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WO2007123853A2 - Five-membered heterocyclic invertebrate pest control agents - Google Patents

Five-membered heterocyclic invertebrate pest control agents Download PDF

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Publication number
WO2007123853A2
WO2007123853A2 PCT/US2007/009181 US2007009181W WO2007123853A2 WO 2007123853 A2 WO2007123853 A2 WO 2007123853A2 US 2007009181 W US2007009181 W US 2007009181W WO 2007123853 A2 WO2007123853 A2 WO 2007123853A2
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alkyl
compound
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nhch
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French (fr)
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WO2007123853A3 (en
Inventor
Dominic Ming-Tak Chan
Jeffrey Keith Long
Thomas Martin Stevenson
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EIDP Inc
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EI Du Pont de Nemours and Co
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Priority to BRPI0710380-8A priority Critical patent/BRPI0710380A2/en
Priority to MX2008013305A priority patent/MX2008013305A/en
Priority to AU2007240952A priority patent/AU2007240952A1/en
Publication of WO2007123853A2 publication Critical patent/WO2007123853A2/en
Publication of WO2007123853A3 publication Critical patent/WO2007123853A3/en
Anticipated expiration legal-status Critical
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D233/30—Oxygen or sulfur atoms
    • C07D233/32—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D291/00—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms
    • C07D291/02—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms not condensed with other rings
    • C07D291/04—Five-membered rings
    • 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
    • C07D401/10—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 carbon chain containing aromatic rings
    • 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
    • C07D403/10—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 carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
    • C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
    • C07D419/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D419/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings

Definitions

  • This invention relates to certain f ⁇ ve-membered heterocyclic derivatives, their iV-oxides, salts and compositions suitable for agronomic and nonagronomic uses, including those uses listed below, and methods of their use for controlling invertebrate pests such as arthropods in both agronomic and nonagronomic environments.
  • invertebrate pests The control of invertebrate pests is extremely important in achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer.
  • invertebrate pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, turf, wood products, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, environmentally safer or have different modes of action.
  • PCT Patent Publication WO 93/22298 discloses oxazolindine derivatives and pharmaceutically acceptable salts thereof as antihyperlipidemics.
  • Japanese Patent Publication 03176476 discloses imidazolidinones as useful chiral auxiliaries for producing penem or carbapenem antibiotics.
  • U.S. Patent 4186129 discloses oxazolidinones useful as neuroleptics and phosphodiesterase inhibitors.
  • This invention is directed to compounds of Formula 1 including all geometric and stereoisomers, ⁇ f-oxides, and salts thereof, and compositions containing them and their use for controlling invertebrate pests:
  • G is O or NR 3 ;
  • Z is N or CR 2 ; AMs CR 4 Or N; A 2 is CR 5 or N; A 3 is CR 6 or N; A 4 is CR 7 or N; Q is a 5- or 6-membered saturated or unsaturated heterocycle optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, C 1 -
  • R 1 is cyano; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 alkylcycloalkyl or C 4 -C 7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R 17 ; each R 2 is independently H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulf
  • R 4 , R 5 , R 6 and R 7 are independently selected from H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, C 1 -C 6 alkylamino, C 2 -Cg dialkylamino, cyano and nitro; or
  • R 6 and R 7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A 3 and A 4 bridgehead atoms, 3 atoms selected from 1 to 2 carbon atoms, O to 2 nitrogen atoms, O to 1 oxygen atom and O to 1 sulfur atom, or 4 atoms selected from 2 to 4 carbon atoms and O to 2 nitrogen atoms; each R 8 , R 12 and R 14 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 alkylcycloalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 7 alkylcarbonyl, C 2 ⁇ C 6 alkoxyalkyl or C 2 -C 7 alkoxycarbonyl; each R 9 , R 10
  • each R 17 and R 18 is independently halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio,
  • each R 19 is independently halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 2 -Cg alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, trimethylsilyl, cyano, nitro or Q 1 ; each Q 1 is independently a phenyl or a 5- or 6-membered saturated or unsaturated heterocycle, each optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1
  • This invention also provides a composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula 1, an ⁇ f-oxide or a salt thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.
  • This invention further provides a spray composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula 1, an ⁇ f-oxide or a salt thereof, or the composition described above, and a propellant.
  • This invention also provides a bait composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula 1, an N-oxide or a salt thereof, or the composition described above, one or more food materials, optionally an attractant, and optionally a humectant.
  • This invention further provides a trap device for controlling an invertebrate pest comprising said bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to said bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
  • This invention also provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula 1, an ⁇ f-oxide or a salt thereof, (e.g., as a composition described herein).
  • This invention also relates to such method wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1, an ⁇ f-oxide or a salt thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.
  • This invention also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of Formula 1, an Af-oxide or a salt thereof, (e.g., as a composition described herein). This invention also relates to the treated seed. This invention further provides a method for protecting an animal from an invertebrate parasitic pest comprising administering to the animal a parasiticidally effective amount of a compound of Formula 1, an iV-oxide or a salt thereof, (e.g., as a composition described herein). DETAILS OF THE INVENTION
  • compositions comprising, “comprising,” “includes,” “including,” “has,” “having,” “contains” or “containing,” or any other variation thereof, are intended to cover a non-exclusive inclusion.
  • a composition, a mixture, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus.
  • “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
  • invertebrate pest includes arthropods, gastropods and nematodes of economic importance as pests.
  • arthropod includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans.
  • gastropod includes snails, slugs and other Stylommatophora.
  • helminths includes worms in the phylum of Nemathelminth, Platyhelminth and Acanthocephala such as: round worms, heartworms, and phytophagous nematodes (Nematoda), flukes (Trematoda), tape worms (Cestoda) and throny-headed worms.
  • invertebrate pest control means inhibition of invertebrate pest development (including mortality, feeding reduction, and/or mating disruption), and related expressions are defined analogously.
  • agronomic refers to the production of field crops such as for food and fiber and includes the growth of corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye, rice, maize), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (berries, cherries) and other specialty crops (e.g., canola, sunflower, olives).
  • wheat e.g., wheat, oats, barley, rye, rice, maize
  • leafy vegetables e.g., lettuce, cabbage, and other cole crops
  • fruiting vegetables e.g., tomatoes, pepper, eggplant, crucifers and cucurbits
  • potatoes e.g., sweet potatoes, grapes, cotton, tree fruits (e.g.
  • nonagronomic refers to other horticultural crops (e.g., greenhouse, nursery or ornamental plants not grown in a field), residential and commercial structures in urban and industrial settings, turf (e.g., sod farm, pasture, golf course, residential lawn, recreational sports field, etc.), wood products, stored product, agro-forestry and vegetation management, public health (human) and animal health (e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife) applications.
  • turf e.g., sod farm, pasture, golf course, residential lawn, recreational sports field, etc.
  • wood products e.g., stored product, agro-forestry and vegetation management
  • public health (human) and animal health e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, /i-propyl, /-propyl, or the different butyl, pentyl or hexyl isomers.
  • Alkenyl includes straight-chain or branched alkenes such as ethenyl, 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 comprising multiple triple bonds such as 2,5-hexadiynyl.
  • Alkoxy includes, for example, methoxy, ethoxy, ⁇ -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)-, (CHs) 2 CHS(O)- and the different butylsulfinyl, pentylsulfinyl and hexylsulf ⁇ nyl 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 ⁇ 2 CHS(O) 2 -, and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers.
  • Alkylamino alkylamino
  • dialkylamino and the like, are defined analogously to the above examples.
  • Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • alkylcycloalkyl denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, j-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl.
  • cycloalkylalkyl denotes cycloalkyl substitution on an alkyl moiety. Examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups.
  • halogen either alone or in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” or “alkyl substituted with halogen” include F 3 C-, ClCH 2 -, CF 3 CH 2 - and CF 3 CCl 2 -.
  • halocycloalkyl haloalkoxy
  • haloalkylthio CF 3 CH 2 O-
  • haloalkylthio examples include CCl 3 S-, CF 3 S-, CCl 3 CH 2 S- and ClCH 2 CH 2 CH 2 S-.
  • haloalkylsulfinyl examples include CF 3 S(O)-, CCl 3 S(O)-, CF 3 CH 2 S(O)- and CF 3 CF 2 S(O)-.
  • haloalkylsulfonyl examples include CF 3 S(O) 2 -, CCl 3 S(O) 2 -, CF 3 CH 2 S(O) 2 - and CF 3 CF 2 S(O) 2 -.
  • Alkylcarbonyl denotes a straight-chain or branched alkyl moieties bonded to a
  • C 1 -C 4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2
  • C 3 alkoxyalkyl designates, for example, CH 3 CH(OCH 3 ), CH 3 OCH 2 CH 2 or CH 3 CH 2 OCH 2
  • C 4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH 3 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • substituents When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independently selected from the group of defined substituents, e.g., (R 2 ) n , n is 1, 2, 3 or 4.
  • substituents When a group contains a substituent which can be hydrogen, for example R 2 , then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.
  • heterocycle denotes rings or ring systems in which at least one ring atom is not carbon, e.g., nitrogen, oxygen or sulfur.
  • a heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs.
  • the heterocyclic ring can be attached through any available carbon or nitrogen by replacement of hydrogen on said carbon or nitrogen.
  • the heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated heterocyclic ring satifies the H ⁇ ckel rule, then said ring is also called a "heteroaromatic ring” or "aromatic heterocyclic ring”.
  • aromatic ring' or “aromatic ring system” denotes fully unsaturated carbocycles and heterocycles in which at least one ring of the polycyclic ring system is aromatic (where aromatic indicates that the H ⁇ ckel rule is satisfied for the ring system).
  • fused bicyclic ring system denotes a ring system containing two fused rings in which either ring can be saturated, partially unsaturated, or fully unsaturated.
  • fused heterobicyclic ring system denotes a ring system containing two fused rings in which at least one ring atom is not carbon and which can be aromatic or nonaromatic, as defined above.
  • optionally substituted in connection with the heterocyclic rings refers to groups which are unsubstituted or have at least one non-hydrogen substituent that does not extinguish the biological activity possessed by the unsubstituted analog. As used herein, the following definitions shall apply unless otherwise indicated.
  • optionally substituted is used interchangeably with the phrase “substituted or unsubstituted” or with the term “(un)substituted.” Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.
  • Q or Q 1 When Q or Q 1 is a 5- or 6-membered nitrogen-containing heterocycle, it may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise indicated.
  • pyridinyl and pyridyl are equivalent alternative names for an organic radical formed by removing a hydrogen atom from a pyridine ring to form an attachment point; accordingly “pyridinyl” and “pyridyl” are used herein as synonyms.
  • Q 1 can be (among others) phenyl optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of Invention.
  • An example of phenyl optionally substituted with from one or more substituents is the ring illustrated as U-I in Exhibit 1, wherein R v is any substituent as defined in the Summary of the Invention for Q 1 and r is an integer from 0 to 5.
  • Q or Q 1 can be (among others) 5- or 6-membered saturated or unsaturated heterocycles optionally substituted with one or more substituents selected from the group of substituents as defined in the Summary of Invention.
  • Examples of 5- or 6-membered unsaturated aromatic heterocycles optionally substituted with from one or more substituents include the rings U-2 through U-61 illustrated in Exhibit 1 wherein R v is any substituent as defined in the Summary of the Invention for Q or Q 1 , and r is an integer from 0 to 4. Note that some U groups can only be substituted with less than 4 R v groups (e.g., U- 2 through U-5, U-7 through U-48, and U-52 through U-61).
  • R v groups are shown in the structures U-I through U-61, it is noted that they do not need to be present since they are optional substituents. Note that when R v is H when attached to an atom, this is the same as if said atom is unsubstituted. The nitrogen atoms that require substitution to fill their valence are substituted with H or R v . Note that when the attachment point between (R v ) r and the U group is illustrated as floating, (R v ) r can be attached to any available carbon atom or nitrogen atom of the U group.
  • Q or Q 1 is a 5- or 6-membered saturated or unsaturated non-aromatic heterocycle optionally substituted with one or more substituents selected from the group of substituents as defined in the Summary of Invention for Q or Q 1
  • one or two carbon ring members of the heterocycle can optionally be in the oxidized form of a carbonyl moiety.
  • 5- or 6-membered saturated or non-aromatic unsaturated heterocycles include the rings Q-I through Q-35 as illustrated in Exhibit 2, wherein R v is any substituent as defined in the Summary of the Invention for Q 1 .
  • (R v ) r when the attachment point between (R v ) r and the Q or Q 1 group is illustrated as floating, (R v ) r can be attached to any available carbon atom or nitrogen atom of the U group. Note that when the attachment point on the Q or Q 1 group is illustrated as floating, the Q or Q 1 group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the Q or Q 1 group by replacement of a hydrogen atom.
  • the optional substituents can be attached to any available carbon or nitrogen by replacing a hydrogen atom.
  • Q or Q 1 comprises a ring selected from Q-28 through Q-35
  • Q 2 is selected from O, S or N.
  • Q 2 is N, the nitrogen atom can complete its valence by substitution with either H or the substituents as defined in the Summary of Invention for Q or Q l .
  • Stereoisomers 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).
  • the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the present invention comprises compounds selected from Formula 1, TV-oxides 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.
  • nitrogen-containing heterocycles can form TV-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form TV-oxides.
  • nitrogen containing heterocycles which can form TV-oxides.
  • tertiary amines can form TV-oxides.
  • Synthetic methods for the preparation of TV-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as /-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.
  • MCPBA peroxy acids
  • alkyl hydroperoxides such as /-butyl hydroperoxide
  • sodium perborate sodium perborate
  • dioxiranes such as dimethyldioxirane
  • 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.
  • the salts of the compounds of the invention also include those formed with organic bases (e.g., pyridine or triethylamine) or inorganic bases (e.g., hydrides, hydroxides, or carbonates of sodium, potassium, lithium, calcium, magnesium or barium) when the compound contains an acidic moiety such as when Q 1 is phenyl substituted with C(O)OR 22 and R 22 is H.
  • organic bases e.g., pyridine or triethylamine
  • inorganic bases e.g., hydrides, hydroxides, or carbonates of sodium, potassium, lithium, calcium, magnesium or barium
  • the present invention comprises compounds selected from Formula 1, /V-oxides and salts thereof.
  • Embodiments of the present invention as described in the Summary of the Invention include:
  • Embodiment 1 A compound of Formula 1 wherein G is O.
  • Embodiment 2. A compound of Formula 1 wherein G is NR 3 .
  • Embodiment 3. A compound of Formula 1 wherein R 3 is H or cyano; or C 1 -C 4 alkyl optionally substituted with one or more substituents selected from halogen.
  • Embodiment 4 A compound of Embodiment 3 wherein R 3 is CH 3 , CH 2 CH 3 or
  • Embodiment 6 A compound of Formula 1 wherein Z is CR 2 .
  • Embodiment 7 A compound of Formula 1 wherein each R 2 is independently selected from H, halogen or C 1 -C 2 haloalkyl.
  • Embodiment 8 A compound of Embodiment 7 wherein each R 2 is independently H, halogen or CF 3 .
  • Embodiment 9 A compound of Formula 1 wherein A 1 is CR 4 .
  • Embodiment 10 A compound of Formula 1 wherein A 2 is CR 5 .
  • Embodiment 11 A compound of Formula 1 wherein A 3 is CR 6 .
  • Embodiment 12 A compound of Formula 1 wherein A 4 is CR 7 .
  • Embodiment 13 A compound of Formula 1 wherein R 4 and R 5 are independently selected from H, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, cyano and nitro.
  • Embodiment 14 A compound for Formula 1 wherein R ⁇ and R 7 are independently selected from H, halogen, Ci-C ⁇ alkyl, C 1 -C 3 haloalkyl, cyano and nitro; or R 6 and R 7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A 3 and A 4 bridgehead atoms, 4 atoms selected from 3 to 4 carbon atoms and 0 to 1 nitrogen atom.
  • Embodiment 15 A compound of Embodiment 14 wherein R 6 and R 7 are independently selected from H, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, cyano and nitro.
  • Embodiment 16 A compound of Embodiment 14 wherein R 6 and R 7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A 3 and A 4 bridgehead atoms, 4 atoms selected from 3 to 4 carbon atoms and 0 to 1 nitrogen atom.
  • Embodiment 17 A compound of Embodiment 14 or 16 wherein the fused aromatic ring contains 4 carbon atoms as ring members in addition to the A 3 and A 4 bridgehead atoms.
  • Embodiment 18 A compound of Formula 1 wherein Q is a pyridinyl ring, a pyrimidinyl ring, a triazinyl ring, a pyrazolyl ring, a triazolyl ring, an imidazolyl ring, an oxazolyl ring, an isoxazolyl ring, a thiazolyl ring or an isothiazolyl ring, each ring optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1
  • Embodiment 19 A compound of Embodiment 18 wherein Q is a pyridinyl ring, a pyrimidinyl ring, a triazinyl ring, a pyrazolyl ring, a triazolyl ring, an imidazolyl ring, an oxazolyl ring, an isoxazolyl ring, a thiazolyl ring or an isothiazolyl ring, each ring optionally substituted with one or more substituents independently selected from halogen, C 1 -Cg alkyl, C 1 -Cg haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl
  • Embodiment 20 A compound of Embodiment 19 wherein Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylamino, C 2 -C 4 dialkylamino, cyano, nitro, C(O)NR 8 R 9 , C(O)OR 10 , phenyl and pyridinyl, each phenyl and pyridinyl optionally substituted with one or more substituents independently selected from
  • Embodiment 21 A compound of Embodiment 20 wherein Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, cyano, nitro, C(O)NR 8 R 9 and C(O)OR 10 .
  • Embodiment 22 A compound of Embodiment 21 wherein Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C 1 -C 3 alkyl and C 1 -C 3 haloalkyl.
  • Embodiment 23 A compound of Embodiment 22 wherein Q is a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C 1 -C 3 alkyl and C 1 -C 3 haloalkyl.
  • Embodiment 24 A compound of Formula 1 wherein each R 8 is independently H, C 1 -C 6 alkyl, C 2 -Cy alkylcarbonyl or C 2 -C 7 alkoxycarbonyl.
  • Embodiment 25 A compound of Embodiment 24 wherein each R 8 is H.
  • Embodiment 26 A compound of Formula 1 wherein each R 9 is independently H; or
  • C 1 -C 4 alkyl C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 4 cycloalkyl, C 4 -C 7 alkylcycloalkyl or C 4 -C 7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R 19 .
  • Embodiment 27 A compound of Embodiment 26 wherein each R 9 is independently
  • Embodiment 28 A compound of Embodiment 27 wherein each R 9 is independently C 1 -C 4 alkyl optionally substituted with one Q 1 and optionally substituted with one or more substituents selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 - C 4 alkylthio, C 1 -C 4 alkylsulfonyl and cyano.
  • Embodiment 29. A compound of Formula 1 wherein each R 10 is independently H; or
  • C 1 -C 4 alkyl C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 4 cycloalkyl, C 4 -C 7 alkylcycloalkyl or C 4 -C 7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R 19 .
  • Embodiment 30 A compound of Embodiment 29 wherein each R 10 is independently C 1 -C 4 alkyl optionally substituted with one or more substituents selected from R l9 .
  • Embodiment 31 A compound of Embodiment 30 wherein each R 10 is independently
  • C 1 -C 4 alkyl optionally substituted with one Q 1 and optionally substituted with one or more substituents selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfonyl and cyano.
  • Embodiment 32 A compound of Formula 1 wherein each R 19 is independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfonyl, cyano, nitro and Q 1 .
  • Embodiment 33 A compound of Embodiment 32 wherein each R 19 is independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfonyl and cyano.
  • Embodiment 35 A compound of Formula 1 wherein R 12 is H, C 1 -C6 alkyl, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl.
  • Embodiment 36 A compound of Embodiment 35 wherein R 12 is H.
  • Embodiment 37 A compound of Formula 1 wherein R 13 is H; or C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 4 cycloalkyl, C 4 -C 7 alkylcycloalkyl or C 4 -C 7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R 19 .
  • Embodiment 38 A compound of Embodiment 37 wherein R 13 is H; or Cj-C 4 alkyl optionally substituted with one or more substituents selected from R 19 .
  • Embodiment 39 A compound of Embodiment 37 wherein R 13 is H; or Cj-C 4 alkyl optionally substituted with one or more substituents selected from R 19 .
  • a compound of Embodiment 38 wherein R 13 is H; or C 1 -C 4 alkyl optionally substituted with one Q 1 and optionally substituted with one or more substituents selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio,
  • Embodiment 40 A compound of Embodiment 39 wherein R 13 is H; or C 1 -C 4 alkyl optionally substituted with one Q 1 and optionally substituted with one or more fluorine.
  • Embodiment 41 A compound of Formula 1 wherein each R 19 is independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, Cj-C 4 alkylthio, C 1 -C 4 alkylsulfinyl,
  • Embodiment 42 A compound of Embodiment 41 wherein each R 19 is independently selected from halogen and Q 1 .
  • Embodiment 43 A compound of Formula 1. wherein each Q 1 is independently selected from phenyl, pyridinyl and thiazolyl, each optionally substituted with one or more substituents independently selected from halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, cyano, phenyl and pyridinyl.
  • Embodiment 44 A compound of Embodiment 43 wherein Q 1 is phenyl, pyridinyl or thiazolyl.
  • Embodiment 45 A compound of Embodiment 18 wherein Q is R 16 .
  • Embodiment 46 A compound of Embodiment 18 wherein Q is S(O) 2 NR 14 R 15 .
  • Embodiment 47 A compound of Formula 1 wherein R 14 is H, C 1 -C ⁇ alkyl, C 2 -C 7 alkylcarbonyl Or C 2 -C 7 alkoxycarbonyl.
  • Embodiment 48 A compound of Embodiment 47 wherein R 14 is H.
  • Embodiment 49 A compound of Formula 1 wherein R 15 is H; or C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 4 cycloalkyl, C 4 -C 7 alkylcycloalkyl or C 4 -C 7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R 19 .
  • Embodiment 50 A compound of Embodiment 49 wherein R 15 is H; or C 1 -C 4 alkyl optionally substituted with one or more substituents selected from R 19 .
  • Embodiment 51 A compound of Embodiment 50 wherein R 15 is H; or C 1 -C 4 alkyl optionally substituted with one or more substituents selected from halogen,
  • Embodiment 52 A compound of Embodiment 51 wherein R 15 is H; or C 1 -C 4 alkyl optionally substituted with one or more fluorine and at most one Q 1 .
  • Embodiment 53 A compound of Formula 1 wherein Q is other than R 16 .
  • Embodiment 54 A compound of Formula 1 wherein R 16 is halogen, C 1 -C3 haloalkyl, C2-C 4 dialkylamino, cyano or nitro.
  • Embodiment 55 A compound of Formula 1 wherein R 1 is C 1 -C3 alkyl optionally substituted with one or more substituents independently selected from R 17 .
  • Embodiment 56 A compound of Embodiment 55 wherein R 1 is C 1 -C 3 alkyl substituted with one or more halogen.
  • Embodiment 57 A compound of Embodiment 56 wherein R 1 is CF 3 .
  • Embodiment 58 A compound of Formula 1 wherein n is 1 or 2.
  • Embodiment 59 A compound of Formula 1 wherein at most 3 of A 1 , A 2 , A 3 and A 4 are
  • Embodiment 60 A compound of Embodiment 59 wherein at most 2 of A 1 , A 2 , A 3 and A 4 are N.
  • Embodiment 61 A compound of Embodiment 60 wherein at most 1 of A*, A 2 , A 3 and
  • Embodiment 62 A compound of Embodiment 61 wherein A 1 , A 2 , A 3 and A 4 are each other than N.
  • Embodiment 63 A compound of Formula 1 wherein when Z is CH, and one R 2 is attached to the phenyl ring at the 4-position, then said R 2 is other than C 1 -Cg alkoxy.
  • Embodiments of this invention including Embodiments 1-64 above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds.
  • embodiments of this invention including Embodiments 1-64 above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.
  • Embodiment A A compound of Formula 1 wherein
  • Q is a pyridinyl ring, a pyrimidinyl ring, a triazinyl ring, a pyrazolyl ring, a triazolyl ring, an imidazolyl ring, an oxazolyl ring, an isoxazolyl ring, a thiazolyl ring or an isothiazolyl ring, each ring optionally substituted with one or more substituents independently selected from halogen, C ] -Cg alkyl, CpCg haloalkyl, C ⁇ -Cg cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -Cg alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfin
  • Z is CR 2 ;
  • R 1 is C 1 -C 3 alkyl optionally substituted with one or more substituents independently selected from R 17 ;
  • each R 2 is independently selected from H, halogen or C 1 -C 2 haloalkyl;
  • R 3 is H or cyano; or C 1 -C 4 alkyl optionally substituted with one or more substituents selected from halogen;
  • R 4 and R 5 are independently selected from halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, cyano and nitro;
  • R 6 and R 7 are independently selected from halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, cyano and nitro; or R 6 and R 7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A 3 and A 4 bridgehead atoms, 4 atoms selected from 3 to 4 carbon atoms and O to 1 nitrogen atom;
  • each R 8 is independently H, C 1 -C 6 alkyl, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl;
  • each R 9 and R 10 is independently H; or C 1
  • R 13 and R 15 are independently H; or C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3- C 4 cycloalkyl, C 4 -C 7 alkylcycloalkyl or C 4 -C 7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R 19 ;
  • R 16 is halogen, C 1 -C 3 haloalkyl, C 2 -C 4 dialkylamino, cyano or nitro; each R 19 is independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfonyl, cyano, nitro and Q 1 ; each Q 1 is independently selected from phenyl, pyridinyl and thiazolyl, each optionally substituted with one or more substituents independently selected from
  • Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C]-C 4 alkoxy, C 1 -C 4 haloalkoxy, cyano, nitro, C(O)NR 8 R 9 and C(O)OR 10 ; or Q is C(O)NR 12 R 13 ; R 1 is CF 3 ;
  • R 6 and R 7 are independently selected from H, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, cyano and nitro; or R 6 and R 7 are taken together to form a fused aromatic ring, the fused aromatic ring containing 4 carbon atoms as ring members in addition to the A 3 and A 4 bridgehead atoms; each R 8 is H; each R 9 and R 10 is independently C 1 -C 4 alkyl optionally substituted with one Q 1 and optionally substituted with one or more substituents selected from halogen,
  • R 12 is H;
  • R 13 is H; or C 1 -C 4 alkyl optionally substituted with one or more substituents selected from R 19 ; and each R 19 is independently selected from halogen and Q 1 .
  • Embodiment D A compound of Embodiment C wherein each R 2 is independently H, halogen or CF 3 ;
  • R 3 is CH 3 , CH 2 CH 3 , or CH 2 CF 3 .
  • Embodiment E A compound of Embodiment D wherein G is O; and provided that A 1 , A 2 , A 3 and A 4 are each other than N.
  • Specific embodiments include compounds of Formula 1 selected from the group consisting of:
  • compounds of this invention are characterized by favorable metabolic and/or soil residual patterns and exhibit activity controlling a spectrum of agronomic and nonagronomic invertebrate pests.
  • compositions for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.
  • Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding
  • Embodiments e.g., as a composition described herein.
  • Embodiments of the invention also include a composition comprising a compound of any of the preceding Embodiments, in the form of a soil drench liquid formulation.
  • Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the soil with a liquid composition as a soil drench comprising a biologically effective amount of a compound of any of the preceding Embodiments.
  • Embodiments of the invention also include a spray composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments and a propellant.
  • Embodiments of the invention further include a bait composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments, one or more food materials, optionally an attractant, and optionally a humectant.
  • Embodiments of the invention also include a device for controlling an invertebrate pest comprising said bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to said bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
  • a compound of Formula 1 can be prepared by treating an amine of Formula 2 with an appropriate reagent of Formula 3 (where L is a suitable nucleophilic reaction leaving group such as halogen or imidazole) in the presence of a base (e.g. triethylamine, JV. ⁇ f-diisopropylethylamine or sodium hydrogen carbonate).
  • a base e.g. triethylamine, JV. ⁇ f-diisopropylethylamine or sodium hydrogen carbonate.
  • polymer-supported acid scavengers such as polymer-bound equivalents of N Jt- diisopropylethylamine and 4-(dimethylamino)pyridine, for example, iV-[(4-ethenylphenyl]- methyl)]-.V-methyl-4-pyridinamine polymer with diethenylbenzene and ethenylbenzene (CAS Registry Number 82942-26-5, hereafter identified as "PS-DMAP").
  • the reaction can be conducted neat or in an solvent such as dichloromethane, chloroform, tetrahydrofuran, acetonitrile or 1,2-dichloroethane. Temperatures for this reaction can range from 0 to 90 0 C.
  • the method of Scheme 1 is illustrated in Step F of Example 1, Step D of Example 2, and Example 3.
  • Compounds of Formula 2a can be made by the ring- opening of an appropriate epoxide of Formula 4 by treatment with an amine of Formula 5 in a solvent such as methanol, ethanol, chloroform, tetrahydrofuran, acetonitrile or 1,2-dichloroethane at temperatures ranging from 25 to 90 0 C, as depicted in Scheme 2.
  • a solvent such as methanol, ethanol, chloroform, tetrahydrofuran, acetonitrile or 1,2-dichloroethane at temperatures ranging from 25 to 90 0 C, as depicted in Scheme 2.
  • the method of Scheme 2 is illustrated in Step E of Example 1 and Step C of Example 2.
  • Epoxides of Formula 4 can be prepared from ketones of Formula 6 by treatment with a sulfonium ylide, which is typically generated in situ by reacting a trimethylsulfoxonium halide of Formula 7 with an appropriate base such as sodium hydride, potassium hydride or sodium re/t-butoxide, in a suitable solvent such as dimethyl sulfoxide, MN-dimethylformamide or tert-butanol, as depicted in Scheme 3.
  • a suitable solvent such as dimethyl sulfoxide, MN-dimethylformamide or tert-butanol
  • Trimethylsulfoxonium halides of Formula 7 are commercially available.
  • ketones of Formula 6 can be obtained by treating compounds of Formula 8 with lithium metal, an organolithium reagent such as, n-butyllithium, sec-butyllithium or terf-butyllithium, or an alkylmagnesium halide such as ethyl or methyl magnesium bromide or chloride at temperatures typically between -78 0 C and room temperature, to form the lithio or Grignard intermediate, respectively.
  • This intermediate is then reacted with a reagent of Formula 9 where L 1 is a leaving group such as Cl, Br, OCH3 or OCOCF3 to give the ketone of Formula 6.
  • the reaction is run in an organic solvent, preferably tetrahydrofuran or diethyl ether.
  • the method of Scheme 4 is illustrated in Step C of Example 1.
  • compounds of Formula Ia can be prepared from oxazolidinones of Formula 10 by reacting with aromatic halide intermediates of Formula 11 (where L2 is a leaving group such as F or Cl) as illustrated in Scheme 5.
  • oxazolidinone of Formula 10 is contacted with a base, such as sodium hydride or potassium rerf-butoxide, and then subsequently treated with a compound of Formula 11 typically in a solvent (e.g., iV.N-dimethylformamide or dimethyl sulfoxide).
  • a base such as sodium hydride or potassium rerf-butoxide
  • a compound of Formula 11 typically in a solvent (e.g., iV.N-dimethylformamide or dimethyl sulfoxide).
  • a solvent e.g., iV.N-dimethylformamide or dimethyl sulfoxide
  • the reaction can be conducted with two equivalents of a base such as potassium carbonate and in the presence of a copper(I) catalyst such as copper(I) iodide (typically 3-5 mol %) and fr ⁇ /is-cyclohexanediamine (to solubilize the CuI) using the method described in Organic Letters 2003, 5, 963-965.
  • a base such as potassium carbonate
  • a copper(I) catalyst such as copper(I) iodide (typically 3-5 mol %) and fr ⁇ /is-cyclohexanediamine (to solubilize the CuI) using the method described in Organic Letters 2003, 5, 963-965.
  • compounds of Formula Ia can also be prepared by a copper-mediated iV-arylation reaction of an oxazolidinone of Formula 10 with a compound of Formula 12, where M is a group such as boronic acid, boronic ester, biarylbismuthane, trialkylstannane or trialkylsiloxane.
  • the reaction can be run in an solvent such as dichloromethane, chloroform or tetrahydrofuran, and in the presence of a copper salt such as copper (II) acetate and a base (e.g., triethylamine, or pyridine), as depicted in Scheme 6.
  • a copper salt such as copper (II) acetate and a base (e.g., triethylamine, or pyridine
  • Oxazolidinones of Formula 10 can be prepared by the reaction of amino alcohols of Formula 13 with triphosgene or triphosgene substitutes that result in carbonylation (e.g., diphosgene, phosgene, (bis(trichloromethyl) carbonate) or 1,1' -carbon yl-diimidazole).
  • the reaction is run in a suitable organic solvent, such as dichloromethane, 1,2-dichloroethane or tetrahydrofuran in the presence of a base such as triethylamine, sodium hydrogen carbonate or sodium carbonate as depicted in Scheme 7.
  • Amino alcohols of Formula 13 can be prepared by the reduction of cyanohydrins of Formula 14 with a reducing agent such as lithium tetrahydroaluminate in a suitable organic solvent such as diethyl ether or tetrahydrofuran as depicted in Scheme 8.
  • a reducing agent such as lithium tetrahydroaluminate
  • a suitable organic solvent such as diethyl ether or tetrahydrofuran
  • Cyanohydrins of the Formula 14 can be prepared from the corresponding ketones (i.e., Formula 6) via one of a variety of cyanation methods well known in the art (see, for example, North, M. Science of Synthesis 2004, 19, 235-284).
  • Compounds of Formula Ib can be prepared by reduction of the imide of Formula 15 with sodium borohydride in a suitable solvent such as methanol and then reducing the resulting 5-hydroxy intermediate with sodium borohydride and trifluoroacetic acid.
  • a suitable solvent such as methanol
  • Methods for reduction of ketones and alcohols are well document in the art see, for example, Mehrotra, M. M., et al.; Journal of Medicinal Chemistry 2004, 47, 2037-2061 and Johnson, M. R.; Rickbom, B.; Journal of Organic Chemistry 1970, 35, 1041-1045.
  • the method of Scheme 9 is illustrated in Example 5, Steps E and F as well as Example 6, Steps B and C.
  • compounds of Formula 15 can be prepared from cyclization of ureas of Formula 16 by treatment with aqueous hydrochloric acid according to the general method described by Cook, A. H.; Hunter, G. D.; Journal of the Chemical Society 1952, 3789-3796.
  • R 3 is other than H
  • a suitable base such as sodium hydride
  • compounds of Formula 16 can be obtained by reacting ⁇ -aminonitriles of Formula 17 with isocyanates of Formula 18 according to the general method of Van Dort, M. E.; Jung, Y.-W.; Bioorganic & Medicinal Chemistry Letters 2004, 74(21), 5285-5288.
  • Compounds of Formula 17 can be obtained by coverting ketones of Formula 6 to the corresponding imines 20, followed by addition of a cyanide source (e.g., HCN) to the imine intermediates, followed by the addition of cyanide, which are well documented in the art
  • a cyanide source e.g., HCN
  • a ketone of Formula 6 is first treated with lithium bis(trimethylsily])amide, which results in the formation of an imine intermediate 19, which is then solvolyzed in methanol to afford a stable imine 20 according to the general method of Gosselin, F. et al Organic Letters 2005, 7, 355-358.
  • compounds of Formula 15 can be prepared by heating compounds of Formula 21 with amines of Formula 5 (see Scheme 13) in the presence of a catalyst such as 4-(dimethylamino)pyridine or trifluoroacetic acid.
  • a catalyst such as 4-(dimethylamino)pyridine or trifluoroacetic acid.
  • the cyclized hydantoins formed can then be treated with L ⁇ -R 3 in the presence of a base such as sodium hydride to form compounds of Formula 15.
  • a catalyst such as 4-(dimethylamino)pyridine or trifluoroacetic acid.
  • the cyclized hydantoins formed can then be treated with L ⁇ -R 3 in the presence of a base such as sodium hydride to form compounds of Formula 15.
  • a base such as sodium hydride
  • compounds of Formula 21 can be obtained by reacting ⁇ -ketoesters of Formula 22 with benzyl carbamate, after dehydration to form imines of Formula 23, followed by addition of the Grignard intermediates 24, which can be derived from compounds of Formula 8 as described previously for the method of Scheme 4.
  • Grignard intermediates 24 can be derived from compounds of Formula 8 as described previously for the method of Scheme 4.
  • Step A Preparation of 4-(acetylamino)-2-methyl-iv * -(2,2,2-trifluoroethyl)benzamide
  • Step B Preparation of 4-amino-2-methyI-JV-(2,2,2-trifluoroethyl)benzamide
  • Step A) was added concentrated hydrochloric aeid, and the reaction mixture was heated to 100 0 C for 2 h.
  • the reaction mixture was cooled using an external ice/water bath, and aqueous sodium hydroxide (50 wt%, 20 mL) was added until the reaction mixture was neutralized, causing a solid to precipitate.
  • the solid was filtered, washed with water and dried in a vacuum oven at 60 0 C overnight to provide the title compound as a white powder (0.89 g).
  • Step F 4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]- 2-methyl-7V-(2,2,2-trifluoroethyl)benzamide
  • More l.T-carbonyldiimidazole (0.05 g, 0.31 mmol) was added. After stirring for 22 h, more l,l'-carbonyldiimidazole (0.047 g, 0.28 mmol) and PS-DMAP (0.10 g, 0.14 mmol) were added. After stirring for 4 h, the reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in ethyl acetate (60 mL), washed with water (3 x 30 mL), filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give a solid.
  • Step A Preparation of 4-(acetylamino)-2-methyl-iV-(2-pyridinylmethyl)benzamide A mixture of 4-(acetylamino)-2-methylbenzoic acid (5.0 g, 25.9 mmol),
  • Step C Preparation of 4-[[2-(3,5-dichlorophenyl)-2-hydroxy- 3,3,3-trifluoropropyl]amino]-2-methyl- ⁇ r -(2-pyridinylmethyl)benzamide
  • Step D) (0.75 g) and 4-amino-2-methyI--V-(2-pyridinylmethyl)benzamide (i.e. product of Step B) (0.39 g, 1.7 mmol) in anhydrous ethanol (6 mL) was heated at 65 0 C for 7O h.
  • the reaction mixture was concentrated under reduced pressure, and the residue was purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (6:8) as eluant to provide the title compound as an off-white glassy solid (0.28 g).
  • Step D Preparation of 4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)- 3-oxazolidinyl-2-methyl-7V-(2-pyridinylmethyl)benzamide
  • Step A Preparation of 2-nitro-5-[2-oxo-5-phenyl-5-(trifluoromethyl)-3-oxazolidinyl]benzonitrile
  • Step A Preparation of 5-phenyI-5-(trifluoromethyl)-2-oxazolidinone
  • a cold (below 20 0 C) solution of lithium tetrahydroaluminate (10.0 mL, 1.0 M solution in diethyl ether) was added a solution of ⁇ -hydroxy- ⁇ -(trifluoromethyl)benzeneacetonitrile (Aldrich, 2.01 g, 10.0 mmol) in anhydrous diethyl ether (10 mL).
  • Aldrich 2.01 g, 10.0 mmol
  • the reaction mixture was stirred at ambient temperature for 1 h.
  • the solvent phases were separated, and the organic phase was washed with water, 1 N aqueous hydrochloric acid, and saturated aqueous sodium chloride solution.
  • the organic extracts were dried (MgSC ⁇ ), filtered and the solvent was concentrated under reduced pressure to provide the title compound as a white solid (1.35 g).
  • Step A Preparation of 3,3,3-trifluoro-2-hydroxy-N-[(phenylmethoxy)carbonyl]alanine ethyl ester
  • Step D Preparation of 4-[4-(3,5-dichlorophenyl)-2,5-dioxo-4-(trifluorornethyl)- l-imidazolidinyl]-2-methyl-N-(2-pyridinylmethyl)benzamide
  • Step E Preparation of 4-[4-(3,5-dichlorophenyl)-5-hydroxy-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-.V-(2-pyridinylrnethyl)benzamide
  • Step F Preparation of 4-[4-(3,5-dichlorophenyl)-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl- ⁇ f-(2-pyridinylmethyl)benzamide
  • 4-[4-(3,5-dichlorophenyl)-5-hydroxy-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-N-(2-pyridinylmethyl)benzamide i.e.
  • Step E the product of Step E) (0.18 g, 0.33 mmol) in trifluoroacetic acid (4 mL) at ice-bath temperature was added sodium borohydride (0.10 g, 2.6 mmol) in two batches. After the initial vigorous reaction had subsided, the reaction mixture was stirred at room temperature. An additional batch of sodium borohydride (0.048 g) was added after 2 h. The reaction mixture was stirred for 18 h, and then water (5 mL) was added. The reaction mixture was cooled with an external ice/water bath, and then a solution of sodium hydroxide (4.1 g of 50% aqueous solution and 10 mL of water) was added.
  • reaction mixture was extracted with ethyl acetate (2 X 25 mL), and the combined organic layers were filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give a gummy solid.
  • Another run was conducted using 90 mg of product from Step E, 2 mL of trifluoroacetic acid, and 67 mg of sodium borohydride under similar conditions.
  • the crude products from these two runs were combined and purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (45%-65%) as eluant to provide the title compound, a compound of the present invention, as an off-white solid (0.18 g).
  • Step A Preparation of 4-[4-(3,5-dichlorophenyl)-3-methyl-2,5-dioxo- 4-(trifluorometh y I)- 1 -imi dazolidinyl]-2-meth yl- ⁇ T-(2-pyridinylmethyl)benzamide
  • 4-[4-(3,5-dichlorophenyl)-2,5-dioxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl- ⁇ /'-(2-pyridinylmethyl)benzamide i.e.
  • Step D of Example 5 the product of Step D of Example 5 (0.39 g, 0.73 mmol) in ⁇ /,-V-dimethylformamide (4 mL) was added sodium hydride (60% oil dispersion, 0.0335 g, 2.3 mmol). After stirring for 15 min, iodomethane (0.179 g, 1.26 mmol) was added. The reaction mixture was stirred for 45 min and then partitioned between ethyl acetate (50 mL) and water (25 mL).
  • Step C Preparation of 4-[4-(3,5-dichlorophenyl)-3-methyl-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-N-(2-pyridinylmethyl)benzamide
  • reaction mixture was cooled with an external ice/water bath, and then a solution of sodium hydroxide (6 mL g of 50% aqueous solution and 20 mL of water) was added.
  • the reaction mixture was extracted with ethyl acetate (1 X 50 mL, 1 X 35 mL), and the combined organic layers were filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give a gummy solid, which was purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (45%-65%) as eluant to provide the title compound, a compound of the present invention, as a white solid (0.2O g).
  • m 1, 2, 3, 4 or 5.
  • W-I W-2 W-3 W-4 wherein m is 1, 2, 3, 4 or 5.
  • m 1, 2, 3, 4 or 5.
  • Compounds of this invention can generally be used as an invertebrate pest control active ingredient in a composition, i.e. formulation, with a carrier suitable for agronomic or nonagronomic uses comprising at least one of a liquid diluent, a solid diluent or a surfactant.
  • a carrier suitable for agronomic or nonagronomic uses 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.
  • aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion.
  • nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
  • compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film- forming solutions or flowable suspensions are particularly useful for seed treatment.
  • 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.
  • An emulsif ⁇ able granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. Hugh-strength compositions are primarily used as intermediates for further formulation.
  • Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
  • 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.
  • Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate.
  • Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.
  • Liquid diluents include, for example, water, ⁇ iV-dimethylalkanamides (e.g., TvyV-dimethylformarnide), limonene, dimethyl sulfoxide, ⁇ f-alkylpyrrolidones (e.g., JV-methylpyrrolidinone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone
  • Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C ( j— C 22 ).
  • glycerol esters of saturated and unsaturated fatty acids typically C ( j— C 22 ).
  • plant seed and fruit oils e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel
  • animal-sourced fats e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil
  • mixtures thereof e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil
  • Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation.
  • alkylated fatty acids e.g., methylated, ethylated, butylated
  • Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers 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.
  • the solid and liquid compositions of the present invention often include one or more surfactants.
  • surfactants also known as “surface-active agents”
  • surface-active agents generally modify, most often reduce, the surface tension of the liquid.
  • surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.
  • Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene
  • Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as Hgnosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of e
  • Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as ⁇ f-alkyl propanediamines, tripropylenetriamines and dipropylene- tetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquatemary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
  • amines such as ⁇ f-alkyl propanediamines, tripropylenetriamines and dipropylene- tetramines, and
  • Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.
  • compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants).
  • formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes.
  • Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes.
  • formulation auxiliaries and additives include those listed in McCutcheon's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
  • the compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent.
  • Solutions, including emulsifiable concentrates can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water.
  • Active ingredient slurries, with particle diameters of up to 2,000 ⁇ m can be wet milled using media mills to obtain particles with average diameters below 3 ⁇ m.
  • Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 ⁇ m range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques.
  • 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.
  • Compound 12 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%
  • Compound 16 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0%
  • Compound 18 20.00% polyvinylpyrrolidone-vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%
  • invertebrate pests include invertebrates inhabiting a variety of environments such as, for example, plant foliage, roots, soil, harvested crops or other foodstuffs, building structures or animal integuments.
  • These pests include, for example, invertebrates feeding on foliage (including leaves, stems, flowers and fruits), seeds, wood, textile fibers or animal blood or tissues, and thereby causing injury or damage to, for example, growing or stored agronomic crops, forests, greenhouse crops, ornamentals, nursery crops, stored foodstuffs or fiber products, or houses or other structures or their contents, or being harmful to animal health or public health.
  • foliage including leaves, stems, flowers and fruits
  • seeds wood, textile fibers or animal blood or tissues
  • present compounds and compositions are thus useful agronomically for protecting field crops from phytophagous invertebrate pests, and also nonagronomically for protecting other horticultural crops and plants from phytophagous invertebrate pests.
  • This utility includes protecting crops and other plants (i.e. both agronomic and nonagronomic) that contain genetic material introduced by genetic engineering (i.e. transgenic) or modified by mutagenesis to provide advantageous traits.
  • traits include tolerance to herbicides, resistance to phytophagous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, plant-pathogenic fungi, bacteria and viruses), improved plant growth, increased tolerance of adverse growing conditions such as high or low temperatures, low or high soil moisture, and high salinity, increased flowering or fruiting, greater harvest yields, more rapid maturation, higher quality and/or nutritional value of the harvested product, or improved storage or process properties of the harvested products.
  • Transgenic plants can be modified to express multiple traits.
  • plants containing traits provided by genetic engineering or mutagenesis include varieties of com, cotton, soybean and potato expressing an insecticidal Bacillus thuringiensis toxin such as YIELD GARD ® , KNOCKOUT ® , STARLINK ® , BOLLGARD ® , NuCOTN ® and NEWLEAF ® , and herbicide-tolerant varieties of corn, cotton, soybean and rapeseed such as ROUNDUP READY ® , LIBERTY LINK ® , Evil ® , STS ® and CLEARFIELD ® , as well as crops expressing JV-acetyltransferase (GAT) to provide resistance to glyphosate herbicide, or crops containing the HRA gene providing resistance to herbicides inhibiting acetolactate synthase (ALS).
  • GAT JV-acetyltransferase
  • the present compounds and compositions may interact synergistically with traits introduced by genetic engineering or modified by mutagenesis, thus enhancing phenotypic expression or effectiveness of the traits or increasing the invertebrate pest control effectiveness of the present compounds and compositions.
  • the present compounds and compositions may interact synergistically with the phenotypic expression of proteins or other natural products toxic to invertebrate pests to provide greater-than-additive control of these pests.
  • compositions of this invention can also optionally comprise plant nutrients, e.g., a fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum.
  • a fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum.
  • compositions comprising at least one fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium and magnesium.
  • Compositions of the present invention which further comprise at least one plant nutrient can be in the form of liquids or solids.
  • Solid formulations comprising a fertilizer composition can be prepared by mixing the compound or composition of the present invention with the fertilizer composition together with formulating ingredients and then preparing the formulation by methods such as granulation or extrusion.
  • solid formulations can be prepared by spraying a solution or suspension of a compound or composition of the present invention in a volatile solvent onto a previous prepared fertilizer composition in the form of dimensionally stable mixtures, e.g., granules, small sticks or tablets, and then evaporating the solvent.
  • Nonagronomic uses refer to invertebrate pest control in the areas other than fields of crop plants.
  • Nonagronomic uses of the present compounds and compositions include control of invertebrate pests in stored grains, beans and other foodstuffs, and in textiles such as clothing and carpets.
  • Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in ornamental plants, forests, in yards, along roadsides and railroad rights of way, and on turf such as lawns, golf courses and pastures.
  • Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in houses and other buildings which may be occupied by humans and/or companion, farm, ranch, zoo or other animals.
  • Nonagronomic uses of the present compounds and compositions also include the control of pests such as termites that can damage wood or other structural materials used in buildings.
  • Nonagronomic uses of the present compounds and compositions also include protecting human and animal health by controlling invertebrate pests that are parasitic or transmit infectious diseases.
  • the controlling of animal parasites includes controlling external parasites that are parasitic to the surface of the body of the host animal (e.g., shoulders, armpits, abdomen, inner part of the thighs) and internal parasites that are parasitic to the inside of the body of the host animal (e.g., stomach, intestine, lung, veins, under the skin, lymphatic tissue).
  • External parasitic or disease transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites and fleas.
  • Internal parasites include heartworms, hookworms and helminths.
  • Compounds and compositions of the present invention are suitable for systemic and/or non-systemic control of infestation or infection by parasites on animals.
  • Compounds and compositions of the present invention are particularly suitable for combating external parasitic or .disease transmitting pests.
  • Compounds and compositions of the present invention are suitable for combating parasites that infest agricultural working animals, such as cattle, sheep, goats, horses, pigs, donkeys, camels, buffalos, rabbits, hens, turkeys, ducks, geese and bees; pet animals and domestic animals such as dogs, cats, pet birds and aquarium fish; as well as so-called experimental animals, such as hamsters, guinea pigs, rats and mice.
  • Examples of agronomic or nonagronomic invertebrate pests include eggs, larvae and adults of the order Lepidoptera, such as armyworms, cutworms, loopers, and heliothines in the family Noctuidae (e.g., pink stem borer (Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm ⁇ Spodoptera fugiperda J. E.
  • Noctuidae e.g., pink stem borer (Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm ⁇ Spodoptera fugiperda J. E.
  • agronomic and nonagronomic pests include: eggs, adults and larvae of the order Dermaptera including earwigs from the family Forficulidae (e.g., European earwig ⁇ Forf ⁇ cula auricularia Linnaeus), black earwig ⁇ Chelisoches morio Fabricius)); eggs, immatures, adults and nymphs of the orders Hemiptera and Homoptera such as, plant bugs from the family Miridae, cicadas from the family Cicadidae, leafhoppers (e.g.
  • eggs, larvae, nymphs and adults of the order Acari such as spider mites and red mites in the family Tetranychidae (e.g., European red mite (Panonychus ulmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite (JTetranychus mcdanieli McGregor)); flat mites in the family Tenuipalpidae (e.g., citrus flat mite (Brevipalpus lewisi McGregor)); rust and bud mites in the family Eriophyidae and other foliar feeding mites and mites important in human and animal health, i.e.
  • Tetranychidae e.g., European red mite (Panonychus ulmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite (JTetranychus mcdanie
  • serpentine vegetable leafminer Liriomyza sativae Blanchard
  • midges fruit flies
  • frit flies e.g., Oscinella frit Linnaeus
  • soil maggots e.g., house flies (e.g., Musca domestica Linnaeus), lesser house flies (e.g., Fannia canicularis Linnaeus, F.
  • femoralis Stein stable flies (e.g., Stomoxys calcitrans Linnaeus), face flies, horn flies, blow flies (e.g., Chrysomya spp., Phormia spp.), and other muscoid fly pests, horse flies (e.g., Tabanus spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.), cattle grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.), keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), black flies (e.g., Prosimulium spp., Simulium s
  • Hymenoptera including bees (including carpenter bees), hornets, yellow jackets, wasps, and sawflies (Neodiprion spp.; Cephus spp.); insect pests of the order Isoptera including termites in the Termitidae (e.g., Macrotermes sp., Odontotermes obesus Rambur), Kalotermitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g., Reticulitermes sp., Coptotermes sp., Heterotermes tenuis Hagen) families, the eastern subterranean termite (Reticulitermes flavipes Kollar), western subterranean termite (Reticulitermes hesperus Banks), Formosan subterranean termite (Coptotermes formosanus Shiraki), West Indian drywood termite (lncisitermes immigran
  • insect pests of the order Thysanura such as silverfish (Lepisma saccharina Linnaeus) and firebrat (Thermobia domestica Packard); insect pests of the order Mallophaga and including the head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus Linnaeus), chicken body louse (Menacanthus stramineus Nitszch), dog biting louse (Trichodectes canis De Geer), fluff louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), short-nosed cattle louse (Haematopinus eurysternus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus) and other sucking and chewing parasitic lice that attack man and animals; insect pests of the order Siphonoptera including the oriental rat fle
  • Additional arthropod pests covered include: spiders in the order Araneae such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus).
  • spiders in the order Araneae such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius)
  • centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus).
  • Compounds of the present invention also have activity on members of the Classes Nematoda, Cestoda, Trematoda, and Acanthocephala including economically important members of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida such as but not limited to economically important agricultural pests (i.e. root knot nematodes in the genus Meloidogyne, lesion nematodes in the genus Pratylenchus, stubby root nematodes in the genus Trichodorus, etc.) and animal and human health pests (i.e.
  • Compounds of the invention show particularly high activity against pests in the order Lepidoptera (e.g., Alabama argillacea Hiibner (cotton leaf worm), Archips argyrospila Walker (fruit tree leaf roller), A. rosana Linnaeus (European leaf roller) and other Archips species, Chilo suppressalis Walker (rice stem borer), Cnaphalocrosis medinalis Guenee (rice leaf roller), Crambus caliginosellus Clemens (corn root webworm), Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm), Earias vittella Fabricius (spotted bollworm), Helicoverpa armigera Hiibner (American bollworm), Helicoverpa zea Boddie (corn earworm), Heliothis virescens Fabricius (tobacco bud
  • Homoptera including: Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae Scopoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (rosy apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus pruni Geoffroy (mealy plum a

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  • Plural Heterocyclic Compounds (AREA)

Abstract

Disclosed are compounds of Formula (1), including all geometric and stereoisomers, N-oxides, and salts thereof wherein G is O or NR<SUP>3</SUP>; U is C(=O), S(=O), C(=S), or S(O)<SUB>2</SUB>; Z is N or CR<SUP>2</SUP>; R<SUP>1</SUP> is cyano; or C<SUB>1</SUB>-C<SUB>6</SUB> alkyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkenyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkynyl, C<SUB>3</SUB>-C<SUB>6</SUB> cycloalkyl, C<SUB>4</SUB>-C<SUB>7</SUB> alkylcycloalkyl or C<SUB>4</SUB>-C<SUB>7</SUB> cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R<SUP>17</SUP>; R<SUP>3</SUP> is H, cyano or -CHO; or C<SUB>1</SUB>-C<SUB>6</SUB> alkyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkenyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkynyl, C<SUB>3</SUB>-C<SUB>6</SUB> cycloalkyl, C<SUB>4</SUB>-C<SUB>7</SUB> alkylcycloalkyl, C<SUB>4</SUB>-C<SUB>7</SUB> cycloalkylalkyl, phenyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkylcarbonyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkoxycarbonyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkylaminocarbonyl, C<SUB>3</SUB>-C<SUB>9</SUB> dialkylaminocarbonyl each optionally substituted with one or more substituents independently selected from R<SUB>18</SUB>; Q is a 5- or 6-membered saturated or unsaturated heterocycle optionally substituted; or Q is C(O)NR<SUP>12</SUP>R<SUP>13</SUP>, C(S)NR<SUP>12</SUP>R<SUP>13</SUP>, S(O)<SUB>2</SUB>NR<SUP>14</SUP>R<SUP>15</SUP> or R<SUP>16</SUP>; and R<SUP>2</SUP>, R<SUP>12</SUP>, R<SUP>13</SUP>, R<SUP>14</SUP>, R<SUP>15</SUP>, R<SUP>16</SUP>, R<SUP>17</SUP>, R<SUP>18</SUP>, A<SUP>1</SUP>, A<SUP>2</SUP>, A<SUP>3</SUP>, A<SUP>4</SUP> and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.

Description

TITLE FIVE-MEMBERED HETEROCYCUC INVERTEBRATE PEST CONTROL AGENTS
FIELD OF THE INVENTION
This invention relates to certain fϊve-membered heterocyclic derivatives, their iV-oxides, salts and compositions suitable for agronomic and nonagronomic uses, including those uses listed below, and methods of their use for controlling invertebrate pests such as arthropods in both agronomic and nonagronomic environments.
BACKGROUND OF THE INVENTION
The control of invertebrate pests is extremely important in achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer.
The control of invertebrate pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, turf, wood products, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, environmentally safer or have different modes of action.
PCT Patent Publication WO 93/22298 discloses oxazolindine derivatives and pharmaceutically acceptable salts thereof as antihyperlipidemics.
Japanese Patent Publication 03176476 discloses imidazolidinones as useful chiral auxiliaries for producing penem or carbapenem antibiotics.
U.S. Patent 4186129 discloses oxazolidinones useful as neuroleptics and phosphodiesterase inhibitors.
SUMMARY OF THE INVENTION
This invention is directed to compounds of Formula 1 including all geometric and stereoisomers, Λf-oxides, and salts thereof, and compositions containing them and their use for controlling invertebrate pests:
Figure imgf000002_0001
wherein
G is O or NR3;
U is C(=O), S(=O), C(=S), or S(O)2;
Z is N or CR2; AMs CR4 Or N; A2 is CR5 or N; A3 is CR6 or N; A4 is CR7 or N; Q is a 5- or 6-membered saturated or unsaturated heterocycle optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, cyano, nitro, C(O)NR8R9, C(O)OR10, phenyl and pyridinyl, each phenyl or pyridinyl optionally substituted with one or more substituents independently selected from R11; or Q is C(O)NR12R13, C(S)NRl2RB7 S(O)2NR14R15 Or R1S;
R1 is cyano; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R17; each R2 is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-Cg dialkylamino, C2-C4 alkoxycarbonyl, C2-C4 alkylaminocarbonyl, C3-Cg dialkylaminocarbonyl, cyano or nitro; R3 is H, cyano or -CHO; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, phenyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl or C3-Cg dialkylaminocarbonyl, each optionally substituted with one or more substituents independently selected from R18;
R4, R5, R6 and R7 are independently selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-Cg dialkylamino, cyano and nitro; or
R6 and R7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A3 and A4 bridgehead atoms, 3 atoms selected from 1 to 2 carbon atoms, O to 2 nitrogen atoms, O to 1 oxygen atom and O to 1 sulfur atom, or 4 atoms selected from 2 to 4 carbon atoms and O to 2 nitrogen atoms; each R8, R12 and R14 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl, C2~C6 alkoxyalkyl or C2-C7 alkoxycarbonyl; each R9, R10, R13 and R15 is independently H; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R19; each R11, R23 and R24 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylaminosulfonyl, C1-Cg alkylamino, C2-Cg dialkylamino, C2-C4 alkoxycarbonyl, cyano or nitro; R16 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl,
C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-Cg dialkylamino, cyano or nitro; each R17 and R18 is independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio,
C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, cyano or nitro; each R19 is independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-Cg alkylcarbonyl, C2-C6 alkoxycarbonyl, trimethylsilyl, cyano, nitro or Q1; each Q1 is independently a phenyl or a 5- or 6-membered saturated or unsaturated heterocycle, each optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-Cg dialkylamino, cyano, nitro, C(O)NR20R21, C(O)OR22, phenyl or pyridinyl, each phenyl or pyridinyl optionally substituted with one or more substituents independently selected from R23; each R20 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; each R21 and R22 is independently H; or C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, phenyl or pyridinyl; each phenyl or pyridinyl optionally substituted with one or more substituents independently selected from R24; and n is 1, 2, 3 or 4; and provided that R1^ is other than methoxy.
This invention also provides a composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula 1, an Λf-oxide or a salt thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.
This invention further provides a spray composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula 1, an Λf-oxide or a salt thereof, or the composition described above, and a propellant. This invention also provides a bait composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula 1, an N-oxide or a salt thereof, or the composition described above, one or more food materials, optionally an attractant, and optionally a humectant. This invention further provides a trap device for controlling an invertebrate pest comprising said bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to said bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
This invention also provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula 1, an Λf-oxide or a salt thereof, (e.g., as a composition described herein). This invention also relates to such method wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1, an Λf-oxide or a salt thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent. This invention also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of Formula 1, an Af-oxide or a salt thereof, (e.g., as a composition described herein). This invention also relates to the treated seed. This invention further provides a method for protecting an animal from an invertebrate parasitic pest comprising administering to the animal a parasiticidally effective amount of a compound of Formula 1, an iV-oxide or a salt thereof, (e.g., as a composition described herein). DETAILS OF THE INVENTION
As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains" or "containing," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, a mixture, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus. Further, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
Also, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.
As referred to in this disclosure, the term "invertebrate pest" includes arthropods, gastropods and nematodes of economic importance as pests. The term "arthropod" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans. The term "gastropod" includes snails, slugs and other Stylommatophora. The term "helminths" includes worms in the phylum of Nemathelminth, Platyhelminth and Acanthocephala such as: round worms, heartworms, and phytophagous nematodes (Nematoda), flukes (Trematoda), tape worms (Cestoda) and throny-headed worms.
In the context of this disclosure "invertebrate pest control" means inhibition of invertebrate pest development (including mortality, feeding reduction, and/or mating disruption), and related expressions are defined analogously.
The term "agronomic" refers to the production of field crops such as for food and fiber and includes the growth of corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye, rice, maize), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (berries, cherries) and other specialty crops (e.g., canola, sunflower, olives). The term "nonagronomic" refers to other horticultural crops (e.g., greenhouse, nursery or ornamental plants not grown in a field), residential and commercial structures in urban and industrial settings, turf (e.g., sod farm, pasture, golf course, residential lawn, recreational sports field, etc.), wood products, stored product, agro-forestry and vegetation management, public health (human) and animal health (e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife) applications. In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, /i-propyl, /-propyl, or the different butyl, pentyl or hexyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as ethenyl, 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 comprising multiple triple bonds such as 2,5-hexadiynyl. "Alkoxy" includes, for example, methoxy, ethoxy, π-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)-, (CHs)2CHS(O)- and the different butylsulfinyl, pentylsulfinyl and hexylsulfϊnyl isomers. Examples of "alkylsulfonyl" include CH3S(O)2-, CH3CH2S(O)2-, CH3CH2CH2S(O)2-, (CH^2CHS(O)2-, and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. "Alkylamino", "dialkylamino", and the like, are defined analogously to the above examples. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "alkylcycloalkyl" denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, j-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups.
The term "halogen", either alone or in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" or "alkyl substituted with halogen" include F3C-, ClCH2-, CF3CH2- and CF3CCl2-. The terms "halocycloalkyl", "haloalkoxy", "haloalkylthio", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkoxy" include CF3O-, CCl3CH2O-, HCF2CH2CH2O- and CF3CH2O-. Examples of "haloalkylthio" include CCl3S-, CF3S-, CCl3CH2S- and ClCH2CH2CH2S-. Examples of "haloalkylsulfinyl" include CF3S(O)-, CCl3S(O)-, CF3CH2S(O)- and CF3CF2S(O)-. Examples of "haloalkylsulfonyl" include CF3S(O)2-, CCl3S(O)2-, CF3CH2S(O)2- and CF3CF2S(O)2-. "Alkylcarbonyl" denotes a straight-chain or branched alkyl moieties bonded to a
C(=O) moiety. Examples of "alkylcarbonyl" include CH3C(=O)-, CH3CH2CH2C(=O)- and
(CH3)2CHC(=O)-. Examples of "alkoxycarbonyl" include CH3OC(=O)-, CH3CH2OC(=O),
CH3CH2CH2OC(=O)-, (CH3)2CHOC(=O)- and the different butoxy- or pentoxycarbonyl isomers.
The total number of carbon atoms in a substituent group is indicated by the "Cj-Cj" prefix where i and j are integers from 1 to 9. For example, C1-C4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, CH3CH(OCH3), CH3OCH2CH2 or CH3CH2OCH2; and C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2 and CH3CH2OCH2CH2.
When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independently selected from the group of defined substituents, e.g., (R2)n, n is 1, 2, 3 or 4. When a group contains a substituent which can be hydrogen, for example R2, then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.
The term "heterocycle", "heterocyclic ring" or "heterocyclic ring system" denotes rings or ring systems in which at least one ring atom is not carbon, e.g., nitrogen, oxygen or sulfur. Typically a heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs. The heterocyclic ring can be attached through any available carbon or nitrogen by replacement of hydrogen on said carbon or nitrogen. The heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated heterocyclic ring satifies the Hϋckel rule, then said ring is also called a "heteroaromatic ring" or "aromatic heterocyclic ring".
The term "aromatic ring'" or "aromatic ring system" denotes fully unsaturated carbocycles and heterocycles in which at least one ring of the polycyclic ring system is aromatic (where aromatic indicates that the Hϋckel rule is satisfied for the ring system). The term "fused bicyclic ring system" denotes a ring system containing two fused rings in which either ring can be saturated, partially unsaturated, or fully unsaturated. The term "fused heterobicyclic ring system" denotes a ring system containing two fused rings in which at least one ring atom is not carbon and which can be aromatic or nonaromatic, as defined above. The term "optionally substituted" in connection with the heterocyclic rings refers to groups which are unsubstituted or have at least one non-hydrogen substituent that does not extinguish the biological activity possessed by the unsubstituted analog. As used herein, the following definitions shall apply unless otherwise indicated. The term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or with the term "(un)substituted." Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other. When Q or Q1 is a 5- or 6-membered nitrogen-containing heterocycle, it may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise indicated. One skilled in the art recognizes that "pyridinyl" and "pyridyl" are equivalent alternative names for an organic radical formed by removing a hydrogen atom from a pyridine ring to form an attachment point; accordingly "pyridinyl" and "pyridyl" are used herein as synonyms.
As noted above, Q1 can be (among others) phenyl optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of Invention. An example of phenyl optionally substituted with from one or more substituents is the ring illustrated as U-I in Exhibit 1, wherein Rv is any substituent as defined in the Summary of the Invention for Q1 and r is an integer from 0 to 5.
As noted above, Q or Q1 can be (among others) 5- or 6-membered saturated or unsaturated heterocycles optionally substituted with one or more substituents selected from the group of substituents as defined in the Summary of Invention. Examples of 5- or 6-membered unsaturated aromatic heterocycles optionally substituted with from one or more substituents include the rings U-2 through U-61 illustrated in Exhibit 1 wherein Rv is any substituent as defined in the Summary of the Invention for Q or Q1, and r is an integer from 0 to 4. Note that some U groups can only be substituted with less than 4 Rv groups (e.g., U- 2 through U-5, U-7 through U-48, and U-52 through U-61).
Although Rv groups are shown in the structures U-I through U-61, it is noted that they do not need to be present since they are optional substituents. Note that when Rv is H when attached to an atom, this is the same as if said atom is unsubstituted. The nitrogen atoms that require substitution to fill their valence are substituted with H or Rv. Note that when the attachment point between (Rv)r and the U group is illustrated as floating, (Rv)r can be attached to any available carbon atom or nitrogen atom of the U group.
Figure imgf000009_0001
-2 U-3 U-4 U-5
Figure imgf000010_0001
U-H U- 12 U-13 U-14 U-15
Figure imgf000010_0002
U-16 U-17 U-18 U- 19 U-20
Figure imgf000010_0003
U-21 U-22 U-23 U-24 U-25
Figure imgf000010_0004
-26 -27 U-28 U-29 U-30
Figure imgf000010_0005
U-31 U-32 U-33 U-34 U-35
Figure imgf000010_0006
U-36 u-37 U-38 u-39 U-40
Figure imgf000010_0007
U-41 U-42 u-43 U-44 U-45
Figure imgf000011_0001
U-56 U-57 U-58 U-59 U-60
Figure imgf000011_0002
U-61
Note that when Q or Q1 is a 5- or 6-membered saturated or unsaturated non-aromatic heterocycle optionally substituted with one or more substituents selected from the group of substituents as defined in the Summary of Invention for Q or Q1, one or two carbon ring members of the heterocycle can optionally be in the oxidized form of a carbonyl moiety. Examples of 5- or 6-membered saturated or non-aromatic unsaturated heterocycles include the rings Q-I through Q-35 as illustrated in Exhibit 2, wherein Rv is any substituent as defined in the Summary of the Invention for Q1. Note that when the attachment point between (Rv)r and the Q or Q1 group is illustrated as floating, (Rv)r can be attached to any available carbon atom or nitrogen atom of the U group. Note that when the attachment point on the Q or Q1 group is illustrated as floating, the Q or Q1 group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the Q or Q1 group by replacement of a hydrogen atom. The optional substituents can be attached to any available carbon or nitrogen by replacing a hydrogen atom.
Note that when Q or Q1 comprises a ring selected from Q-28 through Q-35, Q2 is selected from O, S or N. Note that when Q2 is N, the nitrogen atom can complete its valence by substitution with either H or the substituents as defined in the Summary of Invention for Q or Ql. Exhibit 2
(RV)r (Rv)r
Figure imgf000012_0002
Q-I Q-2 Q-3
Figure imgf000012_0003
Figure imgf000012_0001
Q-6 Q-7 Q-8 Q-9 Q-IO
Figure imgf000012_0004
Q- 16 Q-17 Q-18 Q-19 Q-20
Figure imgf000012_0005
Q-21 Q-22 Q-23 Q-24 Q-25
Figure imgf000012_0006
Q-26 Q-21 Q-28 Q-29 Q-30
(Rv)r (RV)rxP
Figure imgf000012_0007
Q-31 Q-32 Q-33 Q-34 Q-35
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). 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 1, TV-oxides 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.
One skilled in the art will appreciate that not all nitrogen-containing heterocycles can form TV-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form TV-oxides. One skilled in the art will also recognize that tertiary amines can form TV-oxides. Synthetic methods for the preparation of TV-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as /-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of TV-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press. 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. The salts of the compounds of the invention also include those formed with organic bases (e.g., pyridine or triethylamine) or inorganic bases (e.g., hydrides, hydroxides, or carbonates of sodium, potassium, lithium, calcium, magnesium or barium) when the compound contains an acidic moiety such as when Q1 is phenyl substituted with C(O)OR22 and R22 is H.
Accordingly, the present invention comprises compounds selected from Formula 1, /V-oxides and salts thereof. Embodiments of the present invention as described in the Summary of the Invention include:
Embodiment 1. A compound of Formula 1 wherein G is O. Embodiment 2. A compound of Formula 1 wherein G is NR3. Embodiment 3. A compound of Formula 1 wherein R3 is H or cyano; or C1-C4 alkyl optionally substituted with one or more substituents selected from halogen.
Embodiment 4. A compound of Embodiment 3 wherein R3 is CH3, CH2CH3 or
CH2CF3. Embodiment 5. A compound of Formula 1 wherein U is C(=O).
Embodiment 6. A compound of Formula 1 wherein Z is CR2.
Embodiment 7. A compound of Formula 1 wherein each R2 is independently selected from H, halogen or C1-C2 haloalkyl.
Embodiment 8. A compound of Embodiment 7 wherein each R2 is independently H, halogen or CF3.
Embodiment 9. A compound of Formula 1 wherein A1 is CR4.
Embodiment 10. A compound of Formula 1 wherein A2 is CR5.
Embodiment 11. A compound of Formula 1 wherein A3 is CR6.
Embodiment 12. A compound of Formula 1 wherein A4 is CR7. Embodiment 13. A compound of Formula 1 wherein R4 and R5 are independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano and nitro.
Embodiment 14. A compound for Formula 1 wherein R^ and R7 are independently selected from H, halogen, Ci-C^ alkyl, C1-C3 haloalkyl, cyano and nitro; or R6 and R7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A3 and A4 bridgehead atoms, 4 atoms selected from 3 to 4 carbon atoms and 0 to 1 nitrogen atom.
Embodiment 15. A compound of Embodiment 14 wherein R6 and R7 are independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano and nitro. Embodiment 16. A compound of Embodiment 14 wherein R6 and R7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A3 and A4 bridgehead atoms, 4 atoms selected from 3 to 4 carbon atoms and 0 to 1 nitrogen atom.
Embodiment 17. A compound of Embodiment 14 or 16 wherein the fused aromatic ring contains 4 carbon atoms as ring members in addition to the A3 and A4 bridgehead atoms.
Embodiment 18. A compound of Formula 1 wherein Q is a pyridinyl ring, a pyrimidinyl ring, a triazinyl ring, a pyrazolyl ring, a triazolyl ring, an imidazolyl ring, an oxazolyl ring, an isoxazolyl ring, a thiazolyl ring or an isothiazolyl ring, each ring optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-Cg haloalkylsulfonyl, C1-C6 alkylamino, C2-Cg dialkylamino, cyano, nitro, C(O)NR8R9, C(O)OR10, phenyl and pyridinyl, each phenyl and pyridinyl optionally substituted with one or more substituents independently selected from R11; or Q is C(=O)NR12R13 , S(O)2ISfR14R15 or R16. Embodiment 19. A compound of Embodiment 18 wherein Q is a pyridinyl ring, a pyrimidinyl ring, a triazinyl ring, a pyrazolyl ring, a triazolyl ring, an imidazolyl ring, an oxazolyl ring, an isoxazolyl ring, a thiazolyl ring or an isothiazolyl ring, each ring optionally substituted with one or more substituents independently selected from halogen, C1-Cg alkyl, C1-Cg haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, cyano, nitro, C(O)NR8R9, C(O)OR10, phenyl and pyridinyl, each phenyl and pyridinyl optionally substituted with one or more substituents independently selected from R".
Embodiment 20. A compound of Embodiment 19 wherein Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylamino, C2-C4 dialkylamino, cyano, nitro, C(O)NR8R9, C(O)OR10, phenyl and pyridinyl, each phenyl and pyridinyl optionally substituted with one or more substituents independently selected from
Embodiment 21. A compound of Embodiment 20 wherein Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, cyano, nitro, C(O)NR8R9 and C(O)OR10.
Embodiment 22. A compound of Embodiment 21 wherein Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C1-C3 alkyl and C1-C3 haloalkyl. Embodiment 23. A compound of Embodiment 22 wherein Q is a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C1-C3 alkyl and C1-C3 haloalkyl.
Embodiment 24. A compound of Formula 1 wherein each R8 is independently H, C1-C6 alkyl, C2-Cy alkylcarbonyl or C2-C7 alkoxycarbonyl. Embodiment 25. A compound of Embodiment 24 wherein each R8 is H. Embodiment 26. A compound of Formula 1 wherein each R9 is independently H; or
C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C4 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R19.
Embodiment 27. A compound of Embodiment 26 wherein each R9 is independently
C1-C4 alkyl optionally substituted with one or more substituents selected from
R19.
Embodiment 28. A compound of Embodiment 27 wherein each R9 is independently C1-C4 alkyl optionally substituted with one Q1 and optionally substituted with one or more substituents selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1- C4 alkylthio, C1-C4 alkylsulfonyl and cyano. Embodiment 29. A compound of Formula 1 wherein each R10 is independently H; or
C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C4 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R19.
Embodiment 30. A compound of Embodiment 29 wherein each R10 is independently C1-C4 alkyl optionally substituted with one or more substituents selected from Rl9. Embodiment 31. A compound of Embodiment 30 wherein each R10 is independently
C1-C4 alkyl optionally substituted with one Q1 and optionally substituted with one or more substituents selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl and cyano.
Embodiment 32. A compound of Formula 1 wherein each R19 is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, cyano, nitro and Q1.
Embodiment 33. A compound of Embodiment 32 wherein each R19 is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl and cyano. Embodiment 34. A compound of Embodiment 18 wherein Q is C(=O)NR12R13.
Embodiment 35. A compound of Formula 1 wherein R12 is H, C1-C6 alkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl.
Embodiment 36. A compound of Embodiment 35 wherein R12 is H. Embodiment 37. A compound of Formula 1 wherein R13 is H; or C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C4 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R19. Embodiment 38. A compound of Embodiment 37 wherein R13 is H; or Cj-C4 alkyl optionally substituted with one or more substituents selected from R19. Embodiment 39. A compound of Embodiment 38 wherein R13 is H; or C1-C4 alkyl optionally substituted with one Q1 and optionally substituted with one or more substituents selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio,
C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl and cyano. Embodiment 40. A compound of Embodiment 39 wherein R13 is H; or C1-C4 alkyl optionally substituted with one Q1 and optionally substituted with one or more fluorine.
Embodiment 41. A compound of Formula 1 wherein each R19 is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, Cj-C4 alkylthio, C1-C4 alkylsulfinyl,
C1-C4 alkylsulfonyl, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, cyano, nitro and Ql. Embodiment 42. A compound of Embodiment 41 wherein each R19 is independently selected from halogen and Q1. Embodiment 43. A compound of Formula 1. wherein each Q1 is independently selected from phenyl, pyridinyl and thiazolyl, each optionally substituted with one or more substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano, phenyl and pyridinyl.
Embodiment 44. A compound of Embodiment 43 wherein Q1 is phenyl, pyridinyl or thiazolyl.
Embodiment 45. A compound of Embodiment 18 wherein Q is R16. Embodiment 46. A compound of Embodiment 18 wherein Q is S(O)2NR14R15. Embodiment 47. A compound of Formula 1 wherein R14 is H, C1-C^ alkyl, C2-C7 alkylcarbonyl Or C2-C7 alkoxycarbonyl.
Embodiment 48. A compound of Embodiment 47 wherein R14 is H. Embodiment 49. A compound of Formula 1 wherein R15 is H; or C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C4 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R19. Embodiment 50. A compound of Embodiment 49 wherein R15 is H; or C1-C4 alkyl optionally substituted with one or more substituents selected from R19. Embodiment 51. A compound of Embodiment 50 wherein R15 is H; or C1-C4 alkyl optionally substituted with one or more substituents selected from halogen,
C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, cyano and at most one Q1. Embodiment 52. A compound of Embodiment 51 wherein R15 is H; or C1-C4 alkyl optionally substituted with one or more fluorine and at most one Q1. Embodiment 53. A compound of Formula 1 wherein Q is other than R16. Embodiment 54. A compound of Formula 1 wherein R16 is halogen, C1-C3 haloalkyl, C2-C4 dialkylamino, cyano or nitro.
Embodiment 55. A compound of Formula 1 wherein R1 is C1-C3 alkyl optionally substituted with one or more substituents independently selected from R17. Embodiment 56. A compound of Embodiment 55 wherein R1 is C1-C3 alkyl substituted with one or more halogen. Embodiment 57. A compound of Embodiment 56 wherein R1 is CF3.
Embodiment 58. A compound of Formula 1 wherein n is 1 or 2. Embodiment 59. A compound of Formula 1 wherein at most 3 of A1, A2, A3 and A4 are
N.
Embodiment 60. A compound of Embodiment 59 wherein at most 2 of A1, A2, A3 and A4 are N.
Embodiment 61. A compound of Embodiment 60 wherein at most 1 of A*, A2, A3 and
A4 is N. Embodiment 62. A compound of Embodiment 61 wherein A1, A2, A3 and A4 are each other than N. Embodiment 63. A compound of Formula 1 wherein when Z is CH, and one R2 is attached to the phenyl ring at the 4-position, then said R2 is other than C1-Cg alkoxy. Embodiment 64. A compound of Formula 1 wherein when U is C(=O) and G is NR3, then R3 is other than H. Embodiments of this invention, including Embodiments 1-64 above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds. In addition, embodiments of this invention, including Embodiments 1-64 above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.
Combinations of Embodiments 1-64 are illustrated by: Embodiment A. A compound of Formula 1 wherein
Q is a pyridinyl ring, a pyrimidinyl ring, a triazinyl ring, a pyrazolyl ring, a triazolyl ring, an imidazolyl ring, an oxazolyl ring, an isoxazolyl ring, a thiazolyl ring or an isothiazolyl ring, each ring optionally substituted with one or more substituents independently selected from halogen, C]-Cg alkyl, CpCg haloalkyl, Cβ-Cg cycloalkyl, C3-C6 halocycloalkyl, C1-Cg alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, cyano, nitro, C(O)NR8R9, C(O)OR10, phenyl and pyridinyl, each phenyl and pyridinyl optionally substituted with one or more substituents independently selected from R11; or Q is C(O)NR12R13,
S(O)2NR14R15 or Ri6; Z is CR2; R1 is C1-C3 alkyl optionally substituted with one or more substituents independently selected from R17; each R2 is independently selected from H, halogen or C1-C2 haloalkyl;
R3 is H or cyano; or C1-C4 alkyl optionally substituted with one or more substituents selected from halogen; R4 and R5 are independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano and nitro; R6 and R7 are independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano and nitro; or R6 and R7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A3 and A4 bridgehead atoms, 4 atoms selected from 3 to 4 carbon atoms and O to 1 nitrogen atom; each R8 is independently H, C1-C6 alkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; each R9 and R10 is independently H; or C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C4 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R19; R12 and R14 are independently H, C1-C6 alkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl;
R13 and R15 are independently H; or C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C4 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R19; R16 is halogen, C1-C3 haloalkyl, C2-C4 dialkylamino, cyano or nitro; each R19 is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, cyano, nitro and Q1; each Q1 is independently selected from phenyl, pyridinyl and thiazolyl, each optionally substituted with one or more substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano, phenyl and pyridinyl; and n is i or 2; provided that at most 1 of A1, A2, A3 and A4 is N. Embodiment B. A compound of Embodiment A wherein R1 is C1-C3 alkyl substituted with halogen; and U is C(=O). Embodiment C. A compound of Embodiment B wherein
Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C]-C4 alkoxy, C1-C4 haloalkoxy, cyano, nitro, C(O)NR8R9 and C(O)OR10; or Q is C(O)NR12R13; R1 is CF3;
R6 and R7 are independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano and nitro; or R6 and R7 are taken together to form a fused aromatic ring, the fused aromatic ring containing 4 carbon atoms as ring members in addition to the A3 and A4 bridgehead atoms; each R8 is H; each R9 and R10 is independently C1-C4 alkyl optionally substituted with one Q1 and optionally substituted with one or more substituents selected from halogen,
C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl and cyano; R12 is H; R13 is H; or C1-C4 alkyl optionally substituted with one or more substituents selected from R19; and each R19 is independently selected from halogen and Q1.
Embodiment D. A compound of Embodiment C wherein each R2 is independently H, halogen or CF3; and
R3 is CH3, CH2CH3, or CH2CF3.
Embodiment E. A compound of Embodiment D wherein G is O; and provided that A1, A2, A3 and A4 are each other than N.
Specific embodiments include compounds of Formula 1 selected from the group consisting of:
4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-2-methyl-
N-(2-pyridinylmethyl)benzamide;
4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-2-methyl-
N-(2,2,2-trifluoroethyl)benzamide;
4-[5-(3,5-dichlorophenyl)-2-oxido-5-(trifluoromethyl)-l,2,3-oxathiazolidin-3-yl]-
2-methyl-iV-(2-pyridinylrnethyl)benzarnide;
2-nitro-5-[2-oxo-5-phenyl-5-(trifluoromethyl)-3-oxazolidinyl]benzonitrile;
4-[4-(3,5-dichlorophenyl)-2-oxo-4-(trifluoromethyl)-l-imidazolidinyl]-2-methyl-
N-(2-pyridinylmethyl)benzamide;
4-[4-(3,5-dichlorophenyl)-3-methyl-2-oxo-4-(trifluoromethyl)-l-imidazolidinyl]- 2-meth yl-JV-(2-pyri di n y 1 methyl)benzamide;
4-[5-(3,4-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-2-methyl- iV-(2-pyridinylmethyl)benzamide;
S-fS-φ.S-dichlorophenyO^-oxo-S-CtrifluoromethyO-S-oxazolidinyl]-
2-( IH- 1 ,2,4-triazol- 1 -yObenzonitrile;
4-[5-(3,5-dichlorophenyl)-2,2-dioxido-5-(trifluoromethyl)-l,2,3-oxathiazolidin-3-yl]-
2-methyl-N-(2-pyridinylmethyl)benzamide; and
4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-2-methyl-
ΛT-[l-(2-pyridinyl)ethyl]benzamide.
Further specific embodiments include any combination of the compounds of Formula 1 selected from the group immediately above.
Of note is that compounds of this invention are characterized by favorable metabolic and/or soil residual patterns and exhibit activity controlling a spectrum of agronomic and nonagronomic invertebrate pests.
Of particular note, for reasons of invertebrate pest control spectrum and economic importance, protection of agronomic crops from damage or injury caused by invertebrate pests by controlling invertebrate pests are embodiments of the invention. Compounds of this invention because of their favorable translocation properties or systemicity in plants also protect foliar or other plant parts which are not directly contacted with a compound of Formula 1 or a composition comprising the compound.
Also noteworthy as embodiments of the present invention are compositions for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent. Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding
Embodiments (e.g., as a composition described herein).
Embodiments of the invention also include a composition comprising a compound of any of the preceding Embodiments, in the form of a soil drench liquid formulation. Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting the soil with a liquid composition as a soil drench comprising a biologically effective amount of a compound of any of the preceding Embodiments.
Embodiments of the invention also include a spray composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments and a propellant. Embodiments of the invention further include a bait composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments, one or more food materials, optionally an attractant, and optionally a humectant. Embodiments of the invention also include a device for controlling an invertebrate pest comprising said bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to said bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
Compounds of Formula 1 can be prepared by one or more of the following methods and variations as described in Schemes 1—14. The definitions of R1, R2, A1 A2, A3, A4, G, U, Q, Z, and n in the compounds of Formulae 1-24 below are as defined above in the Summary of the Invention. Formulae Ia and Ib are subsets of Formula 1, and Formula 2a is a subset of Formula 2.
As shown in Scheme 1, a compound of Formula 1 can be prepared by treating an amine of Formula 2 with an appropriate reagent of Formula 3 (where L is a suitable nucleophilic reaction leaving group such as halogen or imidazole) in the presence of a base (e.g. triethylamine, JV.Λf-diisopropylethylamine or sodium hydrogen carbonate). Also useful as a base are polymer-supported acid scavengers such as polymer-bound equivalents of N Jt- diisopropylethylamine and 4-(dimethylamino)pyridine, for example, iV-[(4-ethenylphenyl]- methyl)]-.V-methyl-4-pyridinamine polymer with diethenylbenzene and ethenylbenzene (CAS Registry Number 82942-26-5, hereafter identified as "PS-DMAP"). The method of Scheme 1 can be done with a wide variety of reagents of Formula 3 such as l,r-carbonyldiimidazole, phosgene, trichloromethyl chloroformate, triphosgene, (i.e. when U is C(=O)), thiophosgene, l.T-thiocarbonyldiimidazole, (i.e. when U is C(=S)), thionyl chloride (i.e. when U is S(=O)), and sulfuryl chloride (i.e. when U is S(O)2).
Scheme 1
Figure imgf000022_0001
The reaction can be conducted neat or in an solvent such as dichloromethane, chloroform, tetrahydrofuran, acetonitrile or 1,2-dichloroethane. Temperatures for this reaction can range from 0 to 90 0C. The method of Scheme 1 is illustrated in Step F of Example 1, Step D of Example 2, and Example 3. Compounds of Formula 2a (Formula 2 wherein G is O) can be made by the ring- opening of an appropriate epoxide of Formula 4 by treatment with an amine of Formula 5 in a solvent such as methanol, ethanol, chloroform, tetrahydrofuran, acetonitrile or 1,2-dichloroethane at temperatures ranging from 25 to 90 0C, as depicted in Scheme 2. The method of Scheme 2 is illustrated in Step E of Example 1 and Step C of Example 2.
Scheme 2
Figure imgf000023_0001
2a
Epoxides of Formula 4 can be prepared from ketones of Formula 6 by treatment with a sulfonium ylide, which is typically generated in situ by reacting a trimethylsulfoxonium halide of Formula 7 with an appropriate base such as sodium hydride, potassium hydride or sodium re/t-butoxide, in a suitable solvent such as dimethyl sulfoxide, MN-dimethylformamide or tert-butanol, as depicted in Scheme 3. The method of Scheme 3 is illustrated in Step D of Example 1.
Trimethylsulfoxonium halides of Formula 7 are commercially available. Scheme 3
Figure imgf000023_0002
X is halogen
Figure imgf000023_0003
As illustrated in Scheme 4, ketones of Formula 6 can be obtained by treating compounds of Formula 8 with lithium metal, an organolithium reagent such as, n-butyllithium, sec-butyllithium or terf-butyllithium, or an alkylmagnesium halide such as ethyl or methyl magnesium bromide or chloride at temperatures typically between -78 0C and room temperature, to form the lithio or Grignard intermediate, respectively. This intermediate is then reacted with a reagent of Formula 9 where L1 is a leaving group such as Cl, Br, OCH3 or OCOCF3 to give the ketone of Formula 6. The reaction is run in an organic solvent, preferably tetrahydrofuran or diethyl ether. The method of Scheme 4 is illustrated in Step C of Example 1.
Scheme 4
Figure imgf000024_0001
Alternatively, compounds of Formula Ia (Formula 1 wherein G is O and U is C(=O)) can be prepared from oxazolidinones of Formula 10 by reacting with aromatic halide intermediates of Formula 11 (where L2 is a leaving group such as F or Cl) as illustrated in Scheme 5.
Scheme 5
Figure imgf000024_0002
In this reaction the oxazolidinone of Formula 10 is contacted with a base, such as sodium hydride or potassium rerf-butoxide, and then subsequently treated with a compound of Formula 11 typically in a solvent (e.g., iV.N-dimethylformamide or dimethyl sulfoxide). The method of Scheme 5 is illustrated in Step B of Example 4. Alternatively, when Formula 11 is an aryl bromide (i.e. L2 is Br) the reaction can be conducted with two equivalents of a base such as potassium carbonate and in the presence of a copper(I) catalyst such as copper(I) iodide (typically 3-5 mol %) and frα/is-cyclohexanediamine (to solubilize the CuI) using the method described in Organic Letters 2003, 5, 963-965.
As depicted in Scheme 6, compounds of Formula Ia can also be prepared by a copper-mediated iV-arylation reaction of an oxazolidinone of Formula 10 with a compound of Formula 12, where M is a group such as boronic acid, boronic ester, biarylbismuthane, trialkylstannane or trialkylsiloxane. The reaction can be run in an solvent such as dichloromethane, chloroform or tetrahydrofuran, and in the presence of a copper salt such as copper (II) acetate and a base (e.g., triethylamine, or pyridine), as depicted in Scheme 6. For general procedures for this type of reaction, see Ley, S. V.; Thomas, A. W. Angewandte Chemie, International Edition 2003, 42, 5400-5449.
Scheme 6
Figure imgf000025_0001
Oxazolidinones of Formula 10 can be prepared by the reaction of amino alcohols of Formula 13 with triphosgene or triphosgene substitutes that result in carbonylation (e.g., diphosgene, phosgene, (bis(trichloromethyl) carbonate) or 1,1' -carbon yl-diimidazole). The reaction is run in a suitable organic solvent, such as dichloromethane, 1,2-dichloroethane or tetrahydrofuran in the presence of a base such as triethylamine, sodium hydrogen carbonate or sodium carbonate as depicted in Scheme 7.
Scheme 7
Figure imgf000025_0002
13 10
Amino alcohols of Formula 13 can be prepared by the reduction of cyanohydrins of Formula 14 with a reducing agent such as lithium tetrahydroaluminate in a suitable organic solvent such as diethyl ether or tetrahydrofuran as depicted in Scheme 8. The methods of Schemes 7 and 8 are illustrated in Step A of Example 4. Scheme 8
Figure imgf000026_0001
14 13
Cyanohydrins of the Formula 14 can be prepared from the corresponding ketones (i.e., Formula 6) via one of a variety of cyanation methods well known in the art (see, for example, North, M. Science of Synthesis 2004, 19, 235-284).
Compounds of Formula Ib (i.e. Formula 1 wherein G is NR3 and U is C(=O)) can be prepared by reduction of the imide of Formula 15 with sodium borohydride in a suitable solvent such as methanol and then reducing the resulting 5-hydroxy intermediate with sodium borohydride and trifluoroacetic acid. Methods for reduction of ketones and alcohols are well document in the art see, for example, Mehrotra, M. M., et al.; Journal of Medicinal Chemistry 2004, 47, 2037-2061 and Johnson, M. R.; Rickbom, B.; Journal of Organic Chemistry 1970, 35, 1041-1045. The method of Scheme 9 is illustrated in Example 5, Steps E and F as well as Example 6, Steps B and C.
Scheme 9
Figure imgf000026_0002
15 Ib
As shown in Scheme 10, compounds of Formula 15 can be prepared from cyclization of ureas of Formula 16 by treatment with aqueous hydrochloric acid according to the general method described by Cook, A. H.; Hunter, G. D.; Journal of the Chemical Society 1952, 3789-3796. For compounds of Formula 15 where R3 is other than H, then treating the cyclized intermediate (where R3 is H) with L3-R3 (wherein L3 is a leaving group) in the presence of a suitable base such as sodium hydride to yield compounds of Formula 15. The second step of the method of Scheme 10 is illustrated in Example 6, Step A. Scheme 10
Figure imgf000027_0001
As shown in Scheme 11, compounds of Formula 16 can be obtained by reacting α-aminonitriles of Formula 17 with isocyanates of Formula 18 according to the general method of Van Dort, M. E.; Jung, Y.-W.; Bioorganic & Medicinal Chemistry Letters 2004, 74(21), 5285-5288.
Scheme 1 1
Figure imgf000027_0002
Compounds of Formula 17 can be obtained by coverting ketones of Formula 6 to the corresponding imines 20, followed by addition of a cyanide source (e.g., HCN) to the imine intermediates, followed by the addition of cyanide, which are well documented in the art
(see, for example, Organic Reactions 2002, 59, 1-714 and Koos, M.; Mosher, H. S.;
Tetrahedron 1993, 49, 1541-1546).
The method shown in Scheme 12 is particularly useful for the preparation of the imines 20 when R1 is CF3.
Scheme 12
Figure imgf000027_0003
As shown above, a ketone of Formula 6 is first treated with lithium bis(trimethylsily])amide, which results in the formation of an imine intermediate 19, which is then solvolyzed in methanol to afford a stable imine 20 according to the general method of Gosselin, F. et al Organic Letters 2005, 7, 355-358.
Alternatively, compounds of Formula 15 can be prepared by heating compounds of Formula 21 with amines of Formula 5 (see Scheme 13) in the presence of a catalyst such as 4-(dimethylamino)pyridine or trifluoroacetic acid. The cyclized hydantoins formed can then be treated with L^-R3 in the presence of a base such as sodium hydride to form compounds of Formula 15. For reference, see Pozzo, A. D. et al.; Tetrahedron 1998, 6019-6028. The method of Scheme 13 is illustrated in Example 5, Step D.
Scheme 13
Figure imgf000028_0001
As shown in Scheme 14, compounds of Formula 21 can be obtained by reacting α-ketoesters of Formula 22 with benzyl carbamate, after dehydration to form imines of Formula 23, followed by addition of the Grignard intermediates 24, which can be derived from compounds of Formula 8 as described previously for the method of Scheme 4. For general reference, see Dessipri, E.; Tirrell, D. A.; Macramolecules 1994, 27, 5463-5470. The method of Scheme 14 is illustrated in Example 5, Steps A-C.
Scheme 14
Figure imgf000028_0002
One skilled in the art will recognize that compounds of Formula 1 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. It is also recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 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 1. 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 1.
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. 1H NMR spectra are reported in ppm downfield from tetramethylsilane; 19F NMR spectra are reported in ppm using trichlorofluoromethane as reference; "s" means singlet, "d" means doublet, "t" means triplet, "m" means multiplet, "dd" means doublet of doublet, "dt" means doublet of triplet, "br s" means broad singlet and "br t" means broad triplet.
EXAMPLE 1 ■ Preparation of 4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-
2-methyl-N-(2,2,2-trifluoroethyl)benzamide
Step A: Preparation of 4-(acetylamino)-2-methyl-iv*-(2,2,2-trifluoroethyl)benzamide
To a stirred solution of 4-(acetylamino)-2-methylbenzoic acid (Aldrich, 1.9 g, 9.8 mmol) in tetrahydrofuran (9 mL) at room temperature was added l,l'-carbonyldiimidazole (1.65 g, 10.1 mmol). After 18 h, 2,2,2-trifluoroethanamine (1.6 g, 16.0 mmol) was added, followed by a catalytic amount of 4-(dimethylamino)pyridine (also known as iV.N-dimethyl-
4-pyridinamine). After 24 h, water was added to the reaction mixture, and the resulting precipitate was collected by filtration and dried to provide the title compound as a white powder (2.1 g). 1H NMR (DMSO-^5): δ 10.01 (s, IH), 8.80 (t, IH), 7.46 (d, IH), 7.45 (s, IH), 7.31 (d, IH),
4.02 (m, 2H), 2.31 (s, 3H), 2.05 (s, 3H).
Step B: Preparation of 4-amino-2-methyI-JV-(2,2,2-trifluoroethyl)benzamide
To 4-(acetylamino)-2-methyl-iV-(2,2,2-trifluoroethyl)benzamide (i.e. the product of
Step A) was added concentrated hydrochloric aeid, and the reaction mixture was heated to 100 0C for 2 h. The reaction mixture was cooled using an external ice/water bath, and aqueous sodium hydroxide (50 wt%, 20 mL) was added until the reaction mixture was neutralized, causing a solid to precipitate. The solid was filtered, washed with water and dried in a vacuum oven at 60 0C overnight to provide the title compound as a white powder (0.89 g). lH NMR (DMSO-^6): δ 8.42 (t, IH), 7.18 (d, IH), 6.38 (s, IH), 6.39 (d, 2H), 5.43 (br s, 2H), 3.96 (m, 2H), 2.57 (s, 3H). Step C: Preparation of l-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone
To a stirred slurry of l-bromo-3,5-dichlorobenzene (Aldrich, 15.0 g, 65.1 mmol) in anhydrous ether (300 mL) at -70 0C was added dropwise w-butyllithium (2.5 M in hexane, 26.0 mL, 65.0 mmol) over 30 minutes. After 5 minutes, methyl trifluoroacetate (9.17 g, 71.6 mmol) in ether (7 mL) was added dropwise over 45 minutes. After a further 45 minutes, the reaction mixture was warmed to 0 0C and then poured into a saturated solution of aqueous potassium dihydrogen phosphate (50 g in 200 mL of water) and stirred for 30 minutes at room temperature. The layers were separated, and the organic layer was washed with saturated sodium chloride (100 mL), dried (MgSC^), and concentrated under reduced pressure to provide the title compound as a yellow oil (13.0 g). lH NMR (CDCl3): δ 7.74 (s, 2H), 7.44 (s, IH). 19F NMR (CDCl3): δ -76.82.
Step D: Preparation of 2-(3,5-dichlorophenyl)-2-(trifluoromethyl)oxirane
Sodium hydride (60%, 0.36 g, 9.0 mmol) was added to a stirred solution of trimethylsulfoxonium iodide (1.88 g, 8.5 mmol) in dimethyl sulfoxide (17 mL) under a nitrogen atmosphere. After stirring for 0.5 h, the solution was added dropwise over 5 minutes to a solution of l-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (i.e. the product of Step C) (1.7 g, 7.0 mmol) in tetrahydrofuran. The resulting yellow slurry was stirred for 5 minutes, and then the reaction mixture was partitioned between ether (100 mL) and water (50 mL). The organic layer was separated, and the aqueous layer was extracted with ether (70 mL). The combined ether extracts were washed with water (40 mL) and dried (MgSO1^.). The ether solution was filtered, and the solvent was concentrated under reduced pressure to provide the title compound as an orange oil (1.71 g). The crude product (70-80% by 1H NMR) was used without purification.
1H NMR (CDCl3): δ 7.42 (m, 3H), 3.43 (d, IH), 2.91 (m, IH). 19F NMR (CDCl3): δ -74.57. Step E: 4-[[2-(3,5-dichlorophenyl)-2-hydroxy-3,3,3-trifluoropropyl]amino]-2-methyl- iV-(2,2,2-trifluoroethyl)benzamide
A solution of 2-(3,5-dichIorophenyl)-2-(trifluorornethyl)oxirane (i.e. the product of Step D) (0.82 g) and 4-amino-2-methy]-N-(2,2,2-trifluoroethyl)benzarnide (i.e. the product of Step B) (0.42 g, 1.7 mmol) in anhydrous ethanol (8 mL) was heated at 75 0C for 18 h. After cooling, the solvent was concentrated under reduced pressure. The residue was purified by medium pressure silica gel chromatography using ethyl acetate-hexanes (2:3) as eluant to provide the title compound as an off-white glassy solid (0.36 g). IH NMR (CDCl3): 67.51 (s, 2H), 7.37 (s, IH), 7.18 (d, IH), 6.42 (m, 2H), 6.30 (s, IH), 6.29 (d, IH), 5.13 (s, IH), 3.96 (m, 2H), 3.74 (dd, IH), 3.62 (dd, IH), 2.00 (s, 3H). 19F NMR (CDCl3): 8 -72.80, -78.47. Step F: 4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]- 2-methyl-7V-(2,2,2-trifluoroethyl)benzamide
A slurry of 4-[[2-(3,5-dichlorophenyl)-2-hydroxy-3,3,3-trifluoropropyl]amino]- 2-methyl-N-(2,2,2-trifluoroethyl)benzamide (i.e. the product of Step E) (0.28 g, 0.57 mmol), l,l'-carbonyldiimidazole (0.15 g, 0.93 mmol) and PS-DMAP (Riley Co., 1.4 mmol/g) (0.085 g, 0.12 mmol) in dichloromethane (7 mL) was stirred at room temperature for 5 h. More l.T-carbonyldiimidazole (0.05 g, 0.31 mmol) was added. After stirring for 22 h, more l,l'-carbonyldiimidazole (0.047 g, 0.28 mmol) and PS-DMAP (0.10 g, 0.14 mmol) were added. After stirring for 4 h, the reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in ethyl acetate (60 mL), washed with water (3 x 30 mL), filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give a solid. The crude solid was purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (2:3) as eluant to provide the title product, a compound of the present invention, as an off-white solid (0.20 g). 1H NMR (CDCl3): 67.48 (m, 3H), 7.41 (d, IH), 7.37 (d, IH), 7.31 (s, IH), 6.38 (br s, IH), 4.62 (d, IH), 4.30 (d, IH), 4.07 (m, 2H), 2.43 (s, 3H). 19F NMR (CDCl3): δ -72.79, -81.57.
EXAMPLE 2
Preparation of 4-[5-(3,5-dichIorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-
2-methyl-7v*-(2-pyridinylmethyl)benzamide
Step A: Preparation of 4-(acetylamino)-2-methyl-iV-(2-pyridinylmethyl)benzamide A mixture of 4-(acetylamino)-2-methylbenzoic acid (5.0 g, 25.9 mmol),
2-pyridinemethanamine (2.94 g, 2.8 mL, 27.2 mmol), and ΛT-(ethylcarbonimidoyl)- -V,Λf-dimethyl-l,3-propanediamine, monohydrochloride (5.2 g, 27.1 mmol) in dichloromethane (250 mL) was stirred at room temperature overnight. Then water was added to the reaction mixture, and the resulting two layers were separated. The dichloromethane layer was passed through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian) and concentrated under reduced pressure. The resulting amber oil was triturated with dichloromethane, π-butyl chloride, and hexanes to provide the title compound as a pale yellow solid (5.5 g). IH NMR (CDCl3): δ 8.53 (d, IH), 7.92 (br s, IH), 7.69 (m, IH), 7.42-7.16 (m, 6H), 4.72 (d, 2H), 2.42 (s, 3H), 2.15 (s, 3H). Step B: Preparation of 4-amino-2-methyl-Λf-(2-pyridinylmethyl)benzarnide
A mixture of 4-(acetylamino)-2-methyl-iV-(2-pyridinylmethyl)benzamide (i.e. the product of Step A) (5.5 g, 19.4 mmol) and concentrated hydrochloric acid (100 mL) was stirred and heated at reflux for 1 h. After cooling, ice was added and the pH adjusted to 10 by adding aqueous sodium hydroxide (50 wt%). The reaction mixture was filtered to collect the solid precipitate, which was washed with water and dried to provide the title compound as a light yellow solid (4.02 g). lH NMR (DMSO-Cf6): B 8.49 (d, IH), 8.41 (br s, IH), 7.76 (m, IH), 7.31 (d, IH), 7.22-7.27
(m, 2H), 6.36-6.40 (m, 2H), 5.36 (s, 2H), 4.47 (s, 2H), 2.28 (s, 3H). Step C: Preparation of 4-[[2-(3,5-dichlorophenyl)-2-hydroxy- 3,3,3-trifluoropropyl]amino]-2-methyl-Λr-(2-pyridinylmethyl)benzamide
A solution of 2-(3,5-dichlorophenyl)-2-(trifluoromethyl)oxirane (i.e. the product of
Example 1, Step D) (0.75 g) and 4-amino-2-methyI--V-(2-pyridinylmethyl)benzamide (i.e. product of Step B) (0.39 g, 1.7 mmol) in anhydrous ethanol (6 mL) was heated at 65 0C for 7O h. The reaction mixture was concentrated under reduced pressure, and the residue was purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (6:8) as eluant to provide the title compound as an off-white glassy solid (0.28 g).
*H ISfMR (CDCl3): δ 8.50 (d, IH), 7.70 (t, IH), 7.52 (s, 2H), 7.40 (s, IH), 7.31 (m, 2H), 7.21
(m, IH), 7.08 (br t, IH), 6.37 (s, IH), 6.36 (d, IH), 5.02 (br s, IH), 4.68 (d, 2H), 3.88 (t, IH), 3.81 (dd, IH), 3.61 (dd, IH), 2.39 (s, 3H). 19F NMR (CDCl3): δ -78.43.
Step D: Preparation of 4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)- 3-oxazolidinyl-2-methyl-7V-(2-pyridinylmethyl)benzamide
4-[[2-(3,5-dichlorophenyl)-2-hydroxy-3,3,3-trifluoropropyl]amino-2-methyl-
Λf-(2-pyridinylmethyl)benzamide (i-e. the product of Step C) (0.21 g, 0.42 mmol), l,l'-carbonyldiimidazole (0.13 g, 0.79 mmol), PS-DMAP (Riley Co., 0.065 g, 0.12 mmol), and dichloromethane (7 mL) were combined and stirred at room temperature for 5 h. More l,r-carbonyldiimidazole (0.05g, 0.31 mmol) was added. After stirring for 22 h, more l,l'-carbonyldiimidazole (0.15 g, 0.92 mmol) and PS-DMAP (0.31 g, 0.43 mmol) were added. After stirring for 24 h, the reaction mixture was concentrated under reduced pressure and purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (6:8) as eluant to provide the title product, a compound of the present invention, as an off-white glassy solid (0.20 g).
1H NMR (CDCl3): 6 8.52 (d, IH), 7.71 (t, IH), 7.54-7.20 (m, 9H), 4.73 (d, 2H), 4.63(d,
IH), 4.30 (d, IH), 2.51 (s, 3H). 19F NMR (CDCl3): δ -81.52. EXAMPLE 3
Preparation of 4-[5-(3,5-dichlorophenyl)-2-oxido-5-(trifluoromethyl)-l,2,3-oxathiazolidin-
3-yl]-2-methyl-iV-(2-pyridinylmethyl)benzamide
To a stirred solution of 4-[[2-(3,5-dichlorophenyl)-2-hydroxy-3,3,3-trifluoro- propyl]amino]-2-methyl-N-(2-pyridinylmethyl)benzamide (i.e. the product of Example 2, Step C) (0.11 g, 0.22 mmol), triethylamine (0.096 g, 0.95 mmol), and 4-(dimethylamino)pyridine (0.022 g, 0.018 mmol) in dichloromethane (2 mL) was added dropwise thionyl chloride (0.043 g, 0.36 mmol). After stirring for 1 h at room temperature, more thionyl chloride (0.026 g, 0.22 mmol) was added. After stirring 1 h more, the reaction mixture was concentrated under reduced pressure, and the crude product was purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (3:6) as eluant to provide the title product (1:1 mixture of diastereoisomers), a compound of the present invention, as an off-white solid (0.04 g). lH NMR (CDCl3): δ 8.50 (m, IH), 7.69 (br t, IH), 7.49 (m, 4H), 7.33 (m, IH), 7.22 (m, 2H), 6.93 (m, 2H), 4.73 (d, IH), 4.41 (d, IH), 4.70 (d, 0.5H), 4.56 (d, 0.5H), 4.38 (d, 0.5H), 4.20 (d, 0.5H), 2.50 (s, 1.5H), 2.47 (s, 1.5H). 19F NMR (CDCl3): δ -76.31, -79.67.
EXAMPLE 4
Preparation of 2-nitro-5-[2-oxo-5-phenyl-5-(trifluoromethyl)-3-oxazolidinyl]benzonitrile Step A: Preparation of 5-phenyI-5-(trifluoromethyl)-2-oxazolidinone To a cold (below 20 0C) solution of lithium tetrahydroaluminate (10.0 mL, 1.0 M solution in diethyl ether) was added a solution of α-hydroxy- α-(trifluoromethyl)benzeneacetonitrile (Aldrich, 2.01 g, 10.0 mmol) in anhydrous diethyl ether (10 mL). The resulting suspension was stirred at ambient temperature for 3 h. To the reaction mixture was sequentially added water (0.38 mL), aqueous sodium hydroxide solution (15 wt%, 0.38 mL), and more water (1.14 mL). The reaction mixture was filtered through a glass frit, and the filtrate was concentrated under reduced pressure to give a white solid (1.89 g). The white solid (1.23 g, 6.0 mmol) was dissolved in dichloromethane (15 mL) and added to a stirred saturated aqueous sodium hydrogen carbonate solution (15 mL). Then a solution of triphosgene bis(trichloromethyl)carbonate, (0.63 g, 2.17 mmol) in dichloromethane (5 mL) was added dropwise over several minutes. The reaction mixture was stirred at ambient temperature for 1 h. The solvent phases were separated, and the organic phase was washed with water, 1 N aqueous hydrochloric acid, and saturated aqueous sodium chloride solution. The organic extracts were dried (MgSC^), filtered and the solvent was concentrated under reduced pressure to provide the title compound as a white solid (1.35 g).
1H NMR (CDCl3) δ 7.5 - 7.4 (m, 5H), 5.95 (br s, IH), 4.26 (d, IH), 3.93 (d, IH). Step B: Preparation of 2-nitro-5-[2-oxo-5-phenyl-5-(trifluoromethyl)- 3-oxazolidinyI]benzonitrile
To a stirred solution of 5-phenyl-5-(trifluoromethyl)-2-oxazolidinone (i.e. the product of Step A) (0.97 g, 4.2 mmol) in N.N-dimethylformamide (20 mL) under a nitrogen atomosphere was added sodium hydride in one portion (60%, 0.21 g, 5.2 mmol). After 0.33 h, 5-chloro-2-nitrobenzonitrile (1.15 g, 6.3 mmol) was added to the reaction mixture. The reaction mixture was stirred for 16 h, diluted with water, extracted with ether (100 mL), and ethyl acetate (100 mL). The combined organic extracts were washed with water (4 x 75 mL), dried (MgSO4), filtered, and concentrated under reduced pressure to give a solid, which was purified by silica gel chromatography and by trituration with 20% ether/hexanes to provide the title product, a compound of the present invention, as a white solid (0.235 g). 1H NMR (CDCl3) δ 8.4 (m, IH), 8.1 (m, IH), 8.07 (s, IH), 7.6-7.45 (m, 5H), 4.75 (d, IH), 4.41 (d, IH).
EXAMPLE 5 Preparation of 4-[4-(3,5-dichlorophenyl)-2-oxo-4-(trifluoromethyl)-l-imidazolidinyl]-
2-methyl-Λ/-(2-pyridinylmethyl)benzamide
Step A: Preparation of 3,3,3-trifluoro-2-hydroxy-N-[(phenylmethoxy)carbonyl]alanine ethyl ester
A solution of 3,3,3-trifluoro-2-oxo-propionic acid ethyl ester (Alfa Chem. Co., 12.0 g, 70.6 mmol) and benzyl carbamate (9.78 g, 64.8 mmol) in methylene chloride (55 mL) was stirred for 66 h at room temperature under nitrogen. The solvent was removed under reduced pressure. Hexane (100 mL) was added to the crude mixture, and the resulting slurry was allowed to stand overnight. The solid was collected by vacuum filtration, washed with hexane, and air-dried to provide the title compound as a white solid (20.4 g). 1H NMR (CDCl3): δ 7.35 (m, 5H), 5.98 (s, IH), 5.35 (s, IH), 5.23 (s, 2H), 4.36 (m, 2H), 1.30 (t, 3H). Step B: Preparation of ethyl 3,3,3-trifluoro-
2-[[(phenylrnethoxy)carbonyl]imino]propanoate To a solution of 3,3,3-trifluoro-2-hydroxy-Λ/-[(phenylmethoxy)carbonyl]alanine ethyl ester (i.e. the product of Step A) (15.4 g, 48 mmol) and pyridine (7.9 g, 50 mmol) in anhydrous diethyl ether (200 mL) at ice-bath temperature was added dropwise trifluoroacetic anhydride (10.75 g, 51.1 mmol). The resulting slurry was warmed to room temperature and stirred for 1.5 h. The reaction mixture was filtered to remove a white solid. The filtrate was concentrated in vacuo to give a slurry. Hexane (150 mL) was added to the slurry, which was filtered again to remove a white solid. The filtrate was concentrated in vacuo to afford the title product as a colorless oil (14.2 g). 1H NMR (CDCl3): δ 7.41 (m, 5H), 5.33 (s, 2H), 4.31 (q, 2H), 1.30 (t, 3H). Step C: Preparation of ethyl 3,5-dichloro-α-[[(phenylmethoxy)carbonyl]amino]- α-(trifluoromethyl)benzeneacetate
To a solution of ethyl 3,3,3-trifluoro-2-[[(phenylmethoxy)carbonyl]imino]propanoate (i.e. the product of Step B) (7.36 g, 24.3 mmol) in anhydrous tetrahydrofuran (10 mL), cooled with a dry-ice bath, was added a solution of 3,5-dichlorophenyl magnesium bromide (Aldrich Chem. Co., 0.5 M in tetrahydrofuran, 50 mL, 25 mmol) over 45 minutes. The cloudy reaction mixture was stirred for 1 h, and then warmed to room temperature. To this yellow solution was added IN hydrochloric acid (37 mL). The bulk of the tetrahydrofuran was removed in vacuo. The residue was partitioned between ethyl acetate (170 mL) and water (100 mL). The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to afford the title compound as a yellow oil (11. Ig). 1H NMR (CDCl3): δ 7.34 (m, 8H), 6.10 (s, IH), 5.07 (s, 2H), 4.28 (m, 2H), 1.21 (t, 3H). 19F NMR (CDCl3): δ -71.03.
Step D: Preparation of 4-[4-(3,5-dichlorophenyl)-2,5-dioxo-4-(trifluorornethyl)- l-imidazolidinyl]-2-methyl-N-(2-pyridinylmethyl)benzamide
A solution of ethyl 3,5-dichloro-α-[[(phenylmethoxy)carbonyl]amino]- cc-(trifluoromethyl)benzeneacetate (i.e. the product of Step C) (1.11 g, 2.5 mmol), 4-amino- 2-methyl-JV-(2-pyridinylrnethyl)benzarnide (i.e. the product of Step B of Example 2) (0.474 g, 1.95 mmol), 4-(dimethylamino)pyridine (68 mg, 0.55 mmol) in Λf-methyl^-pyrrolidinone (NMP) was heated at 200 0C by microwave irradiation for 350 sec. Another run was made with 0.99 g of the product of step C, 0.44 g of the product from Step B of Example 2, and 71 mg of 4-dimethylaminopyridine in NMP (2 mL) under the same conditions. The reaction mixtures from the two runs were combined and diluted with ethyl acetate (100 mL), washed with water (3 X 50 mL), filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give a dark oil. This was purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (45%-85%) as eluant to provide the title compound as a tan solid (0.84 g). 1H NMR (DMSO-^6): δ 10.65 (s, IH), 8.99 (t, IH), 8.52 (d, IH), 7.89 (br s, 3H), 7.80 (dt, IH), 7.54 (d, IH), 7.39 (d, IH), 7.32-7.27 (m, 3H), 4.54 (d, 2H), 2.39 (s, 3H). Step E: Preparation of 4-[4-(3,5-dichlorophenyl)-5-hydroxy-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-.V-(2-pyridinylrnethyl)benzamide
To a slurry of 4-[4-(3,5-dichlorophenyl)-2,5-dioxo-4-(trifluorornethyl)- l-imidazolidinyl]-2-methyl-iV-(2-pyridinylrnethyl)benzarnide (i.e. the product of Step D),
(0.66 g, 1.23 inmol) in methanol (18 mL) at ice-bath temperature was added sodium borohydride (0.275 g, 7.3 mmol) in small batches over 3 minutes. The resulting orange solution was stirred at room temperature for 18 h. The solvent was removed in vacuo, and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (35 mL). The combined organic layers were filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to afford the title compound as a tan solid (0.59 g). 1H NMR (DMSO-J6): δ 9.17 (s, IH), 8.78 (t, IH), 8.52 (d, IH), 7.79 (dt, IH), 7.75 (t, IH), 7.61 (m, 3H), 7.52 (d, IH), 7.45 (d, IH), 7.37 (d, IH), 7.27 (dd, IH), 6.91 (d, IH), 6.12 (d, IH), 4.52 (d, 2H), 2.39 (s, 3H).
Step F: Preparation of 4-[4-(3,5-dichlorophenyl)-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-Λf-(2-pyridinylmethyl)benzamide To a solution of 4-[4-(3,5-dichlorophenyl)-5-hydroxy-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-N-(2-pyridinylmethyl)benzamide (i.e. the product of Step E) (0.18 g, 0.33 mmol) in trifluoroacetic acid (4 mL) at ice-bath temperature was added sodium borohydride (0.10 g, 2.6 mmol) in two batches. After the initial vigorous reaction had subsided, the reaction mixture was stirred at room temperature. An additional batch of sodium borohydride (0.048 g) was added after 2 h. The reaction mixture was stirred for 18 h, and then water (5 mL) was added. The reaction mixture was cooled with an external ice/water bath, and then a solution of sodium hydroxide (4.1 g of 50% aqueous solution and 10 mL of water) was added. The reaction mixture was extracted with ethyl acetate (2 X 25 mL), and the combined organic layers were filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give a gummy solid. Another run was conducted using 90 mg of product from Step E, 2 mL of trifluoroacetic acid, and 67 mg of sodium borohydride under similar conditions. The crude products from these two runs were combined and purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (45%-65%) as eluant to provide the title compound, a compound of the present invention, as an off-white solid (0.18 g).
*H ISfMR (CDCl3): δ 8.51 (d, IH), 7.70 (dt, IH), 7.52-7.30 (m, 8H), 7.23 (dd, IH), 6.65 (s, IH), 4.74 (d, 2H), 4.52 (d, IH), 4.13 (d, IH), 2.51 (s, 3H).
EXAMPLE 6 Preparation of 4-[4-(3,5-dichlorophenyl)-3-methyl-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-^v*-(2-pyridinylmethyl)benzamide
Step A: Preparation of 4-[4-(3,5-dichlorophenyl)-3-methyl-2,5-dioxo- 4-(trifluorometh y I)- 1 -imi dazolidinyl]-2-meth yl- ΛT-(2-pyridinylmethyl)benzamide To a solution of 4-[4-(3,5-dichlorophenyl)-2,5-dioxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-Λ/'-(2-pyridinylmethyl)benzamide (i.e. the product of Step D of Example 5) (0.39 g, 0.73 mmol) in Λ/,-V-dimethylformamide (4 mL) was added sodium hydride (60% oil dispersion, 0.0335 g, 2.3 mmol). After stirring for 15 min, iodomethane (0.179 g, 1.26 mmol) was added. The reaction mixture was stirred for 45 min and then partitioned between ethyl acetate (50 mL) and water (25 mL). The organic layer was washed with water (2 X 25 mL) and filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give the title compound as a glassy solid (0.39 g). 1H NMR (DMSO-d6): δ 9.00 (t, IH), 8.53 (d, IH), 7.93 (s, IH), 7.80 (dt, IH), 7.69 (s, 2H), 7.56 (s, IH), 7.39 (m, 3H), 7.28 (dd, IH), 4.56 (d, 2H), 3.00 (s, 3H), 2.40 (s, 3H). Step B: Preparation of 4-[4-(3,5-dichlorophenyI)-5-hydroxy-3-methyl-2-oxo-
4-(trifluoromethyl)-l-imidazolidinyl]-2-methyl- -/v"-(2-pyridinylmethyl)benzamide To a cloudy solution of 4-[4-(3,5-dichlorophenyl)-3-methyl-2,5-dioxo-
4-(trifluoromethyl)-l-imidazolidinyl]-2-methyl-iV-(2-pyridinylmethyl)benzamide (i.e. the product of Step A) (0.37 g, 0.67 mmol) in methanol (10 mL) was added sodium borohydride (0.167 g, 4.42 mmol) in small batches over 5 min. After stirring for 4.5 h, methanol was removed in vacuo, and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (35 mL), and the combined organic layers were filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give the title compound as a tan solid (0.32 g). 1H NMR (DMSO-J6): δ 8.75 (t, IH), 8.50 (d, IH), 7.81 (s, IH), 7.78 (dt, IH), 7.56 (d, IH), 7.46-7.31 (m, 6H), 7.26 (dd, IH), 5.81 (d, IH), 4.51 (d, 2H), 2.97 (s, 3H), 2.34 (s, 3H).
Step C: Preparation of 4-[4-(3,5-dichlorophenyl)-3-methyl-2-oxo-4-(trifluoromethyl)- l-imidazolidinyl]-2-methyl-N-(2-pyridinylmethyl)benzamide
To a solution of 4-[4-(3,5-dichlorophenyl)-5-hydroxy-3-methyl-2-oxo- 4-(trifluoromethyl)-l-imidazolidinyl]-2-methyl-iV-(2-pyridinylmethyl)benzamide (i.e. the product of Step B) (0.25 g, 0.45 mmol) in trifluoroacetic acid (6 mL) was added sodium borohydride (0.14 g, 3.7 mmol) in batches over 3 min. After stirring for 1 h at room temperature, an additional amount of sodium borohydride (0.104 g, 2.7 mmol) was added. After stirring for an additional 18 h, water (10 mL) was added. The reaction mixture was cooled with an external ice/water bath, and then a solution of sodium hydroxide (6 mL g of 50% aqueous solution and 20 mL of water) was added. The reaction mixture was extracted with ethyl acetate (1 X 50 mL, 1 X 35 mL), and the combined organic layers were filtered through a Chem Elut cartridge packed with diatomaceous earth (manufactured by Varian), and concentrated under reduced pressure to give a gummy solid, which was purified by medium pressure silica gel chromatography using ethyl acetate/hexanes (45%-65%) as eluant to provide the title compound, a compound of the present invention, as a white solid (0.2O g). 1H NMR (CDCl3): δ 8.53 (d, IH), 7.69 (dt, IH), 7.51 (d, IH), 7.45 (m, 2H), 7.34 (m, 4 H), 7.22 (dd, IH), 7.13 (br t, IH), 4.73 (d, 2H), 4.31 (d, IH), 3.83 (d, IH), 2.90 (s, 3H), 2.51 (s, 3H).
By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 15 can be prepared. The following abbreviations are used in the Tables which follow: CN means cyano, NO2 means nitro, Ph means phenyl, Py means pyridinyl, Me means methyl, Et means ethyl, i-Pr means isopropyl, and OMe means methoxy. (R2)m as shown refers to the combination of (R2)n with the instance of Z being CR2 as specified for Formula 1.
Table 1
Figure imgf000038_0001
wherein m is 1, 2, 3, 4 or 5.
R12
»2>m R5 R12 Rl3 (R2)m R5 Rl3
3-Cl H H CH2CF3 3-Cl H H CH2-2-Py
3-Cl, 4-Cl H H CH2CF3 3-Cl, 4-Cl H H CH2-2-Py
3-Cl, 5-Cl H H CH2CF3 3-Cl, 5-Cl H H CH2-2-Py
3-Cl, 4-F H H CH2CF3 3-Cl, 4-F H H CH2-2-Py
3-Cl, 4-CF3 H H CH2CF3 3-Cl, 4-CF3 H H CH2-2-Py
3-Cl, 4-Br H H CH2CF3 3-Cl, 4-Br H H CH2-2-Py
3-CF3 H H CH2CF3 3-CF3 H H CH2-2-Py
3-CF3, 5-CF3 H H CH2CF3 3-CF3, 5-CF3 H H CH2-2-Py
3-Br H H CH2CF3 3-Br H H CH2-2-Py
3-Br, 5-Br H H CH2CF3 3-Br, 5-Br H H CH2-2-Py
3-Cl NO2 H CH2CF3 3-Cl NO2 H CH2-2-Py
3-Cl, 4-CI NO2 H CH2CF3 3-Cl, 4-Cl NO2 H CH2-2-Py
3-Cl, 5-CI NO2 H CH2CF3 3-Cl, 5-Cl NO2 H CH2-2-Py
3-Cl, 4-F NO2 H CH2CF3 3-Cl, 4-F NO2 H CH2-2-Py
3-Cl, 4-CF3 NO2 H CH2CF3 3-Cl, 4-CF3 NO2 H CH2-2-Py
3-Cl, 4-Br NO2 H CH2CF3 3-Cl, 4-Br NO2 H CH2-2-Py
3-CF3 NO2 H CH2CF3 3-CF3 NO2 H CH2-2-Py
3-CF3, 5-CF3 NO2 H CH2CF3 3-CF3, 5 -CF3 NO2 H CH2-2-Py
3-Br NO2 H CH2CF3 3-Br NO2 H CH2-2-Py R12
(R2)m (R2)m R5 R12 R13
3-Br, 5-Br NO2 H CH2CF3 3-Br, 5-Br NO2 H CH2-2-Py
3-Cl CH3 H CH2CF3 3-Cl CH3 H CH2-2-Py
3-Cl, 4-Cl CH3 H CH2CF3 3-Cl, 4-Cl CH3 H CH2-2-Py
3-Cl, 5-Cl CH3 H CH2CF3 3-Cl, 5-Cl CH3 H CH2-2-Py
3-CI, 4-F CH3 H CH2CF3 3-Cl, 4-F CH3 H CH2-2-Py -Cl, 4-CF3 CH3 H CH2CF3 3-Cl, 4-CF3 CH3 H CH2-2-Py
3-Cl, 4-Br CH3 H CH2CF3 3-Cl, 4-Br CH3 H CH2-2-Py
3-CF3 CH3 H CH2CF3 3-CF3 CH3 H CH2-2-Py -CF3, 5-CF3 CH3 H CH2CF3 3-CF3, 5-CF3 CH3 H CH2-2-Py
3-Br CH3 H CH2CF3 3-Br CH3 H CH2-2-Py
3-Br, 5-Br CH3 H CH2CF3 3-Br, 5-Br CH3 H CH2-2-Py
3-Cl Cl H CH2CF3 3-Cl Cl H CH2-2-Py
3-Cl, 4-Cl Cl H CH2CF3 3-Cl, 4-Cl Cl H CH2-2-Py
3-Cl, 5-Cl Cl H CH2CF3 3-Cl, 5-Cl Cl H CH2-2-Py
3-Cl, 4-F Cl H CH2CF3 3-Cl, 4-F Cl H CH2-2-Py -Cl, 4-CF3 Cl H CH2CF3 3-Cl, 4-CF3 Cl H CH2-2-Py
3-Cl, 4-Br Cl H CH2CF3 3-Cl, 4-Br Cl H CH2-2-Py
3-CF3 Cl H CH2CF3 3-CF3 Cl H CH2-2-Py -CF3, 5-CF3 Cl H CH2CF3 3-CF3, 5-CF3 Cl H CH2-2-Py
3-Br Cl H CH2CF3 3-Br Cl H CH2-2-Py
3-Br, 5-Br Cl H CH2CF3 3-Br, 5-Br Cl H CH2-2-Py
3-Cl CF3 H CH2CF3 3-Cl CF3 H CH2-2-Py
3-Cl, 4-Cl CF3 H CH2CF3 3-Cl, 4-Cl CF3 H CH2-2-Py
3-Cl, 5-Cl CF3 H CH2CF3 3-Cl, 5-Cl CF3 H CH2-2-Py
3-Cl, 4-F CF3 H CH2CF3 3-Cl, 4-F CF3 H CH2-2-Py
3-Cl, 4-CF3 CF3 H CH2CF3 3-Cl, 4-CF3 CF3 H CH2-2-Py
3-Cl, 4-Br CF3 H CH2CF3 3-Cl, 4-Br CF3 H CH2-2-Py
3-CF3 CF3 H CH2CF3 3-CF3 CF3 H CH2-2-Py -CF3, 5-CF3 CF3 H CH2CF3 3-CF3, 5-CF3 CF3 H CH2-2-Py
3-Br CF3 H CH2CF3 3-Br CF3 H CH2-2-Py
3-Br, 5-Br CF3 H CH2CF3 3-Br, 5-Br CF3 H CH2-2-Py
3-Cl CN H CH2CF3 3-Cl CN H CH2-2-Py
3-Cl, 4-Cl CN H CH2CF3 3-Cl, 4-Cl CN H CH2-2-Py
3-Cl, 5-Cl CN H CH2CF3 3-Cl, 5-Cl CN H CH2-2-Py
3-Cl, 4-F CN H CH2CF3 3-Cl, 4-F CN H CH2-2-Py
3-Cl, 4-CF3 CN H CH2CF3 3-Cl, 4-CF3 CN H CH2-2-Py
3-Cl, 4-Br CN H CH2CF3 3-Cl, 4-Br CN H CH2-2-Py R5 R12
(R2)m Rl3 (R2)m R5 R12 R13
3-CF3 CN H CH2CF3 3-CF3 CN H CH2-2-Py -CF3, 5-CF3 CN H CH2CF3 3-CF3, 5-CF3 CN H CH2-2-Py
3-Br CN H CH2CF3 3-Br CN H CH2-2-Py
3-Br, 5-Br CN H CH2CF3 3-Br, 5-Br CN H CH2-2-Py
3-Cl OMe H CH2CF3 3-Cl OMe H CH2-2-Py
3-Cl, 4-Cl OMe H CH2CF3 3-Cl.4-CI OMe H CH2-2-Py
3-Cl.5-Cl OMe H CH2CF3 3-Cl, 5-Cl OMe H CH2-2-Py
3-Cl, 4-F OMe H CH2CF3 3-Cl, 4-F OMe H CH2-2-Py -CI, 4-CF3 OMe H CH2CF3 3-Cl, 4-CF3 OMe H CH2-2-Py
3-CI, 4-Br OMe H CH2CF3 3-Cl, 4-Br OMe H CH2-2-Py
3-CF3 OMe H CH2CF3 3-CF3 OMe H CH2-2-Py -CF3, 5-CF3 OMe H CH2CF3 3-CF3, 5-CF3 OMe H CH2-2-Py
3-Br OMe H CH2CF3 3-Br OMe H CH2-2-Py
3-Br, 5-Br OMe H CH2CF3 3-Br, 5-Br OMe H CH2-2-Py
3-Cl H H CH2CH3 3-Cl CF3 H CH2CH3
3-Cl, 4-Cl H H CH2CH3 3-Cl, 4-Cl CF3 H CH2CH3
3-Cl, 5-Cl H H CH2CH3 3-Cl, 5-Cl CF3 H CH2CH3
3-Cl, 4-F H H CH2CH3 3-Cl, 4-F CF3 H CH2CH3
3-Cl, 4-CF3 H H CH2CH3 3-Cl. 4-CF3 CF3 H CH2CH3
3-Cl, 4-Br H H CH2CH3 3-Cl, 4-Br CF3 H CH2CH3
3-CF3 H H CH2CH3 3-CF3 CF3 H CH2CH3 -CF3, 5-CF3 H H CH2CH3 3-CF3, 5-CF3 CF3 H CH2CH3
3-Br H H CH2CH3 3-Br CF3 H CH2CH3
3-Br, 5-Br H H CH2CH3 3-Br, 5-Br CF3 H CH2CH3
3-Cl NO2 H CH2CH3 3-Cl CN H CH2CH3
3-Cl, 4-Cl NO2 H CH2CH3 3-Cl, 4-Cl CN H CH2CH3
3-Cl, 5-Cl NO2 H CH2CH3 3-Cl, 5-Cl CN H CH2CH3
3-Cl, 4-F NO2 H CH2CH3 3-Cl, 4-F CN H CH2CH3
3-Cl, 4-CF3 NO2 H CH2CH3 3-Cl, 4-CF3 CN H CH2CH3
3-Cl, 4-Br NO2 H CH2CH3 3-Cl, 4-Br CN H CH2CH3
3-CF3 NO2 H CH2CH3 3-CF3 CN H CH2CH3 -CF3, 5-CF3 NO2 H CH2CH3 3-CF3, 5-CF3 CN H CH2CH3
3-Br NO2 H CH2CH3 3-Br CN H CH2CH3
3-Br, 5-Br NO2 H CH2CH3 3-Br, 5-Br CN H CH2CH3
3-Cl CH3 H CH2CH3 3-Cl OMe H CH2CH3
3-Cl, 4-Cl CH3 H CH2CH3 3-Cl, 4-Cl OMe H CH2CH3
3-Cl, 5-Cl CH3 H CH2CH3 3-Cl, 5-Cl OMe H CH2CH3 (R2) m R5 Rl2 Rl3 (R^) m R5 R12 Rl3
3-Cl, 4-F CH3 H CH2CH3 3-Cl, 4-F OMe H CH2CH3
3-Cl, 4-CF3 CH3 H CH2CH3 3-Cl, 4-CF3 OMe H CH2CH3
3-Cl, 4-Br CH3 H CH2CH3 3-Cl, 4-Br OMe H CH2CH3
3-CF3 CH3 H CH2CH3 3-CF3 OMe H CH2CH3 3-CF3, 5-CF3 CH3 H CH2CH3 3-CF3, 5-CF3 OMe H CH2CH3
3-Br CH3 H CH2CH3 3-Br OMe H CH2CH3 3-Br, 5-Br CH3 H CH2CH3 3-Br, 5-Br OMe H CH2CH3
3-Cl Cl H CH2CH3 3-Cl, 4-Br Cl H CH2CH3
3-Cl, 4-CI Cl H CH2CH3 3-CF3 Cl H CH2CH3 3-Cl, 5-Cl Cl H CH2CH3 3-CF3, 5-CF3 Cl H CH2CH3 3-Cl, 4-F Cl H CH2CH3 3-Br Cl H CH2CH3 3-CI, 4-CF3 Cl H CH2CH3 3-Br, 5-Br Cl H CH2CH3 3-Cl, 5-Cl CN Me CH2CF3 3-Cl, 5-Cl CN Me CH2-2-Py 3-Cl, 5-Cl CN CH2OCH3 CH2CF3 3-Cl, 5-Cl CN CH2OCH3 CH2-2-Py 3-Cl, 5-Cl NO2 Me CH2CF3 3-Cl, 5-Cl NO2 Me CH2-2-Py 3-Cl, 5-Cl NO2 CH2OCH3 CH2CF3 3-Cl, 5-Cl NO2 CH2OCH3 CH2-2-Py 3-Cl, 5-Cl Cl Me CH2CF3 3-Cl, 5-Cl Cl Me CH2-2-Py 3-CI, 5-Cl Cl CH2OCH3 CH2CF3 3-Cl, 5-Cl Cl CH2OCH3 CH2-2-Py 3-Cl, 5-Cl CH3 Me CH2CF3 3-Cl, 5-Cl CH3 Me CH2-2-Py 3-Cl, 5-Cl CH3 CH2OCH3 CH2CF3 3-Cl, 5-Cl CH3 CH2OCH3 CH2-2-Py
Table
Figure imgf000041_0001
R3 R5 Rl2 R13 R3 R5 R12 R!3
H H H CH2CF3 H H H CH2-2-Py
Me H H CH2CF3 Me H H CH2-2-Py
CH2CH3 H H CH2CF3 CH2CH3 H H CH2-2-Py
CH2CF3 H H CH2CF3 CH2CF3 H H CH2-2-Py
CN H H CH2CF3 CN H H CH2-2-Py
H NO2 H CH2CF3 H NO2 H CH2-2-Py
Me NO2 H CH2CF3 Me NO2 H CH2-2-Py R3 R5 Rl2 Rl3 R3 R5 Rl2 R13
CH2CH3 NO2 H CH2CF3 CH2CH3 NO2 H CH2-2-Py
CH2CF3 NO2 H CH2CF3 CH2CF3 NO2 H CH2-2-Py
CN NO2 H CH2CF3 CN NO2 H CH2-2-Py
H CH3 H CH2CF3 H CH3 H CH2-2-Py
Me CH3 H CH2CF3 Me CH3 H CH2-2-Py
CH2CH3 CH3 H CH2CF3 CH2CH3 CH3 H CH2-2-Py
CH2CF3 CH3 H CH2CF3 CH2CF3 CH3 H CH2-2-Py
CN CH3 H CH2CF3 CN CH3 H CH2-2-Py
H CI H CH2CF3 H Cl H CH2-2-Py
Me CI H CH2CF3 Me Cl H CH2-2-Py
CH2CH3 Cl H CH2CF3 CH2CH3 Cl H CH2-2-Py
CH2CF3 Cl H CH2CF3 CH2CF3 Cl H CH2-2-Py
CN Cl H CH2CF3 CN Cl H CH2-2-Py
H CF3 H CH2CF3 H CF3 H CH2-2-Py
Me CF3 H CH2CF3 Me CF3 H CH2-2-Py
CH2CH3 CF3 H CH2CF3 CH2CH3 CF3 H CH2-2-Py
CH2CF3 CF3 H CH2CF3 CH2CF3 CF3 H CH2-2-Py
CN CF3 H CH2CF3 CN CF3 H CH2-2-Py
H CN H CH2CF3 H CN H CH2-2-Py
Me CN H CH2CF3 Me CN H CH2-2-Py
CH2CH3 CN H CH2CF3 CH2CH3 CN H CH2-2-Py
CH2CF3 CN H CH2CF3 CH2CF3 CN H CH2-2-Py
CN CN H CH2CF3 CN CN H CH2-2-Py
H OMe H CH2CF3 H OMe H CH2-2-Py
Me OMe H CH2CF3 Me OMe H CH2-2-Py
CH2CH3 OMe H CH2CF3 CH2CH3 OMe H CH2-2-Py
CH2CF3 OMe H CH2CF3 CH2CF3 OMe H CH2-2-Py
CN OMe H CH2CF3 CN OMe H CH2-2-Py
H H H CH2CH3 H CF3 H CH2CH3
Me H H CH2CH3 Me CF3 H CH2CH3
CH2CH3 H H CH2CH3 CH2CH3 CF3 H CH2CH3
CH2CF3 H H CH2CH3 CH2CF3 CF3 H CH2CH3
CN H H CH2CH3 CN CF3 H CH2CH3
H NO2 H CH2CH3 H CN H CH2CH3
Me NO2 H CH2CH3 Me CN H CH2CH3
CH2CH3 NO2 H CH2CH3 CH2CH3 CN H CH2CH3
CH2CF3 NO2 H CH2CH3 CH2CF3 CN H CH2CH3 R3 R5 Rl2 R13 R3 R5 R'2 R13
CN NO2 H CH2CH3 CN CN H CH2CH3
H CH3 H CH2CH3 H OMe H CH2CH3 Me CH3 H CH2CH3 Me OMe H CH2CH3
CH2CH3 CH3 H CH2CH3 CH2CH3 OMe H CH2CH3
CH2CF3 CH3 H CH2CH3 CH2CF3 OMe H CH2CH3
CN CH3 H CH2CH3 CN OMe H CH2CH3
H Cl H CH2CH3 CH2CF3 CI H CH2CH3
Me Cl H CH2CH3 CN Cl H CH2CH3
CH2CH3 Cl H CH2CH3
H CN Me CH2CF3 H CN Me CH2-2-Py Me CN CH2OCH3 CH2CF3 Me CN CH2OCH3 CH2-2-Py
H NO2 Me CH2CF3 H NO2 Me CH2-2-Py Me NO2 CH2OCH3 CH2CF3 Me NO2 CH2OCH3 CH2-2-Py
H Cl Me CH2CF3 H Cl Me CH2-2-Py Me Cl CH2OCH3 CH2CF3 Me Cl CH2OCH3 CH2-2-Py
H CH3 Me CH2CF3 H CH3 Me CH2-2-Py Me CH3 CH2OCH3 CH2CF3 Me CH3 CH2OCH3 CH2-2-Py
Table 3
Figure imgf000043_0001
W-I W-2 W-3 W-4 wherein m is 1, 2, 3, 4 or 5.
(R2)m R5 W (R2)m R5 W
3-Cl, 5-Cl CF3 W-I 3-Cl, 5-Cl H W-I
3-CI, 4-F CF3 W-I 3-Cl, 4-F H W-I
3-C1.4-C1 CF3 W-I 3-Cl, 4-CI H W-I
3-CF3 CF3 W-I 3-CF3 . H W-I
3-Br, 5-Br CF3 W-I 3-Br, 5-Br H W-I
3-Br CF3 W-I 3-Br H W-I (R2>m R5 W (R2)m R5 W
3-C! CF3 W-2 3-Cl H W-2
3-Cl, 4-CI CF3 W-2 3-CI, 4-Cl H W-2
3-CI.5-CI CF3 W-2 3-Cl, 5-Cl H W-2
3-Cl, 4-F CF3 W-2 3-Cl, 4-F H W-2 -Cl, 4-CF3 CF3 W-2 3-CI, 4-CF3 H W-2
3-Cl, 4-Br CF3 W-2 3-Cl, 4-Br H W-2
3-CF3 CF3 W-2 3-CF3 H W-2 -CF3, 5-CF3 CF3 W-2 3-CF3, 5-CF3 H W-2
3-Br CF3 W-2 3-Br H W-2
3-Br, 5-Br CF3 W-2 3-Br, 5-Br H W-2
3-Cl, 5-Cl CF3 W-3 3-Cl, 5-Cl H W-3
3-Cl, 4-F CF3 W-3 3-CI, 4-F H W-3
3-Cl, 4-Cl CF3 W-3 3-Cl, 4-Cl H W-3
3-CF3 CF3 W-3 3-CF3 H W-3
3-Br, 5-Br CF3 W-3 3-Br, 5-Br H W-3
3-Br CF3 W-3 3-Br H W-3
3-Cl, 5-Cl CF3 W-4 3-Cl, 5-CI H W-4
3-Cl, 4-F CF3 W-4 3-Cl, 4-F H W-4
3-Cl, 4-Cl CF3 W-4 3-Cl, 4-Cl H W-4
3-CF3 CF3 W-4 3-CF3 H W-4
3-Br, 5-Br CF3 W-4 3-Br, 5-Br H W-4
3-Br CF3 W-4 3-Br H W-4
3-Cl, 5-Cl CH3 W- I 3-Cl, 5-Cl NO2 W-I
3-Cl, 4-F CH3 W-I 3-Cl, 4-F NO2 W-I
3-Cl, 4-Cl CH3 W-I 3-Cl, 4-Cl NO2 W-I
3-CF3 CH3 W-I 3-CF3 NO2 W-I
3-Br, 5-Br CH3 W-I 3-Br, 5-Br NO2 W-I
3-Br CH3 W-I 3-Br NO2 W-I
3-Cl CH3 W-2 3-Cl NO2 W-2
3-Cl.4-Cl CH3 W-2 3-Cl, 4-Cl NO2 W-2
3-Cl, 5-Cl CH3 W-2 3-Cl, 5-Cl NO2 W-2
3-Cl, 4-F CH3 W-2 3-Cl, 4-F NO2 W-2
3-Cl, 4-CF3 CH3 W-2 3-Cl, 4-CF3 NO2 W-2
3-Cl, 4-Br CH3 W-2 3-Cl, 4-Br NO2 W-2
3-CF3 CH3 W-2 3-CF3 NO2 W-2 -CF3, 5-CF3 CH3 W-2 3-CF3, 5-CF3 NO2 W-2
3-Br CH3 W-2 3-Br NO2 W-2 (R2)m R5 W (R2)m R5 W
3-Br, 5-Br CH3 W-2 3-Br, 5-Br NO2 W-2
3-Cl, 5-CI CH3 W-3 3-Cl, 5-CI NO2 W-3
3-Cl, 4-F CH3 W-3 3-Cl, 4-F NO2 W-3
3-CI, 4-Cl CH3 W-3 3-Cl, 4-Cl NO2 W-3
3-CF3 CH3 W-3 3-CF3 NO2 W-3
3-Br, 5-BΓ CH3 W-3 3-Br, 5-Br NO2 W-3
3-Br CH3 W-3 3-Br NO2 W-3
3-C], 5-CI CH3 W-4 3-Cl, 5-CI NO2 W-4
3-CI, 4-F CH3 W-4 3-Cl, 4-F NO2 W-4
3-Cl, 4-Cl CH3 W-4 3-Cl, 4-Cl NO2 W-4
3-CF3 CH3 W-4 3-CF3 NO2 W-4
3-Br, 5-Br CH3 W-4 3-Br, 5-Br NO2 W-4
3-Br CH3 W-4 3-Br NO2 W-4
3-Cl, 5-CI Cl W-I 3-Cl, 5-CI OMe W-I
3-Cl, 4-F Cl W-I 3-Cl, 4-F OMe W-I
3-Cl, 4-Cl Cl W-I 3-Cl, 4-Cl OMe W-I
3-CF3 Cl W-I 3-CF3 OMe W-I
3-Br, 5-Br Cl W-I 3-Br, 5-Br OMe W-I
3-Br Cl W-I 3-Br OMe W-I
3-Cl Cl W-2 3-Cl OMe W-2
3-Cl, 4-Cl Cl W-2 3-CI, 4-Cl OMe W-2
3-CI, 5-CI Cl W-2 3-Cl, 5-CI OMe W-2
3-CI, 4-F Cl W-2 3-Cl, 4-F OMe W-2 -Cl, 4-CF3 Cl W-2 3-Cl, 4-CF3 OMe W-2
3-Cl, 4-Br Cl W-2 3-Cl, 4-Br OMe W-2
3-CF3 Cl W-2 3-CF3 OMe W-2 -CF3, 5-CF3 CI W-2 3-CF3, 5-CF3 OMe W-2
3-Br Cl W-2 3-Br OMe W-2
3-Br, 5-Br Cl W-2 3-Br, 5-Br OMe W-2
3-Cl, 5-CI Cl W-3 3-CI, 5-CI OMe W-3
3-Cl, 4-F Cl W-3 3-Cl, 4-F OMe W-3
3-Cl, 4-Cl Cl W-3 3-Cl, 4-Cl OMe W-3
3-CF3 Cl W-3 3-CF3 OMe W-3
3-Br, 5-Br Cl W-3 3-Br, 5-Br OMe W-3
3-Br Cl W-3 3-Br OMe W-3
3-CI, 5-CI Cl W-4 3-C1.5-C1 OMe W-4
3-CI, 4-F Cl W-4 3-Cl, 4-F OMe W-4 (R2)m R5 W (R2)m R5 W
3-Cl, 4-Cl Cl W-4 3-Cl, 4-Cl OMe W-4
3-CF3 Cl W-4 3-CF3 OMe W-4
3-Br, 5-Br Cl W-4 3-Br, 5-Br OMe W-4
3-Br Cl W-4 3-Br OMe W-4
3-Cl, 5-Cl CN W-I 3-Cl, 5-Cl CN W-3
3-Cl, 4-F CN W-I 3-Cl, 4-F CN W-3
3-Cl, 4-Cl CN W-I 3-Cl, 4-Cl CN W-3
3-CF3 CN W-I 3-CF3 • CN W-3
3-Br, 5-Br CN W-I 3-Br, 5-Br CN W-3
3-Br CN W-I 3-Br CN W-3
3-Cl CN W-2 3-Cl, 5-Cl CN W-4
3-Cl, 4-Cl CN W-2 3-Cl, 4-F CN W-4
3-Cl, 5-Cl CN W-2 3-Cl, 4-Cl CN W-4
3-Cl, 4-F CN W-2 3-CF3 CN W-4
3-Cl, 4-CF3 CN W-2 3-Br, 5-Br CN W-4
3-Cl, 4-Br CN W-2 3-Br CN W-4
3-CF3 CN W-2 3-Br CN W-2 -CF3, 5-CF3 CN W-2 3-Br, 5-Br CN W-2
Table 4
Figure imgf000046_0001
W-I w-2 W-3 W-4 wherein m is 1, 2, 3, 4
(R2) m R3 R5 W (R2)m R3 R5 W -Cl, 5-Cl H H W-I 3-Cl, 5-Cl H H W-2 -Cl, 5-Cl Me H W-I 3-Cl, 5-Cl Me H W-2 -Cl, 5-Cl CH2CH3 H W-I 3-Cl, 5-Cl CH2CH3 H W-2 -Cl, 5-Cl CH2CF3 H W-I 3-Cl, 5-Cl CH2CF3 H W-2 (R2)m R3 R5 W (R2)m R3 R5 W -Cl, 5-Cl CN H W- I 3-Cl, 5-Cl CN H W-2 -Cl, 5-Cl H NO2 W-I 3-Cl, 5-Cl H NO2 W-2 -CI, 5-CI Me NO2 W-I 3-Cl, 5-Cl Me NO2 W-2 -Cl, 5-C! CH2CH3 NO2 W-I 3-Cl, 5-Cl CH2CH3 NO2 W-2 -Cl, 5-Cl CH2CF3 NO2 W-I 3-Cl, 5-Cl CH2CF3 NO2 W-2 -Cl, 5-Cl CN NO2 W- I 3-Cl, 5-Cl CN NO2 W-2 -Cl, 5-Cl H CH3 W-I 3-Cl, 5-Cl H CH3 W-2 -Cl, 5-Cl Me CH3 W-I 3-Cl, 5-Cl Me CH3 W-2 -Cl, 5-Cl CH2CH3 CH3 W-I 3-Cl, 5-Cl CH2CH3 CH3 W-2 -Cl, 5-Cl CH2CF3 CH3 W- I 3-Cl, 5-CI CH2CF3 CH3 W-2 -Cl, 5-Cl CN CH3 W-I 3-Cl, 5-Cl CN CH3 W-2 -Cl, 5-Cl H Cl W-I 3-Cl, 5-Cl H Cl W-2 -Cl, 5-Cl Me Cl W-I 3-Cl, 5-Cl Me Cl W-2 -Cl, 5-Cl CH2CH3 Cl W-I 3-Cl, 5-Cl CH2CH3 Cl W-2 -Cl, 5-Cl CH2CF3 Cl W-I 3-CI, 5-Cl CH2CF3 Cl W-2 -Cl, 5-Cl CN Cl W- I 3-Cl, 5-Cl CN Cl W-2 -Cl, 5-Cl H CF3 W-I 3-Cl, 5-Cl H CF3 W-2 -Cl, 5-Cl Me CF3 W-I 3-Cl, 5-Cl Me CF3 W-2 -Cl, 5-Cl CH2CH3 CF3 W-I 3-CI, 5-Cl CH2CH3 CF3 W-2 -Cl, 5-Cl CH2CF3 CF3 W-I 3-Cl, 5-Cl CH2CF3 CF3 W-2 -Cl, 5-CI CN CF3 W-I 3-Cl, 5-Cl CN CF3 W-2 -Cl, 5-CI H CN W-I 3-Cl, 5-Cl H CN W-2 -Cl, 5-Cl Me CN W-I 3-Cl, 5-Cl Me CN W-2 -Cl, 5-Cl CH2CH3 CN W-I 3-Cl, 5-Cl CH2CH3 CN W-2 -Cl, 5-Cl CH2CF3 CN W-I 3-Cl, 5-Cl CH2CF3 CN W-2 -Cl, 5-Cl CN CN W-I 3-Cl, 5-Cl CN CN W-2 -Cl, 5-Cl H OMe W-I 3-CI, 5-Cl H OMe W-2 -Cl, 5-Cl . Me OMe W- I 3-Cl, 5-Cl Me OMe W-2 -Cl, 5-Cl CH2CH3 OMe W-I 3-CI, 5-Cl CH2CH3 OMe W-2 -Cl, 5-Cl CH2CF3 OMe W-I 3-Cl, 5-Cl CH2CF3 OMe W-2 -Cl, 5-CI CN OMe W-I 3-Cl, 5-Cl CN OMe W-2 -Cl, 5-Cl H H W-3 3-Cl, 5-Cl H H W-4 -Cl, 5-Cl Me H W-3 3-CI, 5-Cl Me H W-4 -Cl, 5-Cl CH2CH3 H W-3 3-CI, 5-Cl CH2CH3 H W-4 -Cl, 5-Cl CH2CF3 H W-3 3-Cl, 5-Cl CH2CF3 H W-4 -Cl, 5-Cl CN H W-3 3-CI, 5-Cl CN H W-4 -Cl, 5-CI H NO2 W-3 3-Cl, 5-Cl H NO2 W-4 (R2)m R3 R5 W (R2)m R3 R5 W -Cl, 5-Cl Me NO2 W-3 3-Cl, 5-Cl Me NO2 W-4 -CI, 5-Cl CH2CH3 NO2 W-3 3-Cl, 5-Cl CH2CH3 NO2 W-4 -CI, 5-Cl CH2CF3 NO2 W-3 3-Cl, 5-Cl CH2CF3 NO2 W-4 -Cl, 5-Cl CN NO2 W-3 3-Cl, 5-Cl CN NO2 W-4 -CI, 5-Cl H CH3 W-3 3-Cl, 5-Cl H CH3 W-4 -Cl, 5-Cl Me CH3 W-3 3-Cl, 5-Cl Me CH3 W-4 -CI, 5-Cl CH2CH3 CH3 W-3 3-Cl, 5-Cl CH2CH3 CH3 W-4 -Cl, 5-Cl CH2CF3 CH3 W-3 3-Cl, 5-Cl CH2CF3 CH3 W-4 -Cl, 5-Cl CN CH3 W-3 3-Cl, 5-Cl CN CH3 W-4 -CI, 5-Cl H Cl W-3 3-Cl, 5-Cl H Cl W-4 -Cl, 5-Cl Me Cl W-3 3-Cl, 5-Cl Me Cl W-4 -CI, 5-Cl CH2CH3 Cl W-3 3-Cl, 5-Cl CH2CH3 Cl W-4 -CI, 5-Cl CH2CF3 Cl W-3 3-Cl, 5-Cl CH2CF3 Cl W-4 -CI, 5-Cl CN Cl W-3 3-Cl, 5-Cl CN Cl W-4 -Cl, 5-Cl H CF3 W-3 3-CI, 5-Cl W-4
H ) CF3 -Cl, 5-Cl Me CF3 W-3 3-CI, 5-Cl Me CF3 W-4 -Cl, 5-Cl CH2CH3 CF3 W-3 3-Cl, 5-Cl CH2CH3 CF3 W-4 -CI, 5-Cl CH2CF3 CF3 W-3 3-Cl, 5-Cl CH2CF3 CF3 W-4 -Cl, 5-Cl CN CF3 W-3 3-Cl, 5-Cl CN CF3 W-4 -CI, 5-Cl H CN W-3 3-Cl, 5-Cl H CN W-4 -CI, 5-Cl Me CN W-3 3-CI, 5-Cl Me CN W-4 -Cl, 5-Cl CH2CH3 CN W-3 3-Cl, 5-Cl CH2CH3 CN W-4 -Cl, 5-Cl CH2CF3 CN W-3 3-Cl, 5-Cl CH2CF3 CN W-4 -Cl, 5-Cl CN CN W-3 3-Cl, 5-Cl CN CN W-4 -Cl, 5-Cl H OMe W-3 3-Cl, 5-Cl H OMe W-4 -Cl, 5-CI Me OMe W-3 3-Cl, 5-Cl Me OMe W-4 -Cl, 5-Cl CH2CH3 OMe W-3 3-Cl, 5-Cl CH2CH3 OMe W-4 -Cl, 5-Cl CH2CF3 OMe W-3 3-CI, 5-Cl CH2CF3 OMe W-4 -Cl, 5-Cl CN OMe W-3 3-Cl, 5-Cl CN OMe W-4
3-Br H H W-2 3-Br H CF3 W-2
3-BΓ Me H W-2 3-Br Me CF3 W-2
3-Br CH2CH3 H W-2 3-Br CH2CH3 CF3 W-2
3-Br CH2CF3 H W-2 3-Br CH2CF3 CF3 W-2
3-Br CN H W-2 3-Br CN CF3 W-2
3-Br H NO2 W-2 3-Br H CN W-2
3-Br Me NO2 W-2 3-Br Me CN W-2
3-Br CH2CH3 NO2 W-2 3-Br CH2CH3 CN W-2 (R2) m R3 R5 W (R2)m R3 R5 W
3-BΓ CH2CF3 NO2 W-2 3-Br CH2CF3 CN W-2
3-Br CN NO2 W-2 3-Br CN CN W-2
3-Br H CH3 W-2 3-Br H OMe W-2
3-Br Me CH3 W-2 3-Br Me OMe W-2
3-Br CH2CH3 CH3 W-2 3-Br CH2CH3 OMe W-2
3-Br CH2CF3 CH3 W-2 3-Br CH2CF3 OMe W-2
3-Br CN CH3 W-2 3-Br CN OMe W-2
3-Br H Cl W-2 3-Br CH2CF3 Cl W-2
3-Br Me Cl W-2 3-Br CN Cl W-2
3-Br CH2CH3 Cl W-2
Table 5
Figure imgf000049_0001
W-2 W-4 W-5 W-6
R2 R5 zi Z2 W R2 R5 zi Z2 W
Br Cl CH N W-2 Br Cl CH N W-4
Br H CH N W-2 Br H CH N W-4
Br Me CH N W-2 Br Me CH N W-4
CF3 Cl CH N W-2 CF3 Cl CH N W-4
CF3 H CH N W-2 CF3 H CH N W-4
CF3 Me CH N W-2 CF3 Me CH N W-4
Cl Cl CH N W-2 Cl Cl CH N W-4
Cl H CH N W-2 Cl H CH N W-4
Cl Me CH N W-2 Cl Me CH N W-4
CF3 Cl N CCl W-2 CF3 Cl N CCl W-4
CF3 H N CCl W-2 CF3 H N CCl W-4
CF3 Me N CCl W-2 CF3 Me N CCI W-4
Cl Cl N CCl W-2 Cl Cl N CCl W-4 R2 R5 zi Z2 W R2 R5 Zl Z2 W
Cl H N CCl W-2 Cl H N CCl W-4
C! Me N CCl W-2 Cl Me N CCl W-4
Br CI CH N W-5 Br Cl CH N W-6
Br H CH N W-5 Br H CH N W-6
Br Me CH N W-5 Br Me CH N W-6
CF3 Cl CH N W-5 CF3 Cl CH N W-6
CF3 H CH N W-5 CF3 H CH N W-6
CF3 Me CH N W-5 CF3 Me CH N W-6
Cl Cl CH N W-5 Cl Cl CH N W-6
Cl H CH N W-5 Cl H CH N W-6
Cl Me CH N W-5 Cl Me CH N W-6
CF3 Cl N CCI W-5 CF3 Cl N CCl W-6
CF3 H N CCl W-5 CF3 H N CCl W-6
CF3 Me N CCl W-5 CF3 Me N CCl W-6
Cl Cl N CCl W-5 Cl Cl N CCl W-6
Cl H N CCl W-5 Cl H N CCl W-6
Cl Me N CCl W-5 Cl Me N CCl W-6
Table 6
Figure imgf000050_0001
W-5 W-6
R2 R3 R5 Zl Z2 Q R2 R3 R5 zi Z2 Q
Br H H CH N W-2 Br H H CH N W-4
Br Me H CH N W-2 Br Me H CH N W-4
Br H Me CH N W-2 Br H Me CH N W-4
Br Me Me CH N W-2 Br Me Me CH N W-4
Br H Cl CH N W-2 Br H Cl CH N W-4
Br Me Cl CH N W-2 Br Me Cl CH N W-4 R2 R3 R5 z* Z2 Q R2 R3 R5 zi Z2 Q
Cl H H CH N W-2 CI H H CH N W-4
Cl Me H CH N W-2 Cl Me H CH N W-4
C! H Me CH N W-2 Cl H Me CH N W-4
Cl Me Me CH N W-2 Cl Me Me CH N W-4
Cl H Cl CH N W-2 Cl H Cl CH N W-4
Cl Me Cl CH N W-2 CI Me Cl CH N W-4
Cl H H N CCl W-2 CI H H N CCl W-4
Cl Me H N CCl W-2 Cl Me H N CCI W-4
Cl H Me N CCl W-2 Cl H Me N CCl W-4
Cl Me Me N CCl W-2 Cl Me Me N CCl W-4
Cl H Cl N CCl W-2 CI H Cl N CCl W-4
Cl Me Cl N CCl W-2 Cl Me Cl N CCl W-4
Br H H CH N W-5 Br H H CH N W-6
Br Me H CH N W-5 Br Me H CH N W-6
Br H Me CH N W-5 Br H Me CH N W-6
Br Me Me CH N W-5 Br Me Me CH N W-6
Br H Cl CH N W-5 Br H Cl CH N W-6
Br Me Cl CH N W-5 Br Me Cl CH N W-6
Cl H H CH N W-5 Cl H H CH N W-6
Cl Me H CH N W-5 Cl Me H CH N W-6
Cl H Me CH N W-5 Cl H Me CH N W-6
Cl Me Me CH N W-5 Cl Me Me CH N W-6
Cl H Cl CH N W-5 Cl H Cl CH N W-6
Cl Me Cl CH N W-5 Cl Me Cl CH N W-6
Cl H H N CCl W-5 Cl H H N CCl W-6
Cl Me H N CCl W-5 Cl Me H N CCl W-6
Cl H Me N CCl W-5 Cl H Me N CCl W-6
Cl Me Me N CCl W-5 Cl Me Me N CCl W-6
Cl H Cl N CCl W-5 Cl H Cl N CCl W-6
Cl Me Cl N CCl W-5 Cl Me Cl N CCl W-6
Figure imgf000052_0001
R5 R5
Ci SO2NHMe Me SO2NHMe
Cl SO2NMe2 Me SO2NMe2
Cl SO2NHCH2CH2=CH2 Me SO2NHCH2CH2=CH2
Cl SO2N(CH3)CH2CH2=CH2 Me SO2N(CH3)CH2CH2=CH2
Cl SO2NHCH2CF3 Me SO2NHCH2CF3
Cl SO2N(CH3)CH2CF3 Me SO2N(CH3)CH2CF3
Cl SO2NHCH2C=CH Me SO2NHCH2OCH
Cl SO2N(CH3)CH2C≡CH Me SO2N(CH3)CH2OCH
Cl SO2NHCH2-2-Py Me SO2NHCH2-2-Py
Cl SO2N(CH3)CH2-2-Py Me SO2N(CH3)CH2-2-Py
Cl Q=S)NHMe Me C(=S)NHMe
Cl C(=S)NMe2 Me C(=S)NMe2
Cl Q=S)NHCH2CH2=CH2 Me C(=S)NHCH2CH2=CH2
Cl Q=S)N(CH3)CH2CH2=CH2 Me Q=S)N(CH3)CH2CH2=CH2
Cl C(=S)NHCH2CF3 Me Q=S)NHCH2CF3
Cl C(=S)N(CH3)CH2CF3 Me Q=S)N(CH3)CH2CF3
Cl C(=S)NHCH2C≡CH Me Q=S)NHCH2OsCH
Cl Q=S)N(CH3)CH2OCH Me Q=S)NMeCH2CsCH
Cl C(=S)NHCH2-2-Py Me Q=S)NHCH2-2-Py
Cl C(=S)N(CH3)CH2-2-Py Me C(=S)N(CH3)CH2-2-Py
Cl F Me F
Cl Cl Me Cl
Cl CN Me CN
Cl NO2 Me NO2
Cl 4-morpholinyl Me 4-morpholinyl
CN SO2NHMe NO2 SO2NHMe
CN SO2NMe2 NO2 SO2NMe2
CN SO2NHCH2CH2=CH2 NO2 SO2NHCH2CH2=CH2
CN SO2N(CH3)CH2CH2=CH2 NO2 SO2N(CH3)CH2CH2=CH2
Figure imgf000053_0001
Table 8
Figure imgf000053_0002
R3 R5 Q R3 R5 Q
H Cl SO2NHMe H Me SO2NHMe
Me Cl SO2NHMe Me Me SO2NHMe
H Cl SO2NMe2 H Me SO2NMe2
Me Cl SO2NMe2 Me Me SO2NMe2
H Cl SO2NHCH2CH2=CH2 H Me SO2NHCH2CH2=CH2
Me Cl SO2NHCH2CH2=CH2 Me Me SO2NHCH2CH2=CH2 R5 Q R3 R5 Q
H Cl SO2NHCH2CF3 H Me SO2NHCH2CF3
Me Cl SO2NHCH2CF3 Me Me SO2NHCH2CF3
H CI SO2N(CH3)CH2CF3 H Me SO2N(CH3)CH2CF3
Me Cl SO2N(CH3)CH2CF3 Me Me SO2N(CH3)CH2CF3
H Cl SO2NHCH2C=CH H Me SO2NHCH2C≡CH
Me Cl SO2NHCH2G≡CH Me Me SO2NHCH2C≡CH
H Cl SO2NCH2-2-Py H Me SO2NHCH2-2-Py
Me Cl SO2NHCH2-2-Py Me Me SO2NHCH2-2-Py
H Cl SO2N(CH3)CH2-2-Py H Me SO2N(CH3)CH2^-Py
Me Cl SO2N(CH3)CH2-2-Py Me Me SO2N(CH3)CH2-2-Py
H Cl C(=S)NHMe H Me Q=S)NHMe
Me Cl C(=S)NHMe Me Me Q=S)NHMe
H Cl Q=S)NMe2 H Me Q=S)NMe2
Me Cl C(=S)NMe2 Me Me Q=S)NMe2
H Cl C(=S)NHCH2CH2=CH2 " H Me Q=S)NHCH2CH2=CH2
Me Cl Q=S)NHCH2CH2=CH2 Me Me Q=S)NHCH2CH2=CH2
H Cl C(=S)NHCH2CF3 H Me Q=S)NHCH2CF3
Me Cl C(=S)NHCH2CF3 Me Me Q=S)NHCH2CF3
H Cl C(=S)N(CH3)CH2CF3 H Me Q=S)N(CH3)CH2CF3
Me Cl C(=S)N(CH3)CH2CF3 Me Me Q=S)N(CH3)CH2CF3
H Cl Q=S)NHCH2C=CH H Me Q=S)NHCH2C=CH
Me Cl C(=S)NHCH2C≡CH Me Me Q=S)NHCH2C=CH
H Cl Q=S)N(CH3)CH2C=CH H Me Q=S)N(CH3)CH2C=CH
Me Cl C(=S)N(CH3)CH2C≡CH Me Me Q=S)N(CH3)CH2CsCH
H Cl C(=S)NHCH2-2-Py H Me C(=S)NHCH2-2-Py
Me Cl C(=S)NHCH2-2-Py Me Me C(=S)NHCH2-2-Py
H Cl C(=S)N(CH3) CH2-2-Py H Me C(=S)N(CH3)CH2-2-Py
Me Cl Q=S)N(CH3)CH2-2-Py Me Me Q=S)N(CH3)CH2-2-Py
H Cl F H Me F
Me Cl F Me Me F
H Cl Cl H Me Cl
Me Cl Cl Me Me Cl
H Cl CN H Me CN
Me Cl CN Me Me CN
H Cl NO2 H Me NO2
Me Cl NO2 Me Me NO2
H Cl 4-morpholinyl H Me 4-morpholinyl R3 R5 R3 R5 Q
Me CI 4-morpholinyl Me Me 4-morpholinyl
H CN SO2NHMe H NO2 SO2NHMe
Me CN SO2NHMe Me NO2 SO2NHMe
H CN SO2NMe2 H NO2 SO2NMe2
Me CN SO2NMe2 Me NO2 SO2NMe2
H CN SO2NHCH2CH2=CH2 H NO2 SO2NHCH2CH2=CH2
Me CN SO2NHCH2CH2=CH2 Me NO2 SO2NHCH2CH2=CH2
H CN SO2NHCH2CF3 H NO2 SO2NHCH2CF3
Me CN SO2NHCH2CF3 Me NO2 SO2NHCH2CF3
H CN SO2N(CH3)CH2CF3 H NO2 SO2N(CH3)CH2CF3
Me CN SO2N(CH3)CH2CF3 Me NO2 SO2N(CH3)CH2CF3
H CN SO2NHCH2OCH H NO2 SO2NHCH2CSCH
Me CN SO2NHCH2OCH Me NO2 SO2NHCH2CSCH
H CN SO2NHCH2-2-Py H NO2 SO2NHCH2-2-Py
Me CN SO2NHCH2-2-Py Me NO2 SO2NHCH2-2-Py
H CN SO2N(CH3)CH2-2-Py H NO2 SO2N(CH3)CH2-2-Py
Me CN SO2N(CH3)CH2-2-Py Me NO2 SO2N(CH3)CH2-2-Py
H CN Q=S)NHMe H NO2 Q=S)NHMe
Me CN C(=S)NHMe Me NO2 Q=S)NHMe
H CN C(=S)NMe2 H NO2 Q=S)NMe2
Me CN Q=S)NMe2 Me NO2 Q=S)NMe2
H CN Q=S)NHCH2CH2=CH2 H NO2 Q=S)NCH2CH2=CH2
Me CN Q=S)NHCH2CH2=CH2 Me NO2 CC=S)NHCH2CH2=CH2
H CN Q=S)NHCH2CF3 H NO2 Q=S)NHCH2CF3
Me CN Q=S)NHCH2CF3 Me NO2 Q=S)NHCH2CF3
H CN Q=S)N(CH3)CH2CF3 H NO2 Q=S)N(CH3)CH2CF3
Me CN Q=S)N(CH3)CH2CF3 Me NO2 Q=S)N(CH3)CH2CF3
H CN Q=S)NHCH2OCH H NO2 Q=S)NHCH2OCH
Me CN Q=S)NHCH2OCH Me NO2 Q=S)NHCH2OCH
H CN Q=S)N(CH3)CH2OCH H NO2 Q=S)N(CH3)CH2OCH
Me CN C(=S)N(CH3)CH2C≡CH Me NO2 Q=S)N(CH3)CH2OCH
H CN C(=S)NHCH2-2-Py H NO2 C(=S)NHCH2-2-Py
Me CN Q=S)NHCH2-2-Py Me NO2 Q=S)NHCH2-2-Py
H CN C(=S)N(CH3)CH2-2-Py H NO2 C(=S)N(CH3)CH2-2-Py
Me CN Q=S)N(CH3)CH2-2-Py Me NO2 C(=S)N(CH3)CH2-2-Py
H CN F H NO2 F
Me CN F Me NO2 F R3 R5 R3 R5 Q
H CN Cl H NO2 Cl Me CN Cl Me NO2 Cl
H CN CN H NO2 CN Me CN CN Me NO2 CN
H CN NO2 H NO2 NO2 Me CN NO2 Me NO2 NO2
H CN 4-morpholinyl H NO2 4-morpholinyl Me CN 4-morpholinyl Me NO2 4-morpholinyl
Table 9
SO2NHCH2-2-Py
1-imidazoyl l//-l,2,4-triazol-l-yl
4-morpholinyl
C(O)NHEt
C(O)NHCH2CF3
C(O)NHCH2-2-Py
SO2NHCH2CF3
SO2NHCH2-2-Py
1-imidazoyl l«-l ,2,4-triazol-l-yl
4-morpholinyl
C(O)NHEt
C(O)NHCH2CF3
C(O)NHCH2-2-Py
SO2NHCH2CF3
SO2NHCH2-2-Py
1-imidazoyl
Figure imgf000056_0001
IW- 1,2,4-triazol-l-yl R5 R5
Me SO2NHCH2CF3 H 4-moφhoIinyl
Figure imgf000057_0001
R5 U R5 U
CF3 S(=O) ltf-l,2,4-triazol-l-yl H S(=O) l//-l,2,4-triazol-l-yl
CF3 S(O)2 ltf-l,2,4-triazol-l-yl H S(O)2 l//-l,2,4-triazol-l-yl
CF3 S(=O) C(O)NHCH2-2-Py H S(=O) C(O)NHCH2-2-Py
CF3 S(O)2 C(O)NHCH2-2-Py H S(O)2 C(O)NHCH2-2-Py
CF3 S(=O) C(O)NHCH2CF3 H S(=O) C(O)NHCH2CF3
CF3 S(O)2 C(O)NHCH2CF3 H S(O)2 C(O)NHCH2CF3
CF3 S(=O) C(O)NHEt H S(=O) C(O)NHEt
CF3 S(O)2 C(O)NHEt H S(O)2 C(O)NHEt
Cl S(=O) l//-l,2,4-triazol-l-yl Me S(=O) l/M,2,4-triazol-l-yl
Cl S(O)2 l«-l,2,4-triazol-l-yl Me S(O)2 l//-l,2,4-triazol-l-yl
Cl S(=O) C(O)NHCH2-2-Py Me S(=O) C(O)NHCH2-2-Py
Cl S(O)2 C(O)NHCH2-2-Py Me S(O)2 C(O)NHCH2-2-Py
Cl S(=O) C(O)NHCH2CF3 Me S(=O) C(O)NHCH2CF3
Cl S(O)2 C(O)NHCH2CF3 Me S(O)2 C(O)NHCH2CF3
Cl S(=O) C(O)NHEt Me S(=O) C(O)NHEt
Cl S(O)2 C(O)NHEt Me S(O)2 C(O)NHEt
CN S(=O) l//-l,2,4-triazol-l-yl NO2 S(=O) lf/-l,2,4-triazol-l-yl
CN S(O)2 l/M,2.4-triazol-l-yl NO2 S(O)2 l//-l,2,4-triazol-l-yl
CN S(=O) C(O)NHCH2-2-Py NO2 S(=O) C(O)NHCH2-2-Py
CN S(O)2 C(O)NHCH2-2-Py NO2 S(O)2 C(O)NHCH2-2-Py
CN S(=O) C(O)NHCH2CF3 NO2 S(=O) C(O)NHCH2CF3
CN S(O)2 C(O)NHCH2CF3 NO2 S(O)2 C(O)NHCH2CF3
CN S(=O) C(O)NHEt NO2 S(=O) C(O)NHEt
CN S(O)2 C(O)NHEt NO2 S(O)2 C(O)NHEt
Figure imgf000058_0001
R3 R5 Q R3 R5
Me CF3 C(O)NHEt Me H C(O)NHEt
Me CF3 C(O)NHCH2CF3 Me H C(O)NHCH2CF3
Me CF3 C(O)NHCH2-2-Py Me H C(O)NHCH2-2-Py
Me CF3 7tf-l,2,4-triazol-l-yl Me H 7#-l,2,4-triazol-l-yl
H CF3 C(O)NHEt H H C(O)NHEt
H CF3 C(O)NHCH2CF3 H H C(O)NHCH2CF3
H CF3 C(O)NHCH2-2-Py H H C(O)NHCH2-2-Py
H CF3 ///-1,2,4-triazol-l-yl H H 7/f-l,2,4-triazol-l-yl
Me Cl C(O)NHEt Me Me C(O)NHEt
Me Cl C(O)NHCH2CF3 Me Me C(O)NHCH2CF3
Me Cl C(O)NHCH2-2-Py Me Me C(O)NHCH2-2-Py
Me Cl 7f/-l,2,4-triazol-l-yl Me Me 7/7-1,2,4-triazol-l-yl
H Cl C(O)NHEt H Me C(O)NHEt
H Cl C(O)NHCH2CF3 H Me C(O)NHCH2CF3
H Cl C(O)NHCH2-2-Py H Me C(O)NHCH2-2-Py
H Cl 7//-l,2,4-triazol-l-yl H Me 7/7-1,2,4-triazol-l-yl
Me CN C(O)NHEt Me NO2 C(O)NHEt
Me CN C(O)NHCH2CF3 Me NO2 C(O)NHCH2CF3
Me CN C(O)NHCH2-2-Py Me NO2 C(O)NHCH2-2-Py
Me CN 777-1,2,4-triazol-l-yl Me NO2 7//-l,2,4-triazol-l-yl
H CN C(O)NHEt H NO2 C(O)NHEt
H CN C(O)NHCH2CF3 H NO2 C(O)NHCH2CF3
H CN C(O)NHCH2-2-Py H NO2 C(O)NHCH2-2-Py
H CN /«-l,2,4-triazol-l-yl H NO2 7//-l,2,4-triazol-l-yl Table 12
Figure imgf000059_0001
Al A2 Al
CH CH C(O)NHEt CH N C(O)NHCH2-2-Py
N CH C(O)NHEt N N C(O)NHCH2-2-Py CH N C(O)NHEt CH CH 1-imidazoyl
N N C(O)NHEt N CH 1-imidazoyl CH CH C(O)NHCH2CF3 CH N 1-imidazoyl
N CH C(O)NHCH2CF3 N N 1-imidazoyl CH N C(O)NHCH2CF3 CH CH /tt-l,2,4-triazol-l-yl
N N C(O)NHCH2CF3 N CH /«-l,2,4-triazol-l-yl CH CH C(O)NHCH2-2-Py CH N /tf-l,2,4-triazol-l-yl
N CH C(O)NHCH2-2-Py N N /A/-l,2,4-triazol-l-yl
Figure imgf000059_0002
Al Q R3 Al Q
H N 7//-l,2,4-trtazol-l-yl CH2CF3 CH C(O)NHCH2-2-Py
Me CH ς(O)NHEt CH2CF3 N C(O)NHCH2-2-Py
Me N C(O)NHEt CH2CF3 CH 1-imidazoyl
Me CH C(O)NHCH2CF3 CH2CF3 N 1-imidazoyl
Me N C(O)NHCH2CF3 CH2CF3 CH 7«-l,2,4-triazol-l-yl
Me CH C(O)NHCH2-2-Py CH2CF3 N 7tf-l,2,4-triazol-l-yl
Table 14
Figure imgf000060_0001
wherein m is 1, 2, 3, 4 or 5.
(R2)m Al A3 RS Q R2 Al A3 R5 Q -Cl, 4-Cl N N H C(O)NHEt 3-Cl, 4-Cl N N H C(O)NHCH2-2-Py -CI, 4-Cl N CH H C(O)NHEt 3-Cl, 4-Cl N CH H C(O)NHCH2-2-Py -Cl, 4-Cl CH N H C(O)NHEt 3-Cl, 4-Cl CH N H C(O)NHCH2-2-Py -Cl, 5-Cl N N H C(O)NHEt 3-CI, 5-Cl N N H C(O)NHCH2-2-Py -Cl, 5-Cl N CH H C(O)NHEt 3-Cl, 5-Cl N CH H C(O)NHCH2-2-Py -Cl, 5-Cl CH N H C(O)NHEt 3-Cl, 5-Cl CH N H C(O)NHCH2-2-Py -Cl, 4-Cl N N Me C(O)NHEt 3-Cl, 4-Cl N N Me C(O)NHCH2-2-Py -Cl, 4-Cl N CH Me C(O)NHEt 3-CI, 4-Cl N CH Me C(O)NHCH2-2-Py -Cl, 4-Cl CH N Me C(O)NHEt 3-CI, 4-Cl CH N Me C(O)NHCH2-2-Py -Cl, 5-Cl N N Me C(O)NHEt 3-Cl, 5-Cl N N Me C(O)NHCH2-2-Py -Cl, 5-Cl N CH Me C(O)NHEt 3-Cl, 5-Cl N CH Me C(O)NHCH2-2-Py -Cl, 5-Cl CH N Me C(O)NHEt 3-Cl, 5-Cl CH N Me C(O)NHCH2-2-Py -Cl, 4-Cl N N CF3 C(O)NHEt 3-Cl, 4-Cl N N CF3 C(O)NHCH2-2-Py -Cl, 4-Cl N CH CF3 C(O)NHEt 3-Cl, 4-Cl N CH CF3 C(O)NHCH2-2-Py -Cl, 4-Cl CH N CF3 C(O)NHEt 3-Cl, 4-Cl CH N CF3 C(O)NHCH2-2-Py -Cl, 5-Cl N N CF3 C(O)NHEt 3-Cl, 5-Cl N N CF3 C(O)NHCH2-2-Py -Cl, 5-Cl N CH CF3 C(O)NHEt 3-Cl, 5-Cl N CH CF3 C(O)NHCH2-2-Py -Cl, 5-Cl CH N CF3 C(O)NHEt 3-Cl, 5-Cl CH N CF3 C(O)NHCH2-2-Py -Cl, 4-Cl N N H C(O)NHCH2CF3 3-Cl, 4-CI N N H l//- l,2,4-triazol-l-yl -Cl, 4-Cl N CH H C(O)NHCH2CF3 3-Cl, 4-Cl N CH H l«-l,2,4-triazol- l-yl -Cl, 4-Cl CH N H C(O)NHCH2CF3 3-Cl, 4-Cl CH N H l«- l,2,4-triazol-l-yl N H l//-l,2,4-triazol-l-yl CH H l//-l,2,4-triazol-l-yl
N H l//-l,2,4-triazol-l-yl
N Me l/M,2,4-triazol-l-yl
CH Me ltf-l,2,4-triazol-l-yl
N Me lΛ/-l,2,4-triazol-l-yl
N Me l«-l,2,4-triazol-l-yl
CH Me l//-l,2,4-triazol-l-yl
N Me lf/-l,2,4-triazol-l-yl
N CF3 l//-l,2,4-triazol-l-yl
CH CF3 l//-l,2,4-triazol-l-yl
N CF3 l//-l,2,4-triazol-l-yl
N CF3 l«-I,2,4-triazol-l-yl
CH CF3 l//-l,2,4-triazol-l-yl
Figure imgf000061_0001
N CF3 lW-l,2,4-triazol-l-yl
Table 15
Figure imgf000061_0002
R3 A1 A3 _R5_ Q R3 Al A3 R5
H CH N Me C(O)NHEt H N N H C(O)NHEt H CH N Me C(O)NHEt H N N H C(O)NHEt H CH N Me C(O)NHCH2CF3 H N N H C(O)NHCH2CF3 H CH N Me C(O)NHCH2CF3 H N N H C(O)NHCH2CF3 H CH N Me C(O)NHCH2-2-Py H N N H C(O)NHCH2-2-Py H CH N Me C(O)NHCH2-2-Py H N N H C(O)NHCH2-2-Py H CH N Me l//-l,2,4-triazol-l-yl H N N H l//-l,2,4-triazol-l-yl H CH N Me l#-l,2,4-triazol-l-yl H N N H lΛ/-l,2,4-triazol-l-yl Me CH N Me C(O)NHEt Me N N H C(O)NHEt Me CH N Me C(O)NHEt Me N N H C(O)NHEt Me CH N Me C(O)NHCH2CF3 Me N N H C(O)NHCH2CF3 Me CH N Me C(O)NHCH2CF3 Me N N H C(O)NHCH2CF3 R3 A1 A3 R5 R3 Al A3 R5
Me CH N Me C(O)NHCH2-2-Py Me N N H C(O)NHCH2-2-Py
Me . CH N Me C(O)NHCH2-2-Py Me N N H C(O)NHCH2-2-Py
Me CH N Me l//-l,2,4-triazol-l-yl Me N N H l/M,2,4-triazol-l-yl
Me CH N Me l/M,2,4-triazoI-l-yl Me N N H l//-l,2,4-triazol-l-yl
H N CH Me C(O)NHEt H CH N CF3 C(O)NHEt
H N CH Me C(O)NHEt H CH N CF3 C(O)NHEt
H N CH Me C(O)NHCH2CF3 H CH N CF3 C(O)NHCH2CF3
H N CH Me C(O)NHCH2CF3 H CH N CF3 C(O)NHCH2CF3
H N CH Me C(O)NHCH2-2-Py H CH N CF3 C(O)NHCH2-2-Py
H N CH Me C(O)NHCH2-2-Py H CH N CF3 C(O)NHCH2-2-Py
H N CH Me l//-l,2,4-triazol-l-yl H CH N CF3 ltf-l,2,4-triazol-l-yl
H N CH Me l/M,2,4-triazol-l-yl H CH N CF3 ltf-l,2,4-triazol-l-yl
Me N CH Me C(O)NHEt Me CH N CF3 C(O)NHEt
Me N CH Me C(O)NHEt Me CH N CF3 C(O)NHEt
Me N CH Me C(O)NHCH2CF3 Me CH N CF3 C(O)NHCH2CF3
Me N CH Me C(O)NHCH2CF3 Me CH N CF3 C(O)NHCH2CF3
Me N CH Me C(O)NHCH2-2-Py Me CH N CF3 C(O)NHCH2-2-Py
Me N CH Me C(O)NHCH2-2-Py Me CH N CF3 C(O)NHCH2-2-Py
Me N CH Me ltf-l,2,4-triazol-l-yl Me CH N CF3 l//-l,2,4-triazol-l-yl
Me N CH Me lff-l,2,4-triazol-l-yl Me CH N CF3 l//-l,2,4-triazol-l-yl
H N N Me C(O)NHEt H N CH CF3 C(O)NHEt
H N N Me C(O)NHEt H N CH CF3 C(O)NHEt
H N N Me C(O)NHCH2CF3 H N CH CF3 C(O)NHCH2CF3
H N N Me C(O)NHCH2CF3 H N CH CF3 C(O)NHCH2CF3
H N N Me C(O)NHCH2-2-Py H N CH CF3 C(O)NHCH2-2-Py
H N N Me C(O)NHCH2-2-Py H N CH CF3 C(O)NHCH2-2-Py
H N N Me lf/-l,2,4-triazol-l-yl H N CH CF3 l«-l,2,4-triazol-l-yl
H N N Me lH-l,2,4-triazol-l-yl H N CH CF3 l//-l,2,4-triazol-l-yl
Me N N Me C(O)NHEt Me N CH CF3 C(O)NHEt
Me N N Me C(O)NHEt Me N CH CF3 C(O)NHEt
Me N N Me C(O)NHCH2CF3 Me N CH CF3 C(O)NHCH2CF3
Me N N Me C(O)NHCH2CF3 Me N CH CF3 C(O)NHCH2CF3
Me N N Me C(O)NHCH2-2-Py Me N CH CF3 C(O)NHCH2-2-Py
Me N N Me C(O)NHCH2-2-Py Me N CH CF3 C(O)NHCH2-2-Py
Me N N Me l«-l,2,4-triazol-l-yl Me N CH CF3 ltf-l,2,4-triazol-l-yl
Me N N Me l«-l,2,4-triazol-l-yl Me N CH CF3 l//-l,2,4-triazol-l-yl
H CH N H C(O)NHEt H N N CF3 C(O)NHEt R3 A1 A3 R5 R3 A1 A3 R5
H CH N H C(O)NHEt H N N CF3 C(O)NHEt
H CH N H C(O)NHCH2CF3 H N N CF3 C(O)NHCH2CF3
H CH N H C(O)NHCH2CF3 H N N CF3 C(O)NHCH2CF3
H CH N H C(O)NHCH2-2-Py H N N CF3 C(O)NHCH2-2-Py
H CH N H C(O)NHCH2-2-Py H N N CF3 C(O)NHCH2-2-Py
H CH N H l//-l,2,4-triazol-l-yl H N N CF3 ltf-l,2,4-triazol-l-yl
H CH N H l//-l,2,4-triazol-l-yl H N N CF3 l/M,2,4-triazol-l-yl
Me CH N H C(O)NHEt Me N N CF3 C(O)NHEt
Me CH N H C(O)NHEt Me N N CF3 C(O)NHEt
Me CH N H C(O)NHCH2CF3 Me N N CF3 C(O)NHCH2CF3
Me CH N H C(O)NHCH2CF3 Me N N CF3 C(O)NHCH2CF3
Me CH N H C(O)NHCH2-2-Py Me N N CF3 C(O)NHCH2-2-Py
Me CH N H C(O)NHCH2-2-Py Me N N CF3 C(O)NHCH2-2-Py
Me CH N H lW-I,2,4-triazol-l-yl Me N N CF3 ltf-l,2,4-triazol-l-yl
Me CH N H l//-l,2,4-triazol-l-yl Me N N CF3 l//-l,2,4-triazol-l-yl
Formulation/Utility
Compounds of this invention can generally be used as an invertebrate pest control active ingredient in a composition, i.e. formulation, with a carrier suitable for agronomic or nonagronomic uses 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. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film- forming solutions or flowable suspensions are particularly useful for seed treatment. 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. An emulsifϊable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. Hugh-strength compositions are primarily used as intermediates for further formulation.
Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
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
Acti vein predi ent Diluent Surfactant
Water-Dispersible and Water-soluble 0.001-90 0-99.999 0-15 Granules, Tablets and Powders.
Oil Dispersions, Suspensions, 1-50 40-99 0-50 Emulsions, Solutions (including Emulsifiable Concentrates)
Dusts 1-25 70-99 0-5 Granules and Pellets 0.001-99 5-99.999 0-15
High Strength Compositions 90-99 0-10 0-2
Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.
Liquid diluents include, for example, water, Λ^iV-dimethylalkanamides (e.g., TvyV-dimethylformarnide), limonene, dimethyl sulfoxide, Λf-alkylpyrrolidones (e.g., JV-methylpyrrolidinone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobomyl acetate, other esters such as alkylated lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, π-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C(j— C22). such as plant seed and fruit oils (e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers 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.
The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as "surface-active agents") generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.
Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides. Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as Hgnosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as Λ^^V-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts.
Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as Λf-alkyl propanediamines, tripropylenetriamines and dipropylene- tetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquatemary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
Also useful for the present compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.
Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 μm range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). 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 T. S. Woods, 'The Formulator's Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food— Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also 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; Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.
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- D. 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 constructed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated.
Example A High Strength Concentrate
Compound 2 98.5% silica aerogel . 0.5% synthetic amorphous fine silica 1.0%
Example B
Wettable Powder
Compound 12 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%
Example C
Granule
Compound 16 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0%
U.S.S. No. 25-50 sieves)
Example D
Extruded Pellet
Compound 18 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0% Example E
Emulsifiable Concentrate
Compound 19 . 10.0% polyoxyethylene sorbitol hexoleate 20.0%
Cfc-Cio fatty acid methyl ester 70.0%
Example F
Microemulsion
Compound 2 5.0% polyvinylpyrrolidone-vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%
Example G
Seed Treatment
Compound 18 20.00% polyvinylpyrrolidone-vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%
Example H
Fertilizer Stick
Compound 19 2.5% pyrrolidone-styrene copolymer 4.8% tristyrylphenyl 16-ethoxylate 2.3% talc 0.8% corn starch 5.0%
Nitrophoska® Permanent 15-9-15 slow-release fertilizer 36.0%
(BASF) kaolin 38.0% water 10.6%
Compounds of this invention exhibit activity against a wide spectrum of invertebrate pests. These pests include invertebrates inhabiting a variety of environments such as, for example, plant foliage, roots, soil, harvested crops or other foodstuffs, building structures or animal integuments. These pests include, for example, invertebrates feeding on foliage (including leaves, stems, flowers and fruits), seeds, wood, textile fibers or animal blood or tissues, and thereby causing injury or damage to, for example, growing or stored agronomic crops, forests, greenhouse crops, ornamentals, nursery crops, stored foodstuffs or fiber products, or houses or other structures or their contents, or being harmful to animal health or public health. Those skilled in the art will appreciate that not all compounds are equally effective against all growth stages of all pests.
These present compounds and compositions are thus useful agronomically for protecting field crops from phytophagous invertebrate pests, and also nonagronomically for protecting other horticultural crops and plants from phytophagous invertebrate pests. This utility includes protecting crops and other plants (i.e. both agronomic and nonagronomic) that contain genetic material introduced by genetic engineering (i.e. transgenic) or modified by mutagenesis to provide advantageous traits. Examples of such traits include tolerance to herbicides, resistance to phytophagous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, plant-pathogenic fungi, bacteria and viruses), improved plant growth, increased tolerance of adverse growing conditions such as high or low temperatures, low or high soil moisture, and high salinity, increased flowering or fruiting, greater harvest yields, more rapid maturation, higher quality and/or nutritional value of the harvested product, or improved storage or process properties of the harvested products. Transgenic plants can be modified to express multiple traits. Examples of plants containing traits provided by genetic engineering or mutagenesis include varieties of com, cotton, soybean and potato expressing an insecticidal Bacillus thuringiensis toxin such as YIELD GARD®, KNOCKOUT®, STARLINK®, BOLLGARD®, NuCOTN® and NEWLEAF®, and herbicide-tolerant varieties of corn, cotton, soybean and rapeseed such as ROUNDUP READY®, LIBERTY LINK®, Evil®, STS® and CLEARFIELD®, as well as crops expressing JV-acetyltransferase (GAT) to provide resistance to glyphosate herbicide, or crops containing the HRA gene providing resistance to herbicides inhibiting acetolactate synthase (ALS). The present compounds and compositions may interact synergistically with traits introduced by genetic engineering or modified by mutagenesis, thus enhancing phenotypic expression or effectiveness of the traits or increasing the invertebrate pest control effectiveness of the present compounds and compositions. In particular, the present compounds and compositions may interact synergistically with the phenotypic expression of proteins or other natural products toxic to invertebrate pests to provide greater-than-additive control of these pests.
Compositions of this invention can also optionally comprise plant nutrients, e.g., a fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum. Of note are compositions comprising at least one fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium and magnesium. Compositions of the present invention which further comprise at least one plant nutrient can be in the form of liquids or solids. Of note are solid formulations in the form of granules, small sticks or tablets. Solid formulations comprising a fertilizer composition can be prepared by mixing the compound or composition of the present invention with the fertilizer composition together with formulating ingredients and then preparing the formulation by methods such as granulation or extrusion. Alternatively solid formulations can be prepared by spraying a solution or suspension of a compound or composition of the present invention in a volatile solvent onto a previous prepared fertilizer composition in the form of dimensionally stable mixtures, e.g., granules, small sticks or tablets, and then evaporating the solvent. Nonagronomic uses refer to invertebrate pest control in the areas other than fields of crop plants. Nonagronomic uses of the present compounds and compositions include control of invertebrate pests in stored grains, beans and other foodstuffs, and in textiles such as clothing and carpets. Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in ornamental plants, forests, in yards, along roadsides and railroad rights of way, and on turf such as lawns, golf courses and pastures. Nonagronomic uses of the present compounds and compositions also include invertebrate pest control in houses and other buildings which may be occupied by humans and/or companion, farm, ranch, zoo or other animals. Nonagronomic uses of the present compounds and compositions also include the control of pests such as termites that can damage wood or other structural materials used in buildings.
Nonagronomic uses of the present compounds and compositions also include protecting human and animal health by controlling invertebrate pests that are parasitic or transmit infectious diseases. The controlling of animal parasites includes controlling external parasites that are parasitic to the surface of the body of the host animal (e.g., shoulders, armpits, abdomen, inner part of the thighs) and internal parasites that are parasitic to the inside of the body of the host animal (e.g., stomach, intestine, lung, veins, under the skin, lymphatic tissue). External parasitic or disease transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites and fleas. Internal parasites include heartworms, hookworms and helminths. Compounds and compositions of the present invention are suitable for systemic and/or non-systemic control of infestation or infection by parasites on animals. Compounds and compositions of the present invention are particularly suitable for combating external parasitic or .disease transmitting pests. Compounds and compositions of the present invention are suitable for combating parasites that infest agricultural working animals, such as cattle, sheep, goats, horses, pigs, donkeys, camels, buffalos, rabbits, hens, turkeys, ducks, geese and bees; pet animals and domestic animals such as dogs, cats, pet birds and aquarium fish; as well as so-called experimental animals, such as hamsters, guinea pigs, rats and mice. By combating these parasites, fatalities and performance reduction (in terms of meat, milk, wool, skins, eggs, honey, etc.) are reduced, so that applying a composition comprising a compound of the present invention allows more economic and simple husbandry of animals.
Examples of agronomic or nonagronomic invertebrate pests include eggs, larvae and adults of the order Lepidoptera, such as armyworms, cutworms, loopers, and heliothines in the family Noctuidae (e.g., pink stem borer (Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm {Spodoptera fugiperda J. E. Smith), beet armyworm {Spodoptera exigua Hϋbner), cotton leafworm (Spodoptera littoralis Boisduval), yellowstriped armyworm (Spodoptera ornithogalli Guenee), black cutworm (Agrotis ipsilon Hufnagel), velvetbean caterpillar (Anticarsia gemmatalis Hϋbner), green fruitworm (Lithophane antennata Walker), cabbage armyworm (Barathra brassicae Linnaeus), soybean looper (Pseudoplusia includens Walker), cabbage looper (Trichoplusia ni Hϋbner), tobacco budworm (Heliothis virescens Fabricius)); borers, casebearers, webworms, coneworms, cabbageworms and skeletonizers from the family Pyralidae (e.g., European corn borer (Ostrinia nubilalis Hϋbner), navel orangeworm (Amyelois transitella Walker), corn root webworm (Crambus caliginosellus Clemens), sod webworms (Pyralidae: Crambinae) such as sod worm (Herpetogramma licarsisalis Walker), sugarcane stem borer (Chϊlo infuscatellus Snellen), tomato small borer (Neoleucinodes elegantalis Guenee), green leafroller (Cnaphalocerus medinalis), grape leaffolder (Desmia funeralis Hϋbner), melon worm (Diaphania nitidalis Stoll), cabbage center grub (Helluala hydralis Guenee), yellow stem borer (Scirpophaga incertulas Walker), early shoot borer (Scirpophaga infuscatellus Snellen), white stem borer (Scirpophaga innotata Walker), top shoot borer (Scirpophaga nivella Fabricius), dark- headed rice borer (Chilo polychrysus Meyrick), cabbage cluster caterpillar (Crocidolomia binotalis English)); leafrollers, budworms, seed worms, and fruit worms in the family Tortricidae (e.g., codling moth (Cydia pomonella Linnaeus), grape berry moth (Endopiza viteana Clemens), oriental fruit moth (Grapholita molesta Busck), citrus false codling moth (Cryptophlebia leucotreta Meyrick), citrus borer (Ecdytolopha aurantiana Lima), redbanded leafroller (Argyrotaenia velutinana Walker), obliquebanded leafroller (Choristoneura rosaceana Harris), light brown apple moth (Epiphyas postvittana Walker), European grape berry moth (Eupoecilia ambiguella Hϋbner), apple bud moth (Pandemis pyrusana Kearfott), omnivorous leafroller (Platynota stultana Walsingham), barred fruit-tree tortrix (Pandemis cerasana Hϋbner), apple brown tortrix (Pandemis heparana Denis & Schiffermϋller)); and many other economically important lepidoptera (e.g., diamondback moth (Plutella xylostella Linnaeus), pink bollworm (Pectinophora gossypiella Saunders), gypsy moth (Lymantria dispar Linnaeus), peach fruit borer (Carposina niponensis Walsingham), peach twig borer (Anarsia lineatella Zeller), potato tuberworm (Phthorimaea operculella Zeller), spotted teniform leafminer (Lithocolletis blancardella Fabricius), Asiatic apple leafminer (Lithocolletis ringoniella Matsumura), rice leaffolder (Lerodea eufala Edwards), apple leafminer (Leucoptera scitella Zeller)); eggs, nymphs and adults of the order Blattodea including cockroaches from the families Blattellidae and Blattidae (e.g., oriental cockroach (Blatta oήentalis Linnaeus), Asian cockroach (βlatella asahinai Mizukubo), German cockroach {Blattella germanica Linnaeus), brownbanded cockroach {Supella longipalpa Fabricius), American cockroach {Periplaneta americana Linnaeus), brown cockroach {Periplaneta brunnea Burmeister), Madeira cockroach {Leucophaea maderae Fabricius)), smoky brown cockroach {Periplaneta fuliginosa Service), Australian Cockroach {Periplaneta australasiae Fabr.), lobster cockroach {Nauphoeta cinerea Olivier) and smooth cockroach (Symploce pallens Stephens)); eggs, foliar feeding, fruit feeding, root feeding, seed feeding and vesicular tissue feeding larvae and adults of the order Coleoptera including weevils from the families Anthribidae, Bruchidae, and Curculionidae (e.g., boll weevil {Anthonomus grandis Boheman), rice water weevil {Lissorhoptrus oryzophilus Kuschel), granary weevil {Sitophilus granarius Linnaeus), rice weevil {Sitophilus oryzae Linnaeus)), annual bluegrass weevil {Listronotus maculicollis Dietz), bluegrass billbug {Sphenophorus parvulus Gyllenhal), hunting billbug {Sphenophorus venatus vestitus), Denver billbug {Sphenophorus cicatristriatus Fahraeus)); flea beetles, cucumber beetles, rootworms, leaf beetles, potato beetles, and leafminers in the family Chrysomelidae (e.g., Colorado potato beetle (Leptinotarsa decemlineata Say), western corn rootworm {Diabrotica virgifera virgifera LeConte)); chafers and other beetles from the family Scarabaeidae (e.g., Japanese beetle (Popillia japonica Newman), oriental beetle {Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), northern masked chafer {Cyclocephala borealis Arrow), southern masked chafer {Cyclocephala immaculata Olivier or C. lurida Bland), dung beetle and white grub (Aphodius spp.), black turfgrass ataenius {Ataenius spretulus Haldeman), green June beetle {Cotinis nitida Linnaeus), Asiatic garden beetle {Maladera castanea Arrow), May/June beetles {Phyllophaga spp.) and European chafer (Rhizotrogus majalis Razoumowsky)); carpet beetles from the family Dermestidae; wireworms from the family Elateridae; bark beetles from the family Scolytidae and flour beetles from the family Tenebrionidae. In addition, agronomic and nonagronomic pests include: eggs, adults and larvae of the order Dermaptera including earwigs from the family Forficulidae (e.g., European earwig {Forfϊcula auricularia Linnaeus), black earwig {Chelisoches morio Fabricius)); eggs, immatures, adults and nymphs of the orders Hemiptera and Homoptera such as, plant bugs from the family Miridae, cicadas from the family Cicadidae, leafhoppers (e.g. Empoasca spp.) from the family Cicadellidae, bed bugs (e.g., Cimex lectularius Linnaeus) from the family Cimicidae, planthoppers from the families Fulgoroidae and Delphacidae, treehoppers from the family Membracidae, psyllids from the family Psyllidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, phylloxera from the family Phylloxeridae, mealybugs from the family Pseudococcidae, scales from the families Coccidae, Diaspididae and Margarodidae, lace bugs from the family Tingidae, stink bugs from the family Pentatomidae, chinch bugs (e.g., hairy chinch bug (Blissus leucopterus hirtus Montandon) and southern chinch bug (Blissus insularis Barber)) and other seed bugs from the family Lygaeidae, spittlebugs from the family Cercopidae squash bugs from the family Coreidae, and red bugs and cotton stainers from the family Pyrrhocoridae. Also included are eggs, larvae, nymphs and adults of the order Acari (mites) such as spider mites and red mites in the family Tetranychidae (e.g., European red mite (Panonychus ulmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite (JTetranychus mcdanieli McGregor)); flat mites in the family Tenuipalpidae (e.g., citrus flat mite (Brevipalpus lewisi McGregor)); rust and bud mites in the family Eriophyidae and other foliar feeding mites and mites important in human and animal health, i.e. dust mites in the family Epidermoptidae, follicle mites in the family Demodicidae, grain mites in the family Glycyphagidae, ticks in the family Ixodidae, commonly known as hard ticks (e.g., deer tick (Ixodes scapularis Say), Australian paralysis tick (Ixodes holocyclus Neumann), American dog tick (Dermacentor variabilis Say), lone star tick (Amblyomma americanum Linnaeus)) and ticks in the family Argasidae, commonly known as soft ticks (e.g., relapsing fever tick (Ornithodoros turicatά), common fowl tick (Argas radiatus)); scab and itch mites in the families Psoroptidae, Pyemotidae, and Sarcoptidae; eggs, adults and immatures of the order Orthoptera including grasshoppers, locusts and crickets (e.g., migratory grasshoppers (e.g., Melanoplus sanguinipes Fabricius, M. differentialis Thomas), American grasshoppers (e.g., Schistocerca americana Drury), desert locust (Schistocerca gregaria Forskal), migratory locust (Locusta migratoria Linnaeus), bush locust (Zonocerus spp.), house cricket (Acheta domesticus Linnaeus), mole crickets (e.g., tawny mole cricket (Scapteriscus vicinus Scudder) and southern mole cricket (Scapteriscus borellii Giglio-Tos)); eggs, adults and immatures of the order Diptera including leafminers (e.g., Liriomyza spp. such as serpentine vegetable leafminer (Liriomyza sativae Blanchard)), midges, fruit flies (Tephritidae), frit flies (e.g., Oscinella frit Linnaeus), soil maggots, house flies (e.g., Musca domestica Linnaeus), lesser house flies (e.g., Fannia canicularis Linnaeus, F. femoralis Stein), stable flies (e.g., Stomoxys calcitrans Linnaeus), face flies, horn flies, blow flies (e.g., Chrysomya spp., Phormia spp.), and other muscoid fly pests, horse flies (e.g., Tabanus spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.), cattle grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.), keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), black flies (e.g., Prosimulium spp., Simulium spp.), biting midges, sand flies, sciarids, and other Nematocera; eggs, adults and immatures of the order Thysanoptera including onion thrips (Thrips tabaci Lindeman), flower thrips (Frankliniella spp.), and other foliar feeding thrips; insect pests of the order Hymenoptera including ants of the Family Formicidae including the Florida carpenter ant (Camponotus floήdanus Buckley), red carpenter ant (Camponotus ferrugineus Fabricius), black carpenter ant (Camponotus pennsylvanicus De Geer), white-footed ant (Technomyrmex albipes fr. Smith), big headed ants (Pheidole sp.), ghost ant (Tapinoma melanocephalum Fabricius); Pharaoh ant (Monomorium pharaonis Linnaeus), little fire ant (Wasmannia auropunctata Roger), fire ant (Solenopsis geminata Fabricius), red imported fire ant (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), crazy ant (Paratrechina longicornis Latreille), pavement ant (Tetramorium caespitum Linnaeus), cornfield ant (Lasius alienus Fόrster) and odorous house ant (Tapinoma sessile Say). Other Hymenoptera including bees (including carpenter bees), hornets, yellow jackets, wasps, and sawflies (Neodiprion spp.; Cephus spp.); insect pests of the order Isoptera including termites in the Termitidae (e.g., Macrotermes sp., Odontotermes obesus Rambur), Kalotermitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g., Reticulitermes sp., Coptotermes sp., Heterotermes tenuis Hagen) families, the eastern subterranean termite (Reticulitermes flavipes Kollar), western subterranean termite (Reticulitermes hesperus Banks), Formosan subterranean termite (Coptotermes formosanus Shiraki), West Indian drywood termite (lncisitermes immigrans Snyder), powder post termite (Cryptotermes brevis Walker), drywood termite (lncisitermes snyderi Light), southeastern subterranean termite (Reticulitermes virginicus Banks), western drywood termite (lncisitermes minor Hagen), arboreal termites such as Nasutitermes sp. and other termites of economic importance; insect pests of the order Thysanura such as silverfish (Lepisma saccharina Linnaeus) and firebrat (Thermobia domestica Packard); insect pests of the order Mallophaga and including the head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus Linnaeus), chicken body louse (Menacanthus stramineus Nitszch), dog biting louse (Trichodectes canis De Geer), fluff louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), short-nosed cattle louse (Haematopinus eurysternus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus) and other sucking and chewing parasitic lice that attack man and animals; insect pests of the order Siphonoptera including the oriental rat flea (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), dog flea (Ctenocephalides canis Curtis), hen flea (Ceratophyllus gallinae Schrank), sticktight flea (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus) and other fleas afflicting mammals and birds. Additional arthropod pests covered include: spiders in the order Araneae such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus). Compounds of the present invention also have activity on members of the Classes Nematoda, Cestoda, Trematoda, and Acanthocephala including economically important members of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida such as but not limited to economically important agricultural pests (i.e. root knot nematodes in the genus Meloidogyne, lesion nematodes in the genus Pratylenchus, stubby root nematodes in the genus Trichodorus, etc.) and animal and human health pests (i.e. all economically important flukes, tapeworms, and roundworms, such as Strongylus vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofilaria immitis Leidy in dogs, Anoplocephala perfoliate/, in horses, Fasciola hepatica Linnaeus in ruminants, etc.).
Compounds of the invention show particularly high activity against pests in the order Lepidoptera (e.g., Alabama argillacea Hiibner (cotton leaf worm), Archips argyrospila Walker (fruit tree leaf roller), A. rosana Linnaeus (European leaf roller) and other Archips species, Chilo suppressalis Walker (rice stem borer), Cnaphalocrosis medinalis Guenee (rice leaf roller), Crambus caliginosellus Clemens (corn root webworm), Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm), Earias vittella Fabricius (spotted bollworm), Helicoverpa armigera Hiibner (American bollworm), Helicoverpa zea Boddie (corn earworm), Heliothis virescens Fabricius (tobacco budworm), Herpetogramma licarsisalis Walker (sod webworm), Lobesia botrana Denis & Schiffermϋller (grape berry moth), Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus (small white butterfly), Plutella xylostella Linnaeus (diamondback moth), Spodoptera exigua Hiibner (beet armyworm), Spodoptera litura Fabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperda J. E. Smith (fall armyworm), Trichoplusia ni Hϋbner (cabbage looper) and Tuta absoluta Meyrick (tomato leafminer)). Compounds of the invention also have significant activity on members from the order
Homoptera including: Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae Scopoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (rosy apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus pruni Geoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach (turnip aphid), Metopolophium dirrhodwn Walker (cereal aphid), Macrosiphum euphorbiae Thomas (potato aphid), Myzus persicae Sulzer (peach-potato aphid, green peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (bird cherry-oat aphid), Schizaphis graminum Rondani (greenbug), Sitobion avenae Fabricius (English grain aphid), Therioaphis maculata Buckton (spotted alfalfa aphid), Toxoptera aurantii Boyer de Fonscolombe (black citrus aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (adelgids); Phylloxera devastatrix Pergande (pecan phylloxera); Bemisia tabaci Gennadius (tobacco whitefly, sweetpotato whitefly), Bemisia argentifolii Bellows & Perring (silverleaf whitefly), Dialeurodes citri Ashmead (citrus whitefly) and Trialeurodes vaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris (potato leafhopper), Laodelphax striatellus Fallen (smaller brown planthopper), Macrolestes quadrilineatus Forbes (aster leafhopper), Nephotettix cinticeps Uhler (green leafhopper), Nephotettix nigropictus Stal (rice leafhopper), Nilaparvata lugens Stal (brown planthopper), Peregrinus maidis Ashmead (corn planthopper), Sogatella furcifera Horvath (white-backed planthopper), Sogatodes orizicola Muir (rice delphacid), Typhlocyba pomaria McAtee white apple leafhopper, Erythroneoura spp. (grape leafhoppers); Magicidada septendecim Linnaeus (periodical cicada); Icerya purchasi Maskell (cottony cushion scale), Quadraspidiotus perniciosus Comstock (San Jose scale); Planococcus citri Risso (citrus mealybug); Pseudococcus spp. (other mealybug complex); Cacopsylla pyricola Foerster (pear psylla), Trioza diospyri Ashmead (persimmon psylla).
Compounds of this invention also have activity on members from the order Hemiptera including: Acrosternum hilare Say (green stink bug), Anasa tristis De Geer (squash bug), Blissus leucopterus leucopterus Say (chinch bug), Cimex lectularius Linnaeus (bed bug) Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus Herrich-Schaffer (cotton stainer), Euchistus servus Say (brown stink bug), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug), Graptosthetus spp. (complex of seed bugs), Leptoglossus corculus Say (leaf-footed pine seed bug), Lygus lineolaris Palisot de Beauvois (tarnished plant bug), Nezara viridula Linnaeus (southern green stink bug), Oebalus pugnax Fabricius (rice stink bug), Oncopeltus fasciatus Dallas (large milkweed bug), Pseudatomoscelis seriatus Reuter (cotton fleahopper). Other insect orders controlled by compounds of the invention include Thysanoptera (e.g., Frankliniella occidentalis Pergande (western flower thrips), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips), and Thrips tabaci Lindeman (onion thrips); and the order Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican bean beetle) and wireworms of the genera Agriotes, Athous or Limonius).
Note that some contemporary classification systems place Homoptera as a suborder within the order Hemiptera.
Of note is use of compounds of this invention for controlling diamondback moth (Plutella xylostella). Of note is use of compounds of this invention for controlling fall armyworm (Spodoptera frugiperdά). Of note is use of compounds of this invention for controlling western flower thrip (Frankliniella occidentalis). Of note is use of compounds of this invention for controlling potato leafhopper (Empoasca fabae). Of note is use of compounds of this invention for controlling cotton melon aphid (Aphis gossypii). Of note is use of compounds of this invention for controlling green peach aphid (Myzus persicae).
Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including insecticides, fungicides, nematocides, bactericides, acaricides, herbicides, growth regulators such as rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agronomic and nonagronomic utility. Thus the present invention also pertains to a composition comprising a biologically effective amount of a compound of Formula 1, an iV-oxide or salt thereof, and an effective amount of at least one additional biologically active compound or agent and can further comprise at least one of surfactants, solid diluents or liquid diluents. For mixtures of the present invention, the other biologically active compounds or agents can be formulated together with the present compounds, including the compounds of Formula 1, to form a premix, or the other biologically active compounds or agents can be formulated separately from the present compounds, including the compounds of Formula 1, and the two formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
Other biologically active compounds or agents useful in the compositions of the present invention can be selected from invertebrate pest control agents having a different mode of action or a different chemical class including macrocyclic lactones, neonicotinoids, octopamine receptor ligands, ryanodine receptor ligands, ecdysone agonists, sodium channel modulators, chitin synthesis inhibitors, nereisotoxin analogs, mitochondrial electron transport inhibitors, cholinesterase inhibitors, cyclodiene insecticides, molting inhibitors, GABA (γ-aminobutyric acid)-regulated chloride channel blockers, juvenile hormone mimics, lipid biosynthesis inhibitors and biological agents including nucleopolyhedro viruses (NPV), members of Bacillus thuringiensis, encapsulated delta-endotoxins of Bacillus thuringiensis, and other naturally occurring or genetically modified insecticidal viruses.
Of note are additional biologically active compounds or agents selected from insecticides of the group consisting of pyrethroids, carbamates, neonicotinoids, neuronal sodium channel blockers, insecticidal macrocyclic lactones, γ-aminobutyric acid antagonists, insecticidal ureas and juvenile hormone mimics, a member of Bacillus thuringiensis, a Bacillus thuringiensis delta-endotoxin, and a naturally occurring or a genetically modified viral insecticide.
Examples of such biologically active compounds or agents with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, acetamiprid, acetoprole, amidoflumet (S- 1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chlorfenapyr, chlorfluazuron, chlorantraniliprole (DPX-E2Y45), chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, fonophos, halofenozide, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide, monocrotophos, nitenpyram, nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen (BSN 2060), spirotetramat, sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon and triflumuron; fungicides such as acibenzolar, aldimorph, amisulbrøm, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, binomial, biphenyl, bitertanol, blasticidin-S, Bordeaux mixture (Tribasic copper sulfate), boscalid/nicobifen, bromuconazole, bupirimate, buthiobate, carboxin, caφropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper oxychloride, copper salts such as copper sulfate and copper hydroxide, cyazofamid, cyflunamid, cymoxaπil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, discostrobin, dithianon, dodemorph, dodine, econazole, etaconazole, edifenphos, epoxiconazole, ethaboxam, ethirimol, ethridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fencaramid, fenfuram, fenhexamide, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferfurazoate, ferimzone, fluazinam, fludioxonil, flumetover, fluopicolide, fluoxastrobin, fluquinconazole, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminum, fuberidazole, furalaxyl, furametapyr, hexaconazole, hymexazole, guazatine, imazalil, imibenconazole, iminoctadine, iodicarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoconazole, isoprothiolane, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mapanipyrin, mefenoxam, mepronil, metalaxyl, metconazole, methasulfocarb, metiram, metominostrobin/fenominostrobin, mepanipyrim, metrafenone, miconazole, myclobutanil, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, paclobutrazol, penconazole, pencycuron, penthiopyrad, perfurazoate, phosphonic acid, phthalide, picobenzamid, picoxystrobin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pryazophos, pyrifenox, pyrimethanil, pyrifenox, pyrolnitrine, pyroquilon, quinconazole, quinoxyfen, quintozene, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, techrazene, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolyfluanid, triadimefon, triadimenol, triarimol, triazoxide, tridemoφh, trimoprhamide tricyclazole, trifloxystrobin, triforine, triticonazole, uniconazole, validamycin, vinclozolin, zineb, ziram, and zoxamide; nβmatocides such as aldicarb, imicyafos, oxamyl 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 including entomopathogenic bacteria, such as Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic virus including baculovirus, nucleopolyhedro virus (NPV) such as Helicoverpa zea nucleopolyhedro virus (HzNPV), Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus (GV) such as Cydia pomonella granulosis virus (CpGV).
Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). The effect of the exogenously applied invertebrate pest control compounds of this invention may be synergistic with the expressed toxin proteins.
General references for these agricultural protectants (i.e. insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop Protection Council, Famham, Surrey, U.K., 2001.
Of note is a composition of the present invention wherein at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole, chlorpyrifos, chlorpyrifos- methyl, chlorobenzilate, chromafenozide, clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim, flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquiπazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen, spirotetramat, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, nucleopolyhedro viruses, an encapsulated delta-endotoxins of Bacillus thuringiensis, baculoviruses, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.
Of particular note is a composition of the present invention wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acephate, acetamiprid, acetoprole, amidoflumet (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chlorfenapyr, chlorfluazuron, chloφyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda- cyhalothrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, halofenozide, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, protrifenbute, pymetrozine, pyrethrin, pyridalyl, pyriproxyfen, rotenone, ryanodine, S 1812 (Valent), spinosad, spiridiclofen, spiromesifen (BSN 2060), sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, aldicarb, fenamiphos, amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpyroximate, hexythiazox, propargite, pyridaben, tebufenpyrad, Bacillus thuringiensis aizawai, Bacillus thuringiensis kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, entomopathogenic virus and entomopathogenic fungi. Also of note is a composition of the present invention wherein at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acetamiprid, amitraz, avermectin, azadirachtin, bifenthrin, buprofezin, cartap, chlorantraniliprole, chlorfenapyr, chloφyrifos, clothianidin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, flubendiamide, flufenoxuron, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, metaflumizone, methomyl, methoprene, methoxyfenozide, nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, tebufenozide, thiacloprid, thiamethoxam, thiodicarb, thiosultap- sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, nucleopolyhedro viruses and an encapsulated delta- endotoxins of Bacillus thuringiensis.
Of further note is a composition of the present invention wherein the at least one additional biologically active compound or agent is selected from the group consisting of cypermethrin, cyhalothrin, cyfluthrin and beta-cyfluthrin, esfenvalerate, fenvalerate, tralomethrin, fenothiocarb, methomyl, oxamyl, thiodicarb, acetamiprid, clothianidin, imidacloprid, thiamethoxam, thiacloprid, indoxacarb, spinosad, abamectin, avermectin, emamectin, endosulfan, ethiprole, fipronil, flufenoxuron, triflumuron, diofenolan, pyriproxyfen, pymetrozine, amitraz, Bacillus thuringiensis aizawai, Bacillus thuringiensis kurstaki, Bacillus thuringiensis delta endotoxin and entomophagous fungi.
For embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound of Formula 1 is typically between about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300 and about 300:1 (for example ratios between about 1:30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components may expand the spectrum of invertebrate pests controlled beyond the spectrum controlled by the compound of Formula 1 alone.
In certain instances, combinations of a compound of this invention with other biologically active (particularly invertebrate pest control) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of invertebrate pest control active ingredients occurs at application rates giving agronomically satisfactory levels of invertebrate pest control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
Of note is a combination of a compound of Formula 1 with at least one other invertebrate pest control active ingredient. Of particular note is such a combination where the other invertebrate pest control active ingredient has a different site of action from the compound of Formula 1. In certain instances, a combination with at least one other invertebrate pest control active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise a biologically effective amount of at least one additional invertebrate pest control active ingredient having a similar spectrum of control but a different site of action. Contacting a plant genetically modified to express an invertebrate pest compound (e.g., protein) or the locus of the plant with a biologically effective amount of a compound of this invention can also provide a broader spectrum of plant protection and be advantageous for resistance management. Table A lists specific combinations of a compound of Formula 1 with other invertebrate pest control agents illustrative of the mixtures, compositions and methods of the present invention. The first column of Table A lists the specific invertebrate pest control agents (e.g., "Abamectin" in the first line). The second column of Table A lists the mode of action (if known) or chemical class of the invertebrate pest control agents. The third column of Table A lists embodiment(s) of ranges of weight ratios for rates at which the invertebrate pest control agent can be applied relative to a compound of Formula 1, an N-oxide, or a salt thereof, (e.g., "50:1 to 1:50" of abamectin relative to a compound of Formula 1 by weight). Thus, for example, the first line of Table A specifically discloses the combination of a compound of Formula 1 with abamectin can be applied in a weight ratio between 50:1 to 1 :50. The remaining lines of Table A are to be construed similarly. Of further note Table A lists specific combinations of a compound of Formula 1 with other invertebrate pest control agents illustrative of the mixtures, compositions and methods of the present invention and includes additional embodiments of weight ratio ranges for application rates.
Table A
Figure imgf000083_0001
Figure imgf000084_0001
Figure imgf000085_0001
One embodiment of invertebrate pest control agents (e.g., insecticides and acaricides) for mixing with compounds of this invention include sodium channel modulators such as bifenthrin* cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones such as spinetoram, spinosad, abamectin, avermectin and emamectin; GABA ( γ-aminobutyric acid)-regulated chloride channel blockers such as endosulfan, ethiprole and fipronil; chitin synthesis inhibitors such as buprofezin, cyromazine, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron; juvenile hormone mimics such as diofenolan, fenoxycarb, methoprene and pyriproxyfen; octopamine receptor ligands such as amitraz; ecdysone agonists such as azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptor ligands such as ryanodine, anthranilic diamides such as chlorantraniliprole (see U.S. Patent 6,747,047, PCT Publications WO 2003/015518 and WO 2004/067528) and flubendiamide (see U.S. Patent 6,603,044); nereistoxin analogs such as cartap; mitochondrial electron transport inhibitors such as chlorfenapyr, hydramethylnon and pyridaben; lipid biosynthesis inhibitors such as spirodiclofen and spiromesifen; cyclodiene insecticides such as dieldrin; cyflumetofen; fenothiocarb; flonicamid; metaflumizone; pyrafluprole; pyridalyl; pyriprole; pymetrozine; spirotetramat; and thiosultap-sodium. One embodiment of biological agents for mixing with compounds of this invention include nucleopolyhedro virus such as HzNPV and AfNPV; Bacillus thuringiensis and encapsulated delta-endotoxins of Bacillus thuringiensis such as Cellcap, MPV and MPVII; as well as naturally occurring and genetically modified viral insecticides including members of the family Baculoviridae as well as entomophagous fungi. Of note is the composition of the present invention wherein the at least one additional biologically active compound or agent is selected from the Invertebrate Pest Control Agents listed in Table A above.
The weight ratios of a compound, including a compound of Formula 1, an TV-oxide or a salt thereof, to the additional invertebrate pest control agent typically are between 1000:1 and 1:1000, with one embodiment being between 500:1 and 1:500, another embodiment being between 250:1 and 1:200 and another embodiment being between 100:1 and 1:50.
Listed below in Table B are embodiments of specific compositions comprising a compound of Formula 1 (compound numbers refer to compounds in Index Tables A-C) and an additional invertebrate pest control agent.
Table B
Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
A-I 2 and Abamectin B-I 12 and Abamectin
A-2 2 and Acetamiprid B-2 12 and Acetamiprid
A-3 2 and Amitraz B-3 12 and Amitraz
A-4 2 and Avermectin B-4 12 and Avermectin
A-5 2 and Azadirachtin B-5 12 and Azadirachtin
A-6 2 and Beta-cyfluthrin B-6 12 and Beta-cyfluthrin
A-7 2 and Bifeπthrin B-7 12 and Bifenthrin
A-8 2 and Buprofezin B-8 12 and Buprofezin
A-9 2 and Cartap B-9 12 and Cartap
A-10 2 and Chlorantraniliprole B-10 12 and Chlorantraniliprole Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
A-I l 2 and Chlorfenapyr B-I l 12 and Chlorfenapyr
A-12 2 and Chlorpyrifos B-12 12 and Chlorpyrifos
A l 3 2 and Clothianidin B-13 12 and Clothianidin
A-14 2 and Cyfluthrin B-14 12 and Cyfluthrin
A-15 2 and Cyhalothrin B-15 12 and Cyhalothrin
A-16 2 and Cypermethrin B-16 12 and Cypermethrin
A-17 2 and Cyromazine B-17 12 and Cyromazine
A-18 2 and Deltamethrin B-18 12 and Deltamethrin
A-19 2 and Dieldrin B-19 12 and Dieldrin
A-20 2 and Dinotefuran B-20 12 and Dinotefuran
A-21 2 and Diofenolan B-21 12 and Diofenolan
A-22 2 and Emamectin B-22 12 and Emamectin
A-23 2 and Endosulfan B-23 12 and Endosulfan
A-24 2 and Esfenvalerate B-24 12 and Esfenvalerate
A-25 2 and Ethiprole B-25 12 and Ethiprole
A-26 2 and Fenothiocarb B-26 12 and Fenothiocarb
A-27 2 and Fenoxycarb B-27 12 and Fenoxycarb
A-28 2 and Fenvalerate B-28 12 and Fenvalerate
A-29 2 and Fipronil B-29 12 and Fipronil
A-30 2 and Flonicamid B-30 12 and Flonicamid
A-31 2 and Flubendiamide B-31 12 and Flubendiamide
A-32 2 and Flufenoxuron B-32 12 and Flufenoxuron
A-33 2 and Hexaflumuron B-33 12 and Hexaflumuron
A-34 2 and Hydramethylnon B-34 12 and Hydramethylnon
A-35 2 and Imidacloprid B-35 12 and Imidacloprid
A-36 2 and Indoxacarb B-36 12 and Indoxacarb
A-37 2 and Lambda-cyhalothrin B-37 12 and Lambda-cyhalothrin
A-38 2 and Lufenuron B-38 12 and Lufenuron
A-39 2 and Metaflumizone B-39 12 and Metaflumizone
A-40 2 and Methomyl B-40 12 and Methomyl
A-41 2 and Methoprene B-41 12 and Methoprene
A-42 2 and Methoxyfenozide B-42 12 and Methoxyfenozide
A-43 2 and Nitenpyram B-43 12 and Nitenpyram
A-44 2 and Nithiazine B-44 12 and Nithiazine
A-45 2 and Novaluron B-45 12 and Novaluron
A-46 2 and Oxamyl B-46 12 and Oxamyl Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
A-47 2 and Pymetrozine B-47 12 and Pymetrozine
A-48 2 and Pyrethrin B-48 12 and Pyrethrin
A-49 2 and Pyridaben B-49 12 and Pyridaben
A-50 2 and Pyridalyl B-50 12 and Pyridalyl
A-51 2 and Pyriproxyfen B-51 12 and Pyriproxyfen
A-52 2 and Ryanodine B-52 12 and Ryanodine
A-53 2 and Spinetoram B-53 12 and Spinetoram
A-54 2 and Spinosad B-54 12 and Spinosad
A-55 2 and Spirodiclofen B-55 12 and Spirodiclofen
A-56 2 and Spiromesifen B-56 12 and Spiromesifen
A-57 2 and Tebufenozide B-57 12 and Tebufenozide
A-58 2 and Thiacloprid B-58 12 and Thiacloprid
A-59 2 and Thiamethoxam B-59 12 and Thiamethoxam
A-60 2 and Thiodicarb B-60 12 and Thiodicarb
A-61 2 and Thiosultap-sodium B-61 12 and Thiosultap-sodium
A-62 2 and Tralomethrin B-62 12 and Tralomethrin
A-63 2 and Triazamate B-63 12 and Triazamate
A-64 2 and Triflumuron B-64 12 and Triflumuron
A-65 2 and Bacillus thuringiensis B-65 12 and Bacillus thuringiensis
A-66 2 and Bacillus thuringiensis B-66 12 and Bacillus thuringiensis del ta-endo toxin delta-endotoxin
A-67 9 and NPV (e.g., Gemstar) B-67 12 and NPV (e.g., Gemstar)
C-I 18 and Abamectin D-I 19 and Abamectin
C-2 18 and Acetamiprid D-2 19 and Acetamiprid
C-3 18 and Amitraz D-3 19 and Amitraz
C-4 18 and Avermectin D-4 19 and Avermectin
C-5 18 and Azadirachtin D-5 19 and Azadirachtin
C-6 18 and Beta-cyfluthrin D-6 19 and Beta-cyfluthrin
C-7 18 and Bifenthrin D-7 19 and Bifenthrin
C-8 18 and Buprofezin D-8 19 and Buprofezin
C-9 18 and Cartap D-9 19 and Cartap
C-IO 18 and Chlorantraniliprole D lO 19 and Chlorantraniliprole
C-I l 18 and Chlorfenapyr D-I l 19 and Chlorfenapyr
C-12 18 and Chlorpyπfos D-12 19 and Chlorpyrifos
C-13 18 and Clothianidin D-13 19 and Clothianidin
C- 14 18 and Cyfluthπn D- 14 19 and Cyfluthrin Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
C-15 18 and Cyhalothrin D- 15 19 and Cyhalothrin
C-16 18 and Cypermethrin D-16 19 and Cypermethrin
C-17 18 and Cyromazine D-17 19 and Cyromazine
C-18 18 and Delta methrin D-18 19 and Deltamethrin
C-19 18 and Dieldrin D- 19 19 and Dieldrin
C-20 18 and Dinotefuran D-20 19 and Dinotefuran
C-21 18 and Diofenolan D-21 19 and Diofenolan
C-22 18 and Emamectin D-22 19 and Emamectin
C-23 18 and Endosulfan D-23 19 and Endosulfan
C-24 18 and Esfenvalerate D-24 19 and Esfenvalerate
C-25 18 and Ethiprole D-25 19 and Ethiprole
C-26 18 and Fenothiocarb D-26 19 and Fenothiocarb
C-27 18 and Fenoxycarb D-27 19 and Fenoxycarb
C-28 18 and Fenvalerate D-28 19 and Fenvalerate
C-29 18 and Fipronil D-29 19 and Fipronil
C-30 18 and FIonicamid D-30 19 and FIonicamid
C-31 18 and Flubendiamide D-31 19 and Flubendiamide
C-32 18 and Flufenoxuron D-32 19 and Flufenoxuron
C-33 18 and Hexaflumuron D-33 19 and Hexaflumuron
C-34 18 and Hydramethylnon D-34 19 and Hydramethylnon
C-35 18 and Imidacloprid D-35 19 and Imidacloprid
C-36 18 and Indoxacarb D-36 19 and Indoxacarb
C-37 18 and Lambda-cyhalothrin D-37 19 and Lambda-cyhalothrin
C-38 18 and Lufenuron D-38 19 and Lufenuron
C-39 18 and Metaflumizone D-39 19 and Metaflumizone
C-40 18 and Methomyl D-40 19 and Methomyl
C-41 18 and Methoprene D-41 19 and Methoprene
C-42 18 and Methoxyfenozide D-42 19 and Methoxyfenozide
C-43 18 and Nitenpyram D-43 19 and Nitenpyram
C-44 18 and Nithiazine D-44 19 and Nithiazine
C-45 18 and Novaluron D-45 19 and Novaluron
C-46 18 and Oxamyl D-46 19 and Oxamyl
C-47 18 and Pymetrozine D-47 19 and Pymetrozine
C-48 18 and Pyrethrin D-48 19 and Pyrethrin
C-49 18 and Pyridaben D-49 19 and Pyridaben
C-50 18 and Pyridalyl D-50 19 and Pyridalyl Mixture Comp. and Invertebrate Pest Control Mixture Comp. and Invertebrate Pest Control
No. No. Agent No. No. Agent
C-51 18 and Pyriproxyfen D-51 19 and Pyriproxyfen
C-52 18 and Ryanodine D-52 19 and Ryanodine
C-53 18 and Spinetoram D-53 19 and Spinetoram
C-54 18 and Spinosad D-54 19 and Spinosad
C-55 18 and Spirodiclofen D-55 19 and Spirodiclofen
C-56 18 and Spiromesifen D-56 19 and Spiromesifen
C-57 18 and Tebufenozide D-57 19 and Tebufenozide
C-58 18 and Thiacloprid D-58 19 and Thiacloprid
C-59 18 and Thiamethoxam D-59 19 and Thiamethoxam
C-60 18 and Thiodicarb D-60 19 and Thiodicarb
C-61 18 and Thiosultap-sodium D-61 19 and Thiosultap-sodium
C-62 18 and Tralomethrin D-62 19 and Tralomethrin
C-63 18 and Triazamate D-63 19 and Triazamate
C-64 18 and Triflumuron D-64 19 and Triflumuron
C-65 18 and Bacillus thuringiensis D-65 19 and Bacillus thuringiensis
C-66 18 and Bacillus thuringiensis D-66 19 and Bacillus thuringiensis delta-endotoxin delta-endotoxin
C-67 18 and NPV (e.g., Gemstar) D-67 19 and NPV (e.g., Gemstar)
The specific mixtures listed in Table B typically combine a compound of Formula 1 with the other invertebrate pest agent in the ratios specified in Table A.
Invertebrate pests are controlled in agronomic and nonagronomic applications by applying one or more compounds of this invention, typically in the form of a composition, in a biologically 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 comprises a method for controlling an invertebrate pest in agronomic and/or nonagronomic applications, comprising contacting the invertebrate pest or its environment with a biologically effective amount of one or more of the compounds of the invention, or with a composition comprising at least one such compound or a composition comprising at least one such compound and a biologically effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions comprising a compound of the invention and a biologically effective amount of at least one additional biologically active compound or agent include granular compositions wherein the additional active compound is present on the same granule as the compound of the invention or on granules separate from those of the compound of the invention. To achieve contact with a compound or composition of the invention to protect a field crop from invertebrate pests, the compound or composition is typically applied to the seed of the crop before planting, to the foliage (e.g., leaves, stems, flowers, fruits) of crop plants, or to the soil or other growth medium before or after the crop is planted. One embodiment of a method of contact is by spraying. Alternatively, a granular composition comprising a compound of the invention can be applied to the plant foliage or the soil. Compounds of this invention can also be effectively delivered through plant uptake by contacting the plant with a composition comprising a compound of this invention applied as a soil drench of a liquid formulation, a granular formulation to the soil, a nursery box treatment or a dip of transplants. Of note is a composition of the present invention in the form of a soil drench liquid formulation. Also of note is a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of the present invention or with a composition comprising a biologically effective amount of a compound of the present invention. Of further note is this method wherein the environment is soil and the composition is applied to the soil as a soil drench formulation. Of further note is that compounds of this invention are also effective by localized application to the locus of infestation. Other methods of contact include application of a compound or a composition of the invention by direct and residual sprays, aerial sprays, gels, seed coatings, microencapsulations, systemic uptake, baits, ear tags, boluses, foggers, fumigants, aerosols, dusts and many others. One embodiment of a method of contact is a dimensionally stable fertilizer granule, stick or tablet comprising a compound or composition of the invention. The compounds of this invention can also be impregnated into materials for fabricating invertebrate control devices (e.g., insect netting).
Compounds of this invention are also useful in seed treatments for protecting seeds from invertebrate pests. In the context of the present disclosure and claims, treating a seed means contacting the seed with a biologically effective amount of a compound of this invention, which is typically formulated as a composition of the invention. This seed treatment protects the seed from invertebrate soil pests and generally can also protect roots and other plant parts in contact with the soil of the seedling developing from the germinating seed. The seed treatment may also provide protection of foliage by translocation of the compound of this invention or a second active ingredient within the developing plant. Seed treatments can be applied to all types of seeds, including those from which plants genetically transformed to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxin or those expressing herbicide resistance such as glyphosate acetyl transferase, which provides resistance to glyphosate.
One method of seed treatment is by spraying or dusting the seed with a compound of the invention (i.e. as a formulated composition) before sowing the seeds. Compositions formulated for seed treatment generally comprise a film former or adhesive agent. Therefore typically a seed coating composition of the present invention comprises a biologically effective amount of a compound of Formula 1, an Λf-oxide or salt thereof, and a film former or adhesive agent. Seed can be coated by spraying a flowable suspension concentrate directly into a tumbling bed of seeds and then drying the seeds. Alternatively, other formulation types such as wetted powders, solutions, suspoemulsions, emulsifiable concentrates and emulsions in water can be sprayed on the seed. This process is particularly useful for applying film coatings on seeds. Various coating machines and processes are available to one skilled in the art. Suitable processes include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and references listed therein.
The treated seed typically comprises a compound of the present invention in an amount from about 0.1 g to 1 kg per 100 kg of seed (i.e. from about 0.0001 to 1% by weight of the seed before treatment). A flowable suspension formulated for seed treatment typically comprises from about 0.5 to about 70% of the active ingredient, from about 0.5 to about 30% of a film-forming adhesive, from about 0.5 to about 20% of a dispersing agent, from 0 to about 5% of a thickener, from 0 to about 5% of a pigment and/or dye, from 0 to about 2% of an antifoaming agent, from 0 to about 1% of a preservative, and from 0 to about 75% of a volatile liquid diluent. The compounds of this invention can be incorporated into a bait composition that is consumed by an invertebrate pest or used within a device such as a trap, bait station, and the like. Such a bait composition can be in the form of granules which comprise (a) active ingredients, namely a biologically effective amount of a compound of Formula 1, an N-oxide, or salt thereof; (b) one or more food materials; optionally (c) an attractant, and optionally (d) one or more humectants. Of note are granules or bait compositions which comprise between about 0.001-5% active ingredients, about 40-99% food material and/or attractant; and optionally about 0.05-10% humectants, which are effective in controlling soil invertebrate pests at very low application rates, particularly at doses of active ingredient that are lethal by ingestion rather than by direct contact. Some food materials can function both as a food source and an attractant. Food materials include carbohydrates, proteins and lipids. Examples of food materials are vegetable flour, sugar, starches, animal fat, vegetable oil, yeast extracts and milk solids. Examples of attractants are odorants and flavorants, such as fruit or plant extracts, perfume, or other animal or plant component, pheromones or other agents known to attract a target invertebrate pest. Examples of humectants, i.e. moisture retaining agents, are glycols and other polyols, glycerine and sorbitol. Of note is a bait composition (and a method utilizing such a bait composition) used to control at least one invertebrate pest selected from the group consisting of ants, termites and cockroaches. A device for controlling an invertebrate pest can comprise the present bait composition and a housing adapted to receive the bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to the bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
The compounds of this invention can be applied without other adjuvants, but most often application will be of a formulation comprising one or more active ingredients with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. One method of application involves spraying a water dispersion or refined oil solution of a compound of the present invention. Combinations with spray oils, spray oil concentrations, spreader stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance compound efficacy. For nonagronomic uses such sprays can be applied from spray containers such as a can, a bottle or other container, either by means of a pump or by releasing it from a pressurized container, e.g., a pressurized aerosol spray can. Such spray compositions can take various forms, for example, sprays, mists, foams, fumes or fog. Such spray compositions thus can further comprise propellants, foaming agents, etc. as the case may be. Of note is a spray composition comprising a biologically effective amount of a compound or a composition of the present invention and a carrier. One embodiment of such a spray composition comprises a biologically effective amount of a compound or a composition of the present invention and a propellant. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Of note is a spray composition (and a method utilizing such a spray composition dispensed from a spray container) used to control at least one invertebrate pest selected from the group consisting of mosquitoes, black flies, stable flies, deer flies, horse flies, wasps, yellow jackets, hornets, ticks, spiders, ants, gnats, and the like, including individually or in combinations.
Nonagronomic applications include protecting an animal, particularly a vertebrate, more particularly a homeothermic vertebrate (e.g., mammal or bird) and most particularly a mammal, from an invertebrate parasitic pest by administering a parasiticidally effective (i.e. biologically effective) amount of a compound of the invention, typically in the form of a composition formulated for veterinary use, to the animal to be protected. Therefore of note is a method for protecting an animal comprising administering to the animal a parasiticidally effective amount of a compound of the invention. As referred to in the present disclosure and claims, the terms "parasiticidal" and "parasiticidally" refers to observable effects on an invertebrate parasite pest to provide protection of an animal from the pest. Parasiticidal effects typically relate to diminishing the occurrence or activity of the target invertebrate parasitic pest. Such effects on the pest include necrosis, death, retarded growth, diminished mobility or lessened ability to remain on or in the host animal, reduced feeding and inhibition of reproduction. These effects on invertebrate parasite pests provide control (including prevention, reduction or elimination) of parasitic infestation or infection of the animal. Examples of invertebrate parasitic pests controlled by administering a parasiticidally effective amount of a compound of the invention to an animal to be protected include ectoparasites (arthropods, acarines, etc) and endoparasites (helminths, e.g., nematodes, trematodes, cestodes, acanthocephalans, etc.). In particular, the compounds of this invention are effective against ectoparasites including: flies such as Haematobia (Lyperosia) irritans (horn fly), Stomoxys calcitrans (stable fly), Simulium spp. (blackfly), Glossina spp. (tsetse flies), Hydrotaea irritans (head fly), Musca autumnalis (face fly), Musca domestica (house fly), Morellia simplex (sweat fly), Tabanus spp. (horse fly), Hypoderma bovis, Hypoderma lineatum, Lucilia sericata, Lucilia cuprina (green blowfly), Calliphora spp. (blowfly), Protophormia spp., Oestrus ovis (nasal botfly), Culicoides spp. (midges), Hippobosca equine, Gastrophilus instestinalis, Gastrophilus haemorrhoidalis and Gastrophilus naslis; lices such as Bovicola (Damalinia) bovis, Bovicola equi, Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger, Lignonathus setosus and Trichodectes canis; keds such as Melophagus ovinus; mites such as Psoroptes spp., Sarcoptes scabei, Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedres cati, Trombicula spp. and Otodectes cyanotis (ear mites); ticks such as Ixodes spp., Boophilus spp., Rhipicephalus spp., Amblyomma spp., Dermacentor spp., Hyalomma spp. and Haemaphysalis spp.; and fleas such as Ctenocephalides felis (cat flea) and Ctenocephalides canis (dog flea).
Nonagronomic applications in the veterinary sector are by conventional means such as by enteral administration in the form of, for example, tablets, capsules, drinks, drenching preparations, granulates, pastes, boli, feed-through procedures, or suppositories; or by parenteral administration, such as by injection (including intramuscular, subcutaneous, intravenous, intraperitoneal), implants; by nasal administration; by topical administration, for example, in the form of immersion or dipping, spraying, washing, coating with powder, or application to a small area of the animal, and through articles such as neck collars, ear tags, tail bands, limb bands or halters which comprise compounds or compositions of the present invention.
Typically a parasiticidal composition according to the present invention comprises a mixture of a compound of Formula 1, an ΛT-oxide or a salt thereof, with one or more pharmaceutically or veterinarily acceptable carriers comprising excipients and auxiliaries selected with regard to the intended route of administration (e.g., oral, topical or parenteral administration such as injection) and in accordance with standard practice. In addition, a suitable carrier is selected on the basis of compatibility with the one or more active ingredients in the composition, including such considerations as stability relative to pH and moisture content. Therefore of note is a composition for protecting an animal from an invertebrate parasitic pest comprising a parasitically effective amount of a compound of the invention and at least one carrier.
For parenteral administration including intravenous, intramuscular and subcutaneous injection, a compound of the present invention can be formulated in suspension, solution or emulsion in oily or aqueous vehicles, and may contain adjuncts such as suspending, stabilizing and/or dispersing agents. Pharmaceutical compositions for injection include aqueous solutions of water-soluble forms of active ingredients (e.g., a salt of an active compound), preferably in physiologically compatible buffers containing other excipients or auxiliaries as are known in the art of pharmaceutical formulation.
For oral administration including solutions (the most readily available form for absorption), emulsions, suspensions, pastes, gels, capsules, tablets, boluses powders, granules, rumen-retention and feed/water/lick blocks, a compound of the present invention can be formulated with binders/fillers known in the art to be suitable for oral administration compositions, such as sugars (e.g., lactose, sucrose, mannitol, sorbitol), starch (e.g., maize starch, wheat starch, rice starch, potato starch), cellulose and derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (e.g., zein, gelatin), and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g., magnesium stearate), disintegrating agents (e.g., cross-linked polyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments can be added. Pastes and gels often also contain adhesives (e.g., acacia, alginic acid, bentonite, cellulose, xanthangum, colloidal magnesium aluminum silicate) to aid in keeping the composition in contact with the oral cavity and not being easily ejected.
If the parasinoidal compositions are in the form of feed concentrates, the carrier is typically selected from high-performance feed, feed cereals or protein concentrates. Such feed concentrate-containing compositions can, in addition to the parasinoidal active ingredients, comprise additives promoting animal health or growth, improving quality of meat from animals for slaughter or otherwise useful to animal husbandry. These additives can include, for example, vitamins, antibiotics, chemotherapeutics, bacteriostats, fungistats, coccidiostats and hormones.
Compounds of the present invention have been discovered to have favorable pharmacokinetic and pharmacodynamic properties providing systemic availability from oral administration and ingestion. Therefore after ingestion by the animal to be protected, parasiticidally effective concentrations of compounds of the invention in the bloodstream protect the treated animal from blood-sucking pests such as fleas, ticks and lice. Therefore of note is a composition for protecting an animal from an invertebrate parasite pest in a form for oral administration (i.e. comprising, in addition to a parasiticidally effective amount of a compound of the invention, one or more carriers selected from binders and fillers suitable for oral administration and feed concentrate carriers).
Formulations for topical administration are typically in the form of a powder, cream, suspension, spray, emulsion, foam, paste, aerosol, ointment, salve or gel. More typically a topical formulation is a water-soluble solution, which can be in the form of a concentrate that is diluted before use. Parasiticidal compositions suitable for topical administration typically comprise a compound of the present invention and one or more topically suitable carriers. In applications of a parasiticidal composition topically to the exterior of an animal as a line or spot (i.e. "spot-on" treatment), the active ingredient is expected to migrate over the surface of the active to cover most or all of its external surface area. As a result, the treated animal is particularly protected from invertebrate pests that feed off the epidermis of the animal such as ticks, fleas and lice. Therefore formulations for topical localized administration often comprise at least one organic solvent to facilitate transport of the active ingredient over the skin and/or penetration into the epidermis of the animal. Solvents commonly used as carriers in such formulations include propylene glycol, paraffins, aromatics, esters such as isopropyl myristate, glycol ethers, and alcohols such as ethanol and n-propanol.
The rate of application required for effective control (i.e. "biologically effective amount") will depend on such factors as the species of invertebrate 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 ingredients per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.0001 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. One skilled in the art can easily determine the biologically effective amount necessary for the desired level of invertebrate pest control.
In general for veterinary use, a compound of Formula 1, an .V-oxide or a salt thereof, is administered in a parasiticidally effective amount to an animal to be protected from invertebrate parasite pests. A parasiticidally effective amount is the amount of active ingredient needed to achieve an observable effect diminishing the occurrence or activity of the target invertebrate parasite pest. One skilled in the art will appreciate that the parasitically effective dose can vary for the various compounds and compositions of the present invention, the desired parasitical effect and duration, the target invertebrate pest species, the animal to be protected, the mode of application and the like, and the amount needed to achieve a particular result can be determined through simple experimentation. For oral administration to homeothermic animals, the daily dosage of a compound of the present invention typically ranges from about 0.01 mg/kg to about 100 mg/kg, more typically from about 0.5 mg/kg to about 100 mg/kg, of animal body weight. For topical (e.g., dermal) administration, dips and sprays typically contain from about 0.5 ppm to about 5000 ppm, more typically from about 1 ppm to about 3000 ppm, of a compound of the present invention.
The following abbreviations are used in the Index Tables A-D which follow: CF3 means trifluoromethyl, -CN is cyano and -NO2 is nitro. The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared. In Index Tables A, B and C, (R2)m refers to the combination of (R2)n as shown with instance of Z being CR2 as specified for Formula 1.
INDEX TABLE A
Figure imgf000097_0001
Compound CS2Jm U EZ Q m.p.f°O
1 (Ex. 1) 3-CI, 5-Cl C(=O) CH3 H C(=O)NHCH2CF3 **
2 (Ex. 2) 3-Cl.5-Cl C(=O) CH3 H C(=O)NHCH2-2-pyridinyl **
3 (Ex. 4) H C(=O) H -CN -NO2 **
4 (Ex. 3) 3-Cl, 5-Cl S(=O) CH3 H C(=O)NHCH2-2-pyridinyl **
5 3-F C(=O) CH3 H lH-l,2,4-triazol-l-yl *
6 3-Cl, 5-Cl C(=O) CH3 H l«-l,2,4-triazol-l-yl *
7 3-F C(=O) CH3 H C(=O)NHCH2-2-pyridinyl
8 3-Cl, 5-Cl C(=O) Cl H 4-morpholinyl *
9 3-Cl, 5-CI C(=O) H H -CN
10 3-Cl, 4-Cl C(=O) CH3 H l«-l,2,4-triazol-l-yl *
1 1 3-Cl C(=O) CH3 H l«-l,2,4-triazol-l-yl *
12 3-Cl, 4-Cl C(=O) CH3 H C(=O)NHCH2-2-pyridinyl *
13 3-Cl C(=O) CH3 H C(=O)NHCH2-2-pyridinyl *
14 3-Cl, 5-Cl S(=O) CH3 H l//-l,2,4-triazol-l-yl *
15 3-Cl, 5-Cl S(=O)2 CH3 H l«-l,2,4-triazol-l-yl *
16 3-Cl, 5-Cl C(=O) -CN H ltf-l,2,4-triazol-l-yl *
17 3-Cl, 5-Cl C(=O) CH3 H Br *
18 3-CI, 5-Cl S(=O)2 CH3 H C(=O)NHCH2-2-pyridinyl *
19 3-Cl, 5-Cl C(=O) CH3 H C(=O)NHCH(CH3)-2-pyridinyl * *See Index Table C for 1H NMR data **See synthesis example for 1H NMR data.
Index Table B
Figure imgf000098_0001
Compound 101 3-Cl, 5-Cl C(=O) Br 102 3-Cl, 5-Cl C(=O) C(=O)NHCH2-2-pyridinyl 103 3-Cl, 5-Cl C(=O) C(=O)NHCH2CF3
♦See Index Table C for 1H NMR data
Index Table C
Figure imgf000098_0002
Compound (R^) ■m1 U Q
201 (Ex. 5) 3-Cl, 5-Cl H C(=O) C(=O)NHCH2-2-pyridinyl
202 (Ex. 6) 3-Cl, 5-Cl Me C(=O) C(=O)NHCH2-2-pyridinyl
**See synthesis example for Η NMR data.
INDEX TABLE D Compd. No. 1H NMR Data (CDCI3 solution unless indicated otherwise)a
5 δ 8.25 (s, IH), 8.12 (s, IH), 7.58 (br d, 2H), 7.53-7.47 (m, 4H), 7.39-7.33 (m, 6H). 7.21 (dt, 2H), 7.68 (d, IH), 4.68 (d, IH), 4.36 (d, IH), 2.27 (s, 3H).
6 δ 8.26 (s, IH), 8.12 (s, IH), 7.57-7.50 (m.5H), 7.36 (d. IH), 4.68 (d, IH), 4.35 (d, 2H), 2.27 (s, 3H).
7 δ 7.80-7.20 (m, 1 IH), 4.74 (d, 2H), 4.65 (d, IH), 4.34 (d, IH), 2.50 (s, 3H).
8 δ 7.56-7.35 (m, 5H), 7.06 (d, IH), 4.57 (d, IH), 4.24 (d. IH), 3.87 (m, 4H), 3.03 (m, 4H).
9 δ 7.73 - 7.68 (m, 4H), 7.51 (s, IH), 7.48 (s, 2H), 4.64 (d, IH), 4.30 (d. IH).
10 δ 8.60 (s, IH), 8.09 (s, IH), 7.91 (d, IH), 7.81 (d, IH), 7.75-7.69 (m, 3H), 7.47 (d. IH), 5.05 (d, IH), 4.84 (d, IH), 2.26 (s, 3H). Compd. No. *H NMR Data (CDCI3 solution unless indicated otherwise)3
11 δ 8.60 (s, IH), 8.09 (s, IH), 7.76-7.60 (m, 6H), 7.47 (d, IH), 5.05 (d, IH), 4.82 (d, IH), 2.26 (s, 3H).
12 δ 8.50 (d, IH), 8.02 (t, IH), 7.88 (d, IH), 7.78-7.61 (m, 6H), 7.41 (d, IH), 7.21 (dd, IH), 4.98 (d, IH), 4.77 (d, IH), 4.65 (d, 2H), 2.45 (s, 3H).
13 δ 8.48 (d, IH), 8.04 (t, IH), 7.74-7.52 (m, 8H), 7.41 (d, IH), 7.21 (dd, IH), 4.98 (d, IH), 4.75 (d, IH), 4.65 (d, 2H), 2.45 (s, 3H).
14 (1:1 mixture of diastereomers) δ 8.25 (s, 0.5H), 8.22 (s, 0.5H), 8.13 (s, 0.5H), 8.12 (s, 0.5H), 7.50 (m, 3H), 7.34 (t, IH), 7.12-7.04 (m, 2H), 4.75 (d, 0.5H), 4.58 (d, 0.5H), 4.42 (d, 0.5H), 4.22 (d, 0.5H), 2.25 (s, 1.5H), 2.23 (s, 1.5H)
15 δ 8.27 (s, IH), 8.13 (s, IH), 7.54 (t, IH), 7.49 (br s, 2H), 7.40 (d, IH), 7.33 (br d, IH), 7.28 (dd, IH), 4.68 (d, IH), 4.33 (d, IH), 2.27 (s, 3H).
16 δ 8.76 (s, IH), 8.18 (s, IH), 8.02 (m, 2H), 7.84 (d, IH), 7.52 (m, 3H), 4.70 (d, IH), 4.38 (d, IH).
17 δ 7.54 (d, IH), 7.50-7.48 (m, 3H), 7.41 (d, IH), 7.22 (dd, IH), 4.58 (d, IH), 4.24 (d, IH).
18 δ 8.51 (d, IH), 8.03 (br t, IH), 7.79-7.75 (m, 4H), 7.62 (d, IH), 7.46 (d, IH), 7.34 (m, 2H), 7.25 (dd, IH), 5.14 (d, IH), 4.92 (d, IH), 4.68 (d, 2H), 2.47 (s, 3H).
19 δ 8.51 (d, IH), 7.70 (dt, IH), 7.49 (br s, 4H), 7.41 (dd, IH), 7.35-7.29 (m, 3H), 7.21 (dd, IH), 5.31 (quintet, IH), 4.62 (d, IH), 4.28 (d, IH), 2.49 (s, 3H), 1.58 (d, 3H).
101 δ 8.32 (d, IH), 7.81 (d, IH), 7.73 (br d, IH), 7.65 (m, 2H), 7.53 (t, IH), 7.50 (m, 2H), 7.31 (d, IH), 4.63 (d, IH), 4.29 (d, IH).
102 δ 8.47 (d, IH), 8.39 (m, IH), 7.73 (m, IH), 7.64 (m, 2H), 7.57 (m, 3H), 7.51 (br s, 3H), 7.31 (dd, 2H), 7.18 (t, IH), 4.77 (d, 2H), 4.58 (d, IH), 4.28 (d, IH).
103 δ 8.40 (br t, IH), 8.34 (m, IH), 7.95 (m, IH), 7.79-7.66 (m, 8H), 4.97 (d, IH), 4.86 (d, IH), 4.40 (m, 2H). a IH NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (m)-multiplet, (br s)-broad singlet, (br d)-broad doublet, (br t)- broad triplet, (dd)-doublet of doublet and (dt)-doublet of triplet.
BIOLOGICAL EXAMPLES OF THE INVENTTON The following Tests demonstrate the control efficacy of compounds of this invention on specific pests. "Control efficacy" represents inhibition of invertebrate pest development (including mortality) that causes significantly reduced feeding. The pest control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-D for compound descriptions. TEST A
For evaluating control of diamondback moth {Plutella xylostella) the test unit consisted of a small open container with a 12-14-day-old radish plant inside. This was pre- infested with 10-15 neonate larvae on a piece of insect diet by use of a core sampler to remove a plug from a sheet of hardened insect diet having many larvae growing on it and transfer the plug containing larvae and diet to the test unit. The larvae moved onto the test plant as the diet plug dried out.
Test compounds were formulated using a solution containing 10% acetone, 90% water and 300 ppm X-77™ Spreader Lo-Foam Formula non-ionic surfactant containing alkylarylpolyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries, Inc.
Greeley, Colorado, USA). The formulated compounds were applied in 1 mL of liquid through a SUJ2 atomizer nozzle with 1/8 JJ custom body (Spraying Systems Co. Wheaton,
Illinois, USA) positioned 1.27 cm (0.5 inches) above the top of each test unit. All experimental compounds in these tests were sprayed at 50 ppm and replicated three times.
After spraying of the formulated test compound, each test unit was allowed to dry for 1 hour and then a black, screened cap was placed on top. The test units were held for 6 days in a growth chamber at 25 0C and 70% relative humidity. The level of control efficacy of the test compound was then visually assessed based on the foliage feeding damage and the larval mortality of each test unit.
Of the compounds of Formula 1 tested the following provided very good to excellent levels of plant protection (20% or less feeding damage or 80% or more mortality): 1, 2, 6, 10, 12, 13, 15, 16, 18, 19 and 102.
TEST B For evaluating control of fall armyworm (Spodoptera frugiperda) the test unit consisted of a small open container with a 4— 5-day-old com (maize) plant inside. This was pre-infested (using a core sampler) with 10—15 1-day-old larvae on a piece of insect diet.
Test compounds were formulated and sprayed at 250 ppm as described for Test A and replicated three times. After spraying, the test units were maintained in a growth chamber and then visually rated as described for Test A.
Of the compounds of Formula 1 tested, the following provided very good to excellent levels of plant protection (20% or less feeding damage or 80% or more mortality): 1, 2, 16, 18 and 19.
TEST C For evaluating control of the western flower thrips {Frankliniella occidentalis) through contact and/or systemic means, the test unit consisted of a small open container with a 5-7 day old Longio Bean plant inside.
Test compounds were formulated and sprayed at 250 ppm and replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 h and then 22- 27 adult thrips were added to each unit and a black, screened cap was placed on top. The test units were held for 7 days at 25 0C and 45-55% relative humidity. A mortality rating was assessed for each test unit. Of the compounds tested, the following provided very good to excellent levels of plant protection (20% or less feeding damage or 80% or more mortality): 2, 12, 18 and 19.
TEST D
For evaluating control of potato leafhopper {Empoasca fabae Harris) through contact and/or systemic means, the test unit consisted of a small open container with a 5-6 day old Soleil bean plant (primary leaves emerged) inside. White sand was added to the top of the soil and one of the primary leaves was excised prior to application. Test compounds were formulated and sprayed at 250 ppm, and the test was replicated three times as described for Test A. After spraying, the test units were allowed to dry for 1 hour before they were post- infested with 5 potato leafhoppers (18- to 21-day old adults). A black, screened cap was placed on the top of the cylinder. The test units were held for 6 days in a growth chamber at 19-21 0C and 50-70% relative humidity. The control efficacy of each test unit was then visually assessed by the insect mortality.
Of the compounds of Formula 1 tested the following provided very good to excellent levels of control efficacy (70% or more mortality): 2, 12, 16, 18, 19 and 103.
TEST E
For evaluating control of green peach aphid (Myzus persicae) through contact and/or systemic means, the test unit consisted of a small open container with a 12-15-day-old radish plant inside. This was pre-infested by placing on a leaf of the test plant 30-40 aphids on a piece of leaf excised from a culture plant (cut-leaf method). The larvae moved onto the test plant as the leaf piece desiccated. After pre-infestation, the soil of the test unit was covered with a layer of sand.
All test compounds were formulated and sprayed at 250 ppm as described for Test A and replicated three times. After spraying of the formulated test compound, each test unit was allowed to dry for 1 hour and then a black, screened cap was placed on top. The test units were held for 6 days in a growth chamber at 19—21 0C and 50-70% relative humidity.
Each test unit was then visually assessed for insect mortality.
Of the compounds of Formula 1 tested, the following resulted in 50% or more mortality: 2, 18 and 19. TEST F
For evaluating control of cotton melon aphid (Aphis gossypiϊ) through contact and/or systemic means, the test unit consisted of a small open container with a 6-7-day-old cotton plant inside. This was pre-infested with 30—40 insects on a piece of leaf according to the cut-leaf method described for Test C, and the soil of the test unit was covered with a layer of sand. Test compounds were formulated and sprayed at 250 ppm as described for Test A.
The applications were replicated three times. After spraying of the formulated test compound, each test unit was allowed to dry for 1 hour and then a black, screened cap was placed on top. The test units were held for 6 days in a growth chamber at 19-21 0C and 50- 70% relative humidity. Each test unit was then visually assessed for insect mortality.
Of the compounds of Formula 1 tested, the following resulted in 50% or more mortality: 16, 18 and 19. TEST G
For evaluating control of the cat flea (Ctenocephalides felis Bouche), a CD-I® mouse (about 30 g, male, obtained from Charles River Laboratories, Wilmington, MA) was orally dosed with a test compound at 30 ppm solubilized in propylene glycol/glycerol formal (60:40). Two hours after oral administration of the test compound, approximately 8 to 16 adult fleas were applied to each mouse. The fleas were then evaluated for mortality 48 hours after flea application to the mouse.
Of the compounds tested, the following compounds caused 50% or more mortality: 1 , 2, 12, 13, 16, 18, 19 and 102.

Claims

CLAIMSWhat is claimed is:
1. A compound of Formula 1, an iV-oxide, or a salt thereof,
Figure imgf000103_0001
wherein
G is O or NR3;
U is C(=O), S(=O), C(=S), or S(O)2;
Z is N or CR2;
A1 is CR4 or N; A2 is CR5 or N;
A3 is CR6 or N;
A4 is CR7 or N;
Q is a 5 or 6-membered saturated or unsaturated heterocycle optionally substituted with one or more substituents independently selected from halogen, C1-Cg alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, cyano, nitro, C(=O)NR8R9, CC=O)OR1 °, phenyl and pyridinyl, each phenyl or pyridinyl optionally substituted with one or more substituents independently selected from R1 *; or
Q is C(O)NRl2R13, C(S)NR12R13, S(O)2NR14R1^ or R1^;
R1 is cyano; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R17; each R2 is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-Cg dialkylamino, C2-C4 alkoxycarbonyl, C2-C4 alkylaminocarbonyl, C3-Cg dialkylaminocarbonyl, cyano or nitro; R3 is H, cyano or -CHO; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, phenyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl or C3-C9 dialkylaminocarbonyl, each optionally substituted with one or more substituents independently selected from R18; R4, R5, R6 and R7 are independently selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-Cg dialkylamino, cyano and nitro; or
R6 and R7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A3 and A4 bridgehead atoms, 3 atoms selected from 1 to 2 carbon atoms, 0 to 2 nitrogen atoms, 0 to 1 oxygen • atom and 0 to 1 sulfur atom, or 4 atoms selected from 2 to 4 carbon atoms and 0 to 2 nitrogen atoms; each R8, R12 and R14 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2- C7 alkylcarbonyl, C2-C6 alkoxyalkyl or C2-C7 alkoxycarbonyl; each R9, R10, R13 and R15 is independently H; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from RW; each R11, R23 and R24 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, CrC6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylaminosulfonyl, C1-Cg alkylamino, C2-Cg dialkylamino, C2-C4 alkoxycarbonyl, cyano or nitro; R16 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, Ci-C^ haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl,
C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, cyano or nitro; each R17 and R18 is independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio,
C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, cyano or nitro; each R19 is independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-Cg alkylcarbonyl, C2-C6 alkoxycarbonyl, trimethylsilyl, cyano, nitro or Q1; each Q1 is independently a phenyl or a 5- or 6-membered saturated or unsaturated heterocycle, each optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-Cg dialkylamino, cyano, nitro, C(O)NR20R21, C(O)OR22, phenyl or pyridinyl, each phenyl or pyridinyl optionally substituted with one or more substituents independently selected from R23; each R20 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl,
C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; each R21 and R22 is independently H; or C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl,
C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, phenyl or pyridinyl; each phenyl or pyridinyl optionally substituted with one or more substituents independently selected from R24; and n is 1, 2, 3 or 4; and provided that R16 is other than methoxy.
2. The compound of Claim 1 wherein
Q is a pyridinyl ring, a pyrimidinyl ring, a triazinyl ring, a pyrazolyl ring, a triazolyl ring, an imidazolyl ring, an oxazolyl ring, an isoxazolyl ring, a thiazolyl ring or an isothiazolyl ring, each ring optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfmyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, cyano, nitro, C(O)NR8R9, C(O)OR10, phenyl and pyridinyl, each phenyl and pyridinyl optionally substituted with one or more substituents independently selected from R1 *; or Q is C(O)NR12R13, S(O)2NR14R15 or R1^; Z is CR2; R1 is C1-C3 alkyl optionally substituted with one or more substituents independently selected from R17; each R2 is independently selected from H, halogen or C1-C2 haloalkyl;
R3 is H or cyano; or C1-C4 alkyl optionally substituted with one or more substituents selected from halogen; R4 and R5 are independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano and nitro;
R6 and R7 are independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano and nitro; or R6 and R7 are taken together to form a fused aromatic ring, the fused aromatic ring containing as ring members in addition to the A3 and A4 bridgehead atoms, 4 atoms selected from 3 to 4 carbon atoms and 0 to 1 nitrogen atom; each R8 is independently H, C1-C6 alkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; each R9 and R10 is independently H; or C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C4 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R19;
R12 and R14 are independently H, C1-C6 alkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl;
R13 and R15 are independently H; or C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3"C4 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents selected from R19; R16 is halogen, C1-C3 haloalkyl, C2-C4 dialkylamino, cyano or nitro; each R19 is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, cyano, nitro and Q1; each Q1 is independently selected from phenyl, pyridinyl and thiazolyl, each optionally substituted with one or more substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano, phenyl and pyridinyl; and n is 1 or 2; provided that at most 1 of A1, A2, A3 and A4 is N.
3. The compound of Claim 2 wherein
R1 is C1-C3 alkyl substituted with halogen; and U is C(=O).
4. The compound of Claim 3 wherein
Q is a pyrazolyl ring, a triazolyl ring or an imidazolyl ring, each ring attached through nitrogen and optionally substituted with one or more substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, cyano, nitro, C(O)NR8R9 and C(O)OR1O; or Q is C(O)NR12R13; R1 is CF3;
R6 and R7 are independently selected from H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyano and nitro; or R6 and R7 are taken together to form a fused aromatic ring, the fused aromatic ring containing 4 carbon atoms as ring members in addition to the A3 and A4 bridgehead atoms; each R8 is H; each R9 and R10 is independently C1-C4 alkyl optionally substituted with one Q1 and optionally substituted with one or more substituents selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl and cyano; R12 Js H; R13 is H; or C1-C4 alkyl optionally substituted with one or more substituents selected from R19; and each R19 is independently selected from halogen and Q1.
5. The compound of Claim 4 wherein each R2 is independently H, halogen or CF3; and R3 is CH3, CH2CH3, or CH2CF3.
6. The compound of Claim 5 wherein G is O; and [El] provided that A1, A2, A^ and A4 are each other than N.
7. The compound of Claim 1 that is selected from the group consisting of: 4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-2-methyl- 7V-(2-pyridinyImethyl)benzamide;
4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidmyl]-2-methyl- Λ/r-(2,2,2-trifluoroethyl)benzamide;
4-[5-(3,5-dichlorophenyl)-2-oxido-5-(trifluoromethyl)-l,2,3-oxathiazolidin-3-yl]- 2-methyl-Λf-(2-pyridinylmethyl)benzamide;
2-nitro-5-[2-oxo-5-phenyl-5-(trifluoromethyl)-3-oxazolidinyl]benzonitrile; 4-[4-(3,5-dichlorophenyl)-2-oxo-4-(trifluoromethyl)-l-imidazolidinyl]-2-methyl- Λr-(2-pyridinylmethyl)benzamide;
4-[4-(3,5-dichlorophenyl)-3-methyl-2-oxo-4-(trifluoromethyl)-l-imidazolidinyl]- 2-methyl-7v*-(2-pyridinylmethyl)benzamide;
4-[5-(3,4-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-2-methyl- N-(2-pyridinylmethyl)benzamide; 5-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-
2-( IH- 1 ,2,4-triazol-l -yl)benzonitrile;
4-[5-(3,5-dichlorophenyl)-2,2-dioxido-5-(trifluoromethyl)-l,2,3-oxathiazolidin- 3-yl]-2-methyl-N-(2-pyridinylmethyl)benzamide; and
4-[5-(3,5-dichlorophenyl)-2-oxo-5-(trifluoromethyl)-3-oxazolidinyl]-2-methyl- -V-[l-(2-pyridinyl)ethyl]benzamide.
8. A composition comprising a compound of Claim 1 and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said composition optionally further comprising at least one additional biologically active compound or agent.
9. A composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Claim 1 and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.
10. The composition of Claim 9 wherein at least one additional biologically active compound or agent is selected insecticides of the group consisting of macrocyclic lactones, neonicotinoids, octopamine receptor ligands, ryanodine receptor ligands, ecdysone agonists, sodium channel modulators, chitin synthesis inhibitors, nereisotoxin analogs, mitochondrial electron transport inhibitors, cholinesterase inhibitors, cyclodiene insecticides, molting inhibitors, γ— aminobutyric acid-regulated chloride channel blockers, juvenile hormone mimics, lipid biosynthesis inhibitors and biological agents including nucleopolyhedro viruses, members of Bacillus thuringiensis, encapsulated delta-endotoxins of Bacillus thuringiensis, and other naturally occurring or genetically modified insecticidal viruses.
11. The composition of Claim 9 wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole, chlorpyrifos, chlorpyrifos- methyl, chlorobenzilate, chromafenozide, clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim, flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isόfenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen, spirotetramat, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, nucleopolyhedro viruses, encapsulated delta-endotoxins of Bacillus thuringiensis, baculoviruses, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.
12. The composition of Claim 11 wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acetamiprid, amitraz, avermectin, azadirachtin, bifenthrin, buprofezin, cartap, chlorantraniliprole, chlorfenapyr, chloφyrifos, clothianidin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, flubendi amide, flufenoxuron, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, metaflumizone, methomyl, methoprene, methoxyfenozide, nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, tebufenozide, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, nucleopolyhedro viruses and encapsulated delta-endotoxins of Bacillus thuringiensis.
13. The composition of Claim 9 in the form of a soil drench liquid formulation.
14. A spray composition for controlling an invertebrate pest, comprising:(a) a biologically effective amount of the compound of Claim 1 or the composition of Claim 9; and
(b) a propellant.
15. A bait composition for controlling an invertebrate pest, comprising:
(a) a biologically effective amount of the compound of Claim 1 or the composition of Claim 9; (b) one or more food materials;
(c) optionally an attractant; and
(d) optionally a humectant.
16. A trap device for controlling an invertebrate pest, comprising: (a) the bait composition of Claim 15; and (b) a housing adapted to receive the bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to the bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
17. A method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Claim 1.
18. A method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a composition of Claim 9.
19. The method of Claim 18 wherein the environment is soil and the composition is applied to the soil as a soil drench formulation.
20. A method for controlling a cockroach, an ant or a termite, comprising contacting a cockroach, an ant, or a termite with the bait composition in a trap device of Claim 16.
21. A method for controlling a mosquito, a black fly, a stable, fly, a deer fly, a horse fly, a wasp, a yellow jacket, a hornet, a tick, a spider, an ant, or a gnat, comprising contacting a mosquito, a black fly, a stable, fly, a deer fly, a horse fly, a wasp, a yellow jacket, a hornet, a tick, a spider, an ant, or a gnat with the spray composition of Claim 14 dispensed from a spray container.
22. A method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of Claim 1.
23. The method of Claim 22 wherein the seed is coated with the compound of Claim
1 formulated as a composition comprising a film former or adhesive agent.
24. A treated seed comprising a compound of Claim 1 in an amount of from about 0.0001 to 1 % by weight of the seed before treatment.
25. A composition for protecting an animal from an invertebrate parasitic pest comprising a parasiticidally effective amount of a compound of Claim 1 and at least one carrier.
26. The composition of Claim 25 in a form for oral administration.
27. A method for protecting an animal from an invertebrate parasitic pest comprising administering to the animal a parasiticidally effective amount of a compound of Claim 1.
PCT/US2007/009181 2006-04-20 2007-04-13 Five-membered heterocyclic invertebrate pest control agents Ceased WO2007123853A2 (en)

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