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WO1998023156A1 - Methyl substituted fungicides and arthropodicides - Google Patents

Methyl substituted fungicides and arthropodicides Download PDF

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Publication number
WO1998023156A1
WO1998023156A1 PCT/US1997/021944 US9721944W WO9823156A1 WO 1998023156 A1 WO1998023156 A1 WO 1998023156A1 US 9721944 W US9721944 W US 9721944W WO 9823156 A1 WO9823156 A1 WO 9823156A1
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WO
WIPO (PCT)
Prior art keywords
phenyl
pyridinyl
ocf
dime
naphthalenyl
Prior art date
Application number
PCT/US1997/021944
Other languages
French (fr)
Inventor
Richard James Brown
Peter Paul Castro
Dominic Ming-Tak Chan
John Powell Daub
Gerard Michael Koether
Thomas Paul Selby
Paula Louise Sharpe
Original Assignee
E.I. Du Pont De Nemours And Company
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from PCT/US1996/018916 external-priority patent/WO1998023155A1/en
Application filed by E.I. Du Pont De Nemours And Company filed Critical E.I. Du Pont De Nemours And Company
Priority to AU54633/98A priority Critical patent/AU5463398A/en
Priority to EP97948597A priority patent/EP0944314A1/en
Priority to BR9713415-5A priority patent/BR9713415A/en
Priority to JP52488998A priority patent/JP2001506984A/en
Publication of WO1998023156A1 publication Critical patent/WO1998023156A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
    • C07D261/12—Oxygen atoms
    • 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
    • C07D277/34—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C07F7/0814—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring is substituted at a C ring atom by Si

Definitions

  • This invention relates to certain methyl substituted fungicides, their N-oxides, agriculturally suitable salts and compositions, and methods of their use as fungicides and arthropodicides.
  • the control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumers.
  • the control of arthropod pests is also extremely important in achieving high crop efficiency. Arthropod damage to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer.
  • the control of arthropod pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different modes of action.
  • X is OR 1 , SCOJ ⁇ J R 1 or halogen;
  • A is O, S, N, NR 5 or CR 7 ;
  • G is C or N; provided that when G is C, A is O, S or NR 5 and the floating double bond is attached to G; and when G is N, A is N or CR 7 and the floating double bond is attached to A;
  • W is O; S; NH; N(C r C 6 alkyl); or NO(C r C 6 alkyl);
  • Y linkage is defined such that the moiety depicted on the left side of the linkage is bonded to the phenyl ring having the R 3 and R 4 substituents and the moiety on the right side of the linkage is bonded to Z;
  • Z is independently selected from: i) C]-C JO alkyl, CI -CJ Q haloalkyl or phenyl each optionally substituted with R 9 and optionally substituted with one or more R 10 ; ii) a ring selected from 5 or 6-membered aromatic heterocyclic ring, each heterocyclic ring containing 1 to 4 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring contains no more than 3 nitrogens, no more than 1 oxygen, and
  • R 7 is H, halogen or methyl
  • R 8 is H, C r C 3 alkyl, C r C 3 alkoxy, C r C 3 alkylthio, C r C 3 haloalkyl, C 2 -C 3 alkenyl,
  • R 9 is halogen; Ci-C alkyl; C j -Cg haloalkyl; C j -Cg alkoxy; C Cg haloalkoxy; C 2 -Cg alkenyl; C 2 -C 6 haloalkenyl; C 2 -Cg alkynyl; C j -Cg alkylthio;
  • R 12 is halogen, Cj-Cg alkyl, Cj-Cg haloalkyl, C j -C 6 alkoxy, C j -Cg haloalkoxy, C 2 -Cg alkenyl, C 2 -Cg haloalkenyl, C 2 -Cg alkynyl, C j -Cg alkylthio, C r C 6 haloalkylthio, C r C 6 alkylsulfinyl, C r C 6 alkylsulfonyl or C 3 -C 6 cycloalkyl;
  • R 13 is halogen, Cj-Cg alkyl, Cj-Cg haloalkyl, C j -Cg alkoxy, C j -Cg haloalkoxy or cyano; m is 0, 1 or 2; n is 0, 1 or 2; r is 1, 2, 3 or 4; and s is 0 or 1.
  • This invention provides a method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of a compound of Formula I including all geometric and stereoisomers, N-oxide, and agriculturally suitable salts thereof, provided that when T is T 1 , then i) when Y is -O-, X is OMe, R 3 is CH 3 and R 4 is H, then Z is other than 6-chloro-4-pyrimidinyl and 6-chloro-2-pyrazinyl; ii) when Y is a direct bond, X is Cl, R 3 is CH 3 and R 4 is H, then Z is other than
  • This invention also provides selected compounds of Formula I which are considered particularly effective fungicides and arthropodicides. Specifically, this invention provides compounds of Formula I including all geometric and stereoisomers, N-oxides, and agriculturally suitable salts thereof, and agricultural compositions containing them and their use as fungicides and arthropodicides, provided that
  • R 10 other than methyl and halogen; and ix) when Y is -CH 2 O-, R 3 is CH 3 , Z is phenyl substituted with R 10 in the 2-position and R 10 is methyl or halogen, then Z is substituted with at least one
  • R 9 or R 10 other than methyl and halogen
  • haloalkylthio straight-chain or branched alkyl, such as, methyl, ethyl, r ⁇ -propyl, z ' -propyl, or the different butyl, pentyl or hexyl isomers.
  • alkyl used alone or in the compound word “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, «-propyl, z ' -propyl, or the different butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl isomers.
  • Alkenyl includes straight-chain or branched alkenes such as vinyl, 1-propenyl, 2-propenyl and the different butenyl, pentenyl and hexenyl isomers.
  • Alkenyl also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl.
  • Alkynyl includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers.
  • Alkynyl can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
  • Alkoxy includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers.
  • Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers.
  • Alkylsulfinyl includes both enantiomers of an alkylsulfinyl group.
  • alkylsulfinyl examples include CH 3 S(O), CH 3 CH 2 S(O), CH 3 CH 2 CH 2 S(O), (CH 3 ) 2 CHS(O) and the different butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers.
  • alkylsulfonyl examples include CH 3 S(O) 2 , CH 3 CH 2 S(O) 2 , CH 3 CH 2 CH 2 S(O) 2 , (CH 3 ) 2 CHS(O) 2 and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers.
  • Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • halogen either alone or in compound words such as “haloalkyl” includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” include F 3 C, C1CH 2 , CF 3 CH 2 and CF 3 CC1 2 .
  • haloalkenyl “haloalkynyl”, “haloalkoxy”, “haloalkylthio”, and the like, are defined analogously to the term “haloalkyl”.
  • haloalkynyl examples include HC ⁇ CCHCl, CF 3 C ⁇ C, CC1 3 C ⁇ C and FCH 2 C ⁇ CCH 2 .
  • haloalkoxy examples include CF 3 O, CCl 3 CH 2 O, HCF 2 CH 2 CH 2 O and CF 3 CH 2 O.
  • haloalkylthio examples include CC1 3 S, CF 3 S, CC1 3 CH 2 S and C1CH 2 CH 2 CH 2 S.
  • aromatic heterocyclic rings are defined as those rings which satisfy the H ⁇ ckel rule. Examples include: a 5- or 6- membered aromatic heterocyclic ring containing 1 to 4 heteroatoms such as furanyl, furazanyl, thienyl, pyrrolyl, pyrazolyl, oxazolyl, oxadiazolyl, imidazolyl, isoxazolyl, thiazolyl, thiadiazolyl isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl and triazinyl with said ring attached through any available carbon or nitrogen.
  • the aromatic heterocyclic ring when the aromatic heterocyclic ring is furanyl, it can be 2-furanyl or 3-furanyl, for pyrrolyl, the aromatic heterocyclic ring is 1 -pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, for pyridyl, the aromatic ring is 2-pyridyl, 3-pyridyl or 4-pyridyl and similarly for other aromatic heterocyclic rings.
  • the Y substituent is preferably attached to the aromatic ring of the tetrahydronaphthalene (i.e., the ring which satisfies the H ⁇ ckel rule).
  • Cj-C The total number of carbon atoms in a substituent group is indicated by the "Cj-C;" prefix where i and j are numbers from 1 to 10.
  • C j -C 3 alkylthio designates methylthio through propylthio.
  • alkylcarbonyl include C(O)CH 3 , C(O)CH 2 CH 2 CH 3 and C(O)CH(CH 3 ) 2 .
  • a group contains a substituent which can be hydrogen, for example R 2 or R 7 , then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.
  • a group is optionally substituted with a substituent, for example with R 1 , then, when the group is not substituted with that substituent, it is recognized that this is equivalent to said group having a hydrogen substituent.
  • Compounds of this invention can exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). (See, e.g., U.S. Provisional Patent Application Serial No.
  • the present invention comprises compounds selected from Formula I and agriculturally suitable salts thereof.
  • the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form.
  • the salts of the compounds of the invention include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • Preferred compounds for reasons of better activity and/or ease of synthesis are: Preferred 1.
  • Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R 9 and optionally substituted with one or more R 10 ;
  • R 9 is halogen, C j -Cg alkyl, C j -Cg alkoxy, C j -Cg haloalkyl or C Cg haloalkoxy;
  • R 10 is halogen, C r C 6 alkyl, C r C 6 alkoxy, C r C 6 haloalkyl or
  • Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R 9 and optionally substituted with one or more R 10 ;
  • R 9 is halogen, C j -Cg alkyl, C j -Cg alkoxy, C j -Cg haloalkyl or C j -Cg haloalkoxy;
  • R 10 is halogen, C r C 6 alkyl, C r C 6 alkoxy, C r C 6 haloalkyl or
  • G is N
  • Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R 9 and optionally substituted with one or more R 10 ;
  • R 8 is CH 3 ;
  • R 9 is halogen, Cj-Cg alkyl, C j -Cg alkoxy, C j -Cg haloalkyl or
  • R 10 is halogen, C r C 6 alkyl, C r C 6 alkoxy, C r C 6 haloalkyl or Cj-Cg haloalkoxy; provided that i) when X is OMe, R 3 is CH 3 and R 4 is H, then Z is other than 3-(trifluoromethyl)phenyl; and ii) when X is OMe, R 3 is H and R 4 is CH 3 , then Z is other than 3-(trifluoromethyl)phenyl. Preferred 4.
  • T is T 1 ;
  • A is N;
  • G is N;
  • Z is thienyl optionally substituted with R 9 and optionally substituted with one or more R 10 ;
  • R 8 is CH 3 ;
  • R 9 is halogen or C ⁇ -C 3 alkyl; and R 10 is halogen or C r C 3 alkyl.
  • This invention also relates to fungicidal compositions comprising fungicidally effective amounts of the compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent.
  • the preferred compositions of the present invention are those which comprise the above preferred compounds.
  • This invention also relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of the compounds of the invention (e.g., as a composition described herein).
  • the preferred methods of use are those involving the above preferred compounds.
  • This invention also relates to arthropodicidal compositions comprising arthropodicidally effective amounts of the compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent.
  • This invention also relates to a method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of the compounds of the invention (e.g., as a composition described herein).
  • the preferred methods of use are those involving the above preferred compounds.
  • T T 1
  • G G is N
  • A is N and the floating double bond is attached to A
  • W is O
  • X is OCH 3
  • R 8 is H, C r C 3 alkyl, C r C 3 haloalkyl, C 2 -C 3 alkenyl, C -C 3 alkynyl, cyclopropyl or cyano
  • Z is phenyl optionally substituted with R 9 and optionally substituted with R 10
  • R 9 is H, halogen, -C alkyl, C r C 6 haloalkyl, C j -Cg alkoxy, C r C 6 haloalkoxy, C -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C
  • R 9 is H, halogen, C j -C 6 alkyl, C j -Cg haloalkyl, Cj-Cg alkoxy, Cj-Cg haloalkoxy, C -C 6 alkenyl, C -Cg haloalkenyl, C 2 -C 6 alkynyl,
  • Compounds 1-10 and 40 in Index Table A are Compounds 1-10 and 40 in Index Table A. Also of note are compounds of Formula I other than Compounds 1-10 and 40 in Index Table A (e.g., Compounds 11-39 and 41-71 in Index Table A and Compound 72 in Index Table B).
  • the compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-46.
  • the definitions of T, A, G, W, X, Y, Z, R ⁇ -R 21 , m, n, r and s in the compounds of Formulae 1-62 below are as defined above in the Summary of the Invention.
  • Compounds of Formulae Ia-Iy are various subsets of the compounds of Formula I, and all substituents for Formulae Ia-Iy are as defined above for Formula I.
  • a compound of Formula I wherein T is T 1 and R 2 is H may exist as tautomer la or lb, or both la and lb.
  • Procedures 1) to 5 describe syntheses involving construction of the heterocycle after the formation of the aryl moiety.
  • Procedure 5) describes syntheses of the aryl moiety with the T-moiety already in place.
  • Suitable solvents are selected from the group consisting of polar aprotic solvents such as acetonitrile, dimethylformamide or dimethyl sulfoxide; ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; and halocarbons such as dichloromethane or chloroform.
  • polar aprotic solvents such as acetonitrile, dimethylformamide or dimethyl sulfoxide
  • ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether
  • ketones such as
  • Use of trimethylsilyldiazomethane requires a protic cosolvent such as methanol.
  • Suitable Lewis acids include trimethylsilyl triflate and tetrafluoroboric acid.
  • the alkyl trichloroacetimidates can be prepared from the appropriate alcohol and trichloroacetonitrile as described in the literature (J. Danklmaier and H. H ⁇ nig, Synth. Commun., (1990), 10, 203).
  • a trialkyloxonium tetrafluoroborate e.g., Meerwein's salt
  • the use of trialkyloxonium salts as powerful alkylating agents is well known in the art (see U. Sch ⁇ llkopf, U. Groth, C. O.ng, Angew. Chem., Int. Ed. Engl, (1981), 10, 798).
  • Appropriate bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride and potassium carbonate, pyridine, or tertiary amines such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and triethylenediamine.
  • alkali metal alkoxides such as potassium tert-butoxide
  • inorganic bases such as sodium hydride and potassium carbonate
  • pyridine or tertiary amines such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and triethylenediamine.
  • the nucleophiles of Formula 6 are N-substituted hydroxylamines (HO- ⁇ HR 2 ) and substituted hydrazines (H ⁇ (R 5 )- ⁇ HR 2 ). Examples of such nucleophiles are N-methylhydroxylamine and methylhydrazine.
  • Compounds of Formula lb can be prepared by reaction of nitrile esters of Formula 7 with ambident nucleophiles of Formula 6. See M. Scobie and G. Tennant, J Chem. Soc, Chem. Comm., (1994), 2451. Alkylation of lb with alkyl halides in the presence of base provides compounds of Formula lc. Alternatively, treatment of lb with alkylamines or alkoxyamines provides compounds of Formula lc.
  • W N(C j -C alkyl) or NO(C j -Cg alkyl)
  • Esters of Formula 5a can be prepared from copper (I)-catalyzed reaction of malonate esters with substituted iodobenzenes of Formula 8 according to methods adapted from A. Osuka, T. Kobayashi and H. Suzuki, Synthesis , (1983), 67, and illustrated in Scheme 3.
  • R C j -C 4 alkyl
  • malonate esters of Formula 5a can be prepared by treating phenyl acetic acid esters of Formula 9a with a dialkyl carbonate or alkyl chloro formate in the presence of a suitable base such as, but not limited to, sodium metal and sodium hydride (Scheme 4).
  • a suitable base such as, but not limited to, sodium metal and sodium hydride (Scheme 4).
  • Nitrile esters of Formula 7 can be prepared similarly from compounds of Formula 10.
  • R C j -C 4 alkyl
  • Esters of Formula 9a (compounds of Formula 9 wherein E 1 is OR) can be prepared from acid-catalyzed alcoholysis of phenyl acetonitriles of Formula 10 or by esterification of phenyl acetic acids of Formula 11 as illustrated in Scheme 5 (see Org. Synth, Coll. Vol. I, (1941), 270).
  • Phenyl acetic acid esters of Formula 9b (compounds of Formula 9a wherein Y is Y 1 ) can also be prepared by copper (I)-catalyzed condensation of phenyl halides of Formula 12 with compounds of Formula 13 as described in EP-A-307,103 and illustrated below in Scheme 6.
  • Compounds of Formula 12 can be prepared by the Arndt-Eistert synthesis starting from benzoic acids of Formula 14 as illustrated in Scheme 7, (see F. Arndt, B. Eistert, Ber. 68, 200 (1935); T. Aoyama, T. Shioiri, Tetrahedron Letters 11, 4461 (1980)).
  • a halogenating agent such as thionyl chloride
  • an alkylating agent such as diazomethane
  • Compounds of Formula 14 can be prepared from nitrobenzoic acids of Formula 15 by a modification of the Sandmayer Reaction as taught in S. Kanoh, H. Muramoto, N. Kobayashi, M. Motoi and H. Suda, Bull. Chem. Soc. Jpn. 60, 3659 (1987) and M. P. Doyle, J Org. Chem. 41, 2426 (1977) (Scheme 8).
  • the compound can be prepared by nitration and reduction of commercially available 2,5-dimethylbenzoic acid as taught in A.N. Fugiwara, E. M. Acton, Can. J. Chem. 48, 1346 (1970).
  • esters of Formula 9c can also be prepared by forming the Y 2 bridge using conventional nucleophilic substitution chemistry (Scheme 9). Displacement of an appropriate leaving group (Lg) in electrophiles of Formula 17 or 18 with a nucleophilic ester of Formula 16 affords compounds of Formula 9c.
  • a base for example sodium hydride, is used to generate the corresponding alkoxide or thioalkoxide of the compound of Formula 16.
  • R C j -C 4 alkyl
  • Lg Br, Cl, I, OS0 2 CH 3 , OS0 2 (4-Me-Ph)
  • Compounds of Formula 16 can be prepared from compounds of Formula 12 by methods taught in Chem. Pharm. Bull 33 (12), 5184 (1985) or J. Org. Chem. 53 (2) 439, (1988). For example treatment of compounds of Formula 12 with a metal hydroxide, such as sodium hydroxide, in a polar protic solvent in the presence of a metal species such as copper yields compound 16a (compounds of Formula 16 where R 14 is OH).
  • Compounds of Formula 16b (compounds of Formula 16 where R 14 is CH 2 OH or CH 2 SH) can be prepared by metal-halogen exchange in compounds of Formula 12 followed by quenching with the appropriate electrophile.
  • reducing agents sodium borohydride (NaBH 4 ), sodium cyanoborohydride (NaCNBH 4 ) and diisobutylaluminum hydride (DIBAL-H) (Scheme 10).
  • Suitable inert solvents are methanol, ethanol, methylene chloride and THF, (see M. Hudlicky, Reductions in Organic Chemistry; John Wiley & Sons: New York, (1986)).
  • esters of Formula 9d can also be prepared by forming the Y 3 bridge from substituted hydroxylamines 16d and carbonyl compounds 19.
  • the hydroxylamines 16d are in turn prepared from esters 16c.
  • Compounds of Formula 16c where the Lg is Br, Cl, I, OSO 2 CH 3 or OSO 2 (4-Me-Ph) can be prepared from compounds of Formula 16b, (see March, J. Advanced Organic Chemistry, 3rd ed., John Wiley: New York, (1985). This method has been described in EP-A-600,835 and is illustrated in Scheme 11.
  • Compounds of Formula 20a can be prepared from compounds of Formula Id (compounds of Formula 1 wherein X 1 is OH) by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding ⁇ -halo-substituted derivatives (Scheme 13).
  • halogenating agents such as thionyl chloride or phosphorus oxybromide
  • compounds of Formula Id can be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methane sulfonyl chloride, />-toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the corresponding ⁇ -alkylsulfonate of Formula 20b.
  • the reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine).
  • sulfonyl compounds of Formula 20c can be prepared by oxidation of the corresponding thio compound of Formula 21 using well-known methods for the oxidation of sulfur (see Schrenk, K. in The Chemistry ofSulphones and Sulphoxides; Patai, S. et al., Eds.; Wiley: New York, (1988)).
  • Suitable oxidizing reagents include met ⁇ -chloro-peroxybenzoic acid, hydrogen peroxide and Oxone® (KHSO 5 ).
  • halo-compounds of Formula 20d can be prepared from hydrazides of Formula 22 as illustrated in Scheme 15.
  • the compound of Formula 22 is treated with excess of a thionyl halide such as thionyl chloride.
  • the product formed first is the ring-closed compound of Formula 23 which can be isolated or converted in situ to the compound of Formula 20d; see P. Molina, A. Tarraga, A. Espinosa, Synthesis, (1989), 923 for a description of this process.
  • the hydrazides of Formula 22 can be prepared as illustrated in Scheme 16. Condensation of the isocyanate of Formula 24 with the hydrazine of Formula H 2 NNR 2 R 15 in an inert solvent such as tetrahydrofuran affords the hydrazide.
  • R C j -C 4 alkyl 25a
  • Q 4 H, C j -Cg alkyl, C j -Cg alkoxy
  • the carbonylating agents can be alkyl chloroformates or dialkyl carbonates. Some of these carbonylating reactions may require the addition of a base to effect reaction.
  • Appropriate bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride and potassium carbonate, pyridine, or tertiary amines such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or triethylenediamine.
  • Suitable solvents include polar aprotic solvents such as acetonitrile, dimethylformamide, or dimethyl sulfoxide; ethers such as tetrahydrofuran, dimethoxyethane or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; or halocarbons such as dichloromethane or chloroform.
  • the reaction temperature can vary between 0 °C and 150 °C and the reaction time can be from 1 to 72 hours depending on the choice of base, solvent, temperature, and substrates.
  • Q 1 and Q 2 are independently Cl, OCCl 3 , 0(C j -C 4 alkyl), 1 -imidazolyl, 1,2,4-triazolyl
  • N-Amino-ureas of Formula 26 can be prepared as illustrated in Scheme 20.
  • Treatment of an aniline of Formula 27 with phosgene, thiophosgene, NN'-carbonyldiimidazole, or NN'-thiocarbonyldiimidazole produces the isocyanate or isothiocyanate of Formula 28.
  • a base can be added for reactions with phosgene or thiophosgene.
  • Subsequent treatment of the iso(thio)cyanate with an R 2 -substituted hydrazine produces the N-amino-urea of Formula 26.
  • Compounds of Formula 29 can be prepared by contacting benzyl halides, mesylates or tosylates of Formula 30 with various nucleophiles (Scheme 22).
  • the appropriate alcohol or thiol is treated with a base, for example sodium hydride, to form the corresponding alkoxide or thioalkoxide which acts as the nucleophile.
  • Lg Br, Cl, I, OS0 CH 3 , OS0 2 (4-Me-Ph)
  • Formula 30a (compounds of Formula 30 where the Lg group has been replaced with OH) by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding ⁇ -halo-substituted derivatives (Scheme 23).
  • Compounds of Formula 30a can also be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methane sulfonyl chloride, />-toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the corresponding ⁇ -alkylsulfonate of Formula 30.
  • the reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine).
  • Formula 1 f compounds can be prepared by reaction of Formula 28 iso(thio)cyanates or Formula 28a carbodiimides with Formula 35 esters. As described above, base may be added to accelerate the reaction and subsequent cyclization to Formula If compounds.
  • Carbodiimides 28a can be prepared as shown in Scheme 25, starting with compounds of Formula 28 and forming compounds of Formula 34 which are dehydrated to give compounds of Formula 28a.
  • the (thio)ureas or amidines of Formula 32 can be prepared by either of the methods illustrated in Scheme 26.
  • an iso(thio)cyanate of Formula 28 or carbodiimide of Formula 28a can be condensed with an amine of Formula R 2 -NH 2 to form the urea or amidine.
  • the anilines and iso(thio)cyanates of Formulae 27 and 28, respectively, are commercially available or prepared by well-known methods.
  • isothiocyanates can be prepared by methods described in J. Heterocycl. Chem. , (1990), 17, 407.
  • Isocyanates can be prepared as described in March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), pp 944, 1166.
  • Compounds of Formula Im (compounds of Formula I where T is T 1 , X is OR 1 , R 1 is CH 3 , R 2 is CH 3 , W is O, A is N, G is N, Y 5 is -O-, -OCH 2 - or -SCHR 1 ] -) can be prepared by forming the Y 5 bridge using conventional nucleophilic substitution chemistry (Scheme 30). Displacement of an appropriate leaving group (Lg) in electrophiles of Formula 17 or 18 with nucleophilic compounds of Formula 36 affords compounds of Formula Im.
  • a base for example sodium hydride, is used to generate the corresponding alkoxide or thioalkoxide of the compounds of Formula 37.
  • an additional substituent on Z which activates the leaving group (Lg) can be advantageous (e.g., when Lg-Z is 2-chloro-3 -nitro thiophene, the activating nitro group can be removed after coupling by reduction to the amine followed by diazotization and reduction to provide compounds of Formula Im).
  • Benzyl halides of Formula 38 can be prepared by radical halogenation of the corresponding alkyl compound of Formula 39a, see WO 96/38425. Benzyl halides can also be prepared by the acidic cleavage of the corresponding methyl ether of Formula 39b under conditions which provide the halide, see Scheme 31. Methods for preparing the corresponding compounds of Formula 38 wherein the T 1 group has been replaced by T 2 are described in WO 94/05620. Methods for preparing the corresponding compounds of Formula 38 wherein the T 1 group has been replaced by T 3 are described in EP-A-254,426, EP-A-299,694 and AU-A-55899/90.
  • compounds of Formula 38 can be prepared from the corresponding alcohol of Formula 40 by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding ⁇ -halo-substituted derivatives.
  • compounds of Formula 40 can be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methane sulfonyl chloride, / toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the corresponding ⁇ -alkylsulfonate of Formula 41.
  • the reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine) see Scheme 32.
  • Compounds of Formula 40 can be prepared by reducing esters of Formula 44 or aldehydes of Formula 43 with an appropriate reducing agent, (M. Hudlicky, Reductions in Organic Chemistry; John Wiley & Sons pp. 147-160, (1986)).
  • an appropriate reducing agent M. Hudlicky, Reductions in Organic Chemistry; John Wiley & Sons pp. 147-160, (1986)
  • DIBAL-H diisobutylaluminum hydride
  • Compounds of Formula 43 can be reduced with sodium borohydride in a protic solvent such as methanol or ethanol, Scheme 34.
  • Esters of Formula 44 can be prepared from anthranilic acid esters of Formula 45 according to the procedures described in Scheme 35.
  • Esters 45 can be prepared from readily accessible anthranilic acids by esterification techniques well known in the art.
  • a formaldehyde equivalent i.e., dimethylformamide or methyl chloro formate
  • compounds of Formula 48 can be prepared from compounds of Formula 46 by metallation using an alkyllithium followed by quenching with a trialkoxy borane, (Scheme 38), see Organic Synthesis via Boranes; Wiley: New York, (1975).
  • R Cj-C 4 alkyl
  • Compounds of Formula 54 are prepared by nitration of commercially available 2,5-dimethylphenol 53 as taught in M. Quertani, P. Girard and H. B. Kagan, Tetrahedron Letters, 13, 4315 (1982), Scheme 40.
  • R 0 P(CgH 5 ) 3 + (Cl. Br or l)
  • R 0 P(O(Cj-C4 alkyl)) 2
  • the olefin of Formula Ip can also be prepared by reversing the reactivity of the reactants in the Wittig or Horner-Emmons condensation.
  • 2-alkylphenyl derivatives of Formula 56 can be converted into the corresponding dibromo -compounds of Formula 57a as illustrated in Scheme 42 (see Synthesis, (1988), 330).
  • the dibromo- compounds can be hydrolyzed to the carbonyl compounds of Formula 57b, which in turn can be condensed with a phosphorus-containing nucleophile of Formula 58 or 59 to afford the olefins of Formula Ip.
  • NBS jV-bromosuccinimide 57b
  • Carbamates of Formula lu can be prepared by reacting benzyl alcohols of Formula 61 with iso(thio)cyanates of Formula 62 (Scheme 44).
  • a base such as triethylamine can be added to catalyze the reaction.
  • Compounds of Formula Iw may be prepared by methods described in EP-A- 178,826, EP-A-341,845 and EP-A-464,381.
  • a triarylbismuth compound or a substituted phenylboronic acid in the presence of cupric acetate and a tertiary amine such as pyridine or triethylamine as illustrated in Scheme 46.
  • organobismuth reagents in the preparation of diary 1 ethers is well known in the art (see Tetrahedron Lett., (1986), 17, 3619, and Tetrahedron Lett., (1987), 18, 887).
  • Boronic acids are well known in the literature (see Ada Chem. Scand. 1993, 47, 221 and references therein).
  • Step A Preparation of N-(2-methoxy-6-methylphenyl)-2,2- dimethylhvdrazinecarboxamide
  • phosgene 108 g, 1.09 moles
  • 2-methoxy-6-methylaniline 125.0 g, 911 mmol
  • Step B Preparation of 5-chloro-2.4-dihvdro-4-(2-methoxy-6-methylphenyl)-2- methyl-3H-l,2,4-triazol-3-one
  • the title compound of Step A (100.0 g, 447.9 mmol) was suspended in ethyl acetate (1 L) and added dropwise, via mechanical pump, over 3.5 h to a stirring solution of phosgene (177 g, 1.79 moles) in ethyl acetate (1.5 L) which was heated at reflux. After the addition was complete, the mixture was heated at reflux for a further 3 h, cooled to room temperature and stirred overnight.
  • Step D Preparation of 2.4-dihydro-4-(2-hvdroxy-6-methylphenyl)-5-methoxy-2- methyl-3H- 2.4-triazol-3-one
  • tetrahydrofuran 1.5 L
  • Step E Preparation of 2.4-dihydro-5-methoxy-2-methyl-4-[6-methyl-2-r3- ftrifluoromethyl phenoxy]phenyll-3H- 1.2.4-triazol-3-one
  • 2,4-dihydro-4-(2-hydroxy-6-methylphenyl)-5-methoxy-2-methyl-3H- l,2,4-triazol-3-one (0.50 g, 2.13 mmol)
  • methylene chloride 15 mL
  • Step B 2,4-dihydro-5-methoxy-2-methyl-4- 2-methyl-6-( ' 2-thienyloxy phenyll-3H-
  • 6-OCHF 2 -2-pyridinyl 3-Et-phenyl 1-naphthalenyl 1 ,2,3 ,4-tetrahydro-2-naphthalenyl
  • 6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl) 4-OCF 3 -phenyl 3-NBu-phenyl 4-/-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF 3 -phenyl 4-SCF 3 -phenyl pyrazinyl 4-CF 3 -6-Me-2-pyridinyl 4 ,6-diMe-2-pyridiny 1 3,5-di(CF 3 )-phenyl 3-(CH 3 C ⁇ C)-phenyl Y -CH 2 0-
  • Y -OCH 2 - Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF 3 -phenyl 4-CF -phenyl 4-Me-phenyl 4-?-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-?-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
  • 6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7, 8-tetrahydro-2-naphthalenyl) 4-OCF 3 -phenyl 3-Z-Bu-phenyl 4-/-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF 3 -phenyl 4-SCF 3 -phenyl pyrazinyl 4-CF 3 -6-Me-2-pyridiny 1 4,6-diMe-2-pyridinyl 3,5-di(CF 3 )-phenyl 3-(CH 3 C ⁇ C)-phenyl Y -CH 2 0-
  • 6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 4-OCF 3 -phenyl 3-t-Bu-phenyl 4-t-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF 3 -phenyl 4-SCF 3 -phenyl pyrazinyl 4-CF3-6-Me-2 -pyridinyl 4,6-diMe-2-pyridinyl 3,5-di(CF 3 )-phenyl Y -CH 2 0-

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Abstract

Compounds of Formula (I), and their N-oxides and agriculturally suitable salts, are disclosed which are useful as fungicides and arthropodicides wherein T is (T?1), (T2), (T3) or (T4); R3 and R4¿ are each independently H or CH¿3?, provided that R?3 and R4¿ are not both H; and A, G, W, X, Y, Z, R?1, R2, R5, R6¿ and s are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula (I) and a method for controlling plant diseases caused by fungal plant pathogens which involves applying an effective amount of a compound of Formula (I). Also disclosed are compositions containing the compounds of Formula (I) and a method for controlling arthropods which involves contacting the arthropods or their environment with an effective amount of a compound of Formula (I).

Description

TITLE METHYL SUBSTITUTED FUNGICIDES AND ARTHROPODICIDES BACKGROUND OF THE INVENTION This invention relates to certain methyl substituted fungicides, their N-oxides, agriculturally suitable salts and compositions, and methods of their use as fungicides and arthropodicides.
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumers. The control of arthropod pests is also extremely important in achieving high crop efficiency. Arthropod damage to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. The control of arthropod pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different modes of action.
International Publication No. WO 95/14009, WO 96/26190, WO 96/38425, WO 97/00612 and European Patent Publications EP-A-178,826 and EP-A-226,917 disclose certain methyl substituted fungicides.
SUMMARY OF THE INVENTION This invention involves compounds of Formula I including all geometric and stereoisomers, N-oxides, and agriculturally suitable salts thereof:
Figure imgf000003_0001
wherein T is
Figure imgf000003_0002
Figure imgf000004_0001
3 or T ;
X is OR1, SCOJΠJR1 or halogen; A is O, S, N, NR5 or CR7;
G is C or N; provided that when G is C, A is O, S or NR5 and the floating double bond is attached to G; and when G is N, A is N or CR7 and the floating double bond is attached to A;
W is O; S; NH; N(CrC6 alkyl); or NO(CrC6 alkyl);
Y is -O-, -CH2O-, -OCH2-, -CHRπO-N=C(R8)-, a direct bond, -(CH2)r-,
-CCR^Cf 1 1)-, -CH2S(O)n-, -C(R8) =N-O-CHR1 1-, -CHRπSC(R8)=N-, - R1 l)=N-N=C(Rl !)-, -CHR1 1O-N=C(R8)CH2S-, -CHR1 1O-N=C(R8)CH2O-, -C(R] 1)=N-N(CH3)-, -CHR1 lOC(R8)=N-, -CHR1 1OC(=S)NR1 1-,
-CHR1 1SC(=S)NR1 1-, -SCHR1 !-, or -CHR1 1O-N=C(R1 1)C(=N-OR1 !)-; and the directionality of the Y linkage is defined such that the moiety depicted on the left side of the linkage is bonded to the phenyl ring having the R3 and R4 substituents and the moiety on the right side of the linkage is bonded to Z; Z is independently selected from: i) C]-C JO alkyl, CI -CJQ haloalkyl or phenyl each optionally substituted with R9 and optionally substituted with one or more R10; ii) a ring selected from 5 or 6-membered aromatic heterocyclic ring, each heterocyclic ring containing 1 to 4 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring contains no more than 3 nitrogens, no more than 1 oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring optionally substituted with R9 and optionally substituted with one or more R10; iii) a naphthalene ring optionally substituted with R9 and optionally substituted with one or more R10; and iv) a tetrahydronaphthalene ring optionally substituted with R9 and optionally substituted with one or more R10; R1 is CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-Cg haloalkynyl, C3-Cg cycloalkyl, C2-C alkylcarbonyl or C2-C alkoxycarbonyl; R2 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-Cg cycloalkyl, C -C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, hydroxy, C]-C2 alkoxy or acetyloxy; R3 and R4 are each independently H or CH3, provided that R3 and R4 are not both H; R5 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C alkylcarbonyl or C2-C4 alkoxycarbonyl; R6 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-Cg haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2-C alkoxycarbonyl, hydroxy, Cj-C2 alkoxy or acetyloxy;
R7 is H, halogen or methyl; R8 is H, CrC3 alkyl, CrC3 alkoxy, CrC3 alkylthio, CrC3 haloalkyl, C2-C3 alkenyl,
C2-C3 alkynyl, cyclopropyl, cyano or NH2; R9 is halogen; Ci-C alkyl; Cj-Cg haloalkyl; Cj-Cg alkoxy; C Cg haloalkoxy; C2-Cg alkenyl; C2-C6 haloalkenyl; C2-Cg alkynyl; Cj-Cg alkylthio;
CrC6 haloalkylthio; CrC6 alkylsulfinyl; CrC6 alkylsulfonyl; C3-C6 cycloalkyl; trimethylsilyl; C2-Cg alkynyl substituted with trimethylsilyl or C3-Cg cycloalkyl; or phenyl or phenoxy, each phenyl or phenoxy optionally substituted with R12 and optionally substituted with one or more R13; provided that when R9 is phenyl or phenoxy each optionally substituted with R12 and optionally substituted with one or more R13, then T is other than T1; R10 is halogen, C]-Cg alkyl, Ci-Cg haloalkyl, C Cg alkoxy, C Cg haloalkoxy or cyano; or R9 and R10 when attached to adjacent carbon atoms can be taken together as -CH2CH2O- or -OCH2CH2O-; each R1 1 is independently H, Cj-C3 alkyl or cyclopropyl;
R12 is halogen, Cj-Cg alkyl, Cj-Cg haloalkyl, Cj-C6 alkoxy, Cj-Cg haloalkoxy, C2-Cg alkenyl, C2-Cg haloalkenyl, C2-Cg alkynyl, Cj-Cg alkylthio, CrC6 haloalkylthio, CrC6 alkylsulfinyl, CrC6 alkylsulfonyl or C3-C6 cycloalkyl;
R13 is halogen, Cj-Cg alkyl, Cj-Cg haloalkyl, Cj-Cg alkoxy, Cj-Cg haloalkoxy or cyano; m is 0, 1 or 2; n is 0, 1 or 2; r is 1, 2, 3 or 4; and s is 0 or 1.
This invention provides a method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of a compound of Formula I including all geometric and stereoisomers, N-oxide, and agriculturally suitable salts thereof, provided that when T is T1, then i) when Y is -O-, X is OMe, R3 is CH3 and R4 is H, then Z is other than 6-chloro-4-pyrimidinyl and 6-chloro-2-pyrazinyl; ii) when Y is a direct bond, X is Cl, R3 is CH3 and R4 is H, then Z is other than
CH2Br; iii) when Y is -O- and Z is l,2,4-thiadiazol-5-yl or 2-thiazolyl optionally substituted with R9 and optionally substituted with R10, then neither R9 nor R10 is C(CH3)3; and iv) Y-Z is other than Ci-C JO alkyl and Cj-C |o alkoxy.
This invention also provides selected compounds of Formula I which are considered particularly effective fungicides and arthropodicides. Specifically, this invention provides compounds of Formula I including all geometric and stereoisomers, N-oxides, and agriculturally suitable salts thereof, and agricultural compositions containing them and their use as fungicides and arthropodicides, provided that
(a) when T is T1, then i) when Y is -O-, X is OMe, R3 is CH3 and R4 is H, then Z is other than
6-chloro-4-pyrimidinyl and 6-chloro-2-pyrazinyl; ii) when Y is a direct bond, X is Cl, R3 is CH3 and R4 is H, then Z is other than CH2Br; iii) when Y is -O- and Z is l,2,4-thiadiazol-5-yl or 2-thiazolyl optionally substituted with R9 and optionally substituted with R10, then neither R9 nor R10 is C(CH3)3; iv) Y-Z is other than CJ-CI Q alkyl and CJ-CJQ alkoxy; v) when Y is -CH2O-Ν=C(CH3)-, X is OMe, R3 is CH3 and R4 is H, then Z is other than 3-(trifiuorornethyl)phenyl; vi) when Y is -CH2O-N=C(CH3)-, X is OMe, R3 is H and R4 is CH3, then Z is other than 3-(trifluorornethyl)phenyl; vii) when Z is 2-naphthalenyl or 5,6,7,8-tetrahydro-2-naphthalenyl, then Y is other than -CH2O- and -CH2O-N=C(CH3)-; viii) when Y is -CH2O-, R3 is CH3, Z is phenyl substituted with R9 in the
2-position and R9 is methyl or halogen, then Z is substituted with at least one
R10 other than methyl and halogen; and ix) when Y is -CH2O-, R3 is CH3, Z is phenyl substituted with R10 in the 2-position and R10 is methyl or halogen, then Z is substituted with at least one
R9 or R10 other than methyl and halogen;
(b) when T is T2, then i) Y is other than -OCH2-, -CCR11)=C(R1 1)- and -SCHR1 i-; ii) when Y is -O- or -(CH2)r-, then Z is pyrimidinyl optionally substituted with R9 and optionally substituted with one or more R10; iii) when Y is -CH2O-, then Z is pyridinyl optionally substituted with R9 and optionally substituted with one or more R10; and iv) when Y is -CH2O-N=C(CH3)-, then s is 1.
(c) when T is T3, then i) Y is other than -SCHR1 1-; and ii) when Y is -CH2O-, then Z is phenyl optionally substituted with R9 and optionally substituted with one or more R10; and (d) when T is T4, then i) Y is other than -C(R] 1)=C(R1 1)- and -CH2S(O)n-; and ii) when Y is -CH2O-, then Z is phenyl or naphthalenyl, each optionally substituted with R9 and optionally substituted with one or more R10. DETAILS OF THE INVENTION In the above recitations, the term "alkyl", used in the compound words "alkylthio"
"haloalkylthio", "alkylsulfinyl" and "alkylsulfonyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, rø-propyl, z'-propyl, or the different butyl, pentyl or hexyl isomers. The term "alkyl", used alone or in the compound word "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, «-propyl, z'-propyl, or the different butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as vinyl, 1-propenyl, 2-propenyl and the different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
"Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylsulfinyl" includes both enantiomers of an alkylsulfinyl group. Examples of "alkylsulfinyl" include CH3S(O), CH3CH2S(O), CH3CH2CH2S(O), (CH3)2CHS(O) and the different butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH3S(O)2, CH3CH2S(O)2, CH3CH2CH2S(O)2, (CH3)2CHS(O)2 and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F3C, C1CH2, CF3CH2 and CF3CC12. The terms "haloalkenyl", "haloalkynyl", "haloalkoxy", "haloalkylthio", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include (C1)2C=CHCH2 and CF3CH2CH=CHCH2. Examples of "haloalkynyl" include HC≡CCHCl, CF3C≡C, CC13C≡C and FCH2C≡CCH2. Examples of "haloalkoxy" include CF3O, CCl3CH2O, HCF2CH2CH2O and CF3CH2O. Examples of "haloalkylthio" include CC13S, CF3S, CC13CH2S and C1CH2CH2CH2S.
The term "aromatic heterocyclic rings" are defined as those rings which satisfy the Hϋckel rule. Examples include: a 5- or 6- membered aromatic heterocyclic ring containing 1 to 4 heteroatoms such as furanyl, furazanyl, thienyl, pyrrolyl, pyrazolyl, oxazolyl, oxadiazolyl, imidazolyl, isoxazolyl, thiazolyl, thiadiazolyl isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl and triazinyl with said ring attached through any available carbon or nitrogen. For example, when the aromatic heterocyclic ring is furanyl, it can be 2-furanyl or 3-furanyl, for pyrrolyl, the aromatic heterocyclic ring is 1 -pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, for pyridyl, the aromatic ring is 2-pyridyl, 3-pyridyl or 4-pyridyl and similarly for other aromatic heterocyclic rings.
When Z is a tetrahydronaphthalene ring optionally substituted with R9 and optionally substituted with one or more R10, the Y substituent is preferably attached to the aromatic ring of the tetrahydronaphthalene (i.e., the ring which satisfies the Hϋckel rule).
The total number of carbon atoms in a substituent group is indicated by the "Cj-C;" prefix where i and j are numbers from 1 to 10. For example, Cj-C3 alkylthio designates methylthio through propylthio. Examples of "alkylcarbonyl" include C(O)CH3, C(O)CH2CH2CH3 and C(O)CH(CH3)2. Examples of "alkoxycarbonyl" include CH3OC(=O), CH3CH2OC(=O), CH3CH2CH2OC(=O) and (CH3)2CHOC(=O). "Acetyloxy" denotes CH3C(=O)O.
When a group contains a substituent which can be hydrogen, for example R2 or R7, then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted. When a group is optionally substituted with a substituent, for example with R1, then, when the group is not substituted with that substituent, it is recognized that this is equivalent to said group having a hydrogen substituent.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). (See, e.g., U.S. Provisional Patent Application Serial No.
[Docket No. BA-9183-P1] filed September 4, 1997, which is hereby incorporated by reference in its entirety.) Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. Accordingly, the present invention comprises compounds selected from Formula I and agriculturally suitable salts thereof. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form. The salts of the compounds of the invention include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
Preferred compounds for reasons of better activity and/or ease of synthesis are: Preferred 1. Compounds of Formula I above, and agriculturally suitable salts thereof, wherein: T is T1; A is N; G is N; Y is -O-;
Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R9 and optionally substituted with one or more R10; R9 is halogen, Cj-Cg alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or C Cg haloalkoxy; and R10 is halogen, CrC6 alkyl, CrC6 alkoxy, CrC6 haloalkyl or
Cj-Cg haloalkoxy; provided that when Z is l,2,4-thiadiazol-5-yl or 2-thiazolyl optionally substituted with R9 and optionally substituted with one or more R10, then neither R9 nor R10 is C(CH3)3. Preferred 2. Compounds of Formula I above, and agriculturally suitable salts thereof, wherein: T is T1; A is N; G is N; Y is -CH2O-;
Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R9 and optionally substituted with one or more R10; R9 is halogen, Cj-Cg alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or Cj-Cg haloalkoxy; and R10 is halogen, CrC6 alkyl, CrC6 alkoxy, CrC6 haloalkyl or
Cj-Cg haloalkoxy; provided that i) when R3 is CH3 and Z is phenyl substituted with R9 in the 2-position and R9 is methyl or halogen, then Z is substituted with at least one R10 other than methyl and halogen; and ii) when R3 is CH3 and Z is phenyl substituted with R10 in the 2-position and R10 is methyl or halogen, then Z is substituted with at least one R9 or R10 other than methyl and halogen. Preferred 3. Compounds of Formula I above, and agriculturally suitable salts thereof, wherein: T is T1; A is N;
G is N;
Y is -CH2O-N=C(R8)-;
Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R9 and optionally substituted with one or more R10; R8 is CH3;
R9 is halogen, Cj-Cg alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or
Cj-Cg haloalkoxy; and R10 is halogen, CrC6 alkyl, CrC6 alkoxy, CrC6 haloalkyl or Cj-Cg haloalkoxy; provided that i) when X is OMe, R3 is CH3 and R4 is H, then Z is other than 3-(trifluoromethyl)phenyl; and ii) when X is OMe, R3 is H and R4 is CH3, then Z is other than 3-(trifluoromethyl)phenyl. Preferred 4. Compounds of Formula I above, and agriculturally suitable salts thereof, wherein: T is T1; A is N; G is N; Y is -O-, -CH2O- or -CH2O-N=C(R8)-;
Z is thienyl optionally substituted with R9 and optionally substituted with one or more R10; R8 is CH3;
R9 is halogen or Cι-C3 alkyl; and R10 is halogen or CrC3 alkyl.
Preferred 5. Compounds of Preferred 4 wherein Y is -O-. Most preferred are compounds selected from the group: 4-[2-(3-fluorophenoxy)-6-methylphenyl]-2,4-dihydro-5-methoxy-2-methyl-
3H-1 ,2,4-triazol-3-one; 2,4-dihydro-5-methoxy-2-methyl-4-[2-methyl-6-(3-methylphenoxy)phenyl]- 3H-1 ,2,4-triazol-3-one; 2,4-dihydro-5-methoxy-2-methyl-4-(2-methyl-6-phenoxyphenyl)-3H- 1 ,2,4- triazol-3-one; 2,4-dihydro-5-methoxy-2-methyl-4-[2-methyl-6-(4-methylphenoxy)phenyl]-
3H- 1 ,2,4-triazol-3-one; 2,4-dihydro-5-methoxy-2-methyl-4-[6-methyl-2-[3- (trifluoromethyl)phenoxy]phenyl]-3H-l,2,4-triazol-3-one;
2,4-dihydro-5-methoxy-2-methyl-4-[2-methyl-6-[[[[l-[4-(trifluoromethyl)-2- pyridinyl]ethylidene]amino]oxy]methyl]phenyl]-3H-l,2,4-triazol-3-one; 4-[2-[[[[l-[2-fluoro-5-(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]- 6-methylphenyl]-2,4-dihydro-5-methoxy-2-methyl-3H-l,2,4-triazol-3- one;
4-[2-[[[[l-(2-fluoro-5-methylphenyl)ethylidene]amino]oxy]methyl]-6- methylphenyl]-2,4-dihydro-5-methoxy-2-methyl-3H-l,2,4-triazol-3- one; and 2,4-dihydro-5-methoxy-2-methyl-4-[2-methyl-6-(2-thienyloxy)phenyl]-3H- l,2,4-triazol-3-one.
This invention also relates to fungicidal compositions comprising fungicidally effective amounts of the compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent. The preferred compositions of the present invention are those which comprise the above preferred compounds. This invention also relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of the compounds of the invention (e.g., as a composition described herein). The preferred methods of use are those involving the above preferred compounds. This invention also relates to arthropodicidal compositions comprising arthropodicidally effective amounts of the compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent. The preferred compositions of the present invention are those which comprise the above preferred compounds.
This invention also relates to a method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of the compounds of the invention (e.g., as a composition described herein). The preferred methods of use are those involving the above preferred compounds. Of note are compounds wherein T is T1, G is N, A is N and the floating double bond is attached to A; W is O; X is OCH3; Y is -O-, -CH2O-, -OCH2-, -CH2O-N=C(R3)- or a direct bond; R8 is H, CrC3 alkyl, CrC3 haloalkyl, C2-C3 alkenyl, C -C3 alkynyl, cyclopropyl or cyano; Z is phenyl optionally substituted with R9 and optionally substituted with R10; R9 is H, halogen, -C alkyl, CrC6 haloalkyl, Cj-Cg alkoxy, CrC6 haloalkoxy, C -C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, CrC6 alkylthio, CrC6 haloalkylthio, CrC6 alkylsulfinyl, Cj-Cg alkylsulfonyl or C3-Cg cycloalkyl; and R10 is H, 1-2 halogen, Ci-Cg alkyl, Cj-Cg haloalkyl, Cj-Cg alkoxy Cj-C6 haloalkoxy or cyano.
Of note are compounds wherein R9 is H, halogen, Cj-C6 alkyl, Cj-Cg haloalkyl, Cj-Cg alkoxy, Cj-Cg haloalkoxy, C -C6 alkenyl, C -Cg haloalkenyl, C2-C6 alkynyl,
CrC6 alkylthio, CrC6 haloalkylthio, CrC6 alkylsulfinyl, CrC6 alkylsulfonyl, C3-C6 cycloalkyl, trimethylsilyl, phenyl or phenoxy each phenyl or phenoxy optionally substituted with R12 and optionally substituted with one or more R13; provided that when R9 is phenyl or phenoxy each optionally substituted with R12 and optionally substituted with one or more R13, then T is other than T1.
Of note are Compounds 1-10 and 40 in Index Table A. Also of note are compounds of Formula I other than Compounds 1-10 and 40 in Index Table A (e.g., Compounds 11-39 and 41-71 in Index Table A and Compound 72 in Index Table B).
Of note are Compounds 1-19 in Index Table A. Also of note are Compounds 20-71 in Index Table A and Compound 72 in Index Table B.
DETAILS OF THE SYNTHESIS The compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-46. The definitions of T, A, G, W, X, Y, Z, Rϊ-R21, m, n, r and s in the compounds of Formulae 1-62 below are as defined above in the Summary of the Invention. Compounds of Formulae Ia-Iy are various subsets of the compounds of Formula I, and all substituents for Formulae Ia-Iy are as defined above for Formula I.
One skilled in the art will recognize that some compounds of Formula I can exist in one or more tautomeric forms. For example, a compound of Formula I wherein T is T1 and R2 is H may exist as tautomer la or lb, or both la and lb. The present invention comprises all tautomeric forms of compounds of Formula I where T = T1.
Figure imgf000013_0001
The compounds of Formula I where T = T1 can be prepared as described below in Procedures 1) to 5). Procedures 1) to 4) describe syntheses involving construction of the heterocycle after the formation of the aryl moiety. Procedure 5) describes syntheses of the aryl moiety with the T-moiety already in place. 1) Alkylation Procedures
The compounds of Formula Ic, compounds of Formula I where T = T1, are prepared by treating compounds of Formula 1 with an appropriate alkyl transfer reagent in an inert solvent with or without additional acidic or basic reagents or other reagents (Scheme 1). Suitable solvents are selected from the group consisting of polar aprotic solvents such as acetonitrile, dimethylformamide or dimethyl sulfoxide; ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; and halocarbons such as dichloromethane or chloroform.
Scheme 1
Figure imgf000013_0002
1 Ic χ! = OH or SH X = OR1 or SR1 Method 1 : U-CH=N2 (U = H or (CH3)3Si) 2
Method 2: - Lewis acid
Figure imgf000014_0001
Method 3: (R1)30+ BF4- 4
Method 4: (R!)2S04; R]OS02Q; or RΪ-hal; optional base (hal = F, Cl, Br, or I) (Q = Cj-Cg alkyl, Cj-Cg haloalkyl)
For example, compounds of Formula Ic, compounds of Formula I where T = T1, can be prepared by the action of diazoalkane reagents of Formula 2 such as diazomethane (U = H) or trimethylsilyldiazomethane (U = (CH3)3Si) on compounds of Formula 1 (Method 1). Use of trimethylsilyldiazomethane requires a protic cosolvent such as methanol. For examples of these procedures, see Chem. Pharm. Bull, (1984), 31, 3759.
As indicated in Method 2, compounds of Formula Ic, compounds of Formula I where T = T1, can also be prepared by contacting carbonyl compounds of Formula 1 with alkyl trichloroacetimidates of Formula 3 and a Lewis acid catalyst. Suitable Lewis acids include trimethylsilyl triflate and tetrafluoroboric acid. The alkyl trichloroacetimidates can be prepared from the appropriate alcohol and trichloroacetonitrile as described in the literature (J. Danklmaier and H. Hδnig, Synth. Commun., (1990), 10, 203).
Compounds of Formula Ic, compounds of Formula I where T = T1, can also be prepared from compounds of Formula 1 by treatment with a trialkyloxonium tetrafluoroborate (e.g., Meerwein's salt) of Formula 4 (Method 3). The use of trialkyloxonium salts as powerful alkylating agents is well known in the art (see U. Schδllkopf, U. Groth, C. O.ng, Angew. Chem., Int. Ed. Engl, (1981), 10, 798).
Other alkylating agents which can convert compounds of Formula 1 to compounds of Formula Ic where T = T1, are dialkyl sulfates such as dimethyl sulfate, haloalkyl sulfonates such as methyl trifluoromethanesulfonate, and alkyl halides such as iodomethane and propargyl bromide (Method 4). These alkylations can be conducted with or without additional base. Appropriate bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride and potassium carbonate, pyridine, or tertiary amines such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and triethylenediamine. See R. E. Benson, T. L. Cairns, J. Am. Chem. Soc, (1948), 70, 2115 for alkylation examples using agents of this type. Compounds of Formula la (compounds of Formula 1 wherein G = C, W = O and X1 - OH) can be prepared by condensation of malonates or malonate derivatives of Formula 5 with an ambident nucleophile of Formula 6 (Scheme 2). The nucleophiles of Formula 6 are N-substituted hydroxylamines (HO-ΝHR2) and substituted hydrazines (HΝ(R5)-ΝHR2). Examples of such nucleophiles are N-methylhydroxylamine and methylhydrazine. The malonate esters of Formula 5 (E = O(Cj-C4 alkyl)) can be prepared by methods described hereinafter. The esters of Formula 5 can also be activated by first hydrolyzing the ester to form the corresponding carboxylic acid, and then converting the acid into the acid chloride (E = Cl) using thionyl chloride or oxalyl chloride, or into the acyl imidazole (E = 1 -imidazolyl) by treating with 1,1 '-carbonyldiimidazole. Compounds of Formula lb can be prepared by reaction of nitrile esters of Formula 7 with ambident nucleophiles of Formula 6. See M. Scobie and G. Tennant, J Chem. Soc, Chem. Comm., (1994), 2451. Alkylation of lb with alkyl halides in the presence of base provides compounds of Formula lc. Alternatively, treatment of lb with alkylamines or alkoxyamines provides compounds of Formula lc.
Scheme 2
Figure imgf000015_0001
la
E = 0(Cj-C4 alkyl), Cl, 1 -imidazolyl
Figure imgf000016_0001
lc
W = N(C j-C alkyl) or NO(Cj-Cg alkyl)
Esters of Formula 5a can be prepared from copper (I)-catalyzed reaction of malonate esters with substituted iodobenzenes of Formula 8 according to methods adapted from A. Osuka, T. Kobayashi and H. Suzuki, Synthesis , (1983), 67, and illustrated in Scheme 3.
Scheme 3
Figure imgf000016_0002
5a
R = Cj-C4 alkyl
Additionally, the malonate esters of Formula 5a can be prepared by treating phenyl acetic acid esters of Formula 9a with a dialkyl carbonate or alkyl chloro formate in the presence of a suitable base such as, but not limited to, sodium metal and sodium hydride (Scheme 4). For example, see J. Am. Chem. Soc, (1928), 50, 2758. Nitrile esters of Formula 7 can be prepared similarly from compounds of Formula 10.
Scheme 4
Figure imgf000017_0001
base
5a
9a E1 = OR R = Cj-C4 alkyl
Figure imgf000017_0002
10
R = Cj-C4 alkyl
Esters of Formula 9a (compounds of Formula 9 wherein E1 is OR) can be prepared from acid-catalyzed alcoholysis of phenyl acetonitriles of Formula 10 or by esterification of phenyl acetic acids of Formula 11 as illustrated in Scheme 5 (see Org. Synth, Coll. Vol. I, (1941), 270).
Scheme 5
Figure imgf000018_0001
10 9a 11 R = Cj-C4 alkyl
Phenyl acetic acid esters of Formula 9b (compounds of Formula 9a wherein Y is Y1) can also be prepared by copper (I)-catalyzed condensation of phenyl halides of Formula 12 with compounds of Formula 13 as described in EP-A-307,103 and illustrated below in Scheme 6.
Scheme 6
Figure imgf000018_0002
Compounds of Formula 12 can be prepared by the Arndt-Eistert synthesis starting from benzoic acids of Formula 14 as illustrated in Scheme 7, (see F. Arndt, B. Eistert, Ber. 68, 200 (1935); T. Aoyama, T. Shioiri, Tetrahedron Letters 11, 4461 (1980)). For example, treatment of benzoic acids of Formula 14 with a halogenating agent such as thionyl chloride followed by addition of an alkylating agent such as diazomethane yields an intermediate that can be quenched with R-OH in an appropriate solvent to afford the desired ester 12. Scheme 7
Figure imgf000019_0001
Compounds of Formula 14 can be prepared from nitrobenzoic acids of Formula 15 by a modification of the Sandmayer Reaction as taught in S. Kanoh, H. Muramoto, N. Kobayashi, M. Motoi and H. Suda, Bull. Chem. Soc. Jpn. 60, 3659 (1987) and M. P. Doyle, J Org. Chem. 41, 2426 (1977) (Scheme 8). Nitrobenzoic acids of Formula 15 where R3 = CH3 and R4 = H or R3 = H and R4 = CH3 are commercially available as are the corresponding anthranilic acids (where the nitro group is replaced by an amino group). Where R3 = R4 = CH3 the compound can be prepared by nitration and reduction of commercially available 2,5-dimethylbenzoic acid as taught in A.N. Fugiwara, E. M. Acton, Can. J. Chem. 48, 1346 (1970).
Scheme 8
Figure imgf000019_0002
15 14
Some esters of Formula 9c can also be prepared by forming the Y2 bridge using conventional nucleophilic substitution chemistry (Scheme 9). Displacement of an appropriate leaving group (Lg) in electrophiles of Formula 17 or 18 with a nucleophilic ester of Formula 16 affords compounds of Formula 9c. A base, for example sodium hydride, is used to generate the corresponding alkoxide or thioalkoxide of the compound of Formula 16. Scheme 9
Figure imgf000020_0001
16 9c
R = Cj-C4 alkyl
R14 = OH, SH, CH OH, CH2SH γ2 = .Q-, -OCH2-, -SCHR1 1-, -CH2O-, -CH S(0)n-
Lg = Br, Cl, I, OS02CH3, OS02(4-Me-Ph)
Compounds of Formula 16 can be prepared from compounds of Formula 12 by methods taught in Chem. Pharm. Bull 33 (12), 5184 (1985) or J. Org. Chem. 53 (2) 439, (1988). For example treatment of compounds of Formula 12 with a metal hydroxide, such as sodium hydroxide, in a polar protic solvent in the presence of a metal species such as copper yields compound 16a (compounds of Formula 16 where R14 is OH). Compounds of Formula 16b (compounds of Formula 16 where R14 is CH2OH or CH2SH) can be prepared by metal-halogen exchange in compounds of Formula 12 followed by quenching with the appropriate electrophile. For example, treatment of compounds of Formula 12 with a suitable alkyllithium such as π-Butyllithium in an inert solvent such as ether or tetrahydrofuran (THF) followed by quenching with an electrophile such as paraformaldehyde would yield compound of Formula 16b (where R14 is CH2OH), (see B. J. Wakefield Organolithium Methods; Academic Press: New York, (1988)). Alternatively quenching the metalated species with a formaldehyde equivalent D-CHO (where D is (CH3)2N, or OMe) followed by reduction of the aldehyde with a suitable reducing agent yields compounds of Formula 16b. Examples of such reducing agents are sodium borohydride (NaBH4), sodium cyanoborohydride (NaCNBH4) and diisobutylaluminum hydride (DIBAL-H) (Scheme 10). Suitable inert solvents are methanol, ethanol, methylene chloride and THF, (see M. Hudlicky, Reductions in Organic Chemistry; John Wiley & Sons: New York, (1986)). Scheme 10
Figure imgf000021_0001
Some esters of Formula 9d can also be prepared by forming the Y3 bridge from substituted hydroxylamines 16d and carbonyl compounds 19. The hydroxylamines 16d are in turn prepared from esters 16c. Compounds of Formula 16c where the Lg is Br, Cl, I, OSO2CH3 or OSO2(4-Me-Ph) can be prepared from compounds of Formula 16b, (see March, J. Advanced Organic Chemistry, 3rd ed., John Wiley: New York, (1985). This method has been described in EP-A-600,835 and is illustrated in Scheme 11. Esters of Formula 9d can be used to prepare compounds of Formula Id wherein T = T2 or T3 by methods described in EP-A-600,835.
Scheme 11
Figure imgf000021_0002
16c B = CHRULg
Figure imgf000021_0003
16d B = CHR1 ONH2 HCl Y3 = -CHRHθN=C(R8)
2) Displacement and Conjugate Addition/Elimination Procedures Compounds of Formula Ic, compounds of Formula I where T = T1, can also be prepared by reaction of Formula 20 compounds with alkali metal alkoxides (R^'M-1-) or alkali metal thioalkoxides (R^'M^ in a suitable solvent (Scheme 12). The leaving group Lg1 in the amides of Formula 20 is any group known in the art to undergo a displacement reaction of this type. Examples of suitable leaving groups include chlorine, bromine, and sulfonyl and sulfonate groups. Examples of suitable inert solvents are dimethylformamide or dimethyl sulfoxide. Scheme 12
Figure imgf000022_0001
20 Ic
Lg1 = Cl, Br, -S02Q, or -OS02Q Q = Cj-Cg alkyl or Cj-Cg haloalkyl M = K or Na
Compounds of Formula 20a can be prepared from compounds of Formula Id (compounds of Formula 1 wherein X1 is OH) by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding β-halo-substituted derivatives (Scheme 13). Alternatively, compounds of Formula Id can be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methane sulfonyl chloride, />-toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the corresponding β-alkylsulfonate of Formula 20b. The reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine).
Scheme 13
Figure imgf000022_0002
Id 20a Lg1 = Cl or Br
Q = Cj-Cg alkyl or Cj-Cg haloalkyl 20b Lg1 = -OS02Q hal = Br, Cl or F
As illustrated in Scheme 14, sulfonyl compounds of Formula 20c (compounds of Formula 20 where Lg1 is QSO2-) can be prepared by oxidation of the corresponding thio compound of Formula 21 using well-known methods for the oxidation of sulfur (see Schrenk, K. in The Chemistry ofSulphones and Sulphoxides; Patai, S. et al., Eds.; Wiley: New York, (1988)). Suitable oxidizing reagents include metα-chloro-peroxybenzoic acid, hydrogen peroxide and Oxone® (KHSO5).
Scheme 14
Figure imgf000023_0001
21 20c
Q = Cj-Cg alkyl or Cj-Cg haloalkyl
Alternatively, halo-compounds of Formula 20d (compounds of Formula 20 wherein A = N, G = N, and W = O) can be prepared from hydrazides of Formula 22 as illustrated in Scheme 15. When R15 = C(=S)S(Cj-C4 alkyl), the compound of Formula 22 is treated with excess of a thionyl halide such as thionyl chloride. The product formed first is the ring-closed compound of Formula 23 which can be isolated or converted in situ to the compound of Formula 20d; see P. Molina, A. Tarraga, A. Espinosa, Synthesis, (1989), 923 for a description of this process.
Alternatively, when R15 = R2 as defined above, the hydrazide of Formula 22 is cyclized with phosgene to form the cyclic urea of Formula 20d wherein hal = Cl. This procedure is described in detail in J. Org. Chem., (1989), 54, 1048.
Rl5
Figure imgf000024_0001
The hydrazides of Formula 22 can be prepared as illustrated in Scheme 16. Condensation of the isocyanate of Formula 24 with the hydrazine of Formula H2NNR2R15 in an inert solvent such as tetrahydrofuran affords the hydrazide.
Scheme 16
Figure imgf000024_0002
R15 = C(=S)S(Cj-C4 alkyl) or R2 3) Conjugate Addition/Cyclization Procedures
In addition to the methods disclosed above, compounds of Formula I wherein T is T1, X = SR1 and G = C (Formula Ie) can be prepared by treating a ketenedithioacetal of Formula 25 with an ambident nucleophile of Formula 6 (Scheme 17). The nucleophiles of Formula 6 are described above.
Scheme 17
Figure imgf000025_0002
alkyl)
Figure imgf000025_0001
25 Ie
Ketene dithioacetals of Formula 25a (compounds of Formula 25 wherein R16 is CO2(Cj-C4 alkyl)) or 25b (compounds of Formula 25 wherein R16 is C(=O)NHQ4) can be prepared by condensing phenyl acetic acid esters of Formula 9a or amides of Formula 9e, (compounds of Formula 9 wherein E1 is NHQ4) respectively, with carbon disulfide in the presence of a suitable base, followed by reaction with two equivalents of an Ri-halide, such as iodomethane or propargyl bromide (Scheme 18). Conversion of 25b to 25c (compounds of Formula 25 wherein R16 is C(=NQ4)OR) can be accomplished by reaction with trialkyl tetrafluoroborates .
Scheme 18
Figure imgf000025_0003
9a R = C j-C4 alkyl 25a
Figure imgf000026_0001
Q4 = H, Cj-Cg alkyl, Cj-Cg alkoxy
Figure imgf000026_0002
25c
Compounds of Formula le (compounds of Formula 1 wherein A = N and G = N) can be prepared by condensation of N-amino-ureas of Formula 26 with a carbonylating agent (Scheme 19). The carbonylating agents are carbonyl or thiocarbonyl transfer reagents such as phosgene, thiophosgene, diphosgene (ClC(=O)OCCl3), triphosgene (Cl3COC(=O)OCCl3), NN'-carbonyldiimidazole, NN'-thiocarbonyldiimidazole, and l,l'-carbonyldi(l,2,4-triazole). Alternatively, the carbonylating agents can be alkyl chloroformates or dialkyl carbonates. Some of these carbonylating reactions may require the addition of a base to effect reaction. Appropriate bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride and potassium carbonate, pyridine, or tertiary amines such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or triethylenediamine. Suitable solvents include polar aprotic solvents such as acetonitrile, dimethylformamide, or dimethyl sulfoxide; ethers such as tetrahydrofuran, dimethoxyethane or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; or halocarbons such as dichloromethane or chloroform. The reaction temperature can vary between 0 °C and 150 °C and the reaction time can be from 1 to 72 hours depending on the choice of base, solvent, temperature, and substrates. Scheme 19
Figure imgf000027_0001
26 le
Q1 and Q2 are independently Cl, OCCl3, 0(Cj-C4 alkyl), 1 -imidazolyl, 1,2,4-triazolyl
X1 = OH or SH X2 = O or S
N-Amino-ureas of Formula 26 can be prepared as illustrated in Scheme 20. Treatment of an aniline of Formula 27 with phosgene, thiophosgene, NN'-carbonyldiimidazole, or NN'-thiocarbonyldiimidazole produces the isocyanate or isothiocyanate of Formula 28. A base can be added for reactions with phosgene or thiophosgene. Subsequent treatment of the iso(thio)cyanate with an R2-substituted hydrazine produces the N-amino-urea of Formula 26.
Scheme 20
Figure imgf000027_0002
w = o, S 26 Anilines of Formula 27a (compounds of Formula 27 where Y = Y4) can be prepared from nitro compounds of Formula 29 by reduction methods well known in the art, Scheme 21 (see M. Hudlicky, Reductions in Organic Chemistry; John Wiley & Sons pp. 69-76 (1986)).
Scheme 21
Figure imgf000028_0001
Y4 = -CH20-, -CHR1 lθ-N= C(R8)-, -CH2S(0)n-
Compounds of Formula 29 can be prepared by contacting benzyl halides, mesylates or tosylates of Formula 30 with various nucleophiles (Scheme 22). The appropriate alcohol or thiol is treated with a base, for example sodium hydride, to form the corresponding alkoxide or thioalkoxide which acts as the nucleophile.
Scheme 22
Figure imgf000028_0002
Lg = Br, Cl, I, OS0 CH3, OS02(4-Me-Ph)
Compounds of Formula 30 can be prepared from corresponding nitrobenzyl alcohols of
Formula 30a (compounds of Formula 30 where the Lg group has been replaced with OH) by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding β-halo-substituted derivatives (Scheme 23). Compounds of Formula 30a can also be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methane sulfonyl chloride, />-toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the corresponding β-alkylsulfonate of Formula 30. The reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine).
Scheme 23
Figure imgf000029_0001
Compounds of Formula 30a can be prepared by reduction of nitrobenzoic acids of
Formula 31 with a suitable reducing agent, such as borane in tetrahydrofuran or dimethyl sulfide as taught in M. Pavia, W. H. Moos and F. M. Hershenson, J. Org. Chem. 55, 560,
(1990) or C. F. Lane, H. L. Myatt, J. Daniels and H. B. Hopps J. Org. Chem. 39, 3052,
(1974) (Scheme 24).
Scheme 24
Figure imgf000029_0002
Compounds of Formula If (compounds of Formula 1 wherein A = CR5, G = N, and X = O) can be prepared by the methods illustrated in Scheme 25. Ureas of Formula 32 are reacted with activated 2-halocarboxylic acid derivatives such as 2-halocarboxylic acid chlorides, 2-halocarboxylic acid esters or 2-haloacyl imidazoles of Formula 33. The initial acylation on the aniline nitrogen is followed by an intramolecular displacement of the 2-halo group to effect cyclization. Base may be added to accelerate the acylation and/or the subsequent cyclization. Suitable bases include triethylamine and sodium hydride. Alternatively, Formula 1 f compounds can be prepared by reaction of Formula 28 iso(thio)cyanates or Formula 28a carbodiimides with Formula 35 esters. As described above, base may be added to accelerate the reaction and subsequent cyclization to Formula If compounds. Carbodiimides 28a can be prepared as shown in Scheme 25, starting with compounds of Formula 28 and forming compounds of Formula 34 which are dehydrated to give compounds of Formula 28a.
Scheme 25
Figure imgf000030_0001
The (thio)ureas or amidines of Formula 32 can be prepared by either of the methods illustrated in Scheme 26. The anilines of Formula 27 can be contacted with an isocyanate or isothiocyanate of Formula R N=C=W as described above. Alternatively, an iso(thio)cyanate of Formula 28 or carbodiimide of Formula 28a can be condensed with an amine of Formula R2-NH2 to form the urea or amidine. The anilines and iso(thio)cyanates of Formulae 27 and 28, respectively, are commercially available or prepared by well-known methods. For example, isothiocyanates can be prepared by methods described in J. Heterocycl. Chem. , (1990), 17, 407. Isocyanates can be prepared as described in March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), pp 944, 1166.
Scheme 26
Figure imgf000031_0001
28 W = O or S 28a W = NQ5
4) Thionation Procedures
Compounds of Formula If (compounds of Formula Ic wherein W = S) can be prepared by treating compounds of Formula Ig (compounds of Formula Ic wherein W = O) with thionating reagents such as P2S5 or Lawesson's reagent [2,4-bis(4- methoxyphenyl)-l,3-dithia-2,4-diphosphetane-2,4-disulfide] as illustrated in Scheme 27 (see Bull. Soc. Chim. Belg, (1978), 87, 229; and Tetrahedron Lett., (1983), 14, 3815). Scheme 27
Figure imgf000032_0001
I X = OR1 or SR1 If
Reaction of compounds of Formula Ih with an alkyl halide in the presence of base provides compounds of Formula Ii, which can be reacted with compounds of Formula Q5NH and then alkylated with R -(C1, Br or I) to provide compounds of Formula Ij.
Scheme 28
Figure imgf000032_0002
Ih
R = Cj-C4 alkyl Q >5D == Cj-C6 alkyl, Cj-C6 alkoxy
5) Aryl Moiety Synthesis Procedures
Compounds of Formula Ik (compounds of Formula I wherein Y is -CH2O-, -CH2S(O)n-, or -CHRuO-N=C(R8)- can be prepared by displacing the appropriate leaving group (Lg) in electrophiles of Formula 36 with various nucleophiles (Scheme 29). Scheme 29
Figure imgf000033_0001
HS-Z: base
36 Ik
Y4 = -CH20-, -CH1 !0-N=C(R8)-, -CH2S(0)n-
The appropriate alcohol or thiol is treated with a base, for example sodium hydride, to form the corresponding alkoxide or thioalkoxide which acts as the nucleophile. Compounds of Formula Ik (compounds of Formula I wherein T = T2 and Y = Y4 is as defined in Scheme 29) can be prepared according to methods described in the following references: for Y4 = -CH2O-, EP-A-278,595 and EP-A-472,224; for Y4 = -CH2S(O)n-, EP-A-379,098; for Y4 = -CHR11O-N=C(R8)-, EP-A-370,629 and WO 94/05620. Compounds of Formula Ik (compounds of Formula I wherein T = T3 and Y = Y4 is as defined in Scheme 29) can be prepared according to methods described in the following references: for Y4 = -CH2O-, EP-A-253,213, EP-A-498,188 and EP-A-554,767; for Y4 = CH2S(O)n, EP-A-374,811 ; for Y4 = -CHRπO-N=C(R8)-, EP-A-414,153, EP-A-472,300, EP-A-515,901, and WO 92/18494.
Compounds of Formula Im (compounds of Formula I where T is T1, X is OR1, R1 is CH3, R2 is CH3, W is O, A is N, G is N, Y5 is -O-, -OCH2- or -SCHR1 ]-) can be prepared by forming the Y5 bridge using conventional nucleophilic substitution chemistry (Scheme 30). Displacement of an appropriate leaving group (Lg) in electrophiles of Formula 17 or 18 with nucleophilic compounds of Formula 36 affords compounds of Formula Im. A base, for example sodium hydride, is used to generate the corresponding alkoxide or thioalkoxide of the compounds of Formula 37. In some cases, an additional substituent on Z which activates the leaving group (Lg) can be advantageous (e.g., when Lg-Z is 2-chloro-3 -nitro thiophene, the activating nitro group can be removed after coupling by reduction to the amine followed by diazotization and reduction to provide compounds of Formula Im).
Figure imgf000034_0001
Benzyl halides of Formula 38 can be prepared by radical halogenation of the corresponding alkyl compound of Formula 39a, see WO 96/38425. Benzyl halides can also be prepared by the acidic cleavage of the corresponding methyl ether of Formula 39b under conditions which provide the halide, see Scheme 31. Methods for preparing the corresponding compounds of Formula 38 wherein the T1 group has been replaced by T2 are described in WO 94/05620. Methods for preparing the corresponding compounds of Formula 38 wherein the T1 group has been replaced by T3 are described in EP-A-254,426, EP-A-299,694 and AU-A-55899/90.
Scheme 31
Figure imgf000034_0002
38
39a R1 8 = H 39b R1 = OCH3
Alternatively compounds of Formula 38 can be prepared from the corresponding alcohol of Formula 40 by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding β-halo-substituted derivatives. Alternatively, compounds of Formula 40 can be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methane sulfonyl chloride, / toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the corresponding β-alkylsulfonate of Formula 41. The reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine) see Scheme 32.
Figure imgf000035_0001
40
38 Lg = Cl, Br
41 Lg2 = OS02 or OS02 (4-Me-Ph)
Compounds of Formula 42a wherein T = T3 can be used to prepare compounds of Formula lo wherein T = T4 and Y3 = -CHR1 !θ-N=C(R8)- according to methods described in EP-A-585,751 and illustrated in Scheme 33. Compounds of Formula 42a are treated with N-hydroxyphthalimide. Treatment of this intermediate with HΝR6R5 yields compounds of Formula 42b wherein T3 is converted to T4 and B is CHR1 1ONH2. Treatment of compounds of Formula 42b with compounds of Formula 19 provides compounds of Formula lo.
Scheme 33
Figure imgf000035_0002
2) aq. HNR6R5
Compounds of Formula 40 can be prepared by reducing esters of Formula 44 or aldehydes of Formula 43 with an appropriate reducing agent, (M. Hudlicky, Reductions in Organic Chemistry; John Wiley & Sons pp. 147-160, (1986)). For example, diisobutylaluminum hydride (DIBAL-H) can be used to reduce 44 in an inert solvent such as methylene chloride, di ethyl ether or tetrahydrofuran. Compounds of Formula 43 can be reduced with sodium borohydride in a protic solvent such as methanol or ethanol, Scheme 34.
Scheme 34
Figure imgf000036_0001
43 40 44
Esters of Formula 44 can be prepared from anthranilic acid esters of Formula 45 according to the procedures described in Scheme 35. Esters 45 can be prepared from readily accessible anthranilic acids by esterification techniques well known in the art.
Figure imgf000036_0002
45 44
Compounds of Formula 43 can be prepared either by metal -halogen exchange in compounds of Formula 46a (when R19 = Cl, Br, I) or by metallation of compounds of Formula 46b (when R19 is H) with alkyllithium reagents in an inert solvent. Quenching of the metalated species with a formaldehyde equivalent (i.e., dimethylformamide or methyl chloro formate) yields compound of Formula 43 (see Scheme 36).
Figure imgf000037_0001
43
46a R19 = Cl, Br or I 46b R19 :
Compounds of Formula 46 are prepared from commercially available anilines of Formula 47 according to the procedures described for the synthesis of 44, Scheme 37.
Scheme 37
Figure imgf000037_0003
e
Figure imgf000037_0002
47
46
Compounds of Formula 37a (Compounds of Formula 37 where R17 = OH) can be prepared by the oxidative work-up of intermediate boronic acids of Formula 48. In turn compounds of Formula 48 can be prepared from compounds of Formula 46 by metallation using an alkyllithium followed by quenching with a trialkoxy borane, (Scheme 38), see Organic Synthesis via Boranes; Wiley: New York, (1975).
Scheme 38
Figure imgf000038_0001
R = Cj-C4 alkyl
Figure imgf000038_0002
37a
Alternatively compounds of Formula 37b (compounds of Formula 37 wherein R3 = CH3, R4- H and R17 = OH) can be prepared according to the route outlined in Scheme 39. Commercially available anilines of Formula 49a (where R3 = CH3 and P is a protecting group) are converted to the triazole of Formula 50 according to the procedures described above. Deprotection of the oxygen followed by alcoholysis yields compounds of Formula 37b. Alternatively compounds of Formula 49b (where R3 = H and P is a protecting group) are converted to the triazole 51 as previously described. Metallation at the ortho- position followed by quenching with an electrophile such as Mel yields compound of Formula 52 which is deprotected to yield compound of Formula 37b, Scheme 39.
Scheme 39
Figure imgf000039_0001
1) "deprotect"
2) CH3OH/NaOMe
Figure imgf000039_0002
37b
deprotect
Figure imgf000039_0003
Figure imgf000039_0004
Figure imgf000039_0005
Compounds of Formula 37c (compounds of Formula 37 where R3 = R4 = CH3 and R17 = OH) can be prepared from compounds of Formula 54 by procedures already described. Compounds of Formula 54 are prepared by nitration of commercially available 2,5-dimethylphenol 53 as taught in M. Quertani, P. Girard and H. B. Kagan, Tetrahedron Letters, 13, 4315 (1982), Scheme 40.
Figure imgf000040_0001
Compounds of Formula I wherein Y is -CR1 1=CR] '- can be prepared as illustrated in Scheme 41. Treatment of compounds of Formula 36a (compounds of Formula 36 where Lg is Cl, Br or I) with triphenylphosphine or a trialkylphosphite produces the corresponding phosphonium salt (Formula 55a) or phosphonate (Formula 55b), respectively. Condensation of the phosphorus compound with a base and a carbonyl compound of Formula Z(R] 1)C=O affords the olefin of Formula Ip. Compounds of Formula Ip wherein T = T2 may be prepared by methods described in EP-A-203,606, EP-A-474,042, EP-A-528,245 and FR 2,670,781. Compounds of Formula Ip wherein T = T3 may be prepared by methods described in EP-A-253,213 and EP-A-254,426.
Scheme 41
Figure imgf000041_0001
55a R 0 = P(CgH5)3+ (Cl. Br or l)
55b R 0 = P(O(Cj-C4 alkyl))2
Figure imgf000041_0002
Figure imgf000041_0003
iq
The olefin of Formula Ip can also be prepared by reversing the reactivity of the reactants in the Wittig or Horner-Emmons condensation. For example, 2-alkylphenyl derivatives of Formula 56 can be converted into the corresponding dibromo -compounds of Formula 57a as illustrated in Scheme 42 (see Synthesis, (1988), 330). The dibromo- compounds can be hydrolyzed to the carbonyl compounds of Formula 57b, which in turn can be condensed with a phosphorus-containing nucleophile of Formula 58 or 59 to afford the olefins of Formula Ip. Scheme 42
Figure imgf000042_0001
57a R21 = rfeR1 1
NBS = jV-bromosuccinimide 57b R21 = C(=0)RU
Figure imgf000042_0002
ip 59
Oximes of Formula Ir (Formula I wherein Y is -C(R8)=N-O-CHR1 J) can be prepared from carbonyl compounds of Formula 60 by condensation with hydroxylamine, followed by O-alkylation with electrophiles of Formula ZCHR1 !-(Cl, Br, or I) (Scheme 43). Alternatively, the O-substituted hydroxylamine can be condensed with the carbonyl compound of Formula 60 to yield oximes of Formula Ir directly. Compounds of Formula Ir wherein T = T2, T3, or T4 may be prepared by methods described in EP-A-499,823 and EP-A-596,254.
Scheme 43
Figure imgf000042_0003
Carbamates of Formula lu can be prepared by reacting benzyl alcohols of Formula 61 with iso(thio)cyanates of Formula 62 (Scheme 44). A base such as triethylamine can be added to catalyze the reaction. Compounds of Formula lu wherein T = T2, T3, or T4 may be prepared by methods described in WO 93/07116. Scheme 44
Figure imgf000043_0001
Compounds of Formula Iw may be prepared by methods described in EP-A- 178,826, EP-A-341,845 and EP-A-464,381.
Compounds of Formula Ix as defined in Scheme 45 may be prepared by methods described in EP-A-398,692.
Scheme 45
Figure imgf000043_0002
Iw γ6 = _0-, -CH2CH -, -CR1 !=CR] ,
-CH 0-, -OCH -, -CH2S(0)n- or -S(0)nCHRπ-
Compounds of Formula Iy (compounds of Formula I wherein Y7 = -O-) can be prepared by treating compounds of Formula 62 with a triarylbismuth compound or a substituted phenylboronic acid in the presence of cupric acetate and a tertiary amine such as pyridine or triethylamine as illustrated in Scheme 46. The use of organobismuth reagents in the preparation of diary 1 ethers is well known in the art (see Tetrahedron Lett., (1986), 17, 3619, and Tetrahedron Lett., (1987), 18, 887). Boronic acids are well known in the literature (see Ada Chem. Scand. 1993, 47, 221 and references therein). Scheme 46
Figure imgf000044_0001
Et3N, CufOA
62 iy γ7 = .o- It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula I may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula I. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula I.
One skilled in the art will also recognize that compounds of Formula I and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. H NMR spectra are reported in ppm downfield from tetramethylsilane; s = singlet, d = doublet, t = triplet, m = multiplet and br s = broad singlet. EXAMPLE 1
Step A: Preparation of N-(2-methoxy-6-methylphenyl)-2,2- dimethylhvdrazinecarboxamide To a stirred solution of phosgene (108 g, 1.09 moles) in ethyl acetate (750 mL) at 0 °C was added dropwise 2-methoxy-6-methylaniline (125.0 g, 911 mmol) dissolved in ethyl acetate (250 mL) over 20 min. The reaction mixture was slowly warmed to room temperature and was then heated at reflux for 1 h. The solution was cooled to room temperature and was concentrated under reduced pressure to provide the crude isocyanate as a dark red liquid which was redissolved in ethyl acetate (1 L) and cooled to 0 °C. 1,1-Dimethylhydrazine (55.0 g, 911 mmol) was added dropwise over 30 min and then the mixture was allowed to warm to room temperature and stir overnight. The mixture was cooled, filtered, and the solid was washed with ethyl acetate and dried to provide 200.0 g of the title compound of Step A as a white solid melting at 151-153 °C. ]H NMR (CDC13) δ 7.58 (br s,lH), 7.10 (t,lH), 6.84 (d,lH), 6.74 (d,lH), 5.22 (br s,lH), 3.80 (s,3H), 2.63 (s,6H), 2.31 (s,3H).
Step B: Preparation of 5-chloro-2.4-dihvdro-4-(2-methoxy-6-methylphenyl)-2- methyl-3H-l,2,4-triazol-3-one The title compound of Step A (100.0 g, 447.9 mmol) was suspended in ethyl acetate (1 L) and added dropwise, via mechanical pump, over 3.5 h to a stirring solution of phosgene (177 g, 1.79 moles) in ethyl acetate (1.5 L) which was heated at reflux. After the addition was complete, the mixture was heated at reflux for a further 3 h, cooled to room temperature and stirred overnight. The solution was concentrated under reduced pressure and the residue was dissolved in ethyl acetate and water and extracted four times with ethyl acetate. The combined organic phases were washed with saturated aqueous NaCl, dried (MgSO4), filtered and concentrated to afford 111.4 g of the title compound of Step B as a pale yellow solid melting at 132-134 °C. ]H NMR (CDC13) δ 7.34 (t,lH), 6.93 (d,lH), 6.85 (d,lH), 3.79 (s,3H), 3.54 (s,3H), 2.20 (s,3H).
Step C: Preparation of 5-chloro-2,4-dihydro-4-f2-hvdroxy-6-methylphenyl)-2-methyl-
3H-L2.4-triazol-3-one To a stirring solution of the title compound of Step B (15.0 g, 59.3 mmol) in benzene
(200 mL) at 0 °C was added aluminum chloride (23.7 g, 178 mmol) in small portions. The mixture was warmed to room temperature and stirred for 2 days. The mixture was poured over ice and water and then extracted four times with ethyl acetate. The combined organic phases were washed with saturated aqueous NaCl, dried (MgSO4), filtered and concentrated to an oil that was purified by flash column chromatography on silica gel to provide 13.6 g of the title compound of Step C as a pale orange solid melting at 175-178 °C. lH NMR (CDC13) δ 8.11 (s,lΗ), 6.92 (t,lH), 6.71 (d,lH), 6.41 (d,lH), 3.56 (s,3H), 2.12 (s,3H). Step D: Preparation of 2.4-dihydro-4-(2-hvdroxy-6-methylphenyl)-5-methoxy-2- methyl-3H- 2.4-triazol-3-one To a stirred solution of the title compound of Step C (133.5 g, 557.0 mmol) in tetrahydrofuran (1.5 L) was added dropwise sodium methoxide (25% by weight in methanol, 382 mL, 1.67 moles). The mixture was heated at reflux for 3 h, cooled to room temperature and then diluted with aqueous ammonium chloride and ethyl acetate. The aqueous layer was acidified (pH 4-5) with IN HCl and extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous NaCl, dried (MgSO4), filtered and concentrated to a dark brown solid which was triturated with ethyl acetate to afford 75.0 g of the title compound of Step D as a white solid melting at 194-196 °C. !H NMR (Me2SO- 6) δ 9.91 (s,lH), 7.17 (t,lH), 6.78 (m,2H), 3.84 (s,3H), 3.30 (s,3H), 2.03 (s,3H).
Step E: Preparation of 2.4-dihydro-5-methoxy-2-methyl-4-[6-methyl-2-r3- ftrifluoromethyl phenoxy]phenyll-3H- 1.2.4-triazol-3-one To a solution of 2,4-dihydro-4-(2-hydroxy-6-methylphenyl)-5-methoxy-2-methyl-3H- l,2,4-triazol-3-one (0.50 g, 2.13 mmol), (similarly prepared as in Steps A-D) in methylene chloride (15 mL) was added 3-trifluoromethylbenzeneboronic acid (0.88 g), anhydrous cupric acetate (0.38 g), and triethylamine (0.43 g). After stirring at room temperature for 27 hours, the crude reaction mixture was directly subjected to flash chromatography purification (silica gel, 30% to 38% ethyl acetate in hexane) to give the title compound (0.39 g, 47%), a compound of the invention, melting at 95-96 °C. lH NMR (CDC13) δ 7.35 (m,3Η), 7.14 (m,3H), 6.86 (d,lH), 3.82 (s,3H), 3.37 (s,3H), 2.28 (s,3H).
EXAMPLE 2 Step A Tris(4-trifluoromethoxyphenyl)bismuth
A solution of 4-(trifluoromethoxy)bromobenzene (Maybridge Chemical Co., 200 g) in 830 mL of anhydrous diethyl ether was added under nitrogen slowly to magnesium turnings (20.2 g) so as to maintain a gentle reflux once the Grignard reaction had been initiated. The reaction was refluxed for an additional 40 min. and cooled to 4 °C. A solution of bismuth trichloride (Aldrich Chemical Co., 74.6 g) in tetrahydrofuran (400 mL) was added dropwise so as to maintain the temperature below 12 °C. The reaction mixture was allowed to warm to room temperature and stirred for an additional 1 hour. A solution of saturated aqueous ammonium chloride (80 mL) was then added at 5 °C to quench the reaction. The reaction mixture was filtered and the filtrate was concentrated in vacuo to give an amber oil which was extracted with several portions of hexane at ice-bath temperature. The solids from the filtration were extracted with diethyl ether (800 mL). The hexane extract was then combined with the diethyl ether extracts and concentrated in vacuo to give a crude semi-solid which was triturated with hexane at dry ice temperature. The triturated solid was then extracted with refluxing hexane and the hexane extract was concentrated in vacuo to afford 74 g of the title compound. Η NMR (CDC13) δ 7.71 (d,6H), 7.25 (d,6H). Ste B Preparation of 214-dihvdro-5-methoxy-2-methyl-4-[6-methyl-2-|~4-
(trifluoromethoxy)phenoxy]phenyl]-3H- 1 ,2,4-triazol-3-one To a solution of 2,4-dihydro-4-(2-hydroxy-6-methylphenyl)-5-methoxy-2-methyl-3H- l,2,4-triazol-3-one (0.50 g, 2.13 mmol) (similarly prepared as in Steps A-D, Example 1) in methylene chloride (15 mL) was added the title compound from Step A, Example 2 above (2.32 g), anhydrous cupric acetate (0.38 g) and triethylamine (0.36 g). After stirring at room temperature for 25 hours, the crude reaction mixture was directly subjected to flash chromatography purification (silica gel, 30% ethyl acetate in hexane) to give the title compound (0.50 g, 59 %), a compound of the invention, melting at 75-77 °C. !H NMR (CDC13) δ 7.28 (t,lH), 7.15 (d,2H), 7.08 (d,lH), 7.00 (d,2H), 6.81 (d,lH), 3.86 (s,3H), 3.37 (s,3H), 2.27 (s, 3 H).
EXAMPLE 3 Preparation of 2,4-dihvdro-5-methoxy-2-methyl-4-[6-methyl-2-[(3- methylphenyl)methoxylphenyl]-3H-1.2.4-triazol-3-one To a solution of 2,4-dihydro-4-(2-hydroxy-6-methylphenyl)-5-methoxy-2-methyl-3H- l,2,4-triazole-3-one (0.24 g, 1 mmol) (similarly prepared as in Steps A-D, Example 1) in tetrahydrofuran (25 mL) was added, with stirring, sodium hydride (0.05 g 60% oil dispersion, washed with hexanes and slurried in 10 mL tetrahydrofuran). After 20 min., -bromo-rø-xylene (0.14 mL) was added and the resulting mixture was stirred at room temperature for 66 hours. The reaction was quenched by the addition of 20 mL of water and extracted with ethyl acetate (3x20 mL). The combined organic phases were dried (MgSO ) and concentrated in vacuo to yield the title compound, a compound of the invention, (0.22 g) as an oil. 'H NMR (CDC13) δ 7.24 (m,2H), 7.1 (m,3H), 6.85 (m,2H), 5.03 (s,2H), 3.88 (s,2H), 3.45 (s,3H), 2.35 (s,2H), 2.22 (s,3H).
EXAMPLE 4 Preparation of 2,4-dihvdro-5-methoxy-2-methyl-4-f 2-methyl-6- phenoxyphenylVSH-l^ -triazol-S-one To a solution of 2,4-dihydro-4-(2-hydroxy-6-methylphenyl)-5-methoxy-2-methyl-3H- l,2,4-triazol-3-one (1.0 g, 4.26 mmol) (similarly prepared as in Steps A-D, Example 1) in methylene chloride (20 mL) was added trisphenylbismuth (Aldrich Chemical Co., 3.76 g), anhydrous cupric acetate (0.77 g) and triethylamine (0.86 g). After stirring at room temperature for 21 hours, the crude reaction mixture was directly subjected to flash chromatography purification (silica gel, 30% ethyl acetate in hexane) to give the title compound (0.92 g, 70 %), a compound of the invention, melting at 58-60 °C. H NMR (CDC13) δ 7.28 (m, 3 H), 7.06 (m, 2H), 7.00 (m, 2H), 6.79 (d, IH), 3.86 (s, 3H), 3.38 (s, 3H), 2.27 (s, 3H).
EXAMPLE 5 Step A: 2.4-dihydro-5 -methoxy-2-methyl-4- 2-methyl-6- [(3 -nitro-2- thienyl)oxylphenyll-3H-1.2.4-triazol-3-one A stirred mixture of 2-chloro-3-nitrothiophene (5.5 g, 33.62 mmol), 2,4-dihydro-4-(2- hydroxy-6-methylphenyl)-5-methoxy-2-methyl-3H-l,2,4-triazol-3-one (7.9 g, 33.62 mmol) and potassium carbonate (13.94 g, 100.86 mmol) in anhydrous acetonitrile (67 mL) was heated at 80 °C for 6 hours under a nitrogen atmosphere. The reaction mixture was allowed to cool to room temperature overnight. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with three portions of ethyl acetate. The combined ethyl acetate layers were dried (MgSO4) and concentrated under reduced pressure to afford 10.1 g of a brown solid. This solid was triturated with hexanes and filtered to afford 9.44 g of the title compound of Step A as brown solid melting at 184-186 °C. !H NMR (CDC13) δ 7.37
(d, IH), 7.37 (t IH), 7.23 (d, IH), 7.07 (d, IH), 6.69 (d, IH), 3.95 (s, 3H), 3.38 (s, 3H), 2.31 (s, 3H). The aqueous layer was further extracted with three portions of dichloromethane. The combined extracts were dried (MgSO4) and concentrated under reduced pressure to afford 0.9 g of a light brown solid. This solid was triturated with hexanes and filtered to afford an additional 0.76 g of the title compound of Step A as a gray solid melting at 199-200 °C.
Step B: 2,4-dihydro-5-methoxy-2-methyl-4- 2-methyl-6-('2-thienyloxy phenyll-3H-
1.2.4-triazol-3-one To a mechanically stirred solution of the title compound of Step A (3.0 g, 8.29 mmol) in acetic acid (96 mL) and water (13 mL) heated to 75 °C under a nitrogen atmosphere was added portionwise iron powder (1.53 g, 27.42 mmol). The reaction mixture was heated at 75-80 °C for 45 minutes and then at 80-90 °C for 3.5 hours. The reaction mixture was cooled (ice bath), diluted with water and dichloromethane and then filtered through a Celite® pad. The layers of the filtrate were separated. The organic layer was washed with one portion of saturated aqueous NaΗC03, dried (Na2SO4) and concentrated under reduced pressure to give 2.4 g of a dark solid. To a stirred solution of this solid in anhydrous tetrahydrofuran (129 mL) cooled to 0 °C under a nitrogen atmosphere was added concentrated aqueous HCl (3.24 mL) and then /7-butyl nitrite (0.87 g, 8.45 mmol). After 1 hour at 0 °C, 50 wt. %> aqueous hypophosphorous acid (1.11 g, 8.41 mmol) was added. The reaction mixture was allowed to warm to room temperature overnight. The reaction mixture was concentrated under reduced pressure and flash chromatography of the residue on silica gel with 3:7 ethyl acetate:hexane afforded a brown oil. This oil was twice dissolved in toluene and concentrated under reduced pressure and the resulting residue was dried in vacuo to give 113 mg of the title compound of Step B, a compound of the invention, as a dark brown oil.
Figure imgf000048_0001
0.45 (silica gel, 2:1 ethyl acetate:hexane). *H NMR (CDC13) δ 7.26 (t, IH), 7.05 (d, IH), 6.91 (d, IH), 6.77-6.83 (m, 2H), 6.55 (dd, IH), 3.93 (s, 3H), 3.45 (s, 3H), 2.27 (s, 3H).
EXAMPLE 6 4- 2-[(5-bromo-2-thienyl)oxy]-6-methylphenyll-214-dihvdro-5-methoxy-2- methyl-3H- 2,4-triazol-3-one
To a stirred solution of the title compound of Step B in Example 5 (43 mg, 0.136 mmol) in NN-dimethylformamide (1 mL) at room temperature under a nitrogen atmosphere was added first N-bromosuccinimide (30 mg, 0.142 mmol) and then 2 drops of a dilute solution of HBr in NN-dimethylformide (prepared by the addition of 2 drops of 48% aqueous HBr to 1 mL of NN-dimethylformamide). After 2 hours at room temperature, the reaction mixture was diluted with water and then ethyl acetate. The layers were separated and the aqueous layer was extracted with two portions of ethyl acetate. The combined organic layers were washed with three portions of water and then one portion of saturated aqueous ΝaCl. After drying (Νa2SO4), the organic layer was concentrated under reduced pressure to give an oil which contained some NN-dimethylformamide. This oil was dissolved in ethyl acetate and the resulting solution was washed with four portions of water and one portion of saturated aqueous ΝaCl. After drying (Νa2SO4), the organic layer was concentrated under reduced pressure to an oil which was dissolved in dichloromethane and reconcentrated followed by drying in vacuo to give 46 mg of the title compound of Example 6, a compound of the invention, as a brown oil. !H NMR (CDCI3) δ 7.28 (t, IH) 7.07 (d, IH), 6.95 (d, IH), 6.79 (d, IH), 6.35 (d, IH), 3.94 (s, 3H), 3.45 (s, 3H), 2.26 (s, 3H). By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 13 can be prepared. The following abbreviations are used in the Tables which follow: t = tertiary, i = iso, F - fluorine, Cl = chlorine, Br = bromine, I = iodine, Me = methyl, Et = ethyl, Pr = propyl, z'-Pr = isopropyl, Bu = butyl, CF3 = trifluoromethyl, SCF3 = trifluoromethylthio, SCHF2 = difluoromethylthio, OMe = methoxy, OCF3 = trifluoromethoxy, OCHF = difluoromethoxy, SMe = methylthio (CH3)3Si = trimethylsilyl and CN = cyano.
Structure for Tables 1 a. 1 b and 1 c
Figure imgf000049_0001
Table la
R3 = CH3, R4 = H
Y = -0-
Phenyl 3-OMe-phenyl 4-CF3 -phenyl
3-Me-phenyl 3-F-phenyl 3-OCF3-phenyl
4-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
2-Me-phenyI 4-SCHF2-phenyl 4-SCH3-phenyl
3-cyclohexyl-phenyI 4-CF3 -2 -pyridinyl 6-CF3-2-pyridinyl 5-CF3 -2 -pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 5,6,7, 8-tetrahydro-2-naphthalenyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 4-/-Bu-phenyl 4-OCF3-phenyl 3-/-Bu-phenyl 4-SCF3-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4,6-diMe-2-pyridinyl pyrazinyl 4-CF3-6-Me-2 -pyridinyl 3,5-di(CF3)-phenyl 3-(CH3C≡C)-phenyl
Y = -CH20-
phenyl 3-CF3-phenyl 2-Me-5-/-Pr-phenyl 2-Me-4-OCH3 -phenyl
4-OCF3-phenyl 2-Me-5-CF3-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl
3,5-di(CF3)-phenyl 2-Me-4-OCHF2-phenyl 6-CF3-2-pyridinyl 3-OCF3-phenyl
4-CF3-2-pyridinyl 4-Me-2-pyridinyl 2-Me-4-OCF3-phenyl 5-Me-2-pyridinyl
3,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 6-OCF3-2-pyridinyl
4-CF3 -6-Me-2-pyridiny 1 3-Me-2-pyridinyl 4-Cl-2-pyrimidinyl 6-Me-2-pyridinyl
4-Cl-2-pyrimidinyl 3-Et-phenyl 2,6-diMe-4-pyridinyl 2,4,6-triMe-phenyl
3-Cl-2-pyridinyl 6-Cl-4-pyrimidinyl 1-napthalenyl 2,3 ,6-triMe-pheny 1
6-Cl-2-pyrazinyl 4-CF3 -2-pyrimidinyl 6-CF3-4-pyrimidinyl 2-/-Pr-phenyl
3-Me-2-pyridinyl 4-Cl-2-pyridinyl
-OCH2-
2-Me-phenyl 2,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 4-Me-phenyl 4-/-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-?-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 2-(5, 6,7,8 tetrahydro)naphthalenyl
Y = -CH20-N=C(CH3)-
Z Z Z 3-Me-phenyl 4-CF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Br-phenyl 3,5-di(CF3)-phenyl 4-0CHF2-phenyl 4- -Bu-phenyl 3-t-Bu-phenyl 5-CF3-2-pyridinyl 4-OCF3-phenyl 3-OCHF2-phenyl 5-Me-2- pyridinyl 4-CF3-6-Me-2-pyridinyl 4-Me-2- pyridinyl 4,6-diMe-2-pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 6-OMe-2-pyridinyl 2,6-diMe-4-pyridinyl
2,6-diCl-4-pyridinyl 5-OCF3-2-pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl _ z
5-OCHF2-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-pyridinyl 3-(2,2,2-trifluoroethoxy)phenyl
6-OCHF2-2-pyridinyl 3-Et-phenyl 1-naphthalenyl 1 ,2,3 ,4-tetrahydro-2-naphthalenyl
3-SMe-phenyl 3-ethynylphenyl r-Bu
Y = -CH=N-OCH(CH3)-
4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl
3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl
3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl
3-OCHF2-phenyl 4-CF3-2 -pyridinyl 5-CF3-2-pyridinyl 6-CF3 -2 -pyridinyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3 -6-Me-2-pyridinyl
4-OCF3 -2-pyridiny 1 5 -OCF3 -2 -pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl
5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-ι'-Bu-phenyl 4- -Bu-phenyl
Y = -CH2-SC(Et)=N-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2-SC(=S)NMe-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl CH2CH2-/-Bu t- u 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl
5-CF3-2-pyridinyl 5-Br-6-Me-2 -pyridinyl
Y = -CH2S-
2-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl l-Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me- 1 ,3,4-thiadiazol-2-yl
Y = -CH20-N=C(CH3)CH2S-
Z Z
3-Me-phenyl 2-Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl 3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3 ,6-diMe-2-pyridinyl
Y = -CH=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3 -CF3 -phenyl 4-CF3-phenyl 2-naphthalenyl 4-CF3-2-pyridinyl 6-CF3-2-pyridinyl Y = -CH=N-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3 -CF -phenyl 4-CF3-phenyl 3-0CF3-phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl
3,5-di(CF3)-phenyl 3 -OCF3 -phenyl 4-OCF3 -phenyl CH3 t-B 2-naphthalenyl 4-r-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl 6-CF3-2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-z-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2 -pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl Y = -SCH2- z
2-Me-phenyl 2,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 4-Me-phenyl 4-/-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-/-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridirιyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y Y direct bond CH2Br direct bond CHBrCH3 -CH20-N=C(SCH3)- 3 -CF3 -phenyl -CH20-N=C(cyclopropyl)- 3 -CF3 -phenyl -CH20-N=C(SCH3 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl -CH20-N=C(SCH3> 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl -CH20-N=C(SCH3)- 4-CF3 -phenyl -CH20-N=C(cyclopropyl)- 4-CF3 -phenyl -CH20-N=C(SCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl -CH20-N=C(SCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl -CH20-N=C(SCH3 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl -CH20-N=C(SCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Table lb
R3 = H, R4 = CH3
Y = -0-
Phenyl 3-OMe-phenyl 3-CF3-phenyl
3-Me-phenyl 3-F-phenyl 4-CF3-phenyl
4-Me-phenyl 4-Cl-phenyl 3-OCF3-phenyl
2-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
3-cyclohexyl-phenyl 4-SCHF2-phenyl 4-SCH3-phenyl
6-Cl-4-pyrimidinyl 6-C1 — 2-pyrazinyl 6-CF3-2-pyridinyl
5-CF3-2-pyridinyl 4-CF3-2-pyridinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl) 4-OCF3 -phenyl 3-NBu-phenyl 4-/-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4-SCF3-phenyl pyrazinyl 4-CF3-6-Me-2-pyridinyl 4 ,6-diMe-2-pyridiny 1 3,5-di(CF3)-phenyl 3-(CH3C≡C)-phenyl Y = -CH20-
2-Me-phenyl 2,5-diMe-phenyl 2-Me-5-/'-Pr-phenyl phenyl
2-Me-5-Cl-phenyl 2-Me-5-CF3-phenyl 2-Me-4-OCH3-phenyl 2,4-diCl-phenyl
3,5-di(CF3)-phenyl 4-Me-phenyl 3 -CF -phenyl 3-OCF3-phenyl
3-OCHF2-phenyl 3-Me-phenyl 2-Me-4-OCF3-phenyl 2-Me-4-OCHF2-phenyl
4-OCF3-phenyl 5-CF3-2 -pyridinyl 4-CF3-2-pyridinyl 4-OCHF2-phenyl
4-CF3 -6-Me-2-pyridiny 1 5-Me-2-pyridinyl 6-CF3-2-pyridinyl 6-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 4-Me-2-pyridinyl 2,6-diMe-4-pyridinyl 3-Me-2-pyridinyl
3,6-diMe-2-pyridinyl 6-Cl-4-pyrimidinyl 4-Cl-2-pyrimidinyl 6-OCF3-2-pyridinyl
6-Cl-2-pyrazinyl 2,4,6-triMe-phenyl 4-Cl-2-pyrimidinyl 2-/-Pr-phenyl
1 -napthalenyl 3-Et-phenyl 3-Me-2-pyridinyl 4-CF3-2-pyrimidinyl
3-Cl-2-pyridinyl 4-Cl-2-pyridinyl 2,3,6-triMe-phenyl 6-CF3-4-pyrimidinyl
Y = -OCH2- Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF -phenyl 4-Me-phenyl 4-?-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-?-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(CH3)-
Z 3-Cl-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3,5-diBr-phenyl 4-CF3 -phenyl 3,5-di(CF3)-phenyl 3 -OCF3 -phenyl 4-Br-phenyl 3-r-Bu-phenyl 4-OCHF2-phenyl 4-/-Bu-phenyl 3-OCHF2-phenyl 5-CF3-2-pyridinyl 4-OCF3-phenyl 4-CF -2-pyridinyl 5-Me-2-pyridinyl 3-4-diCl-phenyl 4-Me-2-pyridinyl 4,6-diMe-2 -pyridinyl 4-CF3 -6-Me-2-pyridinyl 6-CF3-2-pyridinyl 6-OMe-2-pyridinyl 6-Me-2-pyridinyl 2,6-diCl-4-pyridinyl 5-OCF3-2-pyridinyl 2,6-diMe-4-pyridinyl 4-OCF3-2-pyridinyl 5-OCHF2-2-pyridinyl 4-OMe-2-pyridinyl 4-OCHF -pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl 6-OCF3 -2-pyridiny 1 2-naphthalenyl 3-(2,2,2-trifluoroethoxy)phenyl 6-OCHF2-2-pyridinyl 3-Et-phenyl 1 -naphthalenyl 1 ,2,3 ,4-tetrahydro-2-naphthalenyl t-Bu 3-SMe-phenyl 3-ethynylphenyl Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3 -2-pyridiny 1 5-CF3 -2-pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-OCF3 -2-pyridiny 1 5-OCF3 -2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-/-Bu-phenyl 4-/-Bu-phenyl
Y = -CH2-SC(Et)=N-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2-SC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF -2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF -phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl CH2CH2-/-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl Y = -CH2S-
2-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl 1 -Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me-2,( 1 ,3 ,4-thiadiazolyl)
Y = -CH20-N=C(CH3)CH2S- z z
3-Me-phenyl 2-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5- -Pr-phenyl 3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3 -2-pyridiny 1 5-CF3-2-pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3 -OCF3 -phenyl 4-OCF3 -phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3 ,6-diMe-2-pyridiny 1
Y = -CH=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 2-naphthalenyl 4-CF3-2-pyridinyl 6-CF3 -2-pyridiny 1
Y = -CH=N-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl
2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3-phenyl CH3 t-Bu 2-naphthalenyl 4- -Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl
6-CF3 -2-pyridiny 1 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl 6-CF3-2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-^-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl Y = -SCH2- z
2-Me-phenyl 2,5-diMe-phenyl 3-CF -phenyl 4-CF3 -phenyl 4-Me-phenyl 4-/-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-/-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7, 8-tetrahydro-2-naphthalenyl
direct bond CH2Br direct bond CHBrCH3
-CH20-N=C(SCH3)- 3-CF3-phenyl -CH20-N=C(cyclopropyl)- 3 -CF3 -phenyl
-CH20-N=C(SCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl
-CH20-N=C(SCH3 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl
-CH20-N=C(SCH3)- 4-CF3-phenyl -CH20-N=C(cyclopropyl)- 4-CF3 -phenyl
-CH20-N=C(SCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3 -phenyl
-CH20-N=C(SCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl
-CH20-N=C(SCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl
-CH20-N=C(SCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Table lc R3 = R4 = CH3
Y = -0-
Phenyl 3-OMe-phenyl 3-CF3-phenyl
3-Me-phenyl 3-F-phenyl 4-CF3-phenyl
4-Me-phenyl 4-Cl-phenyl 3 -OCF3 -phenyl
2-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
3 -cyclohexyl-pheny 1 4-SCHF2-phenyl 4-SCH3-phenyl
6-Cl-4-pyrimidinyl 6-Cl-2-pyrazinyl 6-CF3-2-pyridinyl
5-CF3-2-pyridinyl 4-CF3 -2 -pyridinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7, 8-tetrahydro-2-naphthalenyl) 4-OCF3-phenyl 3-Z-Bu-phenyl 4-/-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4-SCF3 -phenyl pyrazinyl 4-CF3 -6-Me-2-pyridiny 1 4,6-diMe-2-pyridinyl 3,5-di(CF3)-phenyl 3-(CH3C≡C)-phenyl Y = -CH20-
2-Me-phenyl 2,5-diMe-phenyl 2-Me-5- -Pr-phenyl phenyl
2-Me-5-Cl-phenyl 2-Me-5-CF3-ρhenyl 2-Me-4-OCH3-phenyl 2,4-diCl-phenyl
3,5-di(CF3)-phenyl 4-Me-phenyl 3-CF3-phenyl 3 -OCF3 -phenyl
3-OCHF2-phenyl 3-Me-phenyl 2-Me-4-OCF3-phenyl 2-Me-4-OCHF2-phenyl
4-OCF3-phenyl 5-CF3-2-pyridinyl 4-CF3-2-pyridinyl 4-OCHF2-phenyl
4-CF3 -6-Me-2-pyridiny 1 5-Me-2-pyridinyl 6-CF3-2-pyridinyl 6-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 4-Me-2-pyridinyl 2,6-diMe-4-pyridinyl 3-Me-2-pyridinyl
3 ,6-diMe-2-pyridinyl 6-Cl-4-pyrimidinyl 4-Cl-2-pyrimidinyl 6-OCF3 -2 -pyridinyl
6-Cl-2-pyrazinyl 2,4,6-triMe-phenyl 4-Cl-2-pyrimidinyl 2-/'-Pr-phenyl
1-napthalenyl 3-Et-phenyl 3-Me-2-pyridinyl 4-CF3 -2-pyrimidinyl
3-Cl-2-pyridinyl 4-Cl-2-pyridinyI 2,3 ,6-triMe-pheny 1 6-CF3-4-pyrimidinyl
Y = -OCH2- Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 4-Me-phenyl 4- -Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3- -Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2 -pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-/-Bu-phenyl 3-?-Bu-phenyl 3-0CF3-phenyl 4-OCF3-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3 -2-pyridiny 1 5-CF3-2 -pyridinyl 4-CF3 -6-Me-2-pyridiny 1 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3 -2 -pyridinyl 4,6-diMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2-pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2 -pyridinyl 6-OCF3 -2-pyridinyl 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-Et-phenyl 3-(2,2,2-trifluoroethoxy)phenyl l,2,3,4-tetrahydro-2-naphthalenyl t-Bu 1 -naphthalenyl 3-SMe-phenyl 3-ethynylphenyl Y = -CH=NOCH(CH3>
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF -2-pyridinyl 6-OCHF2-2-pyridinyl 3-/-Bu-phenyl 4-<*-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2 -pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl CH2CH2-/-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5 -Br-6-Me-2-pyridiny 1 Y = -CH2S-
2-Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl 1 -Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me-l,3,4-thiadiazol-2-yl
Y = -CH20-N=C(CH3)CH2S- z z
3-Me-phenyl 2-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl
3-Cl-phenyl 4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl
2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl
4-CF3 -phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl
2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl 3-Et-phenyl 6-CF3-2-pyridinyl
4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl
4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z Z Z Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl
3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl
2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3,6-diMe-2-pyridinyl
Y = -CH=C(CH3)-
Z Z Z Z
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-CF3-phenyl
4-CF3 -phenyl 2-naphthalenyl 4-CF3-2-pyridinyl 6-CF3-2-pyridinyl
Y = -CH=N-N=C(CH3)-
Z Z Z Z
3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl
3-OCF3-phenyl 4-OCF3 -phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl
2-naphthalenyl 4,6-diMe-2 -pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3-phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3-phenyl CH3 t-Bu 2-naphthalenyl 4-/-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3 -2 -pyridinyl
6-CF3-2-pyridinyl 4,6-diMe-2 -pyridinyl 4-CF3-2-pyrimidinyl 6-CF3 -2-pyrimidinyl
Y = -CH=N-N(CH3>
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF -phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-/-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF -2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl Y = -SCH2- z
2-Me-phenyl 2,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 4-Me-phenyl 4-/-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-/-Bu-phenyI 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-terrahydro-2-naphthalenyl
Y direct bond CH2Br direct bond CHBrCH3 -CH20-N=C(SCH3)- 3 -CF3 -phenyl -CH20-N=C(cyclopropyl)- 3-CF3-phenyl -CH20-N=C(SCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl -CH20-N=C(SCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl -CH20-N=C(SCH3)- 4-CF3-phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl -CH20-N=C(SCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl -CH20-N=C(SCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl -CH20-N=C(SCH3)- 3-Cl-phenyl -CH 0-N=C(cyclopropyl)- 3-Cl-phenyl -CH20-N=C(SCH3 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Structure for Tables 2a, 2b and 2c
Figure imgf000064_0001
Table 2a R3 = CH3, R4 = H
Y = -0-
Phenyl 3-OMe-phenyl 4-CF3-phenyl
3-Me-phenyl 3-F-phenyl 3 -OCF3 -phenyl
4-Me-phenyl 3-I-phenyl 3-SCH3-phenyl
2-Me-phenyl 3-SCHF2-phenyl 4-SCH3-phenyl
3-cyclohexyl-phenyl 4-SCHF2-phenyl 6-CF3-2-pyridinyl
5-CF3-2-pyridinyl 4-CF3-2-pyridinyl 6-Me-2-pyridinyl 6-(2,2,2-trifluoroethoxy)-4- 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4- pyrimidinyl 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl 4-Me-2-pyridinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 4-OCF3-phenyl 3-f-Bu-phenyl 4-/-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4-SCF3-phenyl pyrazinyl 4-CF3-6-Me-2-pyridinyl 3-CN-phenyl 5-OCF3-2-thiazolyl 5-(CH3)3Si-2-thiazolyl 4, 6-diMe-2 -pyridinyl 5-Cl-2-thiazolyl 5-Me-2-thiazolyl 3,5-di(CF3)-phenyl 5-I-2-thiazolyl 5-SCH3-2-thiazolyl 5-CF3-2-thiazolyl 4-Me-5-Cl-2-thiazolyl 4-Me-5-I-2-thiazolyl 5-CN-2-thiazolyl 4,5-diMe-2-thiazolyl 4-Me-5-CN-2-thiazolyl 4-Me-5-Br-2-thiazolyl 4-Br-2-thiazolyl 4-I-2-thiazolyl 4-Me-5-CF3-2-thiazolyl 4-Me-2-thiazolyl 4-CF3-5-Me-2-thiazolyl 4-Cl-2-thiazolyl 4-CN-2-thiazolyl 3-(HC≡C)-phenyl 3-(CH3C≡C)-phenyl 3-((CH3)3CC≡C)-phenyl 3-((CH3)3SiC≡C)-phenyl 3-( -C≡C)-phenyl 5-Me-2-thienyl
5-(CH3)3C-2-thienyl 5-Cl-2-thienyI 5-Br-2-thienyl
5-I-2-thienyl 4-Me-2-thienyl 4-(CH3)3C-2-thienyl
4-Cl-2-thienyl 4-Br-2-thienyl 4-I-2-thienyl
4,5-diMe-2-thienyl 4-Me-5-Cl-2-thienyl 4-Me-5-Br-2-thienyl
4-Me-5-I-2-thienyl 3-Cl-2-thienyl 5-Me-3-thienyl
5-(CH3)3C-3-thienyl 5-Cl-3-thienyl 5-Br-3-thienyl
5-I-3-thienyl 4-Me-3-thienyI 4-(CH3)3C-3-thienyl
4-Cl-3-thienyl 4-Br-3-thienyl 4-I-3-thienyl
4,5-diMe-3-thienyl 4-Me-5-Cl-3-thienyl 4-Me-5-Br-3-thienyl
4-Me-5-I-3-thienyl 2-Cl-3-thienyl
Y = -CH20-
phenyl 3-CF3-phenyl 2-Me-5-/-Pr-phenyl 2-Me-4-OCH3-phenyl
4-OCF3-phenyl 2-Me-5-CF3 -phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3,5-di(CF3)-phenyl 2-Me-4-OCHF2-phenyl 6-CF3-2-pyridinyl 3-OCF3-phenyl 4-CF3 -2-pyridiny 1 4-Me-2-pyridinyl 2-Me-4-OCF3-phenyl 5-Me-2-pyridinyl 3 ,6-diMe-2-pyridiny 1 5-CF3 -2-pyridinyl 4,6-diMe-2-pyridinyl 6-OCF3 -2 -pyridinyl 4-CF3 -6-Me-2-py ridinyl 3-Me-2-pyridinyl 4 Cl-2-pyrimidinyl 6-Me-2-pyridinyl 4-Cl-2-pyrimidinyl 3-Et-phenyl 2,6-diMe-4-pyridinyl 2,4,6-triMe-phenyl 3-Cl-2-pyridinyl 6-Cl-4-pyrimidinyl 1-napthalenyl 2,3,6-triMe-phenyl 6-Cl-2-pyrazinyl 4-CF3 -2-pyrimidiny 1 6-CF3-4-pyrimidinyl 2-/-Pr-phenyl 3-Me-2-pyridinyl 4-Cl-2-pyridinyl
Y = -OCH2- Z
2-Me-phenyl 2,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 4-Me-phenyl 4-/-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-^-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(CH3)-
Z 3-Me-phenyl 4-CF3 -phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Br-phenyl 3,5-di(CF3)-phenyl 4-OCHF2-phenyl 4-?-Bu-phenyl 3-/-Bu-phenyl 5-CF3-2-pyridinyl 4-OCF3-phenyl 3-OCHF2-phenyl 5-Me-2- pyridinyl 4-CF3-6-Me-2-pyridinyl 4-Me-2- pyridinyl 4,6-diMe-2-pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 6-OMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 5 -OCF3 -2-pyridiny 1 4-OMe-2-pyridinyI 4-OCF -2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCF3 -2-pyridiny 1 4-OCHF2-pyridinyl 3-(2,2,2-trifluoroethoxy)phenyl 6-OCHF2-2-pyridinyl 3-Et-phenyl 1 -naphthalenyl 2-F-5-CF3-phenyl 3-SMe-phenyl 3-ethynylphenyl 2-F-5-Me-phenyl l,2,3,4-tetrahydro-2-naphthalenyl t-Bu
Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3 -6-Me-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-/-Bu-phenyl 4-/-Bu-phenyl Y = -CH2SC(Et)=N-
Z 4-CF3-phenyl 3-CF3-phenyl 4-0CF3-phenyl 3-0CF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2-SC(=S)NMe-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl CH2CH2-/-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2S-
2-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 2,5-diMe-phenyl
2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me- 1 ,2,4-triazol-3-yl 2-naphthalenyl l-Me-2-imidazolyl
4-Me-2-pyrimidinyl 5-Me- 1 ,3,4-thiadiazol-2-yl
Y = -CH20-N=C(CH3)CH2S-
Z z z Z Z
3-Me-phenyl 2-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et -phenyl 2,5-diMe-phenyl 2-naphthalenyl Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl 3-Et-phenyl 6-CF3 -2-pyridiny 1 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3,6-diMe-2-pyridinyl
Y = -CH=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-CF3-phenyl 4-CF3 -phenyl 2-naphthalenyl 4-CF3 -2-pyridiny 1 6-CF3-2-pyridinyl
Y = -CH=N-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3-phenyl CH3 t-Bu 2-naphthalenyl 4-/-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyi 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-ρyrimidinyl 6-CF3-2-pyrimidinyl Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 2-naphthalenyl 4-/-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3 -2-pyridiny 1 5-CF3 -2-pyridinyl 6-CF -2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3 -2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2 -pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -SCH2-
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Me-phenyl 4- -Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-/-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3-pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6, 7, 8-tetrahydro-2 -naphthalenyl
Y direct bond CH2Br direct bond CHBrCH3
-CH20-N=C(SCH3)- 3-CF3-phenyl -CH20-N=C(cyclopropyl)- 3-CF3-phenyl
-CH20-N=C(SCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-0CF3-phenyl
-CH20-N=C(SCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl
-CH20-N=C(SCH3)- 4-CF3-phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl
-CH20-N=C(SCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-0CF3-phenyl Y
-CH20-N=C(SCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl -CH20-N=C(SCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl -CH20-N=C(SCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Table 2b R3 = H, R4 = CH3 γ = -o-
Phenyl 3-OMe-phenyl 3 -CF3 -phenyl
3-Me-phenyl 3-F-phenyl 4-CF3-phenyl
4-Me-phenyl 3-I-phenyl 3-OCF3-phenyl
2-Me-phenyl 4-Cl-phenyl 3 -SCH3 -phenyl
3 -cyclohexy 1-pheny 1 3-SCHF2-phenyl 4-SCH3-phenyl
6-Cl-4-pyrimidinyl 4-SCHF2-phenyl 6-CF3-2-pyridinyl
5-CF3 -2-pyridmy 1 6-Cl-2-pyrazinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 4-CF -2 -pyridinyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 5-Me-2-pyridinyl pyrimidinyl pyrimidinyl 4-(2,2,2-trifluoroethoxy)-2- 3,5-diMe-phenyl 2-naphthalenyl pyrimidinyl 4-OCF3-phenyl 3-/-Bu-phenyl 5,6,7,8-tetrahydro-2 -naphthalenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4-/-Bu-phenyl pyrazinyl 4-CF3-6-Me-2 -pyridinyl 4-SCF3-phenyl 3,5-di(CF3)-phenyl 5-OCF3-2-thiazolyl 3-CN-phenyl 5-CF3-2-thiazolyl 5-Cl-2-thiazolyl 4,6-diMe-2-pyridinyl 5-CN-2-thiazolyl 5-I-2-thiazolyl 5-(CH3)3Si-2-thiazolyl 4-Me-5-Br-2-thiazolyl 4-Me-5-Cl-2-thiazolyl 5-Me-2-thiazolyl 4-Me-5-CF3-2-thiazolyl 4,5-diMe-2-thiazolyl 5-SCH3-2-thiazolyl 4-Cl-2-thiazolyl 4-Br-2-thiazolyl 4-Me-5-I-2-thiazolyl 4-CN-2-thiazolyl 4-Me-2-thiazolyl 4-Me-5-CN-2-thiazolyl 4-CF3-5-Me-2-thiazolyl 4-I-2-thiazolyl 3-(HC≡C)-phenyl 3-(CH3C≡C)-phenyl 3-((CH3)3CC≡C)-phenyl 3-((CH3)3SiC≡C)-phenyl 3-( [>-C≡C)-phenyl
5-Me-2-thienyl 5-(CH3)3C-2-thienyl 5-Cl-2-thienyl
5-Br-2-thienyl 5-I-2-thienyl 4-Me-2-thienyl
4-(CH3)3C-2-thienyl 4-Cl-2-thienyl 4-Br-2-thienyl
4-I-2-thienyl 4,5-diMe-2-thienyl 4-Me-5-Cl-2-thienyl
4-Me-5-Br-2-thienyl 4-Me-5-I-2-thienyl 3-Cl-2-thienyl 5-Me-3-thienyl 5-(CH3)3C-3-thienyl 5-Cl-3-thienyl
5-Br-3-thienyl 5-I-3-thienyl 4-Me-3-thienyl
4-(CH3)3C-3-thienyl 4-Cl-3-thienyl 4-Br-3-thienyl
4-I-3-thienyl 4,5-diMe-3-thienyl 4-Me-5-Cl-3-thienyl
4-Me-5-Br-3-thienyl 4-Me-5-I-3-thienyl 2-Cl-3-thienyl
Y = -CH20-
2-Me-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl phenyl
2-Me-5-Cl-phenyl 2-Me-5-CF3-phenyl 2-Me-4-OCH3 -phenyl 2,4-diCl-phenyl
3,5-di(CF3)-phenyl 4-Me-phenyl 3-CF3-phenyl 3-OCF3-phenyl
3-OCHF2-phenyl 3-Me-phenyl 2-Me-4-OCF3-phenyl 2-Me-4-OCHF2-phenyl
4-OCF3 -phenyl 5-CF3-2-pyridinyl 4-CF3-2-pyridinyl 4-OCHF2-phenyl
4-CF3-6-Me-2-pyridinyl 5-Me-2-pyridinyl 6-CF3-2-pyridinyl 6-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 4-Me-2-pyridinyl 2,6-diMe-4-pyridinyl 3-Me-2-pyridinyl
3 ,6-diMe-2-pyridiny 1 6-Cl-4-pyrimidinyl 4-Cl-2-pyrimidinyl 6-OCF3 -2-pyridiny 1
6-Cl-2-pyrazinyl 2,4,6-rriMe-phenyl 4-Cl-2-pyrimidinyl 2- -Pr-phenyl
1-napthalenyl 3-Et-phenyl 3-Me-2-pyridinyl 4-CF3-2-pyrimidinyl
3-Cl-2-pyridinyl 4-Cl-2-pyridinyl 2,3,6-triMe-phenyl 6-CF3-4-pyrimidinyl
Y = -OCH2-
2-Me-phenyl 2,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 4-Me-phenyl 4-/-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-/-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(CH3)-
Z 3-Cl-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3,5-diBr-phenyl 4-CF3-phenyl 3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-Br-phenyl 3-Λ-Bu-phenyl 4-OCHF2-phenyl 4-/-Bu-phenyl 3-OCHF2-phenyl 5-CF3-2-pyridinyl 4-OCF3 -phenyl 4-CF3-2-pyridinyl 5-Me-2- pyridinyl 3-4-diCl-phenyl 4-Me-2- pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 6-CF -2-pyridinyl 6-OMe-2-pyridinyl 6-Me-2-pyridinyl 2,6-diCl-4-pyridinyl 5-OCF3-2-pyridinyl 2,6-diMe-4-pyridinyl 4-OCF3 -2 -pyridinyl
5-OCHF2-2-pyridinyl 4-OMe-2-pyridinyl 4-OCHF -pyridinyl
3-(2,2,2-trifluoroethoxy)phenyl 6-OCF3-2-pyridinyl 3-Et-phenyl
1 -naphthalenyl 6-OCHF2-2-pyridinyl t-Bu
3-SMe-phenyl l,2,3,4-tetrahydro-2-naphthalenyl 3-ethynylphenyl
2-F-5-Me-phenyl 2-F-5-CF3-phenyl
Y = -CH=NOCH(CH3)-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF -2-pyridinyl 5-CF3-2-pyridinyl 6-CF3 -2 -pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3 -6-Me-2-pyridiny 1 4-OCF3-2 -pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-/-Bu-phenyl 4-/-Bu-phenyl
Y = -CH2-SC(Et)=N-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2-SC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3 -OCF3 -phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl CH2CH2-/-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5 -Me-2-pyridiny 1 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2S-
2-Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me- 1 ,2,4-triazol-3-y 1 2-naphthalenyl 1 -Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me-2,( 1 ,3 ,4-thiadiazolyl)
Y = -CH20-N=C(CH3)CH2S- z z
3-Me-phenyl 2-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyI 2,5-diMe-phenyl 2-Me-5-;-Pr-phenyl 3-Et-phenyl 6-CF3-2-pyridinyl 4-CF -2 -pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z 2-Me-phenyl 2,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3 ,6-diMe-2-pyridiny 1
Y = -CH=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-CF3-phenyl 4-CF3 -phenyl 2-naphthalenyl 4-CF3-2-pyridinyl 6-CF -2-pyridiny 1 Y = -CH=N-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-0CF3-phenyl 4-OCF3 -phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3 -2 -pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3-phenyl CH3 t-Bu 2-naphthalenyl 4-/-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5 -CF3 -2-pyridiny 1
6-CF3-2-pyridinyl 4,6-diMe-2 -pyridinyl 4-CF3-2-pyrimidinyl 6-CF3-2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 2-naphthalenyl 4-/-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3 -2-pyridiny 1 4,6-diMe-2-pyridinyl 4-CF3 -2-pyrimidiny 1
Y = -CH2OC(SMe)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl Y =-SCH2- Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 4-Me-phenyl 4-/-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-/-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2 -naphthalenyl
direct bond CH2Br direct bond CHBrCH3
-CH20-N=C(SCH3)- 3-CF3-phenyl -CH20-N=C(cyclopropyl 3-CF3-phenyl
-CH20-N=C(SCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl
-CH20-N=C(SCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl
-CH20-N=C(SCH3)- 4-CF3-phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl
-CH20-N=C(SCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3 -phenyl
-CH20-N=C(SCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl
-CH20-N=C(SCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl
-CH20-N=C(SCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Table 2c R3 = R4 = CH3
Y = -0-
Phenyl 3-OMe-phenyl 3-CF3-phenyl
3-Me-phenyl 3-F-phenyl 4-CF3 -phenyl
4-Me-phenyl 3-I-phenyl 3-OCF3-phenyl
2-Me-phenyl 4-Cl-phenyl 3-SCH3-phenyl
3-cyclohexyl-phenyl 3-SCHF2-phenyl 4-SCH3-phenyl
6-Cl-4-pyrimidinyl 4-SCHF2-phenyl 6-CF3 -2 -pyridinyl
5-CF3-2-pyridinyl 6-Cl-2-pyrazinyl 6-Me-2 -pyridinyl
4-Me-2-pyridinyl 4-CF3-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 5-Me-2-pyridinyl pyrimidinyl pyrimidinyl 4-(2,2,2-trifluoroethoxy)-2- 3,5-diMe-phenyl 2-naphthalenyl pyrimidinyl 4-OCF3-phenyl 3-/-Bu-phenyl 5, 6,7, 8-tetrahydro-2 -naphthalenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4- -Bu-phenyl pyrazinyl 4-CF3-6-Me-2-pyridinyl 4-SCF3-phenyl 3,5-di(CF3)-phenyl 5-OCF3-2-thiazolyl 3-CN-phenyl 5-CF3-2-thiazolyl 5-Cl-2-thiazolyl 4,6-diMe-2-pyridinyl 5-CN-2-thiazolyl
5-I-2-thiazolyl 5-(CH3)3Si-2-thiazolyl 4-Me-5-Br-2-thiazolyl
4-Me-5-Cl-2-thiazolyl 5-Me-2-thiazolyl 4-Me-5-CF3-2-thiazolyl
4,5-diMe-2-thiazolyl 5-SCH3-2-thiazolyl 4-Cl-2-thiazolyl
4-Br-2-thiazolyl 4-Me-5-I-2-thiazolyl 4-CN-2-thiazolyl
4-Me-2-thiazolyl 4-Me-5-CN-2-thiazolyl 4-CF3-5-Me-2-thiazolyl
4-I-2-thiazolyl 3-(HC≡C)-phenyl 3-(CH3C≡C)-phenyl
3-((CH3)3CC≡C)-phenyl 3-((CH3)3SiC≡C)-phenyl 3-( [>-C≡C)-phenyl
5-Me-2-thienyl 5-(CH3)3C-2-thienyl 5-Cl-2-thienyl
5-Br-2-thienyl 5-I-2-thienyl 4-Me-2-thienyl
4-(CH3)3C-2-thienyl 4-Cl-2-thienyl 4-Br-2-thienyl
4-I-2-thienyl 4,5-diMe-2-thienyl 4-Me-5-Cl-2-thienyl
4-Me-5-Br-2-thienyl 4-Me-5-I-2-thienyl 3-Cl-2-thienyl
5-Me-3-thienyl 5-(CH3)3C-3-thienyl 5-Cl-3-thienyl
5-Br-3-thienyl 5-I-3-thienyl 4-Me-3-thienyl
4-(CH3)3C-3-thienyl 4-Cl-3-thienyl 4-Br-3-thienyl
4-I-3-thienyl 4,5-diMe-3-thienyl 4-Me-5-Cl-3-thienyl
4-Me-5-Br-3-thienyl 4-Me-5-I-3-thienyl 2-Cl-3-thienyl
Y = -CH20-
2-Me-phenyl 2,5-diMe-phenyl 2-Me-5- -Pr-phenyl phenyl
2-Me-5-Cl-phenyl 2-Me-5-CF3-phenyl 2-Me-4-OCH3 -phenyl 2,4-diCl-phenyl
3,5-di(CF3)-phenyl 4-Me-phenyl 3-CF3-phenyl 3-OCF3-phenyl
3-OCHF2-phenyl 3-Me-phenyl 2-Me-4-OCF3-phenyl 2-Me-4-OCHF2-phenyl
4-OCF3 -phenyl 5-CF3 -2 -pyridinyl 4-CF -2 -pyridinyl 4-OCHF2-phenyl
4-CF -6-Me-2 -pyridinyl 5-Me-2-pyridinyl 6-CF3 -2-pyridiny 1 6-Me-2-pyridinyl
4,6-diMe-2 -pyridinyl 4-Me-2-pyridinyl 2,6-diMe-4-pyridinyl 3-Me-2-pyridinyl
3,6-diMe-2 -pyridinyl 6-Cl-4-pyrimidinyl 4-Cl-2-pyrimidinyl 6-OCF3-2 -pyridinyl
6-Cl-2-pyrazinyl 2,4,6-triMe-phenyl 4-Cl-2-pyrimidinyl 2-/-Pr-phenyl
1-napthalenyl 3-Et-phenyl 3-Me-2-pyridinyl 4-CF3-2-pyrimidinyl
3-Cl-2-pyridinyl 4-Cl-2-pyridinyl 2,3,6-triMe-phenyl 6-CF3 -4-pyrimidiny 1 Y = -OCH2- Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Me-phenyl 4-/-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-/-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-/-Bu-phenyl 3-/-Bu-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3 -2 -pyridinyl 5-CF3-2-pyridinyl 4-CF3 -6-Me-2-pyridiny 1 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2-pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3 -2-pyridiny 1 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-Et-phenyl 3-(2,2,2-trifluoroethoxy)phenyl l,2,3,4-tetrahydro-2-naphthalenyl t-Bu 1 -naphthalenyl 3-SMe-phenyl 3-ethynylphenyl 2-F-5-Me-phenyl 2-F-5-CF3-phenyl
Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3 -2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-OCF3-2-pyridinyl 5 -OCF3 -2-pyridiny 1 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2 -pyridinyl 3-/-Bu-phenyl 4-/-Bu-phenyl Y = -CH2SC(Et)=N-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-0CF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl CH2CH2-/-Bu ?-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
-CH2S-
2-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl 4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl 1 -Me-2-imidazoly 1 4-Me-2-pyrimidinyl 5-Me-2,( 1 ,3 ,4-thiadiazolyl)
Y = -CH20-N=C(CH3)CH2S-
Z Z
3-Me-phenyl 2-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me- phenyl 3-CF3-phenyl 4-CF3-phenyl
4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl
3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3 -2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl
5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z Z Z Z
2-Me-phenyl 2,5-diMe-phen 1 3 -CF3 -phenyl 4-CF3 -phenyl
3-Cl-phenyl 4-Cl-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl
2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3,6-diMe-2-pyridinyl
Y = -CH=C(CH3)-
Z Z Z Z Z
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl
3-OCF3-phenyl 4-OCF3-phenyl 3-CF3-phenyl 4-CF3 -phenyl 2-naphthalenyl
4-CF3-2-pyridinyl 6-CF -2-pyridinyl
Y = -CH=N-N=C(CH3)-
Z Z Z Z
3-Me-phenyl 4-Me-phenyl 3-CF -phenyl 4-CF3-phenyl
3-OCF3-phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2 .-pyridinyl 5-CF3 -2 -pyridinyl
6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl
2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3-phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3-phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5 -CF3 -2-pyridiny 1
6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3 -2-pyrimidiny 1 6-CF3 -2-pyrimidiny 1 Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF -2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF -2-pyridinyl 5-Me-2-pyridinyl
Y = -SCH2-
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7, 8-tetrahydro-2-naphthalenyl
Y direct bond CH2Br direct bond CHBrCH3 -CH20-N=C(SCH3)- 3-CF -phenyl -CH20-N=C(cyclopropyl)- 3 -CF3 -phenyl -CH20-N=C(SCH3)- 3-0CF3-phenyl -CH20-N=C(cyclopropyl)- 3-0CF3-phenyl -CH20-N=C(SCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl 3-Me-phenyl -CH20-N=C(SCH3 4-CF3 -phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl -CH20-N=C(SCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl Y
-CH20-N=C(SCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl -CH20-N=C(SCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl -CH20-N=C(SCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl> 3,5-diCl-phenyl
Structure for Tables 3a, 3b and 3c
Figure imgf000081_0001
Table 3a R3 = CH3, R4 = H
Y = -CH20-, Z = 6-CF3-2-pyridinyl
Y = -CH20-N=C(SCH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-ρyridinyl 5-CF3-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF -2-ρyridinyl 4,6-diMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2 -pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 1 ,2,3 ,4-terrahydro-2-naphthaleny 1 3-Et-phenyl 3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu 1 -naphthalenyl 3-ethynylphenyl Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF -phenyl 3-OCHF2-phenyl 4-CF3 -2 -pyridinyl 5-CF -2-pyridinyl 6-CF3 -2 -pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-OCF3 -2-pyridiny 1 5-OCF3-2-pyridinyl 6-OCF -2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF -2-pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF -2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2 -pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl -CH2S-
2-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl 1 -Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me- 1 ,3,4-thiadiazol-2-yl
Y = -CH20-N=C(CH3)CH2S- z z
3-Me-phenyl 2-Me-phenyl 3-CF -phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl 3-Et-phenyl 6-CF -2-pyridinyl 4-CF -2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3 ,6-diMe-2-pyridinyl
Y = -CH=N-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2 -pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3 z z
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3 -2 -pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3 -2-pyrimidiny 1 6-CF3-2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 2-naphthalenyI 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3 -2 -pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3 -2-pyrimidiny 1
Y = -CH2OC(SMe)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyI 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4, 6-diMe-2 -pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y Y direct bond CH2Br direct bond CHBrCH3
-CH20-N=C(OCH3)- 3-CF3-phenyl -CH20-N=C(cyclopropyl)- 3-CF3-phenyl
-CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl
-CH20-N=C(OCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl
-CH20-N=C(OCH3)- 4-CF3 -phenyl -CH20-N=C(cyclopropyl)- 4-CF3 -phenyl
-CH20-N=C(OCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl
-CH20-N=C(OCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl
-CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl
-CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl Table 3b R3 = H, R4 = CH3
Y = -CH20-, Z = 6-CF3-2-pyridinyl
Y = -CH20-N=C(SCH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-OCHF -phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 4-CF3 -6-Me-2-pyridinyl 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2-pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3 -2-pyridinyl 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 1 ,2,3 ,4-terrahydro-2-naphthaleny 1 3-Et-phenyl 3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu 1 -naphthalenyl 3-ethynylphenyl
Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3-2 -pyridinyl 5-CF3-2-pyridinyl 6-CF3 -2-pyridiny 1 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3 -2 -pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2 -pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF3-phenyl 3 -CF -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl
6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl
4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2 -pyridinyl
Y = -CH2S-
2-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrim idiny 1 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl l-Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me- 1 ,3 ,4-thiadiazol-2-yl
Y = -CH20-N=C(CH3)CH2S- z z
3-Me-phenyl 2-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
Z Z
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl
4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl 3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl
5-Me-2-pyridinyl 4-Me-2-pyridinyl ] I -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z Z z z Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl
2-naphthalenyl 3,6-diMe-2-pyridinyl
Y = -CH=N-N=C(CH3)-
Z Z Z Z
3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl
3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl
2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyI 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF -phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3-phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF -2-pyrimidinyl 6-CF3 -2-pyrimidiny 1
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2 -pyridinyl 4-CF -2-pyrimidiny 1 Y = -CH2OC(SMe)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y direct bond CH2Br direct bond CHBrCH3 -CH20-N=C(OCH3)- 3-CF3-phenyl -CH20-N=C(cyclopropyl> 3-CF3-phenyl -CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl -CH20-N=C(OCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl -CH20-N=C(OCH3)- 4-CF3-phenyl -CH20-N=C(cyclopropyl)- 4-CF3 -phenyl -CH20-N=C(OCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl -CH20-N=C(OCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl -CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl -CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Table 3c R3 = R4 = CH3
Y = -CH20-, Z = 6-CF3-2-pyridinyl
Y = -CH20-N=C(SCH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 4-CF3-6-Me-2 -pyridinyl 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2 -pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2 -pyridinyl 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl 5,6,7,8-tetrahydro-2 -naphthalenyl l,2,3,4-tetrahydro-2-naphthalenyl 3-Et-phenyl 3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu 1 -naphthalenyl 3-ethynylphenyl
Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3-2-pyridinyl 5-CF3-2 -pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF -6-Me-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3 -2 -pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF -2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyI Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2S-
2-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl l-Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me-l,3,4-thiadiazol-2-yl
Y = -CH20-N=C(CH3)CH2S- z z
3-Me-phenyl 2-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl
4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5- -Pr-phenyl
3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl
5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z Z Z Z Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl
2-naphthalenyl 3 ,6-diMe-2-pyridinyl
Y = -CH=N-N=C(CH3)-
Z Z Z Z
3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl
3-0CF3-phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-C1 -phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5 -CF -2-pyridiny 1
6-CF -2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl
2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl
3,5-di(CF3)-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5 -CF3 -2-pyridiny 1
6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3 -2-pyrimidiny 1 6-CF3-2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF -2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3 -2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl direct bond CH2Br direct bond CHBrCH3
-CH20-N=C(OCH3)- 3 -CF3 -phenyl -CH20-N=C(cyclopropyl)- 3-CF3-phenyl
-CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl
-CH20-N=C(0CH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl
-CH20-N=C(OCH3)- 4-CF3 -phenyl -CH20-N=C(cyclopropyl)- 4-CF3 -phenyl
-CH20-N=C(OCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl
-CH20-N=C(OCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl
-CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl 3-Cl-phenyl
-CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Structures for Tables 4a, 4b and 4c
Figure imgf000092_0001
Table 4a R3 = CH3, R4 = H γ = -o-
Phenyl 3-OMe-phenyl 3 -CF3 -phenyl
3-Me-phenyl 3-F-phenyl 4-CF3 -phenyl
4-Me-phenyl 4-Cl-phenyl 3 -OCF3 -phenyl
2-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
3 -cyclohexy 1-pheny 1 4-SCHF2-phenyl 4-SCH3-phenyl
6-Cl-4-pyrimidinyl 6-Cl-2-pyrazinyl 6-CF -2 -pyridinyl
5-CF3-2-pyridinyl 4-CF3-2-pyridinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 4-OCF3-phenyl 3-t-Bu-phenyl 4-t-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4-SCF3-phenyl pyrazinyl 4-CF3-6-Me-2 -pyridinyl 4,6-diMe-2-pyridinyl 3,5-di(CF3)-phenyl Y = -CH20-
2-Me-phenyl ,5. -diMe-phenyl
Y = -OCH2-
Z Z Z Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl
4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl
2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl
3-pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(CH3)-, Z = 3-OCF3-phenyl
Y = -CH20-N=C(SCH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2 -pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2-pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3 -2-pyridinyl 6-OCF3 -2-pyridiny 1 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 1 ,2,3 ,4-terrahydro-2-naphthaleny 1 3-Et-phenyl 3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu 1 -naphthalenyl 3-ethynylphenyl
Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2 -pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl
4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl
5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF -2-pyridinyl 5-Br-6-Me-2 -pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-ρyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2S-
2-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl 1 -Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me- 1 ,3 ,4-thiadiazol-2-yl Y = -CH20-N=C(CH3)CH2S- z z Z Z Z
3-Me-phenyl 2-Me-phenyl 3-CF3-phenyI 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl 3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3 -2 -pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3 -phenyl 4-CF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3 ,6-diMe-2-pyridiny 1
Y = -CH=C(CH3
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3-CF3-phenyl 4-CF3-phenyl 2-naphthalenyl 4-CF3-2-pyridinyl 6-CF3-2-pyridinyl
Y = -CH=N-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3 -2 -pyridinyl 5-CF -2-pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)- z z
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl
3,5-di(CF3)-phenyl 3-0CF3-phenyl 4-OCF3 -phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2 -pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl 6-CF3-2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF -2-pyridiny 1 5-CF3-2-pyridinyl 6-CF3-2 -pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y Y direct bond CH2Br direct bond CHBrCH3 -CH20-N=C(OCH3)- 3 -CF3 -phenyl -CH20-N=C(cyclopropyl)- 3-CF3-phenyl -CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl -CH20-N=C(OCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl -CH20-N=C(OCH3)- 4-CF3 -phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl -CH20-N=C(OCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl -CH20-N=C(OCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl -CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl -CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl Table 4b
R3 = H, R4 = CH3
Y = -0- z z Z
Phenyl 3-OMe-phenyl 3 -CF3 -phenyl
3-Me-phenyl 3-F-phenyl 4-CF3 -phenyl
4-Me-phenyl 4-Cl-phenyl 3-OCF -phenyl
2-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
3-cyclohexyl-phenyl 4-SCHF2-phenyl 4-SCH3-phenyl
6-Cl-4-pyrimidinyl 6-Cl-2-pyrazinyl 6-CF3-2-pyridinyl
5-CF -2-pyridinyl 4-CF3-2-pyridinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl
2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 4-OCF3-phenyl
3-t-Bu-phenyl 4-t-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2-
3-SCF3-phenyl 4-SCF3-phenyl pyrazinyl
4-CF -6-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 3,5-di(CF3)-phenyl
Y = -CH20-
2-Me-phenyl 2,5-diMe-phenyl
Y = -OCH2-
2-Me-phenyl 2,5-diMe-phenyl 3-CF -phenyl 4-CF3-phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3-ρyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(CH3)-, Z = 3-OCF3-phenyl
Y = -CH20-N=C(SCH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF3-phenyl 4-CF -phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-OCHF2-phenyl
4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-pyridinyl
5-CF -2-pyridinyl 4-CF3-6-Me-2 -pyridinyl 4-Me-2- pyridinyl
5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF -2-pyridinyl
4,6-diMe-2 -pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl
6-OMe-2-pyridinyl 4-OMe-2 -pyridinyl 4-OCF3-2-pyridinyl
5-OCF3-2-pyridinyl 6-OCF3 -2 -pyridinyl 4-OCHF2-pyridinyl
5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl
5, 6,7, 8-tetrahydro-2 -naphthalenyl 1 ,2,3 ,4-tetrahydro-2-naphthaleny 1 3-Et-phenyl
3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu
1 -naphthalenyl 3-ethynylphenyl
Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3-CF -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3 -2 -pyridinyl 5-CF3-2-pyridinyl 6-CF3-2 -pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF -2-pyridiny 1 6-OCF3 -2 -pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF -2-pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF -phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2 -pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3 -OCF3 -phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF -2 -pyridinyl 5-Br-6-Me-2 -pyridinyl
Y = -CH2S-
2-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl l-Me-2-imidazolyl 4-Me-2-pyrimidinyl 5 -Me- 1 ,3 ,4-thiadiazol-2-y 1
Y = -CH20-N=C(CH3)CH2S- z z
3-Me-phenyl 2-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
Z
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF -phenyl 4-CF3-phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5- -Pr-phenyl 3-Et-phenyl 6-CF3-2 -pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2- Z
2-Me-phenyl 2,5-diMe-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 3-0CF3-phenyl 4-OCF3-phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl
2-naphthalenyl 3 ,6-diMe-2 -pyridinyl Y = -CH=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 2-naphthalenyl 4-CF3 -2-pyridiny 1 6-CF3 -2-pyridiny 1
Y = -CH=N-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3 -2-pyridiny 1 6-CF -2-pyridiny 1 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3-phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2 -pyridinyl 5-CF3-2-pyridinyl
6-CF -2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl 6-CF -2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3 -2-pyridiny 1 4, 6-diMe-2 -pyridinyl 4-CF3-2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2 -pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl Y = -CH2OC(=S)NMe-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2 -pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y direct bond CH2Br direct bond CHBrCH3 -CH20-N=C(OCH3)- 3-CF3-phenyl -CH20-N=C(cyclopropyl)- 3-CF -phenyl -CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl -CH20-N=C(OCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl -CH20-N=C(OCH3)- 4-CF3-phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl -CH20-N=C(OCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl -CH2O-N=C(0CH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl -CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl -CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Table 4c R3 = R4 = CH3
Y = -0-
Phenyl 3-OMe-phenyl 3-CF3-phenyl
3-Me-phenyl 3-F-phenyl 4-CF3 -phenyl
4-Me-phenyl 4-Cl-phenyl 3-OCF3-phenyl
2-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
3-cyclohexyl-phenyl 4-SCHF2-phenyl 4-SCH3 -phenyl
6-Cl-4-pyrimidinyl 6-C1 — 2-pyrazinyl 6-CF3 -2-pyridinyl
5-CF3-2-pyridinyl 4-CF3 -2-pyridinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl) 4-OCF3-phenyl 3-t-Bu-phenyl 4-t-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4-SCF3-phenyl pyrazinyl 4-CF3-6-Me-2 -pyridinyl 4,6-diMe-2-pyridinyl 3,5-di(CF3)-phenyl
Y = -CH20-
2-Me-phenyl 2,5-diMe-ρhenyl
Y = -OCH2- Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF -phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(CH3)-, Z = 3-OCF3-phenyl
Y = -CH20-N=C(SCH3
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF -phenyl 4-CF3-phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-0CF3-phenyl 4-OCF3 -phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-pyridinyl 5-CF -2-pyridinyl 4-CF3 -6-Me-2-pyridiny 1 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2-pyridinyl 4-OMe-2 -pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 1 ,2,3 ,4-terrahydro-2-naphthaleny 1 3-Et-ρhenyl 3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu 1 -naphthalenyl 3-ethynylphenyl Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3-2-pyridinyl 5-CF3-2 -pyridinyl 6-CF3 -2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2 -pyridinyl 4-OCF3 -2-pyridiny 1 5-OCF3-2-pyridinyl 6-OCF3 -2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3 -phenyl 3-CF -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF -phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5 -Br-6-Me-2-pyridiny 1 Y = -CH2S-
2-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 2,5-diMe-phenyl 2-Et-phenyl 3-Cl-phenyl 2-Cl-phenyl 2,5-diCl-phenyl
4,6-diMe-2-pyrimidinyl 4-Me-l,2,4-triazol-3-yl 2-naphthalenyl 1 -Me-2-imidazolyl 4-Me-2-pyrimidinyl 5-Me- 1 ,3 ,4-thiadiazol-2-yl
Y = -CH20-N=C(CH3)CH2S- z z
3-Me-phenyl 2-Me-phenyI 3 -CF3 -phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl
4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5- -Pr-phenyl
3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3 -2-pyridiny 1 5-CF -2-pyridinyl 6-Me-2-pyridinyl
5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2- z Z Z Z Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl
2-naphthalenyl 3 ,6-diMe-2-pyridinyl
Y = -CH=C(CH3)-
Z Z Z Z Z
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl
3-0CF3-phenyl 4-OCF3-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 2-naphthalenyl
4-CF3 -2-pyridiny 1 6-CF3 -2-pyridinyl
Y = -CH=N-N=C(CH3)-
Z Z Z Z
3-Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4- CF3 -phenyl
3-OCF3-phenyl 4-OCF3 -phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF -2-pyridiny 1 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl
2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3 -2 -pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4,6-diMe-2 -pyridinyl 4-CF3 -2-pyrimidiny 1 6-CF -2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -CF -phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF -2-pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2 -pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl direct bond CH2Br direct bond CHBrCH3
-CH20-N=C(OCH3)- 3-CF3-phenyl -CH20-N=C(cyclopropyl)- 3-CF3-phenyl
-CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3 -OCF3 -phenyl
-CH20-N=C(OCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl
-CH20-N=C(OCH3)- 4-CF3-phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl
-CH20-N=C(OCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl
-CH20-N=C(OCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl
-CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl
-CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Structure for Tables 5 a, 5 b and 5 c
Figure imgf000106_0001
Table 5 a
R3 = CH3, R4 = H
_H
3-Me-phenyl 4- Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl
3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF -phenyl 4-OCHF2-phenyl 3-SCF3 -phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-G≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
Table 5b R3 = H, R4 = CH3
R R? R9 R£
3-Me-phenyl 4- Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl
3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl R£ R? R9
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl 3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
Table 5 c R3 = R4 = CH3
_l R£ E2 3 -Me-phenyl 4- Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-ρhenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl 3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
Structure for Tables 6a, 6b and 6c
Figure imgf000107_0001
Table 6a
R3 = CH3, R4 = H
No R10 substituent (i.e., H) £
3 -Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF -phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl R£ R R9 R?
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 substituent 1 (i.e., H' ) CH3 I Br
R 10 = Br
R£ R?
3 -Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl
3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 substituent (i.e., H) CH3 I Br
R10 = CH3
R9 a? E? R£
3 -Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl
3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3 -SCF3 -phenyl 4-SCF3 -phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 substituent (i.e., H) CH3 I Br
Table 6b R3 = H, R4 = CH3
No R10 substituent (i.e., H)
E9 ^ R9 R9 3-Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl R9 R?. R9. E?.
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3 -cy clopropy 1-pheny 1
No R9 substituent (i.e., H) CH3 I Br
R10 = Br
R? R?. R E9.
3 -Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl
3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 substituent (i.e., H) CH3 I Br
R10 : : CH3
E? E? R? E^
3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl
3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 substituent (i.e., H) CH3 I Br
Table 6c R3 = R4 = CH3
No R10 substituent (i.e., H)
R9 R9 B2 R9. 3 -Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3 -SCF3 -phenyl 4-SCF3 -phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
Figure imgf000110_0001
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 substituent (i.e. , H) CH3 I Br
R10 = Br
E9. E? E9 E? 3 -Me-phenyl 4-Me-phenyl 3 -CF -phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl 3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3 -cyclopropy 1-pheny 1
No R9 substituent (i.e., H) CH3 Br
R 10 CH3
E9. E9. E? E? 3 -Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3 -phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl 3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 substituent (i.e., H) CH3 I Br
Structure for Tables 7a, 7b and 7c
Figure imgf000110_0002
Table 7a
., H)
Figure imgf000111_0001
Table 7b
e., H)
Figure imgf000111_0002
Table 7c
R3 = R4 = = CH3
R12 R13 R!2 ___ R12 R13 o R12 (i.e. , H) 2-CN 2-F 4,6-diF 2-C1 6-C1 -Me No R13 (i.e. H) 2-F 3,5,6-triF 2-F 5-F -C1 No R13 (i.e. H) 2-C1 4,6-diF 2-F 6-F -F No R13 (i.e. , H) 4-Br 2,6-diF 2-F 4-F -OMe No R13 (i.e. , H) 4-1 2,6-diF 2-Et No R13 (i.e., H) -Br No R13 (i.e. , H) 2-F 3,6-diF 4-Me 2,6-diCl -SMe No R13 (i.e. , H) 2-F 4,5-diF 4-Me 2,6-diF Structure for Tables 8a, 8b and 8c
Figure imgf000112_0001
Table 8a
e.,H)
Figure imgf000112_0002
Table 8b
.,H)
Figure imgf000112_0003
Table 8c
R3 = R4 = CH3
R12 El! R12 EH R12 Ell o R12 (i.e. ,H) 2-CN 2-F 4,6-diF 2-C1 6-C1 -Me No R13 (i.e. ,H) 2-F 3,5,6-triF 2-F 5-F -C1 No R13 (i.e. ,H) 2-C1 4,6-diF 2-F 6-F -F No R13 (i.e. ,H) 4-Br 2,6-diF 2-F 4-F -OMe No R13 (i.e. ,H) 4-1 2,6-diF 2-Et No R13 (i.e., H) 2-Br
2-SM
Figure imgf000113_0001
Structure for Tables 9a, 9b and 9c
Figure imgf000113_0002
Table 9a
R3 = CH3, R4 = H
Y = -0- z z Z
Phenyl 3-OMe-phenyl 3-CF3-phenyl
3 -Me-phenyl 3-F-phenyl 4-CF3-phenyl
4-Me-phenyl 4-Cl-phenyl 3-OCF3-phenyl
2-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
3-cyclohexyl-phenyl 4-SCHF2-phenyl 4-SCH3 -phenyl
6-Cl-4-pyrimidiny] 6-Cl-2-pyrazinyl 6-CF3-2-pyridinyl
5-CF3-2-pyridinyl 4-CF3-2-pyridinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4
6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyri idinyl pyrimidinyl 3,5-diMe-phenyl
2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl) 4-OCF3-phenyl
3-t-Bu-phenyl 4-t-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2
3-SCF3-phenyl 4-SCF3 -phenyl pyrazinyl
4-CF3-6-Me-2 -pyridinyl 4,6-diMe-2-pyridinyl 3,5-di(CF3)-phenyl
Y = -CH20-, Z = 2,5-diMe-phenyl Y = -OCH2- Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3-pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(SCH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3 -2-pyridinyl 4-CF3 -6-Me-2 -pyridinyl 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2 -pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2-pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 1 ,2,3 ,4-tetrahydro-2-naphthalenyl 3-Et-phenyl 3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu 1 -naphthalenyl 3-ethynylphenyl
Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3-CF -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF3 -2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2 -pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-ρyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl Y = -CH2SC(Et)=N-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2 -pyridinyl
Y = -CH2SC(SMe)=N-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl
3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl
5-CF3 -2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH20-N=C(CH3)CH2S- z z
3 -Me-phenyl 2-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
Z Z
3 -Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyI
4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-;'-Pr-phenyl
3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3-2-ρyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl
5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl Y = -CH2CH2-
Z Z Z Z Z
2-Me-phenyl 2,5-diMe-phenyl 3 -CF -phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 2-Et-phenyl 2-Me-5-Cl-p
2-naphthalenyl 3,6-diMe-2-pyridinyl
Y = -CH=N-N=C(CH3)-
3 -Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3 -OCF3 -phenyl 4-OCF3 -phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5 -CF3 -2-pyridiny 1 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl 6-CF3 -2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-CF -2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl
Y = -CH2OC(SMe)=N-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3 -phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
-SCH2-
2-Me-phenyl 2,5-diMe-phenyl 3-CF -phenyl 4-CF3 -phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3-pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7, 8-tetrahydro-2-naphthalenyl
Y direct bond CH2Br direct bond CHBrCH3
-CH20-N=C(OCH3)- 3 -CF3 -phenyl -CH20-N=C(cyclopropyl)- 3-CF3-phenyl
-CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl
-CH20-N=C(OCH3)- 3 -Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl
-CH20-N=C(OCH3)- 4-CF3 -phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl
-CH20-N=C(OCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3 -phenyl
-CH20-N=C(0CH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl
-CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl
-CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Table 9b R3 = H, R4 = CH3
Y = -0-
Phenyl 3-OMe-phenyl 3-CF3-phenyl
3 -Me-phenyl 3-F-phenyl 4-CF3-phenyl
4-Me-phenyl 4-Cl-phenyl 3-OCF3-phenyl
2-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
3-cyclohexyl-phenyl 4-SCHF2-phenyl 4-SCH3-phenyl
6-Cl-4-pyrimidinyl 6-Cl-2-pyrazinyl 6-CF3-2-pyridinyl
5-CF3-2-pyridinyl 4-CF3-2-pyridinyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4- 6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-trifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 4-OCF3-phenyl 3-t-Bu-phenyl 4-t-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4-SCF3-ρhenyl pyrazinyl 4-CF3-6-Me-2 -pyridinyl 4,6-diMe-2-pyridinyl 3,5-di(CF3)-phenyl
Y = -CH20-, Z = 2,5-diMe-phenyl
Y = -0CH2-
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2 -naphthalenyl
Y = -CH20-N=C(SCH3)-
Z 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl 6-OMe-2-pyridinyl 4-OMe-2-pyridinyl 4-OCF -2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl 5,6,7,8-tetrahydro-2-naphthalenyl 1 ,2,3 ,4-terrahydro-2-naphthalenyl 3-Et-phenyl 3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu 1 -naphthalenyl 3-ethynylphenyl Y = -CH=NOCH(CH3>
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3 -Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3 -2-pyridinyl 5-CF3-2-pyridinyl 6-CF3 -2-pyridiny 1 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-ρyridinyl 6-OCF3-2-pyridinyl 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2-pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4, 6-diMe-2 -pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF -2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3-phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3 -OCF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(SMe)=N-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl Y = -CH20-N=C(CH3)CH2S- z z z Z Z
3-Me-phenyl 2-Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl
4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl
3-Et-phenyl 6-CF3-2-pyridinyl 4-CF -2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl
5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z Z Z Z Z
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl
2-naphthalenyl 3 ,6-diMe-2-pyridinyl
Y = -CH=N-N=C(CH3
3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3 -2-pyridiny 1 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyI 3-Et-phenyl t-Bu
Y = -CH20-N=C(CH3)C(=NOCH3)-
3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl 5 -CF3 -2-pyridiny 1
6-CF3 -2-pyridiny 1 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl 6-CF3 -2-pyrimidiny 1
Y = -CH=N-N(CH3)-
Z 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-t-Bu-phenyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-2-pyridinyl
5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2 -pyridinyl 4-CF3 -2-pyrimidiny 1
Y = -CH2OC(SMe)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2 -pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -SCH2-
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3-pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
direct bond CH2Br direct bond CHBrCH3
-CH20-N=C(OCH3)- 3 -CF3 -phenyl -CH20-N=C(cyclopropyl)- 3 -CF3 -phenyl
-CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-0CF3-phenyl
-CH20-N=C(OCH3)- 3-Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl
-CH20-N=C(OCH3)- 4-CF3 -phenyl -CH20-N=C(cyclopropyl)- 4-CF3 -phenyl
-CH20-N=C(OCH3 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl
-CH20-N=C(OCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl
-CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl
-CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl Table 9c R3 = R4 = CH3 γ = -o-
Phenyl 3-OMe-phenyl 3-CF3-phenyl
3-Me-phenyl 3-F-phenyl 4-CF -phenyl
4-Me-phenyl 4-Cl-phenyl 3-0CF3-phenyl
2-Me-phenyl 3-SCHF2-phenyl 3-SCH3-phenyl
3-cyclohexyl-phenyl 4-SCHF2-phenyl 4-SCH3 -phenyl
6-Cl-4-pyrimidinyl 6-Cl-2-pyrazinyl 6-CF3-2-pyridinyl
5-CF3-2-pyridinyl 4-CF3-2-pyridinyl 6-Me-2-pyridinyl
4-Me-2-pyridinyl 5-Me-2-pyridinyl 2-(2,2,2-trifluoroethoxy)-4-
6-(2,2,2-trifluoroethoxy)-4- 4-(2,2,2-rrifluoroethoxy)-2- pyrimidinyl pyrimidinyl pyrimidinyl 3,5-diMe-phenyl 2-naphthalenyl 5,6,7,8-tetrahydro-2 -naphthalenyl 4-OCF3-phenyl 3-t-Bu-phenyl 4-t-Bu-phenyl 6-(2,2,2-trifluoroethoxy)-2- 3-SCF3-phenyl 4-SCF3-phenyl pyrazinyl 4-CF3-6-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 3,5-di(CF3)-phenyl
Y = -CH20-, Z = 2,5-diMe-phenyl
Y = -OCH2- Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl
Y = -CH20-N=C(SCH3
Z 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 3,5-di(CF3)-phenyl 3-Cl-phenyl 4-Br-phenyl 3-5-diCl-phenyl 3,5-diBr-phenyl 4-t-Bu-phenyl 3-t-Bu-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-4-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 4-CF3 -6-Me-2-pyridiny 1 4-Me-2- pyridinyl 5-Me-2- pyridinyl 6-Me-2-pyridinyl 6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 2,6-diMe-4-pyridinyl 2,6-diCl-4-pyridinyl
6-OMe-2-pyridinyl 4-OMe-2-pyridinyl 4-OCF3-2-pyridinyl
5-OCF3-2-pyridinyl 6-OCF3 -2-pyridiny 1 4-OCHF -pyridinyl
5-OCHF -2-pyridinyl 6-OCHF2-2-pyridinyl 2-naphthalenyl
5,6,7,8-tetrahydro-2-naphthalenyl 1, 2, 3,4-tetrahydro-2 -naphthalenyl 3-Et-phenyl
3-(2,2,2-trifluoroethoxy)phenyl 3-SMe-phenyl t-Bu
1 -naphthalenyl 3-ethynylphenyl
Y = -CH=NOCH(CH3)-
Z 4-CF3 -phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3 -Me-phenyl 4-Me-phenyl 2-naphthalenyl 4-OCHF2-phenyl 3-OCHF2-phenyl 4-CF3 -2 -pyridinyl 5-CF3-2-pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3-6-Me-2-pyridinyl 4-OCF3-2-pyridinyl 5-OCF3-2-pyridinyl 6-OCF3 -2-pyridiny 1 4-OCHF2-2-pyridinyl 5-OCHF2-2-pyridinyl 6-OCHF2-2 -pyridinyl 3-t-Bu-phenyl 4-t-Bu-phenyl
Y = -CH2SC(Et)=N-
Z 4-CF3 -phenyl 3-CF3-phenyl 4-OCF3 -phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2 -pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF -2-pyridinyl 5-Br-6-Me-2-pyridinyl
Y = -CH2SC(=S)NMe-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3,5-di(CF3)-phenyl 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2-pyridinyl Y = -CH2SC(SMe)=N-
Z 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-OCF -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl CH2CH2-t-Bu t-Bu 2-naphthalenyl 6-Me-2 -pyridinyl 4-Me-2-pyridinyl
4,6-diMe-2 -pyridinyl 5-Cl-2-pyridinyl 4,6-diCl-2-pyridinyl 5-Me-2-pyridinyl 5-CF3-2-pyridinyl 5-Br-6-Me-2 -pyridinyl
Y = -CH20-N=C(CH3)CH2S- z z Z
3-Me-phenyl 2-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3-Cl-phenyl
4-Cl-phenyl 2-Et-phenyl 2,5-diMe-phenyl 2-naphthalenyl
Y = -CH20-N=C(CH3)CH20-
3-Me-phenyl 2-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Cl-phenyl 3-Cl-phenyl 3,5-diMe-phenyl 2,5-diMe-phenyl 2-Me-5-/-Pr-phenyl 3-Et-phenyl 6-CF3-2-pyridinyl 4-CF3-2-pyridinyl 5-CF3-2-pyridinyl 6-Me-2-pyridinyl 5-Me-2-pyridinyl 4-Me-2-pyridinyl 1 -naphthalenyl 2-naphthalenyl
Y = -CH2CH2-
Z 2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3 -phenyl 3-Cl-phenyl 4-Cl-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 2-Et-phenyl 2-Me-5-Cl-phenyl 2-naphthalenyl 3,6-diMe-2 -pyridinyl
Y = -CH=N-N=C(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 4-CF3-2-pyridinyl 5-CF3 -2 -pyridinyl 6-CF3-2-pyridinyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 2-naphthalenyl 4,6-diMe-2-pyridinyl 3-Et-phenyl t-Bu Y = -CH20-N=C(CH3)C(=NOCH3)-
3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl
4-Cl-phenyl 3,5-diCl-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl
3,5-di(CF3)-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl CH3 t-Bu 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl
5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3 -2-pyridiny 1 5-CF3-2-pyridinyl
6-CF3-2-pyridinyl 4,6-diMe-2-pyridinyl 4-CF3-2-pyrimidinyl 6-CF3-2-pyrimidinyl
Y = -CH=N-N(CH3)-
Z 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3-phenyl 2-naphthalenyl 4-t-Bu-phenyl 4-Me-2-pyridinyl 5-Me-2-pyridinyl 6-Me-2-pyridinyl 4-CF3 -2-py ridiny 1 5-CF3-2-pyridinyl 6-CF -2-pyridiny 1 4,6-diMe-2-pyridinyl 4-CF3 -2-pyrimidiny 1
Y = -CH2OC(SMe)=N-
Z 4-CF3-phenyl 3 -CF3 -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4, 6-diMe-2 -pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -CH2OC(=S)NMe-
Z 4-CF3-phenyl 3 -CF -phenyl 4-OCF3-phenyl 3-OCF3-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3 -Me-phenyl 4-Me-phenyl 3,5-diMe-phenyl 2-naphthalenyl 6-Me-2-pyridinyl 4-Me-2-pyridinyl 4,6-diMe-2-pyridinyl 5-CF3-2-pyridinyl 5-Me-2-pyridinyl
Y = -SCH2-
2-Me-phenyl 2,5-diMe-phenyl 3-CF3-phenyl 4-CF3-phenyl 4-Me-phenyl 4-t-Bu-phenyl 3-Cl-phenyl 4-Cl-phenyl 2-Me-5-Cl-phenyl 3-t-Bu-phenyl 2-naphthalenyl 1 -naphthalenyl 3 -pyridinyl 4-pyridinyl 6-Me-2-pyridinyl 5,6,7,8-tetrahydro-2-naphthalenyl Y direct bond CH2Br direct bond CHBrCH3 -CH20-N=C(OCH3)- 3 -CF -phenyl -CH20-N=C(cyclopropyl)- 3 -CF3 -phenyl -CH20-N=C(OCH3)- 3-OCF3-phenyl -CH20-N=C(cyclopropyl)- 3-OCF3-phenyl -CH20-N=C(OCH3)- 3 -Me-phenyl -CH20-N=C(cyclopropyl)- 3-Me-phenyl -CH20-N=C(OCH3)- 4-CF3-phenyl -CH20-N=C(cyclopropyl)- 4-CF3-phenyl -CH20-N=C(OCH3)- 4-OCF3-phenyl -CH20-N=C(cyclopropyl)- 4-OCF3-phenyl -CH20-N=C(OCH3)- 4-Me-phenyl -CH20-N=C(cyclopropyl)- 4-Me-phenyl -CH20-N=C(OCH3)- 3-Cl-phenyl -CH20-N=C(cyclopropyl)- 3-Cl-phenyl -CH20-N=C(OCH3)- 3,5-diCl-phenyl -CH20-N=C(cyclopropyl)- 3,5-diCl-phenyl
Structure for Tables 10a, 10b and 10c
Figure imgf000126_0001
Table 10a R3 = CH3, R4 = H
R9 E9. E? E9. 3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-0CF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyI 3-SCF3-phenyl 4-SCF3-phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl 3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3 -cy clopropy 1-pheny 1 No R9 (i.e., H) CH3 Br I
Table 10b R3 = H, R4 = CH3
E9. _l R£ E9. 3 -Me-phenyl 4-Me-phenyl 3-CF3 -phenyl 4-CF3 -phenyl 3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
Figure imgf000127_0001
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3 -cyclopropyl-pheny 1
No R9 (i.e., H) CH3 Br I
Table 10c R3 = R4 = CH3
E9. E9. E9. E9. 3 -Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3 -SCF3 -phenyl 4-SCF3-phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl 3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl No R9 (i.e., H) CH3 Br I
Structure for Tables 11a, l ib and 11 c
Figure imgf000127_0002
Table 11a R3 = CH3, R4 = H
No R10 (i.e., H)
R£ R9 E£ E^
3 -Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3 -phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl E?. E9. E9. E£
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 (i.e., H) CH3 I Br
R10 = Br
E9. E?. E9. E?
3 -Me-phenyl 4- Me-phenyl 3-CF3-phenyl 4-CF3-phenyl
3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF -phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3 -phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 (i.e., H) CH3 I Br
R, 0 = CH3
E? R9 E? E£
3 -Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl
3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF -phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 (i.e., H) CH3 I Br
Table l ib
R3 = H, R4 = CH3
No R10 (i.e., H)
E E? E? E9.
3-Me-phenyl 4-Me-phenyl 3 -CF3 -phenyl 4-CF3 -phenyl
3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl E? R9 R9 E?, 3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3 -cyclopropyl-pheny 1 No R9 (i.e., H) CH3 I Br
R10 = Br
E9. E9. E9. E9. 3 -Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3-OCF3-phenyl 4-OCF3 -phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl 3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3 -cyclopropyl-pheny 1 No R9 (i.e., H) CH3 I Br
R10 = CH3
E9. R? R£ R9
3 -Me-phenyl 4- Me-phenyl 3-CF3-phenyl 4-CF3-phenyl
3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3 -cyclopropy 1-pheny 1
No R9 (i.e., H) CH3 I Br
Table l ie
1 I3 = R4 = CH3
No R10 (i.e., H)
R£ R? R? E?
3 -Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3-phenyl 3 -OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl 3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4- SCF3 -phenyl 3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl 3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl R? E? R? E?
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 (i.e., H) CH3 I Br
R10 = Br
E? E? E? E9
3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF3 -phenyl
3-OCF3-phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3-phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 (i.e., H) CH3 I Br
R10 = CH3
E? E9 E? E9.
3-Me-phenyl 4-Me-phenyl 3-CF3-phenyl 4-CF -phenyl
3-OCF3 -phenyl 4-OCF3-phenyl 3,5-di(CF3)-phenyl 3,5-diMe-phenyl
3-OCHF2-phenyl 4-OCHF2-phenyl 3-SCF3-phenyl 4-SCF3 -phenyl
3-SCHF2-phenyl 4-SCHF2-phenyl 3-Cl-phenyl 4-Cl-phenyl
3,5-diCl-phenyl 3-Cl-4-Me-phenyl 3,4-diCl-phenyl 3-Br-phenyl
3-SMe-phenyl 4-SMe-phenyl 3-C≡CH-phenyl 4-C≡CH-phenyl t-Bu CF3 3,5-diF-phenyl 3-cyclopropyl-phenyl
No R9 (i.e., H) CH3 I Br
Structure for Tables 12a, 12b and 12c
Figure imgf000130_0001
Table 12a
R3 = CH3, R = H
R12 Ell R12 R13 R12 Ell o R12 (i.e. H) 2-CN 2-F 4,6-diF 2-C1 6-C1 -Me No R13 (i.e. H) 2-F 3,5,6-triF 2-F 5-F -C1 No R13 (i.e. H) 2-C1 4,6-diF 2-F 6-F -F No R13 (i.e. ,H) 4-Br 2,6-diF 2-F 4-F -OMe No R13 (i.e. ,H) 4-1 2,6-diF 2-Et NoR13 (i.e., H) -Br No R13 (i.e. ,H) 2-F 3,6-diF 4-Me 2,6-diCl -SMe No R13 (i.e. ,H) 2-F 4,5-diF 4-Me 2,6-diF
Table 12b
R3 = H,R4 = CH3
___ EH R12 R13 R12 R__ o R12 (i.e. ,H) 2-CN 2-F 4,6-diF 2-C1 6-C1 -Me No R13 (i.e. ,H) 2-F 3,5,6-triF 2-F 5-F -C1 No R13 (i.e. ,H) 2-C1 4,6-diF 2-F 6-F -F No R13 (i.e. ,H) 4-Br 2,6-diF 2-F 4-F -OMe No R13 (i.e. ,H) 4-1 2,6-diF 2-Et NoR13 (i.e., H) -Br No R13 (i.e. ,H) 2-F 3,6-diF 4-Me 2,6-diCl -SMe No R13 (i.e. ,H) 2-F 4,5-diF 4-Me 2,6-diF
Table 12c
R3 = R4 = CH3
R12 R 13 R 12 R12 R13 o R12 (i.e., H) 2-CN 2-F 4,6-diF 2-C1 6-C1 -Me NoR13 .e., H) 2-F 3,5,6-triF 2-F 5-F -C1 NoR13 .e., H) 2-C1 4,6-diF 2-F 6-F -F NoR13 •e., H) 4-Br 2,6-diF 2-F 4-F -OMe NoR ■e., H) 4-1 2,6-diF 2-Et NoR13(i.e.,H) -Br NoR .e., H) 2-F 3,6-diF 4-Me 2,6-diCl -SMe NoR i.e., H) 2-F 4,5-diF 4-Me 2,6-diF Structure for Tables 13a, 13b and 13c
Figure imgf000132_0001
Table 13a
., H)
Figure imgf000132_0002
Table 13b
R3 = H,R4 = CH3
R12 R13 R12 Ell R12 R13
NoR12 (i.e. .H) 2-CN 2-F 4,6-diF 2-C1 6-C1
2-Me NoR13 (i.e. H) 2-F 3,5,6-triF 2-F 5-F
2-C1 NoR13 (i.e. H 2-C1 4,6-diF 2-F 6-F
2-F NoR13 (i.e. H) 4-Br 2,6-diF 2-F 4-F
2-OMe NoR13 (i.e. H) 4-1 2,6-diF 2-Et NoR13 (i.e., H)
2-Br NoR13 (i.e. H) 2-F 3,6-diF 4-Me 2,6-diCl
2-SMe NoR13 (i.e. H) 2-F 4,5-diF 4-Me 2,6-diF
Table 13c
R3 = R4 = CH3
R12 Ell R 12 R13 R 12 Ell
No R12 (i.e. .H) 2-CN 2-F 4,6-diF 2-C1 6-Cl
2-Me No R13 (i.e. H) 2-F 3,5,6-triF 2-F 5-F
2-C1 NoR13 (i.e. ,H) 2-C1 4,6-diF 2-F 6-F
2-F NoR13 (i.e. ,H) 4-Br 2,6-diF 2-F 4-F
2-OMe NoR13 (i.e. ,H) 4-1 2,6-diF 2-Et NoR13 (i.e., H) R 12 R13 Ell R13 R12 R13
2-Br No R13 (i.e., H) 2-F 3,6-diF 4-Me 2,6-diCl
2-SMe No R13 (i.e., H) 2-F 4,5-diF 4-Me 2,6-diF
Formulation/Utility
Compounds of this invention will generally be used as a formulation or composition with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid diluent or a surfactant. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Useful formulations include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels. Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films, and the like which can be water-dispersible ("wettable") or water-soluble. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further formulation.
The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
Weight Percent
Active Ingredient Diluent Surfactant
Water-Dispersible and Water-soluble 5-90 0-94 1-15 Granules, Tablets and Powders.
Suspensions, Emulsions, Solutions 5-50 40-95 0-15 (including Emulsifiable Concentrates)
Dusts 1-25 70-99 •5
Granules and Pellets 0.01-99 5-99.99 15
High Strength Compositions 90-99 0-10 0-2 Typical solid diluents are described in Watkins, et al, Handbook of Insecticide Dust
Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon 's Detergents and Emul sifters Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity.
Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones, N,N-dialkyltaurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and polyoxyethylene/polyoxypropylene block copolymers. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, NN-dimethylformamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins, alkylbenzenes, alkylnaphthalenes, oils of olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.
Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Suspensions are usually prepared by wet-milling; see, for example, U.S. 3,060,084. Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry 's Chemical Engineer 's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
For further information regarding the art of formulation, see U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.
In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A-C. Example A Wettable Powder
Compound 11 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.
Example B
Granule Compound 13 10.0% attapulgite granules (low volatile matter,
0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0%.
Example C Extruded Pellet Compound 14 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%. Example D
Emulsifiable Concentrate
Compound 16 20.0% blend of oil soluble sulfonates and polyoxyethylene ethers 10.0% isophorone 70.0%.
The compounds of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound. The compounds and compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, vegetable, field, cereal, and fruit crops. These pathogens include Plasmopara viticola, Phytophthora infestans, Peronospora tabacina,
Pseudoperonospora cubensis, Pythium aphanidermatum, Alternaria brassicae, Septoria nodorum, Septoria tritici, Cercosporidium personatum, Cercospora arachidicola, Pseudocercosporella herpotrichoides, Cercospora beticola, Botrytis cinerea, Monilinia fructicola, Pyricularia oryzae, Podosphaera leucotricha, Venturia inaequalis, Erysiphe graminis, Uncinula necatur, Puccinia recondita, Puccinia graminis, Hemileia vastatrix, Puccinia striiformis, Puccinia arachidis, Rhizoctonia solani, Sphaerotheca fuliginea, Fusarium oxysporum, Verticillium dahliae, Pythium aphanidermatum, Phytophthora megasperma, Sclerotinia sclerotiorum, Sclerotium rolfsii, Erysiphe polygoni, Pyrenophora teres, Gaeumannomyces graminis, Rynchosporium secalis, Fusarium roseum, Bremia lactucae and other generea and species closely related to these pathogens.
The compounds of this invention also exhibit activity against a wide spectrum of foliar-feeding, fruit-feeding, stem or root feeding, seed-feeding, aquatic and soil-inhabiting arthropods (term "arthropods" includes insects, mites and nematodes) which are pests of growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health. Those skilled in the art will appreciate that not all compounds are equally effective against all growth stages of all pests. Nevertheless, all of the compounds of this invention display activity against pests that include: eggs, larvae and adults of the Order Lepidoptera; eggs, foliar- feeding, fruit-feeding, root-feeding, seed-feeding larvae and adults of the Order Coleoptera; eggs, immatures and adults of the Orders Hemiptera and Homoptera; eggs, larvae, nymphs and adults of the Order Acari; eggs, immatures and adults of the Orders Thysanoptera, Orthoptera and Dermaptera; eggs, immatures and adults of the Order Diptera; and eggs, juveniles and adults of the Phylum Nematoda. The compounds of this invention are also active against pests of the Orders Hymenoptera, Isoptera, Siphonaptera, Blattaria, Thysanura and Psocoptera; pests belonging to the Class Arachnida and Phylum Platyhelminthes. Specifically, the compounds are active against southern corn rootworm (Diabrotica undecimpunctata howardi), aster leafhopper (Mascrosteles fascifrons), boll weevil (Anthonomus grandis), two-spotted spider mite (Tetranychus urticae), fall armyworm (Spodoptera frugiperda), black bean aphid (Aphis fab ae), green peach aphid (Myzus persica), cotton aphid (Aphis gossypii), Russian wheat aphid (Diuraphis noxia), English grain aphid (Sitobion avenae), tobacco budworm (Heliothis virescens), rice water weevil (Lissorhoptrus oryzophilus), rice leaf beetle (Oulema oryzae), whitebacked planthopper (Sogatella furcifera), green leafhopper (Nephotettix cincticeps), brown planthopper
(Nilaparvata lugens), small brown planthopper (Laodelphax striatellus), rice stem borer (Chilo suppressalis), rice leafroller (Cnaphalocrocis medinalis), black rice stink bug (Scotinophara lurida), rice stink bug (Oebalus pugnax), rice bug (Leptocorisa chinensis), slender rice bug (Cletus puntiger), and southern green stink bug (Nezara viridula). The compounds are active on mites, demonstrating ovicidal, larvicidal and chemosterilant activity against such families as Tetranychidae including Tetranychus urticae, Tetranychus cinnabarinus, Tetranychus mcdanieli, Tetranychus pacificus, Tetranychus turkestani, Byrobia rubrioculus, Panonychus ulmi, Panonychus citri, Eotetranychus carpini borealis, Eotetranychus, hicoriae, Eotetranychus sexmaculatus, Eotetranychus yumensis, Eotetranychus banksi and Oligonychus pratensis; Tenuipalpidae including Brevipalpus lewisi, Brevipalpus phoenicis, Brevipalpus calif ornicus and Brevipalpus obovatus; Eriophyidae including Phyllocoptruta oleivora, Eriophyes sheldoni, Aculus cornutus, Epitrimerus pyri and Eriophyes mangiferae. See WO 90/10623 and WO 92/00673 for more detailed pest descriptions.
Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Examples of such agricultural protectants with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, buprofezin, carbofuran, chlorfenapyr, chlorpyrifos, chlorpyrifos-methyl, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, esfenvalerate, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flucythrinate, tau-fluvalinate, fonophos, imidacloprid, isofenphos, malathion, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methyl 7-chloro-2,5-dihydro-2-[[N-(methoxycarbonyl)-N-[4- (trifluoromethoxy)phenyl]amino]carbonyl]indeno[l,2-e][l,3,4]oxadiazine-4a(3H)- carboxylate (DPX-JW062), monocrotophos, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, rotenone, sulprofos, tebufenozide, tefluthrin, terbufos, tetrachlorvinphos, thiodicarb, tralomethrin, trichlorfon and triflumuron; fungicides such as azoxystrobin, benomyl, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), bromuconazole, captafol, captan, carbendazim, chloroneb, chlorothalonil, copper oxychloride, copper salts, cymoxanil, cyproconazole, cyprodinil (CGA 219417), diclomezine, dicloran, difenoconazole, dimethomorph, diniconazole, diniconazole-M, dodine, edifenphos, epoxiconazole (BAS 480F), famoxadone, fenarimol, fenbuconazole, fenpiclonil, fenpropidin, fenpropimorph, fluazinam, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, furalaxyl, hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, kresoxim-methyl, mancozeb, maneb, mepronil, metalaxyl, metconazole, S-methyl 7-benzothiazolecarbothioate (CGA 245704), myclobutanil, neo-asozin (ferric methanearsonate), oxadixyl, penconazole, pencycuron, probenazole, prochloraz, propiconazole, pyrifenox, pyroquilon, quinoxyfen, spiroxamine (KWG4168), sulfur, tebuconazole, tetraconazole, thiabendazole, thiophanate-methyl, thiram, triadimefon, triadimenol, tricyclazole, triticonazole, validamycin and vinclozolin; nematocides such as aldoxycarb and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents such as Bacillus thuringiensis, Bacillus thuringiensis delta endotoxin, baculovirus, and entomopathogenic bacteria, virus and fungi.
In certain instances, combinations with other fungicides or arthropodicides having a similar spectrum of control but a different mode of action will be particularly advantageous for resistance management.
Preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of this invention with a fungicide selected from the group azoxystrobin, benomyl, carbendazim, carpropamid, copper salts, cymoxanil, cyproconazole, cyprodinil, dimethomorph, epoxiconazole, famoxadone, fenpropidin, fenpropimorph, flusilazole, flutolanil, fosetyl-aluminum, kasugamycin, kresoxim-methyl, mancozeb, metalaxyl and oxadixyl, pencycuron, probenazole, propiconazole, pyroquilon, tricyclazole, validamycin. Specifically preferred mixtures (compound numbers refer to compounds in Index Tables A-C) are selected from the group: compound 7 and azoxystrobin, compound 7 and benomyl, compound 7 and carbendazim, compound 7 and carpropamid, compound 7 and copper salts, compound 7 and cymoxanil, compound 7 and cyproconazole, compound 7 and cyprodinil, compound 7 and epoxiconazole, compound 7 and famoxadone, compound 7 and fenpropidin, compound 7 and fenpropimorph, compound 7 and flusilazole, compound 7 and flutolanil, compound 7 and fosetyl-aluminum, compound 7 and kasugamycin, compound 7 and kresoxim-methyl, compound 7 and mancozeb, compound 7 and metalaxyl, compound 7 and oxadixyl, compound 7 and pencycuron, compound 7 and probenazole, compound 7 and propiconazole, compound 7 and pyroquilon, compound 7 and tricyclazole, compound 7 and validamycin, compound 11 and azoxystrobin, compound 11 and benomyl, compound 11 and carbendazim, compound 11 and carpropamid, compound 11 and copper salts, compound 11 and cymoxanil, compound 11 and cyproconazole, compound 11 and cyprodinil, compound 11 and epoxiconazole, compound 11 and famoxadone, compound 11 and fenpropidin, compound 11 and fenpropimorph, compound 11 and flusilazole, compound 11 and flutolanil, compound 11 and fosetyl-aluminum, compound 11 and kasugamycin, compound 11 and kresoxim-methyl, compound 11 and mancozeb, compound 11 and metalaxyl, compound 11 and oxadixyl, compound 11 and pencycuron, compound 11 and probenazole, compound 11 and propiconazole, compound 11 and pyroquilon, compound 11 and tricyclazole, compound 11 and validamycin, compound 13 and azoxystrobin, compound 13 and benomyl, compound 13 and carbendazim, compound 13 and carpropamid, compound 13 and copper salts, compound 13 and cymoxanil, compound 13 and cyproconazole, compound 13 and cyprodinil, compound 13 and epoxiconazole, compound 13 and famoxadone, compound 13 and fenpropidin, compound 13 and fenpropimorph, compound 13 and flusilazole, compound 13 and flutolanil, compound 13 and fosetyl-aluminum, compound 13 and kasugamycin, compound 13 and kresoxim-methyl, compound 13 and mancozeb, compound 13 and metalaxyl, compound 13 and oxadixyl, compound 13 and pencycuron, compound 13 and probenazole, compound 13 and propiconazole, compound 13 and pyroquilon, compound 13 and tricyclazole, compound 13 and validamycin, compound 14 and azoxystrobin, compound 14 and benomyl, compound 14 and carbendazim, compound 14 and carpropamid, compound 14 and copper salts, compound 14 and cymoxanil, compound 14 and cyproconazole, compound 14 and cyprodinil, compound 14 and epoxiconazole, compound 14 and famoxadone, compound 14 and fenpropidin, compound 14 and fenpropimorph, compound 14 and flusilazole, compound 14 and flutolanil, compound 14 and fosetyl-aluminum, compound 14 and kasugamycin, compound 14 and kresoxim-methyl, compound 14 and mancozeb, compound 14 and metalaxyl, compound 14 and oxadixyl, compound 14 and pencycuron, compound 14 and probenazole, compound 14 and propiconazole, compound 14 and pyroquilon, compound 14 and tricyclazole, compound 14 and validamycin, compound 16 and azoxystrobin, compound 16 and benomyl, compound 16 and carbendazim, compound 16 and carpropamid, compound 16 and copper salts, compound 16 and cymoxanil, compound 16 and cyproconazole, compound 16 and cyprodinil, compound 16 and epoxiconazole, compound 16 and famoxadone, compound 16 and fenpropidin, compound 16 and fenpropimorph, compound 16 and flusilazole, compound 16 and flutolanil, compound 16 and fosetyl-aluminum, compound 16 and kasugamycin, compound 16 and kresoxim-methyl, compound 16 and mancozeb, compound 16 and metalaxyl, compound 16 and oxadixyl, compound 16 and pencycuron, compound 16 and probenazole, compound 16 and propiconazole, compound 16 and pyroquilon, compound 16 and tricyclazole, and compound 16 and validamycin, compound 40 and azoxystrobin, compound 40 and benomyl, compound 40 and carbendazim, compound 40 and carpropamid, compound 40 and copper salts, compound 40 and cymoxanil, compound 40 and cyproconazole, compound 40 and cyprodinil, compound 40 and epoxiconazole, compound 40 and famoxadone, compound 40 and fenpropidin, compound 40 and fenpropimorph, compound 40 and flusilazole, compound 40 and flutolanil, compound 40 and fosetyl-aluminum, compound 40 and kasugamycin, compound 40 and kresoxim-methyl, compound 40 and mancozeb, compound 40 and metalaxyl, compound 40 and oxadixyl, compound 40 and pencycuron, compound 40 and probenazole, compound 40 and propiconazole, compound 40 and pyroquilon, compound 40 and tricyclazole, compound 40 and validamycin, compound 118 and azoxystrobin, compound 118 and benomyl, compound 118 and carbendazim, compound 118 and carpropamid, compound 118 and copper salts, compound 118 and cymoxanil, compound 118 and cyproconazole, compound 118 and cyprodinil, compound 118 and epoxiconazole, compound 118 and famoxadone, compound 118 and fenpropidin, compound 118 and fenpropimorph, compound 118 and flusilazole, compound 118 and flutolanil, compound 118 and fosetyl-aluminum, compound 118 and kasugamycin, compound 118 and kresoxim-methyl, compound 118 and mancozeb, compound 118 and metalaxyl, compound 118 and oxadixyl, compound 118 and pencycuron, compound 118 and probenazole, compound 118 and propiconazole, compound 118 and pyroquilon, compound 118 and tricyclazole, and compound 118 and validamycin.
Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to the seed to protect the seed and seedling.
For plant disease control, rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than 1 g/ha to 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from 0.1 to 10 g per kilogram of seed.
Arthropod pests are controlled and protection of agronomic, horticultural and specialty crops, animal and human health is achieved by applying one or more of the compounds of this invention, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. Thus, the present invention further comprises a method for the control of foliar and soil inhabiting arthropods and nematode pests and protection of agronomic and/or nonagronomic crops, comprising applying one or more of the compounds of the invention, or compositions containing at least one such compound, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. A preferred method of application is by spraying. Alternatively, granular formulations of these compounds can be applied to the plant foliage or the soil. Other methods of application include direct and residual sprays, aerial sprays, seed coats, microencapsulations, systemic uptake, baits, eartags, boluses, foggers, fumigants, aerosols, dusts and many others. The compounds can be incorporated into baits that are consumed by the arthropods or in devices such as traps and the like.
For the control arthropod pests, the compounds of this invention can be applied in their pure state, but most often application will be of a formulation comprising one or more compounds with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. A preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. Combinations with spray oils, spray oil concentrations, spreader stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance compound efficacy. The rate of application required for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredient per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square meter but as little as 0.1 mg/square meter may be sufficient or as much as 150 mg/square meter may be required.
The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-D for compound descriptions. The following abbreviations are used in the Index Tables which follow: H = hydrogen, Cl = chlorine and Br = bromine. The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared.
INDEX TABLE A
Figure imgf000141_0001
Cmpd Ex. R3 R4 mp (°C) No. 1 CH3 H CH20-N=C(CH3) 3,5-diCl-Ph 2 CH3 H CH20-N=C(CH3) 3,5-diBr-Ph 163-164 3 CH3 H CH20-N=C(CH3) 3-OCF3-Ph oil* 4 CH3 H CH20-N=C(CH3) 3,4-diCl-Ph 109-110 5 CH3 CH3 CH20-N=C(CH3) 3,5-diCl-Ph * 6 CH3 H CH20-N=C(CH3) 4-CH3-Ph oil* 7 CH3 H O 3-CF3-Ph 95-96
CH3 H O 4-Cl-Ph 87-89
9 H CH3 CH20-N=C(CH3) 3-CH3-Ph 119-122
10 H CH3 CH20-N=C(CH3) 3,5-diCl-Ph 159-161
11 CH3 H O Ph 58-60 Cmpd Ex. RJ El Y z mp (°C)
No.
12 CH3 H O 4-F-Ph 99-101
13 CH3 H O 3-CH3-Ph 70-72
14 CH3 H 0 4-CH3-Ph 72-74
15 CH3 H 0 3,5-diCl-Ph 161-163
16 CH3 H 0 3-F-Ph 108-110
17 2 CH3 H O 4-OCF3-Ph 75-77
18 3 CH3 H OCH2 3-CH3-Ph *
19 CH3 H OCH2 3-CF3-Ph *
20 CH3 H OCH2 4-/-Bu-Ph *
21 CH3 H OCH2 2-CH3-Ph 158-160
22 CH3 H 0 4-OCH3-Ph *
23 CH3 H 0 3-Cl-Ph 105-107
24 CH3 H O 3,5-diCH3-Ph 96-99
25 CH3 H 0 4-Br-Ph 119-121
26 CH3 H 0 3-Br-Ph 90-95
27 CH3 H 0 3-Cl-4-F-Ph 106-108
28 CH3 H 0 3,4-diCl-Ph 90-92
29 CH3 H O 2-CH3-Ph *
30 CH3 H O 3-OCF3-Ph 50-52
31 H CH3 0 3-CF3-Ph 1 13-1 15
32 H CH3 0 Ph 123-124
33 CH3 H 0 2-naphthalenyl 120-122
34 CH3 H CH20-N=C(CH3) 3-CH3-Ph 64-67
35 CH3 H CH2 Br 115-116
36 CH3 H CH20 3-CF3-Ph 120-123
37 CH3 H CH20 2-CH2CH3-Ph sticky solid*
38 CH3 H CH20 2-CH(CH3)2-Ph oil*
39 CH3 H CH20 2-C(CH3)3-Ph 137-139
40 CH3 H CH20-N=C(CH3) 4-CF3-2-pyridinyl oil*
41 CH3 H 0 3-(C≡CH)- 1 ,2,4-thiadiazoi-5-yl *
42 CH3 H O 5-Cl-6-CH2CH3-4-pyrimidinyl 99-103
43 CH3 H 0 3-I-l,2,4-thiadiazol-5-yl 133-136
44 CH3 H 0 6-C(CH3)3-4-pyrimidinyl oil*
45 CH3 H 0 4-CF3-5-Br-2-thiazolyl 144-146
46 CH3 H 0 4-CF3-2-thiazolyl 141-143
47 CH3 H o 4-CF3-5-CH3-2-thiazolyl 118-121 Cmpd Ex. R3 R4 mp (°C) No. 48 CH3 H CH20-N= =C(CH3) 4-CH3-2-pyridinyl 97-98 49 CH3 H 0 2,3 ,5 ,6-tetra-F-4-pyridinyl 103-105 50 CH3 H 0 4-CF3-5-CH2CH3-2-thiazolyl 116-118 51 CH3 H O 2-OCH(CH3)CF3-4-pyrimidinyl 148-150 52 CH3 H O 4-OCH(CH3)CF3-2-pyrimidinyl 141-146 53 CH3 H CH20-N= =C(CH3) 5-CF -2-pyridinyl 77-78 54 CH3 H CH20 1 -naphthalenyl 112-115 55 CH3 H 0 5-CF3-2-pyridinyl 138-139 56 CH3 H 0 4-Br-2-thiazolyl 205-208 57 CH3 H O 5-Br-2-thiazolyl 88-90 58 CH3 H CH20 2-Cl-3-pyridinyl 142-145 59 CH3 H CH20-N= =C(CH3) 4-CF3-6-CH3-2-pyridinyl 1 15-1 16 60 CH3 H O 2-thiazolyl 1 12-113 61 CH3 H CH20-N= =C(CH3) 4-ι*-Bu-2-pyridinyl * 62 CH3 H CH20-N= =C(CH3) 4-CHF2-2-pyridinyl 105-108 63 CH3 H 0 2-Cl-4-pyrimidinyl 103-108 64 CH3 H CH20 2-CH3-5-CH(CH3)2-Ph 93-94 65 CH3 H CH20 2,3,6-triMe-Ph 1 13-1 15 66 CH3 H CH20 2,4,6-triMe-Ph 92-94 67 CH3 H CH20 2,3,5-triMe-Ph 140-142 68 CH3 H CH20 2-F-Ph 82-85 69 CH3 H CH20 3-F-Ph 96-97 70 CH3 H CH20 4-F-Ph 116-118 71 CH3 H O 4-CF3-2-pyrimidinyl 102-106 73 CH3 H 0 3-I-Ph 127-129 74 CH3 H O 6-OCH3-2-naphthalenyl * 75 CH3 H 0 3-CN-Ph 138-140 76 CH3 H 0 3-(C≡CH)-Ph 91-93 77 CH3 H o 2-?-Bu-4-pyrimidinyl 134-136 78 CH3 H 0 5-Cl-2-thiazolyl 191-196 79 CH3 H 0 5-CF3 - 1 ,3 ,4-thiadiazol-2-yl 125-127 80 CH3 H direct bond CH2C1 114-1 17 81 CH3 H O 5-I-2-thiazolyl 133-136 82 CH3 H CH20-N= =C(CH3) 2-F-5-CH3-Ph oil* 83 CH3 H CH20-N= =C(CH3) 2-F-5-CF3-Ph * 84 CH3 H CH20 2-Br-4-F-Ph 144-147 Cmpd Ex. Rj El Y z mp (°C)
No.
85 CH3 H CH20 2-F-4-Br-Ph 191-193
86 CH3 H CH20 3,4-di-F-Ph 1 15-117
87 CH3 H O 5-CH3-2-thiazolyl 107-109
88 CH3 H 0 5-Si(CH3)3-2-thiazolyl 66-68
89 CH3 H 0 4-CF3-2-pyridinyl oil*
90 CH3 H CH20-N=C(CH3) 4-CF3-6-Cl-2-pyridinyl 120-123
91 CH3 H CH20 2,3-di-F-Ph 107-109
92 CH3 H CH20 2,5-di-F-Ph 124-126
93 CH3 H CH20 2,3,5-tri-F-Ph 124-126
94 CH3 H CH20 2,4,5-tri-F-Ph 169-170.5
95 CH3 H CH20 2,3,5,6-tetra-F-Ph 119-121
96 CH3 H CH2S 2,5-di-CH3-Ph 94-96
97 CH3 H O 4-CH3-5-Br-2-thiazolyl 157-158
98 CH3 H CH20 2-F-5-CH3-Ph 122-125
99 CH3 H O 4-CH3-5-I-2-thiazolyl 170-172
100 CH3 H o 3-(CH3C≡C)-Ph *
101 CH3 H 0 3-(/-Bu-C≡C)-Ph 141-143
102 CH3 H OCH2 3-pyridinyl 147-151
103 CH3 H OCH2 4-pyridinyl 127-131
104 CH3 H O 5-(CH3S)-2-thiazolyl 60-64
105 CH3 H o 4-CH3-5-Cl-2-thiazolyl 132-134
106 CH3 H o 5-«-Bu-2-thiazolyl 100-101
107 H CH3 CH20-N 1=C(CH3) 4-CF -2-pyridinyl oil*
108 CH3 H O 6-/-BuO-4-pyrimidinyl oil*
109 CH3 H CH20- I=C(CH3) 3-Si(CH3)3-Ph *
110 CH3 H O 3-( [>-C≡C)-Ph *
111 CH3 H O 3-(HC≡C)-Ph 91-93
112 CH3 H O 3-((CH3)3SiC≡C)-Ph *
Figure imgf000144_0001
114 CH3 H CH20-JN l=C(CH3) 6-CF3-2-pyridinyl 105-108 Cmpd Ex. RJ R4 mp (°C) No.
Figure imgf000145_0001
1 16 CH3 H O 5-( H2<r;CH-C≡C)-2-thiazolyl H2C
117 CH3 H O 5-((CH3)3C)-Ph *
118 5 CH3 H O 2-thienyl oil*
119 CH3 H CH20-N= =C(CH3) 3-CF3-Ph 62-65
120 CH3 H O 4,5-di-Br-2-thiazolyl 174-176
121 CH3 H O 5-(CH3CH2CH2)-2-thiazolyl 100-101
122 6 CH3 H O 5-Br-2-thienyl oil*
123 CH3 H CH20-N= =C(CH3) 3-CF3-2-pyridinyl 11 1-112
*See Index Table D for Η NMR data.
INDEX TABLE B
Cmpd No. Structure mp (°C)
Figure imgf000145_0002
INDEX TABLE C
Figure imgf000146_0001
125 CH3S(O) 108-111
INDEX TABLE D
Cmpd No. lU NMR Data (CDC13 solution unless indicated otherwise)3
δ 7.49 (d,2H), 7.37-7.26 (m,4H), 5.15 (ABq,2H), 3.89 (s,3H), 3.43 (s,3H),
2.18 (s,3H), 2.15 (s,3H). δ 7.50 (m,2H), 7.34 (m,4H), 7.20 (m,lH), 5.18 (dd,2H), 3.87 (s,3H),
3.40 (s,3H), 2.18 (s,6H). δ 7.48 (d,2H), 7.32 (d,lH), 7.21 (d,2H), 5.16 (d,2H), 3.86 (s,3H),
3.46 (d,3H), 2.47 (d,3H), 2.10 (d,6H). δ 7.48 (d,lH), 7.46 (s,lH), 7.41 (dd,2H), 7.35 (d, lH), 7.16 (d,2H),
5.15 (ABq, 2H), 3.46 (s,3H), 2.34 (s,3H), 2.18 (s,6H), 1.95 (s,3H). δ 7.24 (m,2H), 7.1 (m,3H), 6.85 (m,2H), 5.03 (s,2H), 3.88 (s,3H),
3.45 (s,3H), 2.35 (s,3H), 2.22 (s,3H).
19 δ 7.51 (m,4H), 7.37 (m,lH), 6.94 (d,lH), 6.83 (d, lH), 5.11 (s,2H),
3.88 (s,3H), 3.44 (s,3H), 2.24 (s,3H).
20 δ 7.36 (m,2H), 7.25 (m,3H), 6.87 (m,2H), 5.05 (s,2H), 3.88 (s,3H), 3.45
(s,3H), 2.23 (s,3H), 1.31 (s,9H).
22 δ 7.23 (m,lH), 6.95 (m,3H), 6.84 (m,2H), 6.67 (d,lH), 3.90 (s,3H), 3.79
(s,3H), 3.42 (s,3H), 2.26 (s,3H).
29 δ 7.22 (m,3H), 7.07 (t,lH), 7.00 (d,lH), 6.92 (d,lH), 6.55 (d,lH), 3.89
(s,3H), 3.42 (s, 3H), 2.27 (s, 3H), 2.18 (s,3H).
37 δ 7.46 (d, J = 7 Hz, IH) 7.38, (t, J = 7 Hz, IH) 7.28, (d, J = 7 Hz, IH)
7.12, (m,2H), 6.89 (t, J = 7 Hz, IH), 6.78 (d, J = 8 Hz, IH), 4.98
(s,2H), 3.90 (s,3H), 3.44 (s,3H), 2.66 (q, J = 7.5 Hz, 2H), 2.18 (s,3H),
1.20 (t, J = 7.5 Hz, 3H). δ 7.47 (d, J = 7.5 Hz, IH), 7.39 (t, J = 7.5 Hz, 1H), 7.29 (d, J = 7.5 Hz,
IH), 7.22 (dd, J = 7.5, 1.7 Hz, IH), 7.10 (td, J = 7.5, 1.7 Hz, 1H), 6.93 (t, J = 7.5 Hz, IH), 6.79 (d, J = 7.5 Hz, IH), 4.97 (s,2H), 3.90 (s,3H), 3.45 (s,3H), 3.36 (m,lH), 2.18 (s,3H), 1.22 (d, J = 7 Hz, 6H). δ 8.74 (d, J = 5 Hz, IH), 8.10 (s,lH), 7.45-7.30 (m,4H), 5.23 (ABq,2H),
3.89 (s,3H), 3.43 (s,3H), 2.31 (s,3H), 2.18 (s,3H). δ 7.44(t,lH), 7.34(m,2H), 3.83(s,3H), 3.40(s,3H), 3.07(s,lH), 2.29(s,3H). δ 8.71(d,lH,J=1.0), 7.41(t,lH,J=7.9), 7.23(d, lH,J=7.7), 7.14(d, lH,J=8.0),
6.87(d,lH,J=1.0), 3.75(2,3H), 3.33(s,3H), 2.27(s,3H), 1.34(s,9H). δ 8.48 (d, J = 5 Hz, IH), 7.83 (s,lH), 7.39 (m,2H), 7.26 (m,2H), 5.21
(m,2H), 3.89 (s,3H), 3.42 (s,3H), 2.30 (s,3H), 2.18 (s,3H), 1.33 (s,9H). δ 7.69 (d,lH), 7.61 (d, lH), 7.31 (s,lH), 7.17 (m,4H), 7.04 (d,lH), 6.79
(d,lH), 3.91 (s,3H), 3.83 (s, 3H), 3.36 (s, 3H), 2.28 (s,3H) δ 7.40-7.37 (m,2H), 7.35-7.20 (m, 2H), 7.15-7.05 (m, IH), 6.95 (dd,lH),
5.15 (ABq,2H), 3.89 (s,3H), 3.43 (s,3H), 2.31 (s,3H), 2.20 (s,3H), 2.19 (s,3H). δ 7.85 (d,lH), 7.63-7.58 (m,lH), 7.38 (d,lH), 7.32-7.29 (m,2H), 7.18
(t,lH), 5.17 (ABq,2H), 3.89 (s,3H), 3.42 (s,3H), 2.22 (d,3H), 2.18
(s,3H). δ 8.31(d,lH,J=5.0), 7.4(m,lH), 7.2(m,2H), 7.1(m,2H), 3.8(s,3H),
3.3(s,3H), 2.26(s,3H). δ 7.27 (m,lH), 7.21 (m,lH), 7.10 (m,2H), 7.00 (s,lH), 6.92 (d,lH), 6.80
(d,lH), 3.84 (s,3H), 3.39 (s, 3H), 2.27 (s, 3H), 2.02 (s,3H) δ 8.73 (d,lH,J=4.0), 8.10 (s,lH), 7.43( d,lH,J=3.8, 7.35 (m,2H), 7.08
(m,lH), 5.26 (s,2H), 3.86 (s,3H), 3.43 (s,3H), 2.54 (s,3H), 2.25 (s,3H). δ 8.35 (s,lH), 7.4 (m,lH), 7.2 (m,lH), 7.1 (m,lH), 6.05 (s,lH), 3.79
(s,3H), 3.34 (s,3H), 2.25 (s,3H), 1.60 (s,9H). δ 7.72 (s,lH), 7.56 (d,lH), 7.50 (d,lH), 7.25-7.40 (m,4H), 5.16 (ABq,2H),
3.88 (s,3H), 3.41 (s,3H), 2.21 (s,3H), 2.18 (s,3H), 0.28 (s,9H). δ 7.26 (m,lH), 7.19 (t,lH), 7.10 (d,lH), 7.06 (d,lH), 6.99 (s,lH), 6.89
(m,lH), 6.79 (d,lH), 3.84 (s,3H), 3.39 (s,3H), 2.26 (s,3H), 1.41 (m,lH)
0.85 (m,2H), 0.78 (m,2H). δ 7.23 (m,3H), 7.08 (m,2H), 6.96 (m,lH), 6.79 (d,lH), 3.84 (s,3H), 3.39
(s,3H), 2.27 (s,3H), 0.23 (s,9H). δ 7.38 (m,lH), 7.21 (m,3H), 3.82 (s,3H), 3.41 (s,3H), 2.27 (s,3H), 1.42 (m,lH), 0.89 (m,2H), 0.79 (m,2H). δ 7.38 (t,lH), 7.22 (m,2H), 7.17 (s,lH), 3.83 (s,3H), 3.41 (s,3H), 2.28 (s,3H), 1.28 (s,9H). 118 δ 7.26 (t,lH), 7.05 (d,lH), 6.91 (d,lH), 6.77-6.83 (m,2H), 6.55 (dd,lH),
3.93 (s,3H), 3.45 (s,3H), 2.27 (s,3H). 122 δ 7.28 (t, IH) 7.07 (d, IH), 6.95 (d, IH), 6.79 (d, IH), 6.35 (d, IH), 3.94
(s, 3H), 3.45 (s, 3H), 2.26 (s, 3H). a *H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (m)-multiplet, (t)-triplet, (ABq)-AB quartet, (dd)-doublet of doublets and (td)-triplet of doublets.
BIOLOGICAL EXAMPLES OF THE INVENTION Test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-F. Spraying these 200 ppm test suspensions to the point of run-off on the test plants is the equivalent of a rate of 500 g/ha.
TEST A The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Erysiphe graminis f sp. tritici, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20°C for 7 days, after which disease ratings were made.
TEST B The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 6 days, after which disease ratings were made.
TEST C The test suspension was sprayed to the point of run-off on rice seedlings. The following day the seedlings were inoculated with a spore suspension of Pyricularia oryzae (the causal agent of rice blast) and incubated in a saturated atmosphere at 27°C for 24 h, and then moved to a growth chamber at 30°C for 5 days, after which disease ratings were made.
TEST D The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of potato and tomato late blight) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 5 days, after which disease ratings were made. TEST E The test suspension was sprayed to the point of run-off on grape seedlings. The following day the seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20°C for 24 h, moved to a growth chamber at 20°C for 6 days, and then incubated in a saturated atmosphere at 20°C for 24 h, after which disease ratings were made.
TEST F The test suspension was sprayed to the point of run-off on cucumber seedlings. The following day the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of gray mold on many crops) and incubated in a saturated atmosphere at 20°C for 48 h, and moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.
Results for Tests A-F are given in Table A. In the table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (--) indicates no test results. ND indicates disease control not determined due to phytotoxicity.
Table A
Cmpd No. Test A TestB TestC TestD TestE TestF
1 99 100 97 ND 100* ND
2 100 100 98 85 100* 77
3 99 100 100 100 100* 96
4 77 99 90 100 100* 0
5 99 100 99 0 100* 0
6 99 100 91 99 100* 0
7 100 100 99 76 100* 0
8 100 100 100 100 99* 0
9 100 100 99 - 100* 0
10 99 100 86 ND 100* 0
11 100 100 97 99 94* 94
12 100 100 99 100 99* 0
13 100 100 94 ND 54* 0
14 100 100 97 90 77* 0
15 100 100 94 96 9* 0
16 100 100 99 100 86* 0
17 100 100 97 ND 49* 0
18 99 94 97 81 16* 0
19 98 94 0 51 55* 0
20 91 94 53 18 47* 94 Cmpd No. Test A Test B Test C Test D Test E Test F
21 99 97 97 76 0* 0
22 99 100 99 94 33* 43
23 99 100 100 ND 87* 0
24 98 99 97 72 13* 94
25 100* 96* 32** - 100* ~
26 100 100 97 99 100* 95
27 100 100 97 96 87* 82
28 99 97 94 0 100* 83
29 98 99 0 0 ~ 0
30 97 100 100 ND ~ 94
31 98 86 0 19 0* 0
32 95 86 0 0 8* 0
34 98 99 91 0 100* 0
35 56 0 0 24 ~ 0
36 100 100 97 ND 100* 0
37 99 99 86 0 ~ 0
38 100 100 97 0 28* 0
39 98 94 53 16 7* 0
40 100 100 93 73** 100* 0
41 11* 52* 0* - 13* -
42 98 93 86 74 12* 97
43 86 93 86 74 - 0
44 98 99 94 86 41* 73
45 100 99 53 92 100* 0
46 99 100 74 61 99* 0
47 100 100 99 86 100* 0
48 95 100 74 0 78* 0
49 91 28 0 0 6* 86
50 99 100 97 ND 25* 0
51 100 100 97 92 16* 0
52 100 100 97 96 16* 94
53 100 100 97 0 97* 94
54 90 93 53 0 15* 48
55 99* 39* 0* - 59* -
56 95 97 94 99 45* 0
57 100 99 100 ND 100* 0 Cmpd No. Test A Test B Test C Test D Test E Test F
58 84 67 0 24 0* 0
59 100* 100* 78* ~ 100* -
60 98 100 74 88 9* 0
61 97 100 99 ND 85* 0
62 98 100 97 100 - 0
63 92 86 32 90 3* 0
64 100 100 97 86 42* 95
65 98 100 86 24 96* 83
66 100 100 94 46 49* 0
67 99 100 97 0 82* 0
68 98 97 52 ND - 0
69 95 97 52 ND - 0
70 97 94 52 86 - 0
71 100 94 53 ND 37* 95
72 80** 97** 53** 25** ~ g**
73 100 100 94 100a ~ 83
74 97 100 86 97 - 0
75 99 99 74 93 12* 0
76 100 100 97 100 68* 0
77 100 100 74 ND 40* 94
78 99 97 86 ND 94* 69
79 86 86 0 ND 65* 6
81 100 100 94 100 100* 98
82 98 99 94 9 71* 90
83 100 100 99 ND 100* 0
84 100 100 91 ND 72* 0
85 100 99 86 ND 83* 0
86 100 97 53 ND 0* 0
87 100 100 94 ND 45* 0
88 100 100 86 ND 69* 0
89 100 100 100 ND 73* 0
90 100 100 100 ND 100* 98
91 100 94 86 91 15* 83
92 100 99 100 100 4* 0
93 100 97 91 83a 31* 0
94 100 86 91 96a 84a>* 0 Cmpd No. Test A Test B Test C Test D Test E Test F
95 100 99 99 96 38* 98
96 100 99 86 99a 80* 98
97 100 99 74 ND - 0
98 100 94 53 46 ~ 83
99 99 100 99 ND 100* 83
100 100 100 100 100 94* 0
101 100 100 97 99 100* 0
102 38 0 0 0 - 0
103 38 0 0 88 - 0
104 100 100 97 ND - 0
105 100 100 100 ND - 85
106 100 100 97 ND ~ 55
107 98a 100a 100 71 100* 97
108 98 97 94 ND 1* 20
109 98 100 90 70 100a>* 0
110 98 100 97 100 100* 0
111 100 100 97 100 68* 0
112 100 100 100 98 70* 0
113 30 0 0 0 ~ 0
114 100 100 97 100a 43* 74
116 100 100 88 ND ~ 0
117 100 100 97 100 ~ 98
118 100 100 100 93 ~ 99
119 100 100 94 93 - 0
120 99 100 97 100 ~ 98
121 99 99 94 ND ~ 98
124 100** 100** 97** 92** ~ 9g**
125 100 99 53 0 36 a Indicates a 20% burn rating.
* Tested at 10 ppm (equivalent to 25 g/ha).
** Tested at 40 ppm (equivalent to 100 g/ha). TABLE B
Comparison of Activity on Wheat Powdery Mildew (WPM)b
Figure imgf000153_0001
Compound A Compound B (WO 97/00612 (WO 96/38425 Compound 13 Compound 1 Index Table C) Table 1)
Rate (ppm) Compound A Compound B Compound 13c
10 9 100 100
2 38 78 98 b The test protocol is described in Test A. c Number refers to compound descriptions in Index Table A.
TEST G Fall Armyworm
Test units, each consisting of a H.I.S. (high impact styrene) tray with 16 cells were prepared. Wet filter paper and approximately 8 cm2 of lima bean leaf was placed into twelve of the cells. A 0.5-cm layer of wheat germ diet was placed into the four remaining cells. Fifteen to twenty third-instar larvae of fall armyworm (Spodoptera frugiperda) were placed into a 230-mL (8-ounce) plastic cup. Solutions of each of the test compounds in 75:25 acetone-distilled water solvent were sprayed into the tray and cup. Spraying was accomplished by passing the tray and cup on a conveyer belt directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of 0.138 kilograms of active ingredient per hectare (about 0.13 pounds per acre) at 207 kPa (30 p.s.i.). The insects were transferred from the 230-mL cup to the H.I.S. tray (one insect per cell). The trays were covered and held at 27°C and 50% relative humidity for 48 hours, after which time readings were taken on the twelve cells with lima bean leaves. Of the compounds tested, the following gave control efficacy levels of 80% or greater: 59, 79 and 112. The four remaining cells were read at 6-8 days for delayed toxicity. Of the compounds tested, the following gave control efficacy levels of 80% or greater: 7, 59 and 112. TEST H Southern Corn Rootworm
Test units, each consisting of a 230-mL (8-ounce) plastic cup containing a 6.5-cm2 (1 -square-inch) plug of a wheatgerm diet, were prepared. The test units were sprayed as described in TEST G with individual solutions of the test compounds. After the spray on the cups had dried, five second-instar larvae of the southern corn rootworm (Diabrotica undecimpunctata howardi) were placed into each cup. The cups were held at 27°C and 50% relative humidity for 48 hours, after which time mortality readings were taken. The same units were read again at 6-8 days for delayed toxicity. Of the compounds tested, the following gave control efficacy levels of 80% or greater: 1, 5, 7, 8, 11, 12, 27 34, 53, 57, 59, 71, 97, 101, 112 and 117.
TEST I Two-Spotted Spider Mite
Pieces of kidney bean leaves, each approximately 6.5 cm2 (1 square inch) in area, that had been infested on the undersides with 25 to 30 adult mites (Tetranychus urticae), were sprayed with their undersides facing up on a hydraulic sprayer with a solution of the test compound in 75:25 acetone-distilled water solvent. Spraying was accomplished by passing the leaves, on a conveyor belt, directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of 0.138 kilograms of active ingredient per hectare (about 0.13 pounds per acre) at 207 kPa (30 p.s.i.). The leaf squares were then placed underside-up on a square of wet cotton in a petri dish and the perimeter of the leaf square was tamped down onto the cotton with forceps so that the mites could not escape onto the untreated leaf surface. The test units were held at 27°C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested, the following gave mortality levels of 80% or higher: 1, 10, 17, 34, 45, 46, 47, 55, 59, 64, 79, 84, 85, 95, 96, 98, 101, 112 and 124.
TEST J Corn Planthopper Test
Test Unit: The test unit consists of a plastic cup containing 126 +/- 4 grams of sterilized, non-fertilized sassafras (sandy loam) soil. One pre-germinated Pioneer variety 3394 corn seed is placed in a 1 inch depression in the soil and covered. The test unit is watered with 15ml of distilled water and placed in a closed plexiglas box inside a greenhouse operating at 24 degrees centigrade and 36% relative humidity for 4 days at which time it is ready for test. A snug fitting test unit lid with a small opening at the top is placed on all test units prior to test.
Compound Application: Test compounds are formulated at 200ppm in 20% acetone: 80% water containing 500ppm Ortho X-77 surfactant. Compounds are applied through the opening in the test unit lid with an atomizer sprayer fitted with a Model 17690- 1/8 JJAU nozzle and a spray set-up consisting of a J2850 Fluid Cap and J70 Air Cap (Spray Sytems, Inc.). The sprayer was operated at 12-13psi. For each compound, 2 test units are sprayed with a total of 2ml each of test solution. After spraying, test units are placed in a ventilated enclosure for 10-15 minutes to dry.
Insect Infesting/Evaluation: After drying, a thin layer of white quartz sand is poured onto the soil of each test unit to aid in the evaluation of live and dead insects at the conclusion of the test. Each unit is infested with a minimum of 15 nymphs of the corn planthopper, Peregrinus maidis, which are approximately 21 days old. Infested test units are held in a growth chamber operating at 22 degrees centigrade and 50% relative humidity with a 16:8 light: dark photoperiod. Insect mortality is evaluated at 6 days post-infestation. Moribund insects are counted as dead. Of the compounds tested, the following gave mortality of 80% or greater: 71.
TABLE C
Comparisons of activity on Southern Corn Rootworm (SCRW)d
Figure imgf000155_0001
Compound C Compound D (WO 97/00612 Compound 7 Index Table C)
Rate (ppm) Compound C Compound l le Compound D Compound 12e
250 87 100 60 93
50 0 53 d The test protocol is described in Test H. e Number refers to compound descriptions in Index Table A.

Claims

CLAIMS What is claimed is:
1. A method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of a compound selected from Formula I, N-oxides and agriculturally suitable salts thereof,
Figure imgf000156_0001
wherein T is
Figure imgf000156_0002
T2
Tl
Figure imgf000156_0003
T3 or χ4
X is OR1, SCOJmR1 or halogen;
A is O, S, N, NR5 or CR7;
G is C or N; provided that when G is C, A is O, S or NR5 and the floating double bond is attached to G; and when G is N, A is N or CR7 and the floating double bond is attached to A;
W is O; S; NH; N(CrC6 alkyl); or NO(CrC6 alkyl);
Y is -O-, -CH2O-, -OCH2-, -CHRπO-N=C(R8)-, a direct bond, -(CH2)r-,
-C(R1 1)=C(R1 1)-, -CH2S(O)n-, -C(R8) =N-O-CHR1 1-, -CHRHSC(R8)=N-, -C(R! 1)=N-N=C(R1 !)-, -CHR1 !O-N=C(R8)CH2S-, -CHR1 1O-N=C(R8)CH2O-, -C(R1 1)=N-N(CH3)-, -CHR1 1OC(R8)=N-, -CHR1 1OC(=S)NR1 1-, -CHR1 1SC(=S)NR1 1-, -SCHR1 1-, or -CHR1 1O-N=C(R1 1)C(=N-OR1 1)-; and the directionality of the Y linkage is defined such that the moiety depicted on the left side of the linkage is bonded to the phenyl ring having the R3 and R4 substituents and the moiety on the right side of the linkage is bonded to Z; Z is independently selected from: i) C Cjo alkyl, C j-C10 haloalkyl or phenyl each optionally substituted with R9 and optionally substituted with one or more R10; ii) a ring selected from 5 or 6-membered aromatic heterocyclic rings, each heterocyclic ring containing 1 to 4 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring contains no more than 3 nitrogens, no more than 1 oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring optionally substituted with R9 and optionally substituted with one or more R10; iii) a naphthalene ring optionally substituted with R9 and optionally substituted with one or more R10; and iv) a tetrahydronaphthalene ring optionally substituted with R9 and optionally substituted with one or more R10;
R1 is CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl,
C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl or C2-C4 alkoxycarbonyl; R2 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2-C alkoxycarbonyl, hydroxy, Cj-C2 alkoxy or acetyloxy; R3 and R4 are each independently H or CH3, provided that R3 and R4 are not both H; R5 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C -C4 alkylcarbonyl or C2-C4 alkoxycarbonyl;
R6 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C -C alkoxycarbonyl, hydroxy, Cι-C2 alkoxy or acetyloxy; R7 is H, halogen or methyl; R8 is H, CrC3 alkyl, CrC3 alkoxy, CrC3 alkylthio, CrC3 haloalkyl, C2-C3 alkenyl,
C2-C3 alkynyl, cyclopropyl, cyano or NH2; R9 is halogen; CrC6 alkyl; CrC6 haloalkyl; CrC6 alkoxy; CrC6 haloalkoxy; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-Cg alkynyl; C;-C6 alkylthio;
CrC6 haloalkylthio; CrC6 alkylsulfinyl; CrC6 alkylsulfonyl; C3-C6 cycloalkyl; trimethylsilyl; C -C6 alkynyl substituted with trimethylsilyl or C3- cycloalkyl; or phenyl or phenoxy, each phenyl or phenoxy optionally substituted with R12 and optionally substituted with one or more R13; provided that when R9 is phenyl or phenoxy each optionally substituted with R12 and optionally substituted with one or more R13, then T is other than T1; R10 is halogen, CrC6 alkyl, CrC6 haloalkyl, CrC6 alkoxy, CrC6 haloalkoxy or cyano; or R9 and R10 when attached to adjacent carbon atoms can be taken together as
-CH2CH2O- or -OCH2CH2O-; each R1 1 is independently H, Cj-C3 alkyl or cyclopropyl;
R12 is halogen, C^Cg alkyl, Cj-Cg haloalkyl, Cj-Cg alkoxy, Cj-C6 haloalkoxy, C2-C6 alkenyl, C2- haloalkenyl, C2-Cg alkynyl, Cj-C^ alkylthio, CrC6 haloalkylthio, CrC6 alkylsulfinyl, CrC6 alkylsulfonyl or C3-C6 cycloalkyl; R13 is halogen, Cj-Cg alkyl, Cj-C6 haloalkyl, Cj-Cg alkoxy, Cj-C6 haloalkoxy or cyano; m is 0, 1 or 2; n is 0, 1 or 2; r is 1, 2, 3 or 4; and s is 0 or 1 ; provided that when T is T1, then i) when Y is -O-, X is OMe, R3 is CH3 and R4 is H, then Z is other than 6-chloro-4-pyrimidinyl and 6-chloro-2-pyrazinyl; ii) when Y is a direct bond, X is Cl, R3 is CH3 and R4 is H, then Z is other than CH2Br; iii) when Y is -O- and Z is l,2,4-thiadiazol-5-yl or 2-thiazolyl optionally substituted with R9 and optionally substituted with R10, then neither R9 nor R10 is C(CH3)3; and iv) Y-Z is other than Cj-C10 alkyl and Cj-C j0 alkoxy. 2. A compound selected from Formula I, N-oxides and agriculturally suitable salts thereof,
Figure imgf000158_0001
wherein T is
R ofc
Figure imgf000159_0001
COOR5
Figure imgf000159_0002
T2
Tl
Figure imgf000159_0003
T3 or T4 ;
X is OR1, SCO^R1 or halogen;
A is O, S, N, NR5 or CR7;
G is C or N; provided that when G is C, A is O, S or NR5 and the floating double bond is attached to G; and when G is N, A is N or CR7 and the floating double bond is attached to A;
W is O; S; NH; N(CrC6 alkyl); or NO(CrC6 alkyl);
Y is -O-, -CH2O-, -OCH2-, -CHR11O-N=C(R8)-, a direct bond, -(CH2)r-,
-C(R1 1)=C(R1 1)-, -CH2S(O)n-, -C(R8) =N-O-CHR -, -CHR 1SC(R8)=N-, -C(R! i)=N-N=C(R! 1)-, -CHR1 1O-N=C(R8)CH2S-, -CHR1 1O-N=C(R8)CH2O-, -C(R1 1)=N-N(CH3)-, -CHR1 1OC(R8)=N-, -CHR1 1OC(=S)NR11-, -CHR11SC(=S)NR11-, -SCHR11-, or -CHR1 1O-N=C(R11)C(=N-OR11)-; and the directionality of the Y linkage is defined such that the moiety depicted on the left side of the linkage is bonded to the phenyl ring having the R3 and R4 substituents and the moiety on the right side of the linkage is bonded to Z;
Z is independently selected from: i) Cj-Cjo alkyl, CJ-CJQ haloalkyl or phenyl each optionally substituted with R9 and optionally substituted with one or more R10; ii) a ring selected from 5 or 6-membered aromatic heterocyclic ring, each heterocyclic ring containing 1 to 4 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring contains no more than 3 nitrogens, no more than 1 oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring optionally substituted with R9 and optionally substituted with one or more R10; iii) a naphthalene ring optionally substituted with R9 and optionally substituted with one or more R10; and iv) a tetrahydronaphthalene ring optionally substituted with R9 and optionally substituted with one or more R10; R1 is Cj-Cg alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-Cg cycloalkyl, C2-C4 alkylcarbonyl or C2-C4 alkoxycarbonyl; R2 is H, Cj-Cg alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C -C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, hydroxy, Cj-C2 alkoxy or acetyloxy; R3 and R4 are each independently H or CH3, provided that R3 and R4 are not both H;
R5 is H, Cj-Cg alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-Cg cycloalkyl, C2-C4 alkylcarbonyl or C2-C4 alkoxycarbonyl; R6 is H, Cj-Cg alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, hydroxy, Cj-C2 alkoxy or acetyloxy; R7 is H, halogen or methyl;
R8 is H, Cj-C3 alkyl, C C3 alkoxy, Cj-C3 alkylthio, Cj-C3 haloalkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, cyano or NH2; R9 is halogen; Cj-Cg alkyl; Cj-Cg haloalkyl; Cj-Cg alkoxy; Cj-Cg haloalkoxy; C2-Cg alkenyl; C2-C6 haloalkenyl; C2-Cg alkynyl; Cj-C6 alkylthio; Cj-Cg haloalkylthio; Cj-C6 alkylsulfinyl; Cj-C6 alkylsulfonyl; C3-C6 cycloalkyl; trimethylsilyl; C2-Cg alkynyl substituted with trimethylsilyl or C3-Cg cycloalkyl; or phenyl or phenoxy, each phenyl or phenoxy optionally substituted with R12 and optionally substituted with one or more R13; provided that when R9 is phenyl or phenoxy each optionally substituted with R12 and optionally substituted with one or more R13, then T is other than T1; R10 is halogen, Cj-Cg alkyl, Cj-Cg haloalkyl, Cj-Cg alkoxy, Cj-Cg haloalkoxy or cyano; or R9 and R10 when attached to adjacent carbon atoms can be taken together as
-CH2CH2O- or -OCH2CH2O-; each R1 1 is independently H, Cj-C alkyl or cyclopropyl;
R12 is halogen, Cj-C6 alkyl, Cj-Cg haloalkyl, Cj-Cg alkoxy, Cj-Cg haloalkoxy, C2-Cg alkenyl, C2-C6 haloalkenyl, C -C6 alkynyl, Cj-Cg alkylthio, Cj-C6 haloalkylthio, Cj-Cg alkylsulfinyl, C,-C6 alkylsulfonyl or C3-C6 cycloalkyl; R13 is halogen, Cj-Cg alkyl, Cj-C6 haloalkyl, Cj-Cg alkoxy, Cj-C6 haloalkoxy or cyano; m is 0, 1 or 2; n is 0, 1 or 2; r is 1, 2, 3 or 4; and s is 0 or 1 ; provided that
(a) when T is T1, then i) when Y is -O-, X is OMe, R3 is CH3 and R4 is H, then Z is other than
6-chloro-4-pyrimidinyl and 6-chloro-2-pyrazinyl; ii) when Y is a direct bond, X is Cl, R3 is CH3 and R4 is H, then Z is other than CH2Br; iii) when Y is -O- and Z is l,2,4-thiadiazol-5-yl or 2-thiazolyl optionally substituted with R9 and optionally substituted with R10, then neither R9 nor R10 is C(CH3)3; iv) Y-Z is other than C j-Cj0 alkyl and C j-C 10 alkoxy; v) when Y is -CH2O-N=C(CH3)-, X is OMe, R3 is CH3 and R4 is H, then Z is other than 3-(trifluoromethyl)phenyl; vi) when Y is -CH2O-N=C(CH3)-, X is OMe, R3 is H and R4 is CH3, then Z is other than 3-(trifluoromethyl)phenyl; vii) when Z is 2-naphthalenyl or 5,6,7,8-tetrahydro-2-naphthalenyl, then Y is other than -CH2O- and -CH2O-N=C(CH3)-; viii) when Y is -CH2O-, R3 is CH3 and Z is phenyl substituted with R9 in the
2-position and R9 is methyl or halogen, then Z is substituted with at least one
R10 other than methyl and halogen; and ix) when Y is -CH2O-, R3 is CH3 and Z is phenyl substituted with R10 in the 2-position and R10 is methyl or halogen, then Z is substituted with at least one
R9 or R10 other than methyl and halogen;
(b) when T is T2, then i) Y is other than -OCH2-, -C(R] ^(R1 1)- and -SCHR11-; ii) when Y is -O- or -(CH2)r-, then Z is pyrimidinyl optionally substituted with R9 and optionally substituted with one or more R10; iii) when Y is -CH2O-, then Z is pyridinyl optionally substituted with R9 and optionally substituted with one or more R10; and iv) when Y is -CH2O-N=C(CH3)-, then s is 1.
(c) when T is T3, then i) Y is other than -SCHR11-; and ii) when Y is -CH2O-, then Z is phenyl optionally substituted with R9 and optionally substituted with one or more R10; and
(d) when T is T4, then i) Y is other than -QΕ.1 l)=C(Rl !)- and -CH2S(O)n-; and ii) when Y is -CH O-, then Z is phenyl or naphthalenyl, each optionally substituted with R9 and optionally substituted with one or more R10.
3. A compound of Claim 2 wherein T is T1;
A is N; G is N;
Y is -O-;
Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R9 and optionally substituted with one or more R10;
R9 is halogen, Cj-Cg alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or Cj-Cg haloalkoxy; and
R10 is halogen, Cj-C6 alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or Cj-Cg haloalkoxy.
4. A compound of Claim 2 wherein
T is T1;
A is N;
G is N;
Y is -CH2O-; Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R9 and optionally substituted with one or more R10; R9 is halogen, Cj-Cg alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or
Cj-Cg haloalkoxy; and R10 is halogen, Cj-Cg alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or Cj-Cg haloalkoxy.
5. A compound of Claim 2 wherein T is T1; A is N; G is N; Y is -CH2O-N=C(R8)-;
Z is phenyl, pyridinyl, thiazolyl or thiadiazolyl, each optionally substituted with R9 and optionally substituted with one or more R10; R8 is CH3;
R9 is halogen, Cj-Cg alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or Cj-Cg haloalkoxy; and
R10 is halogen, Cj-C6 alkyl, Cj-Cg alkoxy, Cj-Cg haloalkyl or Cj-Cg haloalkoxy.
6. A compound of Claim 2 wherein
T is T1; A is N; G is N; Y is -O-, -CH2O- or -CH2O-N=C(R8)-;
Z is thienyl optionally substituted with R9 and optionally substituted with one or more R10; R8 is CH3;
R9 is halogen or Cj-C3 alkyl; and R10 is halogen or Cj-C3 alkyl.
7. A compound of Claim 6 wherein Y is -O-.
8. A compound of Claim 2 selected from the group consisting of
4-[2-(3-fluorophenoxy)-6-methylphenyl]-2,4-dihydro-5-methoxy-2-methyl-
3H-1 ,2,4-triazol-3-one; 2,4-dihydro-5-methoxy-2-methyl-4-[2-methyl-6-(3-methylphenoxy)phenyl]-
3H-1 ,2,4-triazol-3-one; 2,4-dihydro-5-methoxy-2-methyl-4-(2-methyl-6-phenoxyphenyl)-3H-l,2,4- triazol-3-one; 2,4-dihydro-5-methoxy-2-methyl-4-[2-methyl-6-(4-methylphenoxy)phenyl]- 3H-l,2,4-triazol-3-one;
2,4-dihydro-5-methoxy-2-methyl-4-[6-methyl-2-[3-
(trifluoromethyl)phenoxy]phenyl]-3H-l,2,4-triazol-3-one; 2,4-dihydro-5-methoxy-2-methyl-4-[2-methyl-6-[[[[l-[4-(trifluoromethyl)-2- pyridinyl]ethylidene]amino]oxy]methyl]phenyl]-3H-l,2,4-triazol-3-one; 4-[2-[[[[l-[2-fluoro-5-(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]-
6-methylphenyl]-2,4-dihydro-5-methoxy-2-methyl-3H-l,2,4-triazol-3- one; 4-[2-[[[[l-(2-fluoro-5-methylphenyl)ethylidene]amino]oxy]methyl]-6- methylphenyl]-2,4-dihydro-5-methoxy-2-methyl-3H-l,2,4-triazol-3- one; and
2,4-dihydro-5-methoxy-2-methyl-4-[2-methyl-6-(2-thienyloxy)phenyl]-3H- l,2,4-triazol-3-one.
9. A fungicidal composition comprising a fungicidally effective amount of a compound of Claim 2 and at least one of a surfactant, a solid diluent or a liquid diluent.
10. An arthropodicidal composition comprising an arthropodicidally effective amount of a compound of Claim 2 and at least one of a surfactant, a solid diluent or a liquid diluent.
11. A method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound of Claim 2.
12. A method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of a compound of Claim 2.
PCT/US1997/021944 1996-11-26 1997-11-25 Methyl substituted fungicides and arthropodicides WO1998023156A1 (en)

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