Classifications

• • 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
  • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
  • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
  • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
  • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
  • C07D239/72—Quinazolines; Hydrogenated quinazolines
  • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
  • C07D239/88—Oxygen atoms
  • C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
• • 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
  • C07D401/14—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 three or more hetero rings
• • 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
  • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
  • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
  • C07D471/04—Ortho-condensed systems

Definitions

• This invention relates to certain quinazolinones and pyridinylpyrimidinones, their
• N-oxides N-oxides, agriculturally suitable salts and compositions, and a method of use for controlling invertebrate pests 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.
• the control of invertebrate pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, environmentally safer or have different modes of action.
• WO 99/14202 discloses pyrimidin-4-one and pyrimidin-4-thiones of Formula i as fungicides
• X is O or S
• A is fused phenyl or pyridyl
• Rl and R2 are selected from H, halogen or trimethylsilyl
• R3 is -Cg alkyl, Cj-Cg alkenyl or C j -Cg alkynyl, each optionally substituted;
• R4 is optionally substituted phenyl.
• This invention pertains to 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 I, its N-oxide or an agriculturally suitable salt of the compound (e.g., as a composition described herein)
• B is O or S
• J is a phenyl ring substituted with 1 to 4 R 5 , or a naphthyl ring system, a 5- or
• K is, together with the two contiguous linking carbon atoms, a fused phenyl or a fused pyridinyl ring selected from the group consisting of K-l, K-2, K-3, K-4 and K-5, each optionally substituted with 1 to 4 R 4
• R 3 is G; Ci-C6 alkyl, C 2 -Cg alkenyl, C 2 -Cg alkynyl, C3-C 6 cycloalkyl, each optionally substituted with one or more substituents selected from the group consisting of halogen, G, CN, NO 2 , hydroxy, Cj- alkoxy, Cj-C 4 haloalkoxy, C r C 4 alkylthio, C r C 4 alkylsulfinyl, C,-C 4 alkylsulfonyl, C 2 -C 6 alkoxycarbonyl, C 2 -Cg alkylcarbonyl, C3-C6 trialkylsilyl, or a phenoxy ring optionally substituted with one to three substituents independently selected from R 6 ; hydroxy; C r C 4 alkoxy; C j -C4 alkylamino; C 2 -C 8 dialkylamino; C 3 -C 6 cycloal
• each R 4 is independently a phenyl, benzyl, phenoxy or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents independently selected from R 6 ;
• each R 5 is independently H, alkyl, C 2 -C6 alkenyl, C 2 -CG alkynyl, C3-C6 cycloalkyl, C Cg haloalkyl, C -Cg haloalkenyl, C 2 -C6 haloalkynyl, C3-C6 halocycloalkyl, halogen, CN, CO 2 H, CONH 2 , NO 2 , hydroxy, C r C 4 alkoxy, C C 4 haloalkoxy, C1-C4 alkylthio, Cj-C 4 alkylsulfinyl,
• haloalkylsulfonyl C C 4 alkylamino, C -Cg dialkylamino, C3-C6 cycloalkylamino, C2-C5 alkylcarbonyl, C 2 -Cg alkoxycarbonyl, C -Cg alkylaminocarbonyl, C3 ⁇ C dialkylaminocarbonyl,
• each R 5 is independently a phenyl, benzyl, benzoyl, phenoxy, 5- or 6-membered heteroaromatic ring or an aromatic S-, 9- or 10-membered fused heterobicyclic ring system, each ring optionally substituted with one to three substituents independently selected from R 6 ; or
• each R 6 is independently C C 4 alkyl, C 2 -C 4 alkenyl, C -C 4 alkynyl, C3-C6 cycloalkyl, Cj-C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C3-C6 halocycloalkyl, halogen, CN, NO 2 , -C4 alkoxy, Cj-C haloalkoxy, C r C alkylthio, C alkylsulfinyl, C C 4 alkylsulfonyl, -C4 alkylamino, C 2 -Cg dialkylamino, C3-C6 cycloalkylamino, C3-C6
• RU is H or - alkyl; each R 12 is independently Cj-C 2 alkyl, halogen, CN, NO 2 and C!-C 2 alkoxy; and n is 1 to 4.
• This invention also relates to such a method wherein the invertebrate pest or its environment is contacted with a biologically effective amount of a compound of Formula I or a composition comprising a compound of Formula I and a biologically effective amount of at least one additional compound or agent for controlling invertebrate pests.
• This invention also pertains to a compound of Formula la, its N-oxide or an agriculturally suitable salt of the compound
• K is, together with the two contiguous linking carbon atoms, a fused phenyl or a fused pyridinyl ring selected from the group consisting of K-l, K-2, K-3, K-4 and K-5, each optionally substituted with 1 to 4 R 4
• J substituted with 1 to 3 R 5 is selected from the group consisting of J-6, J-7, J-8, J-9, J-10, J-l l, J-12 and J-13
• R 3 is Cj-Cg alkyl, C 2 -Cg alkenyl, C 2 -C 6 alkynyl or C3-C6 cycloalkyl each optionally substituted with one or more substituents selected from the group consisting of halogen, CN, C r C 2 alkoxy, Cj-C 2 alkylthio, Cj-C 2 alkylsulfinyl and C1-C2 alkylsulfonyl; one R 4 group is attached to the K-ring at the 2-position or 5-position, and said R 4 is C r C 4 alkyl, C r C 4 haloalkyl, halogen, CN, NO 2 , C r C 4 alkoxy, C r C 4 haloalkoxy, C ⁇ -C 4 alkylthio, C ⁇ -C 4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio,
• V is N, CH, CF, CC1, CBr or CI; each R 6 is independently C1-C4 alkyl, C 2 -C alkenyl, C 2 -C 4 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C haloalkynyl, C3-C6 halocycloalkyl, halogen, CN, NO 2 , C!-C alkoxy, C C4 haloalkoxy, C1-C4 alkylthio, C r C 4 alkylsulfinyl, C r C 4 alkylsulfonyl, C1-C4 alkylamino, C 2 -Cg dialkylamino, C 3 - C 6 cycloalkylamino, C_t,-C 6 (alkyl)cycloalkylamino, C2-C4 al
• R 9 is H, C 2 -C 6 alkyl, C r C 6 haloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 haloalkenyl, C 3 -C 6 alkynyl or C3-C6 haloalkynyl, provided that R 7 and R 9 are not both H;
• R 1 0 is H or C !-C 4 alkyl or C ⁇ -C 4 haloalkyl;
• R 11 is H or C 1 -C 4 alkyl; and n is 0, 1 or 2.
• This invention also pertains to a composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula la and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
• This invention also pertains to a composition comprising a biologically effective amount of a compound of Formula la and an effective amount of at least one additional biologically active compound or agent.
• alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as methyl, ethyl, 72-propyl, t-propyl, or the different butyl, pentyl or hexyl isomers.
• alkenyl includes straight-chain or branched alkenes such as 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers.
• Alkenyl can also include polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl.
• Alkynyl includes straight-chain or branched alkynes such as
• Alkynyl can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
• Alkoxy includes, for example, methoxy, ethoxy, 77-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers.
• Alkoxyalkyl denotes alkoxy substitution on alkyl.
• alkoxyalkyl examples include CH3OCH9, CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
• Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers.
• Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
• heteroaromatic ring denotes fully aromatic rings in which at least one ring atom is not carbon and can contain 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each heteroaromatic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs (where aromatic indicates that the Hiickel rule is satisfied).
• the heteroaromatic ring can be attached through any available carbon or nitrogen by replacement of hydrogen on said carbon or nitrogen.
• halogen either alone or in compound words such as “haloalkyl” includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” include F 3 C, C1CH 2 , CF 3 CH 2 and CF 3 CC1 2 .
• haloalkenyl “haloalkynyl”, “haloalkoxy”, and the like, are defined analogously to the tenn "haloalkyl".
• haloalkynyl examples include HC ⁇ CCHCl, CF 3 C ⁇ C, CC1 3 C ⁇ C and FCH 2 C ⁇ CCH 2 .
• haloalkoxy examples include CF 3 O, CCl 3 CH 2 O, HCF 2 CH 2 CH 2 O and CF 3 CH 2 O.
• C1-C3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl
• C 2 alkoxyalkyl designates CH 3 OCH 2
• C3 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 .
• 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. Accordingly, the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form.
• the present invention comprises compounds selected from Formula I, N-oxides and agriculturally suitable salts thereof, compositions thereof and methods of their use for invertebrate pest control.
• nitrogen containing heterocycles can form N-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 N-oxides.
• tertiary amines can form N-oxides.
• N-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 ??.-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethydioxirane.
• MCPBA peroxy acids
• alkyl hydroperoxides such as t-butyl hydroperoxide
• sodium perborate sodium perborate
• dioxiranes such as dimethydioxirane
• the salts of the compounds of the invention include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
• inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
• Preferred 2 Methods of Preferred 1 wherein J is a phenyl group substituted with 1 to
• each R 5 is independently H, halogen, C r C 4 alkyl, C ⁇ -C 2 alkoxy, C C 4 haloalkyl, CN, NO 2 , C r C 4 haloalkoxy, C r C 4 alkylthio, C r C 4 alkylsulfinyl, C1-C4 alkylsulfonyl, -C4 haloalkylthio, C r C 4 haloalkylsulfinyl, C ⁇ -C 4 haloalkylsulfonyl or C 2 -C alkoxy
• R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, CF 3 , OCF3, OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 , CN or halogen;
• a second R 4 is H, F, Cl, Br, I or CF 3 ;
• each R 5 is independently H, halogen, methyl, CF 3 , OCF 3 , OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 , OCH 2 CF 3 , OCF 2 CHF 2 , S(O) p CH 2 CF 3 or S(O) p CF 2 CHF 2 ; or a phenyl, pyrazole, imidazole, triazole, pyridine or pyrimidine ring, each ring optionally substituted with C ] -C 4 alkyl, Cj-C 4 haloalkyl,
• J is a 5- or 6-membered heteroaromatic ring selected from the group consisting of J-l, J-2, J-3, J-4 and J-5, each J optionally substituted with 1 to 3 R 5
• Q is O, S or NR 5 ;
• W, X, Y and Z are independently N or CR 5 , provided that in J-4 and J-5 at least one of W, X, Y or Z is N.
• R 4 is C r C 4 alkyl, C r C 4 haloalkyl, halogen, CN, NO 2 , C r C 4 alkoxy, C r C 4 haloalkoxy, C r C 4 alkylthio, C r C 4 alkylsulfinyl, C r C 4 alkylsulfonyl, 0 ⁇ 4 haloalkylthio, C1-C4 haloalkylsulfinyl, or C1-C4 haloalkylsulfonyl; and each R 5 is independently H, C r C 4 alkyl, C r C 4 haloalkyl, halogen, CN, NO 2 ,
• J substituted with 1 to 3 R 5 is selected from the group consisting of J-6, J-7, J-S, J-9, J-10, J-l l, J-12 and J-13
• V is N, CH, CF, CC1, CBr or CI; each R 7 is independently H, C Cg alkyl, C j -Cg haloalkyl, halogen, CN,
• R 9 is H, C 2 -C 6 alkyl, C r C 6 haloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 haloalkenyl, C3-C6 alkynyl or C3-C6 haloalkynyl, provided that R 7 and R 9 are not both H; and n is 0, 1 or 2.
• Preferred 10 Methods of Preferred 9 wherein J substituted with 1 to 3 R 5 is J-6;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 ,
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 , Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and
• R 7 is halogen or CF 3 .
• Methods of Preferred 9 wherein J substituted with 1 to 3 R 5 is J-7;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 ,
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN;
• R 9 is C 2 -C 6 alkyl or C r C 6 haloalkyl; and
• p is 0, lor 2.
• R 6 is Cl or Br
• R9 is CF 3 , CHF 2 , CBrF 2 , CC1F 2 , CH 2 CF 3 , or CF 2 CHF 2 .
• Preferred 14 Methods of Preferred 9 wherein J substituted with 1 to 3 R 5 is J-S; R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 ,
• a second R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN R 6 is CH 3 , CF 3 or halogen;
• R 7 is CH 3 , CF 3 or halogen; and p is 0, 1 or 2.
• Preferred 15 Methods of Preferred 14 wherein R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 , Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and
• R 7 is halogen or CF 3 .
• Preferred 16 Methods of Preferred 9 wherein J substituted with 1 to 3 R 5 is J-9;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 ,
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN;
• R 7 is CH 3 , CF 3 or halogen; and p is 0, 1 or 2.
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 , Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is Cl or Br; and R 7 is CF 3 .
• Preferred 18 Methods of Preferred 9 wherein J substituted with 1 to 3 R 5 is J-10; R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 ,
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN;
• R 9 is C 2 -C 6 alkyl or C r C 6 haloalkyl; and
• p is O, lor 2.
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is Cl or Br
• R 9 is CF 3 , CHF 2 , CBrF 2 , CC1F 2 , CH 2 CF 3 , or CF 2 CHF 2 .
• Preferred 20 Methods of Preferred 9 wherein J substituted with 1 to 3 R 5 is J-l 1;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, CF 3 , OCF3, OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 , CN or halogen; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is C r C 4 alkyl, C C 4 haloalkyl, halogen or CN; R 7 is CH 3 , CF 3 , OCHF 2 or halogen; and p is 0, 1 or 2.
• Preferred 21 Methods of Preferred 20 wherein
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 , Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and
• R 7 is halogen or CF3.
• Preferred 22 Methods of Preferred 9 wherein J substituted with 1 to 3 R 5 is J-l 2;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3,
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, Cj-C haloalkyl, halogen or CN;
• R 9 is C 2 -C 6 alkyl or C r C 6 haloalkyl; and
• p is 0, lor 2.
• R 3 is C r C 4 alkyl
• one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, Cl or Br
• a second R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is Cl or Br
• R 9 is CF 3 . CHF 2 , CBrF 2 , CC1F 2 , CH 2 CF 3 , or CF 2 CHF 2 .
• Preferred 24 Methods of Preferred 9 wherein J substituted with 1 to 3 R 5 is J-l 3; R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 ,
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN;
• R 9 is C 2 -C 6 alkyl or C r C 6 haloalkyl; and
• p is 0, lor 2.
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 , Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and R 9 is CF 3 , CHF 2 , CBrF 2 , CC1F 2 , CH 2 CF 3 , or CF 2 CHF 2 .
• the compound of Formula I is selected from the group consisting of: 8-methyl-3-(l-methylethyl)-2-[2-methyl-6-(trifluoromethyl)-3-pyridinyl]-4(3H)- quinazolinone, 2-[3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl]-6-chloro-3,8-dimethyl-
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN;
• R 7 is CH 3 , CF 3 , OCHF 2 or halogen; and
• p is 0, 1 or 2.
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and R 7 is halogen or CF3.
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, CF 3 , OCF3, OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 , CN or halogen; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN; R 9 is C 2 -C 6 alkyl or C r C 6 haloalkyl; and p is 0, lor 2.
• Preferred D Compounds of Preferred C wherein
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 , Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and
• R 9 is CF 3 , CHF 2 , CBrF 2 , CC1F 2 , CH 2 CF 3 , or CF 2 CHF 2 .
• Preferred E. Compounds of Formula la wherein J substituted with 1 to 3 R 5 is J-8;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3,
• a second R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN
• R 6 is CH 3 , CF 3 or halogen
• R 7 is CH 3 , CF 3 or halogen
• p is 0, 1 or 2.
• Preferred F Methods of Preferred E wherein R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and R 7 is halogen or CF3.
• Preferred G Compounds of Formula la wherein J substituted with 1 to 3 R 5 is J-9;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, CF 3 , OCF3, OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 , CN or halogen; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN; R 7 is CH 3 , CF 3 or halogen; and p is 0, 1 or 2.
• Preferred H Compounds of Preferred G wherein
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and
• R 7 is CF 3 .
• Preferred I Compounds of Formula la wherein J substituted with 1 to 3 R 5 is J-10;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3,
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN;
• R 9 is C 2 -C 6 alkyl or C r C 6 haloalkyl; and
• p is 0, lor 2.
• Preferred J Compounds of Preferred I wherein R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 , Cl or Br; a second R is H, F, Cl, Br, I or CF 3 ;
• R 6 is Cl or Br
• R 9 is CF 3 , CHF 2 , CBrF 2 , CC1F 2 , CH 2 CF 3 , or CF 2 CHF 2 .
• Preferred K Compounds of Formula la wherein J substituted with 1 to 3 R 5 is J-l 1; R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 ,
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C1-C4 alkyl, C r C 4 haloalkyl, halogen or CN;
• R 7 is CH 3 , CF 3 , OCHF 2 or halogen; and
• p is 0, 1 or 2.
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and R 7 is halogen or CF3.
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 , CF 3 , OCF3, OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 , CN or halogen; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN; R 9 is C 2 -C 6 alkyl or C r C 6 haloalkyl; and p is O, lor 2.
• Preferred N Methods of Preferred M wherein
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and
• R 9 is CF 3 , CHF 2 , CBrF 2 , CC1F 2 , CH 2 CF 3 , or CF 2 CHF 2 .
• Compounds of Formula la wherein J substituted with 1 to 3 R 5 is J-l 3;
• R 3 is C r C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH 3 ,
• R 4 is H, F, Cl, Br, I or CF 3 ;
• R 6 is C r C 4 alkyl, C r C 4 haloalkyl, halogen or CN;
• R 9 is C 2 -C 6 alkyl or C r C 6 haloalkyl; and
• p is 0, lor 2.
• R 3 is C r C 4 alkyl; one R 4 group is attached to the K-ring at the 2-position and said R 4 is CH3, Cl or Br; a second R 4 is H, F, Cl, Br, I or CF 3 ; R 6 is Cl or Br; and R 9 is CF 3 , CHF 2 , CBrF 2 , CC1F 2 , CH 2 CF 3 , or CF 2 CHF 2 .
• This invention also pertains to a composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of Formula la and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
• Preferred compositions are those comprising the above preferred compounds.
• a method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of a compound of Formula 1 , its N-oxides or agriculturally suitable salts thereof
• B is O or S;
• J is a phenyl group substituted with 1 to 2 R 5 and optionally substituted with 1 to 3 R 6 , or a 5- or 6-membered heteroaromatic ring optionally substituted with 1 to 4 R 7 ;
• n is 1 to 4;
• R 3 is C Cg alkyl, C 2 -Cg alkenyl, C 2 -C 6 alkynyl, C3-C6 cycloalkyl, each optionally substituted with one or more substituents selected from the group consisting of halogen, CN, NO 2 , hydroxy, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl and C1-C4 alkylsulfonyl; C1-C4 alkoxy; C1-C4 alkylamino; C2-Cg dialkylamino; C3-C6 cycloalkylamino; C 2 -Cg alkoxycarbonyl or C 2 -Cg alkylcarbonyl; each R 4 is independently H, Cj-Cg alkyl, C 2 -Cg alkenyl, C 2 -C6 alkynyl, C3-C6 cycloalkyl, C j -
• each R 4 is independently phenyl, benzyl or phenoxy, each optionally substituted with C1-C4 alkyl, C 2 -C4 alkenyl, C 2 -C 4 alkynyl, C3-C6 cycloalkyl, C 1 -C4 haloalkyl, C 2 -C4 haloalkenyl, C 2 -C4 haloalkynyl, C3-C6 halocycloalkyl, halogen, CN, NO 2 , C r C 4 alkoxy, C r C 4 haloalkoxy, C r C 4 alkylthio, C r C 4 alkylsulfinyl,
• each R 5 is independently Cj-Cg alkyl, C 2 -Cg alkenyl, C 2 -Cg alkynyl, C3-C6 cycloalkyl, C Cg haloalkyl, C 2 -C haloalkenyl, C -Cg haloalkynyl, C3-C6 halocycloalkyl, halogen, CN, CO 2 H, CONH 2 , NO 2 ,
• each R 6 is independently H, halogen, C r Cg alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl,
• each R 6 is independently a phenyl, benzyl, phenoxy or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted with - alkyl, C -C 4 alkenyl, C 2 -C4 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C -C4 haloalkenyl, C 2 -C 4 haloalkynyl, C3-C6 halocycloalkyl, halogen, CN, NO 2 , C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, Cj-C 4 alkylsulfinyl, C1-C4 alkylsulfonyl, Cj-C alkylamino,
• each R 7 is independently a phenyl, benzyl, benzoyl, phenoxy or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted with C1-C4 alkyl, -C4 alkenyl, C -C4 alkynyl, C3-C6 cycloalkyl, C1-
• J is a phenyl group substituted with 1 to 2 R 5 and optionally substituted with 1 to 3 R 6 ; or J is selected from the group consisting of pyridine, pyrimidine, pyrazole, thiophene and thiazole, each optionally substituted with 1 to 3 R 7 ;
• R 3 is C 2 -C 4 alkyl optionally substituted with halogen, CN, OCH 3 , S(O) p CH 3 ;
• each R 4 is independently CH 3 , CF 3 , OCF 3 , OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 or halogen;
• each R5 is independently CF 3 , OCF 3 , OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 , OCH 2 CF 3 ,
• each R 6 is independently halogen or methyl; or phenyl, pyrazole, imidazole, triazole, pyridine or pyrimidine, each ring optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, halogen or CN; each R 7 is independently H, halogen, CH 3 , CF 3 , OCHF 2 , S(O) p CF 3 , S(O) p CHF 2 , OCH 2 CF 3 , OCF 2 CHF 2 , S(O) p CH 2 CF 3 , S(O) p CF 2 CHF 2 ; or phenyl, pyrazole, imidazole, triazole, pyridine or pyrimidine, each ring optionally substituted with C1-C4 alkyl, C 1 -C4
• J is a phenyl ring, a naphthyl ring system, a 5- or 6-membered heteroaromatic ring or an aromatic 8-, 9- or 10-membered fused heterobicyclic ring system wherein each ring or ring system is optionally substituted with 1 to 4 R 5 .
• the term "optionally substituted" in connection with these J groups 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.
• R 5 An example of phenyl optionally substituted with 1 to 4 R 5 is the ring illustrated as U-l in Exhibit 1, wherein R v is R 5 and r is an integer from 1 to 4.
• R v is R 5 and r is an integer from 1 to 4.
• R v is R 5 and r is an integer from 1 to 4.
• Examples of 5- or 6-membered heteroaromatic rings optionally substituted with 1 to 4 R 5 include the rings U-2 through U-53 illustrated in Exhibit 1 wherein R v is R 5 and r is an integer from 1 to 4.
• J-l through J-5 below also denote 5- or 6-membered heteroaromatic rings.
• U-2 through U-20 are examples of J-l
• U-21 through LI-35 and U-40 are examples of J-2
• U-36 through U-39 are examples of J-3
• U-41 through U-48 are examples of J-4
• LT-49 through U-53 are examples of J-5.
• Examples of aromatic 8-, 9- or 10-membered fused heterobicyclic ring systems optionally substituted with 1 to 4 R 5 include U-54 through LT-84 illustrated in Exhibit 1 wherein R v is R 5 and r is an integer from 1 to 4.
• R v groups are shown in the structures U-l through U-85, 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 some U groups can only be substituted with less than 4 R v groups (e.g.
• G groups include those illustrated as G-l through G-41 in Exhibit 2 wherein m is an integer from 1 to 4.
• the term "optionally substituted" in connection with these G groups 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.
• (R 12 ) m are illustrated in the examples, they need not be present since they are optional substituents. Note that when the attachment point on these G groups is illustrated as floating, the G group can be attached to the remainder of Formula I through any available carbon or nitrogen of the G 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 G comprises a ring selected from G-24 through G-29 and G-32 through G-35, A is selected from O, S, NH or NR 12 .
• R 3 can be (among others) Cj-Cg alkyl, C 2 -C6 alkenyl, C 2 -Cg alkynyl, C3-C6 cycloalkyl, each optionally substituted with one or more substituents selected from (among others) a phenyl, phenoxy or 5- or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents independently selected from R 6 .
• the tem "optionally substituted" in connection with these groups 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.
• substituents include the rings illustrated as U-l through U-53 and U-8S illustrated in Exhibit 1, except that such rings are optionally substituted with 1 to 3 substituents independently selected from R 6 rather than (R v ) r Note that R 6 substituents do not need to be present since they are optional substituents.
• each R 4 is independently (among others) a phenyl, benzyl, phenoxy or a 5- or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents independently selected from R 6 .
• the term "optionally substituted" in connection with these R 4 groups 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. Examples of such R 4 groups include the rings illustrated as U-l through U-53, U-86 and U-88 illustrated in Exhibit 1, except that such rings are optionally substituted with 1 to 3 substituents independently selected from R 6 rather than (R v ) r . Note that R 6 substituents do not need to be present since they are optional substituents.
• each R 5 is independently (among others) a phenyl, benzyl, benzoyl, phenoxy, 5- or 6-membered heteroaromatic ring or an aromatic S-, 9- or 10-membered fused heterobicyclic ring system, each ring optionally substituted with one to three substituents independently selected from R 6 .
• R 5 groups include the rings illustrated as U-l through U-88 illustrated in Exhibit 1, except that such rings are optionally substituted with 1 to 3 substituents independently selected from R 6 rather than (R v ) r . Note that R 6 substituents do not need to be present since they are optional substituents.
• K is, together with the two contiguous linking carbon atoms, a fused phenyl or a fused pyridinyl ring optionally substituted with 1 to 4 R 4 .
• the tenn "optionally substituted" in connection with these K groups 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. Examples of such K groups include the rings illustrated as K-l through K-5 in Exhibit 3. Note that K-2 through K-5 can be optionally substituted with one to three 3 R 4 groups.
• the wavy line indicates that the K-ring is attached to the remainder of Formula I as illustrated below.
• K-rings are K-l , K-2 and K-5. Most preferred is K-l .
• the compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-13.
• the definitions of B, J, K, R 3 , R 4 , R 5 and n in the compounds of Formulae I and 2-24 below are as defined above in the Summary of the Invention. Of note are compounds wherein K is K-l .
• Compounds of Formula lb (Formula I wherein B is O) can be prepared by procedures outlined in Schemes 1-13. A typical procedure is detailed in Scheme 1 and involves dehydration of an o-amido amide of Formula 2 with sodium hydride and ethyl chloro fomiate in a suitable solvent (See e.g. Example 1).
• Other methods for preparing compounds of Formula I include treating a compound of Formula 2 with acetic anhydride and sodium acetate, heating at greater than 70 °C neat or optionally in an appropriate solvent such as tetrahydrofuran, and treating 2 with a suitable acid scavenger and trimethylsilyl chloride in a suitable solvent. Further useful methods include heating o-amido amides of Formula 2 adsorbed on surface-active materials such as zeolites or clay, generally in the range of 50-150 °C. A specific example of this type is described in Example 2 and involves heating the anthranilic amide on Montmorillonite clay.
• Compounds of Formula Ic can be prepared by conventional methods for conversion of amides to thioamides such as by treatment with phosphorus pentasulfide or Lawesson's reagent. (See (Bull. Soc. Chim. Belg.), 1978, 87, 229; and (Tetrahedron Lett.), 1983, 24, 3815 for general procedures).
• Compounds of Formula 2 can be prepared by procedures outlined in Scheme 2.
• a typical procedure involves coupling of an o-amino amide of Formula 3 with an acid chloride of Formula 4 in the presence of an acid scavenger to provide the compound of Formula 2.
• Typical acid scavengers include amine bases such as triethylamine, diisopropylethylamine and pyridine; other scavengers include hydroxides such as sodium and potassium hydroxide and carbonates such as sodium carbonate and potassium carbonate.
• polymer-supported acid scavengers such as polymer-bound diisopropylethylamine and polymer-bound dimethylaminopyridine.
• An alternate procedure for the preparation of compounds of Formula 2 involves coupling of an o-amino amide of Formula 3 with an acid of Formula 5 in the presence of a dehydrating agent such as dicyclohexylcarbodiimide (DCC).
• a dehydrating agent such as dicyclohexylcarbodiimide (DCC).
• DCC dicyclohexylcarbodiimide
• Polymer supported reagents can be useful here, such as polymer-bound cyclohexylcarbodiimide.
• acid chlorides of Formula 4 may be prepared from acids of Formula 5 by numerous well-known methods.
• Formula 3 o- Amino amides are typically available from the corresponding o-nitro amides of Formula 6 via catalytic hydrogenation of the nitro group. Typical procedures involve reduction with hydrogen in the presence of a metal catalyst such as palladium on carbon or platinum oxide and in hydroxylic solvents such as ethanol and isopropanol. These procedures are well documented in the chemical literature.
• the intermediate amides of Formula 6 are readily prepared from commercially available o-nitro acids of Formula 7. Typical methods for amide formation can be applied here. These include direct dehydrative coupling of acids of Fo ⁇ nula 7 with amines of Formula 8 using for example DCC, and conversion of the acids to an activated form such as the'acid chlorides or anhydrides and subsequent coupling with amines to form amides of Formula 6. Ethylchloro formate is an especially useful reagent for this type of reaction. Scheme 5
• hitermediate o-amino amides of Formula 3 may also be prepared from anhydrides of Fomiula 9 (Scheme 6). Typical procedures involve combination of equimolar amounts of the amine 8 with the anhydride of Fomiula 9 in polar aprotic solvents such as pyridine and dimethylformamide at temperatures ranging from room temperature to 100 °C.
• polar aprotic solvents such as pyridine and dimethylformamide
• An alternate procedure for the preparation of compounds of Formula 2 involves reaction of an amine 8 with a compound of Formula 10.
• Typical procedures involve combination of the amine with the compound of Formula 10 in solvents such as tetrahydrofuran or pyridine at temperatures ranging from room temperature to the reflux temperature of the solvent.
• solvents such as tetrahydrofuran or pyridine
• Benzoxazinones are well documented in the chemical literature and are available via known methods that involve the coupling of either an anthranilic acid or an isatoic anhydride with an acid chloride.
• Compounds of Fo ⁇ nula I may also be prepared by modification of known procedures (J. Med. Chem. 1985, 28, 568). Usually this involves condensation of an aryl aldehyde of Formula 11 with a compound of Formula 3 in an alcoholic solvent and with a catalytic amount of base to produce intem ediate 12, which is then further oxidized to the Formula I compound by known methods. This reaction is shown in Scheme 8.
• Preferred catalysts for the synthesis of compounds of Formula Id include but are not limited to Pd(PPh 3 ) , PdCl 2 (PPh 3 ) 2 , PdCl 2 (diphenyl ⁇ hosphinoferrocene), NiCl (PPh 3 )2, and Tetrakis(tri-2- furylphosphino)palladium.
• Pd(PPh 3 ) PdCl 2 (PPh 3 ) 2
• PdCl 2 (diphenyl ⁇ hosphinoferrocene) NiCl (PPh 3 )2, and Tetrakis(tri-2- furylphosphino)palladium.
• the exact conditions for each reaction depend upon the catalyst used and the metal attached to the pyrazole.
• the additional presence of an external base is necessary for reactions involving pyrazoles of Formula 14 where Met is B(OH) 2 . Similar procedures also can be used for other K-rings and J-groups.
• Pyrazoles of Formula 14 can be made by lithiation of the pyrazole 17 followed by transmetallation with the appropriate metal as described in Scheme 10.
• Pyridylpyrazoles 17 are prepared by the reaction of pyrazoles 15 with a 2,3-dihalopyridine of Formula 16 to afford the 1 -pyridylpyrazole 17 with good specificity for the desired regiochemistry.
• Metallation of 17 with lithium diisopropylamide (LDA) followed by transmetallation with the appropriate metal affords the metal pyrazole of Formula 14.
• LDA lithium diisopropylamide
• For conditions and catalysts used in transmetallation and cross coupling reactions see Metal-catalyzed Cross-coupling Reactions. Diederich, Francois; Stang, Peter J.; Editors. 1998, p. 517, (Wiley-VCH, Weinheim, Germany) and references cited therein.
• the starting pyrazoles 15 are known compounds. Pyrazole 15 wherein R 5 is CF3 is commercially available. Pyrazoles 15 wherein R 5 is Cl or Br can be prepared by literature procedures (Chem. Ber. 1966, 99(10), 3350-7). A useful alternative method for the preparation of 15 wherein R 5 is Cl or Br is depicted in Scheme 11. Metallation of the sulfamoyl pyrazole 19 with ⁇ -butyllithium followed by direct halogenation of the anion with either hexachloroethane (for R 5 being Cl) or 1,2-dibromotetrachloroethane (for R 5 being Br) affords the halogenated derivatives 20.
• the benzoxazinones of Formula 21 are available by the method of Scheme 13. Coupling of a pyrazole acid of Fomiula 23 with an anthranilic acid of Formula 24 via sequential addition of methanesulfonyl chloride and triethylamine affords the benzoxazinone of Fomiula 21.
• the intermediate acid of Formula 23 is available from the lithiated pyrazole 18 by quenching with carbon dioxide. Similar procedures also can be used for other K-rings and J-groups.
• Step C Preparation of S,S-dimethyl-N-[4-(trifluoromethyl)phenyllsulfilimine
• N-chlorosuccinimide (12.43 g, 93.1 mmol) in -170 mL of dichloromethane was added to a mixture of 4-(trifluoromethyl) aniline (15 g, 93.1 mmol) and dimethyl sulphide (6.35 g, 102 mmol) in 230 mL of dichloromethane at -5 to 0 °C.
• N-chlorosuccinimide (0.02 g, 4.64 mmol) was added. After a further 30 minutes, the mixture was washed with 500 mL of IN sodium hydroxide.
• Raney nickel 500 g wet paste, ⁇ 50 ⁇ was added portionwise to a solution of 2-[(methylthio)methyl]-4-(trifluoromethyl)benzenamine (55.3 g, 0.25 mole) in 1 L of ethanol over 30 minutes at 25-30 °C. The heterogeneous mixture was stirred vigorously for
• This diazonium salt solution was then added portionwise via cannula to a stirred, 95 °C mixture of potassium cyanide (22 g, 0.34 mole), copper sulfate pentahydrate (20 g, 80 mmol) and 140 mL of water. After the addition the mixture was stirred for 30 minutes at 95 °C and then allowed to cool to room temperature. Ether was added and the heterogeneous mixture was filtered through celite. The solids were washed with ether, and the filtrate was partitioned. The aqueous phase was extracted with ether, and the combined organic extracts were dried over magnesium sulfate and concentrated under reduced pressure to afford 13.1 g of the title compound as a brown oil.
• *H NMR (CDCI3) ⁇ 7.74 (d,lH), 7.60 (s,lH), 7.55 (d,lH), 2.64 (s,3H).
• Step I Preparation of 2-methyl-N-[2-methyl-6-[ ( l-methylethyl)amino]- carbonyl1phenyl1-4-(trifluoromethyl)benzamide
• the benzoyl chloride of Step H (0.29 g, 1.3 mmol) was added to a mixture of the aniline from Step B (0.36 g, 1.9 mmol) and diisopropylethylamine (0.26 g, 2.0 mmol) in 10 mL of chloro fo ⁇ n at room temperature. The reaction was allowed to stir overnight. The solid precipitate was filtered and dried to afford 0.38 g of the title compound, as a solid melting at 247-248 °C.
• Step C Preparation of l-(3-chloro-2-pyridinyl ' )-3-(trifluoromethyl -lH-pyrazole-5- carboxylic acid
• a solution of the pyrazole product from Step B (105.0 g, 425 mmol) in dry tetrahydrofuran (700 mL) at -75 °C was added via cannula a -30 °C solution of lithium diisopropylamide (425 mmol) in dry tetrahydrofuran (300 mL).
• the deep red solution was stirred for 15 minutes, after which time carbon dioxide was bubbled through at -63 °C until the solution became pale yellow and the exothermicity ceased.
• the reaction was stirred for an additional 20 minutes and then quenched with water (20 mL).
• the solvent was removed under reduced pressure, and the reaction mixture partitioned between ether and 0.5 ⁇ aqueous sodium hydroxide solution.
• the aqueous extracts were washed with ether (3x), filtered through Celite® diatomaceous filter aid to remove residual solids, and then acidified to a p ⁇ of approximately 4, at which point an orange oil formed.
• the aqueous mixture was stirred vigorously and additional acid was added to lower the p ⁇ to 2.5-3.
• Step D Preparation of 6-chloro-2-[T -(3-chloro-2-pyridinyl)-3-(trifluoiOmethyl)-lH- pyrazol-5-yl "
• acetonitrile 75 mL
• reaction temperature was then maintained at 0 °C throughout successive addition of reagents.
• 2-amino-3-methyl-5-chlorobenzoic acid from Step A (5.1 g, 27.0 mmol) was added and stirring was continued for an additional 5 minutes.
• a solution of triethylamine (7.5 mL, 54.0 mmol) in acetonitrile (15 mL) was then added dropwise, and the reaction mixture was stirred 45 minutes, followed by the addition of methanesulfonyl chloride (2.2 mL, 28.3 mmol).
• the reaction mixture was then warmed to room temperature and stirred overnight.
• Approximately 75 mL of water was then added to precipitate 5.8 g of a yellow solid.
• An additional 1 g of product was isolated by extraction from the filtrate to provide a total of 6.8 g of the title compound as a yellow solid.
• Step E Preparation of N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl " j-l-(3- chloro-2-pyridinyl)-3-(trifluoromethyl -lH-pyrazole-5-carboxamide
• Step F Preparation of 6-chloro-2-[l-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-lH- pyrazol-5-vH-3,8-dimethyl-4(3H)-quinazoline
• Step A Preparation of 8-chloro-2-[ l-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-lH- p yrazol-5-yll -4H-3 , 1 -benzoxazin-4-one
• Step D Application of the procedure of Example 2, Step D with 2.91 g of the carboxylic acid of Example 2, Step C and 1.71 g of 2-amino-3-chlorobenzoic acid affords 2.5 g of the title benzoxazinone.
• Step B Preparation of 8-chloro-2-[T -(3-chloro-2-pyridinyl)-3-(trifluoromethylV 1H- pyrazol-5-yll-3-methyl-4(3H -quinazolinone
• methylamine 2.0 M solution in T ⁇ F, 10 mL
• the solvent was removed under reduced pressure and the solid residue was washed with ether.
• the ether soluble material was purified by chromatography on silica gel using hexanes/ethyl acetate (1 : 1) as eluant.
• the title compound, a compound of the invention was isolated as a solid, m.p. 155-157 °C. ! ⁇ NMR (CDC1 3 ) ⁇ 3.8 (s,3 ⁇ ), 7.1 (s,lH), 7.4 (m,2H). 7.7 (d,lH), 7.9 (d,lH), 8.15 (d,lH), 8.35 (m,lH).
• Me is methyl, Et is ethyl, Pr is propyl, z ' -Pr is isopropyl, t-Bu is tert butyl, Ph is phenyl, OMe is methoxy, OEt is ethoxy, SMe is methylthio, SEt is ethylthio, CN is cyano, NO 2 is nitro, TMS is trimethylsilyl, S(O)Me is methylsulfinyl, and S(O) 2 Me is methylsulfonyl.
• R 5b is Cl
• R 5b is CF 3
• R 5b is OCF3
• R 5b is CF(CF 3 ⁇ -
• R 5b is Cl
• R 5b is CF 3
• R 5b is OCF3
• R 5b is CF(CF 3 ⁇
• R 5b is CHF-> R 5b is CH 2 CF 3 R 5b is CFoCHFo

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• Plural Heterocyclic Compounds (AREA)

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• 2001
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  • 2001-12-03 JP JP2002549646A patent/JP2004515543A/ja not_active Withdrawn
  • 2001-12-03 WO PCT/US2001/046629 patent/WO2002048115A2/en not_active Application Discontinuation

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