Em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
147. (1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
148. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-propionyl-5,6-
Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
149. (1S, 5R, 6S) -2- (5- (2-Ethoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
150. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isobutyryl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) 1- (Cyclohexyloxycarbonyloxy) ethyl 1-methyl-1-carbapene-2-em-3-carboxylate (mixture of diastereomers)

151. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-methylsulfonyl-5
, 6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
152. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (5- (2-methoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole -2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
153. (1S, 5R, 6S) -2- (5- (2-Acetamidoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
154. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-methoxypropanoyl) -5,6-dihydro-4H-thieno [2,3-c] Pyrrole-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
155. (1S, 5R, 6S) -2- (5-Cyclopropanecarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxy 1- (cyclohexyloxycarbonyloxy) ethyl (diastereomeric mixture) ethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
156. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5- (oxazole-4-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
157. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-4-carbonyl) -5,6-dihydro- 4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
158. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-3-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
159. (1S, 5R, 6S) -2- (5- (3-Acetamidepropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
160. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (5-methoxycarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -1-Methyl-1-carbapene-2-em-3-carboxylate sodium 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers) 161. (1S, 5R, 6S) -2- (5-Cyclopropyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
162. (1S, 5R, 6S) -2- (5- (2-Dimethylaminoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) 1- (Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
163. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-hydroxypropanoyl) -5,6-dihydro-4H-thieno- [2,3-c ] Pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
164. (1S, 5R, 6S) -2- (6-Acetyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine-2-
Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
165. (1S, 5R, 6S) -2- (5- (4,5-Dihydrooxazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
166. (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
167. (1S, 5R, 6S) -2- (5- (2-Cyanoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
168. (1S, 5R, 6S) -2- (5-hydroxyacetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1-hydroxy 1- (cyclohexyloxycarbonyloxy) ethyl (diastereomeric mixture) ethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
169. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl)- 4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (diastereomeric mixture) )
170. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (N-methylcarbamothioyl) -5,6-dihydro-4H-thieno [2 , 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
171. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
172. (1S, 5R, 6S) -2- (5- (1-acetyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-
Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid 1- (Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
173. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-((S) -2-hydroxypropanoyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
174. (1S, 5R, 6S) -2- (5- (2-Acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
175. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-methyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine -2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
176. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-6-oxo-5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (
(Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
177. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isopropyl-6-oxo-5,6-
1- (Cyclohexyloxycarbonyloxy) ethyl dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (mixture of diastereomers)
178. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
179. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
180. (1S, 5R, 6S) -2- (5-Benzyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
181. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (5- (2-methoxyethyl) -6-oxo-5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
182. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-hydroxyethyl) -6-oxo-5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapen-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers) 183. (1S, 5R, 6S) -2- (5-Cyclopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c]
1- (cyclohexyloxycarbonyloxy) ethyl (diastereomeric mixture) of pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid )
184. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (
(Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
185. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxy-5- (pyridin-4-ylmethyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
186. (1S, 5R, 6S) -2- (5-Benzyl-4-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
187. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-4,5,6,7-tetrahydrothieno [3,2 -c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
188. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-methyl-7-oxo-4,5,6,7-tetrahydrothieno [2,3 -c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
189. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (6- (2-methoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2, 3-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
190. (1S, 5R, 6S) -6-((1R) -1-hydroxyethyl) -1-methyl-2- [7-oxo-6- (pyridin-3-yl) -4,5,6,7- Tetrahydrothieno [2,3-c] pyridin-2-yl] -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
191. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5- (2- (N-methylacetamido) acetyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium 192. (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5- (2- (N-methylacetamido) acetyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
193. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2- (2-oxopyrrolidin-1-yl) acetyl) -5, 6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 194. (1S, 5R, 6S) -2- (5-carbamoyl) -5,6-Dihydro-4H-thieno [2,3-c] pyrrole-2-
Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 195. (1S, 5R, 6S) -2- (5-carbamoyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1- (Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers) -1-methyl-1-carbapene-2-em-3-carboxylic acid
196. (1S, 5R, 6S) -2- (5- (Ethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 197. (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyrrolidine-1-carbonyl) -5,6-dihydro-4H-thieno [2, 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 198. (1S, 5R, 6S) -2- (6-acetyl-N, N-dimethyl-4,5 , 6,7-Tetrahydrothieno [2,3-c] pyridin-3-carboxamido-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em- Sodium 3-carboxylate 199. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-hydroxypropoxycarbonyloxy) methyl 200. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 2-methyl-1-carba-2-ene-2-em-3-carboxylic acid (2-acetamidoethoxycarbonyloxy) methyl201. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methoxypropoxycarbonyloxy) methyl 202. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methoxypropanoyloxy) methyl 203. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (phenyloxycarbonyloxy) methyl 204. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid (pentan-3-yloxy) carbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Methyl-1-carbapene-2-em-3-carboxylic acid (2- (tetrahydro-2H-pyran-4-yl) acetoxy) methyl 206. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Methyl-1-carbapene-2-em-3-carboxylic acid (2-cyclopentylacetoxy) methyl207. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2- (tetrahydro-2H-pyran-4-yl) acetoxy) methyl 208. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-ethylbutoxycarbonyloxy) methyl 209. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-diethylamino-2-oxoethoxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Methyl-1-carbapene-2-em-3-carboxylic acid (2-oxo-2- (piperidin-1-yl) ethoxycarbonyloxy) methyl 211. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Methyl-1-carbapene-2-em-3-carboxylic acid (2-diethylamino-2-oxoethoxycarbonyloxy) methyl 212. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1,3-dimethoxypropan-2-yloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methylbutanoyloxy) methyl 214. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclopentyloxycarbonyloxy) methyl; (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate isobutyryloxymethyl 216. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-ethylpentanoyloxy) methyl 217; (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-diisopropylaminoethoxycarbonyloxy) methyl 218. (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 2-methyl-1-carbapene-2-em-3-carboxylic acid (3-methyl-2-butenyloxycarbonyloxy) methyl 219. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (isopentyloxycarbonyloxy) methyl 220. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (heptan-4-yloxycarbonyloxy) methyl 221. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-ethylpentanoyloxy) methyl 222. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3,3-dimethylbutoxycarbonyloxy) methyl 223. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (4-methylpentyloxycarbonyloxy) methyl 224. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclohexylmethoxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3,3,5,5-tetramethylcyclohexyloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclopentyloxycarbonyloxy) methyl227. (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methylbutanoyloxy) methyl 228. (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid (pentan-3-yloxycarbonyloxy) methyl 229. (1S, 5R, 6S) -2- (5- (2-Acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (tetrahydro-2H-pyran-4-yloxycarbonyloxy) methyl (1S, 5R, 6S) -2- (5- (2-Acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methylbutanoyloxy) methyl 231. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid benzoyloxymethyl 232. (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (tert-butoxycarbonyloxy) methyl 233. (5R, 6S) -2- (5- (3,4-Dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 234. (5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1 -Sodium carbapen-2-em-3-carboxylate 235. (5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-carbapene-2-em-3-carboxylate sodium

Compounds of formula (I), in particular formula (II) and formula (III) according to the invention can be prepared according to scheme 1. However, it is not limited to this scheme.
Scheme 1

[In the above scheme, R ¹ , R ² , R ⁴ , R ⁵ , X, Y and PG are as defined in formula (I), formula (II) or formula (III), and R ^3a is hydrogen Represents an atom or a metal ion (for example, potassium, sodium, etc.), and R ⁶ represents a hydrogen atom or a hydroxyl protecting group (for example, tert-butyldimethylsilyl group, trimethylsilyl group, triethylsilyl group, 4-nitrobenzyloxycarbonyl) Represents a 4-methoxybenzyloxycarbonyl group, an allyloxycarbonyl group, etc.), and R ⁷ represents a lower alkyl group (preferably a methyl group or an n-butyl group). ]

The compound of the formula (IV) in the first step in the scheme can be synthesized by a method described in a conventional method (for example, JP-A-57-123182, JP-A-64-2579, etc.).
In the first step, the conversion from the compound of formula (IV) to formula (V) can be carried out by the following method. That is, 1 equivalent or excess amount of trifluoromethanesulfonic anhydride is added to the compound of formula (IV), and 1 equivalent or excess amount of organic base (preferably N, N--) is added to trifluoromethanesulfonic anhydride. And diisopropylethylamine, triethylamine, etc.) In the presence of an inert solvent such as acetonitrile, tetrahydrofuran, methylene chloride, toluene, or a mixed solvent thereof, after reacting at −78 to 50 ° C. for 10 minutes to 24 hours, The compound of the formula (V) can be obtained by ordinary separation purification (hereinafter referred to as separation purification well known to those skilled in the art).

  Next, in the second step, the conversion from the formula (V) to the formula (VII) of the compound can be performed by the following method. That is, one equivalent or an excess of the compound of the formula (VI) with respect to the compound of the formula (V) is converted into a palladium catalyst (for example, tetrakis (triphenylphosphine) palladium (0), tris (dibenzylideneacetone) dipalladium 0), tris (dibenzylideneacetone) dipalladium (0) -chloroform adduct, etc.) 0.001 to 1 equivalent and a phosphine ligand (for example, triphenylphosphine, tri-2-furylphosphine, Tri-2-thienylphosphine, tris (2,4,6-trimethoxyphenyl) phosphine, etc.) 0.01 to 1 equivalent and additives (for example, zinc chloride, lithium chloride, cesium fluoride, iodine) In the presence of 0.1 to 10 equivalents, an inert solvent (e.g., tetrahydrosilane) is used. , Dimethoxyethane, 1,4-dioxane, acetonitrile, acetone, ethanol, dimethyl sulfoxide, sulfolane, N, N-dimethylformamide, N, N-dimethylacetamide, N, N-dimethylimidazolidinone, N-methylpyrrolidinone, Hexamethylphosphoric triamide, etc.) or by reacting in these mixed solvents at 0 to 100 ° C. for 10 minutes to 7 days and then subjecting to usual post-treatment well known to those skilled in the art. A compound of formula (VII) can be obtained. Compounds of formula (VI) can be prepared with reference to Scheme 5 below.

Finally, in the third step, the protecting group (PG group) of the compound of formula (VII) is removed by a deprotection reaction in one step or a plurality of steps depending on the type of the protecting group, and the compound of formula (IIa) of the present invention is removed. Compounds can be obtained.
At this time, the deprotection reaction for removal of the protecting group varies depending on the type of the protecting group used, but is generally an ordinary method well known to those skilled in the art,
ps in Organic Synthesis (Theodora W. Greene, Peter GM Wuts, John Wiley & Sons, Inc.).
If any or all of them can be deprotected under acidic conditions, use a mineral acid such as hydrochloric acid, an organic acid such as formic acid, acetic acid, or citric acid, or a Lewis acid such as aluminum chloride. In the case of removal by, catalytic reduction with various catalysts or metal reducing agents such as zinc and iron can be used.
Further, when R ⁶ is a silyl protecting group (for example, tert-butyldimethylsilyl group, trimethylsilyl group, triethylsilyl group, etc.), a fluorine ion reagent (for example, tetrabutylammonium fluoride) Further, when R ⁶ is an allyloxycarbonyl group and PG is an allyl group, various palladium complexes (for example, tetrakis (triphenylphosphine) palladium (0)) can be used. Therefore, it can be easily removed.
The compound of the formula (II) thus obtained is isolated by using chromatography using a nonionic macro-hypoporous resin, gel filtration using Sephadex, etc., reverse phase silica gel column chromatography, etc. Can be purified.

Moreover, when X and Y are C1-2 alkylene groups among the compounds of Formula (II), they can also be produced according to Scheme 2.
Scheme 2

[In the above scheme, R ¹ , R ² , R ^2a (excluding a hydrogen atom in the above definition), R ⁴ , R ⁵ , Xa, Ya, and PG are represented by formula (I), formula (II) or R ^3a represents a hydrogen atom or a metal ion (for example, potassium, sodium, etc.), and R ⁶ represents a hydrogen atom or a hydroxyl protecting group (
Examples include tert-butyldimethylsilyl group, trimethylsilyl group, triethylsilyl group, 4-nitrobenzyloxycarbonyl group, 4-methoxybenzyloxycarbonyl group, allyloxycarbonyl group and the like. ). ]

In the first step, the amino protecting group (R ^2a ) of formula (VIII) can be removed by a deprotection reaction in one or more steps depending on the type of protecting group to give formula (VIII _a ).
At this time, the deprotection reaction for removing the protecting group varies depending on the kind of the protecting group used. For example, when the protecting group is a tert-butyloxycarbonyl group, a mineral acid such as hydrochloric acid, trifluoro When it is a 4-nitrobenzyloxycarbonyl group using an organic acid such as acetic acid, a Lewis acid such as aluminum chloride, etc., and when it is a 9-fluorenylmethyloxycarbonyl group using catalytic reduction with various catalysts Is an organic base such as piperidine, diethylamine, diisopropylamine, or a fluorine ion reagent (for example, tetrabutylammonium fluoride). In the case of a trifluoroacetyl group, inorganic substances such as potassium carbonate and sodium carbonate are used. It can be easily removed by using a reducing agent such as a base or sodium borohydride. In addition, Protective Groups in Organ
ic Synthesis (Theodora W. Greene, Peter GM
Wuts, John Wiley & Sons, Inc. Reference can be made to the method described in Publication).

Next, in the second step, the conversion to formula (VIII _b ) can be performed by the following method when R ² is an alkylcarbonyl group. That is, 1 equivalent or an excess amount of R ² —Cl is added to the formula (VIII _a ) in the presence of 1 equivalent or an excess amount of an organic base (preferably N, N-diisopropylethylamine, triethylamine, etc.). , Acetonitrile, tetrahydrofuran, methylene chloride, toluene and the like, or a mixed solvent thereof, at −78 to 50 ° C. for 10 to 24 hours, followed by normal separation and purification to obtain a compound of the formula (VIII _b ) Can be obtained.
In addition, 1 equivalent or an excess amount of R ² —OH with respect to the formula (VIII _a ) is changed to 1 equivalent or an excess amount of a peptide synthesis reagent (preferably 1-ethyl-3- (3-dimethylaminopropyl)
Examples thereof include carbodiimide hydrochloride. ) In the presence of an inert solvent such as N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, methylene chloride using a catalytic amount or excess amount of an activator such as 1-hydroxybenzotriazole if necessary Alternatively, after reacting in these mixed solvents at 0 to 100 ° C. for 10 minutes to 24 hours, the formula (VIII _b ) can be obtained by ordinary separation and purification.
When R ² is an alkyl group, it can be carried out according to the usual method of reductive aminoalkylation reaction. That is, an aldehyde corresponding to 1 equivalent or an excess amount of R ² with respect to the formula (VIII _a ) is added in an inert solvent (preferably methylene chloride and the like) at 0 to 50 ° C. for 10 minutes to 24 minutes. The reaction is carried out for a period of time to give a Schiff base, to which a reducing agent (for example, sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, etc.) is added, and at 0-50 ° C. for 10 minutes to 24 hours. After the reaction, the formula (VIII _b ) is obtained by ordinary separation and purification.
Finally, the third step can be performed according to the method described in Scheme 1 above.

Furthermore, in the formula (II) of the present invention, when X and Y are a C1-2 alkylene group and R ² is an alkylcarbonyl group, they can also be produced according to Scheme 3.
Scheme 3

[In the above scheme, R ¹ , R ^2a (provided that the hydrogen atom is excluded in the above definition) R
⁴ , R ⁵ , Xa, Ya and PG have the same meaning as defined in formula (I), formula (II) or formula (III). The amino protecting group for R ^2a is preferably 4-methoxybenzyl group, 2,4-dimethoxybenzyl group, 3,4-dimethoxybenzyl group, etc., and R ^2b is defined by formula (I) or formula (II). An optionally substituted alkylcarbonyl group (for example, formyl group, acetyl group, propionyl group, isobutyryl group, cyclopropanecarbonyl group, cyanoacetyl group, methoxyacetyl group, ethoxyacetyl group, 2- (2-oxopyrrolidine- 1-yl) acetyl group, methoxypropionyl group, ethoxypropionyl group, acetamide acetyl group, 3-acetamidopropionyl group, (S) -2-acetamidopropionyl group, (R) -2-acetamido represents a propionyl group, a (S) -2- acetamido-3-methyl butanoyl group and the like.), R ^a represents a hydrogen atom or a metal ion, (e.g. potassium, sodium and the like.), R ⁶ is a hydrogen atom or a hydroxyl protecting group, (for example, tert- butyldimethylsilyl group, a trimethylsilyl group, triethylsilyl group, 4 -Nitrobenzyloxycarbonyl group, 4-methoxybenzyloxycarbonyl group, allyloxycarbonyl group, etc.). ]

In the first step, the conversion to the formula (IX _a ) can be performed by the following method. That is,
1 equivalent or excess of R ^2b —Cl (represents acid chloride of R ^2b with respect to formula (IX), for example, formyl chloride, acetyl chloride, propionyl chloride, isobutyryl chloride, cyclopropanecarbonyl chloride, cyanoacetyl Chloride, methoxyacetyl chloride, ethoxyacetyl chloride, 2- (2-oxopyrrolidin-1-yl) acetyl chloride, methoxypropionyl chloride, ethoxypropionyl chloride, acetamide acetyl chloride, 3-acetamidopropionyl chloride, (S) 2-acetamide propionyl chloride, (R) -2-acetamidopropionyl chloride, (S) -2-acetamido-3-methylbutanoyl chloride, etc.). In the presence of an excess amount of an inorganic base (for example, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.) and an organic base (for example, triethylamine, N, N-diisopropylethylamine, etc.), acetonitrile, tetrahydrofuran, methylene chloride. The reaction can be carried out in an inert solvent such as chloroform, toluene, or a mixed solvent thereof at −78 to 50 ° C. for 10 minutes to 24 hours, and then subjected to usual liquid separation purification to obtain the formula (IX _a ). it can.
The second step can then be performed according to the method described in Scheme 1 above.

In the scheme 4, the formula (II _d ) corresponds to a compound represented by the formula (I) or the formula (II) according to the present invention, in which R ³ is an ester group that is hydrolyzed in vivo. Among the compounds represented by formula (I) or Formula (II), R ³ is an ester group which is hydrolyzed in vivo, R ³ of formula (I) or formula (II) or a hydrogen atom It can manufacture by converting the compound which is a metal ion (for example, potassium, sodium etc.) into an ester body.
Scheme 4

[In the above scheme, R ¹ , R ² , R ⁴ , R ⁵ , X and Y have the same meaning as defined in formula (I), formula (II) or formula (III)). A represents a halogen atom (preferably represents iodine, bromine, chlorine, etc.), R ^3a represents a hydrogen atom or a metal ion (for example, potassium, sodium, etc.), and R ^3b represents in vivo An ester group that is hydrolyzed with, for example, a C1-6 alkyl group, a C2-6 alkenyl group, a C1-6 alkylcarbonyloxy C1-6 alkyl group, a C3-6 cycloalkylcarbonyloxy C1-6 alkyl group, a C3- 6 cycloalkylmethylcarbonyloxy C1-6 alkyl group, C2-6 alkenylcarbonyloxy C1-6 alkyl group, arylcarbonyloxy C1-6 alkyl group, tetrahydrofuranylcarbonyloxymethyl group, C1-6 alkyloxy C1-6 alkyl group C1-6 alkyloxy C1-6 alkyloxy C1 6 alkyl group, arylmethyloxy C1-6 alkyl group, arylmethyloxy C1-6 alkyloxy C1-6 alkyl group, C1-7 alkyloxycarbonyloxy C1-6 alkyl group, C1-6 alkyloxycarbonyloxy C1-6 Alkyloxy group, C3-6 cycloalkyloxycarbonyloxy C1-6 alkyl group, C3-6 cycloalkylmethoxycarbonyloxy C1-6 alkyl group, aryloxycarbonyloxy C1-6 alkyl group, having a substituent on the aromatic ring 3-phthalidyl group which may be substituted, 2- (3-phthalidylidene) ethyl group which may have a substituent on the aromatic ring, 2-oxotetrahydrofuran-5-yl group, mono C1-6 alkylaminocarbonyloxymethyl Group, di-C1-6 alkylaminocarbonyloxy Methyl group, 2-oxo-5-C1-6 alkyl-1,3-dioxolen-4-ylmethyl group, piperidinylcarbonyloxy C1-6 alkyl group optionally having substituent (s), diC1-6 alkylamino Carbonylmethyl group, 1,3-dioxoisoindolyl-C1-6 alkyl group, optionally substituted arylcarbonylaminocarbonyl C1-6 alkyl group, optionally substituted arylcarbonylamino C1 -6 alkyl group, di-C3-6 cycloalkylaminocarbonyl C1-6 alkyl group, tetrahydropyranyloxycarbonyloxymethyl group, 1,3-dioxanyloxycarbonyloxymethyl group, or C1-6 alkyl C3-6 Examples include cycloalkylaminocarbonyloxy C1-6 alkyl group. ]

That is, in the presence of 1 equivalent or excess amount of base, 1 equivalent or excess amount of alkyl halide (R ^3b -A) is added to formula (II _a ) in an inert solvent at −70 to 50 ° C. (preferably The compound of the formula (II _d ) can be obtained by reacting at 30 to 20 ° C. for 10 minutes to 24 hours.
Examples of additives in this reaction include organic bases such as N, N-diisopropylethylamine, diazabicyclo [2,2,2] undecene, 2,6-lutidine, sodium hydroxide, potassium hydroxide, sodium bicarbonate, carbonate Inorganic bases such as potassium hydrogen, sodium carbonate, potassium carbonate, cesium carbonate, and / or quaternary ammonium salts (for example, triethylbenzylammonium chloride, tetraethylammonium chloride, tetrabutylammonium chloride, tetrabutylammonium bromide, etc.) .).

Examples of the alkyl halide (R ^3b -A) include methyl chloride, ethyl chloride, n-hexyl chloride, 2-ethylbutyl chloride, allyl chloride, pivaloyloxymethyl chloride, (3-methylbutanoyloxy) Methyl chloride, acetoxymethyl chloride, (3,3-dimethylbutanoyloxy) methyl chloride, (2-cyclohexylacetoxy) methyl chloride, isobutyryloxymethyl chloride, (propan-1-yl) oxymethyl chloride, methoxycarbonyloxy Methyl chloride, ethoxycarbonyloxymethyl chloride, neopentyloxycarbonyloxymethyl chloride, (n-pentyloxycarbonyloxy) methyl chloride, (pentan-1-yl) o Xyloxycarbonyloxymethyl chloride, (pentan-3-yl) oxycarbonyloxymethyl chloride, (tert-butyloxycarbonyloxy) methyl chloride, isopropyloxycarbonyloxymethyl chloride, isobutyloxycarbonyloxymethyl chloride, isopentyloxycarbonyloxymethyl Chloride, n-butoxycarbonyloxymethyl chloride, (heptan-4-yloxycarbonyloxy) methyl chloride, (1-ethylpropan-1-yl) oxycarbonyloxymethyl chloride, 1- (methoxycarbonyloxy) ethyl chloride, 1 -(Ethoxycarbonyloxy) ethyl chloride, 1- (isopropyloxycarbonyloxy) ethyl chloride, 1- (isobutylio) Xyloxycarbonyloxy) ethyl chloride, 1- (tert-butoxycarbonyloxy) ethyl chloride, 1- (neopentyloxycarbonyloxy) ethyl chloride, 1- (cyclohexyloxycarbonyloxy) ethyl chloride, cyclopentyloxycarbonyloxymethyl chloride, cyclohexyl Oxycarbonyloxymethyl chloride, 1- (cyclohexyloxycarbonyloxy) -2-methylpropan-1-yl chloride, 1- (cyclopentyloxycarbonyloxy) ethyl chloride, (cyclohexylmethyloxycarbonyloxy) methyl chloride, benzoyloxymethyl chloride , Phenyloxycarbonyloxymethyl chloride, phthalidyl chloride, (5-methyl-2-oxo- 1,3-dioxolen-4-yl) methyl chloride, N, N-diisobutylaminocarbonyloxymethyl chloride, N, N-diisopropylaminocarbonyloxymethyl chloride, N, N-di-n-propylaminocarbonyloxymethyl chloride, N-cyclohexyl-N-methylaminocarbonyloxymethyl chloride, N-pentan-1-ylaminocarbonyloxymethyl chloride, N-isobutyl-N-isopropylaminocarbonyloxymethyl chloride, N-tert-butyl-N-ethylaminocarbonyl Oxymethyl chloride, N-ethyl-N-isoamylaminocarbonyloxymethyl chloride, N, N-di- (butan-1-yl) aminocarbonyloxymethyl chloride, N- (hexane-1-y ) -N-methylaminocarbonyloxymethyl chloride, N-cyclohexyl-N-ethylaminocarbonyloxymethyl chloride, 1- (N, N-diisopropylaminocarbonyloxy) ethyl chloride, (cis-2,6-dimethylpiperidine- 1-yl) carbonyloxymethyl chloride, 1-[(cis-2,6-dimethylpiperidin-1-yl) carbonyloxy] ethyl chloride, (piperidin-1-yl) carbonyloxymethyl chloride, N, N-diisobutylamino Carbonyl methyl chloride, (1,3-dioxoisoindoline-2-yl) methyl chloride, (N-methylbenzamido) methyl chloride, (2- (N, N-dicyclohexylamino) -2-oxo) ethyl chloride, ( Tetrahi Examples thereof include dro-2H-pyran-4-yloxycarbonyloxy) methyl chloride, (1,3-dioxan-5-yloxycarbonyloxy) methyl chloride, and the like and corresponding iodides.

As an inert solvent usable for the reaction, N, N-dimethylformamide, N, N-dimethylacetamide, N, N-diethylformamide, N, N-diethylacetamide, N-methylpyrrolidinone, N, N-dimethylimidazo Lidinone, dimethyl sulfoxide, sulfolane, acetonitrile, acetone, ethyl acetate, tetrahydrofuran, 1,4-dioxane, diethyl ether, anisole, methylene chloride, 1,2-dichloroethane, chloroform, toluene, benzene, hexamethylphosphoric triamide, Methanol, ethanol, etc. can be used alone or in a mixed solvent.
The compound of formula (II _d ) thus obtained is isolated and purified by subjecting it to normal post-treatment, precipitation, gel filtration using Sephadex, etc., silica gel column chromatography, etc. be able to.

The compound of the formula (X) used in the above scheme 1 can be synthesized by the following method.
Scheme 5

[In the above scheme, R ² , R ⁴ , R ⁵ , X, and Y have the same meaning as defined in formula (I) or formula (II), and M represents Li, MgCl, MgBr, MgI. , Z is C
l, Br, represents I or -OSO ₂ CF _3. ]

Conversion from the formula (X) to the formula (VI) can be performed by the following method. That is, an inert solvent (for example, tetrahydrofuran, diethyl ether, 1,4-dioxane, anisole, dimethoxyethane, methylene chloride, toluene or the like is used alone or in a mixed solvent) of the compound of the formula (X) in a solution of the formula ( By adding one equivalent or an excess amount of tin reagent (R ⁷ ₃ Sn-Z) to the compound of X), reacting at −100 to 50 ° C. for 15 minutes to 24 hours, and then subjecting to normal post-treatment A compound of formula (VI) can be obtained.
Examples of the tin reagent (R ⁷ ₃ Sn—Z) include trimethyltin chloride, tributyltin chloride, and triphenyltin chloride.
Formula (X) is available, or can be produced and used by a known method or a reference example described later.
The compound of the formula (VI) thus obtained can be isolated and purified by distillation, precipitation, gel filtration using Sephadex, etc., silica gel column chromatography or the like depending on its physical properties.

  In all steps, side chain substitution, protection, and deprotection can be performed by methods well known to those skilled in the art. In addition, the compound formulas (I) and (II) of the present invention and the intermediate (III) thereof may have tautomeric and stereoisomeric structures, and these compounds are also included in the present invention.

  The salts of formula (I), (II) and (III) which are compounds according to the invention are pharmaceutically acceptable salts, for example inorganic salts such as lithium, sodium, potassium, calcium, magnesium, Or salt with organic base such as ammonium salt, triethylamine, N, N-diisopropylethylamine, salt with mineral acid such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, or acetic acid, carbonic acid, citric acid, apple And salts with organic acids such as acid, oxalic acid and methanesulfonic acid. Preferred are sodium salt, potassium salt, hydrochloride and the like.

  Furthermore, the compounds according to the invention may be solvates, which include hydrates, alcohol solvates (for example methanol solvates, ethanol solvates), and ether solvates (for example diethyl). Ethers).

Use of Compound / Pharmaceutical Composition The compound according to the present invention inhibits the growth of pathogenic bacteria in vitro and exhibits antibacterial activity (see Test Example 1). In addition, it has been confirmed that the compound according to the present invention inhibits the growth of pathogenic bacteria and exhibits antibacterial activity in in vivo tests. That is, the carbapenem derivative of the formula (I) according to the present invention is suitable for pneumococci including penicillin-resistant pneumococci (PRSP), influenza bacteria including β-lactamase non-producing ampicillin-resistant Haemophilus influenzae (BLNAR), and various pathogens including catalum. It shows strong antibacterial activity. Therefore, it can be said that the compound according to the present invention is extremely effective in preventing or treating infections caused by these bacteria or symptoms associated therewith.
The compounds according to the invention can therefore be used for the prevention or treatment of bacterial infections and associated symptoms. The bacteria causing such bacterial infections are selected from the group consisting of pneumococci including penicillin-resistant pneumococci (PRSP), β-lactamase non-producing ampicillin-resistant Haemophilus influenzae (BLNAR), and cataracts. Can be mentioned.

According to the present invention there is provided a pharmaceutical composition comprising a compound according to the present invention or a pharmacologically acceptable salt thereof. Preferably, the pharmaceutical composition can further comprise a pharmaceutically acceptable carrier. The pharmaceutical composition according to the present invention can be used for the prevention or treatment of bacterial infections. That is, it can be used as an antibacterial agent.
According to another aspect of the present invention, as described above, comprising administering to a patient in need thereof an effective amount of a compound of formula (I) according to the present invention or a pharmaceutically acceptable salt thereof. A method of treating or preventing a bacterial infection or a symptom associated therewith is provided.
As used herein, “effective amount” means the amount of an active ingredient that is at least required for exerting its effect in order to treat, prevent, suppress progression, or ameliorate a disease or symptom or condition. The “patient” refers to a human or a mammal other than a human (eg, mouse, rat, rabbit, dog, cat, cow, horse, pig, monkey, etc.) to which the compound or composition of the present invention is to be administered. means. “Administration” means that a target substance is taken into a living body orally or parenterally to a subject patient.

The present invention also provides an antibacterial agent comprising the compound according to the present invention or a pharmaceutically acceptable salt thereof as an active ingredient.
The compound according to the present invention or a pharmaceutically acceptable salt thereof can be administered to humans and humans by any of the oral and parenteral routes (eg, intravenous administration, intramuscular administration, subcutaneous administration, rectal administration, transdermal administration). Can be administered to other animals.

Accordingly, a pharmaceutical composition comprising a compound according to the present invention is formulated into a suitable dosage form depending on the route of administration. Specifically, examples of oral preparations include tablets, capsules, powders, granules, pills, fine granules, troches, syrups, and parenterals such as intravenous injection or intramuscular injection. Injections, suppositories, tapes, ointments and the like can be mentioned.
These various preparations are commonly used excipients, extenders, disintegrants, binders, lubricants, colorants, diluents, wetting agents, surfactants, dispersants, buffers, storage. Can be produced by a conventional method using additives (carriers) such as an agent, a solubilizer, a preservative, a flavoring agent, a soothing agent, and a stabilizer.
Examples of excipients include lactose, fructose, glucose, corn starch, sorbite, and crystalline cellulose. Examples of disintegrants include starch, sodium alginate, gelatin powder, calcium carbonate, calcium citrate, and dextrin. Examples of the agent include dimethyl cellulose or a salt thereof, polyvinyl alcohol, polyvinyl ether, methyl cellulose, ethyl cellulose, gum arabic, gelatin, hydroxypropyl cellulose, and polyvinyl pyrrolidone. Examples of the lubricant include talc, magnesium stearate, and polyethylene glycol. And hydrogenated vegetable oils. Other non-toxic additives that can be used include, for example, syrup, petrolatum, lanolin, glycerin, ethanol, propylene glycol, citric acid, sodium chloride, sodium sulfite, sodium phosphate, β-cyclodextrin, hydroxypropyl- β-cyclodextrin, Tween 80 and the like can be mentioned.
Moreover, the said injection can be manufactured by adding a buffer, a pH adjuster, a stabilizer, an isotonic agent, a preservative, etc. as needed.

In the pharmaceutical composition according to the present invention, the content of the compound according to the present invention varies depending on the dosage form, but is usually 0.01 to 100% by weight, preferably 0.1 to 90% by weight, based on the total composition. Preferably it is 0.5 to 50 weight%. The dose is appropriately determined according to the individual case in consideration of the patient's age, weight, sex, disease difference, symptom level, etc. Usually, the dose is about 1 to 2000 mg, preferably 10 to 1000 mg per adult per day, which can be administered once to 6 times a day depending on the symptoms.
The compounds according to the present invention are, for example, DHP-1 inhibitors (dehydrogenase)
-1 inhibitor), organic ion transport inhibitors such as betamipron, and the like, or may be administered in combination.

  EXAMPLES Hereinafter, although an Example and an example demonstrate this invention, this invention is not limited to these.

Example 1 (1S, 5R, 6S) -2- (5- (3,4-dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c
] Pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 15.3 g (25.16 mmol) and 5- (3,4-dimethoxybenzyl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole 17.5 g (31.03 mmol) anhydrous 1 -1.19 g (5.13 mmol) of tri (2-furyl) phosphine, 1.17 g (1.28 mmol) of tris (dibenzylideneacetone) dipalladium and 6.95 g (51.0 mmol) of zinc chloride sequentially at room temperature in 160 ml solution The mixture was further stirred at room temperature for 2 hours. The mixture was diluted with ethyl acetate, washed 3 times with water, and washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1) to give the title compound (14.5 g) 79%).
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.26 (3H, dd, J = 7.0 and
3.0 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.05 (3H, s), 3.28 (1H, dd, J = 5.6 and 2.6 Hz), 3.53-3.61 (1H, m), 4.28-4.33 ( 2H, m), 4.62-4.67 (2H, m), 4.78-4.83 (2H, m), 5.26 (1H, dd, J = 13.9 and 3.9 Hz), 5.50 (1H, dd, J = 13.9 and 3.4 Hz) , 7.43 (0.45H, s), 7.51 (0.55H, s), 7.68 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
MS (FAB ⁺ ); m / z 734 [M + 1] ⁺

Example 2 (1S, 5R, 6S) -2- (5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1- Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(a) (1S, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2- (5- (2,2,2-trifluoroacetyl) -5,6- Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-
M-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5- (3,4-Dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6 -((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 7.34 g (10 mmol) in anhydrous methylene chloride 50 ml under ice-cooling, triethylamine 4.18 ml (30 mmol) and 2.09 ml (15 mmol) of trifluoroacetic anhydride were sequentially added. After stirring at the same temperature for 15 minutes, 100 ml of tetrahydrofuran and 50 ml of saturated aqueous sodium hydrogen carbonate were added, and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with ethyl acetate, washed with saturated brine, and the organic layer was dried over anhydrous magnesium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluting with hexane: ethyl acetate = 2: 1) to obtain 6.43 g (yield 79%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.9 Hz), 1.24-1.27 (3H, m), 1.30 (3H, d, J = 6.1 Hz ), 2.05 (3H, s), 3.30 (1H, dd, J = 5.6 and 2.6 Hz), 3.51-3.61 (1H, m), 4.27-4.34 (2H, m), 4.75-5.06 (4H, m), 4.78-4.83 (2H, m), 5.26 (1H, d, J = 13.9 Hz), 5.49 (1H, d, J = 13.9 Hz), 7.47 (1H, s), 7.69 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
MS (ESI ⁺ ); m / z 680 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1- Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2- (5- (2,2,2-trifluoroacetyl) -5,6-dihydro-4H 4-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 6.43 g (9.46 mmol) of anhydrous methylene chloride 40 ml and anhydrous methanol 40 ml Under ice cooling, 537 mg (14.2 mmol) of sodium borohydride was added to the solution, and the mixture was stirred at the same temperature for 2 hours. After adding saturated ammonium chloride aqueous solution to the reaction solution to terminate the reaction,
Extracted 3 times with chloroform. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 19: 1) to give 4.22 g of the title compound (yield) 76%).
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.9 Hz), 1.26 (3H, d, J = 7.3 Hz),
1.30 (3H, d, J = 6.3 Hz), 3.27 (1H, dd, J = 5.8 and 2.7 Hz), 3.52-3.60 (1H, m), 4.07-4.10 (2H, m), 4.23-4.32 (4H, m), 5.25 (1H, d, J = 13.9 Hz), 5.49 (1H, d, J = 13.9 Hz), 7.46 (1H, s), 7.68 (2H, d, J = 8.7 Hz), 8.23 (2H, d, J = 8.7 Hz)
MS (ESI ⁺ ); m / z 584 [M + 1] ⁺

Example 3 (1S, 5R, 6S) -1-methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1 4- (Nitrobenzyl)-(triethylsiloxy) ethyl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (9H-Fluoren-9-yl) methyloxycarbonyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2 4-ylbenzyl-1-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl And 5- (9H-fluoren-9-yl) methyloxycarbonyl-2-tributylstannyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine Gave the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.65 (6H, m), 0.95 (9H, t, J = 7.9 Hz), 1.23-1.32 (6H, m), 2.75-2.90 (2H, m), 3.25 -3.31 (1H, brs), 3.51-3.61 (1H, m), 3.65-3.88 (2H, m), 4.24-4.33 (3H, m), 4.46-4.57 (4H, m), 5.27 (1H, d, J = 13.9 Hz), 5.51 (1H, d, J = 13.9 Hz), 7.27-7.43 (5H, m), 7.57 (2H, d, J = 7.3 Hz), 7.69 (2H, d, J = 8.7 Hz) , 7.71-7.81 (2H, m), 8.23 (2H, d, J = 8.7 Hz)
MS (FAB ⁺ ); m / z 820 [M + 1] ⁺
(b) (1S, 5R, 6S) -1-Methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1 -Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5- (9H-Fluoren-9-yl) methyloxycarbonyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) 1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 400 mg (0.49 mmol) anhydrous N, N-dimethylformamide 5 To the ml solution, 0.69 ml (4.97 mmol) of diisopropylamine was added at room temperature, and the mixture was stirred at 50 ° C. for 1 hour. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic layer was dried over anhydrous sodium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 19: 1) to obtain 255 mg (yield 88%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.56-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.25 (3H, d, J = 7.6 Hz),
1.30 (3H, d, J = 6.0 Hz), 2.88-2.97 (2H, m), 2.82 (2H, t, J = 5.6 Hz), 3.16 (2H, t, J = 5.6 Hz), 3.25 (1H, dd , J = 5.8 and 2.6 Hz), 3.50-3.59 (1H, m), 3.87-3.96 (2H, brs), 4.22-4.32 (2H, m), 5.26 (1H, d, J = 1 3.9 Hz), 5.50 (1H, d, J = 13.9 Hz), 7.34 (1H, s), 7.69 (2H, d, J = 8.7 Hz), 8.23 (2H, d, J = 8.7 Hz)
MS (ESI ⁺ ); m / z 597 [M + 1] ⁺

Example 4 (1S, 5R, 6S) -1-methyl-2- (4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1 -Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(a) (1S, 5R, 6S) -2- (6- (3,4-dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1 4-Nitrobenzyl 4-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-em-3-carboxylate
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl And 6- (3,4-dimethoxybenzyl) -2-tributylstannyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine in the same manner as in Example 1, To give a compound.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.94 (9H, t, J = 8.1 Hz), 1.23 (3H, d, J = 7.1 Hz),
1.29 (3H, d, J = 6.3 Hz), 2.72-2.78 (4H, m), 3.24 (1H, dd, J = 5.9 and 2.7), 3.51-3.55 (1H, m), 3.65-3.67 (4H, m ), 3.89 (6H, s), 4.23-4.29 (2H, m), 5.24 (1H, d, J = 13.9 Hz), 5.47 (1H, d, J = 13.9 Hz), 6.78-6.92 (3H, m) , 7.37 (1H, s), 7.66 (2H, d, J = 8.2 Hz), 8.20 (2H, d, J = 8.2 Hz)
MS (FAB ⁺ ); m / z 748 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (6- (9H-Fluoren-9-yl) methyloxycarbonyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-2 -Yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (6- (3,4-Dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl- 6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 490 mg (0.66 mmol) in anhydrous chloroform 7 ml solution under ice-cooling, potassium bicarbonate 79 mg (0.79 mmol) and (9H-fluoren-9-yl) methoxycarbonyl chloride 203 mg (0.79 mmol) were added. After warming to room temperature and stirring for 30 minutes, the reaction was quenched with saturated brine and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was subjected to silica gel flash column chromatography (
Elution with hexane: ethyl acetate = 3: 1) to obtain 398 mg (yield 74%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.64 (6H, m), 0.86-0.97 (9H, m), 1.26-1.31 (6H, m), 2.69-2.72 (2H, m), 3.27-3.29 ( 1H, m), 3.54-3.56 (1H, m), 3.69-3.71 (2H, m), 4.29-4.31 (4H, m),
4.47 (2H, d, J = 6.6 Hz), 5.24-5.28 (1H, m), 5.48-5.52 (1H, m), 7.26-7.76 (11H, m), 8.23 (2H, d, J = 8.8 Hz)
MS (FAB ⁺ ); m / z 842 [M + Na] ⁺
(c) (1S, 5R, 6S) -1-Methyl-2- (4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1 -Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (6- (9H-Fluoren-9-yl) methyloxycarbonyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) In the same manner as in Example 3 (b), using 4-nitrobenzyl-1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate To give the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.1 Hz), 1.25 (3H, d, J = 7.3 Hz),
1.30 (3H, d, J = 6.1 Hz), 2.63-2.67 (2H, m), 3.10-3.14 (2H, m), 3.26 (1H, dd, J = 5.9and 2.7 Hz), 3.52-3.57 (1H, m), 4.04 (2H, s), 4.24-4.30 (2H, m), 5.24-5.31 (1H, m), 5.50 (1H, d, J = 14.0 Hz), 7.38 (1H, s), 7.69 (2H , d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8 Hz)

MS (FAB ⁺ ); m / z 598 [M + 1] ⁺

Example 5 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate (a) (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2 , 3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
(1S, 5R, 6S) -2- (5- (3,4-Dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6 3-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 2.2 g (3 mmol) in anhydrous chloroform 40 ml solution under ice-cooling, potassium bicarbonate 330 mg (3.3 mmol) and 0.24 ml (3.3 mmol) of acetyl chloride were sequentially added and stirred at the same temperature for 10 minutes. After dilution with chloroform, the mixture was washed with half-saturated saline. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluted with ethyl acetate: methanol = 19: 1) to give 1.8 g (yield) of the title compound. 96%).
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.24-1.28 (3H, m), 1.30 (3H, d, J = 6.3 Hz ), 2.15 (3H, s), 3.28 (1H, dd, J = 5.6 and 2.6 Hz), 3.53-3.61 (1H, m), 4.28-4.33 (2H, m), 4.62-4.67 (2H, m), 4.78-4.83 (2H, m), 5.26-5.29 (1H, m), 5.47-5.52 (1H, m), 7.43 (0.45H, s), 7.51 (0.55H, s), 7.68 (2H, d , J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
MS (ESI ⁺ ); m / z 626 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1 -Triethylsiloxyethyl) -1-carbapent-2-em-3-carboxylic acid 4-nitrobenzyl 388 mg (0.62 mmol) in tetrahydrofuran 6 ml and water 0.6 ml mmol) was added dropwise. After stirring for 1 hour at the same temperature, saturated sodium bicarbonate solution 0.31 ml
Then, 12 ml of tetrahydrofuran and 15 ml of 0.1 N phosphate buffer were sequentially added, and 390 mg of 10% palladium-carbon (hydrous water content: 52%) was added to the solution, followed by stirring at room temperature in a hydrogen atmosphere for 1.5 hours. Palladium-carbon was filtered using Celite, washed with water, and saturated aqueous sodium hydrogen carbonate was added to the filtrate to adjust the pH to 7.5. After washing with ethyl acetate, the aqueous layer was concentrated to about 5 ml and purified by Cosmosil 40C18-PREP column chromatography (eluting with water: methanol = 9: 1) to give the title compound 200 mg (yield 81%) Got.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.04-1.08 (3H, m), 1.16 (3H, d, J = 6.4 Hz), 3.31 (1H, dt, J = 6.4 and 2.4 Hz ), 3.38-3.48 (1H, m), 4.08-4.13 (2H, m), 4.36-4.73 (4H, m), 7.00 (1H, s)
MS (FAB ⁺ ); m / z 399 [M + 1] ⁺

Example 6 (1S, 5R, 6S) -2- (5-acetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5-acetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl-6-(( R) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -1-Methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1-triethylsiloxy Ethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl (277 mg, 0.46 mmol) in anhydrous methylene chloride (4 ml) under an argon atmosphere at 0 ° C. with N, N-diisopropylethylamine (0.15 ml) 0.95 mmol) and 46 μl (0.65 mmol) of acetyl chloride were added dropwise and stirred at the same temperature for 20 minutes. The reaction solution was diluted with methylene chloride, washed with half-saturated saline, and the organic layer was dried over anhydrous sodium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluting with chloroform: methanol = 49: 1) to obtain 292 mg (yield 99%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.65 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.20-1.26 (3H, m), 1.30 (3H, d, J = 6.4 Hz ), 2.17 (1.35H, s), 2.20 (1.65H, s), 2.84-2.95 (2H, m), 3.26-3.29 (1H, m), 3.50-3.61 (1H, m), 3.72-3.93 (2H , m), 4.25-4.32 (2H, m), 4.50-4.60 (1H, m), 4.66 (1H, s), 5.26 (1H, d, J = 13.9 H z), 5.50 (1H, d, J = 13.9 Hz), 7.30 (0.55H, s), 7.49 (0.45H, s), 7.66-7.71 (2H, m), 8.20-8.25 (2H, m)
MS (EI); m / z 639 M ⁺
(b) (1S, 5R, 6S) -2- (5-acetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(1S, 5R, 6S) -2- (5-acetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl-6-((R)- The title compound was obtained in the same manner as in Example 5 (b) using 4-nitrobenzyl 1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.0 Hz), 1.15 (3H, d, J = 6.3 Hz), 2.01 (1.5H, s), 2.05 (1.5H, s), 2.66-2.80 (2H, m), 3.27-3.31 (1H, m), 3.36-3.45 (1H, m), 3
.66 (2H, q, J = 6.0 Hz), 4.06-4.13 (2H, m), 4.40 (1H, s), 4.13 (1H, s), 6.94 (1H, s)
MS (FAB ⁺ ); m / z 413 [M + 1] ⁺

Example 7 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c]
Sodium pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl- 6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-
4-Nitrobenzyl carboxylate
(1S, 5R, 6S) -2- (5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl ) -1-Carbapent-2-em-3-carboxylic acid 4-nitrobenzyl 1.2 g (2.07 mmol) in anhydrous N, N-dimethylformamide 20 ml solution under argon atmosphere at room temperature 190 mg (2.50 mmol) hydroxyacetic acid 1-hydroxybenzotriazole 365 mg (2.70 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride 518 mg (2.70 mmol) were sequentially added, and the mixture was stirred for 30 minutes. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic layer was dried over anhydrous sodium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 49: 1) to give the title compound 1.2.
g (yield 92%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.65 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.24-1.28 (3H, m), 1.30 (3H, d, J = 6.0 Hz ), 3.29 (1H, dd, J = 5.4 and 2.5 Hz), 3.42-3.50 (1H, br s), 3.52-3.62 (1H, m), 4.20 (2H, s), 4.26-4.37 (2H, m) , 4.57-4.87 (4H, m), 5.22-5.30 (1H, m), 5.46-5.54 (1H, m), 7.47 (0.45H, s), 7.49 (0.55H, s), 7.69 (2H, d, J = 8.5 Hz), 8.22 (2H, d, J = 8.5 Hz)
MS (ESI ⁺ ); m / z 642 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6- ( (R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl 1.22 g (1.90 mmol) in tetrahydrofuran 30 ml and water 2 ml mixed with 1N hydrochloric acid 1.43 ml (1.43 mmol) was added dropwise, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with chloroform, washed with saturated brine, and the organic layer was dried over anhydrous sodium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 19: 1) to obtain 736 mg (yield 73%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 1.26-1.30 (3H, m), 1.40 (3H, d, J = 6.3 Hz), 1.80-1.85 (1H, br s), 3.31-3.36 (1H, m), 3.39-3.45 (1H, brs), 3.58-3.67 (1H, m), 4.20 (2H, s), 4.27-4.34 (2H, m), 4.50-4.88 (4H, m), 5.24-5.30 (1H, m ), 5.50-5.56 (1H, m), 7.48 (0.45H, s), 7.50 (0.55H, s), 7.68 (2H, d, J = 9.0 Hz), 8.24 (2H, d, J = 9.0 Hz)
MS (ESI ⁺ ); m / z 528 [M + 1] ⁺
(c) (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-
To a solution of nitrobenzyl 800 mg (1.52 mmol) in tetrahydrofuran 15 ml and 0.1 N phosphate buffer solution 15 ml, 10% palladium-carbon (water content 52% water) 800 mg was added and stirred at room temperature for 5 hours in a hydrogen atmosphere. . 10% Palladium-carbon was filtered using Celite, washed with water, and saturated aqueous sodium hydrogen carbonate was added to the filtrate to adjust the pH to 7.5. After washing with ethyl acetate, the aqueous layer was concentrated to about 5 ml and purified by Cosmosil 40C18-PREP column chromatography (eluting with water: methanol = 9: 1) to give the title compound 388 mg (yield 62% )
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.3 Hz), 1.16 (3H, d, J = 6.3 Hz), 3.29 (1H, dd, J = 6.1 and 2.4Hz), 3.36-3.46 (1H, m), 4.05-4.13 (2H, m), 4.16 (2H, s), 4.39-4.60 (4H, m), 7.97 (0.45H, s), 7.99 (0.55) H, s)
MS (FAB ⁺ ); m / z 415 [M + 1] ⁺

Example 8 (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate
(a) (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl ) -1-Carbapen-2-em-3-carboxylic acid 4-nitrobenzyl 1.40
g (2.40 mmol) was dissolved in 14 ml of N, N-dimethylformamide, and under an argon atmosphere, 256 mg (2.88 mmol) of ogitamic acid, 389 mg (2.88 mmol) of 1-hydroxybenzotriazole, and 1-ethyl-3- ( 3-Dimethylaminopropyl) carbodiimide hydrochloride 552 mg (2.88 mmol) was added and stirred at room temperature for 1 hour. Brine and aqueous sodium bicarbonate were added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layers were combined and washed 3 times with saturated brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with chloroform: ethyl acetate = 2: 1 to 1: 1) to give the title compound 1.03 g ( Yield 66%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.68 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.24-1.31 (6H, m), 3.28 (1H, dd, J = 5.9 and 2.7 Hz), 3.52-3.60 (1H, m), 4.27-4.34 (2H, m), 4.70-5.35 (5H, m), 5.49 (1H, d, J = 13.8 Hz), 5.56-5.65 (1H, m ), 7.40-7.50 (2H, m), 7.67 (2H, d, J = 8.7 Hz), 8.23 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid sodium salt
(1S, 5R, 6S) -2- (5- (2-Amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl 1N in a mixed solution of 1.03 g (1.57 mmol) of 4-nitrobenzyl 4-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate in 30 ml of tetrahydrofuran and 7 ml of water Hydrochloric acid 0.787 ml (0.787 mmol) was added dropwise. After stirring for 1 hour at room temperature, add 47 ml of 1/15 N phosphate buffer, add 1.33 g of 10% palladium-carbon (water content 52% water) to the solution, and stir for 1 hour at room temperature in a hydrogen atmosphere. did. 10% Palladium-carbon was filtered using Celite, washed with water, and saturated aqueous sodium hydrogen carbonate was added to the filtrate to adjust the pH to 6.9. After washing with ethyl acetate, the aqueous layer was concentrated to about 5 ml and purified by Cosmosil 40C18-PREP column chromatography (eluting with water: methanol = 20: 1) to give the title compound 457 mg (68% yield) )
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.21 (3H, d, J = 7.5 Hz), 1.31 (3H, d, J = 6.6 Hz), 3.40-3.62 (2H, m), 4.18-4.32 (2H, m), 4.60-5.10 (4H, m), 7.13 (0.5H, s), 7.16 (0.5H, s)
MS (FAB ⁺ ); m / z 428 [M + 1] ⁺

Example 9 (1S, 5R, 6S) -2- (5- (4,5-dihydrooxazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
M-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (N- (2-chloroethyl) carbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl ) -1-Carbapent-2-em-3-carboxylic acid 4-nitrobenzyl 281 mg (0.48 mmol) was dissolved in tetrahydrofuran 5 ml, and 0.045 ml (0.53) of 2-chloroethyl isocyanate at −30 ° C. under an argon atmosphere. mmol) was added. After stirring at the same temperature for 20 minutes, brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1 to ethyl acetate) to give 254 mg (yield) of the title compound. Rate 77%).
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.5 Hz), 0.95 (9H, t, J = 7.5 Hz), 1.20-1.35 (6H, m), 3.29 (1H, dd, J = 5.7 and 3.0 Hz), 3.50-3.72 (5H, m), 4.26-4.33 (2H, m), 4.56 (2H, s), 4.70-4.80 (3H, m), 5.26 (1H, d, J = 14.1 Hz), 5.50 (1H, d, J = 14.1 Hz), 7.47 (1H, s), 7.68 (2H, d, J = 9.0 Hz), 8.22 (2H, d, J = 9.0 Hz)
(b) (1S, 5R, 6S) -2- (5- (4,5-Dihydrooxazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5- (N- (2-Chloroethyl) carbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl In a mixed solution of 4-nitrobenzyl 254 mg (0.369 mmol) of 4-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate in 4 ml of tetrahydrofuran and 4 ml of water, N, N-diisopropylethylamine 0.077 ml (0.443 mmol) was added, and the mixture was stirred at 60 ° C. for 8 hours. Brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layers were combined and washed twice with brine. After drying over anhydrous magnesium sulfate, the residue obtained by distilling off the solvent was subjected to silica gel flash column chromatography (chloroform: methanol = 30: 1 to 20: 1).
The title compound 203 mg (yield 84%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.2 Hz), 0.95 (9H, t, J = 7.2 Hz), 1.20-1.35 (6H, m), 3.29 (1H, dd, J = 5.7 and 2.7 Hz), 3.50-3.62 (1H, m), 3.80-3.92 (2H, m), 4.24-4.43 (4H, m), 4.54-4.60 (2H, m), 4.70-4.76 (2H, m ), 5.26 (1H, d, J = 13.5 Hz), 5.50 (1H, d, J = 13.5 Hz), 7.45 (1H, s), 7.68 (2H, d, J = 8.7 Hz), 8.22 (2H, d , J = 8.7 Hz)
(c) (1S, 5R, 6S) -2- (5- (4,5-dihydrooxazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(1S, 5R, 6S) -2- (5- (4,5-Dihydrooxazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1 -Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-
The title compound was obtained in a similar manner to Example 5 (b) using 4-nitrobenzyl em-3-carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.20 (3H, d, J = 6.9 Hz), 1.31 (3H, d, J = 6.3 Hz), 3.40-3.50 (1H, m), 3.50-3.64 (1H, m), 3.92-4.05 (2H, m), 4.18-4.32 (2H, m), 4.60-4.70 (2H,
m), 7.14 (1H, s)

Example 10 (1S, 5R, 6S) -2- (5-formyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (5-Formyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R ) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl Acetic anhydride 0.066 ml (0.70 mmol) and formic acid 0.13 ml (3.4 mmol) were mixed and mixed at 50 ° C. Stir for 5 minutes. (1S, 5R, 6S) -2- (5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl ) Dissolve 273 mg (0.468 mmol) of 4-nitrobenzyl 4-carbapene-2-em-3-carboxylate in 5 ml of methylene chloride, add the above mixture at −40 ° C. under an argon atmosphere, and add −10 ° C. The mixture was stirred for 1 hour while heating up. Sodium bicarbonate water was added to the reaction solution, and the mixture was extracted twice with chloroform. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1 to ethyl acetate) to give 145 mg (yield) of the title compound. 51%).
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.5 Hz), 0.95 (9H, t, J = 7.5 Hz), 1.20-1.35 (6H, m
), 3.29 (1H, dd, J = 5.4 and 2.7 Hz), 3.50-3.62 (1H, m), 4.25-4.36 (2H, m), 4.60-4.93 (4H, m), 5.26 (1H, d, J = 13.8 Hz), 5.50 (1H, d, J = 13.8Hz), 7.45 (0.5H, s), 7.51 (0.
5H, s), 7.69 (2H, d, J = 8.7 Hz), 8.23 (2H, d, J = 8.7 Hz), 8.40 (1H, s)
(b) (1S, 5R, 6S) -2- (5-Formyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(1S, 5R, 6S) -2- (5-Formyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1 -Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 145 mg (0.237 mmol) was dissolved in 3 ml of tetrahydrofuran, 0.123 ml (1.08 mmol) of acetic acid and 1M tetrabutyl under argon atmosphere Ammonium fluoride tetrahydrofuran solution 0.356 ml (0.356 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Brine and aqueous sodium bicarbonate were added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The combined organic layers were washed twice with brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 30: 1). The fraction containing the desired product was concentrated and dried, and dissolved in a mixed solution of 7 ml of tetrahydrofuran and 7 ml of 1/15 N phosphate buffer. 200 mg of 10% palladium-carbon (hydrous water: 52%) was added, and the mixture was stirred at room temperature for 1 hour in a hydrogen atmosphere. 10% Palladium-carbon was filtered using Celite, washed with water, and saturated aqueous sodium hydrogen carbonate was added to the filtrate to adjust the pH to 7.1. After washing with ethyl acetate, the aqueous layer was concentrated to about 5 ml and purified by Cosmosil 40C18-PREP column chromatography (eluted with water: methanol = 20: 1) to give the title compound 65.6 mg (yield 72%) )
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.20 (3H, d, J = 7.2 Hz), 1.31 (3H, d, J = 6.3 Hz), 3.40-3.63 (2H, m), 4.20-4.30 (2H, m), 4.50-4.90 (4H, m), 7.14 (1H, s), 8.25 (1H, s)

Example 11 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (N-methylcarbamothioyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (N-methylcarbamothioyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl ) 1-Carbapen-2-em-3-carboxylic acid 4-nitrobenzyl (448 mg, 0.768 mmol) was dissolved in tetrahydrofuran (8 ml), and methyl isothiocyanate (67 mg, 0.92 mmol) was added under ice-cooling in an argon atmosphere. added. After stirring at the same temperature for 1 hour, brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the residue obtained by distilling off the solvent was subjected to silica gel flash column chromatography (hexane: ethyl acetate = 1: 3).
To elute at ˜1: 1) to give 354 mg (70% yield) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.1 Hz), 0.95 (9H, t, J = 8.1 Hz), 1.26 (3H, d, J = 6.9
Hz), 1.30 (3H, d, J = 6.3 Hz), 3.22 (3H, d, J = 4.2 Hz), 3.29 (1H, dd, J = 5.4 and 2.4Hz), 3.50-3.63 (1H, m), 4.25-4.36 (2H, m), 4.63-4.75 (2H, m), 4.75-5.10 (2H, m), 5.26 (1H, d, J = 14.1 Hz), 5.35-5.47 (1H, m), 5.50 ( 1H, d, J = 14.1 Hz), 7.48 (1H, s), 7.69 (2H, d, J = 8.1 Hz), 8.23 (2H, d, J = 8.1 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (N-methylcarbamothioyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium
(1S, 5R, 6S) -1-Methyl-2- (5- (N-methylcarbamothioyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 -((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-
The title compound was obtained in the same manner as in Example 5 (b) using 4-nitrobenzyl carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.80ppm): 1.19 (3H, d, J = 7.2 Hz), 1.32 (3H, d, J = 5.7 Hz), 3.03 (3H, s), 3.40- 3.47 (1H, m), 3.47-3.62 (1H, m), 4.20-4.30 (2H, m), 4.30-4.90 (4H, m), 7.11 (1H, s)
MS (FAB ⁺ ); m / z 430 [M + 1] ⁺

Example 12 (1S, 5R, 6S) -2- (5- (1-acetyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (N- (2-allyloxycarbonylaminoethyl) carbamothioyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole -2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5,6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl ) 1-Carbapen-2-em-3-carboxylic acid 4-nitrobenzyl 738 mg (1.27 mmol) in tetrahydrofuran 10 ml was cooled with ice in an argon atmosphere, and 2-allyloxycarbonylaminoethyl isothiocyanate 259 mg ( 1.39 mmol) was added. 30 at the same temperature
After stirring for 5 minutes, brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 3 to 1: 1) to give the title compound 892 mg ( Yield 92%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8 Hz), 1.20-1.35 (6H, m),
3.25-3.32 (1H, m), 3.45-3.65 (3H, m), 3.74-3.83 (2H, m), 4.25-4.40 (2H, m), 4.55-4.62 (2H, m), 5.18-5.36 (3H , m), 5.50 (1H, d, J = 13.8 Hz), 5.82-5.98 (1H, m), 6.88-6.96 (1H, m), 7.40-7.60 (1H, m), 7.69 (2H, d, J = 8.4 Hz), 8.23 (2H, d, J = 8.4 Hz)
(b) (1S, 5R, 6S) -2- (5-((2-allyloxycarbonylaminoethylimino) (ethylthio) methyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole -2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5- (N- (2-allyloxycarbonylaminoethyl) carbamothioyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-2- Yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl 892 mg (1.16 mmol) in acetone 6 ml solution in argon atmosphere Then, 1.85 ml (23.2 mmol) of ethyl iodide was added and stirred at 50 ° C. for 14 hours. Sodium bicarbonate water was added to the reaction solution, and the mixture was extracted twice with chloroform. After drying over anhydrous magnesium sulfate, the residue obtained by evaporating the solvent was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 30: 1) to give the title compound 890 mg (yield 96
%).
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.4 Hz), 0.95 (9H, t, J = 8.4 Hz), 1.22-1.35 (9H, m
), 2.82 (2H, q, J = 7.2 Hz), 3.28 (1H, dd, J = 5.7 and 2.7Hz), 3.32-3.43 (2H, m), 3.50-3.68 (3H, m), 4.25-4.35 ( 2H, m), 4.54-4.86 (6H, m), 5.20-5.37 (4H, m), 5.50 (1H, d,
J = 14.1 Hz), 5.85-6.00 (1H, m), 7.46 (1H, s), 7.68 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(c) (1S, 5R, 6S) -2- (5- (4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-Nitrobenzyl 2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
(1S, 5R, 6S) -2- (5-((2-allyloxycarbonylaminoethylimino) (ethylthio) methyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-2- Yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 890 mg (1.12 mmol) was dissolved in tetrahydrofuran 18 ml. Under an argon atmosphere, 88 mg (0.34 mmol) of triphenylphosphine, 234 mg (1.68 mmol) of dimedone and 517 mg (0.447 mmol) of tetrakistriphenylphosphine palladium (0) were added and stirred at room temperature for 1 hour. Sodium bicarbonate water was added to the reaction solution, and the mixture was extracted twice with chloroform. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by amino silica gel flash column chromatography (eluted with ethyl acetate-chloroform: methanol = 30: 1) to give 548 mg (yield) of the title compound. Rate 75%).
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.1 Hz), 0.95 (9H, t, J = 8.1 Hz), 1.26 (3H, d, J = 6.9 Hz), 1.30 (3H, d, J = 6.0 Hz), 3.28 (1H, dd, J = 5.7 and 2.4 Hz), 3.50-3.62 (1H, m),
3.65 (4H, s), 4.24-4.34 (2H, m), 4.52-4.62 (2H, m), 4.70-4.78 (2H, m), 5.25 (1H, d, J = 13.8 Hz), 5.49 (1H, d, J = 13.8 Hz), 7.46 (1H, s), 7.68 (2H, d, J = 8.7 Hz), 8.22 (2H,
d, J = 8.7 Hz)
(d) (1S, 5R, 6S) -2- (5- (1-acetyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5- (4,5-Dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl 167 mg (0.257 mmol) in methylene chloride 3 ml Under an atmosphere, 0.076 ml (0.44 mmol) of N, N-diisopropylethylamine and 0.029 ml (0.41 mmol) of acetyl chloride were added at −20 ° C., and the mixture was stirred at the same temperature for 1.5 hours. Sodium bicarbonate water was added to the reaction solution, and the mixture was extracted twice with chloroform. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was subjected to silica gel flash column chromatography (chloroform: methanol = 30
: Eluted with 1) to give 132 mg (yield 74%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.4Hz), 0.95 (9H, t, J = 8.4 Hz), 1.25 (3H, d, J = 7.5 Hz), 1.30 (3H, d, J = 6.0 Hz), 2.29 (3H, s), 3.27 (1H, dd, J = 5.7 and 2.7Hz), 3.50-3.60 (1H, m), 3.60-3.73 (2H, m), 3.88-3.97 (2H, m), 4.23-4.33 (2H, m), 4.62-4.68 (2H, m), 4.75-4.83 (2H, m), 5.25 (1H, d, J = 14.1 Hz), 5.49 (1H, d , J = 14.1Hz), 7.40 (1H,
s), 7.67 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(e) (1S, 5R, 6S) -2- (5- (1-acetyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(1S, 5R, 6S) -2- (5- (1-acetyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole 2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate, similar to Example 5 (b) To give the title compound.
¹ H-NMR (D ₂ O) δ (HOD = 4.80ppm): 1.18 (3H, d, J = 6.9 Hz), 1.29 (3H, d, J = 6.6 Hz), 2.37 (3H, s), 3.40- 3.60 (2H, m), 3.64-3.82 (2H, m), 4.15-4.34 (4H, m), 4.66 (2H, s), 7.10 (1H, s)
MS (FAB ⁺ ); m / z 445 [M + 1] ⁺

Example 13 (1S, 5R, 6S) -2- (5- (1-benzoyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (1-benzoyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (5- (4,5-Dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl 251 mg (0.386 mmol) in methylene chloride 5 ml Under an atmosphere, 0.107 ml (0.617 mmol) of N, N-diisopropylethylamine and 0.068 ml (0.578 mmol) of benzoyl chloride were added at −20 ° C., followed by stirring for 3 hours while raising the temperature to 0 ° C. Sodium bicarbonate water was added to the reaction solution, and the mixture was extracted twice with chloroform. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 30: 1) to give the title compound 160 mg (yield 55%) Got. ¹ H-NMR (CDCl ₃ ) δ: 0.60 (6H, q, J = 7.8Hz), 0.94 (9H, t, J = 7.8 Hz), 1.25 (3H, d, J = 7.2
Hz), 1.30 (3H, d, J = 6.0 Hz), 3.27 (1H, dd, J = 5.7 and 2.7Hz), 3.48-3.62 (1H, m), 3.62-3.73 (2H, m), 3.90-3.97 (2H, m), 4.23-4.35 (2H, m), 4.66-4.73 (2H, m), 4.75-4.88 (2H, m), 5.25 (1H, d, J = 13.8 Hz), 5.48 (1H, d , J = 13.8Hz), 7.40 (1H, s), 7.44-7.78 (7H, m), 8.22 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -2- (5- (1-Benzoyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(1S, 5R, 6S) -2- (5- (1-Benzoyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole 2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate using 4-nitrobenzyl and Example 5 (b) In a similar manner, the title compound was obtained.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.00 (3H, d, J = 7.1 Hz), 1.14 (3H, d, J = 6.3 Hz), 3.24-3.47 (2H, m), 3.59-3.67 (2H, m), 4.00-4.18 (4H, m), 4.45-4.60 (2H, m), 6.94 (1H, s), 7.38-7.70 (5H, m)
MS (FAB ⁺ ); m / z 507 [M + 1] ⁺
Example 14 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridine- 2-yl) -1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (tert-butyloxycarbonyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1- 4-nitrobenzyl methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-em-3-carboxylate
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 8.71 g (14.2 mmol) and 5- (tert-butyloxycarbonyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-ylboronic acid 2.92 g (10.3 mmol) in anhydrous tetrahydrofuran 100 To the ml solution, tris (dibenzylideneacetone) dipalladium (0) 2.80 g (3.10 mmol) at room temperature and 5.7 ml of a 5.4 M aqueous potassium hydroxide solution at −70 ° C. were sequentially added. After stirring at 45 ° C. for 3 hours, saturated brine was added, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was subjected to silica gel flash column chromatography (hexane: ethyl acetate = 7: 3
To obtain 1.36 g (yield 19%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.9 Hz), 1.24 (3H, d, J = 7.1 Hz), 1.29 (3H, d, J = 6.3 Hz), 1.49 (9H, s), 2.81-2.88 (2H, m), 3.26 (1H, dd, J = 6.0 and 2.7 Hz), 3.48-3.59 (1H, m), 3.68-3.76 (2H, m), 4.24-4.30 (2H, m), 4.47-4.51 (2H, m), 5.25 (1H, d, J = 3.9Hz), 5.50 (1H, d, J = 3.9 Hz), 7.26 (1H, s ), 7.68 (2H, d, J = 8.6 Hz), 8.22 (2H, d, J = 8.6 Hz)
MS (FAB ⁺ ); m / z 698 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridine- 2-yl) -1-carbapent-2-em-3-carboxylic acid 4-nitrobenzyl
A 4 M hydrochloric acid-1,4-dioxane solution (4.2 ml), 1,4-dioxane (8.7 ml) and water (0.9 ml) were cooled to 4 ° C. and cooled to (1S, 5R, 6S) -2- (5- (tert- Butyloxycarbonyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene A solution of 600 mg (0.860 mmol) of 4-nitrobenzyl 4-em-3-carboxylate in 3 ml of 1,4-dioxane was slowly added at the same temperature. After stirring at 10 ° C. for 1.5 hours, the reaction mixture was adjusted to pH 4 by adding 1 M aqueous sodium hydroxide solution. The residue obtained by evaporating the solvent was purified by silica gel flash column chromatography (eluted with methylene chloride: methanol = 7: 1) to obtain 220 mg (yield 53%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 6.6 Hz), 1.40 (3H, d, J = 6.1 Hz), 2.81-2.86 (2H, m), 3.18 (2H, br t, J = 5.9 Hz), 3.30 (1H, dd, J = 6.7 and 2.6 Hz), 3.57-3.62 (1H, m), 3.91-3.94 (2H, m), 4.25-4.32 (2H, m), 5.26 (1H , d, J = 14.0 Hz), 5.53 (1H, d, J = 14.0 Hz), 7.35 (1H, s), 7.68 (2H, d, J = 8.4 Hz), 8.23 (2H, d, J = 8.4 Hz )
MS (FAB ⁺ ); m / z 484 [M + 1] ⁺
(c) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridine- 2-yl) -1-carbapene-2-em-3-carboxylic acid
(1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl The title compound was obtained in the same manner as in Example 7 (c) using 4-nitrobenzyl) -1-carbapene-2-em-3-carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.1 Hz), 1.16 (3H, d, J = 6.3 Hz), 2.97
(2H, br t, J = 6.3 Hz), 3.31 (1H, br d, J = 6.6 Hz), 3.35-3.45 (3H, m), 4.07-4.14 (4H, m), 6.95 (1H, s)
MS (FAB ⁺ ); m / z 349 [M + 1] ⁺

Example 15 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4,5,6,7-
Tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4,5,6,7-tetrahydrothieno [3,2- c] Pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl ) -1-Carbapen-2-em-3-carboxylic acid 4-nitrobenzyl 173 mg (0.358 mmol) in anhydrous methylene chloride 3.6 ml and anhydrous methanol 3.6 ml in 37% formaldehyde aqueous solution 0.0872 ml (1.07 mmol), acetic acid 0.102 ml and 114 mg (0.537 mmol) of sodium triacetoxyborohydride were sequentially added at 4 ° C. and stirred at the same temperature for 50 minutes. Saturated aqueous sodium hydrogen carbonate was added to stop the reaction, and the mixture was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was subjected to silica gel flash column chromatography (methylene chloride:
Elution with methanol = 15: 1) to obtain 132 mg (yield 74%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 1.25 (3H, d, J = 7.3 Hz), 1.40 (3H, d, J = 6.1 Hz), 2.47 (3H, s), 2.70-2.78 (2H, m), 2.90-2.96 (2H, m), 3.29 (1H, dd, J = 6.8 and 2.3 Hz), 3.46-3.50 (2H, m), 3.59 (1H, dq, J = 9.1 and 7.3 Hz), 4.24 (1H , dd, J = 9.1 and 2.3 Hz), 4.29 (1H, dq, J = 6.8 and 6.1 Hz), 5.25 (1H, d, J = 13.8 Hz), 5.52 (1H, d, J = 13.8 Hz), 7.32 (1H, s), 7.67 (2H, d, J = 8.4 Hz), 8.23 (2H, d, J = 8.4 Hz)
MS (FAB ⁺ ); m / z 498 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4,5,6,7-tetrahydrothieno [3,2- c] Pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid
(1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5-methyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine The title compound was obtained in the same manner as in Example 7 (c) using 2-nitrobenzyl-2-yl) -1-carbapene-2-em-3-carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.21 (3H, d, J = 7.6 Hz), 1.33 (3H, d, J = 5.8 Hz), 3.01
(3H, s), 3.18 (2H, br t, J = 5.7 Hz), 3.31 (1H, br d, J = 5.8 Hz), 3.50-3.62 (3H, m), 4.20-4.34 (4H, m), 7.07 (1H, s)
MS (FAB ⁺ ); m / z 363 [M + 1] ⁺

Example 16 (1S, 5R, 6S) -2- (5- (4,5-dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl And 5- (4,5-dihydrothiazol-2-yl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole in the same manner as in Example 1. To give the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.55-0.64 (6H, m), 0.94 (9H, t, J = 7.8 Hz), 1.26 (3H, d, J = 7.3 Hz), 1.30 (3H, d, J = 6.3 Hz), 3.28 (1H, dd, J = 5.3 and 2.1 Hz), 3.39-3.45 (2H, m), 3.51-3.61 (1H, m), 4.09 (2H, t, J = 7.8Hz), 4.26 -4.33 (2H, m), 4.64-4.67 (2H, m), 4.79-4.83 (2H, m), 5.24 (1H, d, J = 14.2Hz), 5.49 (1H, d, J = 14.2 Hz), 7.45 (1H, s), 7.68 (2H, d,
J = 8.5 Hz), 8.22 (2H, d, J = 8.5 Hz)
MS (FAB ⁺ ); m / z 669 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (4,5-dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,
3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-
carboxylic acid
(1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1 Using 4-nitrobenzyl 4-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate in the same manner as in Example 5 (b), the title The compound of
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.0 Hz), 1.16 (3H, d, J = 6.3 Hz), 3.29-3.33 (1H, m), 3.42-3.57 (3H, m), 3.54 (2H, t, J = 7.8 Hz), 4.06-4.14 (2H, m), 4.40-4.80 (4H, m), 7.00 (1H, s)
MS (FAB ⁺ ); m / z 420 [M + 1] ⁺

Example 17 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-propionyl-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium The compound of Example 17 was synthesized in the same manner as Example 5.
(a) (1S, 5R, 6S) -1-Methyl-2- (5-propionyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.20-1.31 (9H, m), 2.37 (2H, q, J = 7.2 Hz ), 3.28-3.30 (1H, m), 3.52-3.60 (1H, m), 4.29-4.32 (2H, m), 4.63-4.66 (2H, br s), 4.77-4.81 (2H, brs), 5.24- 5.28 (1H, m), 5.47-5.52 (1H, m), 7.43 (0.4H, s), 7.52 (0.6H, s), 7.68 (2H, d, J = 8.4 Hz), 8.23 (2H, d, (J = 8.4 Hz)
MS (FAB ⁺ ); m / z 640 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-propionyl-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate ¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.95 (3H, t, J = 7.2 Hz), 1.03 (3H, d, J = 7.2 Hz), 1.15 (3H, d, J = 6.4 Hz), 2.25 (2H, q, J = 7.2 Hz), 3.26-3.28 (1H, m), 3.37-3.40 (1H , m), 4.03-4.10 (2H, m), 4.29-4.31 (1H, br s), 4.41-4.46 (2H, m), 4.50-4.53 (1H, m), 6.97 (1H, s)
MS (FAB ⁺ ); m / z 413 [M + 1] ⁺

Example 18 (1S, 5R, 6S) -2- (5- (2-ethoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium The compound of Example 18 was synthesized in the same manner as Example 8.
(a) (1S, 5R, 6S) -2- (5- (2-Ethoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl- 4-Nitrobenzyl 6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.6 Hz), 1.24-1.31 (9H, m), 3.28-3.30 (1H, m), 3.53 -3.59 (1H, m), 3.63 (2H, q, J = 6.8 Hz), 4.29-4.31 (2H, m), 4.67-4.72 (2H, m), 4.83-4.89 (2H, m), 5.24-5.31 (1H, m), 5.46-5.51 (1H, dd, m), 7.43 (0.4H, s), 7.50 (0.6H, s), 7.68 (2H, d, J = 8.4 Hz), 8.22 (2H, d , J = 8.4 Hz)
MS (FAB ⁺ ); m / z 670 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (2-Ethoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05-1.11 (6H, m), 1.16 (3H, d, J = 6.4 Hz), 3.29-3.31 (1H, m), 3.39-3.44 (1H, m), 3.51 (2H, q, J = 6.8 Hz), 4.06-4.10 (2H, m), 4.13 (2H, s), 4.40-4.43 (2H, m), 4.57-4.61 (2H, m ), 6.99 (0.5H, s), 7.01 (0.5H, s)
MS (FAB ⁺ ); m / z 443 [M + 1] ⁺

Example 19 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isobutyryl-5,6-dihydro-4H-thieno [2,3-c] pyrrole-2 -Yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium The compound of Example 19 was synthesized in the same manner as Example 5.
(a) (1S, 5R, 6S) -2- (5-isobutyryl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R ) -1-Triethylsiloxyethyl) -1-carbaben-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.66 (6H, m), 0.93 (9H, t, J = 8.0 Hz), 1.20 (6H, d, J = 6.8 Hz),
1.24-1.31 (6H, m), 2.67-2.81 (1H, m), 3.27-3.30 (1H, m), 3.52-3.60 (1H, m), 4.28-4.31 (2H, m), 4.62-4.87 (4H , m), 5.24-5.27 (1H, m), 5.47-5.52 (1H, m), 7.43 (0.4H, s),
7.52 (0.6H, s), 7.68 (2H, d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8 Hz)
MS (ESI ⁺ ); m / z 654 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isobutyryl-5,6-dihydro-4H-thieno [2,3-c] pyrrole-2 -Yl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.97 (6H, d, J = 6.4 Hz), 1.05 (3H, d, J = 7.2 Hz), 1.16 (3H, d, J = 6.4 Hz), 2.69-2.74 (1H, m), 3.30 (1H, dd, J = 6.4 and 2.4 Hz), 3.39-3.43 (1H, m), 4.06−4.13 (2H, m), 4.34-4.82 (4H, m), 6.99 (1H, s)
MS (FAB ⁺ ); m / z 427 [M + 1] ⁺

Example 20 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methylsulfonyl-5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium The compound of Example 20 was synthesized in the same manner as Example 6.
(a) (1S, 5R, 6S) -1-methyl-2- (5-methylsulfonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.26 (3H, d, J = 7.3 Hz), 1.29 (3H, d, J = 6.1 Hz), 2.91 (3H, s), 3.29 (1H, dd, J = 5.6 and 2.7 Hz), 3.51-3.59 (1H, m), 4.26-4.33 (2H, m), 4.55-4.58 (2H, m), 4.70-4.73 (2H, m), 5.26 (1H, d, J = 13.6
Hz), 5.49 (1H, d, J = 13.6 Hz), 7.43 (1H, s), 7.69 (2H, d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8 Hz)
MS (FAB ⁺ ); m / z 661 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methylsulfonyl-5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.3 Hz), 1.15 (3H, d, J = 6.3 Hz), 2.89 (3H, s), 3.29- 3.33 (1H, m), 3.38-3.47 (1H, m), 4.07-4.12 (2H, m), 4.37-4.41 (2H, m), 4.53-4.56 (2H, m), 6.97 (1H, s)
MS (FAB ⁺ ); m / z 435 [M + 1] ⁺

Example 21 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyacetyl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid The compound of Example 21 was synthesized in the same manner as Example 5.
(a) (1S, 5R, 6S) -2- (5- (2-methoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl- 4-Nitrobenzyl 6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.93 (9H, t, J = 8.0 Hz), 1.24-1.28 (3H, m), 1.30
(3H, d, J = 6.3 Hz), 3.29 (1H, dd, J = 5.6 and 2.7 Hz), 3.48 (3H, s), 3.48-3.56 (1H, m), 4.13-4.15 (2H, m), 4.28-4.31 (2H, m), 4.66-4.71 (2H, m), 4.83-4.86 (2H, m), 5.23-5.29 (1H, m), 5.46-4.53 (1H, m), 7.43 (0.4H, s), 7.49 (0.6H, s), 7.68 (2H, d, J = 8.8 Hz), 8.22 (2H, d, J = 8.8 Hz)
MS (ESI ⁺ ); m / z 656 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -2- (5- (2-methoxyacetyl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.3 Hz), 1.15 (3H, d, J = 6.3 Hz), 3.28-3.32 (4H, m), 3.38-3.47 (1H, m), 4.07-4.11 (4H, m), 4.42-4.46 (2H, m), 4.52-4.65 (2H,
m), 6.97 (0.5H, s), 7.06 (0.5H, s)
MS (FAB ⁺ ); m / z 407 [M + 1] ⁺

The compounds of Examples 22 to 24 were synthesized in the same manner as Example 8.

Example 22 (1S, 5R, 6S) -2- (5- (2-acetamidoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium salt
(a) (1S, 5R, 6S) -2- (5- (2-Acetamidoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1- Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-em-3-
4-Nitrobenzyl carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.26 (3H, d, J = 7.2 Hz),
1.30 (3H, d, J = 6.4 Hz), 2.08 (3H, s), 3.30 (1H, dd, J = 5.6and 2.6 Hz), 3.53-3.62 (1H, m), 4.10 (2H, d, J = 4.2 Hz), 4.25-4.34 (2H, m), 4.60-4.83 (4H, m), 5.27 (1H, d, J = 13.7 Hz), 5.51 (1H, d, J = 13.7 Hz), 6.59 (1H, t, J = 4.2 Hz), 7.46 (1H, s), 7.69 (2H,
d, J = 8.7 Hz), 8.23 (2H, d, J = 8.7 Hz)
MS (FAB ⁺ ); m / z 683 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (2-Acetamidoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.2 Hz), 1.16 (3H, d, J = 6.1 Hz), 1.93 (3H, s), 3.29- 3.33 (1H, m), 3.38-3.48 (1H, m), 3.87-3.99 (2H, m), 4.07-4.14 (2H, m), 4.40-4.65 (4H, m), 7.00 (1H, s)
MS (FAB ⁺ ); m / z 456 [M + 1] ⁺

Example 23 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-hydroxy-2-methylpropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (5- (2-hydroxy-2-methylpropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.26 (3H, d, J = 6.9 Hz), 1.30 (3H, d, J = 6.1 Hz), 1.54 (6H, s), 3.30 (1H, dd, J = 5.6 and 2.7 Hz), 3.50-3.62 (1H, m), 4.28-4.33 (2H, m), 4.60-5.08 (4H, m), 5.26 (1H, d, J = 13.9 Hz), 5.49 (1H, d, J = 13.9 Hz), 7.45 (0.45H, s), 7.49 (0.55H, s), 7.68 (2H, d, J = 9.0 Hz), 8.22 (2H, d, J = 9.0 Hz)
MS (ESI ⁺ ); m / z 670 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-hydroxy-2-methylpropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.08 (3H, d, J = 7.1 Hz), 1.17 (3H, d, J = 6.4 Hz), 1.34 (
6H, s), 3.32 (1H, dd, J = 7.1 and 2.4 Hz), 3.39-3.48 (1H, m), 4.08-4.15 (2H, m), 4.47-5.01 (4H, m), 6.99 (0.45H , s), 7.01 (0.55H, s)
MS (FAB ⁺ ); m / z 443 [M + 1] ⁺

Example 24 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-methoxypropanoyl) -5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (3-methoxypropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.65 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.26 (3H, d, J = 7.3 Hz), 1.30 (3H, d, J = 6.1 Hz), 2.62 (2H, t, J = 6.3 Hz), 3.30 (1H, dd, J = 5.6 and 2.7 Hz), 3.37 (3H, s), 3.52-3.61 (1H, m), 3.78 (2H , t, J = 6.3 Hz), 4.27-4.33 (2H, m), 4.63-4.88 (4H, m), 5.26-5.29 (1H, m), 5.50 (1H, d, J = 14.0 Hz), 6.59 ( 1H, t, 4.2 Hz), 7.44 (0.45H, s), 7.50 (0.55H, s), 7.69 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
MS (ESI ⁺ ); m / z 670 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-methoxypropanoyl) -5,6-
Sodium dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.0 Hz), 1.17 (3H, d, J = 6.3 Hz), 2.55 (2H, t, J = 6.0 Hz), 3.22 (3H, s), 3.30 (1H, dd, J = 6.2 and 2.3 Hz), 3.37-3.46 (1H, m),
3.62 (2H, t, J = 6.0 Hz), 4.05-4.14 (2H, m), 4.35-4.73 (4H, m), 6.99 (1H, s)
MS (FAB ⁺ ); m / z 443 [M + 1] ⁺

Example 25 (1S, 5R, 6S) -2- (5-cyclopropanecarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid The compound of Example 25 was synthesized in the same manner as Example 5.
(a) (1S, 5R, 6S) -2- (5-cyclopropanecarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6- ( (R) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.63 (6H, m), 0.84-0.87 (2H, m), 0.94 (9H, t, J = 7.7 Hz), 1.06-1.08 (2H, m), 1.24 -1.31 (6H, m), 1.60-1.69 (1H, m), 3.27-3.30 (1H, dd, J = 5.6 and 2.6 Hz), 3.50-3.65 (1H, m), 4.28-4.31 (2H, m) , 4.64-4.68 (2H, m), 4.83-5.03 (2H, m), 5.24-5.29 (1H, m), 5.46-5.52 (1H, m), 7.42 (0.4H, s), 7.53 (0.6H , s), 7.68 (2H, d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8 Hz)
MS (ESI ⁺ ); m / z 652 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-cyclopropanecarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.76-0.82 (4H, m), 1.06 (3H, d, J = 7.3 Hz), 1.16 (3H, d, J = 6.3 Hz), 1.68-1.76 (1H, m), 3.30 (1H, d, J = 6.4 Hz), 3.39-3.46 (1H, m), 4.06-4.13 (2H, m), 4.38-4.88 (4H, m), 6.99 ( 0.5H, s), 7.01 (0.5H, s)
MS (FAB ⁺ ); m / z 403 [M + 1] ⁺

The compounds of Examples 26 to 30 were synthesized in the same manner as Example 8.

Example 26 (1S, 5R, 6S) -2- (5-((S) -2-acetamidopropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5-((S) -2-acetamidopropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-2- Yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-
M-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.65 (6H, m), 0.95 (9H, t, J = 7.9 Hz), 1.27 (3H, d, J = 7.3 Hz), 1.30 (3H, d, J = 6.1 Hz), 1.42 (3H, d, J = 6.9 Hz), 2.02 (3H, s), 3.30 (1H, dd, J = 5.5
and 2.5 Hz), 3.53-3.63 (1H, m), 4.26-4.35 (2H, m), 4.58-5.14 (5H, m), 5.27 (1H, d,
J = 13.9 Hz), 5.47-5.53 (1H, m), 6.72-6.82 (1H, m), 7.46 (0.55H, s), 7.47 (0.45H, s),
7.69 (2H, d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8 Hz)
MS (ESI ⁺ ); m / z 697 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-((S) -2-Acetamidepropanoyl) -5,6-dihydro-4H-thieno- [2,3-c] pyrrole-2 -Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-
Sodium carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.1 Hz), 1.16 (3H, d, J = 6.3 Hz), 1.23 (3H, d, J = 6.8 Hz), 1.86 (3H, s), 3.29-3.32 (1H, m), 3.39-3.48 (1H, m), 4.07-4.14 (2H,
m), 4.38-4.96 (5H, m), 6.56 (1H, s)
MS (FAB ⁺ ); m / z 470 [M + 1] ⁺

Example 27 (1S, 5R, 6S) -2- (5-((R) -2-acetamidopropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5-((R) -2-acetamidopropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-2- Yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-
M-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.21 (3H, d, J = 7.3 Hz), 1.30 (3H, d, J = 6.1 Hz), 1.40 (3H, d, J = 6.9 Hz), 2.02 (3H, s), 3.29 (1H, dd, J = 5.6
and 2.6 Hz), 3.52-3.61 (1H, m), 4.27-4.34 (2H, m), 4.56-5.10 (5H, m), 5.27 (1H, d,
J = 13.9 Hz), 5.50 (1H, d, J = 13.9 Hz), 6.38-6.45 (1H, m), 7.44 (0.55H, s), 7.47 (0.45H, s), 7.69 (2H, d, J = 8.7 Hz), 8.23 (2H, d, J = 8.7 Hz)
MS (ESI ⁺ ); m / z 697 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-((R) -2-acetamidopropanoyl) -5,6-dihydro-4H-thieno- [2,3-c] pyrrole-2 -Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-
Sodium carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.0 Hz), 1.16 (3H, d, J = 6.4 Hz), 1.23 (3H, d, J = 7.1 Hz), 1.86 (3H, s), 3.31 (1H, dd, J = 6.4 and 2.4 Hz), 3.38-3.48 (1H, m),
4.07-4.14 (2H, m), 4.41-4.96 (5H, m), 7.00 (1H, s)
MS (FAB ⁺ ); m / z 470 [M + 1] ⁺

Example 28 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (4-methylthiazole-5-carbonyl) -5,6-dihydro- 4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (4-methylthiazole-5-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-2 -Yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.1 Hz), 1.26 (3H, d, J = 7.3 Hz), 1.30 (3H, d, J = 6.1 Hz), 2.62 (3H, s), 3.30 (1H, dd, J = 5.4 and 1.7 Hz), 3.50-3.63 (1H, m), 4.27-4.34 (2H, m), 4.61-5.03 (4H, m), 5.26 (1H, d, J = 13.8 Hz), 5.50 (1H, d, J = 13.8 Hz), 6.38-6.45 (1H, m), 7.44 (0.5H, s), 7.49 (0.5H, s ), 7.69 (2H, d, J = 8.7
Hz), 8.23 (2H, d, J = 8.7 Hz), 8.80 (1H, s)
MS (ESI ⁺ ); m / z 709 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (4-methylthiazole-5
-Carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, t, J = 7.3 Hz), 1.15 (1.5H, d, J = 6.3 Hz), 1.17 (1.5H, d, J = 6.3 Hz), 2.34 (3H, s), 3.29-3.33 (1H, m), 3.37-3.49 (1H, m), 4.06-4.15 (2H, m), 4.46-4.78 (4H, m), 6.93 ( 0.5H, s), 7.04 (0.5H, s), 8.90 (1H, s)
MS (FAB ⁺ ); m / z 482 [M + 1] ⁺

Example 29 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (thiazole-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -1-methyl-2- (5- (thiazol-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.1 Hz), 1.25-1.32 (6H, m), 3.29 (1H, dd, J = 5.4 and 2.7 Hz), 3.53-3.62 (1H, m), 4.28-4.33 (2H, m), 4.87-4.90 (1H, m), 5.03-5.05 (1H, m), 5.24-5.30 (1H, m), 5.32 -5.35 (1H, m), 5.43-5.53 (2H, m), 7.51 (0.4H, s), 7.52 (0.6H, s), 7.59-7.61 (1H, m), 7.69 (2H, d, J = 8.7 Hz), 7.97-7.99 (1H, m), 8.23 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (thiazol-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.04 (3H, d, J = 6.6 Hz), 1.17 (3H, d, J = 6.3 Hz), 3.24-3.30 (1H, m), 3.33-3.45 (1H, m), 4.01-4.13 (2H, m), 4.50-5.06 (4H, m), 6.98-7.0 (1H, m), 7.65-7.70 (1H, m), 7.82-7.86 (1H , m)
MS (FAB ⁺ ); m / z 446 [M + 1] ⁺

Example 30 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (thiazole-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -1-methyl-2- (5- (thiazol-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.25-1.32 (6H, m), 3.25-3.31 (1H, m), 3.50 -3.61 (1H, m), 4.28-4.32 (2H, m), 4.87-4.90 (1H, m), 5.02-5.05 (1H, m), 5.21-5.24 (1H, m), 5.24-5.29 (1H, m), 5.37-5.41 (1H, m), 5.47-5.53 (1H, m), 7.48-7.51 (1H, m), 7.69 (2H, d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8 Hz), 8.28-8.30 (1H, m),
8.83-8.85 (1H, m)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (thiazole-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.04-1.08 (3H, m), 1.14-1.17 (3H, m), 3.28-3.32 (1H, m), 4.06-4.12 (1H, m), 4.03-4.11 (2H, m), 4.65-4.92 (4H, m), 6.97 (0.5H, s), 7.04 (0.5H, s), 8.04-8.06 (1H, m), 8.91-8.94 ( 1H, m)
MS (FAB ⁺ ); m / z 446 [M + 1] ⁺

The compounds of Examples 31 to 33 were synthesized in the same manner as Example 7.

Example 31 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (oxazole-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (oxazol-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.55-0.65 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.25-1.32 (6H, m), 1.44-1.47 (1H, m), 3.29 (1H, dd, J = 6.2and 2.5 Hz), 3.52-3.63 (1H, m), 4.27-4.33 (2H, m), 4.82-4.84 (1H, m), 4.97-5.00 (1H, m), 5.15 -5.21 (1H, m), 5.25-5.30 (1H, m), 5.34-5.53 (2H, m), 7.49 (1H, s), 7.59 (0.6H, d, J = 8.8 Hz), 7.69 (1.4H , d, J = 8.8 Hz), 7.92 (1H, s), 8.23 (1.4H, d, J = 8.8 Hz), 8.26 (0.6H, d, J = 8.8 Hz), 8.35-8.37 (1H, m)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (oxazole-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.27-1.32 (3H, m), 1.41 (3H, d, J = 6.1 Hz), 3.33 (1H, dd, J = 6.3 and 2.1 Hz), 3.60-3.69 (1H , m), 4.27-4.35 (2H, m), 4.83-4.85 (1H, m), 4.98-5.00 (1H, m), 5.19-5.22 (1H, m), 5.27 (1H, d, J = 13.7 Hz ), 5.36-5.39 (1H, m), 5.50-5.56 (1H, m),
7.49-7.52 (1H, m), 7.69 (2H, d, J = 8.8 Hz), 7.92-7.93 (1H, m), 8.24 (2H, d, J = 8.8Hz), 8.35-8.37 (1H, m)
(c) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (oxazole-4-carbonyl) -5,6-dihydro-4 H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.3 Hz), 1.17 (3H, d, J = 6.6 Hz), 3.30 (1H, dd, J = 6.1 and 2.2Hz), 3.38-3.48 (1H, m), 4.05-4.15 (2H, m), 4.54-4.56 (1H, m),
4.70-4.99 (3H, m), 7.02 (1H, s), 8.09-8.12 (1H, m), 8.29-8.32 (1H, m)
MS (FAB ⁺ ); m / z 452 [M + 1] ⁺

Example 32 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-4-carbonyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (1-methyl-1H-imidazole-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] 4-Pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.24-1.32 (6H, m), 3.28 (1H, dd, J = 5.6 and 2.7 Hz), 3.53-3.63 (1H, m), 3.76 (3H, s), 4.26-4.33 (2H, m), 4.82-4.85 (1H, m), 4.97-5.00 (1H, m), 5.24-5.29 (2H, m), 5.42-5.45 (1H, m), 5.46-5.53 (1H, m), 7.43-7.44 (1H, m), 7.47 (0.5H, s), 7.51 (0.5H, s), 7.67 (1H, s), 7.68 (2H, d, J = 8.8Hz), 8.23 (2H, d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-4-carbonyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.27-1.31 (3H, m), 1.41 (3H, d, J = 6.3 Hz), 1.77-1.82 (1H, m), 3.31-3.34 (1H, m), 3.48 -3.50 (1H, m), 3.76 (3H, s), 4.28-4.33 (2H, m), 4.82-4.84 (1H, m), 4.97-5.00 (1H, m), 5.24-5.30 (2H, m) , 5.43-5.46 (1H, m), 5.50-5.56 (1H, m), 7.42-7.45 (1H, m), 7.47 (0.5H, s), 7.52 (0.5H, s), 7.66-7.71 (3H, m), 8.23 (2H, d, J = 8.8 Hz)
(c) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-4-carbonyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.01-1.05 (3H, m), 1.17 (3H, d, J = 6.1 Hz), 3.24-3.28 (1H, m), 3.33-3.43 (1H, m), 3.57 (1.5H, s), 3.58 (1.5H, s), 3.92-4.02 (1H, m), 4.05-4.14 (1H, m), 4.43-4.47 (1H, m), 4.60 -4.81 (3H, m), 6.96-6.99 (1H, m), 7.48-7.52 (2H, m)
MS (FAB ⁺ ); m / z 443 [M + 1] ⁺

Example 33 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-2-carbonyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -1-methyl-2- (5- (1-methyl-1H-imidazol-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] 4-Pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
¹ H -NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.25-1.32 (6H, m), 3.27-3.31 (1H, m), 3.52 -3.62 (1H, m), 4.02 (1.5H, s), 4.03 (1.5H, s), 4.27-4.32 (2H, m),
4.81-4.83 (1H, m), 4.96-4.99 (1H, m), 5.24-5.29 (2H, m), 5.41-5.45 (1H, m), 5.46-5.54 (1H, m), 6.99 (1H, s ), 7.11 (1H, s), 7.43 (0.5H, s), 7.54 (0.5H, s), 7.69 (2H, d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-2-carbonyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl ester
¹ H-NMR (CDCl ₃ ) δ: 1.27-1.31 (3H, m), 1.41 (3H, d, J = 6.3 Hz), 3.31-3.36 (1H, m), 3.59-3.69 (1H, m), 4.03 (1.5H, s), 4.04 (1.5H, s), 4.28-4.33 (2H, m), 4.82-4.84 (1H, m), 4.97-4.99 (1H, m), 5.24-5.30 (2H, m) , 5.43-5.46 (1H, m), 5.50-5.57 (1H, m), 7.00 (1H,
s), 7.11 (1H, s), 7.44 (0.5H, s), 7.56 (0.5H, s), 7.69 (2H, d, J = 8.8 Hz), 8.24 (2H,
d, J = 8.8 Hz)
(c) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-2-carbonyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.04-1.10 (3H, m), 1.16 (3H, d, J = 6.4 Hz), 3.29-3.34 (1H, m), 3.36-3.50 (1H, m), 3.68 (3H, s), 4.05-4.15 (2H, m), 4.56-4.95 (4H, m), 6.97-7.06 (2H, m), 7.10 (1H, s)
MS (FAB ⁺ ); m / z 443 [M + 1] ⁺

The compounds of Examples 34 to 36 were synthesized in the same manner as Example 8.

Example 34 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-3-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
(a) (1S, 5R, 6S) -1-methyl-2- (5- (pyridin-3-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-
4-Nitrobenzyl carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.92-1.00 (9H, m), 1.23-1.31 (6H, m), 3.27-3.32 (1H, m), 3.50-3.62 ( 1H, m), 4.27-4.35 (2H, m), 4.62-5.05 (4H, m), 5.25 (0.6H, d, J = 13.8 Hz), 5.23-5.28 (1H, m), 5.46-5.52 (1H , m), 7.40 (0.6H, s), 7.41-7.45 (1H, m),
7.50 (0.4H, s), 7.68 (2H, d, J = 8.8 Hz), 7.91 (1H, dt, J = 7.8 and 1.7 Hz), 8.22 (2H, d, J = 8.8 Hz), 8.72 (1H, dd, J = 4.9 and 1.7 Hz), 8.84 (1H, d, J = 1.7 Hz)
MS (ESI ⁺ ); m / z 689 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-3-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (1.5H, d, J = 7.3 Hz), 1.07 (1.5H, d, J = 7.3 Hz), 1.15 (1.5H, d, J = 6.3 Hz), 1.16 (1.5H, d, J = 6.3 Hz), 3.28-3.34 (1H, m), 3.35-3.50 (1H, m), 4.06-4.13 (2H, m), 4.47-4.80 ( 4H, m), 6.92 (0.5H, s), 7.05 (0.5H, s), 7.43-7.47 (1H, m), 7.89-7.93 (1H, m), 8.53 (1H, dd, J = 5.0 and 1.6 Hz), 8.57-8.59 (1H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 35 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (pyridin-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-
4-Nitrobenzyl carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.65 (6H, m), 0.92-0.97 (9H, m), 1.23-1.32 (6H, m), 3.28-3.32 (1H, m), 3.50-3.62 ( 1H, m), 4.27-4.35 (2H, m), 4.54-5.02 (4H, m), 5.22-5.28 (1H, m),
5.45-5.51 (1H, m), 7.40 (0.55H, s), 7.38-7.40 (2H, m), 7.50 (0.45H, s), 7.68 (2H, d,
J = 8.3 Hz), 8.22 (2H, d, J = 8.7 Hz), 8.74-8.77 (2H, m)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.08-1.22 (3H, m), 1.29 (3H, d, J = 6.3 Hz), 3.38-3.58 (2H, m), 4.10-4.27 (2H, m), 4.38-4.75 (4H, m), 7.02 (0.5H, s), 7.15 (0.5H, s), 7.52-7.58 (2H, m), 8.62-8.72 (2H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 36 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (pyridin-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-
4-Nitrobenzyl carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.1 Hz), 0.95 (9H, t, J = 8.1 Hz), 1.20-1.35 (6H, m),
3.26-3.32 (1H, m), 3.50-3.65 (1H, m), 4.25-4.36 (2H, m), 4.88-5.55 (6H, m), 7.38-7.43 (1H, m), 7.45 (0.5H, s), 7.51 (0.5H, s), 7.68 (2H, d, J = 8.7 Hz), 7.82-7.88 (1H, m), 7.96-8.04 (1H, m), 8.22 (2H, d, J = 8.7 Hz), 8.62-8.66 (1H, m)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.14-1.23 (3H, m), 1.30 (3H, d, J = 6.3 Hz), 3.40-3.63 (2H, m), 4.16-4.28 (2H, m), 4.57-4.95 (4H, m), 7.04 (0.5H, s), 7.17 (0.5H, s), 7.55-7.73 (2H, m), 8.00-8.07 (1H, m), 8.57 -8.64 (1H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

The compounds of Examples 37 to 38 were synthesized in the same manner as Example 5.

Example 37 (1S, 5R, 6S) -2- (5- (furan-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c]
Sodium pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (furan-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl -6-((R) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate sodium 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.62 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.24-1.31 (6H, m), 3.28-3.30 (1H, dd, J = 5.6 and 2.7 Hz), 3.50-3.65 (1H, m), 4.28-4.31 (2H, m), 4.83-5.02 (2H, m), 5.08-5.30 (3H, m), 5.48-5.53 (1H, m) , 6.55 (1H, dd, J = 3.4 and 1.7 Hz), 7.21-7.24 (1H, m), 7.47 (0.4H, s), 7.53 (0.6H, s), 7.57 (1H, s), 7.68 (2H , d, J = 8.7 Hz), 8
.23 (2H, d, J = 8.7 Hz)
MS (ESI ⁺ ); m / z 678 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (furan-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.04-1.08 (3H, m), 1.23 (3H, d, J = 6.3 Hz), 3.25-3.30 (1H, m), 3.33-3.38 (1H, m), 3.99-4.05 (1H, m), 4.11-4.17 (1H, m), 4.49-4.95 (4H, m), 6.49-6.54 (1H, m), 6.95-7.05 (2H, m) , 7.59 (1H, d, J = 3.7 Hz)
MS (FAB ⁺ ); m / z 451 [M + 1] ⁺

Example 38 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (thiophen-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (thiophen-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.0 Hz), 0.95 (9H, t, J = 8.0 Hz), 1.27 (3H, d, J = 7.2
Hz), 1.30 (3H, d, J = 6.0 Hz), 3.29 (1H, dd, J = 5.6 and 2.8 Hz), 3.51-3.63 (1H, m), 4.26-4.34 (2H, m), 4.85-5.18 (4H, m), 5.26 (1H, d, J = 14.4 Hz), 5.50 (1H, d, J = 14.4Hz), 7.13-7.16 (1H, m), 7.46-7.66 (3H, m), 7.69 ( 2H, d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8
Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (thiophen-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.11-1.18 (3H, m), 1.30 (3H, d, J = 6.6 Hz), 3.35-3.50 (2H, m), 4.00-4.10 (1H, m), 4.15-4.26 (1H, m), 4.50-5.00 (4H, m), 7.08-7.20 (2H, m), 7.58-7.70 (2H, m)
MS (FAB ⁺ ); m / z 467 [M + 1] ⁺

The compounds of Examples 39 to 41 were synthesized in the same manner as Example 8.

Example 39 (1S, 5R, 6S) -2- (5- (3-acetamidopropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate
(a) (1S, 5R, 6S) -2- (5- (3-acetamidopropanoyl) -5,6-dihydro-4H-thieno [2,3-c]
Pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.27 (3H, d, J = 7.1 Hz), 1.30 (3H, d, J = 6.1 Hz), 1.97 (3H, s), 2.57 (2H, t, J = 5.0 Hz), 3.30 (1H, dd, J = 5.6
and 2.6 Hz), 3.52-3.64 (3H, m), 4.30-4.38 (2H, m), 4.57-4.86 (4H, m), 5.26 (1H, d,
J = 13.9 Hz), 5.50 (1H, d, J = 13.9 Hz), 6.47-6.55 (1H, m), 7.47 (1H, s), 7.69 (2H, d, J = 8.8 Hz), 8.23 (2H, d, J = 8.8 Hz)
MS (ESI ⁺ ); m / z 697 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (3-Acetamidepropanoyl) -5,6-dihydro-4H-thieno [2,3-c]
Sodium pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.3 Hz), 1.17 (3H, d, J = 6.4 Hz), 1.81 (3H, s), 2.51 ( 2H, t, J = 6.4Hz), 3.30-3.37 (3H, m), 3.40-3.49 (1H, m), 4.07-4.15 (2H,
m), 4.39-4.65 (4H, m), 7.00 (1H, s)
MS (FAB ⁺ ); m / z 470 ([M + 1] ⁺ )

Example 40 (1S, 5R, 6S) -2- (5-((S) -1-acetylpyrrolidine-2-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-2 -Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5-((S) -1-acetylpyrrolidine-2-carbonyl) -5,6-dihydro-4H-
Thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.25 (3H, d, J = 7.0 Hz),
1.30 (3H, d, J = 6.1 Hz), 1.98-2.38 (7H, m), 3.29 (1H, dd, J = 5.5 and 2.6 Hz), 3.52-3.62 (2H, m), 3.70-3.78 (1H, m), 4.28-4.35 (2H, m), 4.54-4.90 (5H, m), 5.26 (1H, d, J = 13.8 Hz), 5.42-5.49 (1H, m), 7.44 (0.45H, s), 7.48 (0.55H, s), 7.70 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
MS (ESI ⁺ ); m / z 723 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-((S) -1-acetylpyrrolidine-2-carbonyl) -5,6-dihydro-4H-
Thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.1 Hz), 1.17 (3H, d, J = 6.4 Hz), 1.80-2.40 (7H, m), 3.31 (1H, dd, J = 6.1 and 2.1 Hz), 3.39-3.47 (1H, m), 3.53 (2H, t, J = 6.7 Hz), 4.08-4.15 (2H, m), 4.35-4.95 (5H, m), 7.00 (0.45H, s), 7.02 (0.55H, s)
MS (FAB ⁺ ); m / z 496 [M + 1] ⁺

Example 41 (1S, 5R, 6S) -2- (5-((S) -2-Acetamido-3-methylbutanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5-((S) -2-Acetamido-3-methylbutanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-Nitrobenzyl 2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.65 (6H, m), 0.95 (9H, t, J = 7.9 Hz), 1.01 (6H, d, J = 5.6 Hz),
1.26 (3H, d, J = 7.0 Hz), 1.30 (3H, d, J = 6.0 Hz), 2.00-2.14 (4H, m), 3.30 (1H, dd, J = 5.5 and 2.6 Hz), 3.52-3.61 (1H, m), 4.25-4.35 (2H, m), 4.57-5.52 (7H, m), 6.50-6.56 (1H, m), 7.44 (0.5H, s), 7.48 (0.5 H, s), 7.69 (2H, d, J = 8.5 Hz), 8.23 (2H, d, J = 8.5
Hz)
MS (FAB ⁺ ); m / z 725 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-((S) -2-Acetamido-3-methylbutanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
Em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.84 (3H, d, J = 7.0 Hz), 0.87 (3H, d, J = 7.0 Hz), 1.09 (3H, d, J = 6.8 Hz), 1.19 (3H, d, J = 6.3 Hz), 1.88-2.00 (4H, m), 3.31-3.35 (1H, m), 3.41-3.50 (1H, m), 4.09-4.16 (2H, m) , 4.22-4.98 (5H, m), 7.02 (1H, s)
MS (FAB ⁺ ); m / z 498 [M + 1] ⁺

Example 42 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid The compound of Example 42 was synthesized in the same manner as Example 15.
(a) (1S, 5R, 6S) -1-Methyl-2- (5-methyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole-2-
Yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (3H, t, J = 8.0 Hz), 1.23-1.41 (6H, m), 2.64 (3H, s), 3.25-3.28 (1H, m), 3.50-3.59 (1H, m), 3.82-3.86 (2H, m), 3.97-4.01 (2H, m), 4.22-4.32 (2H, m), 5.25 (1H, d, J = 14.0 Hz), 5.49 (1H, d, J = 14.0 Hz), 7.44 (1H, s),
7.68 (2H, d, J = 8.8 Hz), 8.22 (2H, d, J = 8.8 Hz)
MS (FAB ⁺ ); m / z 598 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
MS (FAB ⁺ ); m / z 399 [M + 1] ⁺

Example 43 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-methoxycarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium The compound of Example 43 was synthesized in the same manner as Example 6.
(a) (1S, 5R, 6S) -2- (5-methoxycarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-(( R) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.23-1.28 (3H, m), 1.30 (3H, d, J = 6.3 Hz ), 3.28 (1H, dd, J = 5.8 and 2.7 Hz), 3.49-3.61 (1H, m), 3.78 (3H, s), 4.27-4.33 (2H, m), 4.51-4.55 (1H, m), 4.57-4.61 (1H, m), 4.67-4.70 (1H, m), 4.72-4.75 (1H, m), 5.25 (2H, d, J = 14.0 Hz), 5.49 (2H, d, J = 14.0 Hz), 7.44 (0.5H, s), 7.47 (0.5H, s), 7.68 (2H, d, J = 8.8 Hz), 8.22 (2H, d, J = 8.8 Hz)
MS (ESI ⁺ ); m / z 642 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-methoxycarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.02 (3H, d, J = 7.1 Hz), 1.16 (3H, d, J = 6.1 Hz), 3.23-3.27 (1H, m), 3.29-3.40 (1H, m), 3.57 (3H, s), 4.00-4.41 (6H, m), 6.89 (0.5H, s), 6.92 (0.5H, s)
MS (FAB ⁺ ); m / z 415 [M + 1] ⁺

Example 44 (1S, 5R, 6S) -2- (5- (2-amino-2-oxoethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (2-amino-2-oxoethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1 4-Nitrobenzyl 4-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-em-3-carboxylate
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl To a suspension of 583 mg (0.381 mmol) and potassium carbonate 138 mg (0.572 mmol) in anhydrous N, N-dimethylformamide was added 185 mg (0.495 mmol) of iodoacetamide under an argon atmosphere and stirred at the same temperature for 15 hours. . The reaction mixture was diluted with ethyl acetate, washed with half-saturated brine three times, and the organic layer was dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluted with methylene chloride: methanol = 19: 1) to obtain 101 mg (yield 41%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.23-1.31 (6H, m), 3.26-3.29 (1H, m), 3.49 -3.60 (3H, m), 3.98-4.02 (2H, m), 4.13-4.16 (2H, m), 4.25-4.33 (2H, m), 5.25 (1H, d, J = 14.0Hz), 5.49 (1H , d, J = 14.0 Hz), 7.53 (0.4H, s), 7.56 (0.6H,
s), 7.66-7.70 (2H, m), 8.20-8.25 (2H, m)
MS (ESI ⁺ ); m / z 641 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (2-amino-2-oxoethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 -((R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(1S, 5R, 6S) -2- (5- (2-Amino-2-oxoethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl- 6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-
The title compound was obtained in the same manner as in Example 5 (b) using 4-nitrobenzyl carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.6 Hz), 1.15 (3H, d, J = 6.8 Hz), 3.29-3.33 (1H, m), 3.37-3.47 (1H, m), 3.73-3.78 (2H, m), 4.05-4.12 (4H, m), 4.21-4.26 (2H,
m), 6.97 (1H, s)
MS (FAB ⁺ ); m / z 392 [M + 1] ⁺

Example 45 (1S, 5R, 6S) -2- (5-cyclopropyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid The compound of Example 45 was synthesized in the same manner as Example 15.
(a) (1S, 5R, 6S) -2- (5-Cyclopropyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-(( R) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.52-0.64 (10H, m), 0.95 (9H, t, J = 7.8 Hz), 1.24 (3H, d, J = 7.3 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.13-2.19 (1H, m), 3.26 (1H, dd, J = 5.8 and 2.7 Hz), 3.50-3.60 (1H, m), 3.95-3.98 (2H, m), 4.11-4.14 ( 2H, m), 4.24-4.32 (2H, m), 5.25 (1H, d, J = 13.6 Hz), 5.49 (1H, d, J = 13.6 Hz), 7.43 (1H, s), 7.67 (2H, d , J = 8.8 Hz), 8.22 (2H,
d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -2- (5-cyclopropyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.40-0.52 (4H, m), 1.04 (3H, d, J = 7.3 Hz), 1.15 (3H, d, J = 6.3 Hz), 2.26-2.32 (1H, m), 3.29 (1H, dd, J = 6.3 and 2.4 Hz), 3.35-3.45 (1H, m),
3.87-3.90 (2H, m), 4.02-4.13 (4H, m), 6.95 (1H, s)
MS (FAB ⁺ ); m / z 375 [M + 1] ⁺

Example 46 (1S, 5R, 6S) -2- (5-cyanomethyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid The compound of Example 46 was synthesized in the same manner as Example 44.
(a) (1S, 5R, 6S) -2- (5-Cyanomethyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R ) -1-Triethylsiloxyethyl) -1-carbaben-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.26 (3H, d, J = 7.3 Hz), 1.30 (3H, d, J = 6.1 Hz), 3.28 (1H, dd, J = 5.6 and 2.4 Hz), 3.48-3.59 (1H, m), 3.83 (2H, s), 4.01-4.05 (2H, m), 4.17-4.20 (2H, m), 4.26-4.33 (2H, m), 5.25 (1H, d, J = 13.6
Hz), 5.49 (1H, d, J = 13.6 Hz), 7.44 (1H, s), 7.6 8 (2H, d, J = 8.5 Hz), 8.23 (2H, d, J = 8.5 Hz)
(b) (1S, 5R, 6S) -2- (5-cyanomethyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.1 Hz), 1.16 (3H, d, J = 6.3 Hz), 3.28-3.34 (1H, m), 3.40-3.49 (1H, m), 3.80-3.87 (4H, m), 3.38-4.01 (2H, m), 4.07-4.12 (2H,
m), 5.29 (1H, s)
MS (ESI ⁺ ); m / z 374 [M + 1] ⁺

The compounds of Examples 47 to 51 were synthesized in the same manner as Example 6.

Example 47 (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -5,6-dihydro-4H-thieno [2,3
-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-
M-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.24-1.32 (6H, m), 2.35 (6H, s), 3.16 (2H , s), 3.28 (1H, dd, J = 5.8 and 2.9 Hz), 3.49-3.61 (1H, m), 4.27-4.32 (2H, m), 4.65-4.68 (1H, m), 4.76-4.85 (2H , m), 4.93-4.96 (1H, m), 5.23-5.29 (1H, m), 5.47-5.52 (1H, m), 7.44 (0.5H, s), 7.50 (0.5H, s), 7.69 (2H , d, J = 8.5 Hz), 8.23 (2H, d, J = 8.5 Hz)
(b) (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 6.8 Hz), 1.16 (3H, d, J = 6.3 Hz), 2.82-2.89 (8H, m), 3.30-3.34 (1H, m), 3.39-3.49 (1H, m), 4.07-4.16 (4H, m), 4.43-4.50 (2H,
m), 6.99-7.02 (1H, m)
MS (FAB ⁺ ); m / z 420 [M + 1] ⁺

Example 48 (1S, 5R, 6S) -2- (5- (N, N-dimethylsulfamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid sodium salt
(a) (1S, 5R, 6S) -2- (5- (N, N-dimethylsulfamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid-4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.63 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.24-1.30 (6H, m), 2.84 (6H, s), 3.27-3.31 (1H, m), 3.51-3.59 (1H, m), 4.26-4.31 (1H, m), 4.2-4.55 (2H, m), 4.66-4.70 (2H, m), 5.25 (1H, d, J = 13.9 Hz), 5.48 (1H, d, J = 13.9 Hz), 7.41 (1H, s), 7.68 (2H, d, J = 8.5 Hz), 8.23 (2H, d, J = 8.5 Hz)
MS (ESI ⁺ ); m / z 691 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (N, N-dimethylsulfamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.3 Hz), 1.15 (3H, d, J = 6.4 Hz), 2.71 (6H, s), 3.30 ( 1H, dd, J = 6.3and 2.4 Hz), 3.38-3.46 (1H, m), 4.08-4.12 (2H, m), 4.42-4.46 (2H, m), 4.52-4.65 (2H, m), 6.96 ( 1H, s)
MS (FAB ⁺ ); m / z 464 [M + 1] ⁺

Example 49 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-hydroxypropanoyl) -5,6-dihydro-4H-thieno- [2, 3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (3-hydroxypropanoyl) -5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -1- 4-nitrobenzyl methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 15.6 Hz), 1.24-1.28 (3H, m), 1.30 (3H, d, J = 6.0 Hz ), 2.59 (2H, br t, J = 5.2 Hz), 3.29 (1H, dd, J = 5.6 and 2.4 Hz), 3.50-3.60 (1H, m), 3.96 (2H, t, J = 5.2 Hz), 4.27-4.32 (2H, m), 4.62 -4.68 (2H, m), 4.78-4.82 (2H, m), 5.23-5.29 (1H, m), 5.47-5.52 (1H, m), 7.44 (0.47H, s), 7.50 (0.53H, s), 7.68 (2H, d, J = 8.6 Hz), 8.23 (2H, d, J = 8.6 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-hydroxypropanoyl) -5,6-dihydro-4H-thieno- [2, 3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.2 Hz), 1.17 (3H, d, J = 6.4 Hz), 2.55 (2H, t, J = 6.1 Hz), 3.32 (1H, dd, J = 6.4 and 2.4 Hz), 3.44 (1H, br sex, J = 6.8 Hz), 3.
77 (2H, t, J = 6.1 Hz), 4.07-4.15 (2H, m), 4.41-4.78 (4H, m), 7.01 (1H, s)
MS (FAB ⁺ ); m / z 429 [M + 1] ⁺

Example 50 (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-
Sodium carboxylate
(a) (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c]
Pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.60 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8 Hz), 1.25 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 6.0 Hz), 2.92 (6H, s), 3.27 (1H, dd, J = 5.7 and 2.7 Hz), 3.50-3.60 (1H, m), 4.24-4.35 (2H, m), 4.61 (2H , s), 4.78 (2H, s), 5.25 (1H, d, J = 13.8 Hz),
5.49 (1H, d, J = 13.8 Hz), 7.45 (1H, s), 7.68 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c]
Sodium pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.00 (3H, d, J = 7.2 Hz), 1.13 (3H, d, J = 6.3 Hz), 2.70 (6H, s), 3.24 ( 1H, dd, J = 6.6 and 2.4Hz), 3.28-3.40 (1H, m), 3.98-4.10 (2H, m), 4.28 (2H, s), 4.34-4.54 (2H, m), 6.89 (1H, s)

Example 51 (1S, 5R, 6S) -2- (5- (2-cyanoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (2-cyanoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl- 4-Nitrobenzyl 6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8 Hz), 1.20-1.34 (6H, m),
3.29 (1H, dd, J = 5.4 and 2.7 Hz), 3.50-3.60 (3H, m), 4.25-4.36 (2H, m), 4.62-4.92 (4H, m), 5.26 (1H, d, J = 13.5 Hz), 5.49 (1H, d, J = 13.5 Hz), 7.44 (0.5H, s), 7.49 (0.5H,
s), 7.68 (2H, d, J = 8.4 Hz), 8.23 (2H, d, J = 8.4 Hz)
(b) (1S, 5R, 6S) -2- (5- (2-cyanoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.19 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 6.3 Hz), 3.40-3.60 (2H, m), 4.14-4.28 (2H, m), 4.48-4.90 (6H, m), 7.12 (1H, s)

Example 52 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethoxy) carbonyl-5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate The compound of Example 52 was synthesized in the same manner as Example 5.
(a) (1S, 5R, 6S) -2- (5- (2-methoxyethoxy) carbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-
M-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8 Hz), 1.22-1.33 (6H, m
), 3.28 (1H, dd, J = 5.4 and 2.4 Hz), 3.41 (3H, s), 3.50-3.67 (3H, m), 4.25-4.35 (4H,
m), 4.55-4.62 (2H, m), 4.70-4.78 (2H, m), 5.26 (1H, d, J = 13.8 Hz), 5.49 (1H, d, J = 13.8 Hz), 7.44 (1H, s ), 7.68 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethoxy) carbonyl-5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.22-1.33 (3H, m), 1.40 (3H, d, J = 6.3 Hz), 3.32 (1H, dd, J = 6.9 and 2.7 Hz), 3.41 (3H, s ), 3.60-3.68 (4H, m), 4.26-4.36 (4H, m), 4.58 (2H, s), 4.74 (1H, s), 5.26 (1H, d, J = 14.1 Hz), 5.53 (1H, d, J = 14.1 Hz), 7.45 (1H, s), 7.68 (2H, d, J = 9.0 Hz), 8.23 (2H, d, J = 9.0 Hz)
(c) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethoxy) carbonyl-5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80ppm): 1.19 (3H, d, J = 7.2 Hz), 1.31 (3H, d, J = 6.3 Hz), 3.42 (3H, s), 3.42- 3.60 (2H, m), 3.70-3.78 (2H, m), 4.16-4.32 (4H, m), 4.36-4.70 (4H, m), 7.08 (0.5H, s), 7.10 (0.5H, s)
MS (FAB ⁺ ); m / z 459 [M + 1] ⁺

The compounds of Examples 53 to 54 were synthesized in the same manner as Example 6.

Example 53 (1S, 5R, 6S) -2- (5- (2-N, N-dimethylamino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (2-N, N-dimethylamino-2-oxoacetyl) -5,6-dihydro-4H-
Thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.4 Hz), 0.95 (9H, t, J = 8.4 Hz), 1.20-1.35 (6H, m),
3.04 (3H, s), 3.08 (3H, s), 3.29 (1H, dd, J = 5.7 and 2.7 Hz), 3.50-3.65 (1H, m), 4.25-4.38 (2H, m), 4.68-4.76 ( 2H, m), 4.83-4.92 (2H, m), 5.20-5.55 (2H, m), 7.42 (0.5H, s), 7.47 (0.5H, s), 7.68 (2H, d, J = 8.1 Hz) , 8.22 (2H, d, J = 8.1 Hz)
(b) (1S, 5R, 6S) -2- (5- (2-N, N-dimethylamino-2-oxoacetyl) -5,6-dihydro-4H-
Thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.21 (3H, d, J = 6.9 Hz), 1.31 (3H, d, J = 6.3 Hz), 3.04 (3H, s), 3.08 ( 3H, s), 3.44-3.66 (2H, m), 4.20-4.30 (2H, m), 4.64-4.70 (2H, m), 4.81-4.86 (2H, m), 7.13 (0.5H, s), 7.18 (0.5H, s)
MS (FAB ⁺ ); m / z 456 [M + 1] ⁺

Example 54 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2-N-phenylamino-2-oxoacetyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (2-N-phenylamino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] 4-Pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.1 Hz), 0.95 (9H, t, J = 8.1 Hz), 1.22-1.35 (6H, m),
3.29 (1H, dd, J = 5.4 and 2.4 Hz), 3.50-3.64 (1H, m), 4.25-4.35 (2H, m), 4.80 (1H, s), 4.95 (1H, s), 5.20-5.45 ( 3H, m), 5.50 (1H, d, J = 14.1 Hz), 7.15-7.23 (1H, m), 7.35-7.73 (7H, m), 8.23 (2H, d, J = 8.7 Hz), 9.46 (1H , s)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2-N-phenylamino-2-oxoacetyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.13 (3H, d, J = 6.3 Hz), 1.23-1.35 (3H, m), 3.32-3.50 (2H, m), 3.96-4.20 (2H, m), 4.50-5.12 (4H, m), 7.00-7.23 (2H, m), 7.30-7.52 (4H, m)
MS (FAB ⁺ ); m / z 504 [M + 1] ⁺

The compounds of Examples 55 to 56 were synthesized in the same manner as Example 8.

Example 55 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-((S) -2-hydroxypropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (5-((S) -2-hydroxypropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-
M-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.4 Hz), 0.95 (9H, t, J = 8.4 Hz), 1.20-1.35 (6H, m),
1.42 (3H, d, J = 6.9 Hz), 3.29 (1H, dd, J = 5.7 and 2.7 Hz), 3.50-3.62 (1H, m), 4.25-4.43 (3H, m), 4.55-4.97 (4H, m), 5.20-5.28 (1H, m), 5.44-5.53 (1H, m), 7.45 (0.5H, s),
7.50 (0.5H, s), 7.68 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-((S) -2-hydroxypropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.80ppm): 1.20 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 6.3 Hz), 1.38 (3H, d, J = 6.6 Hz), 3.40-3.63 (2H, m), 4.20-4.30 (2H, m), 4.46-4.95 (5H, m), 7.13 (1H,
s)
MS (FAB ⁺ ); m / z 429 [M + 1] ⁺

Example 56 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2-N-methylamino-2-oxoacetyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (2-N-methylamino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] 4-Pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8 Hz), 1.27 (3H, d, J = 7.3
Hz), 1.30 (3H, d, J = 6.1 Hz), 2.92 (3H, d, J = 5.4 Hz), 3.29 (1H, dd, J = 5.6 and 2.7 Hz), 3.52-3.62 (1H, m), 4.26-4.33 (2H, m), 4.73 (1H, s), 4.88 (1H, s), 5.21 (1H, s), 5.26 (1H, d, J = 13.9 Hz), 5.36 (1H, s), 5.50 (1H, d, J = 13.9 Hz), 7.42 (0.5H, s), 7.50 (0.5H, s), 7.58-7.64 (1H, m), 7.68 (2H, d, J = 8.7 Hz), 8.23 ( (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2-N-methylamino-2-
Oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80ppm): 1.20 (3H, d, J = 7.2 Hz), 1.31 (3H, d, J = 6.3 Hz), 2.84 (3H, s), 3.40- 3.64 (2H, m), 4.16-4.32 (2H, m), 4.55-5.14 (4H, m), 7.11 (0.5H, s), 7.14 (0.5H, s)
MS (FAB ⁺ ); m / z 442 [M + 1] ⁺

Example 57 (1S, 5R, 6S) -2- (5- (2-acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid The compound of Example 57 was synthesized in the same manner as Example 5.
(a) (1S, 5R, 6S) -2- (5- (2-acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.30 (3H, m), 1.40 (3H, d, J = 6.3 Hz), 1.70-1.73 (1H, m), 2.21 (3H, s), 3.33 (1H , dd, J = 7.2and 2.7 Hz), 3.57-3.67 (1H, m), 4.28-4.34 (2H, m), 4.65-4.69 (2H, m), 4.71 (2H, s), 4.81-4.85 (2H) , m), 5.24-5.29 (1H, m), 5.50-5.56 (1H, m), 7.45 (0.4H, s), 7.51 (0.6H, s), 7.69 (2H, d, J = 8.8 Hz), 8.24 (2H, d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -2- (5- (2-acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.0 Hz), 1.16 (3H, d, J = 6.3 Hz), 2.06 (3H, s), 3.30 ( 1H, dd, J = 6.3 and 2.4 Hz), 3.37-3.47 (1H, m), 4.05-4.13 (2H, m), 4.40-4.43 (1H, m), 4.50-4.53 (1H, m), 4.55- 4.59 (1H, m), 4.64-4.67 (1H, m), 4.69 (2H, s),
6.99-7.01 (1H, m)
MS (FAB ⁺ ); m / z 435 [M + 1] ⁺

The compounds of Examples 58 to 61 were synthesized in the same manner as Example 8.

Example 58 (1S, 5R, 6S) -2- (5- (2-acetamidoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate
(a) (1S, 5R, 6S) -2- (5- (2-Acetamidoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1 4-Nitrobenzyl 4-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.22-1.26 (3H, m), 1.30 (3H, d, J = 6.1 Hz ), 2.06 (3H, s), 2.88-2.97 (2H, m), 3.28 (1H, dt, J = 5.6 and 2.7 Hz), 3.49-3.58 (1H, m), 3.71 (1H, t, J = 5.7 Hz), 3.96 (1H, q, J = 5.7 Hz), 4.13 (1H, d,
J = 5.7 Hz), 4.16 (1H, d, J = 5.7 Hz), 4.25-4.33 (2H, m), 4.44-4.54 (1H, m), 4.68 (1H, s), 5.26 (1H, d, J = 13.9 Hz), 5.49 (1H, d, J = 13.9 Hz), 6.58-6.65 (1H, m), 7.34 (0.5H,
s), 7.36 (0.5H, s), 7.66-7.71 (1H, m), 8.23 (2H, d, J = 8.5 Hz)
MS (ESI ⁺ ); m / z 697 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (2-Acetamidoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c]
Pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.0 Hz), 1.17 (3H, d, J = 6.3 Hz), 1.90 (1.2H, s), 1.92 (1.8H, s), 2.70-2.83 (2H, m), 3.30 (1H, dd, J = 6.1 and 2.0 Hz), 3.37-3.46 (1H, m), 3.63 (1H, t, J = 6.0 Hz) , 3.72 (1H, t, J = 6.0 Hz), 4.01-4.14 (4H, m), 4.42-4.46 (2H, m), 6.97 (1H, s)
MS (FAB ⁺ ); m / z 470 [M + 1] ⁺

Example 59 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyacetyl) -4,5,6,7-tetrahydrothieno [3,2 -c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (2-methoxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.65 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.25 (3H, d, J = 7.4 Hz), 1.30 (3H, d, J = 6.1 Hz), 2.87-2.96 (2H, m), 3.27 (1H, dd, J = 5.7 and 2.5 Hz), 3.44 (3H, s), 3.46-3.60 (1H, m), 3.78 (1H, t, J = 5.7 Hz), 3.88-3.97 (1H, m), 4.17 (0.8H, s), 4.20 (1.2H, s), 4.25-4.33 (2H, m), 4.56-4.68 (2H, m), 5.27 (1H, d, J = 13.9 Hz), 5.49 (1H, d, J = 13.9 Hz), 6.58-6.65 (1H, m), 7.31 (0.6H, s), 7.44 (0.4H, s), 7.66- 7.71 (2H, m), 8.23 (2H, d, J = 8.6 Hz)
MS (ESI ⁺ ); m / z 670 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyacetyl) -4,5,6,7-
Sodium tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.04 (3H, d, J = 7.1 Hz), 1.17 (3H, d, J = 6.3 Hz), 2.60-
2.81 (2H, m), 3.26-3.31 (4H, m), 3.35-3.44 (1H, m), 3.51 (1H, t, J = 5.7 Hz), 3.59-3.77 (1H, m), 4.04-4.13 ( 2H, m), 4.16-4.21 (2H, s), 4.29-4.41 (2H, m), 6.92 (0.45H, s), 6.94 (0.55H, s)
MS (FAB ⁺ ); m / z 443 [M + 1] ⁺

Example 60 (1S, 5R, 6S) -2- (5- (3-acetamidopropanoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid sodium salt
(a) (1S, 5R, 6S) -2- (5- (3-Acetamidepropanoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl)- 1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-
M-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.22-1.26 (3H, m), 1.30 (3H, d, J = 6.1 Hz ), 1.94 (1.35H, s), 1.95 (1.65H, s), 2.57-2.65 (2H, m), 2.85-2.94 (2H, m), 3.25-3.28 (1H, m), 3.49-3.61 (3H , m), 3.70-3.94 (2H, m), 4.25-4.31 (2H, m), 4.48-4.67 (2H, m), 5.26 (1H, d, J = 14.1 Hz), 5.49 (1H, d, J = 14.1Hz), 6.33-6.38 (1H, m), 7.34 (0.55H, s), 7.36 (0.45H, s), 7.66-7.71 (2H, m), 8.23 (2H, d, J = 8.3 Hz)
MS (FAB ⁺ ); m / z 711 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (3-Acetamidopropanoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.0 Hz), 1.16 (3H, d, J = 6.3 Hz), 1.51 (1.65H, s), 1.79 (1.35H, s), 2.50-2.79 (4H, m), 3.26-3.46 (4H, m), 3.62-3.75 (2H, m),
4.06-4.14 (2H, m), 4.40-4.48 (2H, m), 6.95 (1H, s)
MS (FAB ⁺ ); m / z 484 [M + 1] ⁺

Example 61 (1S, 5R, 6S) -2- (5- (2-ethoxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (5- (2-Ethoxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.65 (6H, m), 0.95 (9H, t, J = 8.0 Hz), 1.20-1.28 (6H, m), 1.30 (3H, d, J = 6.1 Hz ), 2.87-2.97 (2H, m), 3.29 (1H, dd, J = 5.6 and 2.6 Hz), 3.50-3.56 (3H, m), 3.81 (1H, t, J = 5.6 Hz), 3.89-3.95 ( 1H, m), 4.20-4.32 (4H, m), 4.60-4.65 (2H, m), 5.26 (1H, d, J = 13.9 Hz), 5.50 (1H, d, J = 13.9 Hz), 7.32 (0.6 H, s), 7.44 (0.4H, s), 7.69 (2H, d, J = 8.6 Hz), 8.22 (2H, d, J = 8.6 Hz)
MS (FAB ⁺ ); m / z 684 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (2-Ethoxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.03-1.09 (6H, m), 1.16 (3H, d, J = 6.3 Hz), 2.67-2.78 (2H, m), 3.29 (1H , dd, J = 6.4 and 2.5 Hz), 3.36-3.50 (3H, m), 3.54 (1H, t, J = 5.7 Hz),
3.62-3.74 (1H, m), 4.05-4.13 (2H, m), 4.19 (0.9H, s), 4.25 (1.1H, s), 4.33-4.41 (2H,
m), 6.93 (0.45H, s), 6.95 (0.55 H, s)
MS (FAB ⁺ ); m / z 457 [M + 1] ⁺

Example 62 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate The compound of Example 62 was synthesized in the same manner as Example 6.
(a) (1S, 5R, 6S) -2- (5- (2-tert-butyldimethylsiloxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) 4-Nitrobenzyl-1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
_{^{1 H-NMR (CDCl 3)}} δ: 0.09 (2.4H, s), 0.12 (3.6H, s), 0.61 (6H, q, J = 7.5 Hz), 0.80-1.00 (18H, m), 1.24 (3H , d, J = 7.5 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.83-2.98 (2H, m), 3.27 (1H, dd, J = 5.7 and 2.4 Hz), 3.48-3.60 (1H, m), 3.80-3.94 (2H, m), 4.23-4.40 (4H, m), 4.63 (2H, s), 5.26 (1H, d, J = 13.8 Hz), 5.50 (1H, d, J = 13.8 Hz) ), 7.30 (0.6H, s), 7.40 (0.4H, s), 7.69 (2H, d, J = 8.4 Hz), 8.22 (2H, d, J = 8.4 Hz)
(b) (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -4,5,6,7-tetrahydrothieno [3,2-c]
Pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.19 (3H, d, J = 6.9 Hz), 1.31 (3H, d, J = 6.3 Hz), 2.80-2.94 (2H, m), 3.40-3.88 (4H, m), 4.18-4.28 (2H, m), 4.37 (0.8H, s), 4.43 (2H, s), 4.56 (1.2H, s), 7.07 (0.4H, s), 7.10 (0.6H, s)

Example 63 (1S, 5R, 6S) -2- (5- (4,5-dihydrooxazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid The compound of Example 63 was synthesized in the same manner as Example 9.
(a) (1S, 5R, 6S) -2- (5- (N- (2-chloroethyl) carbamoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8 Hz), 1.25 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.86-2.94 (2H, m), 3.27 (1H, dd, J = 5.7 and 3.0 Hz), 3.48-3.78 (7H, m), 4.24-4.34 (2H, m), 4.47 (2H, s), 4.92-5.00 (1H, m), 5.25 (1H, d, J = 14.1 Hz), 5.49 (1H, d, J = 14.1 Hz), 7.40 (1H, s), 7.68 (2H, d, J = 9.0 Hz), 8.22 (2H, d, J = 9.0 Hz)
(b) (1S, 5R, 6S) -2- (5- (4,5-Dihydrooxazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2- Yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.63 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8 Hz), 1.24 (3H, d, J = 7.5
Hz), 1.30 (3H, d, J = 6.3 Hz), 2.86-2.94 (2H, m), 3.26 (1H, dd, J = 5.7 and 2.4 Hz), 3.48-3.60 (1H, m), 3.68-3.86 (4H, m), 4.22-4.38 (4H, m), 4.48 (2H, s), 5.25 (1H, d, J = 13.8 Hz), 5.48 (1H, d, J = 13.8 Hz), 7.31 (1H, s), 7.67 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(c) (1S, 5R, 6S) -2- (5- (4,5-Dihydrooxazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
M-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.05-1.38 (6H, m), 2.50-3.00 (2H, m), 3.35-4.90 (12H, m), 6.95 (0.3H, s ), 7.07 (0.4H, s), 7.27 (0.3H, s)
MS (FAB ⁺ ); m / z 418 [M + 1] ⁺

The compounds of Examples 64-66 were synthesized in the same manner as Example 6.

Example 64 (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6 -((R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1 -Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapen-2-
M-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.5Hz), 0.95 (9H, t, J = 7.5 Hz), 1.25 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 6.0 Hz), 2.87 (6H, s), 2.90-2.98 (2H, m), 3.26 (1H, dd, J = 5.7 and2.4 Hz), 3.48-3.60 (3H, m), 4.23- 4.35 (4H, m), 5.25 (1H, d, J = 14.1 Hz), 5.50 (1H, d, J = 14.1 Hz), 7.38 (1H, s), 7.68 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6 -((R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.19 (3H, d, J = 7.2 Hz), 1.31 (3H, d, J = 6.3 Hz), 2.80-2.90 (8H, m), 3.40-3.60 (4H, m), 4.18-4.30 (4H, m), 7.05 (1H, s)
MS (FAB ⁺ ); m / z 442 [M + 1] ⁺

Example 65 (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl ) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.5 Hz), 0.95 (9H, t, J = 7.5 Hz), 1.20-1.36 (6H, m), 2.29 (6H, s), 2.80-2.97 (2H, m), 3.17-3.22 (2H, m), 3.27 (1H, dd, J = 5.7 and 2.7 Hz), 3.50-3.60 (1H, m), 3.82-3.90 (2H, m), 4.22-4.35 (2H, m), 4.60-4.73 (2H, m), 5.26 (1H, d, J = 14.1 Hz), 5.50 (1H, d, J = 14.1 Hz), 7.30 (0.6H, s), 7.46 (0.4H, s), 7.69 (2H, d, J = 7.5 Hz), 8.22 (2H, d, J = 7.5 Hz)
(b) (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.18 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.80-2.97 (8H, m), 3.40-3.93 (4H, m), 4.16-4.30 (4H, m), 4.47 (1H, s), 4.57 (1H, s), 7.06 (0.5H, s), 7.09 (0.5H, s)
MS (FAB ⁺ ); m / z 434 [M + 1] ⁺

Example 66 (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.4 Hz), 0.95 (9H, t, J = 8.4 Hz), 1.25 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.90-3.06 (2H, m), 3.28 (1H, dd, J = 6.0 and 2.7 Hz), 3.47-3.58 (1H, m), 3.90-4.00 (1H, m), 4.24 -4.34 (3H, m), 4.68 (1H, s), 5.12 (1H, s), 5.26 (1H, d, J = 14.1 Hz), 5.49 (1H, d, J = 14.1 Hz), 5.80-5.90 ( 1H, m), 7.08-7.20 (1H, m), 7.34 (0.5H, s), 7.36 (0.5H, s), 7.68 (2H, d, J = 9.0 Hz), 8.22 (2H, d, J = 9.0 Hz)
(b) (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.20 (3H, d, J = 7.5 Hz), 1.30 (3H, d, J = 6.3 Hz), 2.87-3.00 (2H, m), 3.40-3.62 (2H, m), 3.78-3.93 (2H, m), 4.20-4.30 (2H, m), 4.58-4.65 (2H,
m), 7.06 (0.4H, s), 7.12 (0.6H, s)
MS (FAB ⁺ ); m / z 442 [M + 1] ⁺

Example 67 (1S, 5R, 6S) -2- (6-acetyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine-2
-Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate The compound of Example 67 was synthesized in the same manner as Example 5.
(a) (1S, 5R, 6S) -2- (6-Acetyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl-6-(( R) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.94 (9H, t, J = 7.8 Hz), 1.22-1.26 (3H, m), 1.29 (3H, d, J = 6.1 Hz ), 2.16 (1.2H, s), 2.19 (1.8H, s), 2.71-2.77 (2H, m), 3.26-3.28 (1H, m), 3.49-3.54 (1H, m), 3.69-3.78 (2H , m), 4.26-4.30 (2H, m), 4.65-4.82 (2H, m), 5.24-5.28 (1H, m), 5.47-5.51 (1H, m), 7.32 (0.4 H, s), 7.42 ( 0.6H, s), 7.67-7.70 (2H, m), 8.21-8.24 (2H, m)
MS (FAB ⁺ ); m / z 640 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (6-Acetyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate ¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.0 Hz) , 1.16 (3H, d, J = 6.3 Hz), 2.02 (1.2H, s), 2.05 (1.8H, s), 2.53-2.61 (2H, m), 3.28-3.43 (2H, m), 3.59-3.62 (2H, m), 4.06-4.12 (2H, m), 4.55-4.62 (2H, m), 6.94-6.96 (1H, m)
MS (FAB ⁺ ); m / z 413 [M + 1] ⁺

Example 68 (1S, 5R, 6S) -2- (6- (2-hydroxyacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate The compound of Example 68 was synthesized in the same manner as Example 6.
(a) (1S, 5R, 6S) -2- (6- (2-tert-butyldimethylsiloxyacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) 4-Nitrobenzyl-1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.09-0.12 (9H, m), 0.72-1.30 (27H, m), 2.73-2.77 (2H, m), 3.26-3.27 (1H, m), 3.50-3.58 ( 1H, m), 3.78-3.85 (2H, m), 4.25-4.37 (4H, m), 4.77 (2H, br s), 5.25 (1H, d, J = 13.9 Hz), 5.48 (1H, d, J = 13.9 Hz), 7.33 (0.4H, s), 7.43 (0.6H, s), 7.67 (2H, d, J = 8.6 Hz), 8.21 (2H, d, J = 8.6 Hz)
(b) (1S, 5R, 6S) -2- (6- (2-hydroxyacetyl) -4,5,6,7-tetrahydrothieno [2,3-c]
Pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.77 (3H, d, J = 7.0 Hz), 0.88 (3H, d, J = 6.3 Hz), 2.28-2.32 (2H, m), 3.02 (1H, dd, J = 6.4 and 2.0 Hz), 3.12-3.38 (3H, m), 3.79-4.34 (6H, m),
6.67 (1H, s)
MS (FAB ⁺ ); m / z 429 [M + 1] ⁺

Example 69 (1S, 5R, 6S) -2- (6- (4,5-dihydrooxazol-2-yl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid The compound of Example 69 was synthesized in the same manner as Example 9.
(a) (1S, 5R, 6S) -2- (6- (2-Chloroethylcarbamoyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1- 4-nitrobenzyl methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.63 (6H, m), 0.94 (9H, t, J = 7.8 Hz), 1.24 (3H, t, J = 7.3 Hz),
1.30 (3H, t, J = 6.1 Hz), 2.73-2.78 (2H, m), 3.26 (1H, dd, J = 5.6 and 2.5 Hz), 3.51-3.68 (7H, m), 4.25-4.30 (2H, m), 4.64 (2H, s), 4.96-4.99 (1H, m), 5.25 (1H, d, J = 13.9 Hz), 5.48 (1H, d, J = 13.9 Hz), 7.52 (1H, s), 7.67 (2H, d, J = 8.8 Hz), 8.21 (2H, d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -2- (6- (4,5-Dihydrooxazol-2-yl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-2- Yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.87-0.96 (9H, m), 1.23-1.30 (6H, m), 2.75 (2H, br s), 3.25-3.29 (1H , m), 3.50-3.67 (3H, m), 3.81 (2H, t, J = 8.5 Hz), 4.24-4.35 (4H, m), 4.63 (2H, s), 5.25 (1H, d, J = 13.8 Hz), 5.48 (1H, d, J = 13.8 Hz), 7.38 (1H, s), 7.68 (2H, d, J = 8.2Hz), 8.22 (2H, d, J = 8.2 Hz)
MS (FAB ⁺ ); m / z 667 [M + 1] ⁺
(c) (1S, 5R, 6S) -2- (6- (4,5-Dihydrooxazol-2-yl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
M-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.0 Hz), 1.16 (3H, d, J = 6.4 Hz), 2.66-2.70 (2H, m), 3.30-3.44 (2H, m), 3.63-3.67 (2H, m), 3.80 (2H, t, J = 8.5 Hz), 4.08-4.13 (2H, m), 4.61-4.73 (4H, m), 6.96 ( 1H, s)
MS (FAB ⁺ ); m / z 418 [M + 1] ⁺

The compounds of Examples 70 to 71 were synthesized in the same manner as in Example 6.

Example 70 (1S, 5R, 6S) -2- (6- (2-N, N-dimethylaminoacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (6- (2-N, N-dimethylaminoacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl ) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.63 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.23-1.30 (6H, m), 2.26 (2.4H, s), 2.30 ( 3.6H, s), 2.70-2.80 (2H, m), 3.16-3.28 (3H, m), 3.49-3.58 (1H, m), 4.24-4.30 (2H, m), 4.78-4.88 (2H, m) , 5.23-5.26 (1H, m), 5.46-5.51 (1H, m), 7.30 (0.4H, s), 7.41 (0.6H, s), 7.66-7.68 (2H, m), 8.21 (2H, d, (J = 8.5 Hz)
MS (ESI ⁺ ); m / z 683 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (6- (2-N, N-dimethylaminoacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.04 (3H, d, J = 7.3 Hz), 1.14 (3H, d, J = 6.3 Hz), 2.60-2.64 (2H, m), 2.77 (3H, s), 2.78 (3H, s), 3.26-3.30 (1H, m), 3.37-3.44 (1H, m), 3.47-3.70 (2H, m), 4.06-4.17 (4H, m), 4.48-4.60 (2H, m), 6.93 (1H, s)
MS (FAB ⁺ ); m / z 434 [M + 1] ⁺

Example 71 (1S, 5R, 6S) -2- (6- (2-amino-2-oxoacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (6- (2-amino-2-oxoacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) 4-Nitrobenzyl-1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.63 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.23-1.30 (6H, m), 2.80-2.87 (2H, m), 3.27 (1H, dd, J = 5.8and 2.9 Hz), 3.50-3.56 (1H, m), 3.90-3.94 (1H, m), 4.24-4.31 (3H, m), 4.82 (1H, s), 5.23-5.50 (3H, m), 7.52 (1H, s), 7.66 (2H, d, J = 8.7 Hz), 8.21 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -2- (6- (2-amino-2-oxoacetyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.1 Hz), 1.16 (3H, d, J = 6.6 Hz), 2.61-2.68 (2H, m), 3.29-3.46 (2H, m), 3.62-3.71 (2H, m), 4.07-4.11 (2H, m), 4.62-4.65 (2H,
m), 6.96 (1H, s)
MS (FAB ⁺ ); m / z 442 [M + 1] ⁺

Example 72 (1S, 5R, 6S) -2- (5- (4,5-dihydrothiazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2- Yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl And 5- (4,5-dihydrothiazol-2-yl) -2-tributylstannyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine Gave the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.9 Hz), 1.24 (3H, d, J = 7.3 Hz), 1.30 (3H, d , J = 6.4 Hz), 2.93 (2H, t, J = 5.6 Hz), 3.27 (1H, dd, J = 5.8 and 2.7 Hz), 3.35 (2H, t, J = 7.4 Hz), 3.49-3.58 (1H , m), 3.77 (2H, d, J = 5.6 Hz), 4.04 (2H, t, J = 7.4 Hz), 4.24-4.32 (2H, m), 4.52-4.60 (2H, m), 5.26 (1H, d, J = 13.9 Hz), 5.48 (1H, d, J = 13.9 Hz), 7.32 (1H, s), 7.67 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
MS (FAB ⁺ ); m / z 683 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid
(1S, 5R, 6S) -2- (5- (4,5-Dihydrothiazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl)- 1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl was used in the same manner as in Example 5 (b). The title compound was obtained.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.99 (3H, d, J = 7.1 Hz), 1.12 (3H, d, J = 6.0 Hz), 2.69-2.84 (2H, m), 3.21-3.25 (1H, m), 3.28-3.38 (1H, m), 3.44 (2H, t, J = 7.3 Hz), 3.62-3.68 (2H, m), 3.88 (2H, t, J = 7.3 Hz) , 3.97-4.08 (2H, m), 4.43 (2H, s), 6.89 (1H, s)
MS (FAB ⁺ ); m / z 434 [M + 1] ⁺

Example 73 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazole-2- Yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapen-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl And 5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl) -2-tributylstannyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine, In the same manner as in Example 1, the title compound was obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.5Hz), 0.95 (9H, t, J = 7.5 Hz), 1.25 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 6.0 Hz), 2.76 (3H, s), 2.92-3.00 (2H, m), 3.26 (1H, dd, J = 6.0 and2.7 Hz), 3.32-3.62 (5H, m), 3.65- 3.74 (2H, m), 4.20-4.34 (4H, m), 5.25 (1H, d, J = 13.5 Hz), 5.49 (1H, d, J = 13.5 Hz), 7.31 (1H, s), 7.68 (2H , d, J = 8.4 Hz), 8.22 (2H, d, J = 8.4 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazole-2- Yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-
Carbapen-2-em-3-carboxylic acid
(1S, 5R, 6S) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl) -4,5,6,7-tetrahydrothieno [3, Example 5 (b) using 4-nitrobenzyl 2-c] pyridin-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate In the same manner as described above, the title compound was obtained.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.00 (3H, d, J = 6.3 Hz), 1.13 (3H, d, J = 6.0 Hz), 2.65-2.82 (2H, m), 2.88 (3H, s), 3.20-3.40 (2H, m), 3.40-3.57 (4H, m), 3.57-3.63 (2H, m), 4.00-4.12 (2H, m), 4.26 (2H, s), 6.85 (1H, s)

Example 74 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazole-2- Yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
(a) (1S, 5R, 6S) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [ 2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl And 5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole In the same manner as in Example 1, the title compound was obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.1 Hz), 0.95 (9H, t, J = 8.1 Hz), 1.25 (3H, d, J = 7.5
Hz), 1.30 (3H, d, J = 6.0 Hz), 2.87 (3H, s), 3.27 (1H, dd, J = 5.7 and 2.7 Hz), 3.40-3.50 (2H, m), 3.50-3.62 (1H , m), 3.64-3.74 (2H, m), 4.24-4.36 (2H, m), 4.58-4.65 (2H, m), 4.73-4.82 (2H, m), 5.25 (1H, d, J = 13.8 Hz ), 5.49 (1H, d, J = 13.8Hz), 7.44 (1H, s), 7.68 (2H, d, J = 8.4 Hz), 8.22 (2H, d, J = 8.4 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazole-2- Yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid
(1S, 5R, 6S) -1-Methyl-2- (5- (1-methyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-
The title compound was obtained in the same manner as in Example 5 (b) using 4-nitrobenzyl carbapen-2-em-3-carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.80ppm): 1.20 (3H, d, J = 6.9 Hz), 1.31 (3H, d, J = 6.3 Hz), 3.17 (3H, s), 3.40- 3.48 (1H, m), 3.55-3.68 (3H, m), 3.70-3.85 (2H, m), 4.14-4.30 (2H, m), 4.52-4.75 (4H, m), 7.14 (1H, s)
MS (FAB ⁺ ); m / z 417 [M + 1] ⁺

Example 75 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c]
4-Pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl And 5- (pyridin-3-yl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole in the same manner as in Example 1 and the title compound Got.
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 8.1 Hz), 0.95 (9H, t, J = 8.1 Hz), 1.22-1.40 (6H, m
), 3.29 (1H, dd, J = 5.4 and 2.7 Hz), 3.53-3.67 (1H, m), 4.25-4.35 (2H, m), 4.53 (2H,
s), 4.69 (2H, s), 5.27 (1H, d, J = 14.4 Hz), 5.51 (1H, d, J = 14.4 Hz), 6.88-6.96 (1H, m), 7.17-7.24 (1H, m ), 7.55 (1H, s), 7.69 (2H, d, J = 8.7 Hz), 8.00-8.08 (2H, m), 8.23
(2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
(1S, 5R, 6S) -1-Methyl-2- (5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- The title compound was obtained in the same manner as in Example 5 (b) using ((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl. .
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.11 (3H, d, J = 6.9 Hz), 1.32 (3H, d, J = 6.0 Hz), 3.30-3.41 (2H, m), 3.96-4.40 (6H, m), 6.84-6.97 (1H, m), 7.05 (1H, s), 7.15-7.23 (1H, m), 7.73-7.80 (2H, m)
MS (FAB ⁺ ); m / z 434 [M + 1] ⁺

Example 76 (1S, 5R, 6S) -2- (5-tert-butyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (5-tert-Butyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1R, 3R, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2-oxo-1-carbapenam-3-carboxylic acid 4-nitrobenzyl 975 mg (2.69 mmol) anhydrous N, N-diisopropylethylamine 0.710 ml (4.08 mmol) and trifluoromethanesulfonic anhydride 0.451 ml (2.69 mmol) were added dropwise to an acetonitrile 30 ml solution at −40 ° C. in an argon atmosphere. After stirring for 10 minutes, the reaction solution was poured into a 1: 1 mixed solution of saturated aqueous ammonium chloride and water, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. To this filtrate was added 20 ml of anhydrous 1-methylpyrrolidinone, and acetonitrile and ethyl acetate were distilled off under reduced pressure. The resulting (1R, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4- Anhydrous 1-methylpyrrolidinone solution of 5-tert-butyl-2-tributylstannyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one in an anhydrous 1-methylpyrrolidinone solution of nitrobenzyl At room temperature, 129 mg (0.553 mmol) of tri (2-furyl) phosphine, 126 mg (0.137 mmol) of tris (dibenzylideneacetone) dipalladium (0) and 0.734 mg (5.38 mmol) of zinc chloride were sequentially added, The mixture was stirred at 50 ° C. for 2 hours. Ethyl acetate and saturated brine were added to the reaction solution, filtered, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed five times with water, washed with saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluted with ethyl acetate: methanol = 100: 0 to 95: 5) to give the title compound 364 mg (yield 71
%).
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 7.4Hz), 1.40 (3H, d, J = 6.4 Hz), 1.54 (9H, s), 2.08 (1H, d, J = 4.8 Hz), 3.35 (1H, dd, J = 6.4 and 2.8 Hz), 3.60 (1H, dq, J = 9.2 and 7.4 Hz), 4.26-4.42 (4H, m), 5.26 (1H, d, J = 13.6 Hz) ), 5.50 (1H, d, J = 13.6 Hz), 7.65 (2H, d,
J = 9.0 Hz), 7.69 (1H, s), 8.23 (2H, d, J = 9.0 Hz)
MS (ESI ⁺ ); m / z 540 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-tert-Butyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(1S, 5R, 6S) -2- (5-tert-Butyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) The title compound was obtained in the same manner as in Example 7 (c) using 4-nitrobenzyl-1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.02 (3H, d, J = 7.2 Hz), 1.16 (3H, d, J = 6.4 Hz), 1.30 (9H, s), 3.33 ( 1H, dd, J = 6.2 and 2.6 Hz), 3.40 (1H, dq, J = 9.2 and 7.2 Hz), 4.06-4.14 (2H, m), 4.26 (1H, d, J = 19.6 Hz), 4.27 (1H , d, J = 19.6 Hz), 7.03 (1H, s)
MS (FAB ⁺ ); m / z 427 [M + 1] ⁺

The compounds of Examples 77 to 83 were synthesized in the same manner as described in Example 76 using the compounds of the corresponding reference examples.

Example 77 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-6-oxo-5,6-dihydro-4H-thieno [2 , 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-6-oxo-5,6-
4-Hydroxybenzyl dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.5Hz), 1.40 (3H, d, J = 6.0 Hz), 2.00 (1H, br d, J = 4.0 Hz), 3.18 (3H , s), 3.36 (1H, dd, J = 6.8 and 2.8 Hz), 3.62 (1H, dq, J = 9.6 and 7.5 Hz), 4.29-4.35 (3H, m), 4.37 (1H, dd, J = 9.6 and 2.8 Hz), 5.27 (1H, d, J = 13.6 Hz),
5.51 (1H, d, J = 13.6 Hz), 7.66 (2H, d, J = 9.0 Hz), 7.73 (1H, s), 8.23 (2H, d, J = 9.0 Hz)
MS (FAB ⁺ ); m / z 498 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-6-oxo-5,6-
Sodium dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.2 Hz), 1.15 (3H, d, J = 6.4 Hz), 2.96 (3H, s), 3.35 ( 1H, dd, J = 6.2 and 2.6 Hz), 3.46 (1H, br qui, J = 7.6 Hz), 4.07-4.16 (2H, m), 4.24 (2H, brs), 7.10 (1H, s)
MS (FAB ⁺ ); m / z 385 [M + 1] ⁺

Example 78 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.3 Hz), 1.28 (6H, d, J = 6.8 Hz), 1.40 (3H, d, J = 6.3
Hz), 3.36 (1H, dd, J = 6.6 and 2.7 Hz), 3.57-3.66 (1H, m), 4.26 (2H, s), 4.28-4.35 (1H, m), 4.37 (1H, dd, J = 9.5 and 2.7 Hz), 4.55-4.62 (1H, m), 5.27 (1H, d, J = 13.9 Hz),
5.51 (1H, d, J = 13.9 Hz), 7.67 (2H, d, J = 8.8 Hz), 7.73 (1H, s), 8.24 (2H, d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.1 Hz), 1.10 (3H, d, J = 6.8 Hz), 1.13 (3H, d, J = 6.8 Hz), 1.16 (3H, d, J = 6.8 Hz), 3.35 (1H, dd, J = 6.1 and 2.7 Hz), 3.42-3.50 (1H, m), 4.08-4.20 (3H, m), 4.22 (2H , s), 7.09 (1H, s)
MS (FAB ⁺ ); m / z 413 [M + 1] ⁺

Example 79 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-
Em-3-carboxylate sodium
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.25-1.30 (3H, m), 1.40 (3H, d, J = 6.1 Hz), 1.80-1.85 (1H, m), 3.36 (1H, dd, J = 6.3 and 2.7 Hz), 3.57-3.67 (1H, m), 4.24 (2H, s), 4.28-4.40 (2H, m), 4.76 (2H, s), 5.26 (1H, d, J = 13.9 Hz), 5.51 ( 1H, d, J = 13.9 Hz), 7.19-7.21 (2H, m), 7.66 (2H, d, J = 8.8 Hz), 7.68 (1H, s), 8.23 (2H, d, J = 8.8 Hz), 8.57-8.60 (2H, m)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.1 Hz), 1.16 (3H, d, 6.3 Hz), 3.34 (1H, dd, J = 6.1 and 2.7 Hz), 3.41-3.50 (1H, m), 4.08-4.16 (2H, m), 4.27 (2H, s), 4.64-4.66 (2H, m), 7.12 (1H, s), 7.13-7.16 (2H, m), 8.29-8.32 (2H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 80 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 7.3 Hz), 1.40 (3H, d, J = 6.4 Hz), 3.36 (1H, dd, J = 6.4 and 2.7 Hz), 3.56- 3.66 (1H, m), 4.22 (2H, s), 4.28-4.38 (2H, m), 4.77 (2H, s), 5.26 (1H, d, J = 13.6 Hz), 5.50 (1H, d, J = 13.6 Hz), 7.25-7.30 (1H, m), 7.64-7.69 (4H, m), 8.23 (2H, d, J = 8.8Hz), 8.55-8.59 (2H, m)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.0 Hz), 1.14 (3H, d, J = 6.1 Hz), 3.32-3.36 (1H, m), 3.39-3.48 (1H, m), 4.06-4.15 (2H, m), 4.23 (2H, s), 4.62 (2H, s), 7.10 (1H, s), 7.24-7.29 (1H, m), 7.58- 7.62 (1H, m), 8.27-8.32 (2H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 81 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-2-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-2-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.28 (3H, m), 1.38-1.44 (3H, m), 3.34-3.41 (1H, m), 3.54-3.69 (1H, m), 4.34-4.42 ( 4H, m), 4.88 (2H, s), 5.26 (1H, d, J = 13.9 Hz), 5.50 (1H, d, J = 13.9 Hz), 7.16-7.23 (1H, m), 7.31-7.35 (1H , m), 7.64-7.70 (4H, m), 8.23 (2H, d, J = 8.8
Hz), 8.54-8.57 (1H, m)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-2-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65ppm): 1.19 (3H, d, J = 7.0 Hz), 1.26-1.32 (3H, m), 3.47 (1H, dd, J = 6.4 and 2.7 Hz ), 3.52-3.62 (1H, m), 4.15-4.29 (2H, m), 4.41 (2H, s), 4.82 (2H, s), 7.25 (1H, s), 7.29-7.36 (2H, m), 7.78-7.83 (1H, m), 8.42-8.45 (1H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 82 (1S, 5R, 6S) -2- (5-benzyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5-Benzyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 7.3Hz), 1.40 (3H, d, J = 6.4 Hz), 3.35 (1H, dd, J = 6.8 and 2.8 Hz), 3.61 ( 1H, dq, J = 9.6and 7.3 Hz), 4.18 (2H, s), 4.31 (1H, br q, J = 6.6
Hz), 4.37 (1H, dd, J = 9.6 and 2.8 Hz), 4.74 (1H, d, J = 15.0 Hz), 4.76 (1H, d, J = 15.0
Hz), 5.25 (1H, d, J = 13.8 Hz), 5.49 (1H, d, J = 13.8 Hz), 7.26-7.37 (5H, m), 7.65 (1H,
s), 7.65 (2H, d, J = 8.8 Hz), 8.22 (2H, d, J = 8.8 Hz)
MS (ESI ⁺ ); m / z 574 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-Benzyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.03 (3H, d, J = 7.0 Hz), 1.16 (3H, d, J = 6.4 Hz), 3.33 (1H, dd, J = 6.2 and 2.5Hz), 3.41 (1H, dq, J = 9.2 and 7.0 Hz), 4.07-4.19 (4H, m), 4.49 (1H, d, J = 15.4 Hz), 4.54 (1H, d, J = 15.4 Hz) ), 7.03 (1H, s), 7.10-7.13 (2H, m), 7.13-7.24 (3H, m)
MS (FAB ⁺ ); m / z 461 [M + 1] ⁺

Example 83 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethyl) -6-oxo-5,6-dihydro-4H-thieno [ 2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethyl) -6-oxo-5,6-dihydro-4H-thieno [ 2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.2Hz), 1.40 (3H, d, J = 6.1 Hz), 2.08 (1H, br s), 3.34-3.37 (1H, m) , 3.35 (3H, s), 3.58-3.65 (3H, m), 3.75 (2H, t, J = 5.0 Hz), 4.31 (1H, qui, J = 6.1 Hz), 4.37 (1H, dd, J = 9.4 and 2.6 Hz), 4.45 (1H, d, J = 18.0 Hz), 4.46 (1H,
d, J = 18.0 Hz), 5.26 (1H, d, J = 13.8 Hz), 5.51 (1H, d, J = 13.8 Hz), 7.66 (2H, d, J = 8.8 Hz), 7.71 (1H, s) , 8.23 (2H, d, J = 8.8 Hz)
MS (ESI ⁺ ); m / z 542 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethyl) -6-oxo-5,6-dihydro-4H-thieno [ 2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.3 Hz), 1.17 (3H, d, J = 6.3 Hz), 3.23 (3H, s), 3.36 ( 1H, dd, J = 6.2 and 2.7Hz), 3.47 (1H, dq, J = 9.2 and 7.3 Hz), 3.54-3.65 (4H, m), 4.12 (1H, qui, J = 6.2 Hz), 4.15 (1H , dd, J = 9.2 and 2.7 Hz), 4.33 (2H, s), 7.13 (1H, s)
MS (FAB ⁺ ); m / z 429 [M + 1] ⁺

Example 84 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-hydroxyethyl) -6-oxo-5,6-dihydro-4H-thieno [ 2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (2-triethylsiloxyethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-
M-3-carboxylic acid 4-nitrobenzyl
(1R, 3R, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2-oxo-1-carbapenam-3-carboxylic acid 4-nitrobenzyl and 2-tributylstannyl- The title compound was obtained in the same manner as in Example 76 (a) using 5- (2-triethylsiloxyethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one. .
¹ H-NMR (CDCl ₃ ) δ: 0.59 (6H, q, J = 7.9Hz), 0.93 (9H, t, J = 7.9 Hz), 1.28 (3H, d, J = 7.2
Hz), 1.40 (3H, d, J = 6.0 Hz), 2.07 (1H, br d, J = 4.4 Hz), 3.36 (1H, dd, J = 6.8 and 2.8 Hz), 3.59-3.70 (3H, m ), 3.85 (2H, t, J = 5.0 Hz), 4.27-4.35 (1H, m), 4.37 (1H, dd, J = 9.6 and 2.8 Hz), 4.49 (2H, s), 5.27 (1H, d, J = 13.8 Hz), 5.51 (1H, d, J = 13.8 Hz), 7.67 (2H, d, J = 9.0 Hz), 7.76 (1H, s), 8.23 (2H, d, J = 9.0 Hz)
MS (FAB ⁺ ); m / z 642 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-hydroxyethyl) -6-oxo-5,6-dihydro-4H-thieno [ 2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (2-triethylsiloxyethyl) -5,6-dihydro-4H- In the same manner as in Example 5 (b) using thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate 4-nitrobenzyl, the title compound Got.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.2 Hz), 1.16 (3H, d, J = 6.4 Hz), 3.35 (1H, dd, J = 6.0 and 2.8Hz), 3.42-3.59 (3H, m), 3.67 (2H, t, J = 5.4 Hz), 4.08-4.17 (2H, m), 4.33 (2H, br s), 7.10 (1H, s)
MS (FAB ⁺ ); m / z 415 [M + 1] ⁺

The compounds of Examples 85 to 99 were synthesized in the same manner as described in Example 76 using the compounds of the corresponding reference examples.

Example 85 (1S, 5R, 6S) -2- (5-cyclopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5-Cyclopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.80-0.97 (4H, m), 1.26 (3H, d, J = 7.2 Hz), 1.40 (3H, d, J = 6.3 Hz),
2.80-2.94 (1H, m), 3.35 (1H, dd, J = 6.6 and 2.7 Hz), 3.53-3.70 (1H, m), 4.25 (2H, s), 4.25-4.40 (2H, m), 5.26 ( 1H, d, J = 13.8 Hz), 5.50 (1H, d, J = 13.8 Hz), 7.66 (2H, d, J = 9.0 Hz), 7.69 (1H, s), 8.23 (2H, d, J = 9.0 Hz)
(b) (1S, 5R, 6S) -2- (5-Cyclopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 0.77-0.96 (4H, m), 1.21 (3H, d, J = 7.2 Hz), 1.32 (3H, d, J = 6.3 Hz), 2.78-2.88 (1H, m), 3.48-3.66 (2H, m), 4.22-4.39 (4H, m), 7.21 (1H, s)
MS (FAB ⁺ ); m / z 411 [M + 1] ⁺

Example 86 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-5,6-dihydro-4H-thieno [2 , 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-5,6-
4-Hydroxybenzyl dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.3 Hz), 1.41 (3H, d, J = 6.3 Hz), 3.17 (3H, s), 3.34 (1H, dd, J = 6.8 and 2.5 Hz), 3.64-3.73 (1H, m), 4.29-4.35 (2H, m), 4.40-4.50 (2H, m), 5.28 (1H, d, J = 13.7 Hz), 5.52 (1H, d, J = 13.7 Hz), 7.57 (1H, s), 7.67 (2H, d, J = 9.0
Hz), 8.21-8.25 (2H, m)
MS (ESI ⁺ ); m / z 498 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-5,6-
Sodium dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.2 Hz), 1.17 (3H, d, J = 6.4 Hz), 2.96 (3H, s), 3.31- 3.33 (1H, m), 3.43-3.51 (1H, m), 4.08-4.14 (2H, m), 4.33-4.44 (2H, m), 7.09 (1H, d, J = 3.6 Hz)
MS (FAB ⁺ ); m / z 385 [M + 1] ⁺

Example 87 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-3-yl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapen-2-em-3-
Sodium carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-3-yl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (DMSO-d ₆ ) δ: 1.16 (3H, d, J = 7.3 Hz), 1.19 (3H, d, J = 6.3 Hz), 3.39 (1H, dd, J = 6.3 and 2.7 Hz), 3.85-3.94 (1H, m), 4.00-4.05 (1H, m), 4.31 (1H, dd, J = 9.7 and 2.7 Hz), 5.15 (1H, d, J = 5.4Hz), 5.19 (2H, s) , 5.38 (1H, d, J = 13.7 Hz) 5.51 (1H, d, J = 13.7 Hz), 7.47 (1H, dd, J = 8.5 and 4.9 Hz), 7.73 (2H, d, J = 8.8 Hz), 7.77 (1H, s), 8.17-8.22 (1H, m), 8.23 (2H, d, J = 8.8 Hz), 8.36-8.37 (1H, m), 8.99 (1H, d, J = 2.4 Hz)
MS (ESI ⁺ ); m / z 561 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-3-yl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (DMSO-d ₆ ) δ: 1.01 (3H, d, J = 7.2 Hz), 1.17 (3H, d, J = 6.4 Hz), 3.27-3.29 (1H, m), 3.35-3.39 (1H , m), 3.98-4.00 (1H, m), 4.07-4.11 (1H, m), 4.62-4.83 (2H, m), 7.09 (1H, s), 7.32 (1H, d, J = 8.3 and 5.1 Hz ), 7.88-7.91 (1H, m), 8.15 (1H, d, J = 4.6 Hz), 8.70 (1H, m)
MS (FAB ⁺ ); m / z 448 [M + 1] ⁺

Example 88 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.29 (3H, d, J = 7.3 Hz), 1.41 (3H, d, J = 6.3 Hz), 3.35 (1H, dd, J = 6.8 and 2.7 Hz), 3.67- 3.72 (1H, m), 4.30-4.40 (4H, m), 4.75 (1H, d, J = 15.8 Hz), 4.79 (1H, d, J = 15.8 Hz), 5.28 (1H, d, J = 13.6 Hz) ), 5.52 (1H, d, J = 13.6 Hz), 7.19 (2H, d, J = 5.8 Hz), 7.62 (1H, s), 7.67 (2H, d, J = 8.8 Hz), 8.21-8.25 (2H , m), 8.58-8.60 (2H, m) MS (FAB ⁺ ); m / z 575 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.09 (3H, d, J = 7.3 Hz), 1.17 (3H, d, J = 6.3 Hz), 3.34-3.37 (1H, m), 3.49-3.54 (1H, m), 4.10-4.16 (2H, m), 4.46-4.47 (2H, m), 4.63-4.68 (2H,
s), 7.15-7.17 (2H, m), 7.21-7.23 (1H, m), 8.32-8.34 (2H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 89 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.28 (3H, d, J = 7.3 Hz), 1.40 (3H, d, J = 6.3 Hz), 3.34 (1H, dd, J = 6.6 and 2.7 Hz), 3.66- 3.71 (1H, m), 4.11-4.37 (4H, m), 4.77 (1H, d, J = 15.3 Hz), 4.80 (1H, d, J = 15.3 Hz), 5.27 (1H, d, J = 13.6 Hz) ), 5.52 (1H, d, J = 13.6 Hz), 7.24-7.29 (1H,
m), 7.61 (1H, s), 7.64-7.68 (3H, m), 8.20-8.25 (2H, m), 8.55-8.58 (2H, m)
MS (ESI ⁺ ); m / z 575 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (3H, d, J = 7.3 Hz), 1.15 (3H, d, J = 6.3 Hz), 3.31 (1H, dd, J = 6.3 and 2.7Hz), 3.43-3.51 (1H, m), 4.06-4.14 (2H, m), 4.36-4.40 (2H, m),
4.64-4.65 (2H, m), 7.17 (1H, s), 7.24-7.29 (1H, m), 7.57-7.61 (1H, m), 8.27-8.31 (2H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 90 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-2-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-2-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.25 (3H, d, J = 7.3 Hz), 1.40 (3H, d, J = 6.1 Hz), 3.34 (1H, dd, J = 6.6 and 2.4 Hz), 3.66- 3.71 (1H, m), 4.28-4.37 (2H, m), 4.55 (1H, d, J = 18.2 Hz), 4.58 (1H, d, J = 18.2 Hz), 4.87 (1H, d, J = 15.6 Hz) ), 4.90 (1H, d, J = 15.6 Hz), 5.27 (1H, d, J = 13.6 Hz), 5.52 (1H, d, J = 13.6 Hz), 7.19-7.24 (1H, m), 7.27 (1H , d, J = 7.8 Hz), 7.61 (1H, s), 7.65-7.70 (3H, m), 8.21-8.25 (2H, m), 8.54-8.57 (1H, m)
MS (ESI ⁺ ); m / z 575 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-2-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.04 (3H, d, J = 7.1 Hz), 1.15 (3H, d, J = 6.3 Hz), 3.31 (1H, dd, J = 6.3 and 2.7Hz), 3.42-3.48 (1H, m), 4.16-4.12 (2H, m), 4.35 (1H, d, J = 19.0 Hz), 4.41 (1H, d, J = 19.0 Hz), 4.60-4.69 (2H, m), 7.12-7.20 (2H, m), 7.15 (1H, s), 7.62-7.67 (1H, m), 8.27-8.28 (1H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 91 (1S, 5R, 6S) -2- (5-benzyl-4-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (5-Benzyl-4-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 7.3 Hz), 1.41 (3H, d, J = 6.1 Hz), 3.33 (1H, dd, J = 6.8 and 2.7 Hz), 3.67- 3.71 (1H, m), 4.28-4.38 (4H, m), 4.72 (1H, d, J = 15.1 Hz), 4.78 (1H, d, J = 15.1 Hz), 5.26 (1H, d, J = 13.7 Hz) ), 5.52 (1H, d, J = 13.7 Hz), 7.23-7.37 (5H,
m), 7.61 (1H, s), 7.76 (2H, d, J = 8.8 Hz), 8.21-8.25 (2H, m)
MS (FAB ⁺ ); m / z 574 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-Benzyl-4-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrole-2
-Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.2 Hz), 1.17 (3H, d, J = 6.4 Hz), 3.33 (1H, dd, J = 6.4 and 2.7Hz), 3.46-3.65 (1H, m), 4.08-4.15 (2H, m), 4.28-4.40 (2H, m),
4.60 (2H, s), 7.14-7.28 (6H, m)
MS (FAB ⁺ ); m / z 461 [M + 1] ⁺

Example 92 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-4,5,6,7-tetrahydrothieno [ 3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-4,5,6,7-tetrahydrothieno [ 3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-
Nitrobenzyl
¹ H -NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.1 Hz), 1.40 (3H, d, J = 6.3 Hz), 3.04-3.11 (5H, m), 3.32 (1H, dd, J = 6.6 and 2.4Hz), 3.61-3.76 (3H, m), 4.28-4.33 (2H, m), 5.28 (1H, d, J = 13.9 Hz), 5.53 (1H, d, J = 13.9 Hz), 7.68 (2H, d, J = 8.8 Hz), 7.71 (1H, s), 8.23 (2H, d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-4,5,6,7-tetrahydrothieno [ 3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 6.8 Hz), 1.16 (3H, d, J = 6.3 Hz), 2.90-2.97 (5H, m), 3.29-3.33 (1H, m), 3.43-3.52 (1H, m), 3.53-3.58 (2H, m), 4.08-4.13 (2H,
m), 7.26 (1H, s)
MS (FAB ⁺ ); m / z 399 [M + 1] ⁺

Example 93 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethyl) -4-oxo-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethyl) -4-oxo-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl-1-carbapen-2-em-3-
4-Nitrobenzyl carboxylate
¹ H-NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.3 Hz), 1.40 (3H, d, J = 6.1 Hz), 3.01-3.08 (2H, m),
3.32 (1H, dd, J = 6.5 and 2.4 Hz), 3.35-3.41 (4H, m), 3.58-3.62 (2H, m), 3.66-3.79 (4H, m), 4.27-4.32 (2H, m), 5.28 (1H, d, J = 13.6 Hz), 5.53 (1H, d, J = 13.6 Hz), 7.67-7.72 (3H, m), 8.23 (2H, d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethyl) -4-oxo-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-methyl-1-carbapen-2-em-3-
Sodium carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.0 Hz), 1.15-1.20 (3H, m), 2.89-2.95 (2H, m), 3.22 (3H , s), 3.31 (1H, dd, J = 6.4 and 2.5 Hz), 3.43-3.61 (7H, m), 4.02-4.14 (2H, m), 7.24-7.26 (1H, m)
MS (FAB ⁺ ); m / z 443 [M + 1] ⁺

Example 94 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-2-ylmethyl) -4,5,6 , 7-Tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-2-ylmethyl) -4,5,6 , 7-Tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.28 (3H, d, J = 7.3 Hz), 1.40 (3H, d, J = 6.3 Hz), 3.07 (2H, t, J = 6.
8 Hz), 3.33 (1H, dd, J = 6.8 and 2.7 Hz), 3.67-3.78 (3H, m), 4.28-4.32 (2H, m), 4.79-4.91 (2H, m), 5.28 (1H, d , J = 13.9 Hz), 5.53 (1H, d, J = 13.9 Hz), 7.18-7.23 (1H, m), 7.34-7.39 (1H, m), 7.64-7.71 (3H, m), 7.76 (1H, s), 8.23 (2H, d, J = 8.8 Hz), 8.53-8.56 (1H, m)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-2-ylmethyl) -4,5,6 , 7-Tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.3 Hz), 1.15-1.20 (3H, m), 2.93-2.98 (2H, m), 3.31 (1H , dd, J = 6.1 and 2.4 Hz), 3.42-3.51 (1H, m), 3.58 (2H, t, J = 7.1 Hz),
4.07-4.14 (2H, m), 4.64-4.66 (2H, m), 7.19-7.25 (2H, m), 7.30 (1H, s), 7.67-7.72 (1H, m), 8.30-8.33 (1H, m )
MS (FAB ⁺ ); m / z 476 [M + 1] ⁺

Example 95 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-4,5,6,7-
Sodium tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapen-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-4,5,6,7-tetrahydrothieno [3,2- c] Pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (DMSO-d ₆ ) δ (DMSO = 2.50 ppm): 1.14 (3H, d, J = 7.1 Hz), 1.18 (3H, d, J = 6.3 Hz),
2.28-3.03 (2H, m), 3.42-3.47 (2H, m), 3.76-3.86 (1H, m), 3.97-4.05 (1H, m), 4.24-4.29 (1H, m), 5.12-5.14 (1H , m), 5.34 (1H, d, J = 13.9 Hz), 5.49 (1H, d, J = 13.9 Hz), 7.68-7.75 (4H, m), 8.24 (2H, d, J = 8.5 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-4,5,6,7-tetrahydrothieno [3,2- c] Pyridin-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.3 Hz), 1.17 (3H, d, J = 6.3 Hz), 2.89-2.94 (2H, m), 3.33 (1H, dd, J = 6.1 and 2.4 Hz), 3.43-3.51 (3H, m), 4.08-4.14 (2H, m),
7.28 (1H, s)
MS (FAB ⁺ ); m / z 385 [M + 1] ⁺

Example 96 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-methyl-7-oxo-4, 5,6,7-tetrahydrothieno [ 2,3-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-methyl-7-oxo-4,5,6,7-tetrahydrothieno [ 2,3-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-
Nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.33 (3H, d, J = 7.3 Hz), 1.46 (2H, d, J = 6.4 Hz), 2.99 (2H, t, J = 7.1
Hz), 3.17 (3H, s), 3.41 (1H, dd, J = 6.8 and 2.7 Hz), 3.61-3.68 (3H, m), 4.37-4.43 (2H, m), 5.33 (1H, d, J = 13.9 Hz), 5.57 (1H, d, J = 13.9 Hz), 7.65 (1H, s), 7.73 (2H, d, J = 9.0 Hz), 8.30 (2H, d, J = 9.0 Hz)
MS (FAB ⁺ ); m / z 512 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-methyl-7-oxo-4,5,6,7-tetrahydrothieno [ 2,3-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.3 Hz), 1.15 (3H, d, J = 6.4 Hz), 2.77 (2H, t, J = 7.3 Hz), 2.91 (3H, s), 3.34 (1H, dd, J = 6.1 and 2.7 Hz), 3.41-3.47 (1H, m),
3.52 (2H, t, J = 7.3 Hz), 4.09-4.15 (2H, m), 7.02 (1H, s)
MS (FAB ⁺ ); m / z 399 [M + 1] ⁺

Example 97 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6-isopropyl-7-oxo-4,5
, 6,7-Tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6-isopropyl-7-oxo-4,5,6,7-tetrahydrothieno [2,3- c] Pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.20 (6H, d, J = 6.8 Hz), 1.25 (3H, d, J = 7.3 Hz), 1.39 (2H, d, J = 6.4
Hz), 2.84 (2H, t, J = 7.1 Hz), 3.34 (1H, dd, J = 6.3 and 2.7 Hz), 3.48 (2H, t, J = 7.1 Hz), 3.55-3.59 (1H, m), 4.31-4.34 (2H, m), 4.96 (1H, q, J = 6.8 Hz), 5.25 (1H, d, J = 13.6 Hz), 5.50 (1H, d, J = 13.6 Hz), 7.57 (1H, s ), 7.64 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6-isopropyl-7-oxo-4,5,6,7-tetrahydrothieno [2,3- c] Pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.05 (6H, d, J = 6.8 Hz), 1.07 (3H, d, J = 7.3 Hz), 1.16 (3H, d, J = 6.4 Hz), 2.71 (2H, t, J = 7.1 Hz), 3.36 (1H, dd, J = 6.3 and 2.7 Hz), 3.40-3.48 (3H, m), 4.08-4.16 (2H, m), 4.58 (1H , q, J = 6.8 Hz), 7.02 (1H, s)
MS (FAB ⁺ ); m / z 427 [M + 1] ⁺

Example 98 (1S, 5R, 6S) -2- (6- (2-N, N-dimethylamino-2-oxoethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3- c] Pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -2- (6- (2-N, N-dimethylamino-2-oxoethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3- c] Pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.1 Hz), 1.39 (3H, d, J = 6.1 Hz), 2.94-3.06 (8H, m),
3.34 (1H, dd, J = 6.8 and 2.9 Hz), 3.54-3.59 (1H, m), 3.73 (2H, t, J = 6.8 Hz), 4.28-4.35 (4H, m), 5.25 (1H, d, J = 13.9 Hz), 5.49 (1H, d, J = 13.9 Hz), 7.55 (1H, s), 7.64 (2H, d, J = 8.8 Hz), 8.21 (2H, d, J = 8.8 Hz)
MS (FAB ⁺ ); m / z 583 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (6- (2-N, N-dimethylamino-2-oxoethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3- c] Pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.08 (3H, d, J = 7.1 Hz), 1.16 (3H, d, J = 6.3 Hz), 2.80-2.92 (8H, m), 3.36 (1H, dd, J = 6.1 and 2.4 Hz), 3.43-3.47 (1H, m), 3.53 (2H, t, J = 7.1
Hz), 4.09-4.15 (2H, m), 4.26 (2H, s), 7.06 (1H, s)
MS (FAB ⁺ ); m / z 470 [M + 1] ⁺

Example 99 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6- (2-methoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6- (2-methoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-
4-Nitrobenzyl carboxylate
¹ H-NMR (CDCl ₃ ) δ: 1.25 (3H, d, J = 7.3Hz), 1.39 (3H, d, J = 6.3 Hz), 1.82 (1H, d, J = 4.7
Hz), 2.88 (2H, t, J = 7.1 Hz), 3.33-3.35 (4H, m), 3.55-3.73 (7H, m), 4.29-4.35 (2H, m), 5.26 (1H, d, J = 13.9 Hz), 5.49 (1H, d, J = 13.9 Hz), 7.56 (1H, s), 7.64 (2H, d, J = 9.1 Hz), 8.21 (2H, d, J = 9.1 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6- (2-methoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.13 (3H, d, J = 7.3 Hz), 1.23 (3H, d, J = 6.3 Hz), 2.83 (2H, t, J = 7.0 Hz), 3.29 (3H, s), 3.42 (1H, dd, J = 6.1 and 2.5 Hz), 3.48-3.57 (1H, m),
3.60-3.64 (6H, m), 4.14-4.21 (2H, m), 7.09 (1H, s)
MS (FAB ⁺ ); m / z 443 [M + 1] ⁺

Example 100 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6- (2-hydroxyethyl) -7-
Sodium oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl-1-carbapen-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (7-oxo-6- (2-triethylsiloxyethyl) -4,5,6 , 7-Tetrahydrothieno [2,3-c] pyridin-2-yl) -1-carbapen-2-em-3-carboxylic acid 4-nitrobenzyl
(1R, 3R, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2-oxo-1-carbapenam-3-carboxylic acid 4-nitrobenzyl and 2-tributylstannyl- Using 6- (2-triethylsiloxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one, the title compound was prepared in the same manner as in Example 76 (a). Obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.60 (6H, q, J = 8.0 Hz), 0.94 (9H, t, J = 8.0 Hz), 1.26 (3H, d, J = 7.1
Hz), 1.39 (3H, d, J = 6.3 Hz), 2.86-2.89 (2H, m), 3.34-3.35 (1H, m), 3.60-3.65 (3H, m), 3.83 (2H, t, J = 4.8 Hz), 4.32 (2H, t, J = 6.0 Hz), 4.32-4.35 (2H, m), 5.27 (1H, d, J = 13.6 Hz), 5.51 (1H, d, J = 13.6 Hz), 7 58 (1H, s), 7.65 (2H, d, J = 8.6 Hz), 8.22 (2H,
d, J = 8.6 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6- (2-hydroxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (7-oxo-6- (2-triethylsiloxyethyl) -4,5,6,7- Tetrahydrothieno [2,3-c] pyridin-2-yl) -1-carbapen-2-
The title compound was obtained in a similar manner to Example 5 (b) using 4-nitrobenzyl em-3-carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.4 Hz), 1.14 (3H, d, J = 6.3 Hz), 2.76 (2H, t, J = 7.1 Hz), 3.34 (1H, dd, J = 6.1 and 2.7 Hz), 3.41-3.49 (3H, m), 3.57 (2H, t, J = 7.1 Hz), 3.62 (2H, t, J = 5.6 Hz), 4.08-4.14 (2H, m), 7.09 (1H, s)
MS (FAB ⁺ ); m / z 429 [M + 1] ⁺

The compounds of Examples 101 to 102 were synthesized in the same manner as described in Example 76 using the compounds of the corresponding reference examples.

Example 101 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (7-oxo-6- (pyridin-3-yl) -4,5,6 , 7-Tetrahydrothieno [2,3-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate
(a) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (7-oxo-6- (pyridin-3-yl) -4,5,6 , 7-Tetrahydrothieno [2,3-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 1.28 (3H, d, J = 6.8 Hz), 1.40 (3H, d, J = 6.0 Hz), 1.75 (1H, d, J = 4.7
Hz), 3.09 (2H, t, J = 6.8 Hz), 3.36 (1H, dd, J = 6.5 and 2.6 Hz), 3.58-3.62 (1H, m), 4.12-4.14 (2H, m), 4.30-4.37 (2H, m), 5.27 (1H, d, J = 13.9 Hz), 5.51 (1H, d, J = 13.9 Hz), 7.34-7.36 (1H, m), 7.63 (1H, s), 7.66 (2H, d, J = 8.7 Hz), 7.74-7.79 (1H, m), 8.23 (2H, d, J = 8.7 Hz), 8.48-8.49 (1H, m), 8.64-8.65 (1H, m)
(b) (1S, 5R, 6S) -6-((R) -1-Hydroxyethyl) -1-methyl-2- (7-oxo-6- (pyridin-3-yl) -4,5,6 , 7-Tetrahydrothieno [2,3-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.1 Hz), 1.16 (3H, d, J = 6.3 Hz), 2.92 (
2H, t, J = 6.8 Hz), 3.36 (1H, dd, J = 6.1 and 2.7 Hz), 3.44-3.48 (1H, m), 3.88-3.94 (2H, m), 4.09-4.16 (2H, m) , 7.07 (1H, s), 7.35-7.38 (1H, m), 7.68-7.71 (1H, m), 8.29-8.30 (1H, m), 8.38-3.39 (1H, m)
MS (FAB ⁺ ); m / z 462 [M + 1] ⁺

Example 102 (1S, 5R, 6S) -2- (6- (2-ethoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
Em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (6- (2-Ethoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
4-Nitrobenzyl carboxylate
¹ H-NMR (CDCl ₃ ) δ: 1.18 (3H, t, J = 7.1 Hz), 1.26 (3H, d, J = 7.3 Hz), 1.38 (3H, d, J = 6.4
Hz), 1.86 (1H, d, J = 4.8 Hz), 2.88 (2H, t, J = 7.1 Hz), 3.34 (1H, dd, J = 6.5 and 2.6Hz), 3.49 (2H, q, J = 7.1 Hz), 3.55-3.75 (7H, m), 4.27-4.35 (2H, m), 5.25 (1H, d, J = 13.9 Hz), 5.50 (1H, d, J = 13.9 Hz), 7.56 (1H, s ), 7.65 (2H, d, J = 8.7 Hz), 8.22 (2H, d, J = 8.7 Hz)
(b) (1S, 5R, 6S) -2- (6- (2-Ethoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-
Sodium carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.01 (3H, t, J = 7.1 Hz), 1.08 (3H, d, J = 6.3 Hz), 1.15 (3H, d, J = 6.3 Hz), 2.78 (2H, t, J = 7.3 Hz), 3.36 (1H, dd, J = 6.1 and 2.7 Hz), 3.45 (2H, q, J = 7.1 Hz), 3.53-3.59 (7H, m), 4.09-4.15 (2H, m), 7.05 (1H, s)
MS (FAB ⁺ ); m / z 457 [M + 1] ⁺

Example 103 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
(1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) Sodium 1-methyl-1-carbapene-2-em-3-carboxylate 76 mg (0.19 mmol) in anhydrous N, N-dimethylacetamide 2 ml solution under argon atmosphere at −20 ° C. Sodium bicarbonate 16 mg (0.19 mmol) and 0.35 M1- (cyclohexyloxycarbonyloxy) ethyl iodide hexane solution 0.82 ml (0.29 mmol) were added, and the mixture was stirred at the same temperature for 1 hour.
Hexane was added to the reaction solution and decanted, then diluted with ethyl acetate and washed with water three times.
The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 49: 1) to give the title compound 86 mg (yield) 83%).
¹ H-NMR (CDCl ₃ ) δ: 1.24-2.03 (19H, m), 2.16 (3H, s), 3.28 (1H, dd, J = 7.0 and 2.6 Hz), 3.53-3.65 (1H, m), 4.24 -4.31 (2H, m), 4.60-4.73 (3H, m), 4.77-4.83 (2H, m), 6.92-6.97 (1H, m), 7.46-7.48 (0.45H, m), 7.58 (0.55H, s)
MS (FAB ⁺ ); m / z 546 [M + 1] ⁺

Example 104 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid pivaloyloxymethyl
(1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) Sodium 1-methyl-1-carbapene-2-em-3-carboxylate 44 mg (0.11 mmol) in anhydrous N, N-dimethylformamide 1 ml solution under argon atmosphere at −20 ° C. Sodium bicarbonate 3 mg (0.04 mmol) and 0.02 ml (0.13 mmol) of iodomethyl pivalate were added and stirred at the same temperature for 1 hour. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic layer was dried over anhydrous sodium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 49: 1) to give the title compound 50
mg (yield 92%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 1.22 (9H, s), 1.25-1.29 (3H, m), 1.38 (3H, d, J = 6.0 Hz), 2.16 (3H, s), 3.29 (1H, dd , J = 7.0 and 2.4 Hz), 3.54-3.66 (1H, m), 4.24-4.32 (2H, m), 4.62-4.83 (4H, m), 5.87-5.90 (1H, m), 5.97 (1H, d, J = 5.5 Hz), 7.44 (0.45H, s), 7.53 (0.55H, s)
MS (FAB ⁺ ); m / z 491 [M + 1] ⁺

Example 105 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (neopentyloxycarbonyloxy) methyl
(1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) 6-((R) -1-hydroxyethyl)- 1-methyl-1-carbapene-2-em-3-carboxylate 199 mg (0.50 mmol) in anhydrous N, N-dimethylacetamide 4 ml solution at room temperature with neopentyloxycarbonyloxymethyl chloride 109 mg (0.60 mmol) And benzyltriethylammonium chloride 57 mg (0.25 mmol) was added, and it stirred at 40 degreeC for 4 hours. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic layer was dried over anhydrous sodium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluted with ethyl acetate: methanol = 19: 1) to obtain 212 mg (yield 81%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.95 (9H, s), 1.26 (3H, d.J = 7.2 Hz), 1.37 (3H, d, J = 6.4 Hz), 2.16 (3H, s), 3.29 ( 1H, dd, J = 7.2and 2.8 Hz), 3.57-3.64 (1H, m), 3.89 (2H, s), 4.26-4.31 (2H, m), 4.64-4.67 (2H, m), 4.79-4.82 ( 2H, m), 5.91-5.96 (2H, m), 7.49 (0.45H, s), 7.59 (0.55H, s)
MS (FAB ⁺ ); m / z 520 M ⁺

The compounds of Examples 106 to 129 were synthesized in the same manner as described in Example 103 or Example 105.

Example 106 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (n-pentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.90 (3H, m), 1.25-1.40 (10H, m), 1.64-1.72 (2H, m), 2.16 (3H,
s), 3.08-3.15 (1H, br s), 3.29 (1H, dd, J = 7.0 and 2.7 Hz), 3.55-3.66 (1H, m), 4.19 (2H, t, J = 6.8 Hz), 4.21- 4.33 (2H, m), 4.61-4.85 (4H, m), 5.89-5.96 (2H, m), 7.48 (0.45H, s), 7.59 (0.55H, s)
MS (ESI ⁺ ); m / z 521 [M + 1] ⁺

Example 107 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclopentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.27 (3H, m), 1.38 (3H, d, J = 6.3 Hz), 1.55-1.90 (8H, m), 2.16 (3H, s), 2.52-2.58 (1H, br s), 3.29 (1H, dd, J = 7.1 and 2.6 Hz), 3.54-3.66 (1H, m),
4.24-4.34 (2H, m), 4.62-4.85 (4H, m), 5.10-5.16 (1H, m), 5.87-5.95 (2H, m), 7.48 (0.45H, s), 7.59 (0.55H, s )
MS (ESI ⁺ ); m / z 519 [M + 1] ⁺

Example 108 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (pentan-3-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.91 (6H, t, J = 7.5 Hz), 1.24-1.28 (3H, m), 1.37 (3H, d, J = 6.3 Hz), 1.59-1.68 (4H, m ), 2.16 (3H, s), 2.97-3.03 (1H, br s), 3.29 (1H, dd, J = 7.0 and 2.5
Hz), 3.55-3.66 (1H, m), 4.23-4.33 (2H, m), 4.60-4.85 (5H, m), 5.91-5.96 (2H, m), 7.48 (0.45H, s), 7.58 (0.55) H, s)
MS (ESI ⁺ ); m / z 521 [M + 1] ⁺

Example 109 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-cyclohexylacetoxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.89-1.85 (17H, m), 2.16 (3H, s), 2.25 (2H, dd, J = 7.0 and 1.5 Hz), 2.95-3.02 (1H, br s), 3.29 (1H, dd, J = 7.1 and 2.7 Hz), 3.55-3.66 (1H, m), 4.23-4.33 (2H, m), 4.61-4.84 (4H, m), 5.89-5.95 (2H, m), 7.46 (0.45H, s), 7.55 (0.55H, s)
MS (ESI ⁺ ); m / z 531 [M + 1] ⁺

Example 110 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- (Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methylbutanoyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.95 (6H, d, J = 6.6 Hz), 1.24-1.28 (3H, m), 1.38 (3H, d, J = 6.1 Hz), 2.08-2.16 (1H, m ), 2.16 (3H, s), 2.24-2.28 (2H, m), 2.54-2.58 (1H, br s), 3.29 (1H,
dd, J = 7.0 and 2.5 Hz), 3.55-3.66 (1H, m), 4.23-4.32 (2H, m), 4.62-4.84 (4H, m), 5.89-5.96 (2H, m), 7.46 (0.45H , s), 7.56 (0.55H, s)
MS (ESI ⁺ ); m / z 491 [M + 1] ⁺

Example 111 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (tert-
Butyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26-1.28 (3H, m), 1.38 (3H, d, J = 6.1 Hz), 1.50 (9H, s), 2.16 (3H, s), 2.71-2.77 (1H , br s), 3.28 (1H, dd, J = 7.1 and 2.7 Hz), 3.54-3.66 (1H, m), 4.23-4.32 (2H, m), 4.62-4.83 (4H, m), 5.84-5.92 ( 2H, m), 7.48 (0.45H, s), 7.58 (0.55H, s) MS (FAB ⁺ ); m / z 507 [M + 1] ⁺

Example 112 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (isobutyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.94 (6H, d, J = 6.8Hz), 1.24-1.28 (3H, m), 1.37 (3H, d, J = 6.4 Hz),
1.92-2.04 (1H, m), 2.16 (3H, s), 2.97-3.04 (1H, br s), 3.29 (1H, dd, J = 7.0 and 2.4Hz), 3.55-3.66 (1H, m), 3.97 (2H, d, J = 6.5 Hz), 4.23-4.33 (2H, m), 4.62-4.84 (4H, m), 5.90-5.96 (2H, m), 7.48 (0.45H, s), 7.59 (0.55H , s)
MS (FAB ⁺ ); m / z 507 [M + 1] ⁺

Example 113 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (N, N-diisopropylaminocarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.21 -1.28 (15H, m), 1.36 (3H, d, J = 6.4 Hz), 2.16 (3H, s), 3.27 (1H, dd, J = 6.8 and 2.8 Hz ), 3.55-3.62 (1H, m), 3.72-3.80 (1H, br s), 4.03-4.08 (1H, br
s), 4.25-4.30 (2H, m), 4.63-4.66 (2H, m), 4.78-4.81 (2H, m), 5.92 (1H, d, J = 5.6Hz), 5.98 (1H, d, J = 5.6 Hz), 7.43 (0.45H, s), 7.52 (0.55H, s)
MS (FAB ⁺ ); m / z 534 [M + 1] ⁺

Example 114 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 7.2Hz), 1.38 (3H, d, J = 6.4 Hz), 2.17 (3H, s), 2.21 (3H, s), 3.30 ( 1H, dd, J = 6.8 and 2.8 Hz), 3.57-3.64 (1H, m), 4.28-4.30 (2H, m), 4.65-4.70 (2H, m), 4.80-4.83 (2H, m), 4.90 -5.10 (2H, m), 7.39 (0.4H, s), 7.45 (0.6H, s)
MS (FAB ⁺ ); m / z 489 [M + 1] ⁺

Example 115 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid acetoxymethyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 6.8Hz), 1.37 (3H, d, J = 6.0 Hz), 2.13 (3H, s), 2.16 (3H, s), 3.29 ( 1H, dd, J = 6.8 and 2.4 Hz), 3.57-3.65 (1H, m), 4.25-4.31 (2H, m), 4.64-4.68 (2H, m), 4.79-4.83 (2H, m), 5.87 -5.89 (1H, m), 5.94-5.96 (1H, m), 7.47 (0.4H, s), 7.57 (0.6H, s)
MS (FAB ⁺ ); m / z 449 [M + 1] ⁺

Example 116 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclohexyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 7.6Hz), 1.30-1.35 (2H, m), 1.37 (3H, d, J = 6.4 Hz),
1.45-1.55 (4H, m), 1.62-1.66 (2H, m), 1.91-1.97 (2H, m), 2.16 (3H, s), 3.28 (1H, dd, J = 6.8 and 2.4 Hz), 3.56- 3.64 (1H, m), 4.27-4.30 (2H, m), 4.64-4.67 (3H, m), 4.79-4.82 (2H, m), 5.89-5.96 (2H, m), 7.48 (0.4H, s) , 7.59 (0.6H, s)
MS (FAB ⁺ ); m / z 533 [M + 1] ⁺

Example 117 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (isopropyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.25-1.27 (3H, m), 1.31 (6H, d. J = 6.0 Hz), 1.37 (3H, d, J = 6.4 Hz),
2.16 (3H, s), 3.28 (1H, dd, J = 6.8 and 2.4 Hz), 3.57-3.64 (1H, m), 4.26-4.31 (2H, m), 4.64-4.67 (2H, m), 4.79- 4.82 (2H, m), 4.90-4.96 (1H, m), 5.88-5.90 (1H, m), 5.94-5.96 (1H, m), 7.49 (0.45H, s), 7.59 (0.55H, s)
MS (FAB ⁺ ); m / z 493 [M + 1] ⁺

Example 118 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid n-hexyl
¹ H-NMR (CDCl ₃ ) δ: 0.88 (3H, t, J = 7.2Hz), 1.24-1.32 (7H, m), 1.39 (3H, d, J = 6.4 Hz),
1.76 (4H, m), 2.16 (3H, s), 3.29 (1H, dd, J = 7.2 and 2.8 Hz), 3.54-3.61 (1H, m), 4.10-4.15 (1H, m), 4.18-4.23 ( 1H, m), 4.26-4.35 (2H, m), 4.63-4.66 (2H, m), 4.78-4.81 (2H, m), 7.38 (0.45H, s), 7.46 (0.55H, s)
MS (FAB ⁺ ); m / z 461 M ⁺

Example 119 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (N, N-diisobutylaminocarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.80-0.84 (6H, m), 0.88 (6H, d, J = 6.8 Hz), 1.24-1.26 (3H, m), 1.37 (3H, d, J = 6.4 Hz) ), 1.82-2.06 (2H, m), 2.16 (3H, s), 3.00-3.12 (4H, m), 3.27 (1H, dd,
J = 6.8 and 2.4 Hz), 3.54-3.62 (1H, m), 4.25-4.28 (2H, m), 4.64-4.67 (2H, m), 4.78-4.81 (2H, m), 5.94 (2H, d, J = 2.4 Hz), 7.44 (0.45H, s), 7.53 (0.55H, s)
MS (FAB ⁺ ); m / z 562 [M + 1] ⁺

Example 120 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (N, N-diisobutylaminocarbonyl) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.86-0.90 (6H, m), 0.93 (6H, m), 1.24 (3H, d, J = 7.2 Hz), 1.36 (3H,
d, J = 6.4 Hz), 1.95-2.02 (2H, m), 2.15 (3H, s), 3.04-3.06 (2H, m), 3.16-3.23 (2H, m), 3.26 (1H, dd, J = 7.6 and 2.4 Hz), 3.55-3.59 (1H, m), 4.20-4.24 (1H, m), 4.27-4.29 (1H, m), 4.57-4.61 (2H, m), 4.72-4.76 (3H, m) , 5.09-5.14 (1H, m), 7.44 (0.45H, s), 7.53 (0.55H, s)
MS (FAB ⁺ ); m / z 546 [M + 1] ⁺

Example 121 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (phenyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26-1.29 (3H, m), 1.38 (3H, d. J = 6.4 Hz), 2.15 (3H, s), 3.31 (1H, dd, J = 6.8 and 2.4 Hz ), 3.58-3.66 (1H, m), 4.28-4.33 (2H, m), 4.62-4.64 (2H, br s), 4.78-4.81 (2H, m), 5.96-5.98 (1H, m), 6.09- 6.11 (1H, m), 7.21-7.28 (3H, m), 7.37-7.41 (2H, m), 7.49 (0.45H, s), 7.59 (0.55H, s)
MS (FAB ⁺ ); m / z 527 [M + 1] ⁺

Example 122 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- 2-hydroxybutyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.90 (6H, t, J = 7.6 Hz), 1.25 (3H, d, J = 7.2 Hz), 1.38-1.42 (7H, m),
1.61-1.64 (1H, m), 2.16 (3H, s), 3.28-3.30 (1H, m), 3.52-3.58 (1H, m), 4.07-4.11 (1H, m), 4.25-4.29 (3H, m ), 4.63-4.66 (2H, m), 4.77-4.80 (2H, m), 7.37 (0.45H, s), 7.45 (0.55H, s)
MS (FAB ⁺ ); m / z 461 M ⁺

Example 123 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cis-2,6 dimethylpiperidin-1-ylcarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.19-1.22 (6H, m), 1.25-1.27 (3H, m), 1.37 (3H, d, J = 6.4 Hz), 1.44-1.76 (6H, m), 2.16 (3H, s), 3.28 (1H, dd, J = 6.8 and 2.4 Hz), 3.55-3.62 (1H, m), 4.26-4.33 (4H, m), 4.63-4.67 (2H, m), 4.78-4.81 (2H, m), 5.93-5.99 (2H, m), 7.45 (0.45H,
s), 7.53 (0.55H, s)
MS (FAB ⁺ ); m / z 546 [M + 1] ⁺

Example 124 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (isopentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.91 (6H, d, J = 6.4Hz), 1.25-1.27 (3H, m), 1.38 (3H, d, J = 6.0 Hz),
1.57 (2H, q, J = 6.8 Hz), 1.68-1.75 (1H, m), 2.16 (3H, s), 3.28 (1H, dd, J = 6.8 and2.4 Hz), 3.55-3.66 (1H, m ), 4.22 (2H, t, J = 6.8 Hz), 4.27-4.30 (2H, m), 4.64-4.67 (2H, m), 4.79-4.82 (2H, m), 5.90-5.96 (2H, m), 7.48 (0.4H, s), 7.59 (0.6H, s)
MS (FAB ⁺ ); m / z 520 M ⁺

Example 125 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid isobutyryloxymethyl
¹ H-NMR (CDCl ₃ ) δ: 1.18-1.21 (6H, m), 1.26-1.27 (3H, m), 1.37 (3H, d, J = 6.4 Hz), 2.16
(3H, s), 2.58-2.65 (1H, m), 3.29 (1H, dd, J = 6.8 and 2.4 Hz), 3.57-3.64 (1H, m), 4.26-4.31 (2H, m), 4.64-4.68 (2H, m), 4.79-4.83 (2H, m), 5.88-5.90 (1H, m), 5.94-5.98 (1H, m), 7.46 (0.4H, s), 7.55 (0.6H, s)
MS (FAB ⁺ ); m / z 477 [M + 1] ⁺

Example 126 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclohexylmethyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.96-1.01 (2H, m), 1.14-1.32 (7H, m), 1.26 (3H, dd, J = 7.2 and 2.4 Hz), 1.38 (3H, d, J = 6.4 Hz), 1.63-1.73 (5H, m), 2.16 (3H, s), 3.28 (1H, dd, J = 6.8 and 2.8 Hz), 3.57-3.64 (1H, m), 3.99 (2H, d, J = 6.4 Hz), 4.27-4.30 (2H, m), 4.64-4.67 (2H, m), 4.79-4.82 (2H, m), 5.90-5.96 (2H, m), 7.48 (0.45H, s), 7.59 (0.55H, s)
MS (FAB ⁺ ); m / z 546 [M + 1] ⁺

Example 127 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (n-butoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.93 (3H, t, J = 7.5Hz), 1.24-1.28 (8H, m), 1.61-1.71 (2H, m), 1.82 (1H, br s), 2.16 ( 3H, s), 3.28 (1H, dd, J = 6.8 and 2.4 Hz), 3.56-3.64 (1H, m), 4.19 (2H, t, J = 6.6 Hz), 4.26-4.31 (2H, m), 4.64 -4.67 (2H, m), 4.79-4.82 (2H, m), 5.89-5.96 (2H, m), 7.49 (0.4H, s), 7.60 (0.6H, s)
MS (ESI ⁺ ); m / z 507 [M + 1] ⁺

Example 128 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (heptan-4-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.90 (6H, t, J = 7.6Hz), 1.25-1.40 (14H, m), 1.77 (1H, br s), 2.16 (3H, s), 3.28 (1H, dd, J = 6.8 and 2.4Hz), 3.56-3.64 (1H, m), 4.25-4.31 (2H, m), 4.63-4.82 (5H, m), 5.91-5.95 (2H, m), 7.48 (0.4H , s), 7.59 (0.6H, s)
MS (ESI ⁺ ); m / z 549 [M + 1] ⁺

Example 129 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid benzoyloxymethyl
¹ H-NMR (CDCl ₃ ) δ: 1.23-1.28 (3H, m), 1.37 (3H, d, J = 6.4 Hz), 1.83 (1H, br s), 2.13-2.14 (3H, m), 3.28 ( 1H, dd, J = 7.0and 2.7 Hz), 3.54-3.64 (1H, m), 4.27-4.32 (2H, m),
4.60-4.62 (2H, m), 4.74-4.89 (2H, m), 6.15-6.16 (2H, m), 7.41-7.59 (4H, m), 8.05-8.07 (2H, m)
MS (ESI ⁺ ); m / z 511 [M + 1] ⁺

Example 130 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1,3-dioxoisoindoline-2-yl) methyl
(1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 2-methyl-1-carbapene-2-em-3-carboxylate 39 mg (0.10 mmol) in anhydrous N, N-dimethylacetamide 2 ml solution at room temperature under argon atmosphere at 2- (
Bromomethyl) isoindoline-1,3-dione (28 mg, 0.12 mmol) was added, and the mixture was heated to 40 ° C. and stirred for 2 hours. Saturated aqueous sodium hydrogen carbonate solution was added to stop the reaction, and the mixture was diluted with ethyl acetate and washed 3 times with water. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 25: 1) to give the title compound 44 mg (yield). 83%).
¹ H-NMR (CDCl ₃ ) δ: 1.21-1.33 (6H, m), 1.74 (1H, d, J = 4.8 Hz), 2.14 (3H, s), 3.15 (1H,
dd, J = 6.8 and 2.6 Hz), 3.49-3.57 (1H, m), 4.21-4.27 (2H, m), 4.56-4.59 (2H, m), 4.70-4.74 (2H, m), 5.77-5.81 ( 1H, m), 5.99-6.02 (1H, m), 7.37 (0.4H, s), 7.48 (0.6H, s), 7.77-7.80 (2H, m), 7.92-7.95 (2H, m)
MS (ESI ⁺ ); m / z 536 [M + 1] ⁺

Example 131 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (N-methylbenzamido) methyl
(1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-Methyl-1-carbapene-2-em-3-carboxylate 56 mg (0.14 mmol) in anhydrous N, N-dimethylacetamide 2 ml solution at room temperature under argon atmosphere at room temperature N-methylbenzeneamide 39 mg (0.21 mmol) was added, and the mixture was stirred at the same temperature for 1 hour. Saturated aqueous sodium hydrogen carbonate solution was added to stop the reaction, and the mixture was diluted with ethyl acetate and washed 3 times with water. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluting with acetone: ethyl acetate = 2: 1) to give 18 mg (yield) of the title compound. Rate 27%).
¹ H-NMR (CDCl ₃ ) δ: 1.26-1.28 (3H, m), 1.41 (3H, d, J = 6.3 Hz), 2.14 (1.2H, s), 2.15 (1.8H, s), 3.14-3.26 (3H, m), 3.30-3.341 (1H, m), 3.59-3.61 (1H, m), 4.29-4.31 (2H, m), 4.62-4.64 (2H, m), 4.77-4.79 (2H, m) , 5.44-5.46 (2H, m), 7.39-7.54 (6H, m)
MS (FAB ⁺ ); m / z 524 [M + 1] ⁺

The compounds of Examples 132 to 190 were synthesized in the same manner as described in Example 103 or Example 105.

Example 132 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2- (N, N-dicyclohexylamino) -2-oxo) ethyl
¹ H-NMR (CDCl ₃ ) δ: 1.16-2.37 (29H, m), 3.17-3.29 (3H, m), 3.52-3.62 (1H, m), 4.20-4.31 (2H, m), 4.57-4.81 ( 5H, m), 5.08-5.14 (1H, m), 7.47 (0.4H, s), 7.54 (0.6H, s)
MS (FAB ⁺ ); m / z 598 [M + 1] ⁺

Example 133 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- (Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3,3-dimethylbutanoyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.02 (9H, s), 1.26 (3H, d, J = 7.2 Hz), 1.38 (3H, d, J = 6.3 Hz), 2.16 (3H, s), 2.26 ( 2H, s), 3.28 (1H, dd, J = 6.9 and 2.4 Hz), 3.50-3.68 (1H, m), 4.20-4.32 (2H, m), 4.60-4.85 (4H, m), 5.87-5.96 ( 2H, m), 7.46 (0.4H, s), 7.55 (0.6H, s)

Example 134 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrole-2-
Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid (tetrahydro-2H-pyran-4-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.29 (3H, m), 1.37 (3H, d, J = 6.1 Hz), 1.72-2.04 (4H, m), 2.16 (3H, s), 3.29 (1H , dd, J = 6.8and 2.4 Hz), 3.49-3.66 (3H, m), 3.89-3.96 (2H, m), 4.26-4.31 (2H, m), 4.63-4.69 (2H, m), 4.78-4.84 (2H, m), 4.85-4.93 (1H, m), 5.87-5.90 (1H, m), 5.98-6.01 (1H, m), 7.50 (0.4H, s), 7.61 (0.6H, s)
MS (FAB ⁺ ); m / z 535 [M + 1] ⁺

Example 135 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrole-2-
Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid (1,3-dioxane-5-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.29 (3H, m), 1.37 (3H, d, J = 6.3 Hz), 1.81-1.86 (1H, m), 2.16 (3H, s), 3.28 (1H , dd, J = 6.8and 2.6 Hz), 3.55-3.66 (1H, m), 4.02-4.05 (4H, m), 4.26-4.31 (2H, m), 4.63-4.69 (3H, m), 4.78-4.84 (3H, m), 4.89-4.93 (1H, m), 5.87-5.90 (1H, m), 6.00-6.04 (1H, m), 7.49 (0.4H, s), 7.61 (0.6H, s)
MS (FAB ⁺ ); m / z 537 [M + 1] ⁺

Example 136 (1S, 5R, 6S) -2- (5-acetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (
(Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.24-2.20 (22H, m), 2.87 (1H, t, J = 5.6 Hz), 2.93 (1H, t, J = 5.6 Hz), 3.26 (1H, dd, J = 7.0 and 2.0Hz), 3.50-3.60 (1H, m), 3.75 (1H, t, J = 5.6 Hz), 3.88-3.94 (1H, m), 4.21-4.30 (2H, m), 4.50-4.80 ( 3H, m), 6.90-6.96 (1H, m), 7.33 (0.5H, s), 7.55 (0.5H, s)
MS (FAB ⁺ ); m / z 560 [M + 1] ⁺

Example 137 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.21-2.00 (19H, m), 3.26-3.29 (1H, m), 3.39-3.44 (1H, m), 3.54-3.62 (1H, m), 4.20 (2H, d, J = 4.8Hz), 4.51-4.89 (4H, m), 6.91-6.97 (1H, m), 7.50-7.56 (1H, m)
MS (FAB ⁺ ); m / z 563 [M + 1] ⁺

Example 138 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (N, N-diisopropylaminocarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.21 (12H, d, J = 5.9 Hz), 1.23-1.27 (3H, m), 1.36 (3H, d, J = 6.4 Hz), 2.89-2.96 (1H, br s), 3.27 (1H, dd, J = 7.0 and 2.5 Hz), 3.47-3.55 (1H, m), 3.55-3.64 (1H, m), 3.73-3.84 (1H, br s), 3.98-4.12 (1H , br s), 4.20 (2H, s), 4.22-4.31 (2H, m), 4.49-4.84 (4H, m), 5.90-5.94 (1H, m), 5.96-5.99 (1H, m), 7.46 ( 0.45H, s), 7.49 (0.55H, s)
MS (ESI ⁺ ); m / z 550 [M + 1] ⁺

Example 139 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (neopentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.95 (9H, s), 1.26 (3H, d, J = 6.4 Hz), 1.37 (3H, d, J = 6.1 Hz), 2.62-2.67 (1H, br s) , 3.29 (1H, dd, J = 6.6 and 2.2 Hz), 3.47-3.54 (1H, m), 3.55-3.67 (1H, m), 3.89 (2H, s), 4.22 (2H, d, J = 3.9 Hz ), 4.24-4.33 (2H, m), 4.53-4.88 (4H, m), 5.91-5.97 (2H, m), 7.52 (0.45H, s), 7.56 (0.55H, s)
MS (ESI ⁺ ); m / z 537 [M + 1] ⁺

Example 140 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclohexyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₆ ) δ: 1.17-1.90 (16H, m), 3.27-3.30 (1H, m), 3.42-3.44 (1H, m), 3.56-3.63 (1H, m), 4.20-4.30 ( 5H, m), 4.51-4.87 (5H, m), 5.87-5.96 (2H, m), 7.50-7.60 (1H, m) MS (ESI ⁺ ); m / z549 [M + 1] ⁺

Example 141 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid acetoxymethyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.29 (3H, m), 1.38 (3H, d, J = 6.4 Hz), 2.13 (3H, s), 3.29 (1H,
dd, J = 7.1 and 2.4 Hz), 3.39-3.45 (1H, m), 3.57-3.66 (1H, m), 4.19-4.22 (2H, m), 4.24-4.31 (2H, m), 4.53-4.57 ( 1H, m), 4.68-4.75 (2H, m), 4.87-4.89 (1H, m), 5.86-5.90 (1H, m), 5.93-5.97 (1H, m), 7.51 (0.5H, s), 7.55 (0.5H, s)
MS (FAB ⁺ ); m / z 465 [M + 1] ⁺

Example 142 ((1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ( (R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (tetrahydro-2H-pyran-4-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.28 (3H, m), 1.37 (3H, d, J = 6.3 Hz), 1.72-1.82 (2H, m), 1.95-2.04 (2H, m), 3.29 (1H, dd, J = 6.8and 2.4 Hz), 3.40-3.45 (1H, m), 3.50-3.65 (3H, m), 3.89-3.96 (2H, m), 4.19-4.22 (2H, m), 4.26 -4.31 (2H, m), 4.53-4.57 (1H, m), 4.69-4.74 (2H, m), 4.85-4.92 (2H, m), 5.87-5.90 (1H, m), 5.98-6.01 (1H, m), 7.54 (0.4H, s), 7.58 (0.6H, s)
MS (FAB ⁺ ); m / z 551 [M + 1] ⁺

Example 143 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1,3-dioxane-5-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.29 (3H, m), 1.37 (3H, d, J = 6.3 Hz), 3.29 (1H, dd, J = 6.6 and
2.4 Hz), 3.40-3.45 (1H, m), 3.58-3.66 (1H, m), 4.02-4.05 (4H, m), 4.19-4.22 (2H, m), 4.26-4.32 (2H, m), 4.54 -4.57 (1H, m), 4.64-4.69 (1H, m), 4.69-4.75 (2H, m), 4.79-4.82 (1H, m), 4.87-4.90 (1H, m), 4.90-4.93 (1H, m), 4.87-5.90 (1H, m), 6.01-6.04 (1H,
m), 7.53 (0.4H, s), 7.58 (0.6H, s)
MS (FAB ⁺ ); m / z 553 [M + 1] ⁺

Example 144 (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.10-2.05 (19H, m), 3.28 (1H, dd, J = 6.6 and 2.4 Hz), 3.52-3.65 (1H, m), 4.20-4.35 (2H, m) , 4.58-4.72 (1H, m), 4.74 (1H, s), 4.89 (1H, s), 5.17 (1H, s),
5.32 (1H, s), 5.63-5.73 (1H, m), 6.90-6.97 (1H, m), 7.38-7.45 (1H, m), 7.46 (0.5H, s), 7.56 (0.5H, s)

Example 145 (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (neopentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.95 (9H, s), 1.26 (3H, d, J = 6.9 Hz), 1.37 (3H, d, J = 6.3 Hz), 3.29 (1H, dd, J = 6.9 and 3.0 Hz), 3.54-3.68 (1H, m), 3.89 (2H, s), 4.22-4.35 (2H, m), 4.75 (1H, s), 4.89 (1H, s), 5.18 (1H, s) , 5.33 (1H, s), 5.60-5.70 (1H, m), 5.92 (1H, d, J = 5.4 Hz), 5.95 (1H, d, J = 5.4 Hz), 7.36-7.45 (1H, m), 7.48 (0.5H, s), 7.57 (0.5H, s)

Example 146 (1S, 5R, 6S) -2- (5- (4,5-dihydrothiazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine-2- Yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.05 (19H, m), 2.92 (2H, t, J = 5.6 Hz), 3.25 (1H, dd, J = 7.1 and 2.4 Hz), 3.34 (2H, t , J = 7.5Hz), 3.52-3.61 (1H, m), 3.77 (2H, t, J = 5.6 Hz), 4.04 (2H, t, J = 7.5 Hz), 4.21-4.34 (2H, m), 4.57 (2H, s), 4.58-4.72 (1H, m), 6.91-6.97 (1H,
m), 7.37 (1H, s)
MS (FAB ⁺ ); m / z 604 [M + 1] ⁺

Example 147 (1S, 5R, 6S) -2- (5- (4,5-dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl ) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-
Em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.24-2.03 (19H, m), 3.27 (1H, dd, J = 7.0 and 2.6 Hz), 3.38-3.44 (2H, m), 3.54-3.63 (1H, m) , 4.09 (2H, t, J = 7.5 Hz), 4.23-4.30 (2H, m), 4.60-4.72 (3H, m), 4.79-4.82 (2H, m), 6.91-6.94 (1H, m), 7.51 (1H, s)
MS (FAB ⁺ ); m / z 590 [M + 1] ⁺

Example 148 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-propionyl-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (
(Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-1.94 (22H, m), 2.37 (2H, q, J = 7.2 Hz), 3.27 (1H, dd, J = 6.8 and 2.4 Hz), 3.55-3.62 (1H , m), 4.25-4.30 (2H, m), 4.59-4.72 (3H, m), 4.76-4.79 (2H, br s), 6.94 (1H, q, J = 5.2 Hz), 7.46 (0.4H, s ), 7.59 (0.6H, s)
MS (FAB ⁺ ); m / z 560 M ⁺

Example 149 (1S, 5R, 6S) -2- (5- (2-ethoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c]
1- (cyclohexyloxycarbonyloxy) ethyl (diastereomeric mixture) of pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid )
¹ H-NMR (CDCl ₃ ) δ: 1.23-2.03 (22H, m), 2.43-2.55 (1H, m), 3.28 (1H, dd, J = 6.6 and 1.9
Hz), 3.55-3.67 (3H, m), 4.18 (2H, s), 4.22-4.30 (2H, m), 4.59-4.77 (3H, m), 4.81-4.90 (2H, m), 6.91-6.97 ( 1H, m), 7.47 (0.5H, s), 7.57 (0.5H, s)
MS (FAB ⁺ ); m / z 590 M ⁺

Example 150 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isobutyryl-5,6-dihydro-4H-thieno [2,3-c] pyrrole-2 -Yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20 (6H, d, J = 6.5 Hz), 1.22-2.05 (19H, m), 2.67-2.84 (2H, m), 3.30 (1H, d, J = 7.0 Hz ), 3.52-3.67 (1H, m), 4.22-4.33 (2H, m), 4.60-4.90 (5H, m), 6.95 (1H, q, J = 5.5 Hz), 7.45 (0.25H, s), 7.46 (0.25H, s), 7.59 (0.5H, s)
MS (ESI ⁺ ); m / z 575 [M + 1] ⁺

Example 151 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methylsulfonyl-5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.23-1.95 (19H, m), 2.29-2.38 (1H, br s), 2.92 (3H, s), 3.28 (1H, dt, J = 7.1 and 2.1 Hz), 3.54-3.62 (1H, m), 4.23-4.30 (2H, m), 4.54-4.72 (4H, m), 6.90-6.96 (1H, m), 7.48 (1H, s)
MS (FAB ⁺ ); m / z 582 [M + 1] ⁺

Example 152 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyacetyl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.00 (19H, m), 2.51-2.55 (1H, br s), 3.28 (1H, d, J = 6.4 Hz), 3.49 (3H, s), 3.54- 3.64 (1H, m), 4.14 (2H, s), 4.25-4.31 (2H, m), 4.58-4.73 (3H, m), 4.82-4.86 (2H, m), 6.91-6.97 (1H, m), 7.47 (0.45H, s), 7.56 (0.55H, s)
MS (ESI ⁺ ); m / z 577 M ⁺

Example 153 (1S, 5R, 6S) -2- (5- (2-acetamidoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.23-2.02 (19H, m), 2.09 (3H, s), 2.44-2.49 (1H, br s), 3.27-3.31 (1H, m), 3.54-3.63 (1H , m), 4.10 (2H, d, J = 4.1 Hz), 4.25-4.32 (2H, m), 4.59-4.73 (3H,
m), 4.78-4.83 (2H, m), 6.62-6.66 (1H, br s), 6.91-6.97 (1H, m), 7.51 (1H, s)
MS (FAB ⁺ ); m / z 604 [M + 1] ⁺

Example 154 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-methoxypropanoyl) -5,6-dihydro-4H-thieno [2,3 -c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.22-2.10 (19H, m), 2.63 (2H, t, J = 6.2 Hz), 2.74-2.82 (1H, br s), 3.28 (1H, dt, J = 7.0 and 2.2 Hz), 3.37 (3H, s), 3.55-3.62 (1H, m), 3.77 (2H, t, J = 6.2
Hz), 4.22-4.30 (2H, m), 4.58-4.72 (3H, m), 4.77-4.88 (2H, m), 6.91-6.96 (1H, m), 7.46 (0.45H, s), 7.56 (0.55) H, s)
MS (FAB ⁺ ); m / z 590 [M + 1] ⁺

Example 155 (1S, 5R, 6S) -2- (5-cyclopropanecarbonyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 0.84-0.90 (2H, m), 1.04-1.10 (2H, m), 1.23-2.10 (20H, m), 2.74-2.90 (1H, m), 3.27 (1H, dd, J = 6.7and 1.4 Hz), 3.52-3.66 (1H, m), 4.20-4.30 (2H, m), 4.58-4.80 (3H, m), 4.82-5.02 (2H, m), 6.94 (1H, q, J = 5.2 Hz), 7.46 (0.45H, s), 7.61 (0.55H, s)
MS (FAB ⁺ ); m / z 572 [M + 1] ⁺

Example 156 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (oxazole-4-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.24-2.01 (19H, m), 3.28 (1H, dd, J = 7.1 and 2.4 Hz), 3.53-3.65 (1H, m), 4.24-4.32 (2H, m) , 4.60-4.73 (1H, m), 4.83-4.85 (1H, m), 4.97-5.00 (1H, m), 5.20-5.23 (1H, m), 5.35-5.38 (1H, m), 6.91-6.98 ( 1H, m), 7.52-7.58 (1H, m), 7.92 (1H, s), 8.34-8.37 (1H, m)
MS (FAB ⁺ ); m / z 599 [M + 1] ⁺

Example 157 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-1H-imidazole-4-carbonyl) -5,6 -Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.24-2.10 (19H, m), 3.27 (1H, dd, J = 7.0 and 2.4 Hz), 3.54-3.64 (1H, m), 3.76 (3H, s), 4.23 -4.29 (2H, m), 4.60-4.72 (1H, m), 4.81-4.85 (1H, m), 5.26-5.29 (1H, m), 5.41-5.45 (1H, m), 6.91-6.98 (1H, m), 7.43-7.46 (1H, m), 7.51-7.58 (1H, m), 7.66-7.68 (1H, m)
MS (FAB ⁺ ); m / z 613 [M + 1] ⁺

Example 158 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridine-3-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-1.94 (19H, m), 3.26-3.28 (1H, m), 3.55-3.61 (1H, m), 4.27-4.31 (2H, m), 4.58-5.04 ( 5H, m), 6.90-6.94 (1H, m), 7.40-7.55 (2H, m), 7.91 (1H, d, J = 7.2 Hz), 8.72 (1H, d, J = 3.6 Hz), 8.85 (1H , s)
MS (FAB ⁺ ); m / z 610 [M + 1] ⁺

Example 159 (1S, 5R, 6S) -2- (5- (3-acetamidopropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6 -((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.23-2.05 (22H, m), 2.58 (2H, t, J = 5.5 Hz), 2.74-2.84 (1H, m), 3.26-3.30 (1H, m), 3.54 -3.64 (3H, m), 4.23-4.32 (2H, m), 4.58-4.80 (5H, m), 6.56-6.61 (1H, m), 6.93 (1H, q, J = 5.3Hz), 7.51 (1H , s)
MS (FAB ⁺ ); m / z 618 [M + 1] ⁺

Example 160 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-methoxycarbonyl-5,6-
Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylate 1- (cyclohexyloxycarbonyloxy) ethyl (diastereomeric mixture) )
¹ H-NMR (CDCl ₃ ) δ: 1.22-2.02 (19H, m), 3.27 (1H, dd, J = 6.8 and 2.4 Hz), 3.53-3.62 (1H, m), 3.78 (3H, s), 4.23 -4.29 (2H, m), 4.52-4.75 (5H, m), 6.90-7.00 (1H, m), 7.47-7.55 (1H, m)
MS (FAB ⁺ ); m / z 562 [M + 1] ⁺

Example 161 (1S, 5R, 6S) -2- (5-cyclopropyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 0.51-0.54 (4H, m), 1.20-2.03 (19H, m), 2.13-2.19 (1H, m), 3.25 (1H, dd, J = 6.8 and 2.7 Hz) , 3.52-3.61 (1H, m), 3.96-3.99 (2H, m), 4.11-4.14 (2H, m), 4.19-4.30 (2H, m), 4.59-4.72 (1H, m), 6.91-6.97 ( 1H, m), 7.50-7.52 (1H, m)
MS (ESI ⁺ ); m / z 545 [M + 1] ⁺

Example 162 (1S, 5R, 6S) -2- (5- (2-N, N-dimethylaminoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.23-2.03 (19H, m), 2.35-2.40 (6H, m), 3.20 (2H, s), 3.28 (1H, dd,
J = 6.8 and 2.4 Hz), 3.51-3.65 (1H, m), 4.23-4.31 (2H, m), 4.58-4.83 (4H, m), 4.91-4.95 (1H, m), 6.91-6.98 (1H, m), 7.48 (0.5H, s), 7.56 (0.5H, s)
MS (FAB ⁺ ); m / z 590 [M + 1] ⁺

Example 163 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (3-hydroxypropanoyl) -5,6-dihydro-4H-thieno- [2, 3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.08 (20H, m), 2.60 (2H, t, J = 5.2 Hz), 3.28 (1H, dd, J = 6.8 an
d 2.8 Hz), 3.39-3.45 (1H, m), 3.53-3.63 (1H, m), 3.96 (2H, br q, J = 5.4 Hz), 4.23-4.32 (2H, m), 4.59-4.73 (3H , m), 4.75-4.85 (2H, m), 6.91-6.97 (1H, m), 7.47-7.58 (1H,
m)
MS (FAB ⁺ ); m / z 577 [M + 1] ⁺

Example 164 (1S, 5R, 6S) -2- (6-acetyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (
(Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.21-1.91 (19H, m), 2.17 (1.2H, s), 2.19 (1.8H, s), 2.71-2.77 (2H, m), 3.24-3.26 (1H, m), 3.51-3.55 (1H, m), 3.68-3.86 (2H, m), 4.22-4.25 (2H, m), 4.62-4.80 (3H, m), 6.91-6.93 (1H, m), 7.35- 7.52 (1H, m)
MS (FAB ⁺ ); m / z 560 M ⁺

Example 165 (1S, 5R, 6S) -2- (5- (4,5-dihydrooxazol-2-yl) -5,6-dihydro-4H-
Thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyl) Oxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.35 (19H, m), 3.26 (1H, dd, J = 6.9 and 2.7 Hz), 3.52-3.64 (1H, m), 3.82-3.90 (2H, m) , 4.20-4.30 (2H, m), 4.30-4.44 (2H, m), 4.54-4.76 (5H, m), 6.94 (1H, q, J = 5.4 Hz), 7.52 (1H, s)

Example 166 (1S, 5R, 6S) -2- (5- (N, N-dimethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers) ¹ H-NMR (CDCl ₃ ) δ: 1.20-2.10 (19H, m), 2.92 (6H, s), 3.26 (1H, dd, J = 6.9and 2.4 Hz), 3.50-3.64 (1H, m), 4.20-4.32 (2H, m), 4.58-4.82 (5H, m), 6.94 (1H, q, J = 5.4 Hz), 7.50 (0.5H, s), 7.51 (0.5H, s)

Example 167 (1S, 5R, 6S) -2- (5- (2-cyanoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.15-2.05 (19H, m), 3.28 (1H, dd, J = 6.6 and 2.4 Hz), 3.53 (2H, s), 3.54-3.62 (1H, m), 4.23 -4.33 (2H, m), 4.57-4.92 (5H, m), 6.94 (1H, q, J = 5.7 Hz), 7.48 (0.4H, s), 7.56 (0.6H, s)

Example 168 (1S, 5R, 6S) -2- (5-hydroxyacetyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -6-((R)- 1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.00 (19H, m), 2.88-2.98 (2H, m), 3.26 (1H, dd, J = 7.2 and 2.7 Hz), 3.48-3.67 (3H, m) , 3.95-4.02 (1H, m), 4.20-4.38 (4H, m), 4.60-4.75 (2H, m), 6.93 (1H, q, J = 5.4 Hz), 7.38 (0.5H, s), 7.50 ( 0.2H, s), 7.51 (0.3H, s)

Example 169 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (1-methyl-4,5-
Dihydro-1H-imidazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) -1-carbapen-2-em-3-carboxylic acid 1- ( (Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.00 (19H, m), 2.79 (3H, s), 2.90-3.00 (2H, m), 3.20-3.28 (1H,
m), 3.30-3.75 (7H, m), 4.20-4.34 (4H, m), 4.60-4.76 (1H, m), 6.90-6.98 (1H, m), 7.36 (1H, s)

Example 170 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (N-methylcarbamothioyl) -5,6-dihydro-4H- Thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers) ¹ H-NMR (CDCl ₃ ) δ: 1.10-2.05 (19H, m), 3.18-3.30 (4H, m), 3.50-3.63 (1H, m), 4.20-4.36 (2H, m), 4.55-5.03 (5H, m), 5.40-5.55 (1H, m), 6.90-7.00 (1H, m), 7.48-7.60 (1H, m)

Example 171 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.10-2.05 (19H, m), 3.27 (1H, dd, J = 7.1 and 2.4 Hz), 3.50-3.61 (1H, m), 4.23-4.32 (2H, m) , 4.50-4.72 (5H, m), 6.89-6.98 (2H, m), 7.20-7.25 (1H, m), 7.59 (0.5H, s), 7.60 (0.5H, s), 8.00-8.10 (2H, m)

Example 172 (1S, 5R, 6S) -2- (5- (1-acetyl-4,5-dihydro-1H-imidazol-2-yl) -5,6-dihydro-4H-thieno [2,3- c) pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (
(Diastereomeric mixture)
¹ H-NMR (CDCl ₃ ) δ: 1.10-2.25 (19H, m), 2.30 (3H, s), 3.20-3.28 (1H, m), 3.50-3.62 (1H,
m), 3.62-3.74 (2H, m), 3.88-3.98 (2H, m), 4.18-4.30 (2H, m), 4.57-4.75 (3H, m), 4.78-4.85 (2H, m), 6.94 ( 1H, q, J = 5.7 Hz), 7.47 (1H, s)

Example 173 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-((S) -2-hydroxypropanoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.00-2.10 (22H, m), 3.28 (1H, dd, J = 6.8 and 2.4 Hz), 3.52-3.65 (1H, m), 4.23-5.00 (8H, m) 6.90-6.97 (1H, m), 7.48 (0.2H, s), 7.49 (0.3H, s), 7.57 (0.5H, s)

Example 174 (1S, 5R, 6S) -2- (5- (2-acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium 1- (cyclohexyloxycarbonyloxy) ethyl (diastereomeric mixture)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.04 (19H, m), 2.22 (3H, s), 3.28 (1H, dd, J = 7.1 and 2.7 Hz), 3.52-3.64 (1H, m), 4.24 -4.30 (2H, m), 4.58-4.74 (5H, m), 4.80-4.84 (2H, m), 6.91-6.97 (1H, m), 7.47 (0.4H, s), 7.58 (0.6H, s)
MS (FAB ⁺ ); m / z 604 [M + 1] ⁺

Example 175 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4,5,6,7-tetrahydrothieno [3,2- c] Pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.18-2.06 (19H, m), 2.48 (3H, s), 2.69-2.77 (2H, m), 2.90-2.96 (2H,
m), 3.23 (1H, dd, J = 7.1 and 2.4 Hz), 3.49 (2H, br s), 3.51-3.60 (1H, m), 4.17-4.30 (2H, m), 4.57-4.73 (1H, m ), 6.90-6.97 (1H, m), 7.40 (1H, s)
MS (FAB ⁺ ); m / z 532 [M + 1] ⁺

Example 176 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-6-oxo-5,6-dihydro-4H-thieno [2 , 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.18-2.05 (19H, m), 2.40 (1H, br s), 3.18 (3H, s), 3.31 (1H, dd, J =
7.2 and 2.8 Hz), 3.55-3.64 (1H, m), 4.23-4.37 (4H, m), 4.58-4.72 (1H, m), 6.93 (1H, br q, J = 5.5 Hz), 7.86 (0.5H , s), 7.87 (0.5H, s)
MS (FAB ⁺ ); m / z 532 M ⁺

Example 177 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5-isopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c ] Pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.23-2.05 (25H, m), 3.18-3.27 (1H, br s), 3.31 (1H, dd, J = 7.4 and 2.4 Hz), 3.57-3.66 (1H, m ), 4.20-4.73 (6H, m), 6.93 (1H, q, J = 5.5 Hz), 7.88 (0.5H, s), 7.90 (0.5H, s)
MS (FAB ⁺ ); m / z 560 [M + 1] ⁺

Example 178 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.23-2.03 (19H, m), 3.31 (1H, dd, J = 6.9 and 3.0 Hz), 3.54-3.63 (1H, m), 4.25-4.36 (4H, m) , 4.58-4.72 (1H, m), 4.77 (2H, s), 6.90-6.95 (1H, m), 7.20-7.22 (2H, m), 7.78 (0.5H, s), 7.79 (0.5H, s) , 8.58-8.61 (2H, m)
MS (ESI ⁺ ); m / z 610 [M + 1] ⁺

Example 179 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-oxo-5- (pyridin-3-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.22-2.03 (19H, m), 3.31 (1H, dd, J = 6.6 and 3.0 Hz), 3.53-3.62 (1H, m), 4.21-4.36 (4H, m) , 4.57-4.72 (1H, m), 4.77 (2H, s), 6.89-6.95 (1H, m), 7.25-7.32 (1H, m), 7.65-7.69 (1H, m), 7.66 (0.5H, s ), 7.68 (0.5H, s), 8.55-8.60 (2H, m)
MS (ESI ⁺ ); m / z 610 [M + 1] ⁺

Example 180 (1S, 5R, 6S) -2- (5-benzyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.03 (19H, m), 2.12 (1H, br s), 3.27 (1H, dd, J = 6.8 and 2.4 Hz), 3.54-3.63 (1H, m), 4.15-4.25 (2H, m), 4.23-4.35 (2H, m), 4.57-4.72 (1H, m), 4.71-4.80 (2H, m), 6.88-6.94 (1H, m), 7.26-7.57 (5H , m), 7.75-7.77 (1H, m)
MS (FAB ⁺ ); m / z 609 [M + 1] ⁺

Example 181 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-methoxyethyl) -6-oxo-5,6-dihydro-4H-thieno [ 2,3-c] pyrrol-2-yl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-2.04 (19H, m), 2.07 (1H, br s), 3.31 (1H, dd, J = 6.8 and 2.4 Hz), 3.36 (3H, s), 3.54- 3.62 (1H, m), 3.62 (2H, t, J = 4.9 Hz), 3.75 (2H, t, J = 4.9 Hz),
4.22-4.35 (2H, m), 4.41-4.52 (2H, m), 4.58-4.72 (1H, m), 6.93 (1H, br q, J = 5.3 Hz),
7.81 (0.6H, s), 7.82 (0.4H, s)
MS (FAB ⁺ ); m / z 577 [M + 1] ⁺

Example 182 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (5- (2-hydroxyethyl) -6-
Oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-1-carbapen-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (Diastereomer mixture)
¹ H-NMR (CDCl ₃ ) δ: 1.18-2.04 (19H, m), 2.75-3.13 (2H, m), 3.29 (1H, dd, J = 7.2 and 2.8
Hz), 3.57-3.69 (2H, m), 3.75-3.95 (3H, m), 4.23-4.33 (1H, m), 4.33-4 .38 (1H, m), 4.40-4.52 (2H, m), 4.58-4.73 (1H, m), 6.93 (1H, q, J = 5.5 Hz), 7.81 (0.5H, s), 7.84 (0.5H, s)
MS (FAB ⁺ ); m / z 563 [M + 1] ⁺

Example 183 (1S, 5R, 6S) -2- (5-cyclopropyl-6-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 0.80-1.00 (4H, m), 1.10-2.00 (19H, m), 2.80-2.93 (1H, m), 3.30 (1H, dd, J = 7.2 and 2.7 Hz) , 3.52-3.66 (1H, m), 4.20-4.38 (4H, m), 4.56-4.74 (1H, m), 6.92 (1H, q, J = 5.7 Hz), 7.82 (0.5H, s), 7.83 ( 0.5H, s)

Example 184 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-5,6-dihydro-4H-thieno [2 , 3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.18-2.18 (19H, m), 3.17 (3H, s), 3.28-3.31 (1H, m), 3.63-3.71 (1H,
m), 4.27-4.31 (2H, m), 4.40-4.51 (2H, m), 4.59-4.73 (1H, m), 6.92-6.97 (1H, m), 7.55 (1H, s)
MS (ESI ⁺ ); m / z 533 [M + 1] ⁺

Example 185 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (4-oxo-5- (pyridin-4-ylmethyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.25-2.30 (19H, m), 3.30-3.32 (1H, m), 3.65-3.70 (1H, m), 4.27-4.45 (4H, m), 4.59-4.82 ( 3H, m), 6.92-6.96 (1H, m), 7.19-7.21 (2H, m), 7.60 (1H, s), 8.58-8.59 (2H, m)
MS (ESI ⁺ ); m / z 610 [M + 1] ⁺

Example 186 (1S, 5R, 6S) -2- (5-benzyl-4-oxo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.20-1.98 (19H, m), 3.28-3.31 (1H, m), 3.65-3.69 (1H, m), 4.27-4.34 (4H, m), 4.59-4.82 ( 3H, m), 6.91-6.96 (1H, m), 7.24-7.37 (5H, m), 7.59 (1H, s)
MS (ESI ⁺ ); m / z 609 [M + 1] ⁺

Example 187 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5-methyl-4-oxo-4,5,6,7-tetrahydrothieno [ 3,2-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.24-2.03 (19H, m), 3.06-3.11 (5H, m), 3.27 (1H, dd, J = 6.6 and 2.7
Hz), 3.60-3.74 (3H, m), 4.23-4.29 (2H, m), 4.59-4.73 (1H, m), 6.92-6.97 (1H, m), 7.68 (0.5H, s), 7.69 (0.5 H, s)

Example 188 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (6-methyl-7-oxo-4,5,6,7-tetrahydrothieno [ 2,3-c] pyridin-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.21-2.09 (19H, m), 2.91-2.95 (2H, m), 3.10 (3H, s), 3.28 (1H, dd,
J = 6.8 and 2.6 Hz), 3.51-3.62 (3H, m), 4.26-4.31 (2H, m), 4.62-4.68 (1H, m), 6.91-6.93 (1H, m), 7.71 (0.5H, s ), 7.72 (0.5H, s)
MS (FAB ⁺ ); m / z 547 [M + 1] ⁺

Example 189 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -2- (6- (2-methoxyethyl) -7-oxo-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-methyl-1-carbapen-2-
Em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 1.21-1.63 (19H, m), 2.90 (2H, t, J = 6.8 Hz), 3.28 (1H, dd, J = 6.9 and 2.7 Hz), 3.35 (1.5H. s), 3.36 (1.5H, s), 3.52-3.73 (7H, m), 4.28-4.31 (2H, m), 4.59-4.70 (1H, m), 6.89-6.94 (1H, m), 7.69 (0.5 H, s), 7.70 (0.5H, s)
MS (FAB ⁺ ); m / z 591 [M + 1] ⁺

Example 190 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (7-oxo-6- (pyridin-3-yl) -4,5,6 , 7-Tetrahydrothieno [2,3-c] pyridin-2-yl) -1-carbapen-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.93 (19H, m), 3.09-3.12 (2H, m), 3.31 (1H, dd, J = 6.6 and 2.7
Hz), 3.55-3.59 (1H, m), 4.09-4.13 (2H, m), 4.30-4.34 (2H, m), 4.63-4.70 (1H, m), 6.93-7.00 (1H, m), 7.34- 7.37 (1H, m), 7.74-7.78 (2H, m), 8.48-8.49 (1H, m), 8.65 (1H, br s)
MS (FAB ⁺ ); m / z 610 [M + 1] ⁺

Example 191 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2- (N-methylacetamido) acetyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate The compound of Example 191 was synthesized in the same manner as Example 8.
(a) (1S, 5R, 6S) -1-Methyl-2- (5- (2- (N-methylacetamido) acetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole- 2-Nitrobenzyl 2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.24-1.30 (6H, m), 2.17 (3H, s), 3.17 (1.8 H, s), 3.18 (1.2H, s), 3.28 (1H, dd, J = 5.6 and 2.6 Hz), 3.52-3.58 (1H, m), 4.17-4.30 (4H, m), 4.64-4.87 (4H , m), 5.23-5.50 (2H, m), 7.43 (0.4H, s), 7.47 (0.6H, s), 7.67 (2H, d, J = 8.5 Hz), 8.22 (2H, d, J = 8.5 Hz)
MS (ESI ⁺ ); m / z 697 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2- (N-methylacetamido) acetyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.3 Hz), 1.16 (3H, d, J = 6.4 Hz), 1.90 (1.2H, s), 2.04 (1.8H, s), 2.79 (1.2H, s), 2.99 (1.8H, s), 3.30-3.48 (2H, m), 4.09-4.71 (8H, m), 7.02 (1H, s)
MS (FAB ⁺ ); m / z 470 [M + 1] ⁺

Example 192 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2- (N-methylacetamido) acetyl) -5,6-dihydro -4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 1- (cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
The compound of Example 192 was synthesized in the same manner as Example 103.
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.77 (19H, m), 2.17 (3H, s), 3.17-3.18 (3H, m), 3.26-3.29 (1H,
m), 3.54-3.61 (1H, m), 4.19-4.26 (4H, m), 4.65-4.87 (5H, m), 6.93-6.94 (1H, m), 7.5
0-7.55 (1H, m)
MS (FAB ⁺ ); m / z 618 [M + 1] ⁺

Example 193 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2- (2-oxopyrrolidin-1-yl) acetyl) -5 , 6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate The compound of Example 193 was synthesized in the same manner as Example 7.
(a) (1S, 5R, 6S) -1-methyl-2- (5- (2- (2-oxopyrrolidin-1-yl) acetyl) -5,6-dihydro-4H-thieno [2,3- c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.62 (6H, m), 0.89-0.99 (9H, m), 1.21-1.31 (6H, m), 2.08-2.14 (2H, m), 2.43-2.49 ( 2H, m), 3.27-3.30 (1H, m), 3.54-3.62 (3H, m), 4.10-4.14 (2H, m),
4.27-4.32 (2H, m), 4.64-4.86 (4H, m), 5.28-5.47 (2H, m), 7.45-7.48 (1H, m), 7.69 (2H, d, J = 8.8 Hz), 8.23 ( (2H, d, J = 8.8 Hz)
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2- (2-oxopyrrolidin-1-yl) acetyl) -5 , 6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl ester
¹ H-NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.6 Hz), 1.40 (3H, d, J = 6.1 Hz), 2.07-2.17 (2H, m),
2.46 (2H, t, J = 8.2 Hz), 3.32 (1H, dd, J = 6.8 and 2.5 Hz), 3.57-3.65 (3H, m), 4.11-4.36 (4H, m), 4.63-4.86 (4H, m), 5.26 (1H, d, J = 13.8 Hz), 5.52 (1H, d, J = 13.8Hz), 7.46 (0.4H, s), 7.49 (0.6H, s), 7.67 (2H, d, J = 9.0 Hz), 8.22 (2H, d, J = 9.0 Hz)
MS (ESI ⁺ ); m / z 595 [M + 1] ⁺
(c) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (2- (2-oxopyrrolidin-1-yl) acetyl) -5 , 6-Dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.07 (3H, d, J = 7.3 Hz), 1.16 (3H, d, J = 6.3 Hz), 1.94-2.01 (2H, m), 2.36 (2H, t, J = 8.0 Hz), 3.31-3.42 (4H, m), 4.08-4.11 (4H, m), 4.45-4.73 (4H, m), 7.02 (1H, s)
MS (FAB ⁺ ); m / z 482 [M + 1] ⁺

Example 194 (1S, 5R, 6S) -2- (5-carbamoyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium The compound of Example 194 was synthesized in the same manner as Example 6.
(a) (1S, 5R, 6S) -2- (5-carbamoyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl-6-((R ) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.57-0.64 (6H, m), 0.95 (9H, t, J = 8.1 Hz), 1.26 (3H, d, J = 7.4 Hz),
1.30 (3H, d, J = 6.3 Hz), 3.28 (1H, dd, J = 5.9 and 2.9 HZ), 3.53-3.59 (1H, m), 4.28-4.31 (2H, m), 4.45 (2H, s) , 4.57 (2H, s), 4.73 (2H, s), 5.25 (1H, d, J = 13.6Hz), 5.48 (1H, d, J = 13.6 Hz), 7.47 (1H, s), 7.67 (2H, d, J = 8.5 Hz), 8.21 (2H, d, J = 8.5 Hz)
(b) (1S, 5R, 6S) -2 (5-carbamoyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxy Ethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.3 Hz), 1.16 (3H, d, J = 6.3 Hz), 3.30 (1H, dd, J = 6.3 and 2.7 Hz), 3.39-3.47 (1H, m), 4.06-4.14 (2H, m), 4.31-4.33 (2H, m), 4.43-4.45 (2H, m), 6.99 (1H, s)
MS (FAB ⁺ ); m / z 400 [M + 1] ⁺

Example 195 (1S, 5R, 6S) -2- (5-carbamoyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid 1- (
(Cyclohexyloxycarbonyloxy) ethyl (mixture of diastereomers)
The compound of Example 195 was synthesized in the same manner as Example 103.
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.92 (19H, m), 3.27 (1H, dd, J = 6.8 and 2.6 Hz), 3.55-3.61 (1H, m), 4.23-4.30 (2H, m) , 4.45 (2H, s), 4.57-4.73 (5H, m), 6.92-6.97 (1H, m), 7.54 (1H, s)
MS (ESI ⁺ ); m / z 548 [M + 1] ⁺

Example 196 (1S, 5R, 6S) -2- (5- (N-ethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate The compound of Example 196 was synthesized in the same manner as Example 6.
(a) (1S, 5R, 6S) -2- (5- (N-ethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-methyl- 6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-
4-Nitrobenzyl carboxylate
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.65 (6H, m), 0.94 (9H, t, J = 8.0 Hz), 1.21 (3H, d, J = 7.1 Hz),
1.26 (3H, d, J = 7.0 Hz), 1.30 (3H, d, J = 6.1 Hz), 3.27-3.39 (3H, m), 3.53-3.59 (1H, m), 4.21-4.32 (2H, m) , 4.52 (2H, s), 4.71 (2H, s), 5.25 (1H, d, J = 13.9 Hz), 5.48 (1H, d, J = 13.9 Hz), 7.47 (1H, s), 7.67 (2H, d, J = 9.0 Hz), 8.21 (2H, d, J = 9.0 Hz)
(b) (1S, 5R, 6S) -2- (5- (N-ethylcarbamoyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.93-0.97 (3H, m), 1.04 (3H, d, J = 7.1 Hz), 1.14 (3H, d,
J = 6.3 Hz), 3.04 (2H, q, J = 7.1 Hz), 3.28 (1H, dd, J = 6.6 and 2.7 Hz), 3.39-3.43 (1H,
m), 4.05-4.10 (2H, m), 4.26 (2H, s), 4.39-4.44 (2H, m), 6.97 (1H, s)
MS (FAB ⁺ ); m / z 428 [M + 1] ⁺

Example 197 (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyrrolidine-1-
Carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylate sodium The compound of Example 197 is the same as Example 8. Was synthesized.
(a) (1S, 5R, 6S) -1-methyl-2- (5- (pyrrolidin-1-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxyethyl) -1-carbaben-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.63 (6H, m), 0.95 (9H, t, J = 7.8 Hz), 1.25-1.28 (6H, m), 1.88-2.05 (4H, m), 3.27 (1H, dd, J = 5.9and 2.9 Hz), 3.43-3.47 (4H, m), 3.53-3.57 (1H, m), 4.26-4.31 (2H, m), 4.63 (2H, s), 4.79 (2H , s), 5.45 (1H, d, J = 13.9 Hz), 5.48 (1H, d, J = 13.9 Hz), 7.45 (1H, s), 7.67 (2H, d, J = 8.8 Hz), 8.21 (2H , d, J = 8.8 Hz)
MS (ES ⁺ ); m / z 681 [M + 1] ⁺
(b) (1S, 5R, 6S) -6-((R) -1-hydroxyethyl) -1-methyl-2- (5- (pyrrolidine-1-carbonyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -1-carbapene-2-em-3-carboxylic acid sodium salt
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 1.06 (3H, d, J = 7.1 Hz), 1.17 (3H, d, J = 6.4 Hz), 1.69-1.74 (4H, m), 3.24-3.46 (6H, m), 4.06-4.12 (2H, m), 4.42-4.65 (4H, m), 6.98 (1H, s)
MS (FAB ⁺ ); m / z 454 [M + 1] ⁺

Example 198 (1S, 5R, 6S) -2- (6-acetyl-3-N, N-dimethylcarbamoyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(a) (1S, 5R, 6S) -2- (6- (3,4-Dimethoxybenzyl) -3-N, N-dimethylcarbamoyl-4,5,6,7-tetrahydrothieno [2,3-c ] Pyridin-2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1R, 5R, 6S) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl And 6- (3,4-dimethoxybenzyl) -3-N, N-dimethylcarbamoyl-2-tributylstannyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine In the same manner as in 1, the title compound was obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.58-0.63 (6H, m), 0.88-0.97 (9H, m), 1.07 (3H, d, J = 7.3Hz), 1.24 (3H, d, J = 6.1Hz ), 2.70-2.84 (10H, m), 3.31-3.34 (1H, m), 3.53-3.70 (5H, m), 3.88 (6H,
s), 4.22-4.31 (2H, m), 5.20 (1H, d, J = 13.7Hz), 5.34 (1H, d, J = 13.7Hz), 6.82-7.00 (3H, m), 7.53-7.58 (2H) , m), 8.19 (2H, d, J = 8.5Hz)
MS (FAB ⁺ ); m / z 819 M ⁺
(b) (1S, 5R, 6S) -2- (6-acetyl-3-N, N-dimethylcarbamoyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1-Methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(1S, 5R, 6S) -2- (6- (3,4-Dimethoxybenzyl) -3-N, N-dimethylcarbamoyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine- 2-yl) -1-methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate as in Example 5 (a) To give the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.61 (6H, q, J = 7.6Hz), 0.95 (9H, t, J = 7.6Hz), 1.05-1.10 (3H, m), 1.19-1.25 (3H, m ), 2.17 (1.2H, s), 2.19 (1.8H, s), 2.51-3.92 (12H, m), 4.25-4.33 (2H, m), 4.60-4.70 (2H, m), 5.18-5.25 (1H , m), 5.35-5.41 (1H, m), 7.56-7.65 (2H, m), 8.16-8.23 (2H, m)
(c) (1S, 5R, 6S) -2- (6-acetyl-3-N, N-dimethylcarbamoyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylate sodium
(1S, 5R, 6S) -2- (6-Acetyl-3-N, N-dimethylcarbamoyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridin-2-yl) -1- Using 4-nitrobenzyl methyl-6-((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylate in the same manner as in Example 5 (b), the title A compound was obtained.
¹ H-NMR (D ₂ O) δ (HOD = 4.65 ppm): 0.91-0.95 (3H, m), 1.13-1.14 (3H, m), 2.05 (1.2H, s), 2.06 (1.8H, s) , 2.40-2.51 (2H, m), 2.78-3.01 (8H, m), 3.31-3.39 (1H, m), 3.61-3.66 (1H, m), 4.02-4.14 (2H, m), 4.60-4.64 ( 2H, m)
MS (FAB ⁺ ); m / z 484 [M + 1] ⁺

Example 199 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- (Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-hydroxypropoxycarbonyloxy) methyl
(a) (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-tert-butyldiphenylsiloxypropoxycarbonyloxy) methyl In the same manner as in Example 105, the title compound was obtained.
¹ H-NMR (CDCl ₃ ) δ: 1.03 (9H, s), 1.25 (3H, d, J = 7.3 Hz), 1.36 (3H, d, J = 6.1 Hz), 1.88-1.95 (2H, m), 2.14 (3H, s), 2.82 (1H, br s), 3.27 (1H, dd, J = 7.0 and 2.6 Hz), 3.54-3.66 (1H, m), 3.74 (2H, t, J = 5.8 Hz), 4.20-4.32 (2H, m), 4.37 (2H, t, J = 6.4 Hz), 4.61-4.70 (2H, m), 4.76-4.84 (2H, m), 5.89-5.95 (2H, m), 7.34 7.43 (6H, m), 7.48 (0.45H, s), 7.59 (0.55H, s), 7.62-7.66 (4H, m)
MS (FAB ⁺ ); m / z 746 [M + 1] ⁺
(b) (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- (Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-hydroxypropoxycarbonyloxy) methyl
(1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) 1-methyl-1-carbapene-2-em-3-carboxylic acid (3-tert-butyldiphenylsiloxypropoxycarbonyloxy) methyl 134 mg (0.18 mmol) in anhydrous tetrahydrofuran 2 ml at room temperature, 0.1 ml acetic acid (1.80 mmol) and 0.9 ml (0.9 mmol) of 1 M tetrabutylammonium fluoride tetrahydrofuran solution were added. After stirring at room temperature for 8 hours, water was added to stop the reaction, and the mixture was extracted 4 times with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluting with chloroform: methanol = 19: 1) to give the title compound 70 mg (yield 77%) Got.
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 7.3 Hz), 1.35 (3H, d, J = 6.3 Hz), 1.92 (2H, quint, J = 6.0 Hz), 2.16 (3H, s), 3.29 (1H, dd, J = 6.3 and 2.4 Hz), 3.56-3.68 (1H, m), 3.68-3.78 (2H, m), 4.23-4.42 (4H, m), 4.60-4.70 (2H, m), 4.76-4.85 (2H, m), 5.81 (0.55H, d, J = 5.8 Hz), 5.82 (0.45H, d, J = 5.8 Hz), 6.03 (1H, d, J = 5.8 Hz), 7.48 (0.45H, s), 7.60 (0.55H, s)
MS (FAB ⁺ ); m / z 509 [M + 1] ⁺

The compounds of Examples 200 to 232 were synthesized in the same manner as described in Example 103 or Example 105.
Example 200 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-acetamidoethoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.27 (3H, d, J = 7.3 Hz), 1.36 (3H, d, J = 6.1 Hz), 1.98 (3H, s), 2.16 (3H, s), 3.29 ( 1H, dd, J = 6.6 and 2.4 Hz), 3.55 (2H, q, J = 5.2 Hz), 3.59-3.71 (1H, m), 4.21-4.37 (4H, m), 4.62-4.70 (2H, m) , 4.76-4.86 (2H, m), 5.76 (0.55H, d, J = 5.9 Hz), 5.77 (0.45H, d, J = 5.9 Hz), 6.10 (1H, d, J = 5.9 Hz), 6.73 6.80 (1H, m), 7.51 (0.45H, s), 7.61 (0.55H, s)
MS (FAB ⁺ ); m / z 536 [M + 1] ⁺

Example 201 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methoxypropoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (1.75H, d, J = 7.3 Hz), 1.27 (1.25H, d, J = 7.3 Hz), 1.38 (3H, d, J = 6.1 Hz), 1.95 ( 2H, quint, J = 6.2 Hz), 2.16 (3H, s), 2.53 (1H, brs), 3.29 (1H, dd, J = 6.8 and 2.4 Hz), 3.32 (3H, s), 3.46 (2H, t , J = 6.2 Hz), 3.55-3.68 (1H, m), 4.24-4.33 (4H, m), 4.62-4.70 (2H, m), 4.77-4.84 (2H, m), 5.90 (0.55H, d, J = 5.6 Hz), 5.91 (0.45H, d, J = 5.6 Hz), 5.95 (0.55H, d, J = 5.6 Hz), 5.96 (0.45H, d, J = 5.6 Hz), 7.48 (0.45H, s), 7.59 (0.55H, s)
MS (ESI ⁺ ); m / z 523 [M + 1] ⁺

Example 202 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methoxypropanoyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (1.75H, d, J = 7.2 Hz), 1.27 (1.25H, d, J = 7.2 Hz), 1.37 (3H, d, J = 6.3 Hz), 2.16 ( 3H, s), 2.60-2.70 (3H, m), 3.29 (1H, dd, J = 6.7 and 2.5 Hz), 3.34 (3H, s), 3.55-3.70 (3H, m), 4.23-4.33 (2H, m), 4.62-4.70 (2H, m), 4.77-4.85 (2H, m), 5.90 (0.55H, d, J = 5.6 Hz), 5.91 (0.45H, d, J = 5.6 Hz), 5.97 (0.55 H, d, J = 5.6 Hz), 5.98 (0.45H, d, J = 5.6 Hz), 7.46 (0.45H, s), 7.56 (0.55H, s)
MS (ESI ⁺ ); m / z 493 [M + 1] ⁺

Example 203 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (phenyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (1.75H, d, J = 7.3 Hz), 1.27 (1.25H, d, J = 7.3 Hz), 1.38 (3H, d, J = 6.3 Hz), 2.16 ( 1H, br s), 3.32 (1H, dd, J = 6.6 and 2.7 Hz), 3.41-3.46 (1H, m), 3.56-3.67 (1H, m), 4.18 (2H, dd, J = 4.5 and 1.5 Hz ), 4.25-4.34 (2H, m), 4.47-4.87 (4H, m), 5.96 (0.55H, d, J = 5.6 Hz), 5.97 (0.45H, d, J = 5.6 Hz), 6.09 (0.55H) , d, J = 5.6 Hz), 6.10 (0.45H, d, J = 5.6 Hz), 7.20-7.28 (3H, m), 7.36-7.41 (2H, m), 7.52 (0.45H, s), 7.55 ( 0.55H, s)
MS (ESI ⁺ ); m / z 543 [M + 1] ⁺

Example 204 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (pentan-3-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.89-0.94 (6H, m), 1.26 (1.75H, d, J = 7.3 Hz), 1.27 (1.25H, d, J = 7.0 Hz), 1.38 (3H, d , J = 6.3 Hz), 1.59-1.68 (4H, m), 3.28 (1H, dd, J = 6.8 and 2.4 Hz), 3.39-3.44 (1H, m), 3.55-3.63 (1H, m), 4.19- 4.22 (2H, m), 4.25-4.31 (2H, m), 4.53-4.56 (1H, m), 4.60-4.67 (1H, m), 4.68-4.74 (2H, m), 4.84-4.89 (1H, m ), 5.91-5.96 (2H, m), 7.52 (0.4H, s), 7.56 (0.6H, s)
MS (FAB ⁺ ); m / z 537 [M + 1] ⁺

Example 205 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2- (tetrahydro-2H-pyran-4-yl) acetoxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.40 (8H, m), 1.61-1.68 (2H, m), 1.99-2.10 (1H, m), 2.16 (3H, s), 2.34 (2H, d, J = 7.1 Hz), 3.28 (1H, dd, J = 6.6 and 2.6 Hz), 3.35-3.43 (2H, m), 3.55-3.65 (1H, m), 3.90-3.96 (2H, m), 4.25-4.32 (2H, m), 4.63-4.69 (2H, m), 4.78-4.84 (2H, m), 5.88-5.91 (1H, m), 5.95-5.98 (1H, m), 7.48 (0.45H, s), 7.57 (0.55H, s)
MS (FAB ⁺ ); m / z 533 [M + 1] ⁺

Example 206 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-cyclopentylacetoxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.10-1.20 (2H, m), 1.24-1.28 (3H, m), 1.38 (3H, d, J = 6.3 Hz), 1.49-1.65 (4H, m), 1.77 -1.89 (2H, m), 2.16 (3H, s), 2.16-2.26 (1H, m), 2.37-2.40 (2H, m), 3.28 (1H, dd, J = 7.0 and 2.6 Hz), 3.54-3.66 (1H, m), 4.25-4.31 (2H, m), 4.63-4.69 (2H, m), 4.77-4.83 (2H, m), 5.90 (0.55H, d, J = 5.6 Hz), 5.91 (0.45H , d, J = 5.6 Hz), 5.94 (0.55H, d, J = 5.6 Hz), 5.95 (0.45H, d, J = 5.6 Hz), 7.46 (0.45H, s), 7.56 (0.55H, s)
MS (FAB ⁺ ); m / z 517 [M + 1] ⁺

Example 207 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2- (tetrahydro-2H-pyran-4-yl) acetoxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.41 (8H, m), 1.61-1.68 (2H, m), 2.00-2.10 (1H, m), 2.32-2.36 (2H, m), 3.29 (1H, dd, J = 6.6 and 2.7 Hz), 3.35-3.44 (2H, m), 3.55-3.64 (1H, m), 3.90-3.96 (2H, m), 4.19-4.22 (2H, m), 4.26-4.32 ( 2H, m), 4.54-4.57 (1H, m), 4.69-4.75 (2H, m), 4.84-4.89 (1H, m), 5.89 (0.55H, d, J = 5.6 Hz), 5.90 (0.45H, d, J = 5.6 Hz), 5.96 (0.55H, d, J = 5.6 Hz), 5.97 (0.45H, d, J = 5.6 Hz), 7.51 (0.45H, s), 7.54 (0.55H, s)
MS (FAB ⁺ ); m / z 549 [M + 1] ⁺

Example 208 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-ethylbutoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.86-0.91 (6H, m), 1.24-1.28 (3H, m), 1.33-1.41 (7H, m), 1.53-1.59 (1H, m), 1.74 (1H, d, J = 4.6 Hz), 3.27-3.31 (1H, m), 3.39-3.45 (1H, m), 3.58-3.64 (1H, m), 4.10-4.14 (2H, m), 4.19-4.22 (2H, m), 4.26-4.29 (2H, m), 4.53-4.57 (1H, m), 4.68-4.75 (2H, m), 4.86-4.89 (1H, m), 5.90-5.96 (2H, m), 7.53 ( 0.5H, s), 7.57 (0.5H, s)
MS (ESI ⁺ ); m / z 551 [M + 1] ⁺

Example 209 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-diethylamino-2-oxoethoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.98 (3H, t, J = 7.2 Hz), 1.13 (3H, t, J = 7.2 Hz), 1.23-1.28 (3H, m), 1.36 (3H, d, J = 6.4 Hz), 3.22 (2H, q, J = 7.2 Hz), 3.29 (1H, dd, J = 6.4 and 2.4 Hz), 3.36-3.45 (3H, m), 3.53-3.63 (1H, m), 4.20 (2H, d, J = 3.6 Hz), 4.28-4.33 (2H, m), 4.52-4.57 (1H, m), 4.68-4.83 (4H, m), 4.86-4.89 (1H, m), 5.96-5.97 (2H, m), 7.47 (0.45H, s), 7.60 (0.55H, s)
MS (FAB ⁺ ); m / z 580 [M + 1] ⁺

Example 210 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-oxo-2- (piperidin-1-yl) ethoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.25 (1.75H, d, J = 7.4 Hz), 1.26 (1.25H, d, J = 7.4 Hz), 1.36 (3H, d, J = 6.0 Hz), 1.50- 1.70 (6H, m), 2.16 (3H, s), 3.26-3.30 (3H, m), 3.54-3.64 (3H, m), 4.27-4.33 (2H, m), 4.62-4.84 (6H, m), 5.95-5.99 (2H, m), 7.52 (0.45H, s), 7.60 (0.55H, s)
MS (FAB ⁺ ); m / z 576 [M + 1] ⁺

Example 211 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno- [2,3-c] pyrrol-2-yl) -6-((R) -1 -Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-diethylamino-2-oxoethoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.13 (3H, t, J = 7.2 Hz), 1.22 (3H, t, J = 7.2 Hz), 1.26 (1.75H, d, J = 7.0 Hz), 1.27 (1.25 H, d, J = 7.0 Hz), 1.36 (3H, d, J = 6.4 Hz), 2.16 (3H, s), 3.22 (2H, q, J = 7.2 Hz), 3.28 (1H, dd, J = 6.2 and 2.6 Hz), 3.39 (2H, q, J = 7.2 Hz), 3.55-3.64 (1H, m), 4.27-4.33 (2H, m), 4.62-4.83 (6H, m), 5.95-6.00 (2H, m), 7.47 (0.45H, s), 7.60 (0.55H, s)
MS (FAB ⁺ ); m / z 564 [M + 1] ⁺

Example 212 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (1,3-dimethoxypropan-2-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.23-1.29 (3H, m), 1.37 (3H, d, J = 6.0 Hz), 3.27-3.30 (1H, m), 3.36-3.50 (7H, m), 3.55 -3.60 (4H, m), 4.18-4.22 (2H, m), 4.25-4.32 (2H, m), 4.53-4.57 (1H, m), 4.68-4.75 (2H, m), 4.86-4.89 (1H, m), 4.98-5.04 (1H, m), 5.91-5.97 (2H, m), 7.51 (0.45H, s), 7.56 (0.55H, s)
MS (FAB ⁺ ); m / z 569 [M + 1] ⁺

Example 213 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methylbutanoyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.95 (6H, d, J = 6.4 Hz), 1.25 (1.75H, d, J = 7.2 Hz), 1.26 (1.25H, d, J = 7.2 Hz), 1.38 ( 3H, d, J = 6.4 Hz), 2.07-2.17 (1H, m), 2.24-2.28 (2H, m), 3.29 (1H, dd, J = 6.8 and 2.8 Hz), 3.40-3.45 (1H, m) , 3.54-3.64 (1H, m), 4.21 (2H, d, J = 4.4 Hz), 4.26-4.31 (2H, m), 4.53-4.57 (1H, m), 4.67-4.74 (2H, m), 4.86 -4.89 (1H, m), 5.90 (0.55H, d, J = 5.6 Hz), 5.91 (0.45H, d, J = 5.6 Hz), 5.94 (0.55H, d, J = 5.6 Hz), 5.95 (0.45 H, d, J = 5.6 Hz), 7.50 (0.45H, s), 7.54 (0.55H, s)
MS (FAB ⁺ ); m / z 507 [M + 1] ⁺

Example 214 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclopentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.24-1.26 (3H, m), 1.38 (3H, d, J = 6.4 Hz), 1.70-1.92 (8H, m), 3.29 (1H, dd, J = 6.4 and 2.4 Hz), 3.39-3.45 (1H, m), 3.55-3.64 (1H, m), 4.21 (2H, d, J = 4.4 Hz), 4.26-4.32 (2H, m), 4.53-4.57 (1H, m ), 4.68-4.75 (2H, m), 4.86-4.89 (1H, m), 5.11-5.17 (1H, m), 5.88 (0.55H, d, J = 5.6 Hz), 5.89 (0.45H, d, J = 5.6 Hz), 5.93 (0.55H, d, J = 5.6 Hz), 5.94 (0.45H, d, J = 5.6 Hz), 7.52 (0.45H, s), 7.57 (0.55H, s)
MS (FAB ⁺ ); m / z 535 [M + 1] ⁺

Example 215 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid isobutyryloxymethyl
¹ H-NMR (CDCl ₃ ) δ: 0.96 (6H, d, J = 6.4 Hz), 1.25 (1.75H, d, J = 7.2 Hz), 1.26 (1.25H, d, J = 7.2 Hz), 1.38 ( 3H, d, J = 6.0 Hz), 1.77 (1H, d, J = 4.8 Hz), 2.08-2.15 (1H, m), 3.29 (1H, dd, J = 7.0 and 2.6 Hz), 3.40-3.46 (1H , m), 3.56-3.64 (1H, m), 4.21 (2H, d, J = 4.4 Hz), 4.25-4.31 (2H, m), 4.53-4.57 (1H, m), 4.68-4.75 (2H, m ), 4.86-4.89 (1H, m), 5.89 (0.55H, d, J = 5.6 Hz), 5.90 (0.45H, d, J = 5.6 Hz), 5.97 (0.55H, d, J = 5.6 Hz), 5.98 (0.45H, d, J = 5.6 Hz), 7.50 (0.45H, s), 7.54 (0.55H, s)
MS (ESI ⁺ ); m / z 493 [M + 1] ⁺

Example 216 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- (Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-ethylpentanoyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.85 (6H, t, J = 7.5 Hz), 1.25-1.40 (10H, m), 1.70-1.82 (1H, m), 2.16 (3H, s), 2.31 (2H , d, J = 6.9 Hz), 3.23-3.30 (1H, m), 3.50-3.67 (1H, m), 4.20-4.34 (2H, m), 4.60-4.70 (2H, m), 4.75-4.83 (2H , m), 5.86-5.98 (2H, m), 7.46 (0.4H, s), 7.56 (0.6H, s)

Example 217 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (2-diisopropylaminoethoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.01 (12H, d, J = 6.6 Hz), 1.26 (3H, d, J = 6.9 Hz), 1.37 (3H, d, J = 6.3 Hz), 2.16 (3H, s), 2.63-2.77 (2H, m), 2.95-3.07 (2H, m), 3.28 (1H, dd, J = 6.9 and 2.4 Hz), 3.53-3.68 (1H, m), 4.02-4.17 (2H, m), 4.20-4.32 (2H, m), 4.60-4.70 (2H, m), 4.75-4.83 (2H, m), 5.88-5.97 (2H, m), 7.48 (0.4H, s), 7.59 (0.6 H, s)

Example 218 (1S, 5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methyl-2-butenyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 6.3 Hz), 1.38 (3H, d, J = 6.3 Hz), 1.72 (3H, s), 1.76 (3H, s), 2.16 ( 3H, s), 3.28 (1H, dd, J = 6.9 and 2.4 Hz), 3.50-3.68 (1H, m), 4.22-4.34 (2H, m), 4.60-4.85 (6H, m), 5.33-5.43 ( 1H, m), 5.86-5.96 (2H, m), 7.47 (0.4H, s), 7.59 (0.6H, s)

Example 219 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (isopentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.91 (6H, d, J = 6.6 Hz), 1.26 (3H, d, J = 6.0 Hz), 1.37 (3H, d, J = 6.0 Hz), 1.50-1.62 ( 2H, m), 1.62-1.80 (1H, m), 3.29 (1H, dd, J = 6.6 and 2.4 Hz), 3.40-3.53 (1H, br s), 3.53-3.66 (1H, m), 4.16-4.34 (6H, m), 4.50-4.90 (4H, m), 5.86-5.98 (2H, m), 7.52 (0.4H, s), 7.56 (0.6H, s)

Example 220 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (heptan-4-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.90 (6H, t, J = 7.5 Hz), 1.20-1.70 (14H, m), 3.29 (1H, dd, J = 6.9 and 2.7 Hz), 3.40-3.53 (1H , br s), 3.53-3.68 (1H, m), 4.16-4.33 (4H, m), 4.50-4.90 (5H, m), 5.88-5.96 (2H, m), 7.52 (0.4H, s), 7.55 (0.6H, s)

Example 221 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-ethylpentanoyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.85 (6H, t, J = 7.5 Hz), 1.20-1.45 (10H, m), 1.70-1.82 (1H, m), 2.30 (2H, d, J = 6.9 Hz ), 3.29 (1H, dd, J = 6.6 and 2.7 Hz), 3.40-3.50 (1H, m), 3.52-3.66 (1H, m), 4.16-4.36 (4H, m), 4.53-4.90 (4H, m ), 5.87-5.95 (2H, m), 7.50 (0.4H, s), 7.53 (0.6H, s)

Example 222 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3,3-dimethylbutoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.93 (9H, s), 1.26 (3H, d, J = 6.0 Hz), 1.38 (3H, d, J = 6.3 Hz), 1.57-1.67 (2H, m), 3.29 (1H, dd, J = 6.9 and 2.7 Hz), 3.38-3.52 (1H, m), 3.52-3.66 (1H, m), 4.16-4.34 (6H, m), 4.52-4.90 (4H, m), 5.88-5.96 (2H, m), 7.52 (0.4H, s), 7.57 (0.6H, s)

Example 223 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (4-methylpentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.88 (6H, d, J = 6.6 Hz), 1.20-1.30 (5H, m), 1.37 (3H, d, J = 6.0 Hz), 1.48-1.75 (3H, m ), 3.26-3.32 (1H, m), 3.42-3.52 (1H, m), 3.52-3.68 (1H, m), 4.13-4.34 (6H, m), 4.52-4.90 (4H, m), 5.88-5.97 (2H, m), 7.52 (0.4H, s), 7.57 (0.6H, s)

Example 224 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (cyclohexylmethoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.80 (17H, m), 3.29 (1H, dd, J = 6.6 and 2.4Hz), 3.40-3.50 (1H, m), 3.50-3.68 (1H, m) , 4.00 (2H, d, J = 6.3 Hz), 4.17-4.35 (4H, m), 4.52-4.90 (4H, m), 5.87-5.97 (2H, m), 7.52 (0.4H, s), 7.56 ( 0.6H, s)

Example 225 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3,3,5,5-tetramethylcyclohexyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.94 (6H, s), 1.05 (6H, s), 1.08-1.30 (7H, m), 1.38 (3H, d, J = 6.0 Hz), 1.78-1.88 (2H , m), 3.29 (1H, dd, J = 6.9 and 2.7 Hz), 3.40-3.56 (1H, br s), 3.50-3.68 (1H, m), 4.21 (2H, s), 4.25-4.33 (2H, m), 4.50-5.00 (5H, m), 5.90-5.97 (2H, m), 7.52 (0.4H, s), 7.57 (0.6H, s)

Example 226 (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid (cyclopentyloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 7.2 Hz), 1.37 (3H, d, J = 6.6 Hz), 1.52-1.94 (8H, m), 3.29 (1H, dd, J = 6.9 and 2.7 Hz), 3.53-3.67 (1H, m), 4.22-4.37 (2H, m), 4.75 (1H, s), 4.89 (1H, s), 5.10-5.20 (2H, m), 5.33 ( 1H, s), 5.63-5.74 (1H, m), 5.89 (1H, d, J = 5.7 Hz), 5.94 (1H, d, J = 5.7 Hz), 7.38-7.47 (1H, m), 7.47 (0.4 H, s), 7.57 (0.6H, s)

Example 227 (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methylbutanoyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.95 (6H, d, J = 6.6 Hz), 1.26 (3H, d, J = 6.3 Hz), 1.37 (3H, d, J = 6.0 Hz), 2.10-2.30 ( 3H, m), 3.25-3.32 (1H, m), 3.53-3.68 (1H, m), 4.23-4.35 (2H, m), 4.75 (1H, s), 4.90 (1H, s), 5.18 (1H, s), 5.33 (1H, s), 5.70-5.80 (1H, br s), 5.90 (1H, d, J = 5.7 Hz), 5.95 (1H, d, J = 5.7 Hz), 7.40-7.50 (1.4H , m), 7.54 (0.6H, s)

Example 228 (1S, 5R, 6S) -2- (5- (2-amino-2-oxoacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl)- 6-((R) -1-hydroxyethyl) -1-methyl-1-carbapen-2-em-3-carboxylic acid (pentan-3-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.91 (6H, t, J = 7.5 Hz), 1.26 (3H, d, J = 6.6 Hz), 1.37 (3H, d, J = 6.6 Hz), 1.60-1.72 ( 4H, m), 3.26-3.32 (1H, m), 3.54-3.68 (1H, m), 4.23-4.34 (2H, m), 4.58-4.70 (1H, m), 4.75 (1H, s), 4.89 ( 1H, s), 5.18 (1H, s), 5.33 (1H, s), 5.68-5.76 (1H, br s), 5.92 (1H, d, J = 6.0 Hz), 5.95 (1H, d, J = 6.0 Hz), 7.40-7.47 (1H, m), 7.48 (0.4H, s), 7.57 (0.6H, s)

Example 229 (1S, 5R, 6S) -2- (5- (2-acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (tetrahydro-2H-pyran-4-yloxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.26 (3H, d, J = 6.0 Hz), 1.37 (3H, d, J = 6.3 Hz), 1.60-2.06 (4H, m), 2.09 (1.2H, s) , 2.22 (1.8H, s), 3.26-3.32 (1H, m), 3.48-3.68 (3H, m), 3.87-3.97 (2H, m), 4.22-4.33 (2H, m), 4.63-4.94 (7H , m), 5.85-6.02 (2H, m), 7.50 (0.4H, s), 7.60 (0.6H, s)

Example 230 (1S, 5R, 6S) -2- (5- (2-acetoxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (3-methylbutanoyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 0.95 (6H, d, J = 6.6 Hz), 1.23-1.28 (3H, m), 1.37 (3H, d, J = 6.6 Hz), 2.06-2.38 (6H, m ), 3.26-3.32 (1H, m), 3.52-3.68 (1H, m), 4.22-4.33 (2H, m), 4.66-4.86 (6H, m), 5.87-5.97 (2H, m), 7.47 (0.4 H, s), 7.55 (0.6H, s)

Example 231 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid benzoyloxymethyl
¹ H-NMR (CDCl ₃ ) δ: 1.24 (1.75H, d, J = 7.2 Hz), 1.25 (1.25H, d, J = 7.6 Hz), 1.36 (3H, d.J = 6.0 Hz), 2.12 ( 1H, br s), 3.29 (1H, dd, J = 6.8 and 2.4 Hz), 3.40-3.50 (1H, m), 3.52-3.63 (1H, m), 4.14-4.21 (2H, m), 4.24-4.33 (2H, m), 4.44-4.84 (4H, m), 6.16 (1.1H, s), 6.17 (0.9H, s), 7.42-7.49 (3H, m), 7.57-7.62 (1H, m), 8.05 -8.10 (2H, m)
MS (FAB ⁺ ); m / z 527 [M + 1] ⁺

Example 232 (1S, 5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Hydroxyethyl) -1-methyl-1-carbapene-2-em-3-carboxylic acid (tert-butoxycarbonyloxy) methyl
¹ H-NMR (CDCl ₃ ) δ: 1.25 (1.75H, d, J = 7.3 Hz), 1.26 (1.25H, d, J = 7.3 Hz), 1.37 (3H, d. J = 6.3 Hz), 1.50 ( 4.95H, s), 1.50 (4.05H, s), 1.83 (1H, br s), 3.28 (1H, dd, J = 6.8 and 2.4 Hz), 3.40-3.50 (1H, m), 3.52-3.63 (1H , m), 4.20-4.22 (2H, m), 4.25-4.31 (2H, m), 4.50-4.56 (1H, m), 4.67-4.75 (2H, m), 4.86-4.88 (1H, br s), 5.85 (0.55H, d, J = 5.8 Hz), 5.85 (0.45H, d, J = 5.8 Hz), 5.91 (0.55H, d, J = 5.8 Hz), 5.91 (0.45H, d, J = 5.8 Hz) ), 7.52 (0.45H, s), 7.56 (0.55H, s)
MS (FAB ⁺ ); m / z 523 [M + 1] ⁺

Example 233 (5R, 6S) -2- (5- (3,4-dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-(( R) -1-Triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(5R, 6S) -6-((R) -1-triethylsiloxyethyl) -2-trifluoromethylsulfonyloxy-1-carbapene-2-em-3-carboxylate 4-nitrobenzyl and 5- (3, In the same manner as in Example 1, the title compound was obtained using 4-dimethoxybenzyl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole.
¹ H-NMR (CDCl ₃ ) δ: 0.55-0.66 (6H, m), 0.85-1.00 (9H, m), 1.30 (3H, d, J = 6.0 Hz), 3.19 (1H, dd, J = 6.0 and 2.8 Hz), 3.28-3.45 (2H, m), 3.80-4.05 (12H, m), 4.18-4.30 (2H, m), 5.28 (1H, d, J = 14.0 Hz), 5.50 (1H, d, J = 14.0 Hz), 6.80-7.00 (3H, m), 7.37 (1H, s), 7.69 (2H, d, J = 8.8 Hz), 8.22 (2H, d, J = 8.8 Hz)

Example 234 was synthesized in the same manner as described in Example 5.
Example 234 (5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Carbapen-2-em-3-carboxylate sodium
(a) (5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-triethylsiloxy Ethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
¹ H-NMR (CDCl ₃ ) δ: 0.50-0.66 (6H, m), 0.96 (9H, t, J = 8.0 Hz), 1.31 (3H, d, J = 6.4 Hz), 2.15 (3H, s), 3.22 (1H, dd, J = 6.0 and 2.1 Hz), 3.30-3.50 (2H, m), 4.22-4.32 (2H, m), 4.60-4.83 (4H, m), 5.26-5.33 (1H, m), 5.48-5.54 (1H, m), 7.36 (0.4H, s), 7.45 (0.6H, s), 7.70 (2H, d, J = 8.0 Hz), 8.23 (2H, d, J = 8.0 Hz)
(b) (5R, 6S) -2- (5-acetyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl ) -1-Carbapen-2-em-3-carboxylate sodium
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.4 Hz), 2.05 (3H, s), 3.17-3.28 (2H, m), 3.37-3.42 (1H , m), 4.13-4.32 (3H, m), 4.42-4.75 (3H, m), 6.96 (1H, s)

Example 235 (5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-carbapene-2-em-3-carboxylate
(a) (5R, 6S) -2- (5- (2-tert-butyldiphenylsiloxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6- ((R) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(5R, 6S) -2- (5- (3,4-Dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R)- 1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl and t-butyldiphenylsiloxyacetyl chloride were used in the same manner as in Example 5 (a) to give the title compound. Got.
¹ H-NMR (CDCl ₃ ) δ: 0.50-0.67 (6H, m), 0.96 (9H, t, J = 8.0 Hz), 1.11 (9H, s), 1.25-1.35 (3H, m), 3.18-3.24 (1H, m), 3.30-3.48 (2H, m), 4.20-4.38 (4H, m), 4.55-4.85 (4H, m), 5.26-5.34 (1H, m), 5.48-5.54 (1H, m) , 7.30-7.50 (7H, m), 7.65-7.78 (6H, m), 8.22 (2H, d, J = 8.8 Hz)
(b) (5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl
(5R, 6S) -2- (5- (2-tert-Butyldiphenylsiloxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R ) -1-triethylsiloxyethyl) -1-carbapene-2-em-3-carboxylic acid 4-nitrobenzyl 261 mg (0.302 mmol) was dissolved in N, N-dimethylformamide 2.4 ml and 1-methylpyrrolidinone 0.9 ml. Under an argon atmosphere, 0.172 ml (3.02 mmol) of acetic acid and 1.20 ml (1.20 mmol) of 1M tetrabutylammonium fluoride tetrahydrofuran solution were added, and the mixture was stirred at room temperature for 1 hour. Brine, aqueous sodium bicarbonate and ethyl acetate were added to the reaction mixture, and the resulting solid was collected by filtration and washed successively with water and ethyl acetate to give the title compound (106 mg, yield 68.4%).
¹ H-NMR (DMSO-d ₆ ) δ: 1.17 (3H, d, J = 6.0 Hz), 3.40-3.53 (3H, m), 3.95-4.23 (4H, m), 4.48-4.80 (4H, m) , 5.14 (1H, d, J = 4.8 Hz), 5.38 (1H, d, J = 14.0Hz), 5.47-5.54 (1H, m), 7.45 (0.5H, s), 7.49 (0.5H, s), 7.75 (2H, d, J = 8.4 Hz), 8.24 (2H, d, J = 8.4 Hz)
(c) (5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1-hydroxyethyl) -1-carbapene-2-em-3-carboxylate
(5R, 6S) -2- (5- (2-hydroxyacetyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-2-yl) -6-((R) -1- The title compound was obtained in the same manner as in Example 7 (c) using 4-nitrobenzyl hydroxyethyl) -1-carbapene-2-em-3-carboxylate.
¹ H-NMR (D ₂ O) δ (HOD = 4.80 ppm): 1.30 (3H, d, J = 6.4 Hz), 3.16-3.32 (2H, m), 3.38-3.44 (1H, m), 4.14-4.34 (4H, m), 4.42-4.48 (2H, m), 4.54-4.66 (2H, m), 6.98 (0.5H, s), 7.00 (0.5H, s)

Reference Example 1 5- (3,4-Dimethoxybenzyl) -5,6-dihydro-4H-thieno- [2,3-c] pyrrole
11.5 ml (158 mmol) of thionyl chloride was added dropwise to a solution of 5.66 g (39.2 mmol) of 2,3-bishydroxymethylthiophene in 80 ml of anhydrous methylene chloride under ice cooling. The mixture was stirred at the same temperature for 30 minutes, neutralized with saturated aqueous sodium hydrogen carbonate, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was dissolved in 380 ml of anhydrous acetonitrile, and 17.0 ml (114 mmol) of veratrylamine was added dropwise. After stirring at 65 ° C. for 2 hours, saturated aqueous sodium hydrogen carbonate was added, the aqueous layer was extracted with ethyl acetate, the organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluting with hexane: ethyl acetate = 3: 1 to 1: 1), and the obtained residue was recrystallized from hexane to give the title 10.8 g (45% yield) of was obtained.
¹ H-NMR (CDCl ₃ ) δ: 3.86 (2H, br t, J = 3.0 Hz), 3.88 (3H, s), 3.90 (3H, s), 3.92 (2H, br s), 3.98 (2H, br t, J = 3.0 Hz), 6.80 (1H, d, J = 5.0 Hz), 6.83 (1H, d, J = 8.0 Hz), 6.90 (1H, dd, J = 8.0 and 2.0 Hz), 6.99 (1H, d, J = 2.0 Hz), 7.20 (1H, br d, J = 5.0 Hz)
MS (ESI ⁺ ); m / z 276 [M + 1] ⁺

Reference Example 2 5- (3,4-Dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine
4,5,6,7-Tetrahydrothieno [3,2-c] pyridine 453 mg (3.26 mmol) anhydrous methylene chloride 20
To the ml solution, 541 mg (3.26 mmol) of 3,4-dimethoxybenzaldehyde, 1 ml of acetic acid and 1.04 g (4.89 mmol) of sodium triacetoxyborohydride were sequentially added at room temperature, and stirred at the same temperature for 1 hour. Saturated aqueous sodium hydrogen carbonate was added to stop the reaction, followed by extraction with chloroform, and the organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1),
This gave 735 mg (75% yield) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 2.79 (2H, t, J = 5.6 Hz), 2.88 (2H, t, J = 5.6 Hz), 3.56 (2H, s), 3.65 (2H, s), 3.88 ( 6H, s), 6.70 (1H, d, J = 5.4 Hz), 6.82 (1H, d, J = 8.1 Hz), 6.89 (1H, dd, J = 8.1 and 2.0 Hz), 6.96 (1H, d, J = 2.0 Hz), 7.07 (1H, d, J = 5.4 Hz)

Reference Example 3 6- (3,4-Dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine
4,5,6,7-tetrahydrothieno [2,3-c] pyridine 400 mg (2.88 mmol) in anhydrous methylene chloride 30
To a solution of ml, 2.8 g (17.25 mmol) of 3,4-dimethoxybenzaldehyde and 1.65 ml (28.8 mmol) of acetic acid were added. After stirring at room temperature for 30 minutes, 3.8 g (17.25 mmol) of sodium triacetoxyborohydride was added. After stirring at room temperature for 5 hours, the mixture was cooled to 0 ° C., quenched with saturated aqueous sodium hydrogen carbonate solution, extracted with ethyl acetate, and the organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 5: 1) to give the title compound 250 mg (yield 30% )
¹ H-NMR (CDCl ₃ ) δ: 2.73-2.80 (4H, m), 3.65 to 3.67 (4H.m), 3.88 (3H, s), 3.89 (3H, s), 6.77-7.08 (5H, m)
MS (EI ⁺ ); m / z 289 M ⁺

Reference Example 4 5- (1-Methyl-4,5-dihydro-1H-imidazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine
4,5,6,7-Tetrahydrothieno [3,2-c] pyridine hydrochloride 1.97 g (11.2 mmol) in ethanol 10
Suspended in ml, 1.79 g (13.8 mmol) of 1-methyl-2-methylthio-4,5-dihydro-1H-imidazole was added and heated to reflux for 6 hours. The solvent was distilled off under reduced pressure, an aqueous potassium carbonate solution was added, and the mixture was extracted 5 times with chloroform. After drying the organic layer over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by flash chromatography on amino silica gel (eluted with hexane: ethyl acetate = 1: 1 to chloroform: methanol = 30: 1). As a result, 1.38 g (yield 56%) of the title compound was obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.77 (3H, s), 2.88-2.98 (2H, m), 3.28-3.48 (4H, m), 3.69 (2H, t, J = 9.3 Hz), 4.26 (2H , s), 6.78 (1H, d, J = 5.1 Hz), 7.11 (1H, d, J = 5.1 Hz)

Reference Example 5 5,6-dihydro-4H-thieno [2,3-c] pyrrole
A solution of 1.08 g (7.48 mmol) of 2,3-bishydroxymethylthiophene in 20 ml of methylene chloride was ice-cooled in an argon atmosphere, 3.1 g (25.7 mmol) of thionyl chloride was added, and the mixture was stirred at the same temperature for 1 hour. Sodium bicarbonate water was added to the reaction solution to adjust the pH to 8, followed by extraction twice with methylene chloride. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off.The resulting residue was dissolved in 50 ml of N, N-dimethylformamide, and 1.48 g (7.29 mmol) of 4-nitrobenzenesulfonamide and 4.04 g of potassium carbonate ( 29.2 mmol) was added and the mixture was stirred at 60 ° C. for 3 hours. The reaction solution was added to a mixture of ethyl acetate and brine, extracted twice with ethyl acetate, and the combined organic layer was washed 4 times with brine. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and 5- (4-nitrophenylsulfonyl) -5,6-dihydro-4H-
A crude product of thieno [2,3-c] pyrrole was obtained. This was suspended in 45 ml of acetonitrile, 3.71 ml (21.5 mmol) of 4-tert-butylbenzenethiol and 7.00 g (21.5 mmol) of cesium carbonate were added under an argon atmosphere, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, hydrochloric acid was added to adjust the pH to 2.8, and insoluble material was removed by filtration through Celite. Celite was washed with water, the filtrate was concentrated under reduced pressure, an aqueous sodium hydroxide solution was added, and the mixture was extracted twice with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated to give the title compound (532 mg, yield 57%).
¹ H-NMR (CDCl ₃ ) δ: 4.06-4.10 (2H, m), 4.20-4.23 (2H, m), 6.82 (1H, d, J = 5.1 Hz), 7.25 (1H, d, J = 5.1 Hz )

Reference Example 6 5- (Pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole
Dissolve 222 mg (1.78 mmol) of 5,6-dihydro-4H-thieno [2,3-c] pyrrole in 8 ml of toluene and add 0.258 ml (2.66 mmol) of 3-bromopyridine, sodium tert-butoxy under argon atmosphere 254 mg (2.66 mmol), tris (dibenzylideneacetone) dipalladium (0) 48 mg (0.053 mmol)
And 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl (65 mg, 0.11 mmol)
Stir at 6 ° C. for 6 hours. An aqueous ammonium chloride solution and ethyl acetate were added to the reaction solution, and insoluble materials were removed by filtration through Celite. The filtrate was extracted twice with ethyl acetate, and the combined organic layers were washed with brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1) to give the title compound 171 mg (yield 48% )
¹ H-NMR (CDCl ₃ ) δ: 4.50-4.57 (2H, m), 4.63-4.70 (2H, m), 6.86-6.92 (1H, m), 6.95 (1H, d, J = 4.8 Hz), 7.15 -7.21 (1H, m), 7.31-7.35 (1H, m), 7.99-8.03 (1H, m), 8.04-8.08 (1H, m)

Reference Example 7 5- (4,5-Dihydrothiazol-2-yl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine
4,5,6,7-tetrahydrothieno [3,2-c] pyridine 453 mg (3.26 mmol) in anhydrous acetonitrile 7 ml at room temperature, 1 ml triethylamine (7.17 mmol) and 2-chloroethyl isocyanate 0.55 ml (5.72 mmol) was sequentially added and the mixture was stirred at the same temperature for 30 minutes. The resulting precipitate was filtered off using Celite, and the filtrate was distilled off. The resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1) to give the title compound 865 mg (81% yield) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.88 (2H, t, J = 5.6 Hz), 3.29 (2H, t, J = 7.5 Hz), 3.72 (2H, t, J = 5.6
Hz), 4.02 (2H, t, J = 7.5 Hz), 4.56 (2H, s), 6.75 (1H, d, J = 5.2 Hz), 7.08 (1H, d, J = 5.2 Hz)

Reference Example 8 5-tert-butyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
Add tert-butylamine 2.90 ml (27.6 mmol) and acetic acid 6.40 ml (112 mmol) to 200 ml of anhydrous methylene chloride 3.09 g (22.0 mmol) of 2,3-thiophenedicarboxaldehyde under ice-cooling and stir at room temperature for 2 hours. did. The reaction mixture was concentrated, and the obtained residue was purified by silica gel flash column chromatography (eluted with hexane-ethyl acetate) to give the title compound (3.32 g, yield 77%).
¹ H-NMR (CDCl ₃ ) δ: 1.54 (9H, s), 4.37 (2H, s), 6.99 (1H, d, J = 4.8 Hz), 7.57 (1H, d, J = 4.8 Hz)
MS (ESI ⁺ ); m / z 196 [M + 1] ⁺

The compounds of Reference Examples 9 to 14 were synthesized in the same manner as Reference Example 8.

Reference Example 9 5-Methyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.17 (3H, s), 4.30 (2H, s), 7.03 (1H, d, J = 4.8 Hz), 7.61 (1H, d, J = 4.8 Hz)
MS (FAB ⁺ ); m / z 154 [M + 1] ⁺

Reference Example 10 5-Isopropyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 1.28 (6H, d, J = 6.8Hz), 4.26 (2H, s), 4.54-4.64 (1H, m), 7.04 (1H, d, J = 4.7 Hz), 7.61 (1H, d, J = 4.7Hz)

Reference Example 11 5- (Pyridin-4-ylmethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 4.25 (2H, s), 4.77 (2H, s), 7.03 (1H, d, J = 4.8 Hz), 7.18-7.22 (2H, m), 7.68 (1H, d , J = 4.8 Hz), 8.56-8.59 (2H, m)
MS (ESI ⁺ ); m / z 231 [M + 1] ⁺

Reference Example 12 5-Benzyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 4.19 (2H, s), 4.76 (2H, s), 6.99 (1H, d, J = 4.8 Hz), 7.25-7.39 (5H, m), 7.63 (1H, d , J = 4.8 Hz)
MS (ESI ⁺ ); m / z 229 M ⁺

Reference Example 13 5- (2-Methoxyethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.36 (3H, s), 3.62 (2H, t, J = 5.0 Hz), 3.75 (2H, t, J = 5.0 Hz), 4.46 (2H, s), 7.03 ( 1H, d, J = 4.8Hz), 7.62 (1H, d, J = 4.8 Hz)
MS (FAB ⁺ ); m / z 198 [M + 1] ⁺

Reference Example 14 5- (2-hydroxyethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.16 (1H, br s), 3.72 (2H, t, J = 5.0 Hz), 3.88 (2H, br s), 4.45 (2H, s), 7.03 (1H, d , J = 5.0 Hz), 7.63 (1H, d, J = 5.0 Hz)
MS (ESI ⁺ ); m / z 184 [M + 1] ⁺

Reference Example 15 N-methylthiophene-3-carboxamide Thiophene-3-carboxylic acid 2.21 g (17.2 mmol) in N, N-dimethylformamide 34 ml solution was added triethylamine 3.12 ml (22.4 mmol), (benzotriazole-1- (Iloxy) Tris (
Dimethylamino) phosphonium hexafluorophosphate (9.90 g, 22.4 mmol) and 2.0 M methylamine tetrahydrofuran solution (17.2 ml, 34.4 mmol) were sequentially added, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, extracted three times with ethyl acetate, and the organic layer was washed successively with water, 1N hydrochloric acid, saturated aqueous sodium bicarbonate and saturated brine 1: 1. After drying the organic layer with anhydrous sodium sulfate,
The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1 to 3: 7) to obtain 2.07 g (yield 85%) of the title compound. It was. ¹ H-NMR (CDCl ₃ ) δ: 2.99 (3H, d, J = 4.9 Hz), 6.00 (1H, br s), 7.34 (1H, d, J = 2.9 Hz), 7.36 (1H, dd, J = 4.9 and 1.5 Hz), 7.84 (1H, dd, J = 2.9 and 1.5 Hz)
MS (FAB ⁺ ); m / z 142 [M + 1] ⁺

Reference Example 16 To a solution of N- (2,4-dimethoxybenzyl) thiophene-3-carboxamidothiophene-3-carboxylic acid 4.556 g (35.55 mmol) in N, N-dimethylformamide 100 ml, 2,4-dimethoxy 6.4 ml (42.60 mmol) of benzylamine, 4.861 g (35.98 mmol) of 1-hydroxybenzotriazole, and 6.821 g (35.58 mmol) of 1-ethyl-3- (3′-dimethylaminopropyl) carbodiimide hydrochloride were added sequentially, and at room temperature. Stir for 2 hours. After dilution with ethyl acetate, the organic layer was washed successively with water, 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate, and saturated brine. The aqueous layer was extracted twice with ethyl acetate, the combined organic layers were dried over anhydrous magnesium sulfate, the solvent was distilled off, and the resulting residue was subjected to silica gel flash column chromatography (hexane: ethyl acetate = 7: 3-4). To elute 6) to give 9.21 g (93% yield) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 3.80 (3H, s), 3.86 (3H, s), 4.53 (2H, d, J = 5.8 Hz), 6.40 (1H, br s), 6.43-6.48 (2H, m), 7.25 (1H, d, J = 5.0 Hz), 7.30 (1H, dd, J = 5.1 and 2.9 Hz), 7.35 (1H, dd, J = 5.1 and 1.2 Hz), 7.82 (1H, dd, J = 2.9 and 1.5 Hz)
MS (FAB ⁺ ); m / z 278 [M + 1] ⁺

Reference Example 17 N-Benzylthiophene-3-carboxamide The compound of Reference Example 17 was synthesized in the same manner as Reference Example 16.
¹ H-NMR (CDCl ₃ ) δ: 4.63 (2H, d, J = 5.6Hz), 6.20 (1H, br s), 7.26-7.40 (7H, m), 7.88 (1
(H, dd, J = 2.9 and 1.5 Hz)
MS (ESI ⁺ ); m / z 218 [M + 1] ⁺

Reference Example 18 2- (hydroxymethyl) -N-methylthiophene-3-carboxamide
To a solution of N-methylthiophene-3-carboxamide (2.07 g, 14.6 mmol) in tetrahydrofuran (100 ml) was added dropwise a 2.67 M normal butyl lithium hexane solution (11.5 ml, 30.7 mmol) at -75 ° C. After heating up to -40 ° C over 20 minutes, the mixture was further stirred at -40 ° C for 10 minutes. After adding 5.7 ml (73.6 mmol) of N, N-dimethylformamide, the temperature was raised to 2 ° C. over 10 minutes, and a saturated aqueous ammonium chloride solution was added to stop the reaction. The mixture was diluted with saturated brine, extracted with chloroform three times, and the organic layer was dried over anhydrous sodium sulfate. 530 mg (14.0 mmol) of sodium borohydride was added to a 100 ml methanol solution of the residue obtained by removing the solvent, and the mixture was stirred at room temperature for 20 minutes.
Saturated aqueous ammonium chloride solution was added to stop the reaction, methanol was distilled off, and the obtained aqueous solution was diluted with saturated brine. After extraction with chloroform 10 times, the organic layer was dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluting with hexane: ethyl acetate = 1: 1 to 1: 4) to obtain 2.06 g of the title compound (yield 86%). It was.
¹ H-NMR (CDCl ₃ ) δ: 2.99 (3H, dd, J = 4.9 and 1.7 Hz), 4.80 (2H, d. J = 6.3 Hz), 4.98 (1H,
t, J = 6.3 Hz), 6.31 (1H, br s), 7.15-7.20 (2H, m)
MS (ESI ⁺ ); m / z 172 [M + 1] ⁺

The compounds of Reference Examples 19 to 20 were synthesized in the same manner as Reference Example 18.

Reference Example 19 N- (2,4-dimethoxybenzyl) -2- (hydroxymethyl) thiophene-3-carboxamide
¹ H-NMR (CDCl ₃ ) δ: 3.81 (3H, s), 3.86 (3H, s), 4.53 (2H, d, J = 5.6 Hz), 4.79 (2H, d, J = 6.7 Hz), 5.14 ( 1H, t, J = 6.7Hz), 6.44-6.49 (2H, m), 6.64 (1H, br s), 7.12 (1H, d, J = 5.4 Hz), 7.14 (1H, d, J = 5.4Hz) , 7.24 (1H, d, J = 8.3 Hz)
MS (FAB ⁺ ); m / z 308 [M + 1] ⁺

Reference Example 20 N-benzyl-2- (hydroxymethyl) thiophene-3-carboxamide
¹ H-NMR (CDCl ₃ ) δ: 4.63 (2H, d, J = 5.6Hz), 4.82-4.88 (2H, m), 6.50 (1H, br s), 7.16-7.18 (1H, m), 7.28- 7.40 (6H, m)
MS (ESI ⁺ ); m / z 248 [M + 1] ⁺

Reference Example 21 5-Methyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
To a solution of 2.39 g (14.0 mmol) of 2- (hydroxymethyl) -N-methylthiophene-3-carboxamide in 70 ml of methylene chloride was added 1.63 ml (22.3 mmol) of thionyl chloride under ice-cooling. After stirring at room temperature for 10 minutes, the reaction was quenched with saturated aqueous sodium hydrogen carbonate and diluted with saturated brine. After extraction three times with chloroform, the organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off. To the 280 ml solution of the resulting residue in tetrahydrofuran, 16.7 ml (16.7 mmol) of 1.0 M lithium bis (triethylsilyl) amide tetrahydrofuran solution was added at −55 ° C., and the temperature was raised to 2 ° C. After stirring at the same temperature for 10 minutes, the reaction was quenched with saturated aqueous ammonium chloride and diluted with saturated brine. After extraction three times with chloroform, the organic layer was dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluting with hexane: ethyl acetate = 1: 6 → ethyl acetate → ethyl acetate: methanol = 9: 1) to give the title compound 697 mg (Yield 31%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 3.16 (3H, s), 4.41 (2H, s), 7.23 (1H, d, J = 4.9 Hz), 7.34 (1H, d, J = 4.9 Hz)
MS (FAB ⁺ ); m / z 154 [M + 1] ⁺

Reference Example 22 5- (2,4-Dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
To a solution of 3.16 g (10.3 mmol) of N- (2,4-dimethoxybenzyl) -2- (hydroxymethyl) thiophene-3-carboxamide in 100 ml of methylene chloride, 4.3 ml (30.9 mmol) of triethylamine, Methanesulfonyl 1.6 ml (20.7 mmol) was added sequentially. 20 minutes at room temperature under ice-cooling for 20 minutes
After stirring for 4 minutes, 0.4 ml (5.17 mmol) of methanesulfonyl chloride was further added and stirred at room temperature for 1 hour. After dilution with ethyl acetate, the organic layer was washed successively with a mixed solution of 0.5N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine 1: 1. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off. To a 100 ml solution of the obtained residue in tetrahydrofuran was added 1.0M lithium bis (triethylsilyl) amide tetrahydrofuran solution 11.3 ml (11.3 mmol) at −78 ° C., and the temperature was raised to −10 ° C. over 15 minutes. The reaction was stopped with a saturated aqueous ammonium chloride solution, diluted with a saturated aqueous sodium chloride solution, and extracted three times with chloroform. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the resulting residue was subjected to silica gel flash column chromatography (hexane: ethyl acetate = 3: 1).
Elution with ˜2: 3) to give 1.77 g (59% yield) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 3.78 (3H, s), 3.85 (3H, s), 4.34 (2H, s), 4.70 (2H, s), 6.42-6.47 (2H, m), 7.20-7.27 (2H, m), 7.29-7.33 (1H, m)
MS (FAB ⁺ ); m / z 290 [M + 1] ⁺

Reference Example 23 5-Benzyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one The compound of Reference Example 23 was synthesized in the same manner as Reference Example 22.
¹ H-NMR (CDCl ₃ ) δ: 4.29 (2H, s), 4.76 (2H, s), 7.23-7.36 (7H, m)
MS (FAB ⁺ ); m / z 230 [M + 1] ⁺

Reference Example 24 5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
5- (2,4-Dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one 1.82 g (6.29 mmol) and anisole 3.4 ml (31.3 mmol) were mixed with trifluoroacetic acid. Dissolve in 16 ml, 50 ° C
For 2.5 hours. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (elution with hexane: ethyl acetate = 2: 3 → ethyl acetate) to obtain 1.77 g (yield 95%) of the title compound. .
¹ H-NMR (CD ₃ OD) δ: 4.40-5.20 (3H, m), 7.20 (1H, d, J = 4.7 Hz), 7.54 (1H, d, J = 4.7 Hz)
MS (ESI ⁺ ); m / z 140 [M + 1] ⁺

Reference Example 25 5- (Pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one 142 mg (1.02 mmol) and 3-bromopyridine 118 μl (1.22 mmol), 4,5-bis (diphenylphosphino) -9 , 9-dimethylxanthene (19 mg, 0.03 mmol) was dissolved in 1,4-dioxane (4 ml), tris (dibenzylideneacetone) dipalladium (0) 9 mg (0.01 mmol), cesium carbonate 480 mg (1.47 mmol). In addition, the mixture was stirred at 100 ° C. for 30 minutes. Furthermore, 3-bromopyridine 118 μl (1.22 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene 53 mg (0.09 mmol), tris (dibenzylideneacetone) dipalladium (0) 28 mg (0.031 mmol) was added, and the mixture was stirred at 100 ° C. for 14 hours. After cooling to room temperature, the mixture was diluted with saturated brine and chloroform. The precipitate was filtered through celite, and the filtrate was extracted three times with chloroform. The combined organic layers were dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was purified by preparative thin layer chromatography (developed with chloroform: methanol = 95: 5) to give the title compound 104 mg (Yield 47%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 4.97 (2H, s), 7.32-7.37 (2H, m), 7.43 (1H, d, J = 5.1 Hz), 8.38-8.43 (2H, m), 8.34 (1H , d, J = 2.4Hz)
MS (ESI ⁺ ); m / z 217 [M + 1] ⁺

Reference Example 26 2-Formyl-3- (hydroxymethyl) thiophene
To a solution of 3.3 g (28.9 mmol) of 3-thiophene methanol in 100 ml of tetrahydrofuran, add -20 ° C.
Then, 22.6 ml (60.8 mmol) of a 2.69 M normal butyl lithium hexane solution was added, and the temperature was raised to 2 ° C. After stirring at the same temperature for 25 minutes, 11.2 ml (144.7 mmol) of N, N-dimethylformamide was added, and the mixture was further stirred for 5 minutes. After stopping the reaction with saturated aqueous ammonium chloride, the reaction mixture was poured into saturated brine and extracted four times with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, the solvent was evaporated, and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 3: 2 to 1: 1) to give the title 4.07 g (99% yield) of was obtained.
¹ H-NMR (CDCl ₃ ) δ3.33 (1H, t, J = 6.4 Hz), 4.91 (2H, d, J = 6.4 Hz), 7.19 (1H, d, J = 4.9 Hz), 7.73 (1H, d, J = 4.9 Hz), 9.96 (1H, s)
MS (FAB ⁺ ); m / z 143 [M + 1] ⁺

Reference Example 27 tert-butyl (3-formylthiophen-2-yl) methyl (pyridin-4-ylmethyl) carbamate
To a solution of 1.81 g (13.23 mmol) of 2-formyl-3- (hydroxymethyl) thiophene in 39 ml of 1,2-dichloroethane was added 2.2 ml (20.3 mmol) of 4-picolylamine and 1.2 ml (21.0 mmol) of acetic acid at room temperature. For 30 minutes. To this solution, 3.71 g (17.5 mmol) of sodium triacetoxyborohydride was added and stirred at room temperature for 4 hours. The reaction mixture was diluted with 100 ml of tetrahydrofuran and 80 ml of water, 5.49 g (39.7 mmol) of potassium carbonate and 6 ml (26.1 mmol) of ditert-butyl dicarbonate were added, and the mixture was stirred at room temperature for 30 minutes. 1,2-Dichloroethane and tetrahydrofuran were distilled off under reduced pressure, 50 ml of 1,4-dioxane was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with saturated brine, and extracted with ethyl acetate and chloroform. The combined organic layers are dried over anhydrous magnesium sulfate, and the solvent is distilled off. The resulting residue is simply purified by short silica gel flash column chromatography (eluting with chloroform: methanol = 99: 1 to 97: 3). went. To a 1,2-dichloroethane 40 ml solution of the obtained compound was added manganese dioxide 3.45 g (39.7 mmol), 50
Stir at 30 ° C. for 30 minutes. Further, 3.45 g (39.7 mmol) of manganese dioxide was added and stirred at 50 ° C. for 2 hours, and then 3.45 g (39.7 mmol) of manganese dioxide was further added and stirred at 50 ° C. for 2 hours. After filtration using Celite, the residue obtained by concentrating the filtrate was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 99: 1 to 97: 3) to give 2.10 g of the title compound ( Yield 47%) was obtained.
¹ H-NMR (CDCl ₃ ) δ1.18-1.62 (9H, m), 4.50 (2H, br s), 4.94-5.00 (2H, m), 7.12-7.14 (2H, m), 7.24 (1H, d , J = 5.2 Hz), 7.36 (1H, d, J = 5.2 Hz), 8.53-8.55 (2H, m), 9.96 (1H, br s)
MS (ESI ⁺ ); m / z 333 [M + 1] ⁺

The compounds of Reference Examples 28 to 29 were synthesized in the same manner as Reference Example 27.

Reference Example 28 tert-butyl (3-formylthiophen-2-yl) methyl (pyridin-3-ylmethyl) carbamate
¹ H-NMR (CDCl ₃ ) δ1.46-1.62 (9H, m), 4.45 (2H, br s), 4.92-4.94 (2H, m), 7.21-7.26 (2H, m), 7.37 (1H, d , J = 5.4 Hz), 7.52-7.59 (1H, m), 8.50-8.54 (2H, m), 9.96 (1H, br s)
MS (ESI ⁺ ); m / z 333 [M + 1] ⁺

Reference Example 29 tert-butyl (3-formylthiophen-2-yl) methyl (pyridin-2-ylmethyl) carbamate
¹ H-NMR (CDCl ₃ ) δ1.44-1.58 (9H, m), 4.56-4.64 (2H, m), 5.02-5.09 (2H, m), 6.99-7.24 (3H, m), 7.38 (1H, d, J = 5.1 Hz), 7.65 (1H, ddd, J = 7.8 and 7.8 and 1.9 Hz), 8.53 (1H,
d, J = 4.4 Hz), 9.99-10.01 (1H, m)
MS (FAB ⁺ ); m / z 333 [M + 1] ⁺

Reference Example 30 Methyl 2- (pyridin-4-ylmethylaminomethyl) thiophene-3-carboxylate
To a solution of tert-butyl (3-formylthiophen-2-yl) methyl (pyridin-4-ylmethyl) carbamate 2.097 g (6.31 mmol) in methanol 63 ml, sodium cyanide 1.548 g (31.60 mmol), acetic acid 0.91 ml (15.90 mmol) and 8.76 g (100.69 mmol) of manganese dioxide were sequentially added, and the mixture was stirred at 40 ° C. for 20 minutes. After filtration using celite, the filtrate was concentrated, and the resulting residue was diluted with a 1: 1 mixed solution of saturated brine and saturated sodium bicarbonate water, and extracted twice with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was dissolved in 32 ml of methylene chloride and 6 ml of trifluoroacetic acid.
And stirred at room temperature for 3.5 hours. After stopping the reaction with saturated aqueous sodium hydrogen carbonate, the aqueous layer was saturated with sodium chloride. After extraction four times with chloroform, the combined organic layers were dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 99: 1 to 97: 3) to obtain 1.45 g (yield 88%) of the title compound. .
¹ H-NMR (CDCl ₃ ) δ: 3.84 (3H, s), 3.88 (2H, s), 4.28 (2H, s), 7.14 (1H, d, J = 5.4 Hz), 7.31-7.33 (2H, m ), 7.43 (1H, d, J = 5.4 Hz), 8.54-8.57 (2H, m)
MS (ESI ⁺ ); m / z 263 [M + 1] ⁺

The compounds of Reference Examples 31 to 32 were synthesized in the same manner as Reference Example 30.

Reference Example 31 2- (Pyridin-3-ylmethylaminomethyl) thiophene-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 3.84 (3H, s), 3.88 (2H, s), 4.28 (2H, s), 7.12 (1H, d, J = 5.4 Hz), 7.25-7.29 (1H, m ), 7.43 (1H, d, J = 5.4 Hz), 7.72-7.76 (1H, m), 8.51 (1H, dd, J = 4.9 and
1.7 Hz), 8.60 (1H, d, J = 1.7 Hz)
MS (FAB ⁺ ); m / z 263 [M + 1] ⁺

Reference Example 32 Methyl 2- (pyridin-2-ylmethylaminomethyl) thiophene-3-carboxylate
¹ H-NMR (CDCl ₃ ) δ: 3.84 (3H, s), 4.00 (2H, s), 4.33 (2H, s), 7.12 (1H, d, J = 5.4 Hz), 7.15-7.18 (1H, m ), 7.36 (1H, d, J = 7.8 Hz), 7.42 (1H, d, J = 5.4 Hz), 7.65 (1H, ddd, J = 7.8 and 7.8 and 7.9 Hz), 8.55-8.57 (1H, m)
MS (ESI ⁺ ); m / z 263 [M + 1] ⁺

Reference Example 33 5- (Pyridin-4-ylmethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
Add 7.2 ml (14.4 mmol) of 2.0 M trimethylaluminum heptane solution to 48 ml of toluene in 1.25 g (4.76 mmol) of methyl 2- (pyridin-4-ylmethylaminomethyl) thiophene-3-carboxylate and heat to 100 ° C. did. The mixture was stirred at the same temperature for 1 hour and then cooled with ice. The reaction was stopped with a mixed solution of a saturated aqueous sodium tartrate-potassium salt solution and saturated aqueous sodium bicarbonate 6: 1, diluted with ethyl acetate, and stirred at room temperature for 1 hour. After extraction with ethyl acetate and chloroform, the combined organic layers were dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluted with ethyl acetate → chloroform: methanol = 95: 5) to obtain 628 mg (yield 57%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 4.38 (2H, s), 4.76 (2H, s), 7.19-7.21 (2H, m), 7.29 (1H, d, J = 5.0 Hz), 7.39 (1H, d , J = 5.0 Hz), 8.56-8.58 (2H, m)
MS (ESI ⁺ ); m / z 231 [M + 1] ⁺

The compounds of Reference Examples 34 to 35 were synthesized in the same manner as Reference Example 33.

Reference Example 34 5- (Pyridin-3-ylmethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one ¹ H-NMR (CDCl ₃ ) δ: 4.34 (2H, s) , 4.77 (2H, s), 7.25-7.30 (2H, m), 7.37 (1H, d, J = 5.1 Hz), 7.66 (1H, ddd, J = 8.0 and 2.2 and 1.7 Hz), 8.55 (1H, dd , J = 4.9 and 1.7 Hz), 8.58 (1H, d, J = 2.2 Hz)
MS (ESI ⁺ ); m / z 230 M ⁺

Reference Example 35 5- (Pyridin-2-ylmethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one ¹ H-NMR (CDCl ₃ ) δ: 4.52 (2H, s) , 4.88 (2H, s), 7.18-7.22 (1H, m), 7.29 (1H, d, J = 5.1 Hz), 7.31-7.36 (2H, m), 7.67 (1H, ddd, J = 7.8 and 7.8 and 1.7 Hz), 8.55-8.56 (1H, m)
MS (ESI ⁺ ); m / z 231 [M + 1] ⁺

Reference Example 36 6-Methyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
87 mg (2.17 mmol, purity) of sodium hydride cooled to 0 ° C with a solution of 7.5 ml of anhydrous N, N-dimethylformamide in 5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one 60%) in anhydrous N, N-dimethylformamide in 7.5 ml. After stirring for 10 minutes, 0.135 ml (2.17 mmol) of methyl iodide was added dropwise. After stirring for 7 hours at room temperature, water and a 20% aqueous sodium chloride solution were added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluting with hexane: ethyl acetate = 2: 1 to 1: 1) to give 209 mg of the title compound (
Yield 86%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.94 (2H, t, J = 7.1Hz), 3.10 (3H, s), 3.61 (2H, t, J = 7.1 Hz), 6.89 (1H, d, J = 4.9 Hz), 7.44 (1H, d, J = 4.9 Hz)

The compounds of Reference Examples 37 to 44 were synthesized in the same manner as Reference Example 36.

Reference Example 37 6-Isopropyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 1.20 (6H, d, J = 6.8 Hz), 2.88 (2H, t, J = 6.8 Hz), 3.49 (2H, t, J = 6.8 Hz), 4.99 (1H, q, J = 6.8 Hz), 6.89 (1H, d, J = 4.9 Hz), 7.44 (1H, d, J = 4.9 Hz)

Reference Example 38 Methyl 2- (7-oxo-4,5-dihydrothieno [2,3-c] pyridin-6 (7H) -yl) acetate
¹ H-NMR (CDCl ₃ ) δ: 3.00 (2H, t, J = 7.2 Hz), 3.60 (2H, t, J = 7.2 Hz), 3.75 (3H, s), 4.30 (2H, s), 6.91 ( 1H, d, J = 4.8 Hz), 7.48 (1H, d, J = 4.8 Hz)

Reference Example 39 6- (2-methoxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 2.91 (2H, t, J = 6.9Hz), 3.36 (3H, s), 3.57-3.73 (6H, m), 6.88 (1H, d, J = 4.8 Hz), 7.43 (1H, d, J = 4.8Hz)

Reference Example 40 6- (2-tert-butyldimethylsiloxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.05 (6H, s), 0.89 (9H, s), 2.91 (2H, t, J = 7.2 Hz), 3.63 (2H, t, J = 5.2 Hz), 3.75 ( 2H, d, J = 7.2Hz), 3.83 (2H, t, J = 5.2 Hz), 6.90 (1H, d, J = 4.8 Hz), 7.44 (1H, d, J = 4.8 Hz)

Reference Example 41 6- (2-Ethoxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 1.19 (3H, t, J = 6.9 Hz), 2.91 (2H, t, J = 7.1 Hz), 3.50 (2H, q, J = 6.9
Hz), 3.62-3.75 (6H, m), 6.89 (1H, d, J = 4.9 Hz), 7.43 (1H, d, J = 4.9 Hz)

Reference Example 42 5-Methyl-6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.08 (2H, t, J = 6.9 Hz), 3.10 (3H, s), 3.64 (2H, t, J = 6.9 Hz), 7.07 (1H, d, J = 5.3 Hz), 7.42 (1H, d, J = 5.3 Hz)

Reference Example 43 5- (2-methoxyethyl) -6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.05 (2H, t, J = 6.9 Hz), 3.36 (3H, s), 3.59-3.63 (2H, m), 3.68-3.72 (2H, m), 3.76 (2H , t, J = 6.9Hz), 7.08 (1H, d, J = 5.2 Hz), 7.42 (1H, d, J = 5.2 Hz)

Reference Example 44 5- (Pyridin-2-ylmethyl) -6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.07 (2H, t, J = 6.8 Hz), 3.74 (2H, t, J = 6.8 Hz), 4.86 (2H, s), 7.10 (1H, d, J = 5.4 Hz), 7.17-7.21 (1H, m), 7.38-7.41 (1H, m), 7.46 (1H, d, J = 5.4 Hz), 7.63-7.68 (1H, m), 8.53-8.56 (1H, m)

Reference Example 45 2- (7-Oxo-4,5-dihydrothieno [2,3-c] pyridin-6 (7H) -yl) acetic acid
Methyl 2- (7-oxo-4,5-dihydrothieno [2,3-c] pyridin-6 (7H) -yl) acetate 794 mg (3.52
mmol) in methanol (15 ml) and 1,4-dioxane (15 ml) were added with 5N aqueous sodium hydroxide solution (0.845 ml). Stir at 50 ° C for 2 hours, then cool to room temperature, 5N hydrochloric acid 0.845 ml
Was added. The reaction solution was concentrated to dryness to obtain 749 mg (yield 100%) of the title compound.
¹ H-NMR (DMSO-d ₆ ) δ: 2.91 (2H, t, J = 6.9 Hz), 3.67 (2H, t, J = 6.9 Hz), 4.65 (2H, s), 7.07 (1H, d, J = 5.2 Hz), 7.80 (1H, d, J = 4.8 Hz), 12.76 (1H, br s)

Reference Example 46 N, N-dimethyl-2- (7-oxo-4,5-dihydrothieno [2,3-c] pyridin-6 (7H) -yl) acetamide
2- (7-oxo-4,5-dihydrothieno [2,3-c] pyridin-6 (7H) -yl) acetic acid 700 mg (3.31 mmol) in anhydrous methylene chloride 15 ml and anhydrous N, N-dimethylformamide 15 To the ml solution, 935 mg (4.97 mmol) of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride and 674 mg (49.7 mmol) of 1-hydroxybenzotriazole were added. After stirring at room temperature for 10 minutes, 5 ml (10 mmol) of 2 M dimethylamine tetrahydrofuran solution was added. After stirring at room temperature for 18 hours, 20% aqueous sodium chloride solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with 20% aqueous sodium chloride solution, dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluted with ethyl acetate) to give the title compound 262 mg (yield 33%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.96-3.07 (8H, m), 3.75 (2H, t, J = 7.0 Hz), 4.35 (2H, s), 6.90 (1H, d, J = 5.1 Hz), 7.45 (1H, d, J = 5.1 Hz)

Reference Example 47 6- (2-hydroxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
6- (2-tert-butyldimethylsilyloxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one 133 mg (0.43 mmol) in anhydrous tetrahydrofuran 5 ml solution with 1 M fluoride Tetrabutylammonium tetrahydrofuran solution 0.64 ml (0.64 mmol) was added. After stirring at room temperature for 30 minutes, water was added to stop the reaction, and the mixture was extracted with methylene chloride. After drying over anhydrous magnesium sulfate, the residue obtained by evaporating the solvent was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 20: 1) to give the title compound 95 mg (yield 100%) Got.
¹ H-NMR (CDCl ₃ ) δ: 2.97 (2H, t, J = 7.1 Hz), 3.70-3.74 (4H, m), 3.87 (2H, t, J = 5.1 Hz), 6.92 (1H, d, J = 4.9 Hz), 7.48 (1H, d, J = 4.9 Hz)

Reference Example 48 6- (Pyridin-3-yl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
To a solution of 1.05-g (6.88 mmol) 5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one and 0.81 ml (8.26 mmol) 3-bromopyridine in 70 ml anhydrous 1,4-dioxane, Cesium 3.14 g (9.63
mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene 119 mg (0.21 mmol)
And tris (dibenzylideneacetone) dipalladium (0) 63 mg (0.06 mmol) were added. After warming to 100 ° C. and stirring for 15 hours, the reaction solution was filtered using Celite. The residue obtained by concentrating the filtrate was subjected to silica gel flash column chromatography (hexane: ethyl acetate = 1: 8).
To give 1.26 g (yield 79%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 3.11 (2H, t, J = 6.6 Hz), 4.10 (2H, t, J = 6.6 Hz), 6.98 (1H, d, J = 5.2
Hz), 7.31-7.34 (1H, m), 7.56 (1H, d, J = 5.2 Hz), 7.74-7.78 (1H, m), 8.47-8.48 (1H, m), 8.65-8.66 (1H, m)

Reference Example 49 2-Bromo-5-tert-butyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
To a solution of 1.51 g (7.74 mmol) of 5-tert-butyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one in 200 ml of anhydrous N, N-dimethylformamide, 2.81 g (15.8 g) of N-bromosuccinimide mmol)
Stir at room temperature for 2 hours. Saturated aqueous sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane → ethyl acetate) to give the title compound (1.71 g, yield 81%). .
¹ H-NMR (CDCl ₃ ) δ: 1.53 (9H, s), 4.32 (2H, s), 7.01 (1H, s)
MS (ESI ⁺ ); m / z 274 [M + 1] ⁺

The compounds of Reference Examples 50 to 70 were synthesized in the same manner as Reference Example 49.

Reference Example 50 2-Bromo-5-methyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.14 (3H, s), 4.28 (2H, s), 7.06 (1H, s)
MS (ESI ⁺ ); m / z 231 M ⁺

Reference Example 51 2-Bromo-5-isopropyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 1.27 (6H, d, J = 6.6Hz), 4.23 (2H, s), 4.52-4.59 (1H, m), 7.07 (1H, s)

Reference Example 52 2-Bromo-5- (pyridin-4-ylmethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one ¹ H-NMR (CDCl ₃ ) δ: 4.22 (2H, s ), 4.74 (2H, s), 7.06 (1H, s), 7.17-7.22 (2H, m), 8.57-8.60 (2H, m)

Reference Example 53 5-Benzyl-2-bromo-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 4.16 (2H, s), 4.72 (2H, s), 7.00 (1H, s), 7.25-7.37 (5H, m)
MS (ESI ⁺ ); m / z 308 [M + 1] ⁺

Reference Example 54 2-Bromo-5- (2-methoxyethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.35 (3H, s), 3.60 (2H, t, J = 4.8 Hz), 3.72 (2H, t, J = 4.8 Hz), 4.43 (2H, s), 7.06 ( 1H, s)
MS (ESI ⁺ ); m / z 275 M ⁺

Reference Example 55 2-Bromo-5- (2-triethylsiloxyethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.58 (6H, q, J = 7.9 Hz), 0.92 (9H, t, J = 7.9 Hz), 3.65 (2H, t, J = 5.2 Hz), 3.83 ( 2H, t, J = 5.2 Hz), 4.47 (2H, s), 7.06 (1H, s)
MS (ESI ⁺ ); m / z 376 [M + 1] ⁺

Reference Example 56 2-Bromo-5-methyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 3.15 (3H, s), 4.37 (2H, s), 7.24 (1H, s)
MS (ESI ⁺ ); m / z 233 [M + 1] ⁺

Reference Example 57 2-Bromo-5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole-4-
on
¹ H-NMR (CDCl ₃ ) δ: 4.92 (2H, s), 7.30 (1H, s), 7.34 (1H, dd, J = 8.5 and 4.7 Hz), 8.35 (1H, ddd, J = 8.5 and 2.7 and1 .4 Hz), 8.42 (1H, dd, J = 4.7 and 1.4 Hz), 8.80 (1H, d, J = 2.7 Hz)
MS (ESI ⁺ ); m / z 297 [M + 1] ⁺

Reference Example 58 2-Bromo-5- (pyridin-4-ylmethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 4.32 (2H, s), 4.74 (2H, s), 7.17-7.20 (2H, m), 7.30 (1H, s), 8.58-8.60 (2H, m)
MS (ESI ⁺ ); m / z 309 [M + 1] ⁺

Reference Example 59 2-Bromo-5- (pyridin-3-ylmethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 4.29 (2H, s), 4.75 (2H, s), 7.25-7.31 (1H, m), 7.29 (1H, s), 7.63-7.66 (1H, m), 8.55 -8.57 (2H, m)
MS (FAB ⁺ ); m / z 309 [M + 1] ⁺

Reference Example 60 2-Bromo-5- (pyridin-2-ylmethyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 4.48 (2H, s), 4.85 (2H, s), 7.19-7.22 (1H, m), 7.30 (1H, s), 7.32 (1H, d, J = 7.8 Hz ), 7.67 (1H, ddd, J = 7.8 and 7.8 and 1.9 Hz), 8.54-8.56 (1H, m)
MS (ESI ⁺ ); m / z 309 [M + 1] ⁺

Reference Example 61 5-Benzyl-2-bromo-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CD ₃ CN) δ: 4.31 (2H, s), 4.66 (2H, s), 7.25-7.36 (6H, m)
MS (FAB ⁺ ); m / z 308 [M + 1] ⁺

Reference Example 62 2-Bromo-5-methyl-6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 3.00 (2H, t, J = 7.0 Hz), 3.07 (3H, s), 3.62 (2H, t, J = 7.0 Hz), 7.37 (1H, s)
MS (ESI ⁺ ); m / z 246,248 [M + 1] ⁺

Reference Example 63 2-Bromo-5- (2-methoxyethyl) -6,7-dihydrothieno [3,2-c] pyridine-4 (5H)-
on
¹ H-NMR (CDCl ₃ ) δ: 2.96 (2H, t, J = 6.9 Hz), 3.35 (3H, s), 3.57-3.61 (2H, m), 3.64-3.69 (2H, m), 3.74 (2H , t, J = 6.9Hz), 7.69 (1H, s)

Reference Example 64 2-Bromo-5- (pyridin-2-ylmethyl) -6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 2.98 (2H, t, J = 7.0 Hz), 3.72 (2H, t, J = 7.0 Hz), 4.82 (2H, s), 7.18-7.22 (1H, m), 7.35-7.38 (1H, m), 7.41 (1H, s), 7.63-7.68 (1H, m), 8.53-8.55 (1H, m)

Reference Example 65 2-Bromo-6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 2.96-3.01 (2H, m), 3.60-3.66 (2H, m), 5.53-5.61 (1H, m), 7.38 (1H,
s)
MS (ESI ⁺ ); m / z 232,234 [M + 1] ⁺

Reference Example 66 2-Bromo-6-methyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 2.89 (2H, t, J = 6.8Hz), 3.07 (3H, s), 3.58 (2H, t, J = 6.8 Hz), 6.88 (1H, s)

Reference Example 67 2-Bromo-6-isopropyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 1.18 (6H, d, J = 6.8 Hz), 2.82 (2H, t, J = 6.8 Hz), 3.45 (2H, t, J = 6.8 Hz), 4.92 (1H, q, J = 6.8 Hz), 6.88 (1H, s)

Reference Example 68 2- (2-Bromo-7-oxo-4,5-dihydrothieno [2,3-c] pyridin-6 (7H) -yl) -N, N
-Dimethylacetamide
¹ H-NMR (CDCl ₃ ) δ: 2.93 (2H, t, J = 6.9Hz), 2.97 (3H, s), 3.05 (3H, s), 3.72 (2H, t, J = 6.9 Hz), 4.30 ( 2H, s), 7.00 (1H, s)

Reference Example 69 2-Bromo-6- (2-methoxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 2.85 (2H, t, J = 7.1 Hz), 3.35 (3H, s), 3.55-3.70 (6H, m), 6.88 (1H,
s)

Reference Example 70 2-Bromo-6- (2-hydroxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 2.90 (2H, t, J = 7.1 Hz), 3.66-3.71 (4H, m), 3.83-3.86 (2H, m), 6.89 (1H, s)

Reference Example 71 2-Bromo-4H-thieno [2,3-c] pyrrol-6 (5H) -one
To 2.5 g (9.12 mmol) of 2-bromo-5-tert-butyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one, add 30 ml of trifluoroacetic acid and 3 ml of water and heat for 24 hours. Refluxed. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluted with ethyl acetate) to obtain the title compound (1.21 g, yield 61%).
¹ H-NMR (CDCl ₃ ) δ: 4.37 (2H, s), 6.26-6.34 (1H, m), 7.09 (1H, s)

Reference Example 72 2-Bromo-5- (pyridin-3-ylmethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one
2-Bromo-4H-thieno [2,3-c] pyrrol-6- (5H) -one 1.21 g (5.55 mmol) in anhydrous N, N-dimethylformamide 28 ml solution under ice-cooling, 666 mg (16.65 sodium hydride) mmol) was added. After stirring for 10 minutes, 1.37 g (8.33 mmol) of 3- (chloromethyl) pyridine hydrochloride was added. After stirring for 1 hour, saturated brine was added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed again with saturated brine, and dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent was purified by silica gel flash column chromatography (eluted with ethyl acetate: methanol = 20: 1) to obtain 882 mg (yield 51%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 4.20 (2H, s), 4.75 (2H, s), 7.04 (1H, s), 7.25-7.31 (1H, m), 7.63-7.68 (1H, m), 8.55 -8.58 (2H, m)

Reference Example 73 2-Bromo-5- (pyridin-2-ylmethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one The compound of Reference Example 73 was synthesized in the same manner as Reference Example 72.
¹ H-NMR (CDCl ₃ ) δ: 4.38 (2H, s), 4.85 (2H, s), 7.05 (1H, s), 7.19-7.23 (1H, m), 7.30-7.33 (1H, m), 7.64 -7.69 (1H, m), 8.54-8.57 (1H, m)
MS (GC / MS); m / z 307 [M + 1] ⁺

Reference Example 74 5-Bromo-2,3-bishydroxymethylthiophene
To a solution of 741 mg (5.14 mmol) of 2,3-bishydroxymethylthiophene in 12 ml of anhydrous tetrahydrofuran, 6 ml of 24% hydrobromic acid and 0.300 ml (5.86 mmol) of bromine were added under ice cooling, and the mixture was stirred at room temperature for 15 minutes. Saturated aqueous sodium bicarbonate was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed successively with 10% aqueous sodium thiosulfate, saturated aqueous sodium bicarbonate, and saturated brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (elution with hexane: ethyl acetate = 2: 1 to 1: 1 → ethyl acetate), This gave 939 mg (82% yield) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 2.42 (1H, br s), 2.75 (1H, br s), 4.61 (2H, s), 4.71 (2H, s), 6.96 (1H, s)
MS (ESI ⁺ ); m / z 222 M ⁺

Reference Example 75 5-Bromothiophene-2,3-dialdehyde
2.25 g (10.09 mmol) of 5-bromo-2,3-bishydroxymethylthiophene was suspended in 30 ml of chloroform, 6.76 g (77.8 mmol) of manganese dioxide was added, and the mixture was stirred at 60 ° C. for 7 hours. The reaction solution was filtered through Celite, and the residue obtained by concentrating the filtrate was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 5: 1 to 3: 1) to give 1.72 g of the title compound ( Yield 78%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 7.59 (1H, s), 10.26 (1H, s), 10.37 (1H, s)

Reference Example 76 2-Bromo-5-cyclopropyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
110 mg (0.50 mmol) of 5-bromothiophene-2,3-dialdehyde was dissolved in 8 ml of methylene chloride, and 0.038 ml (0.55 mmol) of cyclopropylamine and 0.057 ml (1.0% of acetic acid) were added at −40 ° C. under an argon atmosphere. mmol) and stirred for 4 hours while warming to room temperature. Sodium bicarbonate water was added to the reaction solution, and the mixture was extracted twice with chloroform. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluted with chloroform: ethyl acetate = 5: 1) to give the title compound (53.1 mg). 41%).
¹ H-NMR (CDCl ₃ ) δ: 0.80-0.93 (4H, m), 2.77-2.88 (1H, m), 4.23 (2H, s), 7.03 (1H, s)

Reference Example 77 2-Bromo-6- (2-triethylsiloxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
2-Bromo-6- (2-hydroxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one In a solution of 118 mg of anhydrous N, N-dimethylformamide in 5 ml Below, 44 mg (0.64 mmol) of imidazole and 0.09 ml (0.56 mmol) of triethylsilyl chloride were added. After stirring for 30 minutes under ice-cooling, 44 mg (0.64 mmol) of imidazole and 0.09 ml (0.56 mmol) of triethylsilyl chloride were added, and an additional 20
After stirring for minutes, water was added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and a 20% aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The solvent was distilled off, and the resulting residue was subjected to silica gel flash column chromatography (hexane: ethyl acetate = 10: 1). Elution) to give 95 mg (yield 100%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.60 (6H, q, J = 8.4 Hz), 0.94 (9H, t, J = 8.4 Hz), 2.85 (2H, t, J = 7.1
Hz), 3.60 (2H, t, J = 5.4 Hz), 3.73 (2H, d, J = 7.1 Hz), 3.82 (2H, t, J = 5.4 Hz), 6.88 (1H, s)

Reference Example 78 5- (3,4-Dimethoxybenzyl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole
To a solution of 7.6 g (27.64 mmol) of 5- (3,4-dimethoxybenzyl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole in 100 ml of anhydrous tetrahydrofuran at −73 ° C. in an argon atmosphere. 24.3 ml (41.11 mmol) of a 1.59 M normal butyl lithium hexane solution was added dropwise. After stirring for 30 minutes, 8.4 ml (33.17 mmol) of trinormalbutyltin chloride was added at the same temperature. After stirring for 30 minutes, the reaction was stopped by adding a saturated aqueous solution of ammonium chloride, extracted with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 4: 1) to obtain 15.5 g (yield 99%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.88 (9H, t, J = 7.3Hz), 1.04-1.09 (6H, m), 1.26-1.37 (6H, m), 1.50-1.58 (6H, m), 3.85 -3.99 (12H, m), 6.79-6.85 (2H, m), 6.90 (1H, dd, J = 8.0 and 1.9 Hz), 7.00 (1H, d, J = 1.9 Hz)

Reference Example 79 5- (3,4-Dimethoxybenzyl) -2-tributylstannyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine The compound of Reference Example 79 is the same as Reference Example 78. Synthesized.
¹ H-NMR (CDCl ₃ ) δ: 0.89 (9H, t, J = 7.2Hz), 1.03-1.07 (6H, m), 1.24-1.37 (6H, m), 1.50-1.57 (6H, m), 2.77 (2H, t, J = 5.6Hz), 2.91 (2H, t, J = 5.6 Hz), 3.59 (2H, s), 3.65 (2H
, s), 3.88 (6H, s), 6.77 (0.84H, s), 6.77 (0.16H, d, J = 23.2 Hz), 6.82 (1H, d, J = 8.0Hz), 6.89 (1H, dd, J = 8.0 and 1.6 Hz), 6.95-6.99 (1H, br s)

Reference Example 80 5- (9H-Fluoren-9-yl) methyloxycarbonyl-2-tributylstannyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine
A 150 ml chloroform solution of 15.1 g (26.1 mmol) 5- (3,4-dimethoxybenzyl) -2-tributylstannyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine in an argon atmosphere The mixture was ice-cooled with 3.13 g (31.3 mmol) of potassium hydrogen carbonate and 8.12 g (31.3 mmol) of (9H-fluoren-9-yl) methoxycarbonyl chloride, and stirred at the same temperature for 30 minutes. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. After drying the organic layer over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 10: 1) to give the title compound (7.88 g, yield). Rate 46%).
¹ H-NMR (CDCl ₃ ) δ: 0.88-0.95 (9H, m), 1.06-1.14 (6H, m), 1.29-1.41 (6H, m), 1.48-1.70 (6H, m), 2.80-2.90 ( 2H, m), 3.70-3.82 (2H, m), 4.28 (1H, t, J = 6.6 Hz), 4.45 (2H, d,
J = 6.6 Hz), 4.60 (2H, s), 6.84 (0.84H, s), 6.84 (0.16H, d, J = 22.7 Hz), 7.26-7.40 (4H, m), 7.59 (2H, d, J = 7.5 Hz), 7.70- 7.81 (2H, m)

  The compounds of Reference Examples 81 to 83 were synthesized in the same manner as Reference Example 78.

Reference Example 81 6- (3,4-Dimethoxybenzyl) -2- (tributylstannyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.72 (27H, m), 2.75-2.76 (4H, m), 3.64 (2H, s), 3.72 (2H, s), 3.87 (6H, s), 3.79 -6.95 (4H, m)

Reference Example 82 5- (4,5-Dihydrothiazol-2-yl) -2-tributylstannyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine
¹ H-NMR (CDCl ₃ ) δ: 0.88-1.68 (27H, m), 2.94-2.98 (2H, m), 3.33 (2H, t, J = 7.4 Hz), 3.77 (2H, t, J = 5.6 Hz ), 4.05 (2H, t, J = 7.4 Hz), 4.63 (2H, s), 6.83 (0.84H, s), 6.83 (0.16H, d, J = 22.7 Hz)

Reference Example 83 5- (1-Methyl-4,5-dihydro-1H-imidazol-2-yl) -2-tributylstannyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine
¹ H-NMR (CDCl ₃ ) δ: 0.85-0.95 (9H, m), 1.03-1.16 (6H, m), 1.26-1.40 (6H, m), 1.46-1.64 (6H, m), 2.76 (3H, s), 2.95-3.04 (2H, m), 3.36 (2H, t, J = 9.0 Hz), 3.44 (2H, t, J = 5.4
Hz), 3.69 (2H, t, J = 9.0 Hz), 4.29 (2H, s), 6.82 (1H, s)

Reference Example 84 5-((9H-Fluoren-9-yl) methoxycarbonyl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole The compound of Reference Example 84 is a reference example. Synthesized as in 80.
¹ H-NMR (CDCl ₃ ) δ: 0.91 (9H, t, J = 7.2Hz), 1.06-1.17 (6H, m), 1.26-1.42 (6H, m), 1.50-1.64 (6H, m), 4.20 -4.78 (7H, m), 6.90 (1H, s), 7.28-7.45 (4H, m), 7.60-7.66 (2H, m),
7.74-7.80 (2H, m)

Reference Example 85 2-Tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole
5-((9H-Fluoren-9-yl) methoxycarbonyl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole (1.14 g, 1.79 mmol) was converted to N, N- It melt | dissolved in 20 ml of dimethylformamide, 1.26 ml (8.96 mmol) of diisopropylamine was added under argon atmosphere, and it stirred at 40 degreeC for 2 hours. Brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed 3 times with brine. After drying the organic layer over anhydrous magnesium sulfate, the solvent was distilled off and the resulting residue was subjected to silica gel flash column chromatography (elution with hexane: ethyl acetate = 1: 1 to chloroform: methanol = 10: 1 to 5: 1) To give 400 mg (yield 54%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.90 (9H, t, J = 7.2Hz), 1.03-1.12 (6H, m), 1.23-1.40 (6H, m), 1.50-1.67 (6H, m), 4.05 -4.12 (2H, m), 4.18-4.23 (2H, m), 6.84 (1H, s)

Reference Example 86 5- (1-Methyl-4,5-dihydro-1H-imidazol-2-yl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole
198 mg (0.478 mmol) of 2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole was suspended in 1.5 ml of ethanol, and 1-methyl-2-methylthio-4,5-dihydro- 139 mg (1.07 mmol) of 1H-imidazole and 0.087 ml (0.62 mmol) of triethylamine were added, and the mixture was heated to reflux for 8 hours. The residue obtained by distilling off the solvent was subjected to amino silica gel flash column chromatography (
Elution with ethyl acetate: methanol = 20: 1) to obtain 96.3 mg (yield 41%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.90 (9H, t, J = 7.5Hz), 1.04-1.15 (6H, m), 1.24-1.40 (6H, m), 1.50-1.63 (6H, m), 2.87 (3H, s), 3.42 (2H, t, J = 8.7 Hz), 3.68 (2H, t, J = 8.7 Hz), 4.52-4.53 (2H, m), 4.54-4.56 (2H, m), 6.86 ( 1H, s)

Reference Example 87 5- (Pyridin-3-yl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole
316 mg (1.56 mmol) of 5- (pyridin-3-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole was dissolved in 6 ml of tetrahydrofuran, and 1 M tert-butoxy was dissolved in an argon atmosphere. After adding 3.13 ml (3.13 mmol) of potassium tetrahydrofuran solution and stirring at room temperature for 20 minutes, 1.48 ml (2.35 mmol) of 1.58M normal butyl lithium tetrahydrofuran solution and 0.673 ml (2.35 mmol) of trinormal butyltin chloride were successively added dropwise. Stir at warm for 30 minutes. An ammonium chloride solution was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate and washed twice with brine. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 5: 1) to give 436 mg (yield) of the title compound. 57%).
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.96 (9H, m), 1.08-1.17 (6H, m), 1.22-1.42 (6H, m), 1.50-1.70 (6H, m), 4.50-4.54 ( 2H, m), 4.62-4.68 (2H, m), 6.85-6.92 (1H, m), 6.96 (1H, s), 7.14-7.21 (1H, m), 7.97-8.02 (1H, m), 8.04- 8.08 (1H, m)

Reference Example 88 5-tert-butyl-2-tributylstannyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
2-Bromo-5-tert-butyl-4H-thieno [2,3-c] pyrrol-6- (5H) -one 735 mg (2.68 mmol) in anhydrous tetrahydrofuran 10 ml solution under ice-cooling, 0.76 M isopropylmagnesium bromide Tetrahydrofuran solution 4.60 ml (3.50 mmol) was added dropwise. After stirring for 10 minutes under ice cooling, 0.995 ml (3.50 mmol) of trinormalbutyltin chloride was added at the same temperature. After stirring for 10 minutes, a saturated aqueous ammonium chloride solution was added to stop the reaction, extraction was performed with ethyl acetate, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was subjected to silica gel flash column chromatography (hexane → hexane: ethyl acetate = 1: 1).
To yield 1.05 g (yield 81%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 0.89 (9H, t, J = 7.4Hz), 1.03-1.21 (6H, m), 1.25-1.39 (6H, m), 1.45-1.68 (6H, m), 1.53 (9H, s), 4.34 (2H, s), 6.99 (0.84H, s), 6.99 (0.16H, d, J = 19.0 Hz)
MS (ESI ⁺ ); m / z 486 [M + 1] ⁺

The compounds of Reference Examples 89 to 114 were synthesized in the same manner as Reference Example 88.

Reference Example 89 5-Methyl-2-tributylstannyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.90 (9H, t, J = 7.4 Hz), 1.04-1.22 (6H, m), 1.28-1.39 (6H, m), 1.4
5-1.67 (6H, m), 3.16 (3H, s), 4.27 (2H, s), 7.02 (0.84H, s), 7.02 (0.16H, d, J = 18.8Hz)
MS (ESI ⁺ ); m / z 444 [M + 1] ⁺

Reference Example 90 5-Isopropyl-2-tributylstani-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.85-1.64 (33H, m), 4.22 (2H, s), 4.52-4.61 (1H, m), 7.04 (0.84H, s), 7.04 (0.16H, d, (J = 19.2 Hz)

Reference Example 91 5- (Pyridin-4-ylmethyl) -2-tributylstannyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.94 (9H, m), 1.10-1.18 (6H, m), 1.28-1.39 (6H, m), 1.52-1.61 (6H, m), 4.22 (2H, s), 4.75 (2H, s), 7.02 (1H, s), 7.19-7.23 (2H, m), 8.55-8.59 (2H,
m)

Reference Example 92 5- (Pyridin-3-ylmethyl) -2-tributylstannyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.94 (9H, m), 1.04-1.22 (6H, m), 1.28-1.38 (6H, m), 1.45-1.67 (6H, m), 4.19 (2H, s), 4.76 (2H, s), 7.00 (1H, s), 7.25-7.29 (1H, m), 7.65-7.69 (1H,
m), 8.53-8.55 (1H, m), 8.57-8.59 (1H, m)

Reference Example 93 5- (Pyridin-2-ylmethyl) -2-tributylstannyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.94 (9H, m), 1.04-1.22 (6H, m), 1.28-1.38 (6H, m), 1.52-1.60 (6H, m), 4.35 (2H, s), 4.87 (2H, s), 7.01 (1H, s), 7.16-7.21 (1H, m), 7.32-7.35 (1H,
m), 7.62-7.68 (1H, m), 8.53-8.56 (1H, m)

Reference Example 94 5-Benzyl-2-tributylstannyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.89 (9H, t, J = 7.2Hz), 1.04-1.22 (6H, m), 1.23-1.40 (6H, m), 1.43-1.69 (6H, m), 4.16 (2H, s), 4.74 (2H, s), 6.98 (0.84H, s), 6.98 (0.16H, d, J = 19.0 Hz), 7.25-7.37 (5H, m)
MS (FAB ⁺ ); m / z 520 [M + 1] ⁺

Reference Example 95 5- (2-Methoxyethyl) -2-tributylstannyl-4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.90 (9H, t, J = 7.4Hz), 1.04-1.22 (6H, m), 1.28-1.39 (6H, m), 1.45-1.68 (6H, m), 3.35 (3H, s), 3.61 (2H, t, J = 5.1 Hz), 3.73 (2H, t, J = 5.1 Hz), 4.42 (2H, s), 7.02 (0.84H, s), 7.02 (0.16H, d, J = 19.2 Hz)
MS (ESI ⁺ ); m / z 488 [M + 1] ⁺

Reference Example 96 2-Tributylstannyl-5- (2-triethylsiloxyethyl) -4H-thieno [2,3-c] pyrrol-6 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.59 (6H, q, J = 7.9 Hz), 0.89 (9H, t, J = 7.4 Hz), 0.93 (9H, t, J = 7.9 Hz), 1.04-1.23 ( 6H, m), 1.27-1.38 (6H, m), 1.51-1.62 (6H, m), 3.66 (2H, t, J = 5.2 Hz), 3.84 (2H, t, J = 5.2Hz), 4.46 (2H , s), 7.03 (0.84H, s), 7.03 (0.16H, d, J = 18.8 Hz)
MS (ESI ⁺ ); m / z 588 [M + 1] ⁺

Reference Example 97 5-Cyclopropyl-2-tributylstannyl-4H-thieno [2,3-c] pyrrole-6 (5H)-
on
¹ H-NMR (CDCl ₃ ) δ: 0.80-0.96 (13H, m), 1.08-1.17 (6H, m), 1.27-1.38 (6H, m), 1.50-1.6
3 (6H.m), 2.82-2.92 (1H, m), 4.22 (2H, s), 7.00 (1H, s)

Reference Example 98 5-Methyl-2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.93 (9H, m), 1.09-1.14 (6H, m), 1.26-1.34 (6H, m), 1.51-1.60 (6H, m), 3.16 (3H, s), 4.40 (2H, s), 7.27 (1H, s)
MS (FAB ⁺ ); m / z 444 [M + 1] ⁺

Reference Example 99 5- (Pyridin-3-yl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 0.88-0.93 (9H, m), 1.07-1.27 (6H, m), 1.28-1.40 (6H, m), 1.51-1.67 (6H, m), 4.95 (2H, s), 7.33 (1H, s), 7.29-7.37 (1H, m), 8.39-8.43 (2H, m), 8.80 (1H, d, J = 2.4 Hz)
MS (ESI ⁺ ); m / z 507 [M + 1] ⁺

Reference Example 100 5- (Pyridin-4-ylmethyl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 0.88-0.92 (9H, m), 1.06-1.39 (12H, m), 1.49-1.64 (6H, m), 4.35 (2H,
s), 4.76 (2H, s), 7.19-7.21 (2H, m), 7.30 (1H, s), 8.56-8.58 (2H, m)
MS (ESI ⁺ ); m / z 521 [M + 1] ⁺

Reference Example 101 5- (Pyridin-3-ylmethyl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 0.85-0.94 (9H, m), 1.03-1.19 (6H, m), 1.28-1.38 (6H, m), 1.45-1.65 (6H, m), 4.32 (2H, s), 4.77 (2H, s), 7.25-7.31 (1H, m), 7.33 (1H, s), 7.66 (1H, ddd,
J = 7.8 and 1.9 and 1.7 Hz), 8.54 (1H, dd, J = 4.9 and 1.7 Hz), 8.57 (1H, d, J = 1.9Hz)
MS (ESI ⁺ ); m / z 521 [M + 1] ⁺

Reference Example 102 5- (Pyridin-2-ylmethyl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CDCl ₃ ) δ: 0.86-0.94 (9H, m), 1.05-1.16 (6H, m), 1.24-1.38 (6H, m), 1.49-1.65 (6H, m), 4.48 (2H, s), 4.87 (2H, s), 7.17-7.21 (1H, m), 7.31 (1H, s), 7.33 (1H, d, J = 7.8 Hz), 7.65 (1H, ddd, J = 7.8and 7.8 and 1.7 Hz), 8.54-8.56 (1H, m)
MS (ESI ⁺ ); m / z 521 [M + 1] ⁺

Reference Example 103 5-Benzyl-2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrol-4-one
¹ H-NMR (CD ₃ CN) δ: 0.87-0.94 (9H, m), 1.02-1.21 (6H, m), 1.25-1.38 (6H, m), 1.49-1.65 (6H, m), 4.29 (2H , s), 4.75 (2H, s), 7.26-7.35 (6H, m)
MS (ESI ⁺ ); m / z 520 [M + 1] ⁺

Reference Example 104 5-Methyl-2-tributylstannyl-6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.94 (9H, m), 1.07-1.12 (6H, m), 1.27-1.38 (6H, m), 1.50-1.59 (6H, m), 3.09 (3H, s), 3.10 (2H, t, J = 6.8 Hz), 3.61 (2H, t, J = 6.8 Hz), 7.47 (1H, s) MS (ESI ⁺ ); m / z454,456,458 [M + 1] ⁺

Reference Example 105 5- (2-methoxyethyl) -2-tributylstannyl-6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.94 (9H, m), 1.07-1.12 (6H, m), 1.24-1.38 (6H, m), 1.50-1.59 (6H, m), 3.07 (2H, t, J = 6.8Hz), 3.35 (3H, s), 3.59-3.63 (2H, m), 3.68-3.75 (4H, m), 7.47 (1H, s)

Reference Example 106 5- (Pyridin-2-ylmethyl) -2-tributylstannyl-6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.92 (9H, m), 1.07-1.12 (6H, m), 1.24-1.38 (6H, m), 1.51-1.59 (6H, m), 3.09 (2H, t, J = 6.9Hz), 3.71 (2H, t, J = 6.9 Hz), 4.86 (2H, s), 7.16-7.21 (1H, m), 7.39-7.42 (1H, m), 7.52 (1H, s ), 7.62-7.67 (1H, m), 8.53-8.55 (1H, m)

Reference Example 107 2-Tributylstannyl-6,7-dihydrothieno [3,2-c] pyridin-4 (5H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-0.92 (9H, m), 1.07-1.13 (6H, m), 1.28-1.38 (6H, m), 1.51-1.59 (6H, m), 3.10 (2H, t, J = 7.1Hz), 3.59-3.65 (2H, m), 5.54-5.59 (1H, m), 7.44-7.53 (1H, m)

Reference Example 108 6-Methyl-2-tributylstannyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.85-1.58 (27H, m), 2.92 (2H, d, J = 7.2 Hz), 3.07 (3H, s), 3.56 (2H,
t, J = 7.2 Hz), 6.90 (1H, s)

Reference Example 109 6-Isopropyl-2-tributylstannyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.40 (33H, m), 2.88 (2H, t, J = 6.6 Hz), 3.46 (2H, t, J = 6.6 Hz), 4.98 (1H, q, J = 6.7 Hz), 6.92 (1H, s)

Reference Example 110 N, N-dimethyl-2- (7-oxo-2-tributylstannyl-4,5-dihydrothieno [2,3-c] pyridin-6 (7H) -yl) acetamide
¹ H-NMR (CDCl ₃ ) δ: 0.86 (27H, m), 2.96-3.07 (8H, m), 3.72 (2H, t, J = 7.0 Hz), 4.35 (2H,
s), 7.00 (1H, s)

Reference Example 111 6- (2-methoxyethyl) -2-tributylstannyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.58 (27H, m), 2.91 (2H, t, J = 7.1 Hz), 3.35 (3H, s), 3.59-3.71 (6H, m), 6.93 (1H , s)

Reference Example 112 2-Tributylstannyl-6- (2-triethylsiloxyethyl) -5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.60 (6H, q, J = 8.3Hz), 0.87-1.56 (36H, m), 2.90 (2H, t, J = 7.1 Hz), 3.62 (2H, t, J = 5.6 Hz), 3.73 (2H, d, J = 7.1 Hz), 3.82 (2H, t, J = 5.6 Hz), 6.93 (1H, s)

Reference Example 113 6- (Pyridin-3-yl) -2-tributylstannyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.90 (6H, t, J = 7.3Hz), 1.12-1.60 (21H, m), 3.11 (2H, t, J = 6.8 Hz), 4.08 (2H, t, J = 6.8 Hz), 7.00 (1H, s), 7.30-7.34 (1H, m), 7.75-7.78 (1H, m), 8.45-8.46 (1H, m), 8.64-8.65 (1H, m)

Reference Example 114 6- (2-Ethoxyethyl) -2-tributylstannyl-5,6-dihydrothieno [2,3-c] pyridin-7 (4H) -one
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.62 (30H, m), 2.91 (2H, t, J = 7.0 Hz), 3.49 (2H, q, J = 6.8 Hz)
, 3.62-3.73 (6H, m), 6.92 (1H, s)

Reference Example 115 5- (4,5-Dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole
The title compound was synthesized in the same manner as in Reference Example 7 using 5,6-dihydro-4H-thieno [2,3-c] pyrrole.
¹ H-NMR (CDCl ₃ ) δ: 3.41 (2H, t, J = 7.3Hz), 4.09 (2H, t, J = 7.3Hz), 4.63-4.66 (2H, m), 4.77-4.79 (2H, m ), 6.87 (1H, d, J = 4.9Hz), 7.29 (1H, d, J = 4.9Hz)

Reference Example 116 5- (4,5-Dihydrothiazol-2-yl) -2-tributylstannyl-5,6-dihydro-4H-thieno [2,3-c] pyrrole
The title compound was synthesized in the same manner as in Reference Example 78 using 5- (4,5-dihydrothiazol-2-yl) -5,6-dihydro-4H-thieno [2,3-c] pyrrole.

Reference Example 117 1- (3,4-Dimethoxybenzyl) piperidin-4-one
To a solution of 4-piperidone hydrochloride 3.28 g (24.2 mmol) and 3,4-dimethoxybenzyl chloride 5.43 g (29.1 mmol) in anhydrous acetonitrile 100 ml was added triethylamine 8.43 ml (60.5 mmol) and stirred at 50 ° C. for 16 hours. did. After adding saturated brine, acetonitrile was distilled off and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was evaporated, and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 4). 2.68 g (44% yield) of the title compound were obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.46 (4H, t, J = 5.9 Hz), 2.74 (4H, t, J = 5.9 Hz), 3.56 (2H, s), 3.88 (3H, s), 3.91 ( 3H, s), 6.81-7.00 (3H, m)

Reference Example 118 2-Amino-6- (3,4-dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-3-carboxylate
2 ml of morpholine in a solution of 1- (3,4-dimethoxybenzyl) piperidin-4-one 2.68 g (10.7 mmol), ethyl cyanoacetate 1.26 ml (11.8 mmol) and sulfur 378 mg (11.8 mmol) in absolute ethanol 20 ml And stirred at 50 ° C. for 16 hours. After the reaction solution was cooled to 0 ° C., the precipitate was removed by filtration. The residue obtained by concentrating the filtrate was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1) to obtain 1.93 g (yield 48%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 1.32 (3H, t, J = 7.3Hz), 2.72-2.82 (4H, m), 3.40 (2H, s), 3.61 (2H, s), 3.88 (3H, s ), 3.89 (3H, s), 4.24 (2H, q, J = 7.3 Hz), 5.94 (2H, s), 6.81-6.95 (3H, m)

Reference Example 119 6- (3,4-Dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-3-carboxylate tert-butyl nitrite 0.77 ml anhydrous tetrahydrofuran 15 ml To the solution of ethyl 2-amino-6- (3,4-dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-3-carboxylate 1.61 g (4.27 mmol ) Was added dropwise at room temperature. After stirring for 3 hours at the same temperature, 0.77 ml of tert-butyl nitrite was added and stirred for 30 minutes, and then 1N hydrochloric acid was added.
The mixture was neutralized with saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate, and the organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 1) to give the title compound 563
mg (yield 36%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 1.35 (3H, t, J = 7.0 Hz), 2.80 (2H, t, J = 6.1 Hz), 3.00 (2H, t, J = 6.1
Hz), 3.64-3.66 (4H, m), 3.89 (6H, s), 4.29 (2H, q, J = 7.0 Hz), 6.82-7.00 (3H, m), 7.94 (1H, s)

Reference Example 120 6- (3,4-Dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-3-carboxylic acid
5N hydroxylation was carried out in a solution of 268 mg (0.74 mmol) of ethyl 6- (3,4-dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-3-carboxylate in 8 ml of ethanol. Sodium aqueous solution 0.22
ml was added. After stirring at 60 ° C. for 2 hours, the mixture was cooled to room temperature. After neutralizing with 5N hydrochloric acid, the solvent was distilled off to obtain 295 mg (yield 100%) of the title compound.
¹ H-NMR (DMSO-d ₆ ) δ: 3.16-3.26 (2H, m), 3.64-3.66 (2H, m), 3.78 (3H, s), 3.79 (3H, s),
4.34-4.42 (4H, m), 7.01 (1H, d, J = 8.2 Hz), 7.07 (1H, d, J = 8.2 Hz), 7.31 (1H, s), 8.27 (1H, s)
MS (ESI ⁺ ); m / z 334 [M + 1] ⁺

Reference Example 121 6- (3,4-Dimethoxybenzyl) -3-N, N-dimethylcarbamoyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine
In a solution of 6- (3,4-dimethoxybenzyl) -4,5,6,7-tetrahydrothieno [2,3-c] pyridine-3-carboxylic acid 245 mg (0.66 mmol) in anhydrous methylene chloride 6 ml Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride 191 mg (0.99 mmol) and 1-hydroxybenzotriazole 135 mg (0.99 mmol) and 2.0 M dimethylamine tetrahydrofuran solution 1.7 ml (3.4 mmol) were added. After stirring at room temperature for 18 hours, 20% aqueous sodium chloride solution was added to stop the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with a 20% aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The residue obtained by removing the solvent was purified by silica gel flash column chromatography (eluted with chloroform: methanol = 25: 1) to obtain 165 mg (yield 69%) of the title compound.
¹ H-NMR (CDCl ₃ ) δ: 2.72-2.80 (4H, m), 3.02-3.07 (6H, m), 3.66 (4H, s), 3.88 (3H, s), 3.89 (3H, s), 6.81 -7.00 (3H, m), 7.26 (1H, s)
MS (ESI ⁺ ); m / z 361 [M + 1] ⁺

Reference Example 122 6- (3,4-Dimethoxybenzyl) -3-N, N-dimethylcarbamoyl-2-tributylstannyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine
96 ml (0.27 mmol) of 6- (3,4-dimethoxybenzyl) -3-N, N-dimethylcarbamoyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine in 3 ml of anhydrous tetrahydrofuran To the solution was added 0.59 ml (0.59 mmol) of 1 M tert-butoxypotassium tetrahydrofuran solution. After cooling to −78 ° C., 0.53 ml (0.53 mmol) of 1M sec-butyllithium hexane-cyclohexane solution was added dropwise. After stirring for 1 hour, 0.30 ml (1.06 mmol) of trinormalbutyltin chloride was added at the same temperature. After stirring for 1 hour, a saturated aqueous ammonium chloride solution was added to stop the reaction, followed by extraction with ethyl acetate, and the organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off and the resulting residue was purified by silica gel flash column chromatography (eluted with hexane: ethyl acetate = 1: 3) to give the title compound 105 mg (yield 61 %).
¹ H-NMR (CDCl ₃ ) δ: 0.87-1.56 (27H, m), 2.55-2.65 (4H, m), 2.88 (3H, s), 3.05 (3H, s), 3.60-3.70 (4H, m) , 3.88 (3H, m), 3.87 (3H, s), 6.81-7.00 (3H, m)

[Test Example 1] Antibacterial activity
Measured with reference to the method described in CHEMOTHERAPY, vol. 16, No. 1, 99, 1968.
The results are shown in Table 1. The measurement medium is Sensitivity Disk Agar-N with 15 μg / mL β-NAD + (β-Nicotinamide-adenine dinucleotideoxidized form), 5 μg / mL Hemin and 5% Horse blood, and the inoculum is 106 CFU / ml .

Claims (11)

A compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof.

[Where
R ¹ represents a hydrogen atom or a methyl group,
R ² represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, a formyl group, an optionally substituted alkylcarbonyl group, an optionally substituted arylcarbonyl group, or an optionally substituted heterocyclic carbonyl Group, alkyloxycarbonyl group which may be substituted, aminooxoacetyl group which may be substituted, amide group which may be substituted, thioamide group which may be substituted, sulfonyl group which may be substituted Or represents an optionally substituted heterocycle,
R ³ represents a hydrogen atom or a group that can be hydrolyzed in vivo,
R ⁴ represents a C 1-6 alkyl group, a halogen atom, a formyl group, an optionally substituted amide group, a C 1-6 alkylcarbonyl group, or an arylcarbonyl group,
R ⁵ may have 0 to 6 carbon atoms on X or Y, and is a C 1-6 alkyl group, a halogen atom, a formyl group, a carbamoyl group, a C 1-6 alkylcarbonyl group, or an arylcarbonyl group. Represents
X represents C1-2 alkylene or C = O;
Y represents C1-2 alkylene or C═O. ] A compound represented by the following formula (II) or a pharmaceutically acceptable salt thereof.

[Where
R ¹ represents a hydrogen atom or a methyl group,
R ² represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, a formyl group, an optionally substituted alkylcarbonyl group, an optionally substituted arylcarbonyl group, or an optionally substituted heterocyclic carbonyl Group, alkyloxycarbonyl group which may be substituted, aminooxoacetyl group which may be substituted, amide group which may be substituted, thioamide group which may be substituted, sulfonyl group which may be substituted Or represents an optionally substituted heterocycle,
R ³ represents a hydrogen atom or a group that can be hydrolyzed in vivo,
R ⁴ represents a C 1-6 alkyl group, a halogen atom, a formyl group, a carbamoyl group, a C 1-6 alkylcarbonyl group, or an arylcarbonyl group,
R ⁵ may have 0 to 6 carbon atoms on X or Y, and is a C 1-6 alkyl group, a halogen atom, a formyl group, a carbamoyl group, a C 1-6 alkylcarbonyl group, or an arylcarbonyl group. Represents
X represents C1-2 alkylene or C = O;
Y represents C1-2 alkylene or C═O. ] R ² is a hydrogen atom,
A C1-6 alkyl group which may be substituted with the following substituent group A,
Formyl group,
A C1-6 alkylcarbonyl group which may be substituted with the following substituent group B,
Benzoyl group,
A heterocyclic carbonyl group optionally substituted by the following substituent group C,
A C1-6 alkyloxycarbonyl group optionally substituted by a C1-6 alkyloxy group,
An aminooxoacetyl group optionally substituted by the following substituent group D,
An amide group optionally substituted by the following substituent group D,
A thioamido group optionally substituted by the following substituent group D,
The compound according to claim 1 or 2, which represents a C1-6 alkyl group, a sulfonyl group optionally substituted with a C1-6 alkylamino group, or a heterocyclic ring optionally substituted with the following substituent group C, or a compound thereof A pharmaceutically acceptable salt.
[Substituent group A represents a hydroxyl group, a carbamoyl group, a cyano group, a C1-6 alkyloxy group, an aryl group, a heterocyclic ring, an amino group, a mono C1-6 alkylamide group, a diC1-6 alkylamide group,
Substituent group B represents a hydroxyl group, a cyano group, a C1-6 alkyloxy group, an acetamide group, an acetyloxy group, an amino group, a mono C1-6 alkylamino group, a diC1-6 alkylamino group, a heterocyclic ring,
Substituent group C represents a C1-6 alkyl group, an acetyl group, a benzoyl group, a hydroxyl group, an amino group,
The substituent group D represents a C1-6 alkyl group or an aryl group. ] In the above formula (I) or (II), when either X or Y is C = O, the other is not C = O, or the compound according to any one of claims 1 to 3, or a compound thereof A pharmaceutically acceptable salt. The group of R ³ that can be hydrolyzed in vivo is a C 1-6 alkyl group, a C 2-6 alkenyl group, an optionally substituted C 1-6 alkylcarbonyloxy C 1-6 alkyl group, or a C 3-6 cycloalkyl. A carbonyloxy C1-6 alkyl group, a C3-6 cycloalkylmethylcarbonyloxy C1-6 alkyl group, a C2-6 alkenylcarbonyloxy C1-6 alkyl group, an arylcarbonyloxy C1-6 alkyl group, a tetrahydrofuranylcarbonyloxymethyl group, A C1-6 alkyloxy C1-6 alkyl group, a C1-6 alkyloxy C1-6 alkyloxy C1-6 alkyl group, an arylmethyloxy C1-6 alkyl group, an arylmethyloxy C1-6 alkyloxy C1-6 alkyl group, C1-7 alkyloxy which may have a substituent A carbonyloxy C1-6 alkyl group, a C1-6 alkyloxycarbonyloxy C1-6 alkyloxy group, an optionally substituted C3-6 cycloalkyloxycarbonyloxy C1-6 alkyl group, a C3-6 cycloalkylmethoxy Carbonyloxy C1-6 alkyl group, aryloxycarbonyloxy C1-6 alkyl group, 3-phthalidyl group which may have a substituent on the aromatic ring, 2- (optionally substituted on the aromatic ring) 3-phthalidylidene) ethyl group, 2-oxotetrahydrofuran-5-yl group, mono C1-6 alkylaminocarbonyloxymethyl group, diC1-6 alkylaminocarbonyloxymethyl group, 2-oxo-5-C1-6 alkyl- 1,3-dioxolen-4-ylmethyl group, piperidinyl group which may have a substituent Bonyloxy C1-6 alkyl group, diC1-6 alkylaminocarbonylmethyl group, 1,3-dioxoisoindolyl-C1-6 alkyl group, arylcarbonylaminocarbonyl C1-6 alkyl group optionally having substituent (s) Optionally substituted arylcarbonylamino C1-6 alkyl group, diC3-6 cycloalkylaminocarbonyl C1-6 alkyl group, tetrahydropyranyloxycarbonyloxymethyl group, 1,3-dioxanyloxycarbonyl The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, which is an oxymethyl group or a C1-6 alkyl C3-6 cycloalkylaminocarbonyloxy C1-6 alkyl group. A compound represented by the following formula (III) or a pharmaceutically acceptable salt thereof.

[Wherein, Xa represents C1-2 alkylene, Ya represents C1-2 alkylene, R ^2
a represents a protecting group for ^a hydrogen atom or an amino group, and PG represents a protecting group for a carboxyl group. ]   A pharmaceutical composition comprising the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof.   A pharmaceutical composition comprising the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.   The pharmaceutical composition according to claim 7 or 8, which is used as an antibacterial agent.   A bacterial infection or comprising administering an effective amount of a compound according to any one of claims 1 to 5, 7 to 8 or a pharmaceutically acceptable salt thereof to a patient in need thereof. A method of treating or preventing symptoms associated therewith.   Use of the compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating or preventing a bacterial infection or a symptom associated therewith.