CN111574473A - Method for synthesizing aminothiazole compound - Google Patents
Method for synthesizing aminothiazole compound Download PDFInfo
- Publication number
- CN111574473A CN111574473A CN202010499806.5A CN202010499806A CN111574473A CN 111574473 A CN111574473 A CN 111574473A CN 202010499806 A CN202010499806 A CN 202010499806A CN 111574473 A CN111574473 A CN 111574473A
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- reaction
- structure shown
- reacting
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a synthesis method of aminothiazole compounds, belonging to the technical field of medicine synthesis. The synthesis method comprises the following steps: f) reacting the compound with the structure of the formula (VI) with selenium dioxide to obtain a compound with the structure of the formula (VII);
Description
Technical Field
The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of an aminothiazole compound.
Background
Antibiotics are a class of secondary metabolites with antipathogenic or other activities produced by microorganisms (bacteria, fungi, actinomycetes, etc.) or higher animals and plants during life, and chemical substances capable of interfering with other life cell development functions. Antibiotics commonly used in clinical practice include extracts from microbial cultures, chemically synthesized or semi-synthesized compounds. Antibiotics are in a wide variety, and among them, monocyclic β -lactam antibiotics are one of the hot areas of antibiotic development.
Aztreonam (Aztreonam), the first monocyclic β -lactam antibiotic used clinically, was approved by the FDA in 1984 and marketed, and is currently the most widely used monocyclic β -lactam antibiotic.
Monobactam 1, the Basilea pharmaceutical group of California, Switzerland BAL-30072 and LYS228, Nowa, are outstanding in this field.
Researches show that the side chains formed by aminothiazole compounds mostly exist in the monocyclic beta-lactam antibiotics, and the structure only needs oximation and N-acylation to obtain the beta-lactam antibiotics. However, the conventional method for synthesizing aminothiazole compounds is complicated in operation and requires post-treatment after most reactions.
Disclosure of Invention
The invention provides a synthesis method of aminothiazole compounds, which is easy to operate, simple in post-treatment, mild in reaction condition and high in yield.
The invention provides a synthesis method of an aminothiazole compound, wherein the aminothiazole compound has a structure shown as a formula (VII); the method comprises the following steps:
d) reacting a compound with a structure shown in a formula (IV) with thiourea to obtain a compound with a structure shown in a formula (V);
e) reacting a compound with a structure shown in a formula (V) with di-tert-butyl carbonate under the action of a catalyst to obtain a compound with a structure shown in a formula (VI);
f) reacting the compound with the structure of the formula (VI) with selenium dioxide to obtain a compound with the structure of the formula (VII);
further, the compound with the structure of formula (IV) is prepared according to the following steps:
c) reacting a compound with a structure shown in a formula (III) with bromine to obtain a compound with a structure shown in a formula (IV);
further, the compound with the structure of the formula (III) is prepared according to the following steps:
b) reacting the compound with the structure of the formula (II) with oxalyl chloride, dimethyl sulfoxide and triethylamine to obtain a compound with the structure of the formula (III);
further, the compound with the structure of the formula (II) is prepared according to the following steps:
a) reacting a compound with a structure shown in a formula (I) under the action of a catalyst to obtain a compound with a structure shown in a formula (II);
further, in step f):
a compound having a structure of formula (VI) and selenium dioxide (SeO)2) The molar ratio of (1) to (0.5-2);
the solvent for the reaction is 1, 4-dioxane; the reaction temperature is 0-40 ℃.
Further, in step e):
the mol ratio of the compound with the structure of formula (V) to the di-tert-butyl carbonate is 1: (0.5 to 2);
the catalyst for the reaction is 4-Dimethylaminopyridine (DMAP); the molar ratio of the compound with the structure of the formula (V) to the catalyst is 1: 0.1; the reaction temperature is 0-40 ℃.
Further, in step d):
the molar ratio of the compound with the structure of formula (IV) to thiourea is 1: (0.5 to 2); the reaction temperature is 0-40 ℃;
further, in step c):
the molar ratio of the compound with the structure of formula (III) to bromine is 1 (0.5-2); mixing the reaction raw materials at 0 ℃; the reaction temperature is 0-40 ℃.
Further, in step b):
the mol ratio of the compound with the structure of formula (II), oxalyl chloride, dimethyl sulfoxide and triethylamine is (2-6): (2 to 6), (8 to 10) and (22 to 26); mixing the reaction raw materials at-70 to-80 ℃;
further, in step a):
the mass ratio of the compound with the structure of formula (I) to the catalyst is 3-5: 1; the catalyst is ion exchange resin; the ion exchange resin is Amberlyst A-15.
The invention has the following advantages:
the synthesis method of the aminothiazole compound provided by the invention is easy to operate, simple in post-treatment, mild in reaction condition and high in final product yield. The aminothiazole compound obtained by the method can be used as an intermediate for preparing monocyclic beta-lactam antibiotics.
Detailed Description
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict. And the source of the raw material used in the present invention is not particularly limited.
The embodiment of the invention provides a synthesis method of an aminothiazole compound, wherein the aminothiazole compound has a structure shown as a formula (VII); the method comprises the following steps:
d) reacting a compound with a structure shown in a formula (IV) with thiourea to obtain a compound with a structure shown in a formula (V);
e) reacting a compound with a structure shown in a formula (V) with di-tert-butyl carbonate under the action of a catalyst to obtain a compound with a structure shown in a formula (VI);
f) reacting the compound with the structure of the formula (VI) with selenium dioxide to obtain a compound with the structure of the formula (VII);
specifically, in step f):
a compound having a structure of formula (VI) and selenium dioxide (SeO)2) The molar ratio of (1) to (0.5-2); preferably, the compound having the structure of formula (VI) is reacted with selenium dioxide (SeO)2) The molar ratio of (1) to (1-1.2); the solvent of the reaction is organic solvent; preferably, the solvent for the reaction is 1, 4-dioxane.
The reaction temperature is 0-40 ℃; preferably, the reaction temperature is 10-30 ℃; in some embodiments of the invention, the reaction temperature is normal temperature; the reaction time is not limited, and the completion of the reaction can be monitored (TLC).
The post-treatment of the reaction includes: the reaction mixture was filtered through a celite layer, and the solvent was distilled under reduced pressure, and the resulting mixture was subjected to chromatography on a silica gel column to obtain a compound having a structure of formula (vii).
Specifically, in step e):
the mol ratio of the compound with the structure of formula (V) to the di-tert-butyl carbonate is 1: (0.5 to 2); preferably, the molar ratio of the compound with the structure of the formula (V) to the di-tert-butyl carbonate is 1: (1-1.2); in some embodiments of the invention, the compound having the structure of formula (v) has a molar ratio of di-tert-butyl carbonate of 6.99: 7.69; the solvent of the reaction is organic solvent; preferably, the solvent of the reaction is dichloromethane; the catalyst for the reaction is 4-Dimethylaminopyridine (DMAP); the molar ratio of the compound having the structure of formula (v) to the catalyst was 1: 0.1.
The reaction temperature is 0-40 ℃; preferably, the reaction temperature is 10-30 ℃; in some embodiments of the invention, the reaction temperature is normal temperature; the reaction time is not limited, and the completion of the reaction can be monitored (TLC).
The post-treatment of the reaction includes: the reaction mixture was treated with HCl and diluted with EtOAc, washed with water, brine and dried. The organic phase is concentrated and chromatographed on a column of silica gel to give the compound having the structure of formula (VI).
Specifically, in step d):
the molar ratio of the compound with the structure of formula (IV) to thiourea is 1: (0.5 to 2); preferably, the molar ratio of the compound with the structure of formula (IV) to the thiourea is 1: (1-1.2); in some embodiments of the invention, the molar ratio of the compound having the structure of formula (iv) to thiourea is 24.39: 26.83; the solvent of the reaction is organic solvent; preferably, the solvent of the reaction is absolute ethanol.
The reaction temperature is 0-40 ℃; preferably, the reaction temperature is 10-30 ℃; in some embodiments of the invention, the reaction temperature is normal temperature; the reaction time is not limited, and the completion of the reaction can be monitored (TLC).
The post-treatment of the reaction includes: the reaction mixture was evaporated to dryness and diluted with ethyl acetate, then the reaction mixture was washed with water, brine and Na2SO4And (5) drying. The organic phase is concentrated and chromatographed using petroleum ether: ethyl acetate (volume ratio 2: 8) was used as eluent to obtain the desired compound of formula (v).
In one embodiment of the invention, the compound having the structure of formula (IV) is prepared by the following steps:
c) reacting a compound with a structure shown in a formula (III) with bromine to obtain a compound with a structure shown in a formula (IV);
specifically, in step c):
the molar ratio of the compound with the structure of formula (III) to bromine is 1 (0.5-2); preferably, the molar ratio of the compound with the structure of the formula (III) to bromine is 1: 1-1.2; the solvent of the reaction is organic solvent; preferably, the solvent for the reaction is anhydrous dichloromethane.
Mixing the reaction raw materials at 0 ℃; the reaction temperature is 0-40 ℃; preferably, the reaction temperature is 10-30 ℃; in some embodiments of the invention, the reaction temperature is normal temperature; the reaction time is not limited, and the completion of the reaction can be monitored (TLC).
The post-treatment of the reaction includes: with saturated Na2CO3The solution was quenched, stirred, extracted with DCM, brine and dried over anhydrous sodium sulfate and the organic phase was concentrated to give a mixture of compounds having the structure of formula (iv). Purification is not needed, and the post-treatment of the reaction is simplified.
In one embodiment of the present invention, the compound having the structure of formula (iii) is prepared as follows:
b) reacting the compound with the structure of the formula (II) with oxalyl chloride, dimethyl sulfoxide and triethylamine to obtain a compound with the structure of the formula (III);
specifically, in step b):
the mol ratio of the compound with the structure of formula (II), oxalyl chloride, dimethyl sulfoxide and triethylamine is (2-6): (2 to 6), (8 to 10) and (22 to 26); preferably, the mole ratio of the compound with the structure of formula (II), oxalyl chloride, dimethyl sulfoxide and triethylamine is (3-5): (3-5), (8-10), (23-25); in some embodiments of the invention, the compound having the structure of formula (ii), oxalyl chloride, dimethyl sulfoxide, and triethylamine are present in a molar ratio of 4.24: 4.6: 9.3: 24.5; the reaction solvent is an organic solvent; preferably, the reaction solvent is dichloromethane.
Mixing the reaction raw materials at-70 to-80 ℃; preferably, the reaction raw materials are mixed at-78 ℃; the reaction temperature is 0-40 ℃; preferably, the reaction temperature is 10-30 ℃; in some embodiments of the invention, the reaction temperature is normal temperature; the reaction time is not limited, and the completion of the reaction can be monitored (TLC).
The reaction of the compound with the structure of the formula (II) with oxalyl chloride, dimethyl sulfoxide and triethylamine specifically comprises the following steps:
mixing the compound with the structure of formula (II) with oxalyl chloride, dimethyl sulfoxide and triethylamine at-70 to-80 ℃, and heating to the reaction temperature for reaction.
Preferably, the reaction of the compound with the structure of formula (II) with oxalyl chloride, dimethyl sulfoxide and triethylamine specifically comprises the following steps: at the temperature of-70 to-80 ℃, adding oxalyl chloride into dimethyl sulfoxide dropwise, mixing, adding a compound with a structure shown in a formula (II), mixing, adding triethylamine, mixing, and heating to the reaction temperature for reaction;
the post-treatment of the reaction includes: quenching the reaction mixture with cold water; the reaction was extracted with DCM, brine and Na2SO4Drying and concentrating the organic phase to obtain a mixture of the compound with the structure of the formula (III), without purification, thereby simplifying the post-treatment of the reaction.
In one embodiment of the present invention, the compound having the structure of formula (ii) is prepared as follows:
a) reacting a compound with a structure shown in a formula (I) under the action of a catalyst to obtain a compound with a structure shown in a formula (II);
specifically, in step a):
the mass ratio of the compound with the structure of formula (I) to the catalyst is 3-5: 1; in some embodiments of the invention, the mass ratio of the compound having the structure of formula (i) to the catalyst is 20: 5; the catalyst is ion exchange resin; the ion exchange resin is Amberlyst A-15. Amberlyst A-15 is available from Alfa Aesar, Inc., among others. The reaction solvent is absolute ethyl alcohol; the concentration of the compound with the structure of formula (I) in absolute ethyl alcohol is 3-6 mol/L; in some embodiments of the invention, the concentration of the compound having the structure of formula (I) in absolute ethanol is 4.6 mol/L.
The reaction temperature is 0-40 ℃; preferably, the reaction temperature is 10-30 ℃; in some embodiments of the invention, the reaction temperature is normal temperature; the reaction time is not limited, and the completion of the reaction can be monitored (TLC). No post-treatment and purification are needed, and the reaction operation is simplified.
The present invention will be described in detail with reference to examples.
Example 1
a) Reacting a compound 1 with a structure shown in a formula (I) under the action of a catalyst to obtain a compound 2 (4-ethyl hydroxybutyrate (2)) with a structure shown in a formula (II);
the chemical reaction formula is as follows:
to a solution of Compound 1 (. gamma. -butyrolactone) (20g, 232.23mmol) having the structure of formula (I) in absolute ethanol (50mL) was added, with stirring, 5g of Amberlyst A-15. The reaction mixture was stirred at room temperature overnight. After completion of the TLC monitoring reaction, the reaction mixture was filtered after overnight consumption, and then the solvent was concentrated to give compound 2 expected to have the structure of formula (ii) as a mixture which was used in the next reaction without further purification.
b) Reacting the compound 2 with the structure of formula (II) with oxalyl chloride, dimethyl sulfoxide and triethylamine to obtain a compound 3 (4-oxoethyl butyrate) with the structure of formula (III);
the chemical reaction formula is as follows:
to a stirred solution of oxalyl chloride (0.54mL, 4.6mmol) in Dichloromethane (DCM) (30mL) was slowly added dimethyl sulfoxide (DMSO) (0.6mL, 9.3mmol) dropwise at-78 deg.C. After stirring the reaction mixture for two minutes, a mixture of compound 2 having the structure of formula (II) (0.5g, 4.24mmol) dissolved in 10mL of DCM was added. The reaction mixture was then stirred at-78 ℃ for 50 minutes. Triethylamine (2.97mL, 24.5mmol) was then added and stirred at-78 deg.C for 15 minutes. The reaction mixture was allowed to warm to room temperature overnight and after TLC monitoring the reaction was complete, it was quenched with cold water. The reaction was extracted with DCM, brine and Na2SO4And (5) drying. The organic phase is then concentrated to give the desired mixture 3 of compound 3 having the structure of formula (III), which is used in the next reaction without purification due to its instability.
c) Reacting a compound 3 with a structure shown in a formula (III) with bromine to obtain a compound 4 (3-bromine-4-oxoethyl butyrate) with a structure shown in a formula (IV);
the chemical reaction formula is as follows:
to a stirred solution of compound 3(4g, 30.77mmol) having the structure of formula (III) in anhydrous CH at 0 deg.C2Cl2(25mL), bromine (1.6mL, 30.77mmol) was added dropwise. The reaction mixture was then warmed to room temperature and stirred at room temperature overnight. After TLC monitoring of the reaction completion, saturated Na was used2CO3The reaction was quenched with water, stirred for 15 min, extracted with DCM, brine and filtered over Na2SO2And (5) drying. The organic phase is concentrated to give the desired mixture of compound 4 having the structure of formula (IV), which is used in the next reaction without further purification.
d) Reacting a compound 4 with a structure shown in a formula (IV) with thiourea to obtain a compound 5(2- (2-aminothiazole-5-yl) ethyl acetate) with a structure shown in a formula (V);
the chemical reaction formula is as follows:
to a stirred solution of compound 4 having a structure of formula (IV) (5g, 24.39mmol) in absolute ethanol (30mL) at room temperature was added thiourea (2.04g, 26.83 mmol). After six hours of reaction, TLC monitored completion of reaction, the reaction mixture was evaporated to dryness and diluted with ethyl acetate (40mL), then the reaction mixture was washed with water, brine 3 times and Na2SO4And (5) drying. The organic phase is concentrated and chromatographed using petroleum ether: ethyl acetate (2: 8) was used as the eluent to give the desired compound 5 having the structure of formula (v) as a yellow solid (1.54g, 30.8%, total yield from four steps) with nuclear magnetic characterization as follows:
1H NMR(400MHz,DMSO-d6)H1.18(t,J＝7.1Hz,3H),4.08(q,J＝7.1Hz,2H),6.72(s,1H),6.80(s,2H)。
e) reacting a compound 5 with a structure shown in a formula (V) with di-tert-butyl carbonate under the action of a catalyst to obtain a compound 6(2- (2- (((tert-butoxycarbonyl) amino) thiazol-5-yl) ethyl acetate) with a structure shown in a formula (VI);
the chemical reaction formula is as follows:
to a stirred solution of compound 5 having a structure of formula (V) (1.3g, 6.99mmol) in dichloromethane (20mL) at room temperature were added di-tert-butyl carbonate (1.68g, 7.69mmol) and 4-Dimethylaminopyridine (DMAP) (0.1g, 0.699mmol), and the reaction mixture was refluxed for 6 hours. After TLC to monitor completion of the reaction, the reaction mixture was treated with 1N HCl and diluted with EtOAc (30mL), washed with water, brine and Na2SO4And (5) drying. The organic phase was concentrated and chromatographed on a column of silica gel to give the desired compound 6 of formula (vi) as a yellow solid (0.82g, 63%) with nuclear magnetic characterization as follows:
1H NMR(400MHz,DMSO-d6)H1.20(t,J＝7.1Hz,3H),1.47(s,9H),3.83(s,2H),4.10(q,J＝7.1Hz,2H),7.15(s,1H),11.32(s,1H).
f) reacting the compound 6 with the structure shown in the formula (VI) with selenium dioxide to obtain a compound 7(2- (2- (((tert-butoxycarbonyl) amino) thiazole-5-yl) -2-oxyacetic acid ethyl ester) with the structure shown in the formula (VII);
the chemical reaction formula is as follows:
SeO was added to a stirred solution of compound 6 having the structure of formula (VI) (0.19g, 0.66mmol) in 1, 4-dioxane (20mL) at room temperature2(0.07g, 0.66mmol), the reaction mixture was then refluxed at 105 ℃ for 24 hours, TLC monitored for completion of the reaction, the reaction mixture was filtered through a celite layer, and the solvent was distilled under reduced pressure, and the resulting mixture was chromatographed on a silica gel column to give compound 7 having the structure of formula (vii) as a yellow solid (0.21g, 100%). Nuclear magnetic characterization was as follows:
1H NMR(400MHz,DMSO-d6)H1.33(t,J＝7.1Hz,3H),1.51(s,9H),4.36(q,J＝7.1Hz,2H),8.45(s,1H),12.36(s,1H).
the present invention is not limited to the above preferred embodiments, and any modifications, equivalent substitutions, improvements, etc. within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for synthesizing an aminothiazole compound, wherein the aminothiazole compound has a structure shown as a formula (VII); the method comprises the following steps:
d) reacting a compound with a structure shown in a formula (IV) with thiourea to obtain a compound with a structure shown in a formula (V);
e) reacting a compound with a structure shown in a formula (V) with di-tert-butyl carbonate under the action of a catalyst to obtain a compound with a structure shown in a formula (VI);
f) reacting the compound with the structure of the formula (VI) with selenium dioxide to obtain a compound with the structure of the formula (VII);
2. the method of claim 1, wherein the compound having the structure of formula (iv) is prepared by the following steps:
c) reacting a compound with a structure shown in a formula (III) with bromine to obtain a compound with a structure shown in a formula (IV);
3. the method of claim 2, wherein the compound having the structure of formula (iii) is prepared by the steps of:
b) reacting the compound with the structure of the formula (II) with oxalyl chloride, dimethyl sulfoxide and triethylamine to obtain a compound with the structure of the formula (III);
4. the method of claim 3, wherein the compound having the structure of formula (II) is prepared by the following steps:
a) reacting a compound with a structure shown in a formula (I) under the action of a catalyst to obtain a compound with a structure shown in a formula (II);
5. method according to claim 1, characterized in that in step f):
a compound having a structure of formula (VI) and selenium dioxide (SeO)2) The molar ratio of (1) to (0.5-2);
the solvent for the reaction is 1, 4-dioxane; the reaction temperature is 0-40 ℃.
6. Method according to claim 1, characterized in that in step e):
the mol ratio of the compound with the structure of formula (V) to the di-tert-butyl carbonate is 1: (0.5 to 2);
the catalyst for the reaction is 4-Dimethylaminopyridine (DMAP); the molar ratio of the compound with the structure of the formula (V) to the catalyst is 1: 0.1; the reaction temperature is 0-40 ℃.
7. Method according to claim 1, characterized in that in step d):
the molar ratio of the compound with the structure of formula (IV) to thiourea is 1: (0.5 to 2); the reaction temperature is 0-40 ℃.
8. Method according to claim 2, characterized in that in step c):
the molar ratio of the compound with the structure of formula (III) to bromine is 1 (0.5-2); mixing the reaction raw materials at 0 ℃; the reaction temperature is 0-40 ℃.
9. A method according to claim 3, characterized in that in step b):
the mol ratio of the compound with the structure of formula (II), oxalyl chloride, dimethyl sulfoxide and triethylamine is (2-6): (2 to 6), (8 to 10) and (22 to 26); the reaction raw materials are mixed at the temperature of-70 to-80 ℃.
10. Method according to claim 4, characterized in that in step a):
the mass ratio of the compound with the structure of formula (I) to the catalyst is 3-5: 1; the catalyst is ion exchange resin; the ion exchange resin is Amberlyst A-15.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010499806.5A CN111574473A (en) | 2020-06-04 | 2020-06-04 | Method for synthesizing aminothiazole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010499806.5A CN111574473A (en) | 2020-06-04 | 2020-06-04 | Method for synthesizing aminothiazole compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111574473A true CN111574473A (en) | 2020-08-25 |
Family
ID=72114448
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010499806.5A Withdrawn CN111574473A (en) | 2020-06-04 | 2020-06-04 | Method for synthesizing aminothiazole compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111574473A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1496364A (en) * | 2000-06-28 | 2004-05-12 | Substituted quinazoline derivatives and their use as inhibitors | |
| CN102573485A (en) * | 2009-06-08 | 2012-07-11 | 加利福尼亚资本权益有限责任公司 | Triazine derivatives and their therapeutical applications |
| CN104402721A (en) * | 2014-12-05 | 2015-03-11 | 安徽联创生物医药股份有限公司 | Synthetic method of 4-aldehyde butyrate |
| WO2018069863A1 (en) * | 2016-10-13 | 2018-04-19 | Glaxosmithkline Intellectual Property Development Limited | 1,3 di-substituted cyclobutane or azetidine derivatives as hematopoietic prostaglandin d synthase inhibitors |
-
2020
- 2020-06-04 CN CN202010499806.5A patent/CN111574473A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1496364A (en) * | 2000-06-28 | 2004-05-12 | Substituted quinazoline derivatives and their use as inhibitors | |
| CN102573485A (en) * | 2009-06-08 | 2012-07-11 | 加利福尼亚资本权益有限责任公司 | Triazine derivatives and their therapeutical applications |
| CN104402721A (en) * | 2014-12-05 | 2015-03-11 | 安徽联创生物医药股份有限公司 | Synthetic method of 4-aldehyde butyrate |
| WO2018069863A1 (en) * | 2016-10-13 | 2018-04-19 | Glaxosmithkline Intellectual Property Development Limited | 1,3 di-substituted cyclobutane or azetidine derivatives as hematopoietic prostaglandin d synthase inhibitors |
Non-Patent Citations (3)
| Title |
|---|
| INGA KHOLOD ET AL.: "Synthetic Strategies for the Synthesis and Transformation of Substituted Pyrrolinones as Advanced Intermediates for Rhazinilam Analogues", 《EUROPEAN JOURNAL OF ORGANIC CHEMISTRY》 * |
| THEODORA W.GREENE等: "《有机合成中的保护基》", 31 October 2004, 华东理工大学出版社 * |
| 赵利飞 等: "Amberlyst-15型离子交换树脂催化γ-丁内酯酯交换反应的研究", 《化学研究与应用》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR0146931B1 (en) | Oxazolidine derivatives and pharmaceutically acceptable salts thereof | |
| SU1333234A3 (en) | Method of producing the derivatives of n-phenylbenzamide or salts thereof | |
| US20080227976A1 (en) | Process for synthesizing aspartic and glutamic acid derivatives especially useful as intermediates in the manufacture of a caspase inhibitor | |
| EP2215050B1 (en) | Manufacturing method of 2-hydroxy-5-phenylalkylaminobenzoic acid derivatives and their salts | |
| RU2711358C1 (en) | Simple method of producing avibactam | |
| JPS6327462A (en) | Manufacture of o-substituted hydroxylamine | |
| US11760723B2 (en) | Method of preparing a DON prodrug from L-pyroglutamic acid | |
| CN114315823B (en) | Intermediate of berberine hydrochloride and analogues thereof and preparation method thereof | |
| CN112062712A (en) | Preparation method of 2- (5-bromo-3-methylpyridin-2-yl) acetic acid hydrochloride | |
| CN111574473A (en) | Method for synthesizing aminothiazole compound | |
| CN103333180B (en) | Preparation method of aspoxicillin | |
| PL198658B1 (en) | Derivatives of 1-trifluorometyl-4-hydroxy-7-piperidinyl-aminomethylochromane | |
| KR100734069B1 (en) | Process for the preparation of N5-ethylglutamine | |
| CN101343263A (en) | Method for synthesis of 5-nitryl-4, 5-dihydrofuran derivant | |
| CN107629039B (en) | The preparation method and intermediate of deuterated acrylamide | |
| D'ischia et al. | A facile syntesis of 2-oxo-thiazolidines of biological interest | |
| JP4807751B2 (en) | Novel chiral catalyst and method for producing chiral carboxylic acid compound using the same | |
| CN113979932B (en) | Preparation method and application of N- (N-trifluoromethyl imidoyl) pyridine salt | |
| WO2001074795A1 (en) | Process for preparing amic acid esters | |
| CN103724293B (en) | A kind of preparation method of the urea derivative containing 1,2,3-thiadiazoles | |
| CN111662233B (en) | Method for synthesizing 4-chloro-1H-imidazole-2-carboxylic acid ethyl ester by one-step method | |
| CN113912526B (en) | Preparation method of N-acetyl tellurium carbamic acid ester compound | |
| KR102004245B1 (en) | Preparing method of norathyriol using eco-friendly C-deglycosylation | |
| CN110551170B (en) | Synthesis method of C-19 single-acyl triptolide derivative | |
| CN109053513B (en) | Substituted naphthol compound and application thereof in antitumor drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20200825 |
|
| WW01 | Invention patent application withdrawn after publication |