WO2011056463A2 - Fungicidal mixtures - Google Patents

Fungicidal mixtures Download PDF

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Publication number
WO2011056463A2
WO2011056463A2 PCT/US2010/053679 US2010053679W WO2011056463A2 WO 2011056463 A2 WO2011056463 A2 WO 2011056463A2 US 2010053679 W US2010053679 W US 2010053679W WO 2011056463 A2 WO2011056463 A2 WO 2011056463A2
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WO
WIPO (PCT)
Prior art keywords
fungicides
pyridinyl
methyl
chloro
meo
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PCT/US2010/053679
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French (fr)
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WO2011056463A3 (en
WO2011056463A4 (en
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Vann Gregory
Andrew Edmund Taggi
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E. I. Du Pont De Nemours And Company
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Publication of WO2011056463A2 publication Critical patent/WO2011056463A2/en
Publication of WO2011056463A3 publication Critical patent/WO2011056463A3/en
Publication of WO2011056463A4 publication Critical patent/WO2011056463A4/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—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
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-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
    • A01N43/48—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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3

Definitions

  • This invention relates to fungicidal mixtures of certain imidazole derivatives, their N-oxides and salts, and to compositions comprising such mixtures and methods for using such mixtures as fungicides.
  • plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. In addition to often being highly destructive, plant diseases can be difficult to control and may develop resistance to commercial fungicides. Combinations of fungicides are often used to facilitate disease control, to broaden spectrum of control and to retard resistance development. Furthermore, certain rare combinations of fungicides demonstrate a greater-than-additive (i.e. synergistic) effect to provide commercially important levels of plant disease control.
  • This invention relates to a fungicidal composition (i.e. combination) comprising (a) at least one compound selected from the compounds of Formula 1 (including all stereoisomers), N-oxides, and salts thereof:
  • 1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl,
  • Q 2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 4 substituents independently selected from R 5 on carbon atom ring members and R 6 on nitrogen atom ring members;
  • R 1 and R 2 are independently halogen, cyano, nitro, Ci-C ⁇ alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, cyclopropyl, Ci-C ⁇ haloalkyl, C 2 -C 3 haloalkenyl, Ci-C ⁇ alkoxy, Ci-C ⁇ haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio or C ⁇ -C 7 hydroxyalkyl;
  • each R 3 and R 5 is independently halogen, cyano, hydroxy, nitro, C1-C7 alkyl, C 2 -C 7 alkenyl, C 2 -C 7 alkynyl, C 2 -C 7 cyanoalkyl, C ⁇ -C 7 haloalkyl, C 2 -C 7 haloalkenyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halocycloalkyl, C 4 -C 10 alkylcycloalkyl, C 4 -C 10 cycloalkylalkyl, C 6 -C 14 cycloalkylcycloalkyl, C 3 -C 7 cycloalkoxy, C 3 -C 7 halocycloalkoxy, -C7 alkoxy, C 2 -C 7 cyanoalkoxy, C1-C7 haloalkoxy, C j -Cg alkylthio, -C7 haloalkyl
  • dialkylamino C 2 -C7 alkylcarbonyl, C 2 -C7 alkoxycarbonyl, aminocarbonyl, C 2 -C7 alkylaminocarbonyl, C 3 -C7 dialkylaminocarbonyl, C 2 -C7
  • each R 4 and R 6 is independently cyano, C j -Cg alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C j -Cg haloalkyl, C 3 -C 6 cycloalkyl, C j -Cg alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -Cg alkoxycarbonyl, C 2 -Cg alkylaminoalkyl or C 3 -Cg dialkylaminoalkyl;
  • each R 7 is independently H, C j -Cg alkyl, C j -Cg haloalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 (alkylthio)carbonyl, C 2 -C 6 alkoxy(thiocarbonyl), C 4 -C 8 cycloalkylcarbonyl, C 4 -Cg cycloalkoxycarbonyl, C 4 -Cg (cycloalkylthio)carbonyl or C 4 -C 8 cycloalkoxy(thiocarbonyl);
  • each R 8a and R 8b is independently H, C j -Cg alkyl, -Cg haloalkyl, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 (alkylthio)carbonyl, C 2 -C 6 alkoxy(thiocarbonyl), C 4 -C 8 cycloalkylcarbonyl, C 4 -C 8 cycloalkoxycarbonyl, C 4 -C 8
  • each R 9 and R 10 is independently H, C j -Cg alkyl, -Cg haloalkyl, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 (alkylthio)carbonyl, C 2 -C 6 alkoxy(thiocarbonyl), C 4 -C 8 cycloalkylcarbonyl, C 4 -C 8 cycloalkoxycarbonyl, C 4 -C 8
  • each n is independently 0, 1 or 2;
  • This invention also relates to a composition
  • a composition comprising: (a) at least one compound selected from the compounds of Formula 1 described above, N-oxides, and salts thereof; and at least one invertebrate pest control compound or agent.
  • This invention also relates to a composition
  • a composition comprising one of the aforesaid compositions comprising component (a) and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • This invention also relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of one of the aforesaid compositions.
  • the aforedescribed method can also be described as a method for protecting a plant or plant seed from diseases caused by fungal pathogens comprising applying a fungicidally effective amount of one of the aforesaid compositions to the plant (or portion thereof) or plant seed (directly or through the environment (e.g., growing medium) of the plant or plant seed).
  • this invention also relates to a compound selected from the compounds of Formula 1 (including all stereoisomers), N-oxides, and salts thereof, as defined above provided that
  • Q 1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 4 substituents independently selected from R 3a on carbon atom ring members and R 4a on nitrogen atom ring members;
  • each R 3a is independently halogen, cyano, hydroxy, nitro, -C7 alkyl, C 2 -C 7 alkenyl, C 2 -C 7 alkynyl, C ⁇ -C 7 haloalkyl, C 2 -C 7 haloalkenyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halocycloalkyl, C 4 -C 10 alkylcycloalkyl, C 4 -C 10 cycloalkylalkyl, C 6 -C 14 cycloalkylcycloalkyl, C 3 -C 7 cycloalkoxy, C 3 -C 7 halocycloalkoxy, C1-C7 alkoxy, C ⁇ -C 7 haloalkoxy, C ⁇ -Cg alkylthio, C1-C7 haloalkylthio, C1-C7 alkylsulfmyl, -C7 alkylsulfony
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising a fungicidally effective amount of a compound selected from the compounds of the aforedescribed further aspect and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound selected from the compounds of the aforedescribed further aspect (e.g., as a composition described herein).
  • compositions, mixture, process or method 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 or method.
  • plant includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds).
  • Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
  • seedling used either alone or in a combination of words means a young plant developing from the embryo of a seed.
  • alkylating agent refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to a leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom. Unless otherwise indicated, the term “alkylating” does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified, for example, for R 1 and R 2 .
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl, pentyl, hexyl or heptyl isomers.
  • Alkenyl includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl, hexenyl and heptenyl 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, hexynyl and heptynyl isomers.
  • Alkynyl can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
  • Alkylene denotes a straight-chain or branched alkanediyl.
  • alkylene examples include CH 2 , CH 2 CH 2 , CH(CH 3 ), CH 2 CH 2 CH 2 , CH 2 CH(CH 3 ) and the different butylene, pentylene and hexylene isomers.
  • Alkynylene denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of “alkynylene” include CH 2 C ⁇ C, C ⁇ CCH 2 and the different butynylene, pentynylene and hexynylene isomers.
  • Alkoxy includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy, hexyloxy and heptyloxy isomers.
  • Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio, hexylthio and heptylthio isomers.
  • Alkylsulfmyl includes both enantiomers of an alkylsulfmyl group.
  • Alkylamino includes an NH radical substituted with straight-chain or branched alkyl. Examples of “alkylamino” include CH 3 CH 2 NH, CH 3 CH 2 CH 2 NH, and (CH 3 ) 2 CHCH 2 NH. Examples of “dialkylamino” include (CH 3 ) 2 N, (CH 3 CH 2 CH 2 ) 2 N and CH 3 CH 2 (CH 3 )N.
  • Cyanoalkyl denotes an alkyl group substituted with one cyano group. Examples of “cyanoalkyl” include NCCH 2 , NCCH 2 CH 2 and CH 3 CH(CN)CH 2 .
  • Alkoxyalkyl denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH 3 OCH 2 , 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 .
  • Alkylaminoalkyl denotes alkylamino substitution on alkyl.
  • alkylaminoalkyl examples include CH 3 NHCH 2 , CH 3 NHCH 2 CH 2 , CH 3 CH 2 NHCH 2 , CH 3 CH 2 CH 2 CH 2 NHCH 2 and CH 3 CH 2 NHCH 2 CH 2 .
  • dialkylaminoalkyl examples include ((CH 3 ) 2 CH) 2 NCH 2 , (CH 3 CH 2 CH 2 ) 2 NCH 2 and CH 3 CH 2 (CH 3 )NCH 2 CH 2 .
  • Hydroxyalkyl denotes an alkyl group substituted with one hydroxy group.
  • Examples of “hydroxyalkyl” include HOCH 2 CH 2 , CH 3 CH 2 (OH)CH and HOCH 2 CH 2 CH 2 CH 2 .
  • Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
  • alkylcycloalkyl denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, z ' -propylcyclobutyl, methylcyclopentyl and methylcyclohexyl.
  • cycloalkylalkyl denotes cycloalkyl substitution on an alkyl moiety.
  • cycloalkylalkyl examples include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups.
  • cycloalkylcycloalkyl denotes cycloalkyl substitution on another cycloalkyl ring, wherein each cycloalkyl ring independently has from 3 to 7 carbon atom ring members.
  • cycloalkylcycloalkyl examples include cyclopropylcyclopropyl (such as ⁇ , ⁇ -bicyclopropyl-l-yl, ⁇ , ⁇ - bicyclopropyl-2-yl), cyclohexylcyclopentyl (such as 4-cyclopentylcyclohexyl) and cyclohexylcyclohexyl (such as ⁇ , ⁇ -bicyclohexyl-l-yl), and the different cis- and trans- cycloalkylcycloalkyl isomers, (such as (li?,25)-l,l'-bicyclopropyl-2-yl and (1R,2R)-1,1'- bicyclopropyl-2-yl).
  • cycloalkylcycloalkyl examples include cyclopropylcyclopropyl (such as ⁇ , ⁇ -bicyclopropyl-l-yl, ⁇ , ⁇ - bicyclopropyl
  • cycloalkoxy denotes cycloalkyl attached to and linked through an oxygen atom including, for example, cyclopentyloxy and cyclohexyloxy.
  • cycloalkylene denotes a cycloalkanediyl ring.
  • cycloalkylene examples include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene.
  • cycloalkenylene denotes a cycloalkenediyl ring containing one olefmic bond.
  • Examples of “cycloalkenylene” include cylopropenediyl and cyclpentenediyl.
  • Trialkylsilyl includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom, such as trimethylsilyl, triethylsilyl and tert-butyldimethylsilyl.
  • 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, C1CH 2 , CF 3 CH 2 and CF 3 CC1 2 .
  • haloalkoxy include CF 3 0, CC1 3 CH 2 0, F 2 CHCH 2 CH 2 0 and CF 3 CH 2 0.
  • haloalkylthio examples include CC1 3 S, CF 3 S, CC1 3 CH 2 S and C1CH 2 CH 2 CH 2 S.
  • halocycloalkyl examples include 2-chlorocyclopropyl, 2-fluorocyclobutyl, 3-bromocyclopentyl and 4-chlorocyclohexyl.
  • fluoroalkyl fluoromethyl
  • fluoroalkoxy fluoroalkoxy
  • fluoromethoxy includes CH 2 FO, CHF 2 0 and CF 3 0.
  • C1-C4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2
  • C 3 alkoxyalkyl designates, for example, 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 .
  • the number of optional substituents may be restricted by an expressed limitation.
  • the phrase "optionally substituted with up to 4 substituents selected from R 3 on carbon atom ring members and R 4 on nitrogen atom ring members” means that 0, 1, 2, 3 or 4 substituents can be present (if the number of potential connection points allows).
  • a range specified for the number of substituents exceeds the number of positions available for substituents on a ring, the actual higher end of the range is recognized to be the number of available positions.
  • an instance of Q 1 or Q 2 comprises a phenyl, pyridinyl, pyridazinyl, pyrimidinyl or quinolinyl ring
  • the ortho, meta and para positions of each ring is relative to the connection of the ring to the remainder of Formula 1.
  • an instance of Q 1 or Q 2 comprises a phenyl ring attached through the linker CH 2 (i.e. benzyl) to the remainder of Formula 1
  • the ortho, meta and para positions of the phenyl ring is relative to the connection of the ring to the linker CH 2 .
  • 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 stereo isomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the compounds of the invention may be present as a mixture of stereoisomers or as individual stereoisomers (e.g., in optically active form).
  • atropisomers are conformational isomers that occur when rotation about a single bond in a molecule is restricted as a result of steric interaction with other parts of the molecule and the substituents at both ends of the single bond are unsymmetrical.
  • Atropisomerism occurs at a single bond in Formula 1 when the rotational barrier is high enough (about AG > 25 kcal moH) that separation of isomers at ambient temperature becomes possible.
  • one atropisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other atropisomer or when separated from the other atropisomer.
  • the skilled artisan knows how to separate, enrich, and/or to selectively prepare said atropisomers.
  • a detailed description of atropisomers can be found in March, Advanced Organic Chemistry, 4th Ed. 1992, 101-102 and Gawronski et al, Chirality 2002, 14, 689-702.
  • This invention includes compounds or compositions that are enriched in an atropisomer of Formula 1 compared to other atropisomers of the compounds. Also included are the essentially pure atropisomers of compounds of Formula 1.
  • 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.
  • 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 m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.
  • MCPBA peroxy acids
  • alkyl hydroperoxides such as t-butyl hydroperoxide
  • sodium perborate sodium perborate
  • dioxiranes such as dimethyldioxirane
  • salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms.
  • the salts of the compounds of Formula 1 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 present invention relates to compounds selected from Formula 1, N-oxides and agriculturally suitable salts thereof.
  • Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts.
  • Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types).
  • polymorph refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice.
  • polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability.
  • a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1.
  • Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
  • an aspect of the present invention is directed at a composition
  • a composition comprising (a) at least one compound selected from Formula 1, N-oxides, and salts thereof, with (b) at least one additional fungicidal compound. More particularly, Component (b) is selected from the group consisting of
  • N-phenyl carbamate fungicides N-phenyl carbamate fungicides
  • MBI-R melanin biosynthesis inhibitors-reductase
  • MBI-D melanin biosynthesis inhibitors-dehydratase
  • quinone inside inhibitor (Qil) fungicides quinone inside inhibitor (Qil) fungicides
  • glucopyranosyl antibiotic protein synthesis fungicides
  • glucopyranosyl antibiotic trehalase and inositol biosynthesis fungicides; cyanoacetamideoxime fungicides;
  • organo tin fungicides organo tin fungicides
  • pyrimidinamide fungicides (b40) carboxylic acid amide (CAA) fungicides;
  • component (b) comprises at least one fungicide from each of two different groups selected from (bl) through (b46).
  • Methyl benzimidazole carbamate (MBC) fungicides (bl) (FRAC (Fungicide Resistance Action Committee) code 1) inhibit mitosis by binding to ⁇ -tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure.
  • Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides.
  • the benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole.
  • the thiophanates include thiophanate and thiophanate-methy 1.
  • Dicarboximide fungicides (b2) (FRAC code 2) are proposed to inhibit a lipid peroxidation in fungi through interference with NADH cytochrome c reductase. Examples include chlozolinate, iprodione, procymidone and vinclozolin.
  • DMI Demethylation inhibitor fungicides
  • FRAC code 3 “Demethylation inhibitor (DMI) fungicides
  • Sterols such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides result in abnormal growth and eventually death of sensitive fungi.
  • DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines.
  • the triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole.
  • the imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz, pefurazoate and triflumizole.
  • the pyrimidines include fenarimol, nuarimol and triarimol.
  • the piperazines include triforine.
  • the pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
  • Phenylamide fungicides (b4) are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide.
  • Phenylamide fungicides include acylalanine, oxazolidinone and butyrolactone fungicides.
  • the acylalanines include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl, metalaxyl-M (also known as mefenoxam).
  • the oxazolidinones include oxadixyl.
  • the butyrolactones include ofurace.
  • Amine/morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine and spiroketal-amine fungicides.
  • the morpho lines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide.
  • the piperidines include fenpropidin and piperalin.
  • the spiroketal-amines include spiroxamine.
  • Phospholipid biosynthesis inhibitor fungicides (b6) (FRAC code 6) inhibit growth of fungi by affecting phospholipid biosynthesis.
  • Phospholipid biosynthesis fungicides include phosphorothiolate and dithiolane fungicides.
  • the phosphorothiolates include edifenphos, iprobenfos and pyrazophos.
  • the dithiolanes include isoprothiolane.
  • Carboxamide fungicides (b7) inhibit Complex II (succinate dehydrogenase) fungal respiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting respiration prevents the fungus from making ATP, and thus inhibits growth and reproduction.
  • Carboxamide fungicides include benzamide, furan carboxamide, oxathiin carboxamide, thiazole carboxamide, pyrazole carboxamide and pyridine carboxamide.
  • the benzamides include benodanil, flutolanil and mepronil.
  • the furan carboxamides include fenfuram.
  • the oxathiin carboxamides include carboxin and oxycarboxin.
  • the thiazole carboxamides include thifluzamide.
  • the pyrazole carboxamides include bixafen, furametpyr, isopyrazam, fluxapyroxad, penthiopyrad, sedaxane (N-[2-( 1 S,2R)-[ 1 , 1 '-bicyclopropyl] -2-ylphenyl] -3 -(difluoromethyl)- 1 -methyl- IH- pyrazole-4-carboxamide) and penflufen (N-[2-(l,3-dimethylbutyl)phenyl]-5-fluoro-l,3- dimethyl-lH-pyrazole-4-carboxamide) (PCT Patent Publication WO 2003/010149).
  • the pyridine carboxamides include boscalid.
  • Hydroxy(2-amino-)pyrimidine fungicides (b8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol and ethirimol.
  • Anilinopyrimidine fungicides (b9) (FRAC code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydro lytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.
  • N-Phenyl carbamate fungicides (blO)
  • FRAC code 10 inhibit mitosis by binding to ⁇ -tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.
  • Quadrature outside inhibitor (Qol) fungicides (bl l) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the "quinone outside" (Q 0 ) site of the cytochrome bc ⁇ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development.
  • Quinone outside inhibitor fungicides include methoxyacrylate, methoxycarbamate, oximino acetate, oximinoacetamide and dihydrodioxazine fungicides (collectively known as strobilurin fungicides), and oxazolidinedione, imidazolinone and benzylcarbamate fungicides.
  • the methoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) and picoxystrobin.
  • the methoxycarbamates include pyraclostrobin and pyrametostrobin.
  • the oximinoacetates include kresoxim-methyl, pyraoxystrobin and trifloxystrobin.
  • the oximinoacetamides include dimoxystrobin, metominostrobin, orysastrobin and a-(methoxyimino)-N-methyl-2-[[[l-[3-(trifluoro- methyl)phenyl]ethoxy]imino]methyl]benzeneacetamide.
  • the dihydrodioxazines include fluoxastrobin.
  • the oxazolidinediones include famoxadone.
  • the imidazolinones include fenamidone.
  • the benzylcarbamates include pyribencarb.
  • Phenylpyrrole fungicides (bl2) (FRAC code 12) inhibit a MAP protein kinase associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.
  • Quinoline fungicides (bl3) (FRAC code 13) are proposed to inhibit signal transduction by affecting G-proteins in early cell signaling. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powder mildew diseases. Quinoxyfen is an example of this class of fungicide.
  • Lipid peroxidation inhibitor fungicides (bl4) are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etridiazole, may also affect other biological processes such as respiration and melanin biosynthesis.
  • Lipid peroxidation fungicides include aromatic carbon and 1,2,4- thiadiazole fungicides.
  • the aromatic carbons include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos-methyl.
  • the 1,2,4-thiadiazoles include etridiazole.
  • Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides (bl5)) inhibit the naphthal reduction step in melanin biosynthesis.
  • Melanin is required for host plant infection by some fungi.
  • Melanin biosynthesis inhibitors-reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides.
  • the isobenzofuranones include fthalide.
  • the pyrroloquinolinones include pyroquilon.
  • the triazolobenzothiazoles include tricyclazole.
  • Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides.
  • the cyclopropanecarboxamides include carpropamid.
  • the carboxamides include diclocymet.
  • the propionamides include fenoxanil.
  • Haldroxyanilide fungicides (bl7) (FRAC code 17) inhibit C4-demethylase which plays a role in sterol production. Examples include fenhexamid.
  • Squalene-epoxidase inhibitor fungicides (bl8) (FRAC code 18) inhibit squalene- epoxidase in ergosterol biosynthesis pathway.
  • Sterols such as ergosterol are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore exposure to these fungicides result in abnormal growth and eventually death of sensitive fungi.
  • Squalene-epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides.
  • the thiocarbamates include pyributicarb.
  • the allylamines include naftifme and terbinafme.
  • Polyoxin fungicides (bl9) (FRAC code 19) inhibit chitin synthase. Examples include polyoxin.
  • Phenylurea fungicides (b20) (FRAC code 20) are proposed to affect cell division. Examples include pencycuron.
  • Quinone inside inhibitor (Qil) fungicides (b21) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol reductase. Reduction of ubiquinol is blocked at the "quinone inside” (Q j ) site of the cytochrome bc ⁇ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development.
  • Quinone inside inhibitor fungicides include cyanoimidazole and sulfamoyltriazole fungicides.
  • the cyanoimidazoles include cyazofamid.
  • the sulfamoyltriazoles include amisulbrom.
  • Benzamide fungicides (b22) inhibit mitosis by binding to ⁇ -tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include zoxamide.
  • Enopyranuronic acid antibiotic fungicides (b23)
  • FRAC code 23 inhibit growth of fungi by affecting protein biosynthesis. Examples include blasticidin-S.
  • Halopyranosyl antibiotic fungicides (b24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin.
  • Glucopyranosyl antibiotic: protein synthesis fungicides (b25) inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.
  • Glucopyranosyl antibiotic trehalase and inositol biosynthesis fungicides (b26)
  • FRAC code 26 inhibit trehalase in inositol biosynthesis pathway. Examples include validamycin.
  • Cyanoacetamideoxime fungicides (b27) (FRAC code 27) include cymoxanil.
  • “Carbamate fungicides (b28)” (FRAC code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, iodocarb, and prothiocarb are examples of this fungicide class.
  • Oxidative phosphorylation uncoupling fungicides (b29) (FRAC code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development.
  • This class includes 2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.
  • Organic tin fungicides (b30) (FRAC code 30) inhibit adenosine triphosphate (ATP) synthase in oxidative phosphorylation pathway.
  • examples include fentin acetate, fentin chloride and fentin hydroxide.
  • Carboxylic acid fungicides (b31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.
  • Heteroaromatic fungicides (b32) are proposed to affect DNA/ribonucleic acid (RNA) synthesis.
  • Heteroaromatic fungicides include isoxazole and isothiazolone fungicides.
  • the isoxazoles include hymexazole and the isothiazolones include octhilinone.
  • Phosphonate fungicides include phosphorous acid and its various salts, including fosetyl-aluminum.
  • Phthalamic acid fungicides (b34) include teclofthalam.
  • Benzotriazine fungicides (b35) include triazoxide.
  • Benzene-sulfonamide fungicides (b36)
  • FRAC code 36 include flusulfamide.
  • Phyridazinone fungicides (b37) include diclomezine.
  • Thiophene-carboxamide fungicides (b38) are proposed to affect ATP production. Examples include silthiofam.
  • Pyrimidinamide fungicides (b39) inhibit growth of fungi by affecting phospholipid biosynthesis and include diflumetorim.
  • Carboxylic acid amide (CAA) fungicides (b40) (FRAC code 40) are proposed to inhibit phospholipid biosynthesis and cell wall deposition. Inhibition of these processes prevents growth and leads to death of the target fungus.
  • Carboxylic acid amide fungicides include cinnamic acid amide, valinamide carbamate and mandelic acid amide fungicides.
  • the cinnamic acid amides include dimethomorph and flumorph.
  • the valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valifenalate (valiphenal).
  • the mandelic acid amides include mandipropamid, N-[2-[4-[[3-(4- chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]-ethyl]-3-methyl-2-[(methylsulfonyl)- amino]butanamide and N-[2-[4-[[3-(4-chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]- ethyl]-3-methyl-2-[(ethylsulfonyl)amino]-butanamide.
  • Tetracycline antibiotic fungicides (b41) (FRAC code 41) inhibit growth of fungi by affecting complex 1 nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examples include oxytetracycline .
  • Thiocarbamate fungicides (b42) include methasulfocarb.
  • Benzamide fungicides (b43) inhibit growth of fungi by derealization of spectrin-like proteins.
  • examples include acylpicolide fungicides such as fluopicolide and fluopyram.
  • Host plant defense induction fungicides include benzo-thiadiazole, benzisothiazole and thiadiazole-carboxamide fungicides.
  • the benzo-thiadiazoles include acibenzolar-S-methyl.
  • the benzisothiazoles include probenazole.
  • the thiadiazole- carboxamides include tiadinil and isotianil.
  • Multi-site contact fungicides (b45) inhibit fungal growth through multiple sites of action and have contact/preventive activity.
  • This class of fungicides includes: “copper fungicides (b45.1) (FRAC code Ml)", “sulfur fungicides (b45.2) (FRAC code M2)", “dithiocarbamate fungicides (b45.3) (FRAC code M3)", “phthalimide fungicides (b45.4) (FRAC code M4)", “chloronitrile fungicides (b45.5) (FRAC code M5)”, “sulfamide fungicides (b45.6) (FRAC code M6)", “guanidine fungicides (b45.7) (FRAC code M7)” “triazine fungicides (b45.8) (FRAC code M8)” and “quinone fungicides (b45.9) (FRAC code M9)”.
  • Copper fungicides are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate).
  • Sulfur fungicides are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur.
  • Dithiocarbamate fungicides contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram.
  • Phthalimide fungicides contain a phthalimide molecular moiety; examples include folpet, captan and captafol.
  • Chloronitrile fungicides contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil.
  • Sulfamide fungicides include dichlofluanid and tolylfluanid.
  • Guanidine fungicides include dodine, guazatine and iminoctadine.
  • Triazine fungicides include anilazine.
  • Quinone fungicides include dithianon.
  • “Fungicides other than fungicides of component (a) and components (bl) through (b45); (b46)” include certain fungicides whose mode of action may be unknown. These include: (b46.1) “thiazole carboxamide fungicides (FRAC code U5)”, (b46.2) “phenyl- acetamide fungicides (FRAC code U6)", (b46.3) “quinazolinone fungicides (FRAC code U7)", (b46.4) “benzophenone fungicides (FRAC code U8)” and (46.5) "triazolopyrimidylamine fungicides” (alternatively named “triazolopyrimidine fungicides”) (FRAC code 45).
  • the thiazole carboxamides include ethaboxam.
  • the phenyl-acetamides include cyflufenamid and N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3- difluorophenyl]-methylene]benzeneacetamide.
  • the quinazolinones include proquinazid and 2-butoxy-6-iodo-3-propyl-4H-l-benzopyran-4-one.
  • the benzophenones include metrafenone and pyriofenone.
  • the triazolopyrimidylamines include ametoctradin (5-ethyl- 6-octyl[l,2,4]triazolo[l,5-a]pyrimidin-7-amine) and are believed to inhibit Complex III mitochondrial respiration by binding to an unelucidated site on ubiquinone-cytochrome bcl reductase.
  • the (b46) class also includes bethoxazin, neo-asozin (ferric methanearsonate), fenpyrazamine, pyrrolnitrin, quinomethionate, tebufloquin, 2-[[2-fluoro-5-(trifluoromethyl)- phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile (OK-5203), 3-[5-(4- chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine (SYP-Z048), 4-fluorophenyl N-[l- [[ [ 1 -(4-cyanophenyl)ethyl] sulfonyl]methyl]propyl] carbamate (XR-539), N-(4-chloro-2-nitro- phenyl)-N-ethyl-4-methylbenzenesul
  • reference to Formula 1 includes N-oxides and salts thereof, and reference to "a compound of Formula 1" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments.
  • Embodiment 1 The composition comprising components (a) and (b) described in the Summary of the Invention wherein in Formula 1, R 1 and R 2 are independently halogen, cyano, Ci-C ⁇ alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, cyclopropyl, Ci-C ⁇ haloalkyl, C2-C3 haloalkenyl, C1 -C2 alkoxy, C 1 -C2 haloalkoxy, C1 -C2 alkylthio or Ci -C3 hydroxyalkyl.
  • R 1 and R 2 are independently halogen, cyano, Ci-C ⁇ alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, cyclopropyl, Ci-C ⁇ haloalkyl, C2-C3 haloalkenyl, C1 -C2 alkoxy, C 1 -C2 haloalkoxy, C
  • Embodiment 2 The composition of Embodiment 1 wherein R 1 and R 2 are
  • Embodiment 3 The composition of Embodiment 2 wherein R 1 and R 2 are
  • Embodiment 4 The composition of Embodiment 1 wherein R 1 and R 2 are
  • Embodiment 5 The composition of Embodiment 3 or 4 wherein R 1 and R 2 are
  • Embodiment 6 The composition of Embodiment 5 wherein R 1 and R 2 are
  • Embodiment 7 The composition comprising components (a) and (b) described in the
  • Q 1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 3 on carbon atom ring members and R 4 on nitrogen atom ring members.
  • Embodiment 8 The composition of Embodiment 7 wherein Q 1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 3 on carbon atom ring members and R 4 on nitrogen atom ring members.
  • Embodiment 9 The composition of Embodiment 8 wherein Q 1 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 3 on carbon atom ring members.
  • Embodiment 10 The composition of Embodiment 9 wherein Q 1 is a phenyl or
  • pyridinyl ring optionally substituted with up to 3 substituents independently selected from R 3 on carbon atom ring members.
  • Embodiment 1 1. The composition of Embodiment 9 or 10 wherein when Q 1 is an optionally substituted pyridinyl ring, the pyridinyl ring is attached to Formula 1 at the 3-position of the pyridinyl ring (i.e. 3-pyridinyl).
  • Embodiment 12 The composition of Embodiment 10 wherein Q 1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 3 .
  • Embodiment 13 The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 12 wherein in Formula 1, Q 2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 5 on carbon atom ring members and R 6 on nitrogen atom ring members.
  • Q 2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 5 on carbon atom ring members and R 6 on nitrogen atom ring members.
  • Embodiment 14 The composition of Embodiment 13 wherein Q 2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from
  • R 5 on carbon atom ring members and R 6 on nitrogen atom ring members.
  • Embodiment 15 The composition of Embodiment 14 wherein Q 2 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 5 on carbon atom ring members.
  • Embodiment 16 The composition of Embodiment 15 wherein Q 2 is a phenyl or
  • pyridinyl ring optionally substituted with up to 3 substituents independently selected from R 5 on carbon atom ring members.
  • Embodiment 17 The composition of Embodiment 15 or 16 wherein when Q 2 is an optionally substituted pyridinyl ring, the pyridinyl ring is attached to Formula 1 at the 3-position of the pyridinyl ring (i.e. 3-pyridinyl).
  • Embodiment 18 The composition of Embodiment 16 wherein Q 2 is a phenyl ring
  • Embodiment 19 The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 18 wherein in
  • Embodiment 20 The composition of Embodiment 19 wherein when Q 1 and Q 2 each independently comprise a phenyl or pyridinyl ring, then the ring of one of Q 1 and
  • Q 2 is substituted with 2 or 3 substituents and the ring of the other of Q 1 and Q 2 is substituted with 1 or 2 substituents.
  • Embodiment 21 The composition of Embodiment 20 wherein when Q 1 and Q 2 each independently comprise a phenyl or pyridinyl ring, then the ring of one of Q 1 and Q 2 is substituted with 2 or 3 substituents and the ring of the other of Q 1 and Q 2 is substituted with 1 substituent.
  • Embodiment 22 The composition comprising components (a) and (b) described in the
  • Embodiment 23 The composition comprising components (a) and (b) described in the
  • each R 3 and R 5 is independently halogen, cyano, Ci -C3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, C 1 -C3 haloalkyl, cyclopropyl, C1 -C3 alkoxy, C1 -C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl or C2-C4 alkylcarbonylamino.
  • Embodiment 24 is independently halogen, cyano, Ci -C3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, C 1 -C3 haloalkyl, cyclopropyl, C1 -C3 alkoxy, C1 -C3 haloalkoxy, C1-C
  • each R 3 and R 5 is independently halogen, cyano, Ci-C ⁇ alkyl, C 2 -C 3 alkenyl, Ci-C ⁇ haloalkyl, C1 -C3 alkoxy, C 1 -C3 haloalkoxy, C1 -C3 alkylthio or C1-C3 alkylamino.
  • Embodiment 25 The composition of Embodiment 24 wherein each R 3 and R 5 is
  • Embodiment 26 The composition of Embodiment 25 wherein each R 3 and R 5 is
  • Embodiment 27 The composition of Embodiment 26 wherein each R 3 and R 5 is
  • Embodiment 28 The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 27 wherein in Formula 1, each R 4 and R 6 is independently cyano, Ci -C3 alkyl or cyclopropyl.
  • Embodiment 29 The composition of Embodiment 28 wherein each R 4 and R 6 is
  • Embodiment 30 The composition of Embodiment 29 wherein independently each R 4 and R 6 is methyl.
  • Embodiment 31 The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 30 wherein in
  • each X is independently O or NR 7 .
  • Embodiment 32 The composition comprising components (a) and (b) described in the
  • each R 7 is H.
  • Embodiment 33 The composition comprising components (a) and (b) described in the
  • each U is independently C 2 -C 4 alkylene.
  • Embodiment 34 The composition comprising components (a) and (b) described in the
  • each Z is independently NR 8a R 8b or OR 9 .
  • Embodiment 35 The composition comprising components (a) and (b) described in the
  • each R 8a and R 8b is independently H, C j -Cg alkyl or C j -Cg haloalkyl.
  • Embodiment 36 The composition comprising components (a) and (b) described in the
  • each R 9 is independently H, C ⁇ -Cg alkyl or C ⁇ -Cg haloalkyl.
  • Embodiment 37 The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 27 wherein in Formula 1, the ring of one of Q 1 and Q 2 is a phenyl or 3-pyridinyl ring substituted at a meta or para position with one substituent selected from F, CI, methyl, methoxy and fluoromethoxy, and optionally substituted with one F at a remaining position; and the ring of the other of Q 1 and Q 2 is a phenyl ring substituted at both ortho positions with F and substituted at a meta or para position with a substituent selected from cyano and Ci -C2 alkoxy.
  • Embodiment 38 The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 27 and 37 wherein component (a) comprises a compound selected from the group consisting of
  • Embodiment 39 The composition of Embodiment 38 wherein component (a) comprises a compound selected from the group consisting of Compound 516, Compound
  • Embodiment 40 The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 39 wherein in Formula 1, when Q 2 is optionally substituted phenyl, and Q 1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R 20 , optionally substituted at the other ortho position with a substituent selected from halogen or R 20 , and optionally substituted at the para position with a substituent selected from halogen or R 20 , then at least one of the following conditions are true:
  • each R 20 is independently hydroxy, alkoxy, haloalkoxy, cycloalkoxy or -X-U-Z, wherein X is O, U is alkylene, Z is NR 8a R 8b or OR 9 , R 8a is H or alkyl, R 8 ⁇ is alkyl or cycloalkyl, and R 9 is alkyl.
  • Embodiment 41 The composition of Embodiment 40 wherein in Formula 1, when Q 2 is optionally substituted phenyl, and Q 1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R 20 , and optionally substituted at the other ortho position with a substituent selected from halogen or R 20 , then the Q 1 phenyl is substituted at the para position with a substituent other than halogen or R 20 .
  • Embodiment 42 The composition of Embodiment 41 wherein in Formula 1, when Q 2 is optionally substituted phenyl, and Q 1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R 20 , and optionally substituted at the other ortho position with a substituent selected from halogen or R 20 , then the Q 1 phenyl is substituted at the para position with cyano.
  • Embodiment 43 The composition of Embodiment 41 wherein in Formula 1, when Q 2 is optionally substituted phenyl, and Q 1 is a phenyl substituted at a first ortho position with halogen or R 20 , and optionally substituted at the other ortho position with a substituent selected from halogen or R 20 , then the Q 1 phenyl is substituted at the para position with a substituent other than halogen or R 20 .
  • Embodiment 44 The composition of Embodiment 43 wherein in Formula 1, when Q 2 is optionally substituted phenyl, and Q 1 is phenyl substituted at a first ortho position with halogen or R 20 , and optionally substituted at the other ortho position with a substituent selected from halogen or R 20 , then the Q 1 phenyl is substituted at the para position with cyano.
  • Embodiment 45 The composition of Embodiment 40 wherein in Formula 1, when Q 1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R 20 , optionally substituted at the other ortho position with a substituent selected from halogen or R 20 , and optionally substituted at the para position with a substituent selected from halogen or R 20 , then at least one of the following conditions are true:
  • Embodiment 46 The composition of Embodiment 45 wherein in Formula 1, when Q 1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R 20 , and optionally substituted at the other ortho position with a substituent selected from halogen or R 20 , then the Q 1 phenyl is substituted at the para position with a substituent other than halogen or R 20 .
  • Embodiment 47 The composition of Embodiment 46 wherein in Formula 1, when Q 1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R 20 , and optionally substituted at the other ortho position with a substituent selected from halogen or R 20 , then the Q 1 phenyl is substituted at the para position with cyano.
  • Embodiment 48 The composition of Embodiment 45 wherein in Formula 1, when Q 1 is phenyl substituted at a first ortho position with halogen or R 20 , and optionally substituted at the other ortho position with a substituent selected from halogen or
  • Embodiment 49 The composition of Embodiment 48 wherein in Formula 1, when Q 1 is phenyl substituted at a first ortho position with halogen or R 20 , and optionally substituted at the other ortho position with a substituent selected from halogen or
  • Embodiment 50 The composition comprising components (a) and (b) described in the
  • Embodiment 51 The composition of Embodiment 50 wherein in Formula 1, wherein when Q 1 is optionally substituted phenyl, then said Q 1 phenyl is substituted at the para position with cyano (and optionally substituted at other positions as specified in the Summary of the Invention and Embodiments).
  • Embodiment 52 The composition comprising components (a) and (b) described in the
  • Q 1 is phenyl substituted at the para position with cyano (and optionally substituted at other positions as specified in the Summary of the
  • Embodiment 53 The composition comprising components (a) and (b) described in the
  • component (a) consists of a compound selected from the group consisting of
  • component (b) comprises at least two fungicidal compounds.
  • Embodiments of this invention can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compositions comprising compounds of Formula 1 with at least one other fungicide but also to compositions comprising compounds of Formula 1 with at least one invertebrate pest control compound or agent, and also to the compounds of Formula 1 and their compositions, and also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula 1.
  • embodiments of this invention including Embodiments 1-53 above as well as any other embodiments described herein, and any combination thereof, pertain to the methods of the present invention.
  • Embodiment Al The composition comprising components (a) and (b) described in the Summary of the Invention wherein in Formula 1,
  • Q 1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 3 on carbon atom ring members and R 4 on nitrogen atom ring members;
  • Q 2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 5 on carbon atom ring members and R 6 on nitrogen atom ring members; and
  • R 1 and R 2 are independently halogen, cyano, ethenyl, ethynyl, methoxy or methylthio; or methyl optionally substituted with one substituent selected from halogen, -OH and methyl.
  • Embodiment A2 The composition of Embodiment Al wherein in Formula 1,
  • Q 1 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 3 on carbon atom ring members;
  • Q 2 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R 5 on carbon atom ring members;
  • each R 3 and R 5 is independently halogen, cyano, Ci -C3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, C1 -C3 haloalkyl, cyclopropyl, C1 -C3 alkoxy, C 1 -C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino, C 2 -C 4 alkylcarbonyl, C 2 -C 4 alkoxycarbonyl or C 2 -C 4 alkylcarbonylamino.
  • Embodiment A3 The composition of Embodiment A2 wherein in Formula 1,
  • Q 1 is a phenyl or 3 -pyridinyl ring optionally substituted with up to 3
  • Q 2 is a phenyl or 3 -pyridinyl ring optionally substituted with up to 3
  • Embodiment A4 The composition of Embodiment A3 wherein in Formula 1,
  • R 1 and R 2 are independently halogen, cyano or methoxy; or methyl optionally substituted with one substituent selected from F, CI or methyl; and each R 3 and R 5 is independently halogen, cyano, Ci-C ⁇ alkyl, C 2 -C 3 alkenyl, 1 -C3 haloalkyl, C1-C3 alkoxy, C 1 -C3 haloalkoxy, C1 -C3 alkylthio or
  • Embodiment A5 The composition of Embodiment A4 wherein in Formula 1,
  • R 1 and R 2 are independently CI, Br, I or Ci-C 2 alkyl
  • each R 3 and R 5 is independently F, CI, Br, cyano, Ci -C2 alkyl, Ci-C 2 haloalkyl, Ci -C2 alkoxy or Ci -C2 haloalkoxy;
  • Embodiment A6 The composition of Embodiment A5 wherein in Formula 1,
  • R 1 and R 2 are independently CI, Br or methyl
  • the ring of one of Q 1 and Q 2 is a phenyl or 3-pyridinyl ring substituted at a meta or para position with one substituent selected from F, CI, methyl, methoxy and fluoromethoxy, and optionally substituted with one F at a remaining position; and
  • the ring of the other of Q 1 and Q 2 is a phenyl ring substituted at both ortho positions with F and substituted at a meta or para position with a substituent selected from cyano and Ci -C2 alkoxy.
  • Embodiment A7 The composition of Embodiment A6 wherein component (a)
  • Embodiment B 1. The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl) methyl benzimidazole carbamate fungicides such as benomyl, carbendazim and thiophanate -methyl.
  • Embodiment B2 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b2) dicarboximide fungicides such as procymidone, iprodione and vinclozolin.
  • Embodiment B The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b3) demethylation inhibitor fungicides such as epoxiconazole, fluquinconazole, triadimenol, simeconazole, ipconazole, triforine, cyproconazole, difenconazole, flusilazole, flutriafol, metconazole, myclobutanil, prochloraz, propiconazole, prothioconazole, tebuconazole and tetraconazole.
  • demethylation inhibitor fungicides such as epoxiconazole, fluquinconazole, triadimenol, simeconazole, ipconazole, triforine, cyproconazole, difenconazole, flusilazole, flutriafol, metconazole, myclobutanil, prochloraz, propiconazole, prothioconazole, tebu
  • Embodiment B The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b4) phenylamide fungicides such as metalaxyl, metalaxyl-M, benalaxyl, benalaxyl-M, furalaxyl, ofurace and oxadixyl.
  • phenylamide fungicides such as metalaxyl, metalaxyl-M, benalaxyl, benalaxyl-M, furalaxyl, ofurace and oxadixyl.
  • Embodiment B5. The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b5) amine/morpholine fungicides such as aldimorph, dodemorph, fenpropimorph, tridemorph, trimorphamide, fenpropidin, piperalin and spiroxamine.
  • amine/morpholine fungicides such as aldimorph, dodemorph, fenpropimorph, tridemorph, trimorphamide, fenpropidin, piperalin and spiroxamine.
  • Embodiment B6 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b6) phospholipid biosynthesis inhibitor fungicides such as edifenphos and isoprothiolane.
  • Embodiment B7 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b7) carboxamide fungicides such as bixafen, boscalid, carboxin, isopyrazam, oxycarboxin, penflufen and penthiopyrad.
  • carboxamide fungicides such as bixafen, boscalid, carboxin, isopyrazam, oxycarboxin, penflufen and penthiopyrad.
  • Embodiment B8 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b8) hydroxy(2-amino-)pyrimidine fungicides such as ethirimol.
  • Embodiment B9 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b9) anilinopyrimidine fungicides such as cyprodinil.
  • Embodiment BIO The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (blO) N-phenyl carbamate fungicides such as diethofencarb.
  • Embodiment B 11 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl 1) quinone outside inhibitor fungicides such as azoxystrobin, pyraclostrobin, pyrametostrobin, kresoxim-methyl, trifloxystrobin, picoxystrobin, pyraoxystrobin, pyribencarb, famoxadone, fenamidone, discostrobin, enestrobin, dimoxystrobin, metominostrobin, orysastrobin and fluoxastrobin.
  • quinone outside inhibitor fungicides such as azoxystrobin, pyraclostrobin, pyrametostrobin, kresoxim-methyl, trifloxystrobin, picoxystrobin, pyraoxystrobin, pyribencarb, famoxadone, fenamidone, discostrobin, enestrobin, dimoxystrobin, metominostrobin, orysastrobin and
  • Embodiment B 12 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl2) phenylpyrrole fungicides compound such as fenpiclonil and fludioxonil.
  • Embodiment B 13 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl3) quinoline fungicides such as quinoxyfen.
  • Embodiment B 14 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl4) lipid peroxidation inhibitor fungicides such as chloroneb.
  • Embodiment B 15. The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl5) melanin biosynthesis inhibitors-reductase fungicides such as pyroquilon and tricyclazole.
  • Embodiment B 16 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl6) melanin biosynthesis inhibitors-dehydratase fungicides such as carpropamid.
  • Embodiment B 17. The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl7) hydroxyanilide fungicides such as fenhexamid.
  • Embodiment B 18. The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl8) squalene-epoxidase inhibitor fungicides such as pyributicarb.
  • Embodiment B 19 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (bl9) polyoxin fungicides such as polyoxin.
  • Embodiment B20 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b20) phenylurea fungicides such as pencycuron.
  • Embodiment B21 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b21) quinone inside inhibitor fungicides such as cyazofamid and amisulbrom.
  • Embodiment B22 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b22) benzamide fungicides such as zoxamide.
  • Embodiment B23 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b23) enopyranuronic acid antibiotic fungicides such as blasticidin-S.
  • Embodiment B24 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b24) hexopyranosyl antibiotic fungicides such as kasugamycin.
  • Embodiment B25 The composition described in the Summary of the Invention (including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b25) glucopyranosyl antibiotic: protein synthesis fungicides such as streptomycin.
  • Embodiment B26 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides such as validamycin.
  • Embodiment B27 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b27) cyanoacetylamideoxime fungicides such as cymoxanil.
  • Embodiment B28 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b28) carbamate fungicides such as propamacarb, prothiocarb and iodocarb.
  • Embodiment B29 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b29) oxidative phosphorylation uncoupling fungicides such as fluazinam, binapacryl, ferimzone, meptyldinocap and dinocap.
  • Embodiment B30 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b30) organo tin fungicides such as fentin acetate.
  • Embodiment B31 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b31) carboxylic acid fungicides such as oxolinic acid.
  • Embodiment B32 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b32) heteroaromatic fungicides such as hymexazole.
  • component (b) includes at least one compound selected from (b33) phosphonate fungicides such as phosphorous acid and its various salts, including fosetyl-aluminum.
  • Embodiment B34 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b34) phthalamic acid fungicides such as teclofthalam.
  • Embodiment B35 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b35) benzotriazine fungicides such as triazoxide.
  • Embodiment B36 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b36) benzene-sulfonamide fungicides such as flusulfamide.
  • Embodiment B37 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b37) pyridazinone fungicides such as diclomezine.
  • Embodiment B38 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b38) thiophene-carboxamide fungicides such as silthiofam.
  • Embodiment B39 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b39) pyrimidinamide fungicides such as diflumetorim.
  • component (b) includes at least one compound selected from (b39) pyrimidinamide fungicides such as diflumetorim.
  • Embodiment B40 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b40) carboxylic acid amide fungicides such as dimethomorph, benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb, valiphenal, mandipropamid and flumorph.
  • component (b) includes at least one compound selected from (b41) tetracycline antibiotic fungicides such as oxytetracycline.
  • Embodiment B42 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b42) thiocarbamate fungicides such as methasulfocarb.
  • component (b) includes at least one compound selected from (b42) thiocarbamate fungicides such as methasulfocarb.
  • Embodiment B43 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b43) benzamide fungicides such as fluopicolide and fluopyram.
  • Embodiment B44 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b44) host plant defense induction fungicides such as acibenzolar-S-methyl.
  • Embodiment B45 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b45) multi-site contact fungicides such as copper oxychloride, copper sulfate, copper hydroxide, Bordeaux composition (tribasic copper sulfide), elemental sulfur, mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb, ziram, folpet, captan, captafol and chlorothalonil.
  • multi-site contact fungicides such as copper oxychloride, copper sulfate, copper hydroxide, Bordeaux composition (tribasic copper sulfide), elemental sulfur, mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb, ziram, folpet, captan, captafol and chlorothalonil.
  • Embodiment B46 The composition described in the Summary of the Invention
  • component (b) includes at least one compound selected from (b46) fungicides other than fungicides of component (a) and components (bl) through (b45) such as ethaboxam, cyflufenamid, proquinazid, metrafenone, pyriofenone, ametoctradine, bethoxazin, neo-asozin, fenpyrazamine, pyrrolnitrin, quinomethionate, tebufloquin, 5-chloro-6-(2,4,6- trifluorophenyl)-7-(4-methylpiperidin- 1 -yl)[ 1 ,2,4]triazolo[ 1 ,5-a]pyrimidine (BAS600), 2-butoxy-6-iodo-3-propyl-4H-l-benzopyran-4-one, 3-[5-(b46) fungicides other than fungicides of component (a) and components (bl) through
  • Embodiment B47 The composition described in the Summary of the Invention
  • component (b) includes at least one fungicidal compound (fungicide) selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, pyraoxystrobin, pyrametostrobin, picoxystrobin, dimoxystrobin, metominostrobin- /fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, pyriofenone, cyflufenamid, fenpropidin, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, hexaconazole, ipconazole, metconazole, myclobutanil, penconazole, propi
  • fungicidal compound selected from the group consisting of azoxystrobin, kre
  • Embodiment B48 The composition of Embodiment B47 wherein component (b) includes at least one fungicidal compound selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, cyflufenamid, fenpropidin, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, hexaconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, famo
  • Embodiment B49 The composition of Embodiment B47 wherein component (b) includes at least one fungicidal compound selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, pyraclostrobin, pyrametostrobin, picoxystrobin, dimoxystrobin, metominostrobin- /fenominostrobin, quinoxyfen, metrafenone, pyriofenone, cyflufenamid, fenpropidin, fenpropimorph, cyproconazole, difenoconazole, epoxiconazole, flusilazole, metconazole, myclobutanil, propiconazole, proquinazid,
  • fungicidal compound selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, pyra
  • Embodiment B50 The compositon of Embodiment B49 wherein component (b) includes at least one compound selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidin, fenpropimorph, cyproconazole, difenoconazole, epoxiconazole, flusilazole, metconazole, myclobutanil, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, famoxadone and penthiopyrad.
  • component (b) includes at least one compound selected from the group consisting of azoxystrobin, kresoxim-methyl, trif
  • component (a) comprises a compound of Formula 1 or a salt thereof.
  • compositions of the present invention comprising a fungicidally effective amount of a composition of Embodiments 1 to 53, A 1 to A7, and Bl to B50 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • Embodiments of the invention further include methods for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a composition of any one of Embodiments 1 to 53, Al to A7, and Bl to B50 (e.g., as a composition including formulation ingredients as described herein).
  • Embodiments of the invention also include methods for protecting a plant or plant seed from diseases caused by fungal plant pathogens comprising applying a fungicidally effective amount of a composition of any one of Embodiments 1 to 53, Al to A7, and Bl to B50 to the plant or plant seed.
  • Some embodiments of the invention involve control of a plant disease or protection from a plant disease that primarily afflicts plant foliage and/or applying the composition of the invention to plant foliage (i.e. plants instead of seeds).
  • the preferred methods of use include those involving the above preferred compositions; and the diseases controlled with particular effectiveness include plant diseases caused by fungal plant pathogens.
  • Combinations of fungicides used in accordance with this invention can facilitate disease control and retard resistance development.
  • Embodiment CI A method for protecting a plant from a disease selected from
  • powdery mildew, rust and Septoria diseases comprising applying to the plant a fungicidally effective amount of the composition comprising components (a) and
  • Embodiment C2 The method of Embodiment CI wherein the disease is a powdery mildew disease and component (b) of the composition includes at least one fungicidal compound selected from azoxystrobin, myclobutanil and spiroxamine.
  • Embodiment C3 The method of Embodiment C2 wherein the disease is wheat
  • Embodiment C4 The method of Embodiment C2 or C3 wherein component (b)
  • Embodiment C5. The method of Embodiment CI wherein the disease is a rust disease and component (b) of the composition includes at least one fungicidal compound selected from azoxystrobin and tetraconazole.
  • Embodiment C6 The method of Embodiment C5 wherein the disease is wheat leaf rust.
  • Embodiment C7 The method of Embodiment CI wherein the disease is a Septoria disease and component (b) of the composition includes at least one fungicidal compound selected from azoxystrobin, picoxystrobin, quinoxyfen, tetraconazole, fenpropimorph and spiroxamine.
  • Embodiment C8 The method of Embodiment C7 wherein the disease is wheat leaf blotch.
  • Embodiment C9 The method of Embodiment C7 or C8 wherein component (b)
  • fungicidal compound selected from azoxystrobin, tetraconazole, fenpropiomorph and spiroxamine.
  • Embodiment CIO The method of Embodiment CI wherein the disease is a Septoria disease and component (b) of the composition includes at least one fungicidal compound selected from (b5) amine/morpholine fungicides.
  • Embodiment C 11 The method of Embodiment CIO wherein the disease is wheat leaf blotch.
  • Embodiment C12 The method of Embodiment CIO or CI 1 wherein the composition includes at least one fungicidal compound selected from fenpropiomorph and spiroxamine.
  • Embodiment C13 The method of any one of Embodiments CI through C12 wherein components (a) and (b) are applied in synergistically effective amounts (and in a synergistic ratio relative to each other).
  • Embodiments CI through C13 relating to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, a fungicidally effective amount of a fungicidal composition of the invention.
  • halogenation can be achieved using a variety of halogenating reagents known in the art such as elemental halogen (e.g., CI2, Br 2 , I 2 ), sulfuryl chloride, iodine monochloride or a N-halosuccinimide (e.g., NBS, NCS, NIS) in an appropriate solvent such as N,N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane or acetic acid.
  • elemental halogen e.g., CI2, Br 2 , I 2
  • sulfuryl chloride iodine monochloride
  • iodine monochloride iodine monochloride
  • N-halosuccinimide e.g., NBS, NCS, NIS
  • Alkylation is achieved by reacting a compound of Formula 2 with a metalating agent, followed by an alkylating agent of formula Ri-Lg (wherein Lg is a leaving group such as CI, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate).
  • Suitable metalating agents include, for example, as n-butyl lithium (n-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH).
  • alkylation and “alkylating agent” are not limited to R 1 being an alkyl group, and include in addition to alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • Compounds of Formula 1 can be subjected to various nucleophilic and metallation reactions to add substituents or modify existing substituents, and thus provide other functionalized compounds of Formula 1.
  • compounds of Formula 1 wherein R 1 and/or R 2 are halogen can undergo nucleophilic displacements to provide compounds of Formula 1 wherein R 1 and/or R 2 are groups linked to the imidazole ring through an O or S atom (e.g., displacements with alkoxides or thiolates).
  • compounds of Formula 1 wherein R 1 and/or R 2 are bromo or iodo can be cross-coupled with compounds of formulae Ri-Met or R 2 -Met (wherein Met is Sn, Zn, B(OH) 2 , Mg, Li, Cu or other suitable counterions) in the presence of a palladium or nickel catalyst to produce compounds of Formula la wherein R 1 and/or R 2 are cyano, alkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • Preferred catalysts include but are not limited to Pd(PPh 3 ) 4 , PdCl 2 (PPh 3 ) 2 , PdCl 2 (diphenylphosphinoferrocene), NiCl 2 (PPh 3 ) 2 and tetrakis(tri-2-furylphosphino)palladium.
  • the conditions for each reaction will depend upon the catalyst used and the counterions in the compound of formulae Ri-Met or R 2 -Met.
  • the presence of a base (such as an alkali carbonate, tertiary amine or alkali fluoride) is necessary for reactions involving compounds of formulae Ri-Met or R 2 -Met where Met is B(OH) 2 .
  • Examples 9, 11, 12, 13, 14 and 19 illustrate various cross-coupling reactions for the preparation of certain compounds of Formula 1.
  • compounds of Formula 1 can alternatively be prepared by halogenation of a compound of Formula 3 preferentially at the 4-position of the imidazole ring to provide a compound of Formula 4 wherein R 1 is halogen, which can then be treated with a second equivalent of the same or different halogenating reagent to provide a compound of Formula 1 wherein R 1 and R 2 are halogen.
  • R 1 is halogen
  • Scheme 2 for the preparation of a compound of Formula 4 see Step C of Examples 1 and 22.
  • Step D of Example 22 see Step D of Example 22.
  • compounds of Formula 3 can be treated with 2 equivalents of a halogenating reagent to provide a compound of Formula 1 directly wherein R 1 and R 2 are both the same halogen.
  • a halogenating reagent for an example illustrating the method of preparing a compound of Formula 1 wherein R 1 and R 2 are both the same halogen see Example 2 and Step C of Example 3.
  • compounds of Formula 1 wherein R 2 is halogen, alkyl, alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like can be prepared from compounds of Formula 4 by metallation with a reagent such as n-butyllithium (ft-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH) in a solvent such as tetrahydrofuran, dioxane or toluene at temperatures ranging from about 0 °C to room temperature.
  • a reagent such as n-butyllithium (ft-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH)
  • LDA lithium diisopropylamide
  • NaH sodium hydride
  • the anion is then contacted with an electrophile resulting in the introduction of an R 2 group onto Formula 4, thus providing a compound of Formula 1.
  • Synthesis of compounds of Formula 2 can be achieved as outlined in Scheme 3.
  • a compound of Formula 5 is N-arylated with halides of formula Q3 ⁇ 4l wherein X 1 is I, CI, Br or F.
  • X 1 is I, CI, Br or F.
  • a suitable copper source e.g., copper(I) iodide or copper(I) triflate
  • a metal carbonate base e.g., potassium or cesium carbonate
  • a suitable solvent such as xylenes, dioxane or acetonitrile
  • compounds of Formula 6 can be converted directly to Formula 2 by reaction with a halide of formula QiX 1 in the presence of palladium(II) acetate and a triarylphosphine ligand and cesium fluoride in a solvent such as dioxane, tetrahydrofuran or acetonitrile at the reflux temperature of the solvent.
  • a solvent such as dioxane, tetrahydrofuran or acetonitrile at the reflux temperature of the solvent.
  • Step B of Example 6 illustrates the preparation of a compound of Formula 2 using the method of Scheme 3.
  • lithiation of a compound of Formula 6 with n-butyllithium (n-BuLi) or lithium diisopropylamide (LDA), followed by treatment of the anion with trialkylorganostannyl chlorides or boronic acids (or esters) provides compounds of Formula 7.
  • Treatment of compounds Formula 7 with a halide of formula QiX 1 using well-known transition metal-catalyzed cross coupling reaction conditions provides Formula 2 compounds. Typically the reaction is run in the presence of a palladium catalyst.
  • L is (alky 1)3811 or B(OH) 2
  • Compounds of Formula 2 can also be prepared as shown in Scheme 4.
  • a compound Formula 8 is first metallated with a metalating agent such as n-butyllithium (ft-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH) in a solvent such as tetrahydrofuran, dioxane or toluene at temperatures ranging from about 0 °C to room temperature.
  • a metalating agent such as n-butyllithium (ft-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH)
  • LDA lithium diisopropylamide
  • NaH sodium hydride
  • the anion is then contacted with an electrophile resulting in the introduction of an R 2 group onto Formula 8, thus providing a compound of Formula 2.
  • the electrophile can be a halogen derivative such as N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), N-iodosuccinimide (NIS), hexachloroethane or 1,2-dibromotetrachloroethane.
  • NCS N-chlorosuccinimide
  • NBS N-bromosuccinimide
  • NIS N-iodosuccinimide
  • hexachloroethane or 1,2-dibromotetrachloroethane.
  • the electrophile can be an alkylating agent of the formula R 2 -Lg (wherein Lg is a leaving group such as CI, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate) where R 2 is alkyl, alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • the terms "alkylation” and “alkylating agent” are not limited to R 2 being an alkyl group.
  • Step A of Example 4 illustrates the method of Scheme 4 using LDA and iodomethane.
  • compounds of Formula 2 can be prepared by reacting N-chloroamidines of Formula 9 with enamines of Formula 10.
  • cyclization proceeds through the intermediacy of an in sztw-generated 4-morpholino-4,5- dihydroimidazole which undergoes elimination of the morpholino group to provide the compounds of Formula 2.
  • the reaction is run in the presence of a base such as pyridine, 4-(dimethylamino)pyridine or a trialkylamine and in a suitable solvent, such as dichloromethane, trichloromethane, carbon tetrachloride or toluene, at temperatures ranging from about 0 °C to the reflux temperature of the solvent.
  • imidazole rings of Formula 2 can also be prepared by numerous other methods described in the chemistry literature.
  • the general method described by Wiglenda et al., Journal of Medicinal Chemistry 2007, 50(7), 1475-1484 can be used to prepare compounds of Formula 2; the method can also be readily adapted to prepare Formula 2 compounds wherein each Q 1 and/or Q 2 is an optionally substituted benzyl group.
  • compounds of Formula 4 can be prepared by reacting an imine of Formula 11 with a substituted /?-toluenesulfonylmethyl isocyanide of Formula 12 or a substituted benzotriazol-l-ylmethyl isocyanide of Formula 13 in the presence of a suitable base such as potassium carbonate, potassium tert-butoxide, sodium hydroxide, sodium hydride, tert-butylamine or l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in an appropriate solvent such as methanol, dioxane, tetrahydrofuran, dimethylsulfoxide, N,N-dimethylformamide or 1 ,2-dimethoxyethane, at temperatures ranging from about 0 to 150 °C.
  • a suitable base such as potassium carbonate, potassium tert-butoxide, sodium hydroxide, sodium hydride, tert-butylamine or l,8-diazabicyclo
  • Imines of Formula 11 can be readily prepared by contacting an amine of Formula Q 2 NH 2 with an aldehyde of formula QiCHO under dehydrative conditions such as heating in toluene or xylenes with use of a Dean-Stark trap to remove water formed in the reaction.
  • an acid catalyst such as /?-toluenesulfonic acid can be added to the reaction mixture to promote elimination of water.
  • Step A of Examples 1, 3, 7, 22 and 24 illustrate the preparation of a compound of Formula 11.
  • Compounds of Formula 12 can be prepared from the unsubstituted /?-toluene- sulfonylmethyl isocyanide under phase-transfer conditions using methods reported in the chemical literature; see, for example, Leusen et al, Tetrahedron Letters 1975, 40, 3487- 3488.
  • the substituted benzotriazol-l-ylmethyl isocyanides of Formula 13 can be prepared by contacting benzotriazol-l-yl-methyl isocyanide with a compound of formula R 2 X! (wherein X 1 is halogen) in the presence of a base such as potassium carbonate, sodium hydride or potassium tert-butoxide.
  • a base such as potassium carbonate, sodium hydride or potassium tert-butoxide.
  • a base such as potassium carbonate, sodium hydride or potassium tert-butoxide.
  • Katritzky et al. Heterocycles 1997, 44, 67-70.
  • One skilled in the art will recognize other methods for preparing compounds of Formula 13, for example, the method described by Katritzky et al, Journal of the Chemical Society, Perkin Transactions 1, 1990, (7), 1847-1851.
  • Halogenation at the 2-position of the imidazole ring of Formula 4 can be achieved using methods analogous to those already described for Scheme 2 to provide compounds of Formula 2 wherein R 1 is halogen.
  • Step C of Examples 8, 10 and 24, Step B of Example 18, and Step D of Example 22 illustrate this halogenation method.
  • Aminonitriles of Formula 14 are readily available from amines of formula Q 2 NH2, aldehydes of formula QiCHO and a cyanide source by means of the Strecker reaction.
  • a variety of solvents and cyanide sources can be employed.
  • the presence of a Lewis acid such as indium(III) chloride can be advantageous.
  • a Lewis acid such as indium(III) chloride.
  • Methanaminium salts of Formula 15 are commercially available, for example, chloromethylenedimethyliminium chloride (i.e. R 1 and X 1 are CI) can be obtained from commercial sources. Compounds of Formula 15 can also be synthesized by methods documented in the chemistry literature.
  • 2-bromomethyl analogs of Formula lb can be prepared by treating 2-hydroxymethyl compounds of Formula la with hydrobromic acid in a solvent such as glacial acetic acid using the method described by Beukers et al, Journal of Medicinal Chemistry 2004, 47(15), 3707-3709.
  • R 3 , R 4 , R 5 and R 6 substituents attached to the rings and ring systems of Q 1 and Q 2 may be more conveniently incorporated after forming the central imidazole ring with the rings or ring systems of Q 1 and Q 2 .
  • R 3 , R 4 , R 5 and/or R 6 is halogen or another suitable leaving group
  • the leaving group can be replaced using various electrophilic, nucleophilic and organometallic reactions known in the art to introduce other functional groups as R 3 , R 4 , R 5 and R 6 .
  • Example 18 demonstrates the preparation of a compound of Formula 1 wherein an R 3 substituent on the phenyl ring of Q 1 is cyano (-CN) starting from a compound wherein an R 3 substituent on the phenyl ring of Q 1 is bromo.
  • Example 25 illustrates the preparation of a compound of Formula 1 wherein an R 5 on the phenyl ring of Q 2 is thiocyanate (-SCN) starting from the corresponding compound of Formula 1 wherein an R 5 substituent on the phenyl ring of Q 2 is iodo.
  • compounds of Formula 1 wherein an R 3 or R 5 substituent is connected through an oxygen atom e.g., optionally substituted alkoxy
  • sulfur atom e.g., optionally substituted alkylthio
  • nitrogen atom e.g. alkylamino and dialkylamino
  • R 3 or R 5 substituent is OH, SH or NH 2 , respectively.
  • General alkylation methods are well known in the art of organic chemical synthesis.
  • Present Example 26 demonstrates the preparation of a compound of Formula 1 wherein R 3 is OCH 2 CN starting from the corresponding compound of Formula 1 wherein R 3 is OH.
  • Compounds of Formula 1 wherein an R 3 or R 5 substituent is optionally substituted alkyl sulfmyl or sulfonyl can be prepared by oxidizing the corresponding compounds of Formula 1 wherein the R 3 or R 5 substituent is optionally substituted alkylthio through use of general oxidation methods well known in the art.
  • compounds of Formula 1 wherein a ring or ring system of Q 1 or Q 2 is substituted with an R 3 or R 5 substituent which is -X-U-Z can be prepared from the corresponding compounds of Formula 1 wherein R 3 or R 5 is a halogen or other suitable leaving group, such as by the general method described in PCT Patent Publication WO 2007/149448 (see Scheme 15 therein).
  • This reference also describes other general methods for forming an R 3 or R 5 substituent as -X-U-Z (see Schemes 16-19 therein).
  • Present Examples 20 through 21 demonstrate the preparation of a compound of Formula 1 wherein R 3 is -X-U-Z (i.e. -O ⁇ FT ⁇ NHCFy starting from the corresponding compound of Formula 1 wherein R 3 is methoxy.
  • the solvent system was solvent A: water with 0.05% trifluoroacetic acid by volume/volume, and solvent B: acetonitrile with 0.05%) trifluoroacetic acid by volume/volume (gradient started at 0 minutes with 90%> solvent A and 10%> solvent B and increased solvent B to 90%> over 20 minutes, flow rate was 1 mL/minute). Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated.
  • MS mass spectrum
  • Step B Preparation of l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole
  • the resulting residue was diluted with ethyl acetate (200 mL), washed with water (75 mL) and saturated aqueous sodium chloride (75 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as a pale yellow solid (1.30 g, 98.9 area % purity by HPLC) melting at 170-172 °C.
  • Step C Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole
  • the resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as an off-white solid (0.075 g, 98.9 area % purity by HPLC) melting at 102-104 °C.
  • the resulting material was purified by silica gel chromatography using ethyl acetate -hexanes (1 : 4) as eluant to provide the title compound as a pale-yellow solid (0.23 g, 96.7 area % purity by HPLC) melting at 112-119 °C.
  • Step B Preparation of l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole
  • the resulting residue was diluted with ethyl acetate (200 mL), washed with water (75 mL) and saturated aqueous sodium chloride solution (75 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (3 : 7) as eluant to provide the title compound as a pale-yellow solid (1.40 g, 98.9 area % purity by HPLC) melting at 170-172 °C.
  • Step C Preparation of 2,4-dichloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole
  • Step A Preparation of l-(4-chlorophenyl)-5-(2,6-difiuorophenyl)-2-methyl- lH-imidazole
  • the reaction mixture was slowly warmed to room temperature, stirred for 4 h, and then concentrated under reduced pressure.
  • the resulting residue was diluted with dichloromethane (50 mL), washed with water (20 mL) and saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as a pale -ye How solid (0.74 g).
  • Step B Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl- lH-imidazole
  • Step A Preparation of l-(4-chlorophenyl)-2-methyl-lH-imidazole
  • the reaction mixture was diluted with ethyl acetate (80 mL), washed with water (2 x 30 mL) and saturated aqueous sodium chloride solution (40 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (0.5 : 9.5) as eluant to provide the title compound as a brown solid (0.60 g).
  • Step B Preparation of l-(4-chlorophenyl)-5-(4-fiuorophenyl)-2-methyl-lH-imidazole
  • the reaction mixture was diluted with ethyl acetate (40 mL), washed with water (20 mL) and saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by silica gel chromatography using methanol-dichloromethane (1 : 9) as eluant to provide the title compound as an off-white solid (0.20 g, 95.3 area % purity by HPLC) melting at 132-134 °C.
  • Step C Preparation of 4-chloro-l -(4-chlorophenyl)-5-(4-fiuorophenyl)-2-methyl- lH-imidazole
  • Step C Preparation of 2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,5-dimethoxy- phenyl)-4-methyl- lH-imidazole
  • Step A Preparation of 2,6-a-[(3-fluorophenyl)amino)]-4-methoxybenzeneacetonitrile A mixture of 3-fluoroaniline (1.15 g, 10.4 mmol), 2,6-difluoro-
  • Step B Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluoro- phenyl)- lH-imidazole
  • Step C Preparation of 2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3 -fluorophenyl)- lH-imidazole
  • reaction mixture was diluted with saturated aqueous sodium carbonate solution, and the resulting aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by medium pressure liquid chromatography on silica gel
  • Step A Preparation of 2,6-a-[(4-fluorophenyl)amino]-3-methoxybenzeneacetonitrile A mixture of 4-fluoroaniline (1.17 g, 10.6 mmol), 2,6-difluoro-
  • Step B Preparation of 4-bromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluoro- phenyl)- lH-imidazole
  • Step C Preparation of 2,4-dibromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluoro- phenyl)- lH-imidazole
  • N-bromosuccinimide (0.250 g, 1.40 mmol) was added to the reaction mixture and the mixture was again heated at 60 °C overnight, after which time more N-bromosuccinimide (0.250 g, 1.40 mmol) was added and the mixture was again heated at 60 °C overnight.
  • the reaction mixture was diluted with saturated aqueous sodium carbonate solution, and the aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.36 g).
  • reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (30 mg).
  • reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.030 g) melting at 147-149 °C.
  • Step A Preparation of 4-chloro-5-(2,6-difluorophenyl)-l-(3-fluorophenyl)-
  • Ethynyltrimethyl silane (0.216 g, 2.2 mmol) was added to the reaction mixture, stirring was continued for 2 h, and then the mixture was heated at reflux overnight. More dichlorobis(triphenylphosphine)palladium (0.147 g, 0.21 mmol) and ethynyltrimethylsilane (0.216 g, 2.2 mmol) were added to the reaction mixture, and the mixture was heated at reflux for 4 h.
  • the reaction mixture was diluted with saturated aqueous sodium carbonate solution and extracted with ethyl acetate, and the combined organic layers were washed with saturated aqueous ethylenediammetetraacetic acid, dried over magnesium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.244 g).
  • Step B Preparation of 4-chloro-5-(2,6-difluorophenyl)-2-ethynyl-l-(3-fluorophenyl)- lH-imidazole
  • Step A Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluoro- phenyl)-lH-imidazole-2-carboxaldehyde
  • reaction mixture After an additional 1 h of stirring at 0 °C, the reaction mixture was allowed to warm to room temperature. After 1 h, the reaction mixture was diluted with aqueous citric acid solution (20%>, 30 mL) and extracted with diethyl ether (100 mL). The organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel (0 to 20% gradient of ethyl acetate in /? -butyl chloride as eluant) to provide the title compound as a pale-yellow solid (0.397 g).
  • reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.940 g).
  • Step A Preparation of 3-[4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]- 2,4-difluorobenzonitrile
  • reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.217 g).
  • Step B Preparation of 3-[2-bromo-4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]-
  • the reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.196 g).
  • reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.088 g).
  • Step A Preparation of phenylmethyl N-[3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)- lH-imidazol-5-yl]-3,5-difluorophenoxy]propyl]-N-methylcarbamate
  • Step B Preparation of 3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH-imidazol- 5-yl]-3,5-difluorophenoxy]-N-methyl-l-propanamide hydrochloride
  • Step B Preparation of 5-[5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]-
  • reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (4.63 g).
  • Step D Preparation of 5-[2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl]-2-(trifluoromethyl)pyridine
  • reaction mixture was then concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.021 g).
  • Step A Preparation of N-[(6-chloro-3-pyridinyl)methylene]-2,6-difluoro-4-methoxy- benzenamine
  • Step B Preparation of 2-chloro-5-[l-(2,6-difluoro-4-methoxyphenyl)-4-methyl- lH-imidazol-5-yl]pyridine
  • reaction mixture was then concentrated under reduced pressure and purified by medium pressure liquid chromatography on silica gel (0 to 100% ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.28 g).
  • Q 2 is 4-Cl-Ph, R 1 is CI and R 2 is Me.
  • Table 1A the row heading is "Q 2 is 4-Cl-Ph, R 1 is Br and R 2 is Me", and (R ) m is as defined in Table 1 above.
  • Table 1 A specifically discloses 4-bromo- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole.
  • Tables 2A through 715 A are constructed similarly.
  • Q z is 4- ⁇ Cl-Ph.
  • R is Br and R ⁇ is Me.
  • Q 2 is 4- ⁇ Cl-Ph. is CI and R 2 is CFH 2 .
  • Q 2 is 4- Cl-Ph. is I and R 2 is Me.
  • Q 2 is 4- Cl-Ph. is Me and R 2 is Me.
  • Q 2 is 4- Cl-Ph. is Me and R 2 is CI.
  • Q 2 is 4- Cl-Ph. is Me and R 2 is Br.
  • Q 2 is 4- Cl-Ph. is Me and R 2 is I.
  • Q 2 is 4- Cl-Ph. is Me and R 2 is MeO.
  • Q 2 is 4- Cl-Ph. is MeO and R 2 is Me.
  • Q 2 is 4- Cl-Ph. is Br and R 2 is Br.
  • Q 2 is 4- Cl-Ph. is Br and R 2 is CI.
  • Q 2 is 4- Cl-Ph. is CI and R 2 is Br.
  • Q 2 is 4- Cl-Ph. is CI and R 2 is CI.
  • Q 2 is 4- Cl-Ph. is Me and R 2 is MeS.
  • Q 2 is 4- Cl-Ph. is MeS and R 2 is Me.
  • Q 2 is 4- Cl-Ph. is Et and R 2 is Br.
  • Q 2 is 4- Cl-Ph. is Et and R 2 is CI.
  • Q 2 is 4- Cl-Ph. is Et and R 2 is Me.
  • Q 2 is 4- Cl-Ph. is Me and R 2 is Et.
  • Q 2 is 4- Cl-Ph. is CI and R 2 is Et.
  • Q 2 is 4- Cl-Ph. is Me and R 2 is CN.
  • Q 2 is 3- Cl-Ph. is CI and R 2 is Me.
  • Q 2 is 3- Cl-Ph. is CI and R 2 is CFH 2 .
  • Q 2 is 3- Cl-Ph. is Br and R 2 is Me.
  • Q 2 is 3- Cl-Ph. is I and R 2 is Me.
  • Q 2 is 3- Cl-Ph. is Me and R 2 is Me.
  • Q 2 is 3- Cl-Ph. is Me and R 2 is CI.
  • Q 2 is 3- Cl-Ph. is Me and R 2 is Br.
  • Q 2 is 3- Cl-Ph. is Me and R 2 is I.
  • Q 2 is 3- Cl-Ph. is Br and R 2 is Br.
  • Q 2 is 3- Cl-Ph. is Br and R 2 is CI.
  • Q 2 is 3- Cl-Ph. is CI and R 2 is Br.
  • Q 2 is 3- Cl-Ph. is CI and R 2 is CI.
  • Q 2 is 4- F-Ph, R is CI and R 2 is Me.
  • Q 2 is 4- F-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 4- F-Ph, R is Br and R 2 is Me.
  • Q 2 is 4- F-Ph, R is I and R 2 is Me. Row Heading s 4-F-Ph, R is Me and R 2 is Me.
  • Q 2 is 4-F-Ph, R is Me and R 2 is Br.
  • R is Br and R ⁇ is Br.
  • Q is 4-F-Ph, R is Br and R ⁇ is CI.
  • Q 2 is 3-F-Ph, R is CI and R 2 is Me.
  • R is CI and R 2 is CFH 2 .
  • Q 2 is 3-F-Ph, R is Br and R 2 is Me.
  • R is Br and R ⁇ is CI.
  • R is CI and R 2 is Br.
  • Q 2 3 -CF 2 HO- Ph R 1 is CI and R 2 is Me.
  • Q 2 3 -CF 2 HO- Ph R 1 is CI and R 2 is CFH 2 Q 2 3 -CF 2 HO- Ph, R 1 is Br and R 2 is Me.
  • R 1 is I and R 2 is Me.
  • R 1 is Me and R 2 is Me.
  • R 1 is Me and R 2 is CI.
  • R 1 is Br and R 2 is Br.
  • R 1 is Br and R 2 is CI.
  • R 1 is CI and R 2 is Br.
  • R 1 is CI and R 2 is CI.
  • Q 2 4-Me-Ph R is CI and R 2 is CFH 2 .
  • Q z is 4- Me-Ph, R is Me and R 2 is CI.
  • Q 2 is 4- Me-Ph, R is Me and R 2 is Br.
  • Q 2 is 4- Me-Ph, R is Me and R 2 is I.
  • Q 2 is 4- Me-Ph, R is Br and R 2 is Br.
  • Q 2 is 4- Me-Ph, R is Br and R 2 is CI.
  • Q 2 is 4- Me-Ph, R is CI and R 2 is Br.
  • Q 2 is 4- Me-Ph, R is CI and R 2 is CI.
  • Q 2 is 3- Me-Ph, R is CI and R 2 is Me.
  • Q 2 is 3- Me-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 3- Me-Ph, R is Br and R 2 is Me.
  • Q 2 is 3- Me-Ph, R is I and R 2 is Me.
  • Q 2 is 3- Me-Ph, R is Me and R 2 is Me.
  • Q 2 is 3- Me-Ph, R is Me and R 2 is CI.
  • Q 2 is 3- Me-Ph, R is Me and R 2 is Br.
  • Q 2 is 3- Me-Ph, R is Me and R 2 is I.
  • Q 2 is 3- Me-Ph, R is Br and R 2 is Br.
  • Q 2 is 3- Me-Ph, R is Br and R 2 is CI.
  • Q 2 is 3- Me-Ph, R is CI and R 2 is Br.
  • Q 2 is 3- Me-Ph, R is CI and R 2 is CI.
  • Q 2 is 4- Et-Ph, R is CI and R 2 is Me.
  • Q 2 is 4- Et-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 4- Et-Ph, R is Br and R 2 is Me.
  • Q 2 is 4- Et-Ph, R is I and R 2 is Me.
  • Q 2 is 4- Et-Ph, R is Me and R 2 is Me.
  • Q 2 is 4- Et-Ph, R is Me and R 2 is CI.
  • Q 2 is 4- Et-Ph, R is Me and R 2 is Br.
  • Q 2 is 4- Et-Ph, R is Me and R 2 is I.
  • Q 2 is 4- Et-Ph, R is Br and R 2 is Br.
  • Q 2 is 4- Et-Ph, R is Br and R 2 is CI.
  • Q 2 is 4- Et-Ph, R is CI and R 2 is Br.
  • Q 2 is 4- Et-Ph, R is CI and R 2 is CI.
  • Q 2 is 4- CI, 3-F-Ph, R is CI and R 2 is Me.
  • Q 2 is 4- CI, 3-F-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 4- CI, 3-F-Ph, R is Br and R 2 is Me.
  • Q 2 is 4- CI, 3-F-Ph, R is I and R 2 is Me.
  • Q 2 is 4- CI, 3-F-Ph, R is Me and R 2 is Me.
  • Q 2 is 4- CI, 3-F-Ph, R is Me and R 2 is CI.
  • Q 2 is 4-Cl, 3-F-Ph, R is Me and R ⁇ is Br.
  • Q 2 is 4-Cl, 3-F-Ph, R is Me and R 2 is I.
  • Q 2 is 4-Cl, 3-F-Ph, R is Br and R 2 is Br.
  • Q 2 is 4-Cl, 3-F-Ph, R is Br and R 2 is CI.
  • Q 2 is 4-Cl, 3-F-Ph, R is CI and R 2 is Br.
  • Q 2 is 4-Cl, 3-F-Ph, R is CI and R 2 is CI.
  • Q 2 is 2-Cl, 4-F-Ph, R is CI and R 2 is Me.
  • Q 2 is 2-Cl, 4-F-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 2-Cl, 4-F-Ph, R is Br and R 2 is Me.
  • Q 2 is 2-Cl, 4-F-Ph, R is I and R 2 is Me.
  • Q 2 is 2-Cl, 4-F-Ph, R is Me and R 2 is Me.
  • Q 2 is 2-Cl, 4-F-Ph, R is Me and R 2 is CI.
  • Q 2 is 2-Cl, 4-F-Ph, R is Me and R 2 is Br.
  • Q 2 is 2-Cl, 4-F-Ph, R is Me and R 2 is I.
  • Q 2 is 2-Cl, 4-F-Ph, R is Br and R 2 is Br.
  • Q 2 is 2-Cl, 4-F-Ph, R is Br and R 2 is CI.
  • Q 2 is 2-Cl, 4-F-Ph, R is CI and R 2 is Br.
  • Q 2 is 2-Cl, 4-F-Ph, R is CI and R 2 is CI.
  • Q 2 is 4-F, 3-Me-Ph, R is CI and R 2 is Me.
  • Q 2 is 4-F, 3-Me-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 4-F, 3-Me-Ph, R is Br and R 2 is Me.
  • Q 2 is 4-F, 3-Me-Ph, R is I and R 2 is Me.
  • Q 2 is 4-F, 3-Me-Ph, R is Me and R 2 is Me.
  • Q 2 is 4-F, 3-Me-Ph, R is Me and R 2 is CI.
  • Q 2 is 4-F, 3-Me-Ph, R is Me and R 2 is Br.
  • Q 2 is 4-F, 3-Me-Ph, R is Me and R 2 is I.
  • Q 2 is 4-F, 3-Me-Ph, R is Br and R 2 is Br.
  • Q 2 is 4-F, 3-Me-Ph, R is Br and R 2 is CI.
  • Q 2 is 4-F, 3-Me-Ph, R is CI and R 2 is Br.
  • Q 2 is 4-F, 3-Me-Ph, R is CI and R 2 is CI.
  • Q 2 is 3,4-di-F-Ph, R is CI and R 2 is Me.
  • Q 2 is 3,4-di-F-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 3,4-di-F-Ph, R is Br and R 2 is Me.
  • Q 2 is 3,4-di-F-Ph, R is I and R 2 is Me.
  • Q 2 is 3,4-di-F-Ph, R is Me and R 2 is Me.
  • Q 2 is 3,4-di-F-Ph, R is Me and R 2 is CI.
  • Q 2 is 3,4-di-F-Ph, R is Me and R 2 is Br.
  • Q 2 is 3,4-di-F-Ph, R is Me and R ⁇ is I.
  • Q 2 is 3,4-di-F-Ph, R is Br and R 2 is Br.
  • Q 2 is 3,4-di-F-Ph, R is Br and R 2 is CI.
  • Q 2 is 3,4-di-F-Ph, R is CI and R 2 is Br.
  • Q 2 is 3,4-di-F-Ph, R is CI and R 2 is CI.
  • Q 2 is 3,4-di-Cl-Ph, R is CI and R 2 is Me.
  • Q 2 is 3,4-di-Cl-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 3,4-di-Cl-Ph, R is Br and R z is Me.
  • Q 2 is 3,4-di-Cl-Ph, R is I and R 2 is Me.
  • Q 2 is 3,4-di-Cl-Ph, R is Me and R 2 is Me.
  • Q 2 is 3,4-di-Cl-Ph, R is Me and R 2 is CI.
  • Q 2 is 3,4-di-Cl-Ph, R is Me and R 2 is Br.
  • Q 2 is 3,4-di-Cl-Ph, R is Me and R 2 is I.
  • Q 2 is 3,4-di-Cl-Ph, R is Br and R 2 is Br.
  • Q 2 is 3,4-di-Cl-Ph, R is Br and R 2 is CI.
  • Q 2 is 3,4-di-Cl-Ph, R is CI and R 2 is Br.
  • Q 2 is 3,4-di-Cl-Ph, R is CI and R 2 is CI.
  • Q 2 is 3,5-di-MeO-Ph, R is CI and R 2 is Me.
  • Q 2 is 3,5-di-MeO-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 3,5-di-MeO-Ph, R is Br and R 2 is Me.
  • Q 2 is 3,5-di-MeO-Ph, R is I and R 2 is Me.
  • Q 2 is 3,5-di-MeO-Ph, R is Me and R 2 is Me.
  • Q 2 is 3,5-di-MeO-Ph, R is Me and R 2 is CI.
  • Q 2 is 3,5-di-MeO-Ph, R is Me and R 2 is Br.
  • Q 2 is 3,5-di-MeO-Ph, R is Me and R 2 is I.
  • Q 2 is 3,5-di-MeO-Ph, R is Br and R 2 is Br.
  • Q 2 is 3,5-di-MeO-Ph, R is Br and R 2 is CI.
  • Q 2 is 3,5-di-MeO-Ph, R is C and R ⁇ - is Br.
  • Q 2 is 3,5-di-MeO-Ph, R is C and R 2 is CI.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R is CI and R 2 is Me.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R is Br and R 2 is Me.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R is I and R 2 is Me.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R 2 is Me.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R 2 is CI.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R 2 is Br.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R 2 is I.
  • Q 2 is 2- CI. 3,5-di-MeO-Ph, R is Br and R ⁇ is Br.
  • Q 2 is 2- CI, 3,5-di-MeO-Ph, R is Br and R 2 is CI.
  • Q 2 is 2- CI, 3,5-di-MeO-Ph, R is CI and R 2 is Br.
  • Q 2 is 2- CI, 3,5-di-MeO-Ph, R is CI and R 2 is CI.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is CI and R 2 is Me.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is CI and R 2 is CFH 2 .
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is Br and R 2 is Me.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is I and R 2 is Me.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is Me and R 2 is Me.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is Me and R 2 is CI.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is Me and R 2 is Br.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is Me and R 2 is I.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is Br and R 2 is Br.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is Br and R 2 is CI.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is CI and R 2 is Br.
  • Q 2 is 4- CI, 3,5-di-MeO-Ph, R is CI and R 2 is CI.
  • Q 2 is 4- ⁇ Cl-Bn, R is CI and R 2 is Me.
  • Q 2 is 4- ⁇ Cl-Bn, R is CI and R 2 is CFH 2 .
  • Q 2 is 4- Cl-Bn, R is Br and R 2 is Me.
  • Q 2 is 4- Cl-Bn, R is I and R z is Me.
  • Q 2 is 4- Cl-Bn, R is Me and R 2 is Me.
  • Q 2 is 4- Cl-Bn, R is Me and R 2 is CI.
  • Q 2 is 4- Cl-Bn, R is Me and R 2 is Br.
  • Q 2 is 4- Cl-Bn, R is Me and R 2 is I.
  • Q 2 is 4- Cl-Bn, R is Br and R 2 is Br.
  • Q 2 is 4- Cl-Bn, R is Br and R 2 is CI.
  • Q 2 is 4- Cl-Bn, R is CI and R 2 is Br.
  • Q 2 is 4- Cl-Bn, R is CI and R 2 is CI.
  • Q 2 is 4- F-Bn, R 1 is CI and R 2 is Me.
  • Q 2 is 4- F-Bn, R 1 is CI and R 2 is CFH 2 .
  • Q 2 is 4- F-Bn, R 1 is Br and R 2 is Me.
  • Q 2 is 4- F-Bn, R 1 is I and R 2 is Me.
  • Q 2 is 4- F-Bn, R 1 is Me and R 2 is Me.
  • Q 2 is 4- F-Bn, R 1 is Me and R 2 is CI.
  • Q 2 is 4- F-Bn, R 1 is Me and R 2 is Br.
  • Q 2 is 4- F-Bn, R 1 is Me and R 2 is I.
  • Q 2 is 4- F-Bn, R 1 is Br and R 2 is Br. Row Heading
  • Q 2 is 4-F-Bn, R 1 is Br and R 2 is CI.
  • Q 2 is 4-F-Bn, R 1 is CI and R 2 is Br.
  • Q 2 is 4-F-Bn, R 1 is CI and R 2 is CI.
  • Q 2 is 6-C 1-3-pyridinyl, R s CI and R 2 is Me.
  • Q 2 is 6-C 1-3-pyridinyl, R s CI and R 2 is CFH 2 .
  • Q 2 is 6-C 1-3-pyridinyl, R s Br and R 2 is Me.
  • Q 2 is 6-C 1-3-pyridinyl, R s I and R 2 is Me.
  • Q 2 is 6-C 1-3-pyridinyl, R s Me and R 2 is Me.
  • Q 2 is 6-C 1-3-pyridinyl, R s Me and R 2 is CI.
  • Q 2 is 6-C 1-3-pyridinyl, R s Me and R 2 is Br.
  • Q 2 is 6-C 1-3-pyridinyl, R s Me and R 2 is I.
  • Q 2 is 6-C 1-3-pyridinyl, R s Me and R 2 is MeO.
  • Q 2 is 6-C 1-3-pyridinyl, R s MeO and R 2 is Me.
  • Q 2 is 6-C 1-3-pyridinyl, R s Br and R ⁇ is Br.
  • Q 2 is 6-C 1-3-pyridinyl, R s Br and R 2 is CI.
  • Q 2 is 6-C 1-3-pyridinyl, R s CI and R 2 is Br.
  • Q 2 is 6-C 1-3-pyridinyl, R s CI and R 2 is CI.
  • Q 2 is 6-C 1-3-pyridinyl, R s Me and R 2 is MeS.
  • Q 2 is 6-C 1-3-pyridinyl, R s MeS and R 2 is Me.
  • Q 2 is 6-C 1-3-pyridinyl, R s Et and R 2 is Br.
  • Q 2 is 6-C 1-3-pyridinyl, R s Et and R 2 is CI.
  • Q 2 is 6-C 1-3-pyridinyl, R s Et and R 2 is Me.
  • Q 2 is 6-C 1-3-pyridinyl, R s Me and R 2 is Et.
  • Q 2 is 6-C 1-3-pyridinyl, R s CI and R 2 is Et.
  • Q 2 is 6-C 1-3-pyridinyl, R s Me and R 2 is CN. is 6-Me-3-pyridinyl, R is CI and R 2 is Me.
  • Q 2 is 6-Me-3-pyridinyl, R is CI and R 2 is CFH 2 .
  • Q 2 is 6-Me-3-pyridinyl, R is Br and R 2 is Me.
  • Q 2 is 6-Me-3-pyridinyl, R is I and R 2 is Me.
  • Q 2 is 6-Me-3-pyridinyl, R is Me and R 2 is Me.
  • Q 2 is 6-Me-3-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 6-Me-3-pyridinyl, R is Me and R 2 is Br.
  • Q 2 is 6-Me-3-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 6-Me-3-pyridinyl, R is Br and R 2 is Br.
  • Q 2 is 6-Me-3-pyridinyl, R is Br and R 2 is CI.
  • Q 2 is 6-Me-3-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 6-Me-3-pyridinyl, R is CI and R 2 is CI.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is CI and R 2 is Me.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is CI and R 2 is CFH 2 .
  • Q 2 is 6- -MeO- -3-pyridinyl, R is Br and R 2 is Me.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is I and R 2 is Me.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is Me and R 2 is Me.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is Me and R 2 is Br.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is Br and R 2 is Br.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is Br and R 2 is CI.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 6- -MeO- -3-pyridinyl, R is CI and R 2 is CI.
  • Q z is 6-CF3 -3-pyridinyl, R 1 is CI and z is Me.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is CI and R 2 is CFH 2 .
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is Br and R 2 is Me.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is I and R 2 is Me.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is Me and R 2 is Me.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is Me and R 2 is Me.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is Me and R 2 is CI.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is Me and R 2 is Br.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is Me and R 2 is I.
  • Q 2 is 6-CF3 -3-pyridinyl, R ⁇ is Br and R 2 is Br.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is Br and R 2 is CI.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is CI and R 2 is Br.
  • Q 2 is 6-CF3 -3-pyridinyl, R 1 is CI and R 2 is CI.
  • Q 2 is 6- ⁇ Br- ⁇ 3-pyridinyl, R is CI and R 2 is Me.
  • Q 2 is 6- ⁇ Br- ⁇ 3-pyridinyl, R is CI and R 2 is CFH 2 .
  • Q 2 is 6- ⁇ Br- ⁇ 3-pyridinyl, R is Br and R 2 is Me.
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is I and R z is Me.
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is Me and R 2 is Me,
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is Me and R 2 is Br.
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is Br and R 2 is Br.
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is Br and R 2 is CI.
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 6- -Br- ⁇ 3-pyridinyl, R is CI and R 2 is CI.
  • Q 2 is 6-F-3-pyridinyl, is CI and R 2 is Me.
  • Q 2 is 6-F-3-pyridinyl, R ⁇ is CI and R 2 is CFH 2 .
  • Q 2 is 6-F-3-pyridinyl, R ⁇ is Br and R 2 is Me.
  • Q 2 is 6-F-3-pyridinyl, R ⁇ is I and R 2 is Me.
  • Q 2 is 6-F-3-pyridinyl, R 1 is Me and R 2 is Me.
  • Q 2 is 6-F-3-pyridinyl, R 1 is Me and R 2 is CI.
  • Q 2 is 6-F-3-pyridinyl, R ⁇ is Me and R 2 is Br.
  • Q 2 is 6-F-3-pyridinyl, R ⁇ is Me and R 2 is I.
  • Q 2 is 6-F-3-pyridinyl, R ⁇ is Br and R 2 is Br.
  • Q 2 is 6-F-3-pyridinyl, R ⁇ is Br and R 2 is CI.
  • Q 2 is 6-F-3-pyridinyl, R ⁇ is CI and R 2 is Br.
  • Q 2 is 6-F-3-pyridinyl
  • R ⁇ is CI
  • R 2 is CI
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R 2 is Me.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R 2 is CFH 2 .
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is Br and R 2 is Me.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is I and R 2 is Me.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is Me and R 2 is Me.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 2-Cl.
  • 6-Me-4-pyridinyl R is Me and R 2 is Br.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is Br and R 2 is Br.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is Br and R 2 is CI.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R 2 is CI.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is CI and R 2 is Me.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is CI and R 2 is CFH 2 .
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is Br and R 2 is Me.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is I and R 2 is Me.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is Me and R 2 is Me.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is Me and R 2 is Br.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is Br and R 2 is Br.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is Br and R 2 is CI.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 2-Cl 6-MeO-3-pyridinyl, R is CI and R 2 is CI.
  • Q 2 is 2-Cl. 6-CF 3 -3-pyridinyl, R 1 is CI and z is Me.
  • Q 2 is 2-Cl. 6-CF 3 -3-pyridinyl, R 1 is CI and R 2 is CFH 2 .
  • Q 2 is 2-C , 6-CF3-3-pyridinyl, R 1 is Br and R ⁇ is Me.
  • Q 2 is 2-C , 6-CF3-3-pyridinyl, R ⁇ is I and R 2 is Me.
  • Q 2 is 2-C , 6-CF3-3-pyridinyl, R 1 is Me and R 2 is Me.
  • Q 2 is 2-C , 6-CF 3 -3-pyridinyl, R 1 is Me and R 2 is CI.
  • Q 2 is 2-C , 6-CF3-3-pyridinyl, R ⁇ is Me and R 2 is Br.
  • Q 2 is 2-C , 6-CF3-3-pyridinyl, R ⁇ is Me and R 2 is I.
  • Q 2 is 2-C , 6-CF3-3-pyridinyl, R ⁇ is Br and R 2 is Br.
  • Q 2 is 2-C , 6-CF 3 -3-pyridinyl, R 1 is Br and R 2 is CI.
  • Q 2 is 2-C , 6-CF 3 -3-pyridinyl, R 1 is CI and R 2 is Br.
  • Q 2 is 2-C , 6-CF 3 -3-pyridinyl, R 1 is CI and R 2 is CI.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is CI and R 2 is Me.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is CI and R 2 is CFH 2 .
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is Br and R 2 is Me.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is I and R 2 is Me.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is Me and R 2 is Me.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is Me and R 2 is Br.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is Br and R 2 is Br.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is Br and R 2 is CI.
  • Q 2 is 5-C ⁇ 3-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 5-C -3-pyridinyl, R 1 is CI and R 2 is CI.
  • Q z is 5-F-3-pyridinyl, R 1 is CI and R z is Me.
  • Q 2 is 5-F-3-pyridinyl, R 1 is CI and R 2 is CFH 2 .
  • Q 2 is 5-F-3-pyridinyl, R ⁇ is Br and R 2 is Me.
  • Q 2 is 5-F-3-pyridinyl, R ⁇ is I and R 2 is Me.
  • Q 2 is 5-F-3-pyridinyl, R 1 is Me and R 2 is Me.
  • Q 2 is 5-F-3-pyridinyl, R 1 is Me and R 2 is CI.
  • Q 2 is 5-F-3-pyridinyl, R ⁇ is Me and R 2 is Br.
  • Q 2 is 5-F-3-pyridinyl, R ⁇ is Me and R 2 is I.
  • Q 2 is 5-F-3-pyridinyl, R ⁇ is Br and R 2 is Br.
  • Q 2 is 5-F-3-pyridinyl, R ⁇ is Br and R 2 is CI.
  • Q 2 is 5-F-3-pyridinyl
  • R ⁇ is CI
  • R 2 is Br.
  • Q 2 is 5-F-3-pyridinyl
  • R 1 is CI
  • R 2 is CI
  • Q 2 is 5-Me-3-pyridinyl
  • R 1 is CI
  • R 2 is Me.
  • Q 2 is 5-Me-3-pyridinyl, R 1 is CI and R 2 is CFH 2 .
  • Q 2 is 5-Me-3-pyridinyl, R 1 is Br and R 2 is Me.
  • Q 2 is 5 ⁇ ⁇ Me-3-pyridinyl, R is I and is Me.
  • Q 2 is 5 ⁇ ⁇ Me-3-pyridinyl, R is Me and R 2 is Me, Q 2 is 5 ⁇ ⁇ Me-3-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 5 ⁇ Me-3-pyridinyl, R is Me and R 2 is Br.
  • Q 2 is 5 Me-3-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 5- Me-3-pyridinyl, R is Br and R 2 is Br.
  • Q 2 is 5- Me-3-pyridinyl, R is Br and R 2 is CI.
  • Q 2 is 5- Me-3-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 5- Me-3-pyridinyl, R is CI and R 2 is CI.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R is CI and R 2 is Me.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl
  • R is CI and R 2 is CFH 2
  • Q 2 is 5- ⁇ MeO-3-pyridinyl
  • R is Br and R 2 is Me.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R is I and R 2 is Me.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R is Me and R 2 is Me.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R is Me and R 2 is Br.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R is Br and R 2 is Br.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R is Br and R 2 is CI.
  • Q 2 is 5- ⁇ MeO-3-pyridinyl, R 1 is C and is Br.
  • Q 2 is 5- MeO-3-pyridinyl
  • R 1 is C
  • R 2 is CI.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is CI and R 2 is Me.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is CI and R 2 is CFH 2 .
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is Br and R 2 is Me.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is I and R 2 is Me.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R 2 is Me.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R 2 is Me.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R 2 is CI.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R 2 is Br.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R 2 is I.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is Br and R" is Br.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is Br and R" is CI.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is CI and R 2 is Br.
  • Q 2 is 6- CI, 5-MeO-3-pyridinyl, R is CI and R 2 is CI.
  • Q 2 is 6- Cl-3-pyridazinyl, R ⁇ is CI and R 2 is Me.

Abstract

Disclosed is a fungicidal composition comprising (a) at least one compound selected from the compounds of Formula 1, N-oxides, and salts thereof, wherein R1, R2, Q1 and Q2 are as defined in the disclosure; and (b) at least one additional fungicidal compound. Also disclosed is a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1, an N-oxide, or salt thereof (e.g., as a component in the aforesaid composition). Also disclosed is a composition comprising: (a) at least one compound selected from the compounds of Formula 1 described above, N-oxides, and salts thereof; and at least one invertebrate pest control compound or agent.

Description

TITLE
FUNGICIDAL MIXTURES
FIELD OF THE INVENTION
This invention relates to fungicidal mixtures of certain imidazole derivatives, their N-oxides and salts, and to compositions comprising such mixtures and methods for using such mixtures as fungicides.
BACKGROUND OF THE INVENTION
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. In addition to often being highly destructive, plant diseases can be difficult to control and may develop resistance to commercial fungicides. Combinations of fungicides are often used to facilitate disease control, to broaden spectrum of control and to retard resistance development. Furthermore, certain rare combinations of fungicides demonstrate a greater-than-additive (i.e. synergistic) effect to provide commercially important levels of plant disease control. The advantages of particular fungicide combinations are recognized in the art to vary, depending on such factors as the particular plant species and plant disease to be treated, and whether the plants are treated before or after infection with the fungal plant pathogen. Accordingly new advantageous combinations are needed to provide a variety of options to best satisfy particular plant disease control needs. Such combinations have now been discovered.
SUMMARY OF THE INVENTION
This invention relates to a fungicidal composition (i.e. combination) comprising (a) at least one compound selected from the compounds of Formula 1 (including all stereoisomers), N-oxides, and salts thereof:
Figure imgf000002_0001
1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl,
pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 4 substituents independently selected from R3 on carbon atom ring members and R4 on nitrogen atom ring members; Q2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 4 substituents independently selected from R5 on carbon atom ring members and R6 on nitrogen atom ring members;
R1 and R2 are independently halogen, cyano, nitro, Ci-C^ alkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, Ci-C^ haloalkyl, C2-C3 haloalkenyl, Ci-C^ alkoxy, Ci-C^ haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio or C^-C7 hydroxyalkyl;
each R3 and R5 is independently halogen, cyano, hydroxy, nitro, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C2-C7 cyanoalkyl, C^-C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C3-C7 cycloalkoxy, C3-C7 halocycloalkoxy, -C7 alkoxy, C2-C7 cyanoalkoxy, C1-C7 haloalkoxy, Cj-Cg alkylthio, -C7 haloalkylthio, -C7 alkylsulfinyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylsulfinyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7
dialkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, aminocarbonyl, C2-C7 alkylaminocarbonyl, C3-C7 dialkylaminocarbonyl, C2-C7
alkylcarbonylamino, C3-C10 trialkylsilyl, -SCN, C(=S)NH2 or -X-U-Z;
each R4 and R6 is independently cyano, Cj-Cg alkyl, C3-C6 alkenyl, C3-C6 alkynyl, Cj-Cg haloalkyl, C3-C6 cycloalkyl, Cj-Cg alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-Cg alkoxycarbonyl, C2-Cg alkylaminoalkyl or C3-Cg dialkylaminoalkyl;
each X is independently O, S(=0)n, NR7 or a direct bond;
each U is independently Cj-Cg alkylene, C2-C6 alkenylene, C3-C6 alkynylene, C3-C6 cycloalkylene or C3-Cg cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(=0), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, Cj-Cg alkyl, C^-Cg haloalkyl, C^-Cg alkoxy and C^-Cg haloalkoxy;
each Z is independently NR8aR8b, OR9 or S(=0)nR10;
each R7 is independently H, Cj-Cg alkyl, Cj-Cg haloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-Cg cycloalkoxycarbonyl, C4-Cg (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl);
each R8a and R8b is independently H, Cj-Cg alkyl, -Cg haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8
(cycloalkylthio)carbonyl or C4-Cg cycloalkoxy(thiocarbonyl); each R9 and R10 is independently H, Cj-Cg alkyl, -Cg haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8
(cycloalkylthio)carbonyl or C4-Cg cycloalkoxy(thiocarbonyl);
each n is independently 0, 1 or 2; and
(b) at least one additional fungicidal compound.
This invention also relates to a composition comprising: (a) at least one compound selected from the compounds of Formula 1 described above, N-oxides, and salts thereof; and at least one invertebrate pest control compound or agent.
This invention also relates to a composition comprising one of the aforesaid compositions comprising component (a) and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
This invention also relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of one of the aforesaid compositions.
The aforedescribed method can also be described as a method for protecting a plant or plant seed from diseases caused by fungal pathogens comprising applying a fungicidally effective amount of one of the aforesaid compositions to the plant (or portion thereof) or plant seed (directly or through the environment (e.g., growing medium) of the plant or plant seed).
As a further aspect, this invention also relates to a compound selected from the compounds of Formula 1 (including all stereoisomers), N-oxides, and salts thereof, as defined above provided that
when Q1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 4 substituents independently selected from R3a on carbon atom ring members and R4a on nitrogen atom ring members; wherein
each R3a is independently halogen, cyano, hydroxy, nitro, -C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C^-C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C3-C7 cycloalkoxy, C3-C7 halocycloalkoxy, C1-C7 alkoxy, C^-C7 haloalkoxy, C^-Cg alkylthio, C1-C7 haloalkylthio, C1-C7 alkylsulfmyl, -C7 alkylsulfonyl, C1-C7 haloalkylsulfmyl, -C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylcarbonylamino, C3-C^o trialkylsilyl, -SCN, C(=S)NH2 or -X-U-Z; and each R4a is independently cyano, Cj-Cg alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, -Cg alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-Cg alkoxycarbonyl, C2-Cg alkylaminoalkyl or C3-C6 dialkylaminoalkyl; then Q2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each substituted with 1 to 4 substituents independently selected from R5 on carbon atom ring members and R6 on nitrogen atom ring members; provided that least one substituent is C2-C7 cyanoalkyl, C2-C7 cyanoalkoxy, aminocarbonyl, C2-C7 alkylaminocarbonyl or C3"C7 dialkylaminocarbonyl on a carbon atom ring member, or C^-Cg haloalkyl on a nitrogen atom ring member.
This invention also relates to a fungicidal composition comprising a fungicidally effective amount of a compound selected from the compounds of the aforedescribed further aspect and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound selected from the compounds of the aforedescribed further aspect (e.g., as a composition described herein).
DETAILS OF THE INVENTION
As used herein, the terms "comprises," "comprising," "includes," "including," "has,"
"having," "contains", "containing," "characterized by" or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process or method 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 or method.
The transitional phrase "consisting of excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consisting of appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.
The transitional phrase "consisting essentially of is used to define a composition or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of occupies a middle ground between "comprising" and "consisting of. Where applicants have defined an invention or a portion thereof with an open-ended term such as "comprising," it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms "consisting essentially of or "consisting of."
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 the present disclosure and claims, "plant" includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds). Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
As referred to herein, the term "seedling", used either alone or in a combination of words means a young plant developing from the embryo of a seed.
As used herein, the term "alkylating agent" refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to a leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom. Unless otherwise indicated, the term "alkylating" does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified, for example, for R1 and R2.
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, n-propyl, /-propyl, or the different butyl, pentyl, hexyl or heptyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl, hexenyl and heptenyl 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, hexynyl and heptynyl isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl. "Alkylene" denotes a straight-chain or branched alkanediyl. Examples of "alkylene" include CH2, CH2CH2, CH(CH3), CH2CH2CH2, CH2CH(CH3) and the different butylene, pentylene and hexylene isomers. "Alkenylene" denotes a straight-chain or branched alkenediyl containing one olefmic bond. Examples of "alkenylene" include CH=CH, CH2CH=CH, CH=C(CH3). "Alkynylene" denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of "alkynylene" include CH2C≡C, C≡CCH2 and the different butynylene, pentynylene and hexynylene isomers.
"Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy, hexyloxy and heptyloxy isomers. "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio, hexylthio and heptylthio isomers. "Alkylsulfmyl" includes both enantiomers of an alkylsulfmyl group. Examples of "alkylsulfmyl" include CH3S(=0), CH3CH2S(=0), CH3CH2CH2S(=0), (CH3)2CHS(=0) and the different butylsulfmyl, pentylsulfmyl, hexylsulfmyl and heptylsulfmyl isomers. Examples of "alkylsulfonyl" include CH3S(=0)2, CH3CH2S(=0)2, CH3CH2CH2S(=0)2, (CH3)2CHS(=0)2, and the different butylsulfonyl, pentylsulfonyl, hexylsulfonyl and heptylsulfonyl isomers. "Alkylamino" includes an NH radical substituted with straight-chain or branched alkyl. Examples of "alkylamino" include CH3CH2NH, CH3CH2CH2NH, and (CH3)2CHCH2NH. Examples of "dialkylamino" include (CH3)2N, (CH3CH2CH2)2N and CH3CH2(CH3)N.
"Cyanoalkyl" denotes an alkyl group substituted with one cyano group. Examples of "cyanoalkyl" include NCCH2, NCCH2CH2 and CH3CH(CN)CH2. "Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. "(Alkylthio)carbonyl" denotes a straight-chain or branched alkylthio group bonded to a C(=0) moiety. Examples of "(alkylthio)carbonyl" include CH3SC(=0), CH3CH2CH2SC(=0) and (CH3)2CHSC(=0). "Alkoxy(thiocarbonyl)" denotes a straight-chain or branched alkoxy group bonded to a C(=S) moiety. Examples of "alkoxy(thiocarbonyl)" include CH3OC(=S), CH3CH2CH2OC(=S) and (CH3)2CHOC(=S). "Alkylaminoalkyl" denotes alkylamino substitution on alkyl. Examples of "alkylaminoalkyl" include CH3NHCH2, CH3NHCH2CH2, CH3CH2NHCH2, CH3CH2CH2CH2NHCH2 and CH3CH2NHCH2CH2. Examples of "dialkylaminoalkyl" include ((CH3)2CH)2NCH2, (CH3CH2CH2)2NCH2 and CH3CH2(CH3)NCH2CH2. The term "alkylcarbonylamino" denotes alkyl bonded to a C(=0)NH moiety. Examples of "alkylcarbonylamino" include CH3CH2C(=0)NH and CH3CH2CH2C(=0)NH.
"Hydroxyalkyl" denotes an alkyl group substituted with one hydroxy group. Examples of "hydroxyalkyl" include HOCH2CH2, CH3CH2(OH)CH and HOCH2CH2CH2CH2.
"Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The term "alkylcycloalkyl" denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, z'-propylcyclobutyl, methylcyclopentyl and 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 "cycloalkylcycloalkyl" denotes cycloalkyl substitution on another cycloalkyl ring, wherein each cycloalkyl ring independently has from 3 to 7 carbon atom ring members. Examples of cycloalkylcycloalkyl include cyclopropylcyclopropyl (such as Ι,Γ-bicyclopropyl-l-yl, Ι,Γ- bicyclopropyl-2-yl), cyclohexylcyclopentyl (such as 4-cyclopentylcyclohexyl) and cyclohexylcyclohexyl (such as Ι,Γ-bicyclohexyl-l-yl), and the different cis- and trans- cycloalkylcycloalkyl isomers, (such as (li?,25)-l,l'-bicyclopropyl-2-yl and (1R,2R)-1,1'- bicyclopropyl-2-yl). The term "cycloalkoxy" denotes cycloalkyl attached to and linked through an oxygen atom including, for example, cyclopentyloxy and cyclohexyloxy. "Cycloalkylcarbonyl" denotes cycloalkyl bonded to a C(=0) group including, for example, cyclopropylcarbonyl and cyclopentylcarbonyl. The term "cycloalkoxycarbonyl" means cycloalkoxy bonded to a C(=0) group, for example, cyclopropyloxycarbonyl and cyclopentyloxycarbonyl. The term "cycloalkylene" denotes a cycloalkanediyl ring. Examples of "cycloalkylene" include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene. The term "cycloalkenylene" denotes a cycloalkenediyl ring containing one olefmic bond. Examples of "cycloalkenylene" include cylopropenediyl and cyclpentenediyl.
"Alkylcarbonyl" denotes a straight-chain or branched alkyl bonded to a C(=0) moiety. Examples of "alkylcarbonyl" include CH3C(=0), CH3CH2CH2C(=0) and (CH3)2CHC(=0). Examples of "alkoxycarbonyl" include CH3OC(=0), CH3CH2OC(=0), CH3CH2CH2OC(=0), (CH3)2CHOC(=0) and the different butoxy-, pentoxy- and hexoxycarbonyl isomers.
"Trialkylsilyl" includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom, such as trimethylsilyl, triethylsilyl and tert-butyldimethylsilyl.
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, C1CH2, CF3CH2 and CF3CC12. The terms "haloalkenyl", "haloalkoxy", "haloalkylthio", "haloalkylsulfmyl", "haloalkylsulfonyl", "halocycloalkyl", "halocycloalkoxy" and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include C12C=CHCH2 and CF3CH2CH=CHCH2. Examples of "haloalkoxy" include CF30, CC13CH20, F2CHCH2CH20 and CF3CH20. Examples of "haloalkylthio" include CC13S, CF3S, CC13CH2S and C1CH2CH2CH2S. Examples of "haloalkylsulfmyl" include CF3S(=0), CC13S(=0), CF3CH2S(=0) and CF3CF2S(=0). Examples of "haloalkylsulfonyl" include CF3S(=0)2, CC13S(=0)2, CF3CH2S(=0)2 and CF3CF2S(=0)2. Examples of "halocycloalkyl" include 2-chlorocyclopropyl, 2-fluorocyclobutyl, 3-bromocyclopentyl and 4-chlorocyclohexyl. The words "fluoroalkyl", "fluoromethyl", "fluoroalkoxy" and "fluoromethoxy" are defined analogously to "haloalkyl" and "haloalkoxy" unless otherwise specified. Accordingly, "fluoromethoxy" includes CH2FO, CHF20 and CF30.
The total number of carbon atoms in a substituent group is indicated by the "Cj-Cj" prefix where i andj are numbers from 1 to 14. For example, C1-C4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, 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.
The term "unsubstituted" in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1. The term "optionally substituted" means that the number of substituents can be zero. Unless otherwise indicated, optionally substituted groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. As used herein, the term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted".
The number of optional substituents may be restricted by an expressed limitation. For example, the phrase "optionally substituted with up to 4 substituents selected from R3 on carbon atom ring members and R4 on nitrogen atom ring members" means that 0, 1, 2, 3 or 4 substituents can be present (if the number of potential connection points allows). When a range specified for the number of substituents exceeds the number of positions available for substituents on a ring, the actual higher end of the range is recognized to be the number of available positions.
In the context of the present invention when an instance of Q1 or Q2 comprises a phenyl, pyridinyl, pyridazinyl, pyrimidinyl or quinolinyl ring, the ortho, meta and para positions of each ring is relative to the connection of the ring to the remainder of Formula 1. Further, when an instance of Q1 or Q2 comprises a phenyl ring attached through the linker CH2 (i.e. benzyl) to the remainder of Formula 1, the ortho, meta and para positions of the phenyl ring is relative to the connection of the ring to the linker CH2.
A wide variety of synthetic methods are known in the art to enable preparation of aromatic heterocyclic rings and ring systems; for extensive reviews see the eight volume set of Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief, Pergamon Press, Oxford, 1984 and the twelve volume set of Comprehensive Heterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996. Compounds relevant to 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 stereo isomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers or as individual stereoisomers (e.g., in optically active form). Of note are atropisomers, which are conformational isomers that occur when rotation about a single bond in a molecule is restricted as a result of steric interaction with other parts of the molecule and the substituents at both ends of the single bond are unsymmetrical. In the present invention, atropisomerism occurs at a single bond in Formula 1 when the rotational barrier is high enough (about AG > 25 kcal moH) that separation of isomers at ambient temperature becomes possible. One skilled in the art will appreciate that one atropisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other atropisomer or when separated from the other atropisomer. Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said atropisomers. A detailed description of atropisomers can be found in March, Advanced Organic Chemistry, 4th Ed. 1992, 101-102 and Gawronski et al, Chirality 2002, 14, 689-702. This invention includes compounds or compositions that are enriched in an atropisomer of Formula 1 compared to other atropisomers of the compounds. Also included are the essentially pure atropisomers of compounds of Formula 1.
One skilled in the art will appreciate that not all 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. One skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of 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 m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of N-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.
One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 alone and in mixtures are useful for control of plant diseases caused by fungal plant pathogens (i.e. are agriculturally suitable). The salts of the compounds of Formula 1 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. Accordingly, the present invention relates to compounds selected from Formula 1, N-oxides and agriculturally suitable salts thereof.
Compounds selected from Formula 1, geometric and other stereoisomers, N-oxides, and salts thereof, typically exist in more than one form, and Formula 1 thus includes all crystalline and non-crystalline forms of the compounds that Formula 1 represents. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term "polymorph" refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability. One skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
As described in the Summary of the Invention, an aspect of the present invention is directed at a composition comprising (a) at least one compound selected from Formula 1, N-oxides, and salts thereof, with (b) at least one additional fungicidal compound. More particularly, Component (b) is selected from the group consisting of
(bl) methyl benzimidazole carbamate (MBC) fungicides; (b2) dicarboximide fungicides;
(b3) demethylation inhibitor (DMI) fungicides;
(b4) phenylamide fungicides;
(b5) amine/morpholine fungicides;
(b6) phospholipid biosynthesis inhibitor fungicides;
(b7) carboxamide fungicides;
(b8) hydroxy(2-amino-)pyrimidine fungicides;
(b9) anilinopyrimidine fungicides;
N-phenyl carbamate fungicides;
quinone outside inhibitor (Qol) fungicides;
phenylpyrrole fungicides;
quinoline fungicides;
lipid peroxidation inhibitor fungicides;
melanin biosynthesis inhibitors-reductase (MBI-R) fungicides;
melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides;
hydroxyanilide fungicides;
squalene-epoxidase inhibitor fungicides;
polyoxin fungicides;
phenylurea fungicides;
quinone inside inhibitor (Qil) fungicides;
benzamide fungicides;
enopyranuronic acid antibiotic fungicides;
hexopyranosyl antibiotic fungicides;
glucopyranosyl antibiotic: protein synthesis fungicides;
glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides; cyanoacetamideoxime fungicides;
carbamate fungicides;
oxidative phosphorylation uncoupling fungicides;
organo tin fungicides;
carboxylic acid fungicides;
heteroaromatic fungicides;
phosphonate fungicides;
phthalamic acid fungicides;
benzotriazine fungicides;
benzene-sulfonamide fungicides;
pyridazinone fungicides;
thiophene-carboxamide fungicides;
pyrimidinamide fungicides; (b40) carboxylic acid amide (CAA) fungicides;
(b41) tetracycline antibiotic fungicides;
(b42) thiocarbamate fungicides;
(b43) benzamide fungicides;
(b44) host plant defense induction fungicides;
(b45) multi-site contact activity fungicides;
(b46) fungicides other than fungicides of component (a) and components (bl)
through (b45); and
salts of compounds of (bl) through (b46).
Of note are embodiments wherein component (b) comprises at least one fungicide from each of two different groups selected from (bl) through (b46).
"Methyl benzimidazole carbamate (MBC) fungicides (bl)" (FRAC (Fungicide Resistance Action Committee) code 1) inhibit mitosis by binding to β-tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides. The benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole. The thiophanates include thiophanate and thiophanate-methy 1.
"Dicarboximide fungicides (b2)" (FRAC code 2) are proposed to inhibit a lipid peroxidation in fungi through interference with NADH cytochrome c reductase. Examples include chlozolinate, iprodione, procymidone and vinclozolin.
"Demethylation inhibitor (DMI) fungicides (b3)" (FRAC code 3) inhibit C14-demethylase which plays a role in sterol production. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides result in abnormal growth and eventually death of sensitive fungi. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz, pefurazoate and triflumizole. The pyrimidines include fenarimol, nuarimol and triarimol. The piperazines include triforine. The pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
"Phenylamide fungicides (b4)" (FRAC code 4) are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide. Phenylamide fungicides include acylalanine, oxazolidinone and butyrolactone fungicides. The acylalanines include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl, metalaxyl-M (also known as mefenoxam). The oxazolidinones include oxadixyl. The butyrolactones include ofurace.
"Amine/morpholine fungicides (b5)" (FRAC code 5) inhibit two target sites within the sterol biosynthetic pathway, Δ8→ Δ7 isomerase and Δ14 reductase. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Amine/morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine and spiroketal-amine fungicides. The morpho lines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin and piperalin. The spiroketal-amines include spiroxamine.
"Phospholipid biosynthesis inhibitor fungicides (b6)" (FRAC code 6) inhibit growth of fungi by affecting phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phosphorothiolate and dithiolane fungicides. The phosphorothiolates include edifenphos, iprobenfos and pyrazophos. The dithiolanes include isoprothiolane.
"Carboxamide fungicides (b7)" (FRAC code 7) inhibit Complex II (succinate dehydrogenase) fungal respiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting respiration prevents the fungus from making ATP, and thus inhibits growth and reproduction. Carboxamide fungicides include benzamide, furan carboxamide, oxathiin carboxamide, thiazole carboxamide, pyrazole carboxamide and pyridine carboxamide. The benzamides include benodanil, flutolanil and mepronil. The furan carboxamides include fenfuram. The oxathiin carboxamides include carboxin and oxycarboxin. The thiazole carboxamides include thifluzamide. The pyrazole carboxamides include bixafen, furametpyr, isopyrazam, fluxapyroxad, penthiopyrad, sedaxane (N-[2-( 1 S,2R)-[ 1 , 1 '-bicyclopropyl] -2-ylphenyl] -3 -(difluoromethyl)- 1 -methyl- IH- pyrazole-4-carboxamide) and penflufen (N-[2-(l,3-dimethylbutyl)phenyl]-5-fluoro-l,3- dimethyl-lH-pyrazole-4-carboxamide) (PCT Patent Publication WO 2003/010149). The pyridine carboxamides include boscalid.
"Hydroxy(2-amino-)pyrimidine fungicides (b8)" (FRAC code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol and ethirimol. "Anilinopyrimidine fungicides (b9)" (FRAC code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydro lytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.
"N-Phenyl carbamate fungicides (blO)" (FRAC code 10) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.
"Quinone outside inhibitor (Qol) fungicides (bl l)" (FRAC code 11) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the "quinone outside" (Q0) site of the cytochrome bc\ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone outside inhibitor fungicides include methoxyacrylate, methoxycarbamate, oximino acetate, oximinoacetamide and dihydrodioxazine fungicides (collectively known as strobilurin fungicides), and oxazolidinedione, imidazolinone and benzylcarbamate fungicides. The methoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) and picoxystrobin. The methoxycarbamates include pyraclostrobin and pyrametostrobin. The oximinoacetates include kresoxim-methyl, pyraoxystrobin and trifloxystrobin. The oximinoacetamides include dimoxystrobin, metominostrobin, orysastrobin and a-(methoxyimino)-N-methyl-2-[[[l-[3-(trifluoro- methyl)phenyl]ethoxy]imino]methyl]benzeneacetamide. The dihydrodioxazines include fluoxastrobin. The oxazolidinediones include famoxadone. The imidazolinones include fenamidone. The benzylcarbamates include pyribencarb.
"Phenylpyrrole fungicides (bl2)" (FRAC code 12) inhibit a MAP protein kinase associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.
"Quinoline fungicides (bl3)" (FRAC code 13) are proposed to inhibit signal transduction by affecting G-proteins in early cell signaling. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powder mildew diseases. Quinoxyfen is an example of this class of fungicide.
"Lipid peroxidation inhibitor fungicides (bl4)" (FRAC code 14) are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etridiazole, may also affect other biological processes such as respiration and melanin biosynthesis. Lipid peroxidation fungicides include aromatic carbon and 1,2,4- thiadiazole fungicides. The aromatic carbons include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos-methyl. The 1,2,4-thiadiazoles include etridiazole.
"Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides (bl5)" (FRAC code 16.1) inhibit the naphthal reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitors-reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. The isobenzofuranones include fthalide. The pyrroloquinolinones include pyroquilon. The triazolobenzothiazoles include tricyclazole.
"Melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides (bl6)" (FRAC code
16.2) inhibit scytalone dehydratase in melanin biosynthesis. Melanin in required for host plant infection by some fungi. Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides. The cyclopropanecarboxamides include carpropamid. The carboxamides include diclocymet. The propionamides include fenoxanil.
"Hydroxyanilide fungicides (bl7)" (FRAC code 17) inhibit C4-demethylase which plays a role in sterol production. Examples include fenhexamid.
"Squalene-epoxidase inhibitor fungicides (bl8)" (FRAC code 18) inhibit squalene- epoxidase in ergosterol biosynthesis pathway. Sterols such as ergosterol are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore exposure to these fungicides result in abnormal growth and eventually death of sensitive fungi. Squalene-epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides. The thiocarbamates include pyributicarb. The allylamines include naftifme and terbinafme.
"Polyoxin fungicides (bl9)" (FRAC code 19) inhibit chitin synthase. Examples include polyoxin.
"Phenylurea fungicides (b20)" (FRAC code 20) are proposed to affect cell division. Examples include pencycuron.
"Quinone inside inhibitor (Qil) fungicides (b21)" (FRAC code 21) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol reductase. Reduction of ubiquinol is blocked at the "quinone inside" (Qj) site of the cytochrome bc\ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone inside inhibitor fungicides include cyanoimidazole and sulfamoyltriazole fungicides. The cyanoimidazoles include cyazofamid. The sulfamoyltriazoles include amisulbrom.
"Benzamide fungicides (b22)" (FRAC code 22) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include zoxamide.
"Enopyranuronic acid antibiotic fungicides (b23)" (FRAC code 23) inhibit growth of fungi by affecting protein biosynthesis. Examples include blasticidin-S.
"Hexopyranosyl antibiotic fungicides (b24)" (FRAC code 24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin. "Glucopyranosyl antibiotic: protein synthesis fungicides (b25)" (FRAC code 25) inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.
"Glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides (b26)" (FRAC code 26) inhibit trehalase in inositol biosynthesis pathway. Examples include validamycin.
"Cyanoacetamideoxime fungicides (b27) (FRAC code 27) include cymoxanil.
"Carbamate fungicides (b28)" (FRAC code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, iodocarb, and prothiocarb are examples of this fungicide class.
"Oxidative phosphorylation uncoupling fungicides (b29)" (FRAC code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development. This class includes 2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.
"Organo tin fungicides (b30)" (FRAC code 30) inhibit adenosine triphosphate (ATP) synthase in oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride and fentin hydroxide.
"Carboxylic acid fungicides (b31)" (FRAC code 31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.
"Heteroaromatic fungicides (b32)" (FRAC code 32) are proposed to affect DNA/ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides include isoxazole and isothiazolone fungicides. The isoxazoles include hymexazole and the isothiazolones include octhilinone.
"Phosphonate fungicides (b33)" (FRAC code 33) include phosphorous acid and its various salts, including fosetyl-aluminum.
"Phthalamic acid fungicides (b34)" (FRAC code 34) include teclofthalam.
"Benzotriazine fungicides (b35)" (FRAC code 35) include triazoxide.
"Benzene-sulfonamide fungicides (b36)" (FRAC code 36) include flusulfamide.
"Pyridazinone fungicides (b37)" (FRAC code 37) include diclomezine.
"Thiophene-carboxamide fungicides (b38)" (FRAC code 38) are proposed to affect ATP production. Examples include silthiofam.
"Pyrimidinamide fungicides (b39)" (FRAC code 39) inhibit growth of fungi by affecting phospholipid biosynthesis and include diflumetorim.
"Carboxylic acid amide (CAA) fungicides (b40)" (FRAC code 40) are proposed to inhibit phospholipid biosynthesis and cell wall deposition. Inhibition of these processes prevents growth and leads to death of the target fungus. Carboxylic acid amide fungicides include cinnamic acid amide, valinamide carbamate and mandelic acid amide fungicides. The cinnamic acid amides include dimethomorph and flumorph. The valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valifenalate (valiphenal). The mandelic acid amides include mandipropamid, N-[2-[4-[[3-(4- chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]-ethyl]-3-methyl-2-[(methylsulfonyl)- amino]butanamide and N-[2-[4-[[3-(4-chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]- ethyl]-3-methyl-2-[(ethylsulfonyl)amino]-butanamide.
"Tetracycline antibiotic fungicides (b41)" (FRAC code 41) inhibit growth of fungi by affecting complex 1 nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examples include oxytetracycline .
"Thiocarbamate fungicides (b42)" (FRAC code 42) include methasulfocarb.
"Benzamide fungicides (b43)" (FRAC code 43) inhibit growth of fungi by derealization of spectrin-like proteins. Examples include acylpicolide fungicides such as fluopicolide and fluopyram.
"Host plant defense induction fungicides (b44)" (FRAC code P) induce host plant defense mechanisms. Host plant defense induction fungicides include benzo-thiadiazole, benzisothiazole and thiadiazole-carboxamide fungicides. The benzo-thiadiazoles include acibenzolar-S-methyl. The benzisothiazoles include probenazole. The thiadiazole- carboxamides include tiadinil and isotianil.
"Multi-site contact fungicides (b45)" inhibit fungal growth through multiple sites of action and have contact/preventive activity. This class of fungicides includes: "copper fungicides (b45.1) (FRAC code Ml)", "sulfur fungicides (b45.2) (FRAC code M2)", "dithiocarbamate fungicides (b45.3) (FRAC code M3)", "phthalimide fungicides (b45.4) (FRAC code M4)", "chloronitrile fungicides (b45.5) (FRAC code M5)", "sulfamide fungicides (b45.6) (FRAC code M6)", "guanidine fungicides (b45.7) (FRAC code M7)" "triazine fungicides (b45.8) (FRAC code M8)" and "quinone fungicides (b45.9) (FRAC code M9)". "Copper fungicides" are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). "Sulfur fungicides" are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur. "Dithiocarbamate fungicides" contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram. "Phthalimide fungicides" contain a phthalimide molecular moiety; examples include folpet, captan and captafol. "Chloronitrile fungicides" contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil. "Sulfamide fungicides" include dichlofluanid and tolylfluanid. "Guanidine fungicides" include dodine, guazatine and iminoctadine. "Triazine fungicides" include anilazine. "Quinone fungicides" include dithianon. "Fungicides other than fungicides of component (a) and components (bl) through (b45); (b46)" include certain fungicides whose mode of action may be unknown. These include: (b46.1) "thiazole carboxamide fungicides (FRAC code U5)", (b46.2) "phenyl- acetamide fungicides (FRAC code U6)", (b46.3) "quinazolinone fungicides (FRAC code U7)", (b46.4) "benzophenone fungicides (FRAC code U8)" and (46.5) "triazolopyrimidylamine fungicides" (alternatively named "triazolopyrimidine fungicides") (FRAC code 45). The thiazole carboxamides include ethaboxam. The phenyl-acetamides include cyflufenamid and N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3- difluorophenyl]-methylene]benzeneacetamide. The quinazolinones include proquinazid and 2-butoxy-6-iodo-3-propyl-4H-l-benzopyran-4-one. The benzophenones include metrafenone and pyriofenone. The triazolopyrimidylamines include ametoctradin (5-ethyl- 6-octyl[l,2,4]triazolo[l,5-a]pyrimidin-7-amine) and are believed to inhibit Complex III mitochondrial respiration by binding to an unelucidated site on ubiquinone-cytochrome bcl reductase. The (b46) class also includes bethoxazin, neo-asozin (ferric methanearsonate), fenpyrazamine, pyrrolnitrin, quinomethionate, tebufloquin, 2-[[2-fluoro-5-(trifluoromethyl)- phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile (OK-5203), 3-[5-(4- chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine (SYP-Z048), 4-fluorophenyl N-[l- [[ [ 1 -(4-cyanophenyl)ethyl] sulfonyl]methyl]propyl] carbamate (XR-539), N-(4-chloro-2-nitro- phenyl)-N-ethyl-4-methylbenzenesulfonamide (TF-991), 5-chloro-6-(2,4,6-trifluorophenyl)- 7-(4-methylpiperidin-l-yl)[l,2,4]triazolo[l,5-a]pyrimidine (BAS600), iV-[4-[4-chloro- 3 -(trifluoromethyl)phenoxy] -2,5 -dimethylphenyl] -N-ethyl-N-methylmethanimidamide, and 1 -[(2-propenylthio)carbonyl]-2-(l -methylethyl)-4-(2-methylphenyl)-5-amino- lH-pyrazol- 3 -one.
In the embodiments of the present invention, including those described below, reference to Formula 1 includes N-oxides and salts thereof, and reference to "a compound of Formula 1" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments.
Embodiment 1. The composition comprising components (a) and (b) described in the Summary of the Invention wherein in Formula 1, R1 and R2 are independently halogen, cyano, Ci-C^ alkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, Ci-C^ haloalkyl, C2-C3 haloalkenyl, C1 -C2 alkoxy, C 1 -C2 haloalkoxy, C1 -C2 alkylthio or Ci -C3 hydroxyalkyl.
Embodiment 2. The composition of Embodiment 1 wherein R1 and R2 are
independently halogen, cyano, ethenyl, ethynyl, methoxy or methylthio; or methyl optionally substituted with one substituent selected from halogen, -ΟΗ and methyl. Embodiment 3. The composition of Embodiment 2 wherein R1 and R2 are
independently halogen, cyano or methoxy; or methyl optionally substituted with one substituent selected from F, CI or methyl.
Embodiment 4. The composition of Embodiment 1 wherein R1 and R2 are
independently halogen, cyano or Ci-C^ alkyl.
Embodiment 5. The composition of Embodiment 3 or 4 wherein R1 and R2 are
independently CI, Br, I or Ci-C2 alkyl.
Embodiment 6. The composition of Embodiment 5 wherein R1 and R2 are
independently CI, Br or methyl.
Embodiment 7. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 6 wherein in Formula 1, Q1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R3 on carbon atom ring members and R4 on nitrogen atom ring members.
Embodiment 8. The composition of Embodiment 7 wherein Q1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R3 on carbon atom ring members and R4 on nitrogen atom ring members. Embodiment 9. The composition of Embodiment 8 wherein Q1 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R3 on carbon atom ring members.
Embodiment 10. The composition of Embodiment 9 wherein Q1 is a phenyl or
pyridinyl ring optionally substituted with up to 3 substituents independently selected from R3 on carbon atom ring members.
Embodiment 1 1. The composition of Embodiment 9 or 10 wherein when Q1 is an optionally substituted pyridinyl ring, the pyridinyl ring is attached to Formula 1 at the 3-position of the pyridinyl ring (i.e. 3-pyridinyl).
Embodiment 12. The composition of Embodiment 10 wherein Q1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R3.
Embodiment 13. The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 12 wherein in Formula 1, Q2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R5 on carbon atom ring members and R6 on nitrogen atom ring members.
Embodiment 14. The composition of Embodiment 13 wherein Q2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from
R5 on carbon atom ring members and R6 on nitrogen atom ring members.
Embodiment 15. The composition of Embodiment 14 wherein Q2 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R5 on carbon atom ring members.
Embodiment 16. The composition of Embodiment 15 wherein Q2 is a phenyl or
pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5 on carbon atom ring members.
Embodiment 17. The composition of Embodiment 15 or 16 wherein when Q2 is an optionally substituted pyridinyl ring, the pyridinyl ring is attached to Formula 1 at the 3-position of the pyridinyl ring (i.e. 3-pyridinyl).
Embodiment 18. The composition of Embodiment 16 wherein Q2 is a phenyl ring
optionally substituted with up to 3 substituents independently selected from R5. Embodiment 19. The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 18 wherein in
Formula 1, when Q1 and Q2 each independently comprise a phenyl or pyridinyl ring, then the ring of one of Q1 and Q2 is substituted with 2 or 3 substituents and the ring of the other of Q1 and Q2 is substituted with 0 to 3 substituents.
Embodiment 20. The composition of Embodiment 19 wherein when Q1 and Q2 each independently comprise a phenyl or pyridinyl ring, then the ring of one of Q1 and
Q2 is substituted with 2 or 3 substituents and the ring of the other of Q1 and Q2 is substituted with 1 or 2 substituents.
Embodiment 21. The composition of Embodiment 20 wherein when Q1 and Q2 each independently comprise a phenyl or pyridinyl ring, then the ring of one of Q1 and Q2 is substituted with 2 or 3 substituents and the ring of the other of Q1 and Q2 is substituted with 1 substituent.
Embodiment 22. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 21 wherein in
Formula 1, when Q1 and Q2 each independently comprise a phenyl or pyridinyl ring, then the ring of one of Q1 and Q2 is substituted with at least one substituent at an ortho position and the ring of the other of Q1 and Q2 is substituted with at least one substituent at a meta or para position.
Embodiment 23. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 22 wherein in Formula 1, each R3 and R5 is independently halogen, cyano, Ci -C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, C 1 -C3 haloalkyl, cyclopropyl, C1 -C3 alkoxy, C1 -C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl or C2-C4 alkylcarbonylamino. Embodiment 24. The composition of Embodiment 23 wherein each R3 and R5 is independently halogen, cyano, Ci-C^ alkyl, C2-C3 alkenyl, Ci-C^ haloalkyl, C1 -C3 alkoxy, C 1 -C3 haloalkoxy, C1 -C3 alkylthio or C1-C3 alkylamino.
Embodiment 25. The composition of Embodiment 24 wherein each R3 and R5 is
independently halogen, cyano, Ci-C^ alkyl, Ci-C^ haloalkyl, Ci-C^ alkoxy or
C1 -C3 haloalkoxy.
Embodiment 26. The composition of Embodiment 25 wherein each R3 and R5 is
independently F, CI, Br, cyano, Ci -C2 alkyl, Ci -C2 haloalkyl, Ci -C2 alkoxy or C1 -C2 haloalkoxy.
Embodiment 27. The composition of Embodiment 26 wherein each R3 and R5 is
independently F, CI, cyano, methyl, Ci -C2 alkoxy or fluoromethoxy.
Embodiment 28. The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 27 wherein in Formula 1, each R4 and R6 is independently cyano, Ci -C3 alkyl or cyclopropyl. Embodiment 29. The composition of Embodiment 28 wherein each R4 and R6 is
independently Ci -C3 alkyl.
Embodiment 30. The composition of Embodiment 29 wherein independently each R4 and R6 is methyl.
Embodiment 31. The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 30 wherein in
Formula 1, each X is independently O or NR7.
Embodiment 32. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 31 wherein in
Formula 1, each R7 is H.
Embodiment 33. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 32 wherein in
Formula 1, each U is independently C2-C4 alkylene.
Embodiment 34. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 33 wherein in Formula 1, each Z is independently NR8aR8b or OR9.
Embodiment 35. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 34 wherein in
Formula 1, each R8a and R8b is independently H, Cj-Cg alkyl or Cj-Cg haloalkyl.
Embodiment 36. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 35 wherein in Formula 1, each R9 is independently H, C^-Cg alkyl or C^-Cg haloalkyl. Embodiment 37. The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 27 wherein in Formula 1, the ring of one of Q1 and Q2 is a phenyl or 3-pyridinyl ring substituted at a meta or para position with one substituent selected from F, CI, methyl, methoxy and fluoromethoxy, and optionally substituted with one F at a remaining position; and the ring of the other of Q1 and Q2 is a phenyl ring substituted at both ortho positions with F and substituted at a meta or para position with a substituent selected from cyano and Ci -C2 alkoxy.
Embodiment 38. The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 27 and 37 wherein component (a) comprises a compound selected from the group consisting of
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)-2-methyl- lH-imidazole (Compound 181),
3-[4-chloro-l -(4-chlorophenyl)-2-methyl- lH-imidazol-5-yl]-2,4- difluorobenzonitrile (Compound 292),
2-bromo-l-(2,6-difluoro-4-methoxyphenyl)-5-(3-fluorophenyl)-4-methyl- lH-imidazole (Compound 469),
4-[2-chloro- 1 -(6-chloro-3-pyridinyl)-4-methyl- lH-imidazol-5-yl]-3,5- difluorobenzonitrile (Compound 513),
2-bromo-4-chloro-5-(4-ethoxy-2,6-difluorophenyl)-l-(3-fluorophenyl)- lH-imidazole (Compound 514),
4-chloro-5-(4-ethoxy-2,6-difluorophenyl)-2-methyl-l-(4-methylphenyl)- lH-imidazole (Compound 515),
4-chloro-5-(4-ethoxy-2,6-difluorophenyl)-l-(4-fluorophenyl)-2-methyl- lH-imidazole (Compound 516),
4-chloro-5-(4-ethoxy-2,6-difluorophenyl)-l-(3-fluorophenyl)-2-methyl- lH-imidazole (Compound 517),
2-bromo-4-chloro- 1 -[3-(difluoromethoxy)phenyl]-5-(4-ethoxy- 2,6-difluorophenyl)- lH-imidazole (Compound 518),
2.4- dichloro-l-[3-(difluoromethoxy)phenyl]-5-(4-ethoxy-2,6-difluorophenyl)- lH-imidazole (Compound 519),
4-[2-chloro-l-(6-methoxy-3-pyridinyl)-4-methyl-lH-imidazol-5-yl]-
3.5 - difluorobenzonitrile (Compound 520),
4-[2-bromo- 1 -(6-methoxy-3-pyridinyl)-4-methyl- lH-imidazol-5-yl]-
3, 5 -difluorobenzonitrile (Compound 521),
4-[2-bromo-4-chloro-l-(4-methylphenyl)-lH-imidazol-5-yl]- 3, 5 -difluorobenzonitrile (Compound 522), 4-chloro- 1 - [3 -(difluoromethoxy)phenyl] -5 -(4-ethoxy-2,6-difluorophenyl)- 2-methyl-lH-imidazole (Compound 523),
4-[2-bromo-4-chloro- 1 -(3 -fluorophenyl)- lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 524),
4-[4-chloro-l-(3,4-difluorophenyl)-2-methyl-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 525),
4-[4-chloro-l-(3-fluorophenyl)-2-methyl-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 526),
4-[2-bromo-4-chloro-l-(4-fluorophenyl)-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 527),
2-chloro- 1 - [4-(difluoromethoxy)phenyl] -5 -(2,6-difluoro-4-methoxyphenyl)- 4-methyl-lH-imidazole (Compound 528),
4-[2-chloro-l-(4-chlorophenyl)-4-methyl-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 529),
4-[2-chloro-l-(3-fluorophenyl)-4-methyl-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 530),
4-[4-chloro-l-(2,4-difluorophenyl)-2-methyl-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 531),
4-[2-chloro-l-[3-(difluoromethoxy)phenyl]-4-methyl-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 532),
4-[2,4-dichloro-l-[4-(difluoromethoxy)phenyl]-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 533),
4-[4-chloro- 1 -(2-fluoro-4-methylphenyl)-2-methyl- lH-imidazol-5-yl]- 3,5-difluorobenzonitrile (Compound 534),
4-[4-bromo- 1 -(2-fluoro-4-methylphenyl)-2-methyl- lH-imidazol-5-yl]-
3,5-difluorobenzonitrile (Compound 535), and
4-[2,4-dibromo-l-(3-fluorophenyl)-lH-imidazol-5-yl]-3,5-difluorobenzonitrile (Compound 536).
Embodiment 39. The composition of Embodiment 38 wherein component (a) comprises a compound selected from the group consisting of Compound 516, Compound
517, Compound 520, Compound 523, Compound 525, Compound 526,
Compound 529 and Compound 536.
Embodiment 40. The composition comprising components (a) and (b) described in the Summary of the Invention or any one of Embodiments 1 through 39 wherein in Formula 1, when Q2 is optionally substituted phenyl, and Q1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R20, optionally substituted at the other ortho position with a substituent selected from halogen or R20, and optionally substituted at the para position with a substituent selected from halogen or R20, then at least one of the following conditions are true:
(a) when the first ortho position is substituted with halogen, then neither the other ortho position nor the para position is substituted with R20, and
(b) when the first ortho position is substituted with R20, then neither the other ortho position nor the para position is substituted (with halogen or R20), wherein each R20 is independently hydroxy, alkoxy, haloalkoxy, cycloalkoxy or -X-U-Z, wherein X is O, U is alkylene, Z is NR8aR8b or OR9, R8a is H or alkyl, R8^ is alkyl or cycloalkyl, and R9 is alkyl.
Embodiment 41. The composition of Embodiment 40 wherein in Formula 1, when Q2 is optionally substituted phenyl, and Q1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R20, and optionally substituted at the other ortho position with a substituent selected from halogen or R20, then the Q1 phenyl is substituted at the para position with a substituent other than halogen or R20.
Embodiment 42. The composition of Embodiment 41 wherein in Formula 1, when Q2 is optionally substituted phenyl, and Q1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R20, and optionally substituted at the other ortho position with a substituent selected from halogen or R20, then the Q1 phenyl is substituted at the para position with cyano.
Embodiment 43. The composition of Embodiment 41 wherein in Formula 1, when Q2 is optionally substituted phenyl, and Q1 is a phenyl substituted at a first ortho position with halogen or R20, and optionally substituted at the other ortho position with a substituent selected from halogen or R20, then the Q1 phenyl is substituted at the para position with a substituent other than halogen or R20.
Embodiment 44. The composition of Embodiment 43 wherein in Formula 1, when Q2 is optionally substituted phenyl, and Q1 is phenyl substituted at a first ortho position with halogen or R20, and optionally substituted at the other ortho position with a substituent selected from halogen or R20, then the Q1 phenyl is substituted at the para position with cyano.
Embodiment 45. The composition of Embodiment 40 wherein in Formula 1, when Q1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R20, optionally substituted at the other ortho position with a substituent selected from halogen or R20, and optionally substituted at the para position with a substituent selected from halogen or R20, then at least one of the following conditions are true:
(a) when the first ortho position is substituted with halogen, then neither the other ortho position nor the para position is substituted with R20, and (b) when the first ortho position is substituted with R20, then neither the other ortho position nor the para position is substituted (with halogen or R20).
Embodiment 46. The composition of Embodiment 45 wherein in Formula 1, when Q1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R20, and optionally substituted at the other ortho position with a substituent selected from halogen or R20, then the Q1 phenyl is substituted at the para position with a substituent other than halogen or R20.
Embodiment 47. The composition of Embodiment 46 wherein in Formula 1, when Q1 is phenyl unsubstituted at meta positions, substituted at a first ortho position with halogen or R20, and optionally substituted at the other ortho position with a substituent selected from halogen or R20, then the Q1 phenyl is substituted at the para position with cyano.
Embodiment 48. The composition of Embodiment 45 wherein in Formula 1, when Q1 is phenyl substituted at a first ortho position with halogen or R20, and optionally substituted at the other ortho position with a substituent selected from halogen or
R20, then the Q1 phenyl is substituted at the para position with a substituent other than halogen or R20.
Embodiment 49. The composition of Embodiment 48 wherein in Formula 1, when Q1 is phenyl substituted at a first ortho position with halogen or R20, and optionally substituted at the other ortho position with a substituent selected from halogen or
R20, then the Q1 phenyl is substituted at the para position with cyano.
Embodiment 50. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 49 wherein in
Formula 1, wherein when Q2 is optionally substituted phenyl and Q1 is optionally substituted phenyl, then said Q1 phenyl is substituted at the para position with cyano (and optionally substituted at other positions as specified in the Summary of the Invention and Embodiments).
Embodiment 51. The composition of Embodiment 50 wherein in Formula 1, wherein when Q1 is optionally substituted phenyl, then said Q1 phenyl is substituted at the para position with cyano (and optionally substituted at other positions as specified in the Summary of the Invention and Embodiments).
Embodiment 52. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 51 wherein in
Formula 1, Q1 is phenyl substituted at the para position with cyano (and optionally substituted at other positions as specified in the Summary of the
Invention and Embodiments).
Embodiment 53. The composition comprising components (a) and (b) described in the
Summary of the Invention or any one of Embodiments 1 through 52 provided that when component (a) consists of a compound selected from the group consisting of
4-chloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH-imidazole (Compound 1),
2,4-dichloro- 1 -(2-chloro-4-fluorophenyl)-5-(4-chlorophenyl)- lH-imidazole
(Compound 5),
2-bromo-4-chloro-5-(2,6-difluorophenyl)-l-phenyl-lH-imidazole (Compound 6), 2-bromo-4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole (Compound 7),
4-chloro- 1 -(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl- 1H- imidazole (Compound 22),
4-chloro- 1 -(4-chlorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-2-methyl- 1H- imidazole (Compound 77),
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-l-(4-methylphenyl)-lH- imidazole (Compound 105),
4-[4-chloro-l-(4-chlorophenyl)-2-methyl-lH-imidazol-5-yl]-3,5- difluorobenzonitrile (Compound 134),
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3-fluorophenyl)-2-methyl- 1H- imidazole (Compound 181),
4-chloro- 1 -(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-2- methyl-lH-imidazole (Compound 263),
2- chloro-5-[2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 - yl]pyridine (Compound 273),
3- [4-chloro-l-(4-chlorophenyl)-2-methyl-lH-imidazol-5-yl]-2,4- difluorobenzonitrile (Compound 292),
4- chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,4-difluorophenyl)-2-methyl-lH- imidazole (Compound 345),
4-chloro- 1 -(3-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl- 1H- imidazole (Compound 346) and
5-[2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]-2- methylpyridine (Compound 387),
then component (b) comprises at least two fungicidal compounds.
Embodiments of this invention, including Embodiments 1-53 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 compositions comprising compounds of Formula 1 with at least one other fungicide but also to compositions comprising compounds of Formula 1 with at least one invertebrate pest control compound or agent, and also to the compounds of Formula 1 and their compositions, and also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula 1. In addition, embodiments of this invention, including Embodiments 1-53 above as well as any other embodiments described herein, and any combination thereof, pertain to the methods of the present invention.
Combinations of Embodiments 1-53 are illustrated by:
Embodiment Al . The composition comprising components (a) and (b) described in the Summary of the Invention wherein in Formula 1,
Q1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R3 on carbon atom ring members and R4 on nitrogen atom ring members;
Q2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R5 on carbon atom ring members and R6 on nitrogen atom ring members; and
R1 and R2 are independently halogen, cyano, ethenyl, ethynyl, methoxy or methylthio; or methyl optionally substituted with one substituent selected from halogen, -OH and methyl.
Embodiment A2. The composition of Embodiment Al wherein in Formula 1,
Q1 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R3 on carbon atom ring members;
Q2 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R5 on carbon atom ring members; and
each R3 and R5 is independently halogen, cyano, Ci -C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, C1 -C3 haloalkyl, cyclopropyl, C1 -C3 alkoxy, C 1 -C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl or C2-C4 alkylcarbonylamino.
Embodiment A3. The composition of Embodiment A2 wherein in Formula 1,
Q1 is a phenyl or 3 -pyridinyl ring optionally substituted with up to 3
substituents independently selected from R3 on carbon atom ring members; and
Q2 is a phenyl or 3 -pyridinyl ring optionally substituted with up to 3
substituents independently selected from R5 on carbon atom ring members. Embodiment A4. The composition of Embodiment A3 wherein in Formula 1,
R1 and R2 are independently halogen, cyano or methoxy; or methyl optionally substituted with one substituent selected from F, CI or methyl; and each R3 and R5 is independently halogen, cyano, Ci-C^ alkyl, C2-C3 alkenyl, 1 -C3 haloalkyl, C1-C3 alkoxy, C 1 -C3 haloalkoxy, C1 -C3 alkylthio or
C1 -C3 alkylamino.
Embodiment A5. The composition of Embodiment A4 wherein in Formula 1,
R1 and R2 are independently CI, Br, I or Ci-C2 alkyl;
each R3 and R5 is independently F, CI, Br, cyano, Ci -C2 alkyl, Ci-C2 haloalkyl, Ci -C2 alkoxy or Ci -C2 haloalkoxy; and
the ring of one of Q1 and Q2 is substituted with 2 or 3 substituents and the ring of the other of Q1 and Q2 is substituted with 1 or 2 substituents. Embodiment A6. The composition of Embodiment A5 wherein in Formula 1,
R1 and R2 are independently CI, Br or methyl;
the ring of one of Q1 and Q2 is a phenyl or 3-pyridinyl ring substituted at a meta or para position with one substituent selected from F, CI, methyl, methoxy and fluoromethoxy, and optionally substituted with one F at a remaining position; and
the ring of the other of Q1 and Q2 is a phenyl ring substituted at both ortho positions with F and substituted at a meta or para position with a substituent selected from cyano and Ci -C2 alkoxy.
Embodiment A7. The composition of Embodiment A6 wherein component (a)
comprises a compound selected from the group consisting of: Compound 181 , Compound 292, Compound 469, Compound 513, Compound 514, Compound 515, Compound 516, Compound 517, Compound 518, Compound 519,
Compound 520, Compound 521 , Compound 522, Compound 523, Compound 524, Compound 525, Compound 526, Compound 527, Compound 528,
Compound 529, Compound 530, Compound 531 , Compound 532, Compound 533, Compound 534, Compound 535 and Compound 536).
Embodiment B 1. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl) methyl benzimidazole carbamate fungicides such as benomyl, carbendazim and thiophanate -methyl.
Embodiment B2. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b2) dicarboximide fungicides such as procymidone, iprodione and vinclozolin.
Embodiment B3. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b3) demethylation inhibitor fungicides such as epoxiconazole, fluquinconazole, triadimenol, simeconazole, ipconazole, triforine, cyproconazole, difenconazole, flusilazole, flutriafol, metconazole, myclobutanil, prochloraz, propiconazole, prothioconazole, tebuconazole and tetraconazole.
Embodiment B4. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b4) phenylamide fungicides such as metalaxyl, metalaxyl-M, benalaxyl, benalaxyl-M, furalaxyl, ofurace and oxadixyl.
Embodiment B5. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b5) amine/morpholine fungicides such as aldimorph, dodemorph, fenpropimorph, tridemorph, trimorphamide, fenpropidin, piperalin and spiroxamine.
Embodiment B6. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b6) phospholipid biosynthesis inhibitor fungicides such as edifenphos and isoprothiolane.
Embodiment B7. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b7) carboxamide fungicides such as bixafen, boscalid, carboxin, isopyrazam, oxycarboxin, penflufen and penthiopyrad.
Embodiment B8. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b8) hydroxy(2-amino-)pyrimidine fungicides such as ethirimol.
Embodiment B9. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b9) anilinopyrimidine fungicides such as cyprodinil. Embodiment BIO. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (blO) N-phenyl carbamate fungicides such as diethofencarb.
Embodiment B 11. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl 1) quinone outside inhibitor fungicides such as azoxystrobin, pyraclostrobin, pyrametostrobin, kresoxim-methyl, trifloxystrobin, picoxystrobin, pyraoxystrobin, pyribencarb, famoxadone, fenamidone, discostrobin, enestrobin, dimoxystrobin, metominostrobin, orysastrobin and fluoxastrobin.
Embodiment B 12. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl2) phenylpyrrole fungicides compound such as fenpiclonil and fludioxonil.
Embodiment B 13. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl3) quinoline fungicides such as quinoxyfen.
Embodiment B 14. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl4) lipid peroxidation inhibitor fungicides such as chloroneb.
Embodiment B 15. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl5) melanin biosynthesis inhibitors-reductase fungicides such as pyroquilon and tricyclazole.
Embodiment B 16. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl6) melanin biosynthesis inhibitors-dehydratase fungicides such as carpropamid.
Embodiment B 17. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl7) hydroxyanilide fungicides such as fenhexamid. Embodiment B 18. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl8) squalene-epoxidase inhibitor fungicides such as pyributicarb.
Embodiment B 19. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (bl9) polyoxin fungicides such as polyoxin.
Embodiment B20. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b20) phenylurea fungicides such as pencycuron.
Embodiment B21. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b21) quinone inside inhibitor fungicides such as cyazofamid and amisulbrom.
Embodiment B22. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b22) benzamide fungicides such as zoxamide.
Embodiment B23. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b23) enopyranuronic acid antibiotic fungicides such as blasticidin-S.
Embodiment B24. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b24) hexopyranosyl antibiotic fungicides such as kasugamycin. Embodiment B25. The composition described in the Summary of the Invention (including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b25) glucopyranosyl antibiotic: protein synthesis fungicides such as streptomycin.
Embodiment B26. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides such as validamycin.
Embodiment B27. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b27) cyanoacetylamideoxime fungicides such as cymoxanil.
Embodiment B28. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b28) carbamate fungicides such as propamacarb, prothiocarb and iodocarb.
Embodiment B29. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b29) oxidative phosphorylation uncoupling fungicides such as fluazinam, binapacryl, ferimzone, meptyldinocap and dinocap.
Embodiment B30. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b30) organo tin fungicides such as fentin acetate. Embodiment B31. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b31) carboxylic acid fungicides such as oxolinic acid.
Embodiment B32. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b32) heteroaromatic fungicides such as hymexazole. Embodiment B33. The composition described in the Summary of the Invention (including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b33) phosphonate fungicides such as phosphorous acid and its various salts, including fosetyl-aluminum.
Embodiment B34. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b34) phthalamic acid fungicides such as teclofthalam. Embodiment B35. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b35) benzotriazine fungicides such as triazoxide.
Embodiment B36. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b36) benzene-sulfonamide fungicides such as flusulfamide.
Embodiment B37. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b37) pyridazinone fungicides such as diclomezine. Embodiment B38. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b38) thiophene-carboxamide fungicides such as silthiofam.
Embodiment B39. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b39) pyrimidinamide fungicides such as diflumetorim. Embodiment B40. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b40) carboxylic acid amide fungicides such as dimethomorph, benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb, valiphenal, mandipropamid and flumorph. Embodiment B41. The composition described in the Summary of the Invention (including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b41) tetracycline antibiotic fungicides such as oxytetracycline.
Embodiment B42. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b42) thiocarbamate fungicides such as methasulfocarb. Embodiment B43. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b43) benzamide fungicides such as fluopicolide and fluopyram.
Embodiment B44. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b44) host plant defense induction fungicides such as acibenzolar-S-methyl.
Embodiment B45. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b45) multi-site contact fungicides such as copper oxychloride, copper sulfate, copper hydroxide, Bordeaux composition (tribasic copper sulfide), elemental sulfur, mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb, ziram, folpet, captan, captafol and chlorothalonil.
Embodiment B46. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one compound selected from (b46) fungicides other than fungicides of component (a) and components (bl) through (b45) such as ethaboxam, cyflufenamid, proquinazid, metrafenone, pyriofenone, ametoctradine, bethoxazin, neo-asozin, fenpyrazamine, pyrrolnitrin, quinomethionate, tebufloquin, 5-chloro-6-(2,4,6- trifluorophenyl)-7-(4-methylpiperidin- 1 -yl)[ 1 ,2,4]triazolo[ 1 ,5-a]pyrimidine (BAS600), 2-butoxy-6-iodo-3-propyl-4H-l-benzopyran-4-one, 3-[5-(4- chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine (SYP-Z048),
4-fluorophenyl N-[ 1 -[[[1 -(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]- carbamate (XR-539), N-[[(cyclopropylmethoxy)amino] [6-(difluoromethoxy)- 2,3-difluorophenyl]methylene]benzeneacetamide, N'-[4-[4-chloro- 3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methyl- methanimidamide, 2- [ [2-fluoro-5 -(trifluoromethyl)phenyl]thio] -2- [3 -(2- methoxyphenyl)-2-thiazolidinylidene]acetonitrile (OK-5203), N-(4-chloro-2- nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide (TF-991) and l-[(2- propenylthio)carbonyl] -2-( 1 -methylethyl)-4-(2-methylphenyl)-5 -amino- 1H- pyrazol-3-one.
Embodiment B47. The composition described in the Summary of the Invention
(including but not limited to the composition of any one of Embodiments 1 through 53 and Al through A7) wherein component (b) includes at least one fungicidal compound (fungicide) selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, pyraoxystrobin, pyrametostrobin, picoxystrobin, dimoxystrobin, metominostrobin- /fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, pyriofenone, cyflufenamid, fenpropidin, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, hexaconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, famoxadone, prochloraz, penthiopyrad and boscalid (nicobifen).
Embodiment B48. The composition of Embodiment B47 wherein component (b) includes at least one fungicidal compound selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, cyflufenamid, fenpropidin, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, hexaconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, famoxadone, prochloraz, penthiopyrad and boscalid.
Embodiment B49. The composition of Embodiment B47 wherein component (b) includes at least one fungicidal compound selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, pyraclostrobin, pyrametostrobin, picoxystrobin, dimoxystrobin, metominostrobin- /fenominostrobin, quinoxyfen, metrafenone, pyriofenone, cyflufenamid, fenpropidin, fenpropimorph, cyproconazole, difenoconazole, epoxiconazole, flusilazole, metconazole, myclobutanil, propiconazole, proquinazid,
prothioconazole, tebuconazole, triticonazole, famoxadone and penthiopyrad. Embodiment B50. The compositon of Embodiment B49 wherein component (b) includes at least one compound selected from the group consisting of azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidin, fenpropimorph, cyproconazole, difenoconazole, epoxiconazole, flusilazole, metconazole, myclobutanil, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, famoxadone and penthiopyrad.
Of note is the composition of any one of the embodiments described herein, including Embodiments 1 through 53, Al through A7, and Bl through B50, wherein reference to Formula 1 includes salts thereof but not N-oxides thereof; therefore the phrase "a compound of Formula 1" can be replaced by the phrase "a compound of Formula 1 or a salt thereof. In this composition of note, component (a) comprises a compound of Formula 1 or a salt thereof.
Also noteworthy as embodiments are fungicidal compositions of the present invention comprising a fungicidally effective amount of a composition of Embodiments 1 to 53, A 1 to A7, and Bl to B50 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
Embodiments of the invention further include methods for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a composition of any one of Embodiments 1 to 53, Al to A7, and Bl to B50 (e.g., as a composition including formulation ingredients as described herein). Embodiments of the invention also include methods for protecting a plant or plant seed from diseases caused by fungal plant pathogens comprising applying a fungicidally effective amount of a composition of any one of Embodiments 1 to 53, Al to A7, and Bl to B50 to the plant or plant seed.
Some embodiments of the invention involve control of a plant disease or protection from a plant disease that primarily afflicts plant foliage and/or applying the composition of the invention to plant foliage (i.e. plants instead of seeds). The preferred methods of use include those involving the above preferred compositions; and the diseases controlled with particular effectiveness include plant diseases caused by fungal plant pathogens. Combinations of fungicides used in accordance with this invention can facilitate disease control and retard resistance development.
Method embodiments further include:
Embodiment CI . A method for protecting a plant from a disease selected from
powdery mildew, rust and Septoria diseases comprising applying to the plant a fungicidally effective amount of the composition comprising components (a) and
(b) described in the Summary of the Invention or any one of Embodiments 1 through 53. Embodiment C2. The method of Embodiment CI wherein the disease is a powdery mildew disease and component (b) of the composition includes at least one fungicidal compound selected from azoxystrobin, myclobutanil and spiroxamine.
Embodiment C3. The method of Embodiment C2 wherein the disease is wheat
powdery mildew.
Embodiment C4. The method of Embodiment C2 or C3 wherein component (b)
includes azoxystrobin.
Embodiment C5. The method of Embodiment CI wherein the disease is a rust disease and component (b) of the composition includes at least one fungicidal compound selected from azoxystrobin and tetraconazole.
Embodiment C6. The method of Embodiment C5 wherein the disease is wheat leaf rust.
Embodiment C7. The method of Embodiment CI wherein the disease is a Septoria disease and component (b) of the composition includes at least one fungicidal compound selected from azoxystrobin, picoxystrobin, quinoxyfen, tetraconazole, fenpropimorph and spiroxamine.
Embodiment C8. The method of Embodiment C7 wherein the disease is wheat leaf blotch.
Embodiment C9. The method of Embodiment C7 or C8 wherein component (b)
includes at least one fungicidal compound selected from azoxystrobin, tetraconazole, fenpropiomorph and spiroxamine.
Embodiment CIO. The method of Embodiment CI wherein the disease is a Septoria disease and component (b) of the composition includes at least one fungicidal compound selected from (b5) amine/morpholine fungicides.
Embodiment C 11. The method of Embodiment CIO wherein the disease is wheat leaf blotch.
Embodiment C12. The method of Embodiment CIO or CI 1 wherein the composition includes at least one fungicidal compound selected from fenpropiomorph and spiroxamine.
Embodiment C13. The method of any one of Embodiments CI through C12 wherein components (a) and (b) are applied in synergistically effective amounts (and in a synergistic ratio relative to each other).
Of note are embodiments that are counterparts of Embodiments CI through C13 relating to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, a fungicidally effective amount of a fungicidal composition of the invention.
One or more of the following methods and variations as described in Schemes 1-9 can be used to prepare the compounds of Formula 1. The definitions of Q1, Q2, R1 or R2 in the compounds of Formulae 1-16 below are as defined above in the Summary of the Invention unless otherwise noted. Formulae la and lb are subsets of Formula 1, and all substituents for Formulae la and lb are as defined above for Formula 1 unless otherwise noted.
Compounds of Formula 1 can be prepared by halogenation or alkylation of compounds of Formula 2 as illustrated in Scheme 1. Typically halogenation can be achieved using a variety of halogenating reagents known in the art such as elemental halogen (e.g., CI2, Br2, I2), sulfuryl chloride, iodine monochloride or a N-halosuccinimide (e.g., NBS, NCS, NIS) in an appropriate solvent such as N,N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane or acetic acid. Alkylation is achieved by reacting a compound of Formula 2 with a metalating agent, followed by an alkylating agent of formula Ri-Lg (wherein Lg is a leaving group such as CI, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate). Suitable metalating agents include, for example, as n-butyl lithium (n-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH). As used herein, the terms "alkylation" and "alkylating agent" are not limited to R1 being an alkyl group, and include in addition to alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like. For reaction conditions see Almansa et al., Journal of Medicinal Chemistry 2003, 46(\6), 3463-3475 and Katritzky et al., Heterocycles 1997, 44, 67-70. Also, the method of Scheme 1 is illustrated in Example 5, Step B of Example 4, and Step C of Example 6.
Scheme 1
Figure imgf000039_0001
2 1
Compounds of Formula 1 can be subjected to various nucleophilic and metallation reactions to add substituents or modify existing substituents, and thus provide other functionalized compounds of Formula 1. For example, compounds of Formula 1 wherein R1 and/or R2 are halogen can undergo nucleophilic displacements to provide compounds of Formula 1 wherein R1 and/or R2 are groups linked to the imidazole ring through an O or S atom (e.g., displacements with alkoxides or thiolates). Typically these reactions are run in the presence of a suitable base (e.g., sodium hydride, potassium t-butoxide, potassium carbonate or triethylamine) in a solvent such as alcohol, acetonitrile or N,N-dimethylformamide at temperatures ranging from room temperature to the reflux temperature of the solvent. General procedures for conducting nucleophilic displacements of halogens are known in the art and can be readily adapted to prepare compounds of the present invention. For procedures relevant to imidazoles see Grimmett et al, Australian Journal of Chemistry 1987, 40(8), 1399-1413.
Also, compounds of Formula 1 wherein R1 and/or R2 are bromo or iodo can be cross-coupled with compounds of formulae Ri-Met or R2-Met (wherein Met is Sn, Zn, B(OH)2, Mg, Li, Cu or other suitable counterions) in the presence of a palladium or nickel catalyst to produce compounds of Formula la wherein R1 and/or R2 are cyano, alkyl, alkenyl, haloalkenyl, alkynyl, and the like. Preferred catalysts include but are not limited to Pd(PPh3)4, PdCl2(PPh3)2, PdCl2(diphenylphosphinoferrocene), NiCl2(PPh3)2 and tetrakis(tri-2-furylphosphino)palladium. The conditions for each reaction will depend upon the catalyst used and the counterions in the compound of formulae Ri-Met or R2-Met. The presence of a base (such as an alkali carbonate, tertiary amine or alkali fluoride) is necessary for reactions involving compounds of formulae Ri-Met or R2-Met where Met is B(OH)2. Examples 9, 11, 12, 13, 14 and 19 illustrate various cross-coupling reactions for the preparation of certain compounds of Formula 1.
As shown in Scheme 2, compounds of Formula 1 can alternatively be prepared by halogenation of a compound of Formula 3 preferentially at the 4-position of the imidazole ring to provide a compound of Formula 4 wherein R1 is halogen, which can then be treated with a second equivalent of the same or different halogenating reagent to provide a compound of Formula 1 wherein R1 and R2 are halogen. For an example illustrating the method of Scheme 2 for the preparation of a compound of Formula 4 see Step C of Examples 1 and 22. Also, for an example illustrating the method of Scheme 2 for the preparation of a compound of Formula 1 wherein R1 is chloro and R2 is bromo see Step D of Example 22. Alternatively, compounds of Formula 3 can be treated with 2 equivalents of a halogenating reagent to provide a compound of Formula 1 directly wherein R1 and R2 are both the same halogen. For an example illustrating the method of preparing a compound of Formula 1 wherein R1 and R2 are both the same halogen see Example 2 and Step C of Example 3.
Alternatively as also shown in Scheme 2, compounds of Formula 1 wherein R2 is halogen, alkyl, alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like can be prepared from compounds of Formula 4 by metallation with a reagent such as n-butyllithium (ft-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH) in a solvent such as tetrahydrofuran, dioxane or toluene at temperatures ranging from about 0 °C to room temperature. The anion is then contacted with an electrophile resulting in the introduction of an R2 group onto Formula 4, thus providing a compound of Formula 1. Scheme 2
Figure imgf000041_0001
wherein R is halogen
Synthesis of compounds of Formula 2 can be achieved as outlined in Scheme 3. In the first step a compound of Formula 5 is N-arylated with halides of formula Q¾l wherein X1 is I, CI, Br or F. There are a number of conditions published in the chemistry literature which can be used for introduction of a substituted aryl or a heteroaryl group onto Formula 5, including copper-catalyzed conditions involving the use of a suitable copper source (e.g., copper(I) iodide or copper(I) triflate) and a metal carbonate base (e.g., potassium or cesium carbonate) in a suitable solvent such as xylenes, dioxane or acetonitrile (see Buchwald et al., Tetrahedron Letters 1999, 40, 2657-2660 and Jiang et al., Journal of Organic Chemistry 2007, 72, 8943-8946). The method of Scheme 3 for the preparation of a compound of Formula 6 is also illustrated in Step A of Example 6.
In a subsequent step, compounds of Formula 6 can be converted directly to Formula 2 by reaction with a halide of formula QiX1 in the presence of palladium(II) acetate and a triarylphosphine ligand and cesium fluoride in a solvent such as dioxane, tetrahydrofuran or acetonitrile at the reflux temperature of the solvent. For a representative reference see Bellina et al, Journal of Organic Chemistry 2005, 70, 3997-4005. Also, Step B of Example 6 illustrates the preparation of a compound of Formula 2 using the method of Scheme 3. Alternatively, lithiation of a compound of Formula 6 with n-butyllithium (n-BuLi) or lithium diisopropylamide (LDA), followed by treatment of the anion with trialkylorganostannyl chlorides or boronic acids (or esters) provides compounds of Formula 7. Treatment of compounds Formula 7 with a halide of formula QiX1 using well-known transition metal-catalyzed cross coupling reaction conditions provides Formula 2 compounds. Typically the reaction is run in the presence of a palladium catalyst. A wide variety of palladium-containing compounds and complexes are useful as catalysts in the method of Scheme 3, including PdCl2(PPh3)2 (bis(triphenylphosphine)palladium(II) dichloride), Pd(PPh3)4 (tetrakis(triphenylphosphine)palladium(O)) and Pd2(dba)3. For relevant references see, for example, Ragan et al, Organic Process Research & Development 2003, 7(5), 675-683; and Gaare et al., Acta Chemica Scandinavica 1993, 47, 57-62.
Scheme 3
Figure imgf000042_0001
7
wherein L is (alky 1)3811 or B(OH)2
Compounds of Formula 2 can also be prepared as shown in Scheme 4. In this method a compound Formula 8 is first metallated with a metalating agent such as n-butyllithium (ft-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH) in a solvent such as tetrahydrofuran, dioxane or toluene at temperatures ranging from about 0 °C to room temperature. The anion is then contacted with an electrophile resulting in the introduction of an R2 group onto Formula 8, thus providing a compound of Formula 2. For halogenation, the electrophile can be a halogen derivative such as N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), N-iodosuccinimide (NIS), hexachloroethane or 1,2-dibromotetrachloroethane. For alkylation, the electrophile can be an alkylating agent of the formula R2-Lg (wherein Lg is a leaving group such as CI, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate) where R2 is alkyl, alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like. As referred to herein, the terms "alkylation" and "alkylating agent" are not limited to R2 being an alkyl group. For related reference see Almansa et al, Journal of Medicinal Chemistry 2003, 46, 3463-3475. Also, Step A of Example 4 illustrates the method of Scheme 4 using LDA and iodomethane.
Scheme 4
Figure imgf000043_0001
8 2 Compounds of Formula 8 are known and can be prepared by one of several methods disclosed herein. For example, using a method analogous to that disclosed in Scheme 3, starting with a compound of Formula 5 wherein R2 is H provides compounds of Formula 8. Alternatively, compounds of Formula 8 can be prepared by a method analogous to Scheme 6 described below using a compound of Formula 12 or 13 wherein R1 is H (i.e. when R1 is H, Formula 12 is /?-toluenesulfonylmethyl isocyanide and Formula 13 is benzotriazol-l-yl- methyl isocyanide). For synthesis of a compound of Formula 8 using / toluene- sulfonylmethyl isocyanide see Step B of Examples 1 and 3.
In another method illustrated in Scheme 5, compounds of Formula 2 can be prepared by reacting N-chloroamidines of Formula 9 with enamines of Formula 10. In this method cyclization proceeds through the intermediacy of an in sztw-generated 4-morpholino-4,5- dihydroimidazole which undergoes elimination of the morpholino group to provide the compounds of Formula 2. Typically the reaction is run in the presence of a base such as pyridine, 4-(dimethylamino)pyridine or a trialkylamine and in a suitable solvent, such as dichloromethane, trichloromethane, carbon tetrachloride or toluene, at temperatures ranging from about 0 °C to the reflux temperature of the solvent. For a representative reference see Pocar et al., Tetrahedron Letters 1976, 21, 1839-1842. One skilled in the art will recognize that imidazole rings of Formula 2 can also be prepared by numerous other methods described in the chemistry literature. For example, the general method described by Wiglenda et al., Journal of Medicinal Chemistry 2007, 50(7), 1475-1484 can be used to prepare compounds of Formula 2; the method can also be readily adapted to prepare Formula 2 compounds wherein each Q1 and/or Q2 is an optionally substituted benzyl group. Scheme 5
Figure imgf000044_0001
9
2
Compounds of Formula 9 can be easily synthesized from amidines and N-chlorosuccinimide according to the procedure given by Pocar et al, Tetrahedron Letters 1976, 21, 1839-1842. Enamines of Formula 10 can be prepared by known methods; for example, see van der Gen et al, Tetrahedron Letters 1979, 26, 2433-24.
As shown in Scheme 6, compounds of Formula 4 can be prepared by reacting an imine of Formula 11 with a substituted /?-toluenesulfonylmethyl isocyanide of Formula 12 or a substituted benzotriazol-l-ylmethyl isocyanide of Formula 13 in the presence of a suitable base such as potassium carbonate, potassium tert-butoxide, sodium hydroxide, sodium hydride, tert-butylamine or l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in an appropriate solvent such as methanol, dioxane, tetrahydrofuran, dimethylsulfoxide, N,N-dimethylformamide or 1 ,2-dimethoxyethane, at temperatures ranging from about 0 to 150 °C. For reaction conditions see Almansa et al, Journal of Medicinal Chemistry 2003, 46(16), 3463-3475 and Katritzky et al, Heterocycles 1997, 44, 67-70. The method of Scheme 6 is also illustrated in Step B of Examples 7, 22 and 24.
Scheme 6
Figure imgf000045_0001
13
Imines of Formula 11 can be readily prepared by contacting an amine of Formula Q2NH2 with an aldehyde of formula QiCHO under dehydrative conditions such as heating in toluene or xylenes with use of a Dean-Stark trap to remove water formed in the reaction. In some cases, an acid catalyst such as /?-toluenesulfonic acid can be added to the reaction mixture to promote elimination of water. For representative procedures see Almansa et al., Journal of Medicinal Chemistry 2003, 46(16), 3463-3475. Also, Step A of Examples 1, 3, 7, 22 and 24 illustrate the preparation of a compound of Formula 11.
Compounds of Formula 12 can be prepared from the unsubstituted /?-toluene- sulfonylmethyl isocyanide under phase-transfer conditions using methods reported in the chemical literature; see, for example, Leusen et al, Tetrahedron Letters 1975, 40, 3487- 3488.
The substituted benzotriazol-l-ylmethyl isocyanides of Formula 13 can be prepared by contacting benzotriazol-l-yl-methyl isocyanide with a compound of formula R2X! (wherein X1 is halogen) in the presence of a base such as potassium carbonate, sodium hydride or potassium tert-butoxide. For typical reaction conditions see Katritzky et al., Heterocycles 1997, 44, 67-70. One skilled in the art will recognize other methods for preparing compounds of Formula 13, for example, the method described by Katritzky et al, Journal of the Chemical Society, Perkin Transactions 1, 1990, (7), 1847-1851.
Certain compounds of Formula 4 wherein R1 is halogen can be prepared as shown in Scheme 7. In this method an aminonitrile of Formula 14 is combined with a methanaminium salt of Formula 15 to provide a compound of Formula 4 according to the general method taught by Pawar et al, Tetrahedron Letters 2006, 47, 5451-5453. The reaction is run in a suitable solvent such as dichloromethane or toluene at temperatures ranging from about 0 °C to the reflux temperature of the solvent. The method of Scheme 7 is illustrated in Step B of Examples 8 and 10.
Halogenation at the 2-position of the imidazole ring of Formula 4 can be achieved using methods analogous to those already described for Scheme 2 to provide compounds of Formula 2 wherein R1 is halogen. Step C of Examples 8, 10 and 24, Step B of Example 18, and Step D of Example 22 illustrate this halogenation method.
Scheme 7
Figure imgf000046_0001
wherein R and X are halogen
14 wherein R^ is halogen
Aminonitriles of Formula 14 are readily available from amines of formula Q2NH2, aldehydes of formula QiCHO and a cyanide source by means of the Strecker reaction. A variety of solvents and cyanide sources can be employed. The presence of a Lewis acid such as indium(III) chloride can be advantageous. For typical conditions, see, for example, Ranu et al., Tetrahedron 2002, 58, 2529-2532. This reaction has been the subject of a number of reviews. For conditions and variations of this reaction see the following references and references cited therein: D. T. Mowry, Chemical Reviews 1948, 42, 236, H. Groeger, Chemical Reviews 2003, 103, 2795-2827, and M. North in Comprehensive Organic Functional Group Transformations, A. R. Katritsky, O. Meth-Cohn and C. W. Rees Editors., Volume 3, 615-617; Pergamon, Oxford, 1995. Also the preparation of a compound of Formula 14 is illustrated in Step A of Examples 8 and 10. For less reactive amines of formula Q2NH2, such as aryl amines containing ortho electron withdrawing groups, the use of trimethylsilylcyanide in combination with a catalyst such a guanidine hydrochloride can be advantageous. For a reference see, for example, Heydari et al, Journal of Molecular Catalysis A: Chemical 2007 , 277(1-2), 142-144.
Methanaminium salts of Formula 15 are commercially available, for example, chloromethylenedimethyliminium chloride (i.e. R1 and X1 are CI) can be obtained from commercial sources. Compounds of Formula 15 can also be synthesized by methods documented in the chemistry literature.
Compounds of Formula la (i.e. Formula 1 wherein R2 is CH2OH) can be prepared as shown in Scheme 8. In the first step of this method, a compound of Formula 4 is converted to the corresponding 2-imidazolecarboxaldehyde derivative of Formula 16. This reaction involves lithiation of the imidazole ring at the 2-position using a lithium base such as lithium diisopropylamide (LDA), followed by treatment of the resulting anion with N,N-dimethylformamide (DMF) to provide the 2-imidazolecarboxaldehyde derivative. This step is illustrated in Step A of Example 15. In the next step of the method of Scheme 8, the 2-imidazolecarboxaldehyde of Formula 16 is reduced with sodium borohydride in methanol to provide the corresponding compound of Formula la. For reaction conditions see Quan et al, Journal of Medicinal Chemistry 2005, 48(6), 1729-1744. This step is illustrated in Step B of Example 15.
Scheme 8
Figure imgf000047_0001
16 la
In the method of Scheme 9, treatment of the 2-hydroxymethyl compound of Formula 17 with diethylaminosulfur trifluoride (DAST) then results in the 2-fluoromethyl derivative of Formula lb (i.e. Formula 1 wherein R2 is -CFTjF). For reaction conditions see C. J. Wang, Organic Reactions 2005, Vol. 34 (Wiley, New York, 1951) Chapter 2, pp. 319-321. This step is illustrated in Example 16. Other 2-halomethyl analogs of Formula lb can be prepared using methods described in the chemistry literature. For example, 2-bromomethyl analogs of Formula lb can be prepared by treating 2-hydroxymethyl compounds of Formula la with hydrobromic acid in a solvent such as glacial acetic acid using the method described by Beukers et al, Journal of Medicinal Chemistry 2004, 47(15), 3707-3709.
Scheme 9
Figure imgf000047_0002
la lb
Schemes 5 through 7 are representative of just a few methods of preparing imidazole rings of the present invention. One skilled in the art will recognize that imidazole rings of Formula 1 can also be prepared by numerous other methods described in the chemistry literature. For leading references on imidazole synthesis see Grimmett in Imidazole and Benzimidazole Synthesis, Academic Press, California; and Grimmett, Science of Synthesis 2002, 12, 325-528.
Compounds of Formula 1 and the intermediates described above can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation and reduction reactions to add or modify substituents for formation of further compounds of Formula 1. Compounds wherein R1, R2, R3, R4, R5 or R6 is halogen (preferably bromide or iodide) are particularly useful intermediates for transition metal-catalyzed cross-coupling reactions to prepare compounds of Formula 1. These types of reactions are well documented in the literature; see, for example, Tsuji in Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis, John Wiley and Sons, Chichester, 2002; Tsuji in Palladium in Organic Synthesis, Springer, 2005; and Miyaura and Buchwald in Cross-Coupling Reactions: A Practical Guide, Springer, 2002; and references cited therein.
One skilled in the art will recognize that for some compounds of Formula 1, the R3, R4, R5 and R6 substituents attached to the rings and ring systems of Q1 and Q2 may be more conveniently incorporated after forming the central imidazole ring with the rings or ring systems of Q1 and Q2. In particular, when R3, R4, R5 and/or R6 is halogen or another suitable leaving group, the leaving group can be replaced using various electrophilic, nucleophilic and organometallic reactions known in the art to introduce other functional groups as R3, R4, R5 and R6. Example 18 demonstrates the preparation of a compound of Formula 1 wherein an R3 substituent on the phenyl ring of Q1 is cyano (-CN) starting from a compound wherein an R3 substituent on the phenyl ring of Q1 is bromo. Example 25 illustrates the preparation of a compound of Formula 1 wherein an R5 on the phenyl ring of Q2 is thiocyanate (-SCN) starting from the corresponding compound of Formula 1 wherein an R5 substituent on the phenyl ring of Q2 is iodo.
As further examples of functionalization of Q1 or Q2 after forming the central imidazole ring, compounds of Formula 1 wherein an R3 or R5 substituent is connected through an oxygen atom (e.g., optionally substituted alkoxy), sulfur atom (e.g., optionally substituted alkylthio) or nitrogen atom (e.g. alkylamino and dialkylamino) can be prepared by alkylation of the corresponding compounds wherein the R3 or R5 substituent is OH, SH or NH2, respectively. General alkylation methods are well known in the art of organic chemical synthesis. Present Example 26 demonstrates the preparation of a compound of Formula 1 wherein R3 is OCH2CN starting from the corresponding compound of Formula 1 wherein R3 is OH. Compounds of Formula 1 wherein an R3 or R5 substituent is optionally substituted alkyl sulfmyl or sulfonyl can be prepared by oxidizing the corresponding compounds of Formula 1 wherein the R3 or R5 substituent is optionally substituted alkylthio through use of general oxidation methods well known in the art.
Furthermore, compounds of Formula 1 wherein a ring or ring system of Q1 or Q2 is substituted with an R3 or R5 substituent which is -X-U-Z (as defined in the Summary of the Invention) can be prepared from the corresponding compounds of Formula 1 wherein R3 or R5 is a halogen or other suitable leaving group, such as by the general method described in PCT Patent Publication WO 2007/149448 (see Scheme 15 therein). This reference also describes other general methods for forming an R3 or R5 substituent as -X-U-Z (see Schemes 16-19 therein). Present Examples 20 through 21 demonstrate the preparation of a compound of Formula 1 wherein R3 is -X-U-Z (i.e. -O^FT^NHCFy starting from the corresponding compound of Formula 1 wherein R3 is methoxy.
It is 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. Steps in the following Examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other Examples or Steps. In the following Examples HPLC analyses were obtained on an Alltech Altima C 18 analytical column with UV detection. The solvent system was solvent A: water with 0.05% trifluoroacetic acid by volume/volume, and solvent B: acetonitrile with 0.05%) trifluoroacetic acid by volume/volume (gradient started at 0 minutes with 90%> solvent A and 10%> solvent B and increased solvent B to 90%> over 20 minutes, flow rate was 1 mL/minute). Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. The mass spectrum (MS) value given in the following Examples is the molecular weight (m/z) of the highest isotopic abundance parent ion (M+l) formed by addition of H+ (molecular weight of 1) to the molecule having the highest isotopic abundance, observed by mass spectrometry using electrospray ionization (ESI) or atomospheric pressure chemical ionization (APCI). The presence of molecular ions containing one or more higher atomic weight isotopes of lower abundance (e.g., 37C1, 81Br) is not reported. ¾ NMR spectra are reported in ppm downfield from tetramethylsilane; "s" means singlet, "d" means doublet, "t" means triplet, "dd" means doublet of doublets, "m" means multiplet, and "br s" means broad singlet. EXAMPLE 1
Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole Step A: Preparation of (E)-4-chloro-N-[(2,4,6-trifluorophenyl)methylene]benzene
To a mixture of 2,4,6-trifluorobenzaldehyde (3.0 g, 18.7 mmol) in toluene (100 mL) was added 4-chloroaniline (2.39 g, 18.7 mmol). The reaction mixture was heated at reflux with the use of a Dean-Stark trap for the azeotropic removal of water. After 16 h the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 9) as eluant to provide the title compound as a pale-yellow solid (4.20 g).
!H NMR (CDCI3) δ 8.55 (s, 1H), 7.37-7.34 (m, 2H), 7.17-7.13 (m, 2H), 6.83-6.77 (m, 2H). ESI MS m/z 270 (M+l).
Step B: Preparation of l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole
To a mixture of (E)-4-chloro-N-[(2,4,6-trifluorophenyl)methylene]benzene (i.e. the product of Step A) (4.20 g, 15.6 mmol) in methanol and 1 ,2-dimethoxyethane (2 : 1, 152 mL) was added /?-toluenesulfonylmethyl isocyanide (4.57 g, 23.4 mmol) and potassium carbonate (4.30 g, 31.2 mmol). The reaction mixture was heated at 85 °C for 4 h, cooled, and then concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (200 mL), washed with water (75 mL) and saturated aqueous sodium chloride (75 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as a pale yellow solid (1.30 g, 98.9 area % purity by HPLC) melting at 170-172 °C.
!H NMR (DMSO- ) δ 7.29 (s, 1H), 7.11-7.07 (m, 2H), 6.68-6.63 (m, 2H).
MS m/z 309 (M+l).
Step C: Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole
To a mixture of l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole (i.e. the product of Step B) (0.100 g, 0.32 mmol) in chloroform (2 mL) was added N-chlorosuccinimide (0.046 g, 0.34 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (100 mL), washed with water (55 mL) and saturated aqueous sodium chloride (55 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as an off-white solid (0.075 g, 98.9 area % purity by HPLC) melting at 102-104 °C.
!H NMR (CDCI3) δ 7.68 (s, 1H), 7.37-7.33 (m, 2H), 7.11-7.07 (m, 2H), 6.74-6.65 (m, 2H). ESI MS m/z 343 (M+l).
EXAMPLE 2
Preparation of 2,4-dichloro- 1 -(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole
(Compound 4)
To a mixture of l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole (i.e. the product of Step B of Example 1) (0.280 g, 0.90 mmol) in chloroform (10 mL) was added N-chlorosuccinimide (0.420 g, 3.14 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (100 mL), washed with water (55 mL) and saturated aqueous sodium chloride solution (55 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using ethyl acetate -hexanes (1 : 4) as eluant to provide the title compound as a pale-yellow solid (0.23 g, 96.7 area % purity by HPLC) melting at 112-119 °C.
!H NMR (CDCI3) δ 7.40-7.35 (m, 2H), 7.14-7.10 (m, 2H), 6.70-6.61 (m, 2H).
ESI MS m/z 377 (M+l).
EXAMPLE 3
Preparation of 2,4-dichloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole
(Compound 2)
Step A: Preparation of (E)-4-chloro-N-[(2,6-difluorophenyl)methylene]benzene
To a mixture of 2,6-difluorobenzaldehyde (4.0 g, 18.7 mmol) in toluene (100 mL) was added 4-chloroaniline (3.60 g, 28.0 mmol). The reaction mixture was heated at reflux with the use of a Dean-Stark trap for azeotropic removal of water. After 16 h the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (0.5 : 9.5) as eluant to provide the title compound as a pale-yellow solid (6.20 g).
!H NMR (CDCI3): δ 8.64 (s, 1H), 7.44-7.33 (m, 3H), 7.19-7.14 (m, 2H), 7.04-6.96 (m, 2H). Step B: Preparation of l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole
To a mixture of (E)-4-chloro-N-[(2,6-difluorophenyl)methylene]benzene (i.e. the product of Step A) (4.0 g, 16.0 mmol) in methanol and 1 ,2-dimethoxyethane (7 : 3, 160 mL) was added /?-toluenesulfonylmethyl isocyanide (4.67 g, 24.0 mmol) and potassium carbonate (4.65 g, 24.0 mmol). The reaction mixture was heated at 85 °C for 4 h, cooled, and then concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (200 mL), washed with water (75 mL) and saturated aqueous sodium chloride solution (75 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (3 : 7) as eluant to provide the title compound as a pale-yellow solid (1.40 g, 98.9 area % purity by HPLC) melting at 170-172 °C.
!H NMR (CDCI3) δ 7.79 (d, J = 0.9 Hz, 1H), 7.34-7.29 (m, 4H), 7.12-7.08 (m, 2H), 6.91-6.83 (m, 2H).
ESI MS m/z 291 (M+l).
Step C: Preparation of 2,4-dichloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole
To a mixture of l-(4-chlorophenyl)-5-(2,6-difiuorophenyl)-lH-imidazole (i.e. the product of Step B) (0.60 g, 2.1 mmol) in chloroform (24 mL) was added N-chlorosuccinimide (0.69 g, 5.2 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (40 mL), washed with water (30 mL) and saturated aqueous sodium chloride solution (30 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as an off-white solid (0.50 g, 97.9 area % purity by HPLC) melting at 123-125 °C.
!H NMR (CDCI3) δ 7.40-7.30 (m, 3H), 7.16-7.10 (m, 2H), 6.90-6.84 (m, 2H).
ESI MS m/z 360 (M+l).
EXAMPLE 4
Preparation of 4-chloro- 1 -(4-chlorophenyl)-5-(2,6-difiuorophenyl)-2-methyl- lH-imidazole
(Compound 1)
Step A: Preparation of l-(4-chlorophenyl)-5-(2,6-difiuorophenyl)-2-methyl- lH-imidazole
To a stirred mixture of l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole (i.e. the product of Step B of Example 3) (l .OOg, 3.44 mmol) in tetrahydrofuran (34 mL) at -50 °C was added dropwise a solution of lithium diisopropylamide (1.0 M in tetrahydrofuran, 2.60 mL, 5.10 mmol). The reaction mixture was stirred at -50 °C for 1.5 h, and then a solution of iodomethane (1.47 g, 10.3 mmol) in tetrahydrofuran (16 mL) was added. The reaction mixture was slowly warmed to room temperature, stirred for 4 h, and then concentrated under reduced pressure. The resulting residue was diluted with dichloromethane (50 mL), washed with water (20 mL) and saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as a pale -ye How solid (0.74 g).
in NMR (CDCI3) δ 7.35-7.30 (m, 2H), 7.24-7.17 (m, 1H), 7.14 (s, 1H), 7.12-7.06 (m, 2H), 6.85-6.78 (m, 2H), 2.33 (s, 3H). ESI MS m/z 305 (M+l).
Step B: Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl- lH-imidazole
To a stirred mixture of l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl- lH-imidazole (i.e. the product of Step A) (0.740 g, 2.40 mmol) in chloroform (22 mL) was added N-chlorosuccinimide (0.34 g, 2.55 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (50 mL), washed with water (30 mL), saturated aqueous sodium chloride solution (30 mL) and dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate -hexanes (1 : 9) as eluant to provide the title compound as an off- white solid (0.35 g, 98.0 area % purity by HPLC) melting at 143-145° C.
!H NMR (CDCI3) δ 7.35-7.29 (m, 3H), 7.10-7.06 (m, 2H), 6.90-6.83 (m, 2H), 2.33 (s, 3H). ESI MS m/z 339 (M+l).
EXAMPLE 5
Preparation of 4-bromo- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl- lH-imidazole
(Compound 509)
To a solution of l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2 -methyl- lH-imidazole (prepared by the method of Example 4, Step A) (0.300 g, 0.97 mmol) in trichloromethane (5 mL) was added N-bromosuccinimide (0.211 g, 1.18 mmol). The reaction mixture was heated at reflux for 16 h, and then cooled to room temperature. The reaction mixture was diluted with chloroform (20 mL), washed with water (5 mL) and saturated aqueous sodium chloride solution (5 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate -hexanes as eluant to provide the title compound as a light yellow solid (269 mg) melting at 183-185 °C.
in NMR (CDCI3) δ 7.35-7.31 (m, 3H), 7.09-7.06 (d, J = 8.7 Hz, 2H), 6.88-6.82 (t, J = 7.8
Hz, 2H), 2.31 (s, 3H).
ESI MS m/z 383 (M+l).
EXAMPLE 6
Preparation of 4-chloro- 1 -(4-chlorophenyl)-5-(4-fluorophenyl)-2-methyl- lH-imidazole
(Compound 3)
Step A: Preparation of l-(4-chlorophenyl)-2-methyl-lH-imidazole
To a mixture of l-chloro-4-iodobenzene (1.50 g, 6.30 mmol) in A ,N-dimethylformamide (10 mL) was added cesium carbonate (3.50 g, 10.9 mmol), copper(I) iodide (0.10 g, 0.50 mmol), 2-methylimidazole (0.46 g, 5.66 mmol) and (li?,2i?)-l,2-cyclohexanediamine (0.12 g, 1.00 mmol). The reaction mixture was heated at 120 °C for 16 h and then cooled to room temperature. The reaction mixture was diluted with ethyl acetate (80 mL), washed with water (2 x 30 mL) and saturated aqueous sodium chloride solution (40 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (0.5 : 9.5) as eluant to provide the title compound as a brown solid (0.60 g).
!H NMR (CDCI3): δ 7.48-7.44 (m, 2H), 7.26-7.22 (m, 2H), 7.05 (d, J = 16.8 Hz, 2H), 2.35
(s, 3H).
ESI MS m/z 193 (M+l).
Step B: Preparation of l-(4-chlorophenyl)-5-(4-fiuorophenyl)-2-methyl-lH-imidazole
To a mixture of l-(4-chlorophenyl)-2-methyl-lH-imidazole (i.e. the product of Step A) (0.700 g, 0.520 mmol) in N,N-dimethylformamide (10 mL) was added l-fiuoro-4-iodo- benzene (1.61 g, 7.30 mmol), tris(2-methylphenyl)phosphine (0.110 g, 0.360 mmol), cesium fluoride (1.10 g, 7.30 mmol) and palladium(II) acetate (0.041 g, 0.18 mmol). The reaction mixture was stirred under argon, heated at reflux for 16 h, and then cooled to room temperature. The reaction mixture was diluted with ethyl acetate (40 mL), washed with water (20 mL) and saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using methanol-dichloromethane (1 : 9) as eluant to provide the title compound as an off-white solid (0.20 g, 95.3 area % purity by HPLC) melting at 132-134 °C.
!H NMR (CDCI3) δ 7.42-7.39 (m, 2H), 7.11-7.06 (m, 3H), 7.05-6.99 (m, 2H), 6.95-6.87 (m,
2H), 2.31 (s, 3 H).
ESI MS m/z 287 (M+l).
Step C: Preparation of 4-chloro-l -(4-chlorophenyl)-5-(4-fiuorophenyl)-2-methyl- lH-imidazole
To a mixture of l-(4-chlorophenyl)-5-(4-fluorophenyl)-2-methyl-lH-imidazole (i.e. the product of Step B) (0.100 g, 0.340 mmol) in chloroform (2.5 mL) was added N-chlorosuccinimide (0.05 g, 0.4 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (20 mL), washed with water (10 mL) and saturated aqueous sodium chloride solution (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as a yellow solid (0.065 g, 95.2 area % purity by HPLC) melting at 124-126 °C.
!H NMR (CDCI3) δ 7.40-7.36 (m, 2H), 7.14-7.07 (m, 2H), 7.06-7.03 (m, 2H), 6.99-6.92 (m,
2H), 2.29 (s, 3H).
ESI MS m/z 322 (M+l). EXAMPLE 7
Preparation of 2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,5-dimethoxyphenyl)- 4-methyl-lH-imidazole (Compound 473)
Step A: Preparation of N-[(2,6-difluoro-4-methoxyphenyl)methylene]- 3,5-dimethoxybenzenamine
A mixture of 3,5-dimethoxybenzamine (2.00 g, 13.1 mmol) and 2,6-difluoro- 4-methoxybenzaldehyde (2.30 g, 13.1 mmol) in toluene (40 mL) was heated at reflux overnight with use of a Dean-Stark trap for azeotropic removal of water. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to provide the title compound as a solid (4.00 g).
!H NMR (CDCI3) δ 8.56 (s, 1H), 6.53 (m, 2H), 6.36 (m, 3H), 3.85 (s, 3H), 3.81 (s, 6H). Step B: Preparation of 5-(2,6-difluoro-4-methoxyphenyl)-l-(3,5-dimethoxyphenyl)-
4-methyl- lH-imidazole
A mixture of N-[(2,6-difluoro-4-methoxyphenyl)methylene]-3,5-dimethoxy- benzenamine (i.e. the product of Step A) (1.80 g, 6.0 mmol), l-[(l-isocyanoethyl)sulfonyl]- 4-methylbenzene (1.90 g, 9.0 mmol) and potassium tert-butoxide in tetrahydrofuran (20 mL) was heated at reflux overnight. The reaction mixture was cooled and then concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.20 g).
!H NMR (CDCI3) δ 7.73 (s, 1H), 6.45 (m, 2H), 6.38 (s, 1H), 6.27 (s, 2H), 3.78 (s, 3H), 3.70 (m, 6H), 2.18 (s, 3H).
Step C: Preparation of 2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,5-dimethoxy- phenyl)-4-methyl- lH-imidazole
To a mixture of 5-(2,6-difluoro-4-methoxyphenyl)-l-(3,5-dimethoxyphenyl)-4-methyl- lH-imidazole (i.e. the product of Step B) (0.280 g, 0.78 mmol) and hexachloroethane (1.10 g, 4.7 mmol) in tetrahydrofuran (5 mL) at -78 °C was added lithium diisopropylamide (1.0 M in tetrahydrofuran, 0.390 mL, 0.78 mmol). After 1 h more lithium diisopropylamide (1.0 M in tetrahydrofuran, 0.150 mL, 0.30 mmol) was added to the reaction mixture, stirring was continued for an additional 1 h, and then more lithium diisopropylamide (1.0 M in tetrahydrofuran, 0.150 mL, 0.30 mmol) was added to the reaction mixture. The reaction mixture was allowed to slowly warm to room temperature, stirred for 2.5 h, and then concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.011 g).
!H NMR (CDCI3) δ 6.42 (m, 3H), 6.31 (m, 2H), 3.77 (s, 3H), 3.72 (s, 6H), 2.13 (s, 3H). EXAMPLE 8
Preparation of 2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3-fluorophenyl)- lH-imidazole (Compound 170)
Step A: Preparation of 2,6-a-[(3-fluorophenyl)amino)]-4-methoxybenzeneacetonitrile A mixture of 3-fluoroaniline (1.15 g, 10.4 mmol), 2,6-difluoro-
4-methoxybenzaldehyde (2.00 g, 11.6 mmol), potassium cyanide (2.70 g, 41.6 mmol) and indium chloride (2.30 g, 10.4 mmol) in tetrahydrofuran (40 mL) was stirred at room temperature overnight. The reaction mixture was diluted with water (about 100 mL) and extracted with ethyl acetate. The combined ethyl acetate extracts were concentrated under reduced pressure to provide the title compound as an oil, which was carried directly on to Step B.
Step B: Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluoro- phenyl)- lH-imidazole
To a mixture of 2,6-a-[(3-fluorophenyl)amino)]-4-methoxybenzeneacetonitrile (i.e. the product of Step A) (10.4 mmol) in dichloromethane (20 mL) was added N-(chloromethylene)-N-methylmethanaminium chloride (1.60 g, 12.5 mmol). The reaction mixture was heated to reflux for 3 h and then diluted with saturated aqueous sodium carbonate solution. The aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (2.27 g).
!H NMR (CDCI3) δ 7.37 (m, 1H), 7.13 (m, 1H), 6.96 (m, 2H), 6.41 (d, 2H), 3.77 (s, 3H).
Step C: Preparation of 2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3 -fluorophenyl)- lH-imidazole
A stirred mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)- lH-imidazole (i.e. the product of Step B) (1.00 g, 3.0 mmol) and N-bromosuccinimide
(0.641 g, 3.6 mmol) in N,N-dimethylformamide (15 mL) was heated at 60 °C for 2.5 days.
The reaction mixture was diluted with saturated aqueous sodium carbonate solution, and the resulting aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure.
The resulting material was purified by medium pressure liquid chromatography on silica gel
(0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.67 g).
in NMR (CDCI3) δ 7.37 (m, 1H), 7.13 (m, 1H), 7.13 (m, 1H), 6.96 (m, 2H), 6.41 (d, 2H), 3.77 (s, 3H). EXAMPLE 9
Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3-fluorophenyl)-2-methyl- 1H- imidazole (Compound 181)
A mixture of 2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)- lH-imidazole (i.e. the product of Example 8, Step C) (0.200 g, 0.490 mmol), trimethylboroxine (0.062 g, 0.490 mmol), cesium carbonate (0.479 g, 1.47 mmol) and dichlorobis(triphenylphosphine)palladium (0.035 g, 0.05 mmol) in dioxane (5 mL) and water (2 drops) was heated at reflux overnight. More trimethylboroxine (0.062 g, 0.490 mmol) and dichlorobis(triphenylphosphine)palladium (0.035 g, 0.05 mmol) were added to the reaction mixture, and the mixture was again heated at reflux overnight. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.090 g).
in NMR (CDCI3) δ 7.35 (m, 1H), 7.09 (m, 1H), 6.94 (d, 1H), 6.89 (m, 1H), 6.39 (m, 2H), 3.76 (s, 3H), 2.31 (s, 3H).
EXAMPLE 10
Preparation of 2,4-dibromo-5-(2,6-difluoro-3-methoxyphenyl)- 1 -(4-fluorophenyl)- lH-imidazole (Compound 350)
Step A: Preparation of 2,6-a-[(4-fluorophenyl)amino]-3-methoxybenzeneacetonitrile A mixture of 4-fluoroaniline (1.17 g, 10.6 mmol), 2,6-difluoro-
3-methoxybenzaldehyde (2.00 g, 11.6 mmol), potassium cyanide (2.80 g, 42.4 mmol) and indium chloride (2.30 g, 10.4 mmol) in tetrahydrofuran (50 mL) was stirred at room temperature overnight. The reaction mixture was diluted with water (about 100 mL) and extracted with ethyl acetate. The combined ethyl acetate layers were concentrated under reduced pressure to provide the title compound as an oil, which was carried directly on to Step B.
Step B: Preparation of 4-bromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluoro- phenyl)- lH-imidazole
To a mixture of 2,6-a-[(4-fluorophenyl)amino]-3-methoxybenzeneacetonitrile (i.e. the product of Step A) (10.6 mmol) in 1 ,2-dichloroethane (20 mL) was added N-(bromomethylene)-N-methylmethanaminium bromide (2.80 g, 12.7 mmol). The reaction mixture was heated to 80 °C for one minute, then saturated aqueous sodium carbonate solution was added, and the aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (1.78 g). in NMR (CDCI3) δ 7.71 (m, 1H), 7.15 (m, 2H), 7.05 (m, 2H), 6.96 (m, 1H), 6.82 (m, 1H), 3.85 (s, 3H).
Step C: Preparation of 2,4-dibromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluoro- phenyl)- lH-imidazole
A stirred mixture of 4-bromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluoro- phenyl)lH-imidazole (i.e. the product of Step B) (0.500 g, 1.3 mmol) and N-bromosuccinimide (0.285 g, 1.60 mmol) in N,N-dimethylformamide (15 mL) was heated at 60 °C overnight. More N-bromosuccinimide (0.250 g, 1.40 mmol) was added to the reaction mixture and the mixture was again heated at 60 °C overnight, after which time more N-bromosuccinimide (0.250 g, 1.40 mmol) was added and the mixture was again heated at 60 °C overnight. The reaction mixture was diluted with saturated aqueous sodium carbonate solution, and the aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.36 g).
!H NMR (CDCI3) δ 7.19 (m, 2H), 7.07 (m, 2H), 6.95 (m, 1H), 6.79 (m, 1H), 3.83 (s, 3H).
EXAMPLE 11
Preparation of 5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)-2,4-dimethyl- lH-imidazole (Compound 383)
A mixture of 2,4-dibromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)- lH-imidazole (i.e. the product of Example 10) (0.314 g, 0.68 mmol), trimethylboroxine (0.085 g, 0.490 mmol), cesium carbonate (0.665 g, 2.04 mmol) and dichlorobis(triphenyl- phosphine)palladium (0.049 g, 0.07 mmol) in dioxane (5 mL) and water (2 drops) was heated at reflux for 3 days. More trimethylboroxine (0.085 g, 0.68 mmol) and dichlorobis (triphenylphosphine)palladium (0.049 g, 0.70 mmol) were added at the reaction mixture, and the mixture was heated to reflux overnight. The reaction mixture was concentrated under reduced pressure and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.097 g).
in NMR (CDCI3) δ 7.11 (m, 2H), 7.02 (m, 2H), 6.84 (m, 1H), 6.73 (m, 1H), 3.81 (s, 3H), 2.29 (s, 3H), 2.16 (s, 3H).
EXAMPLE 12
Preparation of 4-chloro- 1 -[3-(difluoromethoxy)phenyl]-5-(2,6-difluoro-3-methoxyphenyl)- 2-ethenyl-lH-imidazole (Compound 406)
A mixture of 2-bromo-4-chloro-l-[3-(difluoromethoxy)phenyl]-5-(2,6-difluoro- 3-methoxyphenyl)-lH-imidazole (prepared by a procedure analogous to Example 8, Step C), 2,4,6-trivinylcyclotriboroxane pyridine complex (0.103 g, 0.43 mmol), cesium carbonate (0.420 g, 1.29 mmol) and dichlorobis(triphenylphosphine)palladium (0.028 g, 0.040 mmol) in dioxane (5 mL) and water (2 drops) was heated at reflux for 2.5 days. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (30 mg).
!H NMR (CDCI3) δ 7.37 (m, 1H), 7.16 (m, 1H), 7.05 (d, 1H), 6.93 (m, 2H), 6.78 (m, 1H), 6.35 (m, 3H), 5.43 (m, 1H), 3.82 (s, 3H).
EXAMPLE 13
Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,3,6-trifluorophenyl)-lH-imidazole-
2-carbonitrile (Compound 38)
A mixture of 2-bromo-4-chloro-l-(4-chlorophenyl)-5-(2,3,6-trifluorophenyl)- lH-imidazole (prepared by a procedure analogous to Example 8, Step C), zinc cyanide (0.033 g, 0.280 mmol), dichloro[l, -bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane complex (1 : 1) (0.016 g, 0.02 mmol) and tetramethylethylenediamine (0.01 g, 0.095 mmol) in N,N-dimethylformamide (3 mL) was heated at 60 °C in a Biotage Initiator™ microwave apparatus for 200 seconds. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.030 g) melting at 147-149 °C.
!H NMR (CDCI3) δ 7.45 (m, 2H), 7.28 (m, 1H), 7.21 (m, 2H), 6.89 (m, 1H).
EXAMPLE 14
Preparation of 4-chloro-5-(2,6-difluorophenyl)-2-ethynyl-l-(3-fluorophenyl)-lH-imidazole
(Compound 29)
Step A: Preparation of 4-chloro-5-(2,6-difluorophenyl)-l-(3-fluorophenyl)-
2-[2-(trimethylsilyl)ethynyl]-lH-imidazole
A mixture of 2-bromo-4-chloro-5-(2,6-difluorophenyl)-l-(3-fluorophenyl)- lH-imidazole (prepared by a procedure analogous to Example 8, Step C) (0.823 g, 2.10 mmol), dichlorobis(triphenylphosphine)palladium (0.147 g, 0.21 mmol), copper(I) iodide (0.081 g, 0.74 mmol) in triethylamine (15 mL) was stirred for 5 minutes while nitrogen gas flowed through a syringe needle below the surface of the reaction mixture. Ethynyltrimethyl silane (0.216 g, 2.2 mmol) was added to the reaction mixture, stirring was continued for 2 h, and then the mixture was heated at reflux overnight. More dichlorobis(triphenylphosphine)palladium (0.147 g, 0.21 mmol) and ethynyltrimethylsilane (0.216 g, 2.2 mmol) were added to the reaction mixture, and the mixture was heated at reflux for 4 h. The reaction mixture was diluted with saturated aqueous sodium carbonate solution and extracted with ethyl acetate, and the combined organic layers were washed with saturated aqueous ethylenediammetetraacetic acid, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.244 g).
!H NMR (CDCI3) δ 7.34 (m, 2H), 7.05 (m, 3H), 6.89 (m, 2H), 0.13 (s, 9H).
Step B: Preparation of 4-chloro-5-(2,6-difluorophenyl)-2-ethynyl-l-(3-fluorophenyl)- lH-imidazole
A mixture of 4-chloro-5-(2,6-difluorophenyl)-l-(3-fluorophenyl)-2-[2-(trimethyl- silyl)ethynyl]-lH-imidazole (i.e. the product of Step A) (0.231 mg, 0.570 mmol) in a solution of sodium hydroxide and methanol (1%, w/w, 2 mL) was stirred for 3 h at room temperature. The reaction mixture was diluted with ethyl acetate and saturated aqueous ammonium chloride solution, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as a solid (0.135 g). !H NMR (CDCI3) δ 7.35 (m, 2H), 7.11 (m, 1H), 7.00 (m, 2H), 6.89 (m, 2H), 3.17 (s, 1H).
EXAMPLE 15
Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)- lH-imidazole-2-methanol (Compound 199)
Step A: Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluoro- phenyl)-lH-imidazole-2-carboxaldehyde
To a stirred mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)- lH-imidazole (prepared by a procedure analogous to Example 8, Steps A and B) (1.35 g, 4.0 mmol) in diethyl ether (10 mL) at 0 °C was added lithium diisopropylamide (2 M in tetrahydrofuran, 2.2 mL, 4.4 mmol). The reaction mixture was stirred for 1 h at 0 °C, and then N,N-dimethylformamide (0.47 mL, 6.0 mmol) was added. After an additional 1 h of stirring at 0 °C, the reaction mixture was allowed to warm to room temperature. After 1 h, the reaction mixture was diluted with aqueous citric acid solution (20%>, 30 mL) and extracted with diethyl ether (100 mL). The organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel (0 to 20% gradient of ethyl acetate in /? -butyl chloride as eluant) to provide the title compound as a pale-yellow solid (0.397 g). in NMR (CDCI3) δ 9.71 (s, 1H), 7.19-7.17 (m, 2H), 7.06 (t, J = 7.5 Hz, 2H), 6.44 (m, 1H), 6.42 (s, 1H), 3.78 (s, 3H).
ESI MS m/z 367 (M+l). Step B: Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluoro- phenyl)- lH-imidazole-2-methanol
To a mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)- lH-imidazole-2-carboxaldehyde (i.e. the product of Step A) in methanol (10 mL) was added sodium borohydride (1.10 g, 2.64 mmol). After 1 h, water (25 mL) was added to the reaction mixture, and the aqueous mixture was extracted with diethyl ether (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel (0 to 30% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as an off-white solid (0.156 g).
in NMR (CDCI3) δ 7.26-7.25 (m, 2H), 7.07 (t, J = 7.5 Hz, 2H), 6.42 (s, 1H), 6.39 (s, 1H), 4.54 (d, J= 3 Hz, 2H), 4.13 (t, J= 6 Hz, 1H), 3.77 (s, 3H).
EXAMPLE 16
Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-(fluoromethyl)- 1 -(4-fluoro- phenyl)- lH-imidazole (Compound 221 )
To a mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)- lH-imidazole-2-methanol (i.e. the product of Example 15) in dichloromethane (2 mL) was added diethylaminosulfur trifluoride (60 μί, 0.45 mmol). After 2 h, the reaction mixture was diluted with water, extracted with dichloromethane (100 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel (0 to 20% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a white solid (0.031 g).
in NMR (CDCI3) δ 7.25-7.23 (m, 2H), 7.08 (t, J = 6 Hz, 2H), 6.43 (s, 1H), 6.41 (s, 1H), 5.25 (s, 1H), 5.13 (s, 1H), 3.78 (s, 3H).
EXAMPLE 17
Preparation of 4-bromo-2-(bromomethyl)- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole (Compound 326)
A mixture of 4-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl- lH-imidazole (i.e. the product of Example 5) (1.00 g, 2.6 mmol), N-bromosuccinimide (0.510 g, 2.87 mmol) and 2,2'-azobis(2-methylpropionitrile) (0.021 g, 130 mmol) in carbon tetrachloride (8 mL) was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.940 g).
in NMR (CDCI3) δ 7.35 (m, 3H), 7.24 (m, 2H), 6.87 (m, 2H), 4.36 (s, 2H). EXAMPLE 18
Preparation of 3-[2-bromo-4-chloro- 1 -(4-chlorophenyl)- lH-imidazol-5-yl]- 2,4-difluorobenzonitrile (Compound 283)
Step A: Preparation of 3-[4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]- 2,4-difluorobenzonitrile
A mixture of 5-(3-bromo-2,6-difluorophenyl)-4-chloro-l-(4-chlorophenyl)- lH-imidazole (prepared by a procedure analogous to Example 8, Steps A and B) (0.440 g, 0.490 mmol), zinc cyanide (0.058 g, 0.490 mmol), dichloro[l,l'-bis(diphenylphosphino)- ferrocene]palladium(II) dichloromethane complex (1 : 1) (0.044 g, 0.0545 mmol) and N^N'^-tetramethylethylenediamine (0.022 g, 0.22 mmol) in dimethylacetamide (3 mL) was heated at 200 °C in a Biotage Initiator™ microwave apparatus for 5 minutes. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.217 g).
lU NMR (CDCI3) δ 7.72 (s, 1H), 7.69 (m, 1H), 7.38 (m, 2H), 7.07 (m, 3H).
Step B: Preparation of 3-[2-bromo-4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]-
2,4-difluorobenzonitrile
A mixture of 3-[4-chloro-l -(4-chlorophenyl)- lH-imidazol-5-yl]-2,4-difluorobenzo- nitrile (i.e. the product of Step B) (0.217 g, 0.62 mmol) and N-bromosuccinimide (0.165 g, 0.930 mmol) in dimethylformamide (4 mL) was heated at 60 °C overnight. More N- bromosuccinimide (0.386 g, 2.17 mmol) was added portionwise to the reaction mixture, and the mixture was heated at 60 °C overnight again. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.196 g).
!H NMR (CDCI3) δ 7.67 (m, 1H), 7.40 (m, 2H), 7.13 (m, 2H), 7.03 (m, 1H).
EXAMPLE 19
Preparation of 3-[4-chloro- 1 -(4-chlorophenyl)-2-methyl- lH-imidazol-5-yl]-2,4-difluoro- benzonitrile (Compound 292)
A mixture of 3-[2-bromo-4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]-2,4-difluoro- benzonitrile (i.e. the product of Example 18) (0.150 g, 0.350 mmol), trimethylboroxine (0.088 g, 0.700 mmol), cesium carbonate (0.342 g, 1.05 mmol) and dichlorobis(triphenylphosphine)palladium (0.025 g, 0.035 mmol) in dioxane (4 mL) and water (2 drops) was heated at reflux for 3 h. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.088 g).
!H NMR (CDCI3) δ 7.65 (m, 1H), 7.39 (m, 2H), 7.09 (m, 2H), 7.01 (m, 1H), 2.32 (s, 3H).
EXAMPLE 20
Preparation of 4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH-imidazol-5-yl]-
3,5-difluorophenol (Compound 437)
To a stirred mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl- l-(4-methylphenyl)-lH-imidazole (prepared by a procedure analogous to Example 9) (0.500 g, 1.43 mmol) in dichloromethane (10 mL) at -78 °C was added tribromoborane (1 M in dichloromethane, 4.3 mL, 4.3 mmol). The reaction mixture was allowed to warm to room temperature, and stirred overnight. More boron tribromide (1 M in dichloromethane, 1.4 mL, 1.40 mmol) was added to the reaction mixture at room temperature, and stirring was continued for 4 h. Hydrochloric acid (1 N, 8.0 mL) was added to the reaction mixture, and then the aqueous mixture was brought to a basic pH by the addition of saturated aqueous sodium carbonate solution. The aqueous mixture was extracted with ethyl acetate, and the extract was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.41 g).
!H NMR (CDCI3) δ 10.68 (s, 1H), 7.24 (d, 2H), 7.09 (d, 2H), 6.43 (m, 2H), 2.31 (s, 3H), 2.18 (s, 3H).
EXAMPLE 21
Preparation of 3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH-imidazol-5-yl]-3,5-difluoro- phenoxy]-N-methyl-l-propanamide hydrochloride (Compound 503)
Step A: Preparation of phenylmethyl N-[3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)- lH-imidazol-5-yl]-3,5-difluorophenoxy]propyl]-N-methylcarbamate
A mixture of 4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH-imidazol-5-yl]- 3,5-difluorophenol (i.e. the product of Example 20) (0.200 g, 0.598 mmol) and 4 A molecular sieves (1.55 g) in N,N-dimethylformamide (3 mL) was stirred at room temperature for 3 h, and then a solution of phenylmethyl N-(3-chloropropyl)-N-methylcarbamate (prepared by the method described in PCT Publication WO 2007/149448) (0.434 g, 1.80 mmol) and tetrabutylammonium iodide (0.044 g, 0.120 mmol) in N,N-dimethyl- formamide (1 mL) was added. After 15 minutes, cesium carbonate (0.584 g, 1.80 mmol) was added to the reaction mixture. After 15 minutes, the reaction mixture was heated at 75 °C for 2 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (210 mg).
ESI MS m/z 541 (M+l).
Step B: Preparation of 3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH-imidazol- 5-yl]-3,5-difluorophenoxy]-N-methyl-l-propanamide hydrochloride
A mixture of phenylmethyl N-[3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)- lH-imidazol-5-yl]-3,5-difluorophenoxy]propyl]-N-methylcarbamate (i.e. the product of Step A) (0.197 g, 0.365 mmol), hydrochloric acid (2 M in diethyl ether, 1 mL) and methanol (30 mL) was purged with nitrogen for 30 minutes, and then palladium on carbon (10%>, 0.058 g, 0.055 mmol) was added and the nitrogen purge was maintained for an additional 15 minutes. After 15 minutes, the nitrogen purge was stopped and a balloon filled with hydrogen was connected to the reaction flask, and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was purged with nitrogen and the palladium on carbon catalyst was removed by filtering through a bed of sand and Celite® (diatomaceous filter aid) on a sintered glass frit funnel. The filtrate was concentrated under reduced pressure to provide the title compound as a solid (0.140 g).
in NMR (DMSO- ) δ 8.90 (br s, 2H), 7.25 (d, 2H), 7.11 (d, 2H), 6.76 (d, 2H), 4.08 (t, 2H), 2.98 (m, 2H), 2.54 (m, 3H), 2.31 (s, 3H), 2.19 (s, 3H), 2.04 (d, 2H).
EXAMPLE 22
Preparation of 5-[2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl]-
2-(trifluoromethyl)pyridine (Compound 481)
Step A: Preparation of N-[(2,6-difluoro-4-methoxyphenyl)methylene]-
6-(trifluoromethyl)-3-pyridinamine
A mixture of 6-(trifluoromethyl)-3-pyridinamine (5.00 g, 30.8 mmol) and 2,6-difluoro- 4-methoxybenzaldehyde (5.30 g, 30.8 mmol) in toluene (100 mL) was heated to reflux for 2.5 days. The reaction mixture was then concentrated under reduced pressure to provide the title compound as a solid (9.9 g).
in NMR (CDC13) δ 8.56 (s, 1H), 8.52 (d, 1H), 7.71 (d, 1H), 7.60 (m, 1H), 6.57 (m, 2H), 3.88 (s, 3H).
Step B: Preparation of 5-[5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]-
2-(trifluoromethyl)pyridine
A mixture of N-[(2,6-difluoro-4-methoxyphenyl)methylene]-6-(trifluoromethyl)- 3-pyridinamine (i.e. the product of Step A), l-[(l-isocyanoethyl)sulfonyl]-4-methylbenzene (4.6 g, 24 mmol) and potassium carbonate (4.4 g, 32 mmol) in dimethoxyethane (20 mL) and methanol (20 mL) was heated at 75 °C overnight. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (4.63 g).
!H NMR (CDCI3) δ 8.59 (m, 1H), 7.86 (s, 1H), 7.71 (m, 2H), 7.33 (m, 1H), 6.46 (m, 2H), 3.80 (s, 3H).
Step C: Preparation of 5-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-
1 -yl] -2-(trifluoromethyl)pyridine
A mixture of 5-[5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]-2-(trifluoro- methyl)pyridine (i.e. the product of Step B) (1.50 g, 4.20 mmol), N-chlorosuccinimide (0.56 g, 4.2 mmol) and 2,2'-azobis(2-methylpropionitrile) (0.038 g, 0.23 mmol) in carbon tetrachloride (8 mL) was heated at 65 °C for 3.5 days. The reaction mixture was diluted with saturated aqueous sodium carbonate solution and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.650 g).
in NMR (CDCI3) δ 8.59 (m, 1H), 7.73 (m, 3H), 6.49 (m, 2H), 3.82 (s, 3H).
Step D: Preparation of 5-[2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl]-2-(trifluoromethyl)pyridine
A mixture of 5-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]- 2-(trifluoromethyl)pyridine (i.e. the product of Step C) (0.650 g, 1.70 mmol) and N-bromosuccinimide (0.356 g, 2.0 mmol) in N,N-dimethylformamide (10 mL) was heated at 65 °C overnight. More N-bromosuccinimide (0.195 g, 1.1 mmol) was added to the reaction mixture, and the mixture was heated at 65 °C for 2.5 days. The reaction mixture was diluted with saturated sodium carbonate solution and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.108 g).
!H NMR (CDCI3) δ 8.58 (s, 1H), 7.78 (m, 2H), 6.43 (m, 2H), 3.79 (s, 3H).
EXAMPLE 23
Preparation of 5-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH-imidazol-l-yl]-
2-(trifluoromethyl)pyridine (Compound 487)
A mixture of 5-[2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol- l-yl]-2-(trifluoromethyl)pyridine (i.e. the product of Example 22) (0.093 g, 0.20 mmol), trimethylboroxine (0.025 g, 0.20 mmol), cesium carbonate (0.195 g, 0.60 mmol) and dichlorobis(triphenylphosphine)palladium (0.014 g, 0.20 mmol) in dioxane (3 mL) and water (1 drop) was heated to reflux overnight. The reaction mixture was then concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.021 g).
!H NMR (CDCI3) δ 8.55 (s, 1H), 7.75 (m, 1H), 7.69 (m, 1H), 6.42 (m, 2H), 3.78 (s, 3H), 2.35 (s, 3H).
EXAMPLE 24
Preparation of 2-chloro-5-[2-chloro-l-(2,6-difluoro-4-methoxyphenyl)-4-methyl- lH-imidazol-5-yl]pyridine (Compound 475)
Step A: Preparation of N-[(6-chloro-3-pyridinyl)methylene]-2,6-difluoro-4-methoxy- benzenamine
To a mixture of 2,6-difluoro-4-methoxybenzenamine (0.98 g, 6.9 mmol) in toluene (20 mL) was added 6-chloro-3-pyridinecarboxaldehyde (1.0 g, 6.3 mmol). The reaction mixture was heated at reflux with the use of a Dean-Stark trap for azeotropic removal of water. After 16 h the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting material was dried in a vacuum oven at 55 °C overnight to provide the title compound as a light brown solid (1.66 g).
in NMR (CDCI3) δ 8.74 (s, 1H), 8.73 (d, J = 2.44 Hz, 1H), 8.32 (dd, J = 2.20 Hz, J= 8.29 Hz, 1H), 7.44 (d, J= 8.29 Hz, 1H), 6.59-6.52 (m, 2H), 3.82 (s, 3H).
!9F NMR (CDCI3) δ -121.48 to -121.40 (m, 2F).
Step B: Preparation of 2-chloro-5-[l-(2,6-difluoro-4-methoxyphenyl)-4-methyl- lH-imidazol-5-yl]pyridine
To a mixture of N-[(6-chloro-3-pyridinyl)methylene]-2,6-difluoro-4-methoxy- benzenamine (i.e. the product of Step A) (1.66 g, 5.9 mmol) in tetrahydrofuran (15 mL) was added /?-toluenesulfonylmethyl isocyanide (1.35 g, 6.5 mmol) and potassium tert-butoxide (0.86 g, 7.7 mmol). The reaction mixture was heated at 85 °C for 4 h, cooled, and concentrated. The resulting material was diluted with ethyl acetate and washed with saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated. The resulting material was purified by medium pressure liquid chromatography on silica gel (ethyl acetate in hexanes as eluant), and then triturated with n-butyl chloride -hexanes to provide the title compound as a tan solid (0.50 g) melting at 117-118 °C.
!H NMR (CDCI3) δ 8.16 (d, J= 2.44 Hz, 1H), 7.55 (s, 1H), 7.44 (dd, J = 2.68 and 8.29 Hz,
1H), 7.28 (dd, J= 0.49 and 8.29 Hz, 1H), 6.54-6.48 (m, 2H), 3.81 (s, 3H), 2.33 (s, 3H). 19F NMR (CDC13) 5 -118.21 to -118.15 (m, 2F). Step C: Preparation of 2-chloro-5-[2-chloro-l-(2,6-difluoro-4-methoxyphenyl)-
4-methyl-lH-imidazol-5-yl]pyridine
To a mixture of 2-chloro-5-[l-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol- 5-yl]pyridine (i.e. the product of Step B) (0.150 g, 0.45 mmol) in N,N-dimethylformamide (2.0 mL) was added N-chlorosuccinimide (0.066 g, 0.49 mmol), and the reaction mixture was heated at 60 °C. After 30 minutes, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (40 mL), and washed with water and saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (ethyl acetate in hexanes as eluant) to provide the title compound (0.108 g) as an off- white solid melting at 94-95 °C.
in NMR (CDCI3) δ 8.17 (d, J = 2.20 Hz, 1H), 7.43 (dd, J= 8.29 Hz, J = 2.44 Hz, 1H), 7.26 (d, J= 8.54 Hz, 1H), 6.53 (d, J= 9.02 Hz, 2H), 3.82 (s, 3H), 2.28 (s, 3H).
EXAMPLE 25
Preparation of 4-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH-imidazol-l-yl]- phenyl thiocyanate (Compound 510)
A mixture of 4-chloro-l-(4-iodophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl- lH-imidazole (prepared by a procedure analogous to Example 9) (0.2 g, 0.43 mmol), cuprous thiocyanate (0.08 g, 0.65 mmol) and potassium thiocyanate (0.06 g, 0.65 mmol) in N,N-dimethylformamide (5 mL) was heated to 140 °C overnight. The reaction mixture was cooled to room temperature and then partitioned between water and ethyl acetate, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (20:80 to 60:40 to 80:20 gradient of ethyl acetate in hexane as eluant) to provide the title compound as a solid (0.07 g).
!H NMR (CDCI3) δ 7.53 (d, 2H), 7.22 (d, 2H), 6.40 (d, 2H), 3.78 (s, 3H), 2.31 (s, 3H).
EXAMPLE 26
Preparation of 2-[4-[4-chloro-l-(3-fluorophenyl)-2-methyl-lH-imidazol-5-yl]-3,5-difluoro- phenoxy] acetonitrile (Compound 512)
A mixture of 4-[4-chloro-l-(3-fluorophenyl)-2-methyl-lH-imidazol-5-yl]-3,5-difluoro- phenol (prepared from 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)- 2-methyl-lH-imidazole (i.e. the product of Example 9) by a procedure analogous to Example 20; 0.30 g, 8.9 mmol), bromoacetonitrile (0.13 g, 1.1 mmol) and potassium carbonate in N,N-dimethylformamide (4 mL) was stirred at 40 °C for 2 h. The reaction mixture was then concentrated under reduced pressure and purified by medium pressure liquid chromatography on silica gel (0 to 100% ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.28 g).
!H NMR (CDCI3) δ 7.37 (m, 1H), 7.11 (m, 1H), 6.91 (m, 2H), 6.52 (m, 2H), 4.76 (s, 2H), 2.31 (s, 3H).
By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 62D can be prepared. The following abbreviations are used in the Tables which follow: Me means methyl, Et means ethyl, Ph means phenyl, MeO means methoxy, MeS is methylthio, CN means cyano, Bn means benzyl and N02 means nitro.
Table 1
Figure imgf000068_0001
Q2 is 4-Cl-Ph, R1 is CI and R2 is Me.
Figure imgf000068_0002
constructed the same as Table 1 above except that the row heading in Table 1 (i.e. "Q2 is 4-Cl-Ph, Pv1 is CI and R2 is Me") is replaced with the respective row heading shown below. For example, in Table 1A the row heading is "Q2 is 4-Cl-Ph, R1 is Br and R2 is Me", and (R )m is as defined in Table 1 above. Thus, the first entry in Table 1 A specifically discloses 4-bromo- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole. Tables 2A through 715 A are constructed similarly. Row Heading
Qz is 4- ■Cl-Ph. R is Br and R~ is Me.
Q2 is 4- ■Cl-Ph. is CI and R2 is CFH2.
Q2 is 4- Cl-Ph. is I and R2 is Me.
Q2 is 4- Cl-Ph. is Me and R2 is Me.
Q2 is 4- Cl-Ph. is Me and R2 is CI.
Q2 is 4- Cl-Ph. is Me and R2 is Br.
Q2 is 4- Cl-Ph. is Me and R2 is I.
Q2 is 4- Cl-Ph. is Me and R2 is MeO.
Q2 is 4- Cl-Ph. is MeO and R2 is Me.
Q2 is 4- Cl-Ph. is Br and R2 is Br.
Q2 is 4- Cl-Ph. is Br and R2 is CI.
Q2 is 4- Cl-Ph. is CI and R2 is Br.
Q2 is 4- Cl-Ph. is CI and R2 is CI.
Q2 is 4- Cl-Ph. is Me and R2 is MeS.
Q2 is 4- Cl-Ph. is MeS and R2 is Me.
Q2 is 4- Cl-Ph. is Et and R2 is Br.
Q2 is 4- Cl-Ph. is Et and R2 is CI.
Q2 is 4- Cl-Ph. is Et and R2 is Me.
Q2 is 4- Cl-Ph. is Me and R2 is Et.
Q2 is 4- Cl-Ph. is CI and R2 is Et.
Q2 is 4- Cl-Ph. is Me and R2 is CN.
Q2 is 3- Cl-Ph. is CI and R2 is Me.
Q2 is 3- Cl-Ph. is CI and R2 is CFH2.
Q2 is 3- Cl-Ph. is Br and R2 is Me.
Q2 is 3- Cl-Ph. is I and R2 is Me.
Q2 is 3- Cl-Ph. is Me and R2 is Me.
Q2 is 3- Cl-Ph. is Me and R2 is CI.
Q2 is 3- Cl-Ph. is Me and R2 is Br.
Q2 is 3- Cl-Ph. is Me and R2 is I.
Q2 is 3- Cl-Ph. is Br and R2 is Br.
Q2 is 3- Cl-Ph. is Br and R2 is CI.
Q2 is 3- Cl-Ph. is CI and R2 is Br.
Q2 is 3- Cl-Ph. is CI and R2 is CI.
Q2 is 4- F-Ph, R is CI and R2 is Me.
Q2 is 4- F-Ph, R is CI and R2 is CFH2.
Q2 is 4- F-Ph, R is Br and R2 is Me.
Q2 is 4- F-Ph, R is I and R2 is Me. Row Heading s 4-F-Ph, R is Me and R2 is Me.
Q2 s 4-F-Ph, R is Me and R2 is CI.
Q2 is 4-F-Ph, R is Me and R2 is Br.
Q2 s 4-F-Ph, R is Me and R2 is I.
s 4-F-Ph, R is Br and R^ is Br.
Q is 4-F-Ph, R is Br and R^ is CI.
Q2 s 4-F-Ph, R is CI and R2 is Br.
Q2 s 4-F-Ph, R is CI and R2 is CI.
Q2 is 3-F-Ph, R is CI and R2 is Me.
Q2 s 3-F-Ph, R is CI and R2 is CFH2.
Q2 is 3-F-Ph, R is Br and R2 is Me.
Q2 s 3-F-Ph, R is I and R2 is Me.
Q2 s 3-F-Ph, R is Me and R2 is Me.
Q2 s 3-F-Ph, R is Me and R2 is CI.
Q2 s 3-F-Ph, R is Me and R2 is Br.
Q2 s 3-F-Ph, R is Me and R2 is I.
Q2 s 3-F-Ph, R is Br and R2 is Br.
s 3-F-Ph, R is Br and R^ is CI.
s 3-F-Ph, R is CI and R2 is Br.
Q2 s 3-F-Ph, R is CI and R2 is CI.
Q2 3 -CF2HO- Ph, R1 is CI and R2 is Me. Q2 3 -CF2HO- Ph, R1 is CI and R2 is CFH2 Q2 3 -CF2HO- Ph, R1 is Br and R2 is Me.
3 -CF2HO Ph, R1 is I and R2 is Me.
3 -CF2HO Ph, R1 is Me and R2 is Me.
3 -CF2HO Ph, R1 is Me and R2 is CI.
Q2 3 -CF2HO Ph, R1 is Me and R2 is Br. Q2 3 -CF2HO Ph, R1 is Me and R2 is I.
3 -CFoHO Ph, R1 is Br and R2 is Br.
3 -CF2HO Ph, R1 is Br and R2 is CI.
3 -CF2HO -Ph, R1 is CI and R2 is Br.
3 -CF2HO -Ph, R1 is CI and R2 is CI.
Q2 4-Me-Ph, R is CI and R2 is Me.
Q2 4-Me-Ph, R is CI and R2 is CFH2. Q2 4-Me-Ph, R is Br and R2 is Me.
Q2 4-Me-Ph, R is I and R2 is Me.
4-Me-Ph, R is Me and R2 is Me. Row Heading
Qz is 4- Me-Ph, R is Me and R2 is CI.
Q2 is 4- Me-Ph, R is Me and R2 is Br.
Q2 is 4- Me-Ph, R is Me and R2 is I.
Q2 is 4- Me-Ph, R is Br and R2 is Br.
Q2 is 4- Me-Ph, R is Br and R2 is CI.
Q2 is 4- Me-Ph, R is CI and R2 is Br.
Q2 is 4- Me-Ph, R is CI and R2 is CI.
Q2 is 3- Me-Ph, R is CI and R2 is Me.
Q2 is 3- Me-Ph, R is CI and R2 is CFH2. Q2 is 3- Me-Ph, R is Br and R2 is Me.
Q2 is 3- Me-Ph, R is I and R2 is Me.
Q2 is 3- Me-Ph, R is Me and R2 is Me.
Q2 is 3- Me-Ph, R is Me and R2 is CI.
Q2 is 3- Me-Ph, R is Me and R2 is Br.
Q2 is 3- Me-Ph, R is Me and R2 is I.
Q2 is 3- Me-Ph, R is Br and R2 is Br.
Q2 is 3- Me-Ph, R is Br and R2 is CI.
Q2 is 3- Me-Ph, R is CI and R2 is Br.
Q2 is 3- Me-Ph, R is CI and R2 is CI.
Q2 is 4- Et-Ph, R is CI and R2 is Me.
Q2 is 4- Et-Ph, R is CI and R2 is CFH2.
Q2 is 4- Et-Ph, R is Br and R2 is Me.
Q2 is 4- Et-Ph, R is I and R2 is Me.
Q2 is 4- Et-Ph, R is Me and R2 is Me.
Q2 is 4- Et-Ph, R is Me and R2 is CI.
Q2 is 4- Et-Ph, R is Me and R2 is Br.
Q2 is 4- Et-Ph, R is Me and R2 is I.
Q2 is 4- Et-Ph, R is Br and R2 is Br.
Q2 is 4- Et-Ph, R is Br and R2 is CI.
Q2 is 4- Et-Ph, R is CI and R2 is Br.
Q2 is 4- Et-Ph, R is CI and R2 is CI.
Q2 is 4- CI, 3-F-Ph, R is CI and R2 is Me. Q2 is 4- CI, 3-F-Ph, R is CI and R2 is CFH2. Q2 is 4- CI, 3-F-Ph, R is Br and R2 is Me. Q2 is 4- CI, 3-F-Ph, R is I and R2 is Me. Q2 is 4- CI, 3-F-Ph, R is Me and R2 is Me. Q2 is 4- CI, 3-F-Ph, R is Me and R2 is CI. Row Heading
Q2 is 4-Cl, 3-F-Ph, R is Me and R~ is Br. Q2 is 4-Cl, 3-F-Ph, R is Me and R2 is I. Q2 is 4-Cl, 3-F-Ph, R is Br and R2 is Br. Q2 is 4-Cl, 3-F-Ph, R is Br and R2 is CI. Q2 is 4-Cl, 3-F-Ph, R is CI and R2 is Br. Q2 is 4-Cl, 3-F-Ph, R is CI and R2 is CI. Q2 is 2-Cl, 4-F-Ph, R is CI and R2 is Me. Q2 is 2-Cl, 4-F-Ph, R is CI and R2 is CFH2. Q2 is 2-Cl, 4-F-Ph, R is Br and R2 is Me. Q2 is 2-Cl, 4-F-Ph, R is I and R2 is Me. Q2 is 2-Cl, 4-F-Ph, R is Me and R2 is Me. Q2 is 2-Cl, 4-F-Ph, R is Me and R2 is CI. Q2 is 2-Cl, 4-F-Ph, R is Me and R2 is Br. Q2 is 2-Cl, 4-F-Ph, R is Me and R2 is I. Q2 is 2-Cl, 4-F-Ph, R is Br and R2 is Br. Q2 is 2-Cl, 4-F-Ph, R is Br and R2 is CI. Q2 is 2-Cl, 4-F-Ph, R is CI and R2 is Br. Q2 is 2-Cl, 4-F-Ph, R is CI and R2 is CI. Q2 is 4-F, 3-Me-Ph, R is CI and R2 is Me. Q2 is 4-F, 3-Me-Ph, R is CI and R2 is CFH2. Q2 is 4-F, 3-Me-Ph, R is Br and R2 is Me. Q2 is 4-F, 3-Me-Ph, R is I and R2 is Me. Q2 is 4-F, 3-Me-Ph, R is Me and R2 is Me. Q2 is 4-F, 3-Me-Ph, R is Me and R2 is CI. Q2 is 4-F, 3-Me-Ph, R is Me and R2 is Br. Q2 is 4-F, 3-Me-Ph, R is Me and R2 is I. Q2 is 4-F, 3-Me-Ph, R is Br and R2 is Br. Q2 is 4-F, 3-Me-Ph, R is Br and R2 is CI. Q2 is 4-F, 3-Me-Ph, R is CI and R2 is Br. Q2 is 4-F, 3-Me-Ph, R is CI and R2 is CI. Q2 is 3,4-di-F-Ph, R is CI and R2 is Me. Q2 is 3,4-di-F-Ph, R is CI and R2 is CFH2. Q2 is 3,4-di-F-Ph, R is Br and R2 is Me. Q2 is 3,4-di-F-Ph, R is I and R2 is Me.
Q2 is 3,4-di-F-Ph, R is Me and R2 is Me. Q2 is 3,4-di-F-Ph, R is Me and R2 is CI. Q2 is 3,4-di-F-Ph, R is Me and R2 is Br. Row Heading
Q2 is 3,4-di-F-Ph, R is Me and R~ is I.
Q2 is 3,4-di-F-Ph, R is Br and R2 is Br.
Q2 is 3,4-di-F-Ph, R is Br and R2 is CI.
Q2 is 3,4-di-F-Ph, R is CI and R2 is Br.
Q2 is 3,4-di-F-Ph, R is CI and R2 is CI.
Q2 is 3,4-di-Cl-Ph, R is CI and R2 is Me.
Q2 is 3,4-di-Cl-Ph, R is CI and R2 is CFH2.
Q2 is 3,4-di-Cl-Ph, R is Br and Rz is Me.
Q2 is 3,4-di-Cl-Ph, R is I and R2 is Me.
Q2 is 3,4-di-Cl-Ph, R is Me and R2 is Me.
Q2 is 3,4-di-Cl-Ph, R is Me and R2 is CI.
Q2 is 3,4-di-Cl-Ph, R is Me and R2 is Br.
Q2 is 3,4-di-Cl-Ph, R is Me and R2 is I.
Q2 is 3,4-di-Cl-Ph, R is Br and R2 is Br.
Q2 is 3,4-di-Cl-Ph, R is Br and R2 is CI.
Q2 is 3,4-di-Cl-Ph, R is CI and R2 is Br.
Q2 is 3,4-di-Cl-Ph, R is CI and R2 is CI.
Q2 is 3,5-di-MeO-Ph, R is CI and R2 is Me.
Q2 is 3,5-di-MeO-Ph, R is CI and R2 is CFH2. Q2 is 3,5-di-MeO-Ph, R is Br and R2 is Me.
Q2 is 3,5-di-MeO-Ph, R is I and R2 is Me.
Q2 is 3,5-di-MeO-Ph, R is Me and R2 is Me.
Q2 is 3,5-di-MeO-Ph, R is Me and R2 is CI.
Q2 is 3,5-di-MeO-Ph, R is Me and R2 is Br.
Q2 is 3,5-di-MeO-Ph, R is Me and R2 is I.
Q2 is 3,5-di-MeO-Ph, R is Br and R2 is Br.
Q2 is 3,5-di-MeO-Ph, R is Br and R2 is CI.
Q2 is 3,5-di-MeO-Ph, R is C and R^- is Br.
Q2 is 3,5-di-MeO-Ph, R is C and R2 is CI.
Q2 is 2-Cl, 3,5-di-MeO-Ph, R is CI and R2 is Me. Q2 is 2-Cl, 3,5-di-MeO-Ph, R is CI and R2 is CFH2. Q2 is 2-Cl, 3,5-di-MeO-Ph, R is Br and R2 is Me. Q2 is 2-Cl, 3,5-di-MeO-Ph, R is I and R2 is Me. Q2 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R2 is Me. Q2 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R2 is CI. Q2 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R2 is Br. Q2 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R2 is I. Row Heading
Q2 is 2- CI. 3,5-di-MeO-Ph, R is Br and R~ is Br. Q2 is 2- CI, 3,5-di-MeO-Ph, R is Br and R2 is CI. Q2 is 2- CI, 3,5-di-MeO-Ph, R is CI and R2 is Br. Q2 is 2- CI, 3,5-di-MeO-Ph, R is CI and R2 is CI. Q2 is 4- CI, 3,5-di-MeO-Ph, R is CI and R2 is Me. Q2 is 4- CI, 3,5-di-MeO-Ph, R is CI and R2 is CFH2. Q2 is 4- CI, 3,5-di-MeO-Ph, R is Br and R2 is Me. Q2 is 4- CI, 3,5-di-MeO-Ph, R is I and R2 is Me. Q2 is 4- CI, 3,5-di-MeO-Ph, R is Me and R2 is Me. Q2 is 4- CI, 3,5-di-MeO-Ph, R is Me and R2 is CI. Q2 is 4- CI, 3,5-di-MeO-Ph, R is Me and R2 is Br. Q2 is 4- CI, 3,5-di-MeO-Ph, R is Me and R2 is I. Q2 is 4- CI, 3,5-di-MeO-Ph, R is Br and R2 is Br. Q2 is 4- CI, 3,5-di-MeO-Ph, R is Br and R2 is CI. Q2 is 4- CI, 3,5-di-MeO-Ph, R is CI and R2 is Br. Q2 is 4- CI, 3,5-di-MeO-Ph, R is CI and R2 is CI. Q2 is 4-■Cl-Bn, R is CI and R2 is Me.
Q2 is 4-■Cl-Bn, R is CI and R2 is CFH2.
Q2 is 4- Cl-Bn, R is Br and R2 is Me.
Q2 is 4- Cl-Bn, R is I and Rz is Me.
Q2 is 4- Cl-Bn, R is Me and R2 is Me.
Q2 is 4- Cl-Bn, R is Me and R2 is CI.
Q2 is 4- Cl-Bn, R is Me and R2 is Br.
Q2 is 4- Cl-Bn, R is Me and R2 is I.
Q2 is 4- Cl-Bn, R is Br and R2 is Br.
Q2 is 4- Cl-Bn, R is Br and R2 is CI.
Q2 is 4- Cl-Bn, R is CI and R2 is Br.
Q2 is 4- Cl-Bn, R is CI and R2 is CI.
Q2 is 4- F-Bn, R1 is CI and R2 is Me.
Q2 is 4- F-Bn, R1 is CI and R2 is CFH2.
Q2 is 4- F-Bn, R1 is Br and R2 is Me.
Q2 is 4- F-Bn, R1 is I and R2 is Me.
Q2 is 4- F-Bn, R1 is Me and R2 is Me.
Q2 is 4- F-Bn, R1 is Me and R2 is CI.
Q2 is 4- F-Bn, R1 is Me and R2 is Br.
Q2 is 4- F-Bn, R1 is Me and R2 is I.
Q2 is 4- F-Bn, R1 is Br and R2 is Br. Row Heading
Q2 is 4-F-Bn, R1 is Br and R2 is CI.
Q2 is 4-F-Bn, R1 is CI and R2 is Br.
Q2 is 4-F-Bn, R1 is CI and R2 is CI.
Q2 is 6-C 1-3-pyridinyl, R s CI and R2 is Me. Q2 is 6-C 1-3-pyridinyl, R s CI and R2 is CFH2. Q2 is 6-C 1-3-pyridinyl, R s Br and R2 is Me. Q2 is 6-C 1-3-pyridinyl, R s I and R2 is Me. Q2 is 6-C 1-3-pyridinyl, R s Me and R2 is Me. Q2 is 6-C 1-3-pyridinyl, R s Me and R2 is CI. Q2 is 6-C 1-3-pyridinyl, R s Me and R2 is Br. Q2 is 6-C 1-3-pyridinyl, R s Me and R2 is I. Q2 is 6-C 1-3-pyridinyl, R s Me and R2 is MeO. Q2 is 6-C 1-3-pyridinyl, R s MeO and R2 is Me. Q2 is 6-C 1-3-pyridinyl, R s Br and R^ is Br. Q2 is 6-C 1-3-pyridinyl, R s Br and R2 is CI. Q2 is 6-C 1-3-pyridinyl, R s CI and R2 is Br. Q2 is 6-C 1-3-pyridinyl, R s CI and R2 is CI. Q2 is 6-C 1-3-pyridinyl, R s Me and R2 is MeS. Q2 is 6-C 1-3-pyridinyl, R s MeS and R2 is Me. Q2 is 6-C 1-3-pyridinyl, R s Et and R2 is Br. Q2 is 6-C 1-3-pyridinyl, R s Et and R2 is CI. Q2 is 6-C 1-3-pyridinyl, R s Et and R2 is Me. Q2 is 6-C 1-3-pyridinyl, R s Me and R2 is Et. Q2 is 6-C 1-3-pyridinyl, R s CI and R2 is Et. Q2 is 6-C 1-3-pyridinyl, R s Me and R2 is CN. is 6-Me-3-pyridinyl, R is CI and R2 is Me. Q2 is 6-Me-3-pyridinyl, R is CI and R2 is CFH2. Q2 is 6-Me-3-pyridinyl, R is Br and R2 is Me. Q2 is 6-Me-3-pyridinyl, R is I and R2 is Me. Q2 is 6-Me-3-pyridinyl, R is Me and R2 is Me. Q2 is 6-Me-3-pyridinyl, R is Me and R2 is CI. Q2 is 6-Me-3-pyridinyl, R is Me and R2 is Br. Q2 is 6-Me-3-pyridinyl, R is Me and R2 is I. Q2 is 6-Me-3-pyridinyl, R is Br and R2 is Br. Q2 is 6-Me-3-pyridinyl, R is Br and R2 is CI. Q2 is 6-Me-3-pyridinyl, R is CI and R2 is Br. Q2 is 6-Me-3-pyridinyl, R is CI and R2 is CI. Row Heading
Q2 is 6- -MeO- -3-pyridinyl, R is CI and R2 is Me.
Q2 is 6- -MeO- -3-pyridinyl, R is CI and R2 is CFH2.
Q2 is 6- -MeO- -3-pyridinyl, R is Br and R2 is Me.
Q2 is 6- -MeO- -3-pyridinyl, R is I and R2 is Me.
Q2 is 6- -MeO- -3-pyridinyl, R is Me and R2 is Me.
Q2 is 6- -MeO- -3-pyridinyl, R is Me and R2 is CI.
Q2 is 6- -MeO- -3-pyridinyl, R is Me and R2 is Br.
Q2 is 6- -MeO- -3-pyridinyl, R is Me and R2 is I.
Q2 is 6- -MeO- -3-pyridinyl, R is Br and R2 is Br.
Q2 is 6- -MeO- -3-pyridinyl, R is Br and R2 is CI.
Q2 is 6- -MeO- -3-pyridinyl, R is CI and R2 is Br.
Q2 is 6- -MeO- -3-pyridinyl, R is CI and R2 is CI.
Qz is 6-CF3 -3-pyridinyl, R1 is CI and z is Me. Q2 is 6-CF3 -3-pyridinyl, R1 is CI and R2 is CFH2. Q2 is 6-CF3 -3-pyridinyl, R1 is Br and R2 is Me. Q2 is 6-CF3 -3-pyridinyl, R1 is I and R2 is Me. Q2 is 6-CF3 -3-pyridinyl, R1 is Me and R2 is Me. Q2 is 6-CF3 -3-pyridinyl, R1 is Me and R2 is CI. Q2 is 6-CF3 -3-pyridinyl, R1 is Me and R2 is Br. Q2 is 6-CF3 -3-pyridinyl, R1 is Me and R2 is I. Q2 is 6-CF3 -3-pyridinyl, R^ is Br and R2 is Br. Q2 is 6-CF3 -3-pyridinyl, R1 is Br and R2 is CI. Q2 is 6-CF3 -3-pyridinyl, R1 is CI and R2 is Br. Q2 is 6-CF3 -3-pyridinyl, R1 is CI and R2 is CI.
Q2 is 6- ■Br- ■3-pyridinyl, R is CI and R2 is Me.
Q2 is 6- ■Br- ■3-pyridinyl, R is CI and R2 is CFH2.
Q2 is 6- ■Br- ■3-pyridinyl, R is Br and R2 is Me.
Q2 is 6- -Br- ■3-pyridinyl, R is I and Rz is Me.
Q2 is 6- -Br- ■3-pyridinyl, R is Me and R2 is Me,
Q2 is 6- -Br- ■3-pyridinyl, R is Me and R2 is CI.
Q2 is 6- -Br- ■3-pyridinyl, R is Me and R2 is Br.
Q2 is 6- -Br- ■3-pyridinyl, R is Me and R2 is I.
Q2 is 6- -Br- ■3-pyridinyl, R is Br and R2 is Br.
Q2 is 6- -Br- ■3-pyridinyl, R is Br and R2 is CI.
Q2 is 6- -Br- ■3-pyridinyl, R is CI and R2 is Br.
Q2 is 6- -Br- ■3-pyridinyl, R is CI and R2 is CI.
Q2 is 6-F-3-pyridinyl, is CI and R2 is Me. Row Heading
Q2 is 6-F-3-pyridinyl, R^ is CI and R2 is CFH2.
Q2 is 6-F-3-pyridinyl, R^ is Br and R2 is Me.
Q2 is 6-F-3-pyridinyl, R^ is I and R2 is Me.
Q2 is 6-F-3-pyridinyl, R1 is Me and R2 is Me.
Q2 is 6-F-3-pyridinyl, R1 is Me and R2 is CI.
Q2 is 6-F-3-pyridinyl, R^ is Me and R2 is Br.
Q2 is 6-F-3-pyridinyl, R^ is Me and R2 is I.
Q2 is 6-F-3-pyridinyl, R^ is Br and R2 is Br.
Q2 is 6-F-3-pyridinyl, R^ is Br and R2 is CI.
Q2 is 6-F-3-pyridinyl, R^ is CI and R2 is Br.
Q2 is 6-F-3-pyridinyl, R^ is CI and R2 is CI.
Q2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R2 is Me. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R2 is CFH2. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is Br and R2 is Me. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is I and R2 is Me. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is Me and R2 is Me. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is Me and R2 is CI. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is Me and R2 is Br. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is Me and R2 is I. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is Br and R2 is Br. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is Br and R2 is CI. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R2 is Br. Q2 is 2-Cl. 6-Me-4-pyridinyl, R is CI and R2 is CI. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is CI and R2 is Me. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is CI and R2 is CFH2. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is Br and R2 is Me. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is I and R2 is Me. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is Me and R2 is Me. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is Me and R2 is CI. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is Me and R2 is Br. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is Me and R2 is I. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is Br and R2 is Br. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is Br and R2 is CI. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is CI and R2 is Br. Q2 is 2-Cl 6-MeO-3-pyridinyl, R is CI and R2 is CI. Q2 is 2-Cl. 6-CF3-3-pyridinyl, R1 is CI and z is Me. Q2 is 2-Cl. 6-CF3-3-pyridinyl, R1 is CI and R2 is CFH2. Row Heading
Q2 is 2-C , 6-CF3-3-pyridinyl, R1 is Br and R^ is Me. Q2 is 2-C , 6-CF3-3-pyridinyl, R^ is I and R2 is Me. Q2 is 2-C , 6-CF3-3-pyridinyl, R1 is Me and R2 is Me. Q2 is 2-C , 6-CF3-3-pyridinyl, R1 is Me and R2 is CI. Q2 is 2-C , 6-CF3-3-pyridinyl, R^ is Me and R2 is Br. Q2 is 2-C , 6-CF3-3-pyridinyl, R^ is Me and R2 is I. Q2 is 2-C , 6-CF3-3-pyridinyl, R^ is Br and R2 is Br. Q2 is 2-C , 6-CF3-3-pyridinyl, R1 is Br and R2 is CI. Q2 is 2-C , 6-CF3-3-pyridinyl, R1 is CI and R2 is Br. Q2 is 2-C , 6-CF3-3-pyridinyl, R1 is CI and R2 is CI. Q2 is 5-C ■3-pyridinyl, R is CI and R2 is Me.
Q2 is 5-C■3-pyridinyl, R is CI and R2 is CFH2. Q2 is 5-C■3-pyridinyl, R is Br and R2 is Me.
Q2 is 5-C■3-pyridinyl, R is I and R2 is Me.
Q2 is 5-C■3-pyridinyl, R is Me and R2 is Me.
Q2 is 5-C■3-pyridinyl, R is Me and R2 is CI.
Q2 is 5-C■3-pyridinyl, R is Me and R2 is Br.
Q2 is 5-C■3-pyridinyl, R is Me and R2 is I.
Q2 is 5-C■3-pyridinyl, R is Br and R2 is Br.
Q2 is 5-C■3-pyridinyl, R is Br and R2 is CI.
Q2 is 5-C■3-pyridinyl, R is CI and R2 is Br.
Q2 is 5-C -3-pyridinyl, R1 is CI and R2 is CI.
Qz is 5-F-3-pyridinyl, R1 is CI and Rz is Me.
Q2 is 5-F-3-pyridinyl, R1 is CI and R2 is CFH2. Q2 is 5-F-3-pyridinyl, R^ is Br and R2 is Me.
Q2 is 5-F-3-pyridinyl, R^ is I and R2 is Me.
Q2 is 5-F-3-pyridinyl, R1 is Me and R2 is Me.
Q2 is 5-F-3-pyridinyl, R1 is Me and R2 is CI.
Q2 is 5-F-3-pyridinyl, R^ is Me and R2 is Br.
Q2 is 5-F-3-pyridinyl, R^ is Me and R2 is I.
Q2 is 5-F-3-pyridinyl, R^ is Br and R2 is Br.
Q2 is 5-F-3-pyridinyl, R^ is Br and R2 is CI.
Q2 is 5-F-3-pyridinyl, R^ is CI and R2 is Br.
Q2 is 5-F-3-pyridinyl, R1 is CI and R2 is CI.
Q2 is 5-Me-3-pyridinyl, R1 is CI and R2 is Me.
Q2 is 5-Me-3-pyridinyl, R1 is CI and R2 is CFH2. Q2 is 5-Me-3-pyridinyl, R1 is Br and R2 is Me. Row Heading
Q2 is 5· ■Me-3-pyridinyl, R is I and is Me.
Q2 is 5·■Me-3-pyridinyl, R is Me and R2 is Me, Q2 is 5·■Me-3-pyridinyl, R is Me and R2 is CI.
Q2 is 5· Me-3-pyridinyl, R is Me and R2 is Br.
Q2 is 5 Me-3-pyridinyl, R is Me and R2 is I.
Q2 is 5- Me-3-pyridinyl, R is Br and R2 is Br.
Q2 is 5- Me-3-pyridinyl, R is Br and R2 is CI.
Q2 is 5- Me-3-pyridinyl, R is CI and R2 is Br.
Q2 is 5- Me-3-pyridinyl, R is CI and R2 is CI.
Q2 is 5- ■MeO-3-pyridinyl, R is CI and R2 is Me.
Q2 is 5-■MeO-3-pyridinyl, R is CI and R2 is CFH2 Q2 is 5-■MeO-3-pyridinyl, R is Br and R2 is Me.
Q2 is 5-■MeO-3-pyridinyl, R is I and R2 is Me.
Q2 is 5-■MeO-3-pyridinyl, R is Me and R2 is Me.
Q2 is 5-■MeO-3-pyridinyl, R is Me and R2 is CI.
Q2 is 5-■MeO-3-pyridinyl, R is Me and R2 is Br.
Q2 is 5-■MeO-3-pyridinyl, R is Me and R2 is I.
Q2 is 5-■MeO-3-pyridinyl, R is Br and R2 is Br.
Q2 is 5-■MeO-3-pyridinyl, R is Br and R2 is CI.
Q2 is 5-■MeO-3-pyridinyl, R1 is C and is Br.
Q2 is 5- MeO-3-pyridinyl, R1 is C and R2 is CI.
Q2 is 6- CI, 5-MeO-3-pyridinyl, R is CI and R2 is Me. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is CI and R2 is CFH2. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is Br and R2 is Me. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is I and R2 is Me. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R2 is Me. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R2 is CI. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R2 is Br. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is Me and R2 is I. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is Br and R" is Br. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is Br and R" is CI. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is CI and R2 is Br. Q2 is 6- CI, 5-MeO-3-pyridinyl, R is CI and R2 is CI. Q2 is 6- Cl-3-pyridazinyl, R^ is CI and R2 is Me.
Q2 is 6- Cl-3-pyridazinyl, R1 is CI and R2 is CFH2. Q2 is 6- Cl-3-pyridazinyl, R^ is Br and R2 is Me.
Q2 is 6- Cl-3-pyridazinyl, R^ is I and R2 is Me. Row Heading
Cr is 6-Cl-3-pyridazinyl, R1 is Me and R2 is Me, Q2 is 6-Cl-3-pyridazinyl, R1 is Me and R2 is CI. Q2 is 6-Cl-3-pyridazinyl, R^ is Me and R2 is Br. Q2 is 6-Cl-3-pyridazinyl, R^ is Me and R2 is I. Q2 is 6-Cl-3-pyridazinyl, R^ is Br and R2 is Br. Q2 is 6-Cl-3-pyridazinyl, R^ is Br and R2 is CI. Q2 is 6-Cl-3-pyridazinyl, R^ is CI and R2 is Br. Q2 is 6-Cl-3-pyridazinyl, R1 is CI and R2 is CI. is 6-Me-3-pyridazinyl, R s CI and Rz is Me. Q2 is 6-Me-3-pyridazinyl, R s CI and R2 is CFH2. Q2 is 6-Me-3-pyridazinyl, R s Br and R2 is Me. Q2 is 6-Me-3-pyridazinyl, R s I and R2 is Me. Q2 is 6-Me-3-pyridazinyl, R s Me and R2 is Me. Q2 is 6-Me-3-pyridazinyl, R s Me and R2 is CI. is 6-Me-3-pyridazinyl, R s Me and R2 is Br. Q2 is 6-Me-3-pyridazinyl, R s Me and R2 is I. Q2 is 6-Me-3-pyridazinyl, R s Br and R2 is Br. Q2 is 6-Me-3-pyridazinyl, R s Br and R2 is CI. Q2 is 6-Me-3-pyridazinyl, R s CI and R2 is Br. Q2 is 6-Me-3-pyridazinyl, R s CI and R2 is CI. is 6-MeO-3-pyridazinyl, R is CI and R2 is Me. Q2 is 6-MeO-3-pyridazinyl, R is CI and R2 is CFH2. Q2 is 6-MeO-3-pyridazinyl, R is Br and R2 is Me. Q2 is 6-MeO-3-pyridazinyl, R is I and R2 is Me. Q2 is 6-MeO-3-pyridazinyl, R is Me and R2 is Me. Q2 is 6-MeO-3-pyridazinyl, R is Me and R is CI. is 6-MeO-3-pyridazinyl, R is Me and R2 is Br. Q2 is 6-MeO-3-pyridazinyl, R is Me and R2 is I. Q2 is 6-MeO-3-pyridazinyl, R is Br and R2 is Br. Q2 is 6-MeO-3-pyridazinyl, R is Br and R2 is CI. Q2 is 6-MeO-3-pyridazinyl, R is CI and R2 is Br. Q2 is 6-MeO-3-pyridazinyl, R is CI and R2 is CI. Q2 is 6-CF3-3-pyridazinyl, R1 is CI and R2 is Me. Q2 is 6-CF3-3-pyridazinyl, R1 is CI and R2 is CFH2. Q2 is 6-CF3-3-pyridazinyl, R^ is Br and R2 is Me. Q2 is 6-CF3-3-pyridazinyl, R^ is I and R2 is Me. Q2 is 6-CF3-3-pyridazinyl, R^ is Me and R2 is Me. Table Row Heading
445A Q2 is 6-CF3-3-pyridazinyl, R1 is Me and R2 is CI.
446A Q2 is 6-CF3-3-pyridazinyl, R^ is Me and R2 is Br.
447A Q2 is 6-CF3-3-pyridazinyl, R^ is Me and R2 is I.
448A Q2 is 6-CF3-3-pyridazinyl, R^ is Br and R2 is Br.
449A Q2 is 6-CF3-3-pyridazinyl, R^ is Br and R2 is CI.
450A Q2 is 6-CF3-3-pyridazinyl, R^ is CI and R2 is Br.
451A Q2 is 6-CF3-3-pyridazinyl, R1 is CI and R2 is CI.
452A Q2 is 5-Cl-3-pyridazinyl, R1 is CI and R2 is Me.
453A Q2 is 5-Cl-3-pyridazinyl, R1 is CI and R2 is CFH2.
454A Q2 is 5-Cl-3-pyridazinyl, R^ is Br and R2 is Me.
455A Q2 is 5-Cl-3-pyridazinyl, R^ is I and R2 is Me.
456A Q2 is 5-Cl-3-pyridazinyl, R1 is Me and R2 is Me.
457A Q2 is 5-Cl-3-pyridazinyl, R1 is Me and R2 is CI.
458A Q2 is 5-Cl-3-pyridazinyl, R^ is Me and R2 is Br.
459A Q2 is 5-Cl-3-pyridazinyl, R^ is Me and R2 is I.
460A Q2 is 5-Cl-3-pyridazinyl, R^ is Br and R2 is Br.
461A Q2 is 5-Cl-3-pyridazinyl, R^ is Br and R2 is CI.
462A Q2 is 5-Cl-3-pyridazinyl, R^ is CI and R2 is Br.
463A Q2 is 5-Cl-3-pyridazinyl, R1 is CI and R2 is CI.
464A Q2 is 5-F-3-pyridazinyl, R^ is CI and R2 is Me.
465A Q2 is 5-F-3-pyridazinyl, R^ is CI and R2 is CFH2.
466A Q2 is 5-F-3-pyridazinyl, R^ is Br and R2 is Me.
467A Q2 is 5-F-3-pyridazinyl, R^ is I and R2 is Me.
468A Q2 is 5-F-3-pyridazinyl, R^ is Me and R2 is Me.
469A Q2 is 5-F-3-pyridazinyl, R^ is Me and R2 is CI.
470A Q2 is 5-F-3-pyridazinyl, R^ is Me and R2 is Br.
471A Q2 is 5-F-3-pyridazinyl, R^ is Me and R2 is I.
472A Q2 is 5-F-3-pyridazinyl, R^ is Br and R2 is Br.
473A Q2 is 5-F-3-pyridazinyl, R^ is Br and R2 is CI.
474A Q2 is 5-F-3-pyridazinyl, R^ is CI and R2 is Br.
475A Q2 is 5-F-3-pyridazinyl, R^ is CI and R2 is CI.
476A Q2 is 5-MeO-3-pyridazinyl, R1 is CI and R2 is Me.
477A Q2 is 5-MeO-3-pyridazinyl, R1 is CI and R2 is CFH2.
478A Q2 is 5-MeO-3-pyridazinyl, R^ is Br and R2 is Me.
479A Q2 is 5-MeO-3-pyridazinyl, R^ is I and R2 is Me.
480A Q2 is 5-MeO-3-pyridazinyl, R1 is Me and R2 is Me.
481A Q2 is 5-MeO-3-pyridazinyl, R1 is Me and R2 is CI. Row Heading
Q - is 5-MeO-3-pyridazinyl, R1 is Me and ^ is Br. Q2 is 5-MeO-3-pyridazinyl, R1 is Me and R2 is I. Q2 is 5-MeO-3-pyridazinyl, R^ is Br and R2 is Br. Q2 is 5-MeO-3-pyridazinyl, R1 is Br and R2 is CI. Q2 is 5-MeO-3-pyridazinyl, R1 is CI and R2 is Br. Q2 is 5-MeO-3-pyridazinyl, R1 is CI and R2 is CI. Q2 is 2-Cl-5-pyrimidinyl, R^ is CI and R2 is Me. Q2 is 2-Cl-5-pyrimidinyl, R1 is CI and R2 is CFH2. Q2 is 2-Cl-5-pyrimidinyl, R^ is Br and R2 is Me. Q2 is 2-Cl-5-pyrimidinyl, R^ is I and R2 is Me. Q2 is 2-Cl-5-pyrimidinyl, R^ is Me and R2 is Me. Q2 is 2-C1-5 pyrimidinyl, R^ is Me and R2 is CI. Q2 is 2-Cl-5-pyrimidinyl, R^ is Me and R2 is Br. Q2 is 2-Cl-5-pyrimidinyl, R^ is Me and R2 is I. Q2 is 2-Cl-5-pyrimidinyl, R^ is Br and R2 is Br. Q2 is 2-Cl-5-pyrimidinyl, R^ is Br and R2 is CI. Q2 is 2-Cl-5-pyrimidinyl, R^ is CI and R2 is Br. Q2 is 2-Cl-5-pyrimidinyl, R1 is CI and R2 is CI.
Q2 is 2-Me-5-pyrimidinyl, R^ is CI and R2 is Me.
Q s 2-Me-5-pyrimidinyl, R^ is CI and R2 is CFH2.
Q I-2 s 2-Me-5-pyrimidinyl, R^ is Br and R2 is Me. Q s 2-Me-5-pyrimidinyl, R^ is I and R2 is Me. Q2 s 2-Me-5-pyrimidinyl, R^ is Me and R^ is Me. Q2 s 2-Me-5-pyrimidinyl, R^ is Me and R2 is CI. Q2 s 2-Me-5-pyrimidinyl, R^ is Me and R2 is Br. Q2 s 2-Me-5-pyrimidinyl, R^ is Me and R2 is I. Q2 s 2-Me-5-pyrimidinyl, R^ is Br and R2 is Br. Q2 s 2-Me-5-pyrimidinyl, R^ is Br and R2 is CI. Q2 s 2-Me-5-pyrimidinyl, R^ is CI and R"- is Br. Q2 s 2-Me-5-pyrimidinyl, R^ is CI and R2 is CI.
Q I2 s 2-MeO-5-pyrimidinyl, R^ is CI and R2 is Me. Q s 2-MeO-5-pyrimidinyl, R1 is CI and R2 is CFH2. Q2 s 2-MeO-5-pyrimidinyl, R^ is Br and R2 is Me. Q2 s 2-MeO-5-pyrimidinyl, R1 is I and R^ is Me.
1
Q2 s 2-MeO-5-pyrimidinyl, R1 is Me and R^ is Me. Q2 s 2-MeO-5-pyrimidinyl, R^ is Me and R2 is CI. Q2 s 2-MeO-5-pyrimidinyl, R^ is Me and R2 is Br. Row Heading
Q2 is 2-MeO-5-pyrimidinyl, R1 is Me and R2 is I. Q2 is 2-MeO-5 pyrimidinyl, R^ is Br and R2 is Br. Q2 is 2-MeO-5-pyrimidinyl, R1 is Br and R2 is CI. Q2 is 2-MeO-5-pyrimidinyl, R1 is CI and R2 is Br. Q2 is 2-MeO-5-pyrimidinyl, R1 is CI and R2 is CI.
Q is 2-CF3- -5 -pyrimidinyl, R is CI and R2 is Me.
Q2 is 2-CF3- -5-pyrimidinyl, R is CI and R2 is CFH2.
Q2 is 2-CF3- -5-pyrimidinyl, R is Br and R2 is Me.
Q2 is 2-CF3- -5-pyrimidinyl, R is I and is Me.
Q2 is 2-CF3- -5-pyrimidinyl, R is Me and R2 is Me.
Q2 is 2-CF3- -5-pyrimidinyl, R is Me and R2 is CI.
Q2 is 2-CF3- -5-pyrimidinyl, R is Me and R2 is Br.
Q2 is 2-CF3- -5-pyrimidinyl, R is Me and R2 is I.
Q2 is 2-CF3- -5-pyrimidinyl, R is Br and R2 is Br.
Q2 is 2-CF3- -5-pyrimidinyl, R is Br and R^ is CI.
Q2 is 2-CF3- -5-pyrimidinyl, R is CI and R2 is Br.
Q2 is 2-CF3- -5-pyrimidinyl, R is CI and R2 is CI.
C is 5-C1-2 -pyrimidinyl, R is CI and R2 is Me. Q2 is 5-C1-2 -pyrimidinyl, R is CI and R2 is CFH2. Q"- is 5-C1-2 -pyrimidinyl, R is Br and R2 is Me. Q2 is 5-C1-2 -pyrimidinyl, R is I and R2 is Me. Q2 is 5-C1-2 -pyrimidinyl, R is Me and R2 is Me. Q2 is 5-C1-2 -pyrimidinyl, R is Me and R2 is CI. Q2 is 5-C1-2 -pyrimidinyl, R is Me and R2 is Br. Q2 is 5-C1-2 -pyrimidinyl, R is Me and R2 is I. Q"- is 5 -Cl-2 -pyrimidinyl, R is Br and R2 is Br. Q2 is 5-C1-2 -pyrimidinyl, R is Br and R2 is CI. Q2 is 5-C1-2 -pyrimidinyl, R is CI and R2 is Br.
Q2 is 5-C1-2 -pyrimidinyl, R^ is CI and R2 is CI. Q2 is 5-Me -2 -pyrimidinyl, R1 is CI and R2 is Me. Q2 is 5-Me-2-pyrimidinyl, R1 is CI and R2 is CFH2. Q2 is 5-Me-2-pyrimidinyl, R^ is Br and R2 is Me. Q2 is 5-Me -2 -pyrimidinyl, R^ is I and R2 is Me. Q2 is 5-Me -2 -pyrimidinyl, R^ is Me and R2 is Me. Q2 is 5-Me -2 -pyrimidinyl, R1 is Me and R2 is CI. Q2 is 5-Me -2 -pyrimidinyl, R^ is Me and R2 is Br. Q2 is 5-Me -2 -pyrimidinyl, R^ is Me and R2 is I. Row Heading
Q is 5-Me-2-pyrimidinyl, R1 is Br and R^ is Br. Q2 is 5-Me-2-pyrimidinyl, R^ is Br and R2 is CI. Q2 is 5-Me-2-pyrimidinyl, R^ is CI and R2 is Br. Q2 is 5-Me-2-pyrimidinyl, R1 is CI and R2 is CI.
Q is 5-MeO-2-pyrimidinyl, R is CI and R2 is Me. Q2 is 5-MeO-2-pyrimidinyl, R is CI and R2 is CFH2. Q2 is 5-MeO-2-pyrimidinyl, R is Br and R2 is Me. Q"- is 5-MeO-2-pynmidinyl, R is I and R2 is Me. Q2 is 5-MeO-2-pyrimidinyl, R is Me and R2 is Me. Q2 is 5-MeO-2-pyrimidinyl, R is Me and R2 is CI. Q2 is 5-MeO-2-pyrimidinyl, R is Me and R2 is Br. Q2 is 5-MeO-2-pyrimidinyl, R is Me and R2 is I. Q2 is 5-MeO-2-pyrimidmyl, R is Br and R2 is Br. Q"- is 5-MeO-2-pynmidmyl, R is Br and R2 is CI. Q2 is 5-MeO-2-pyrimidinyl, R is CI and R"- is Br. Q2 is 5-MeO-2-pyrimidinyl, R is CI and R2 is CI. Q2 is 5-Cl-2-pyrimidinyl, R is CI and R2 is Me. Q2 is 5-Cl-2-pyrimidinyl, R is CI and R2 is CFH2. Q2 is 5-Cl-2-pyrimidinyl, R is Br and R2 is Me. Q"- is 5-Cl-2-pyrimidinyl, R is I and R2 is Me.
Q2 is 5-Cl-2-pyrimidinyl, R is Me and R2 is Me. Q2 is 5-Cl-2-pyrimidinyl, R is Me and R2 is CI. Q2 is 5-Cl-2-pyrimidinyl, R is Me and R2 is Br. Q2 is 5-Cl-2-pyrimidinyl, R is Me and R2 is I.
Q2 is 5-Cl-2-pyrimidinyl, R is Br and R2 is Br. Q"- is 5-Cl-2-pyrimidinyl, R is Br and R2 is CI. Q2 is 5-Cl-2-pyrimidinyl, R is CI and is Br.
C is 5-Cl-2-pyrimidinyl, R is CI and R2 is CI. Q2 is 5-CF3-2-pyrimidinyl, R1 is CI and R^ is Me. Q2 is 5-CF3-2-pyrimidinyl, R1 is CI and R2 is CFH2 Q2 is 5-CF3-2-pyrimidinyl, R^ is Br and R2 is Me. Q2 is 5-CF3-2-pyrimidinyl, R^ is I and R2 is Me. Q2 is 5-CF3-2-pyrimidinyl, R^ is Me and R2 is Me. Q2 is 5-CF3-2-pyrimidinyl, R1 is Me and R2 is CI. Q2 is 5-CF3-2-pyrimidinyl, R^ is Me and R2 is Br. Q2 is 5-CF3-2-pyrimidinyl, R^ is Me and R2 is I. Q2 is 5-CF3-2-pyrimidinyl, R^ is Br and R2 is Br. Row Heading 1 1
Q- is 5-CF3-2-pyrimidinyl, R1 is Br and R is CI. Q2 is 5-CF3-2-pyrimidinyl, 1 is CI and R2 is Br. Q2 is 5-CF3-2-pyrimidinyl, R1 is CI and R2 is CI.
Q2 is 5- ■Me- -2-thienyl, R is CI and R2 is Me.
Q2 is 5- ■Me- -2-thienyl, R is CI and R2 is CFH2.
Q2 is 5- ■Me- -2-thienyl, R is Br and R2 is Me.
Q2 is 5- -Me- -2-thienyl, R is I and R2 is Me.
Q2 is 5- -Me- -2-thienyl, R is Me and R2 is Me.
Q2 is 5- -Me- -2-thienyl, R is Me and R2 is CI.
Q2 is 5- -Me- -2-thienyl, R is Me and R2 is Br.
Q2 is 5- -Me- -2-thienyl, R is Me and R2 is I.
Q2 is 5- -Me- -2-thienyl, R is Br and R2 is Br.
Q2 is 5- -Me- -2-thienyl, R is Br and R2 is CI.
Q2 is 5- -Me- -2-thienyl, R is CI and R2 is Br.
Q2 is 5- -Me- -2-thienyl, R is CI and R2 is CI.
Q2 is 5-Cl-2-thienyl, R is CI and R2 is Me.
Q2 is 5-Cl-2-thienyl, R is CI and R2 is CFH2.
Q2 is 5-Cl-2-thienyl, R is Br and R2 is Me.
Q2 is 5-Cl-2-thienyl, R is I and R2 is Me.
Q2 is 5-Cl-2-thienyl, R is Me and R2 is Me.
Q2 is 5-Cl-2-thienyl, R is Me and R2 is CI.
Q2 is 5-Cl-2-thienyl, R is Me and R2 is Br.
Q2 is 5-Cl-2-thienyl, R is Me and R^ is I.
Q2 is 5-Cl-2-thienyl, R is Br and R2 is Br.
Q2 is 5-Cl-2-thienyl, R is Br and R2 is CI.
Q2 is 5-Cl-2-thienyl, R - is CI and R2 is Br.
Q2 is 5-Cl-2-thienyl, R - is CI and R2 is CI.
Q2 is 5-F-2-thienyl, R1 is CI and R2 is Me.
Q2 is 5-F-2-thienyl, R1 is CI and R2 is CFH2.
Q2 is 5-F-2-thienyl, R1 is Br and R2 is Me.
Q2 is 5-F-2-thienyl, R1 is I and R2 is Me.
Q2 is 5-F-2-thienyl, R1 is Me and R2 is Me.
Q2 is 5-F-2-thienyl, R1 is Me and R2 is CI.
Q2 is 5-F-2-thienyl, R1 is Me and R2 is Br.
Q2 is 5-F-2-thienyl, R1 is Me and R2 is I.
Q2 is 5-F-2-thienyl, R1 is Br and R2 is Br.
Q2 is 5-F-2-thienyl, R1 is Br and R2 is CI. Row Heading
Q2 is 5-F-2-thienyl, R1 is CI and R2 is Br. Q2 is 5-F-2-thienyl, R1 is CI and R2 is CI. Q2 is 5-Me-3-thienyl, R1 is CI and R2 is Me. Q2 is 5-Me-3-thienyl, R1 is CI and R2 is CFH2. Q2 is 5-Me-3-thienyl, R1 is Br and R2 is Me. Q2 is 5-Me-3-thienyl, R1 is I and R2 is Me. Q2 is 5-Me-3-thienyl, R1 is Me and R2 is Me. Q2 is 5-Me-3-thienyl, R1 is Me and R2 is CI. Q2 is 5-Me-3-thienyl, R1 is Me and R2 is Br. Q2 is 5-Me-3-thienyl, R1 is Me and R2 is I. Q2 is 5-Me-3-thienyl, R1 is Br and R2 is Br. Q2 is 5-Me-3-thienyl, R1 is Br and R2 is CI. Q2 is 5-Me-3-thienyl, R1 is CI and R2 is Br. Q2 is 5-Me-3-thienyl, R1 is CI and R2 is CI. Q2 is 5-Cl-3-thienyl, R1 is CI and R2 is Me. Q2 is 5-Cl-3-thienyl, R1 is CI and R2 is CFH2. Q2 is 5-Cl-3-thienyl, R1 is Br and R2 is Me. Q2 is 5-Cl-3-thienyl, R1 is I and R2 is Me. Q2 is 5-Cl-3-thienyl, R1 is Me and R2 is Me. Q2 is 5-Cl-3-thienyl, R1 is Me and R2 is CI. Q2 is 5-Cl-3-thienyl, R1 is Me and R2 is Br. Q2 is 5-Cl-3-thienyl, R1 is Me and R2 is I. Q2 is 5-Cl-3-thienyl, R1 is Br and R2 is Br. Q2 is 5-Cl-3-thienyl, R1 is Br and R2 is CI. Q2 is 5-Cl-3-thienyl, R1 is CI and R2 is Br. Q2 is 5-Cl-3-thienyl, R1 is CI and R2 is CI. Q2 is 5-F-3-thienyl, R1 is CI and R2 is Me. Q2 is 5-F-3-thienyl, R1 is CI and R2 is CFH2. Q2 is 5-F-3-thienyl, R1 is Br and R2 is Me. Q2 is 5-F-3-thienyl, R1 is I and R2 is Me. Q2 is 5-F-3-thienyl, R1 is Me and R2 is Me. Q2 is 5-F-3-thienyl, R1 is Me and R2 is CI. Q2 is 5-F-3-thienyl, R1 is Me and R2 is Br. Q2 is 5-F-3-thienyl, R1 is Me and R2 is I. Q2 is 5-F-3-thienyl, R1 is Br and R2 is Br. Q2 is 5-F-3-thienyl, R1 is Br and R2 is CI. Q2 is 5-F-3-thienyl, R1 is CI and R2 is Br. Table Row Heading
667A Q2 is 5 -F-3 -thienyl, R1 is CI and R2 is CI.
668A Q2 is 1 -Me l /-pyrazol-3-yl, R1 is CI and R2 is Me.
669A Q2 is 1 -Me l /-pyrazol-3-yl, R1 is CI and R2 is CFH2.
670A Q2 is 1 -Me l /-pyrazol-3-yl, R^ is Br and R2 is Me.
671A Q2 is 1 -Me l /-pyrazol-3-yl, R^ is I and R2 is Me.
672A Q2 is 1 -Me l /-pyrazol-3-yl, R^ is Me and R2 is Me.
673A Q2 is 1 -Me l /-pyrazol-3-yl, R1 is Me and R2 is CI.
674A Q2 is 1 -Me l /-pyrazol-3-yl, R^ is Me and R2 is Br.
675A Q2 is 1 -Me l /-pyrazol-3-yl, R^ is Me and R2 is I.
676A Q2 is 1 -Me l /-pyrazol-3-yl, R^ is Br and R2 is Br.
677A Q2 is 1 -Me l /-pyrazol-3-yl, R^ is Br and R2 is CI.
678A Q2 is 1 -Me l /-pyrazol-3-yl, R^ is CI and R2 is Br.
679A Q2 is 1 -Me l /-pyrazol-3-yl, R1 is CI and R2 is CI.
680A Q2 is 1 -Me l /-pyrazol-4-yl, R1 is CI and R2 is Me.
681A Q2 is 1 -Me l /-pyrazol-4-yl, R1 is CI and R2 is CFH2.
682A Q2 is 1 -Me l /-pyrazol-4-yl, R^ is Br and R2 is Me.
683A Q2 is 1 -Me l /-pyrazol-4-yl, R^ is I and R2 is Me.
684A Q2 is 1 -Me l /-pyrazol-4-yl, R1 is Me and R2 is Me.
685A Q2 is 1 -Me l /-pyrazol-4-yl, R1 is Me and R2 is CI.
686A Q2 is 1 -Me l /-pyrazol-4-yl, R^ is Me and R2 is Br.
687A Q2 is 1 -Me l /-pyrazol-4-yl, R^ is Me and R2 is I.
688A Q2 is 1 -Me l /-pyrazol-4-yl, R^ is Br and R2 is Br.
689A Q2 is 1 -Me l /-pyrazol-4-yl, R^ is Br and R2 is CI.
690A Q2 is 1 -Me l /-pyrazol-4-yl, R^ is CI and R2 is Br.
691A Q2 is 1 -Me l /-pyrazol-4-yl, R1 is CI and R2 is CI.
692A Q2 is 2 -Me 5-thiazolyl, R1 is CI and R2 is Me.
693A Q2 is 2 -Me 5-thiazolyl, R1 is CI and R2 is CFH2.
694A Q2 is 2 -Me 5-thiazolyl, R^ is Br and R2 is Me.
695A Q2 is 2 -Me 5-thiazolyl, R^ is I and R2 is Me.
696A Q2 is 2 -Me 5-thiazolyl, R1 is Me and R2 is Me.
697A Q2 is 2 -Me 5-thiazolyl, R1 is Me and R2 is CI.
698A Q2 is 2 -Me 5-thiazolyl, R^ is Me and R2 is Br.
699A Q2 is 2 -Me 5-thiazolyl, R^ is Me and R2 is I.
700A Q2 is 2 -Me 5-thiazolyl, R^ is Br and R2 is Br.
701A Q2 is 2 -Me 5-thiazolyl, R^ is Br and R2 is CI.
702A Q2 is 2 -Me 5-thiazolyl, R^ is CI and R2 is Br.
703A Q2 is 2 -Me 5-thiazolyl, R1 is CI and R2 is CI. Table Row Heading
704A Q2 is 2- -Cl-5 thiazolyl, R is CI and R2 is Me.
705A Q2 is 2- -Cl-5 thiazolyl, R is CI and R2 is CFH2
706A Q2 is 2- -Cl-5 thiazolyl, R is Br and R2 is Me.
707A Q2 is 2- -Cl-5 thiazolyl, R is I and R2 is Me.
708A Q2 is 2- -Cl-5 thiazolyl, R is Me and R2 is Me.
709A Q2 is 2- -Cl-5 thiazolyl, R is Me and R2 is CI.
710A Q2 is 2- -Cl-5 thiazolyl, R is Me and R2 is Br.
711A Q2 is 2- -Cl-5 thiazolyl, R is Me and R2 is I.
712A Q2 is 2- -Cl-5 thiazolyl, R is Br and R2 is Br.
713A Q2 is 2- -Cl-5 thiazolyl, R is Br and R2 is CI.
714A Q2 is 2- -Cl-5 thiazolyl, R is CI and R2 is Br.
715A Q2 is 2- -Cl-5 thiazolyl, R is CI and R2 is CI.
Table 2
Figure imgf000088_0001
Q1 is 4-Cl-Ph, R1 is CI and R2 is Me.
(R5)n (R5)n (R5)n (R5)n (R5)n
2,6-di-F 2,4-di-Cl 4-CN, 2,6-di-F 2-CF3, 4-F 2-Cl, 4-N02
2,4,6-tri-F 2-Cl, 4,6-di-F 2,6-di-F, 4-Me 2-CF2HO, 4-F 2-N02, 4-F
2,3,6-tri-F 2-Cl, 6-F 2-Cl, 5-CF3 2-CN, 6-F 2,5-di-Cl, 4-F
2,4,5-tri-F 2-Br, 6-F 2-Cl, 4-Me 2,5-di-Cl 2,3-di-Cl, 4-F
2,3,4-tri-F 2-F, 6-CF3 2-Cl, 4-MeO 2-CF3, 4-MeO 2-Cl, 5-CN
2-Cl, 4-F 2-F, 6-CF2HO 2-Br, 4-MeO 2-F, 6-Me 2,4-di-F, 5-CN
2-Br-4-F 2-1, 4-F 2,6-di-F, 3 -CI 2,6-di-F, 3 -Me 2-Cl, 6-F, 3-MeO
2,4-di-F 4-Cl, 2,6-di-F 2,6-di-F, 3-CN 2-CF3 2,6-di-F, 3-NCCH20
2,6-di-Cl 2,6-di-F, 4-MeO 2,6-di-F, 3-MeO 2-CF3O 2,6-di-F, 4-NCCH20
2,6-di-F, 4-EtO 2-Cl, 6-F, 4-MeO 2,6-di-F, 4-CF2HO 2,6-di-F, 4-N02
2-Cl, 3,6-di-F 2-Cl, 6-F, 5-MeO 2,6-di-F, 3-CF2HO 2,6-di-F, 3-EtO
The present disclosure also includes Tables IB through 715B, each of which is constructed the same as Table 2 above except that the row heading in Table 2 (i.e. "Q1 is 4-Cl-Ph, Pv1 is CI and R2 is Me") is replaced with the respective row heading shown below. Thus, for example, in Table IB the row heading is "Q1 is 4-Cl-Ph, R1 is Br and R2 is Me", and (R5)n is as defined in Table 2 above. Tables 2B through 715B are constructed similarly.
Row Heading
4- -CI- -Ph is Br and P is Me.
4- -CI- -Ph is CI and R2 is CFH2.
4- ■CI- -Ph is I and R2 is Me.
4- -CI- -Ph is Me and R2 is Me.
4- -CI- -Ph is Me and R2 is CI.
4- -CI- -Ph is Me and R2 is Br.
4- -CI- -Ph is Me and R2 is I.
4- -CI- -Ph is Me and R2 is MeO.
4- -CI- -Ph is MeO and R2 is Me.
4- -CI- -Ph is Br and R2 is Br.
4- -CI- -Ph is Br and R2 is CI.
4- -CI- -Ph is CI and R2 is Br.
4- -CI- -Ph is CI and R2 is CI.
4- -CI- -Ph is Me and R2 is MeS.
4- -CI- -Ph is MeS and R2 is Me.
4- -CI- -Ph is Et and R2 is Br.
4- -CI- -Ph is Et and R2 is CI.
4- -CI- -Ph is Et and R2 is Me.
4- -CI- -Ph is Me and R2 is Et.
4- -CI- -Ph is CI and R2 is Et.
4- -CI- -Ph is Me and R2 is CN.
3- -CI- -Ph is CI and R2 is Me.
3- -CI- -Ph is CI and R2 is CFH2.
3- -CI- -Ph is Br and R2 is Me.
3- -CI- -Ph is I and R2 is Me.
3- -CI- -Ph is Me and R2 is Me.
3- -CI- -Ph is Me and R2 is CI.
3- -CI- -Ph is Me and R2 is Br.
3- -CI- -Ph is Me and R2 is I.
3- -CI- -Ph is Br and R2 is Br.
3- -CI- -Ph is Br and R2 is CI.
3- -CI- -Ph is CI and R2 is Br.
3- -CI- -Ph is CI and R2 is CI.
is 4-F-Ph, R1 is CI and R2 is Me.
Figure imgf000089_0001
Row Heading
Q is 4-F-Ph, R is CI and R2 is CFH2.
Q is 4-F-Ph, R is Br and R^ is Me.
Q is 4-F-Ph, R is I and R2 is Me.
Q is 4-F-Ph, R is Me and R2 is Me.
Q is 4-F-Ph, R is Me and R2 is CI.
Q is 4-F-Ph, R is Me and R2 is Br.
Q is 4-F-Ph, R is Me and R2 is I.
Q is 4-F-Ph, R is Br and R^ is Br.
Q is 4-F-Ph, R is Br and R2 is CI.
Q is 4-F-Ph, R is CI and R2 is Br.
Q is 4-F-Ph, R is CI and R2 is CI.
Q is 3-F-Ph, R is CI and R2 is Me.
Q is 3-F-Ph, R is CI and R2 is CFH2.
Q is 3-F-Ph, R is Br and R^ is Me.
Q is 3-F-Ph, R is I and R2 is Me.
Q is 3-F-Ph, R is Me and R2 is Me.
Q is 3-F-Ph, R is Me and R2 is CI.
Q is 3-F-Ph, R is Me and R2 is Br.
Q is 3-F-Ph, R is Me and R2 is I.
Q is 3-F-Ph, R is Br and R^ is Br.
Q is 3-F-Ph, R is Br and R2 is CI.
Q is 3-F-Ph, R is CI and R2 is Br.
Q is 3-F-Ph, R is CI and R2 is CI.
Q is 3-CF2HO-Ph, R is CI and R2 is Me. Q is 3-CF2HO-Ph, R is CI and R2 is CFH2. Q is 3-CF2HO-Ph, R is Br and R2 is Me. Q is 3-CF2HO-Ph, R is I and R2 is Me. Q is 3-CF2HO-Ph, R is Me and R2 is Me. Q is 3-CF2HO-Ph, R is Me and R2 is CI. Q is 3-CF2HO-Ph, R is Me and R2 is Br. Q is 3-CF2HO-Ph, R is Me and R2 is I. Q is 3-CF2HO-Ph, R is Br and R2 is Br. Q is 3-CF2HO-Ph, R is Br and R2 is CI. Q is 3-CF2HO-Ph, R is CI and R2 is Br. Q is 3-CF2HO-Ph, R is CI and R2 is CI. Q is 4-Me-Ph, R1 is CI and z is Me.
Q is 4-Me-Ph, R1 is CI and R2 is CFH2. Row Heading
Q is 4 Me-Ph, R is Br and R~ is Me.
Q is 4 Me-Ph, R is I and R2 is Me.
Q is 4 Me-Ph, R is Me and R2 is Me.
Q is 4 Me-Ph, R is Me and R2 is CI.
Q is 4 Me-Ph, R is Me and R2 is Br.
Q is 4 Me-Ph, R is Me and R2 is I.
Q is 4 Me-Ph, R is Br and R2 is Br.
Q is 4 Me-Ph, R is Br and R2 is CI.
Q is 4 Me-Ph, R is CI and R2 is Br.
Q is 4 Me-Ph, R is CI and R2 is CI.
Q is 3 Me-Ph, R is CI and R2 is Me.
Q is 3 Me-Ph, R is CI and R2 is CFH2. Q is 3 Me-Ph, R is Br and R2 is Me.
Q is 3 Me-Ph, R is I and R2 is Me.
Q is 3 Me-Ph, R is Me and R2 is Me.
Q is 3 Me-Ph, R is Me and R2 is CI.
Q is 3 Me-Ph, R is Me and R2 is Br.
Q is 3 Me-Ph, R is Me and R2 is I.
Q is 3 Me-Ph, R is Br and R2 is Br.
Q is 3 Me-Ph, R is Br and R2 is CI.
Q is 3 Me-Ph, R is CI and R2 is Br.
Q is 3 Me-Ph, R is CI and R2 is CI.
Q is 4 Et-Ph, R is CI and R2 is Me.
Q is 4 Et-Ph, R is CI and R2 is CFH2.
Q is 4 Et-Ph, R is Br and R2 is Me.
Q is 4 Et-Ph, R is I and R2 is Me.
Q is 4 Et-Ph, R is Me and R2 is Me.
Q is 4 Et-Ph, R is Me and R2 is CI.
Q is 4 Et-Ph, R is Me and R2 is Br.
Q is 4 Et-Ph, R is Me and R2 is I.
Q is 4 Et-Ph, R is Br and R2 is Br.
Q is 4 Et-Ph, R is Br and R2 is CI.
Q is 4 Et-Ph, R is CI and R2 is Br.
Q is 4 Et-Ph, R is CI and R2 is CI.
Q is 4■CI, 3-F-Ph, R1 is CI and R2 is Me. Q is 4■CI, 3-F-Ph, R1 is CI and R2 is CFH2. Q is 4■CI, 3-F-Ph, R1 is Br and R2 is Me. Row Heading
Q is 4-Cl. 3-F-Ph, R is I and R~ is Me. Q is 4-Cl, 3-F-Ph, R is Me and R2 is Me. Q is 4-Cl, 3-F-Ph, R is Me and R2 is CI. Q is 4-Cl, 3-F-Ph, R is Me and R2 is Br. Q is 4-Cl, 3-F-Ph, R is Me and R2 is I. Q is 4-Cl, 3-F-Ph, R is Br and R2 is Br. Q is 4-Cl, 3-F-Ph, R is Br and R2 is CI. Q is 4-Cl, 3-F-Ph, R is CI and R2 is Br. Q is 4-Cl, 3-F-Ph, R is CI and R2 is CI. Q is 2-Cl, 4-F-Ph, R is CI and R2 is Me. Q is 2-Cl, 4-F-Ph, R is CI and R2 is CFH2. Q is 2-Cl, 4-F-Ph, R is Br and R2 is Me. Q is 2-Cl, 4-F-Ph, R is I and R2 is Me. Q is 2-Cl, 4-F-Ph, R is Me and R2 is Me. Q is 2-Cl, 4-F-Ph, R is Me and R2 is CI. Q is 2-Cl, 4-F-Ph, R is Me and R2 is Br. Q is 2-Cl, 4-F-Ph, R is Me and R2 is I. Q is 2-Cl, 4-F-Ph, R is Br and R2 is Br. Q is 2-Cl, 4-F-Ph, R is Br and R2 is CI. Q is 2-Cl, 4-F-Ph, R is CI and R2 is Br. Q is 2-Cl, 4-F-Ph, R is CI and R2 is CI. Q is 4-F, 3-Me-Ph, R is CI and R2 is Me. Q is 4-F, 3-Me-Ph, R is CI and R2 is CFH2. Q is 4-F, 3-Me-Ph, R is Br and R2 is Me. Q is 4-F, 3-Me-Ph, R is I and R2 is Me. Q is 4-F, 3-Me-Ph, R is Me and R2 is Me. Q is 4-F, 3-Me-Ph, R is Me and R2 is CI. Q is 4-F, 3-Me-Ph, R is Me and R2 is Br. Q is 4-F, 3-Me-Ph, R is Me and R2 is I. Q is 4-F, 3-Me-Ph, R is Br and R2 is Br. Q is 4-F, 3-Me-Ph, R is Br and R2 is CI. Q is 4-F, 3-Me-Ph, R is CI and R2 is Br. Q is 4-F, 3-Me-Ph, R is CI and R2 is CI. Q is 3,4-di-F-Ph, R1 is CI and R2 is Me. Q is 3,4-di-F-Ph, R1 is CI and R2 is CFH2, Q is 3,4-di-F-Ph, R1 is Br and R2 is Me. Q is 3,4-di-F-Ph, R1 is I and R2 is Me. Row Heading
Q1 is 3,4-di-F-Ph, R is Me and R2 is Me.
Q1 is 3,4-di-F-Ph, R is Me and R2 is CI.
Q1 is 3,4-di-F-Ph, R is Me and R2 is Br.
Q1 is 3,4-di-F-Ph, R is Me and R2 is I.
Q1 is 3,4-di-F-Ph, R is Br and R2 is Br.
Q1 is 3,4-di-F-Ph, R is Br and R2 is CI.
Q1 is 3,4-di-F-Ph, R is CI and R2 is Br.
Q1 is 3,4-di-F-Ph, R is CI and R2 is CI.
Q1 is 3,4-di-Cl-Ph, R is CI and R2 is Me.
Q1 is 3,4-di-Cl-Ph, R is CI and R2 is CFH2.
Q1 is 3,4-di-Cl-Ph, R is Br and R2 is Me.
Q1 is 3,4-di-Cl-Ph, R is I and Rz is Me.
Q1 is 3,4-di-Cl-Ph, R is Me and R2 is Me.
Q1 is 3,4-di-Cl-Ph, R is Me and R2 is CI.
Q1 is 3,4-di-Cl-Ph, R is Me and R2 is Br.
Q1 is 3,4-di-Cl-Ph, R is Me and R2 is I.
Q1 is 3,4-di-Cl-Ph, R is Br and R2 is Br.
Q1 is 3,4-di-Cl-Ph, R is Br and R2 is CI.
Q1 is 3,4-di-Cl-Ph, R is CI and R2 is Br.
Q1 is 3,4-di-Cl-Ph, R is CI and R2 is CI.
Q1 is 3,5-di-MeO-Ph, R is CI and R2 is Me.
Q1 is 3,5-di-MeO-Ph, R is CI and R2 is CFH2. Q1 is 3,5-di-MeO-Ph, R is Br and R2 is Me.
Q1 is 3,5-di-MeO-Ph, R is I and R2 is Me.
Q1 is 3,5-di-MeO-Ph, R is Me and R2 is Me.
Q1 is 3,5-di-MeO-Ph, R is Me and R2 is CI.
Q1 is 3,5-di-MeO-Ph, R is Me and R2 is Br.
Q1 is 3,5-di-MeO-Ph, R is Me and R2 is I.
Q1 is 3,5-di-MeO-Ph, R is Br and R2 is Br.
Q1 is 3,5-di-MeO-Ph, R is Br and R2 is CI.
Q1 is 3,5-di-MeO-Ph, R is C and R^- is Br.
Q1 is 3,5-di-MeO-Ph, R is C and R2 is CI.
Q1 is 2-Cl, 3,5-di-MeO-Ph, R is CI and R2 is Me. Q1 is 2-Cl, 3,5-di-MeO-Ph, R is CI and R2 is CFH2. Q1 is 2-Cl, 3,5-di-MeO-Ph, R is Br and R2 is Me. Q1 is 2-Cl, 3,5-di-MeO-Ph, R is I and R2 is Me. Q1 is 2-Cl, 3,5-di-MeO-Ph, R is Me and R2 is Me. Row Heading
Q is 2 CI. 3,5-di-MeO-Ph, R is Me and R2 is CI. Q is 2 CI, 3,5-di-MeO-Ph, R is Me and R2 is Br. Q is 2 CI, 3,5-di-MeO-Ph, R is Me and R2 is I. Q is 2 CI, 3,5-di-MeO-Ph, R is Br and R2 is Br. Q is 2 CI, 3,5-di-MeO-Ph, R is Br and R2 is CI. Q is 2 CI, 3,5-di-MeO-Ph, R is CI and R2 is Br. Q is 2 CI, 3,5-di-MeO-Ph, R is CI and R2 is CI. Q is 4 CI, 3,5-di-MeO-Ph, R is CI and R2 is Me. Q is 4 CI, 3,5-di-MeO-Ph, R is CI and R2 is CFH2. Q is 4 CI, 3,5-di-MeO-Ph, R is Br and R2 is Me. Q is 4 CI, 3,5-di-MeO-Ph, R is I and R2 is Me. Q is 4 CI, 3,5-di-MeO-Ph, R is Me and R2 is Me. Q is 4 CI, 3,5-di-MeO-Ph, R is Me and R2 is CI. Q is 4 CI, 3,5-di-MeO-Ph, R is Me and R2 is Br. Q is 4 CI, 3,5-di-MeO-Ph, R is Me and R2 is I. Q is 4 CI, 3,5-di-MeO-Ph, R is Br and R2 is Br. Q is 4 CI, 3,5-di-MeO-Ph, R is Br and R2 is CI. Q is 4 CI, 3,5-di-MeO-Ph, R is CI and R2 is Br. Q is 4 CI, 3,5-di-MeO-Ph, R is CI and R2 is CI. Q is 4■Cl-Bn, R is CI and R2 is Me.
Q is 4■Cl-Bn, R is CI and R2 is CFH2.
Q is 4 Cl-Bn, R is Br and Rz is Me.
Q is 4 Cl-Bn, R is I and R2 is Me.
Q is 4 Cl-Bn, R is Me and R2 is Me.
Q is 4 Cl-Bn, R is Me and R2 is CI.
Q is 4 Cl-Bn, R is Me and R2 is Br.
Q is 4 Cl-Bn, R is Me and R2 is I.
Q is 4 Cl-Bn, R is Br and Rz is Br.
Q is 4 Cl-Bn, R is Br and R2 is CI.
Q is 4 Cl-Bn, R is CI and R2 is Br.
Q is 4 Cl-Bn, R is CI and R2 is CI.
Q is 4 F-Bn, R1 is CI and R2 is Me.
Q is 4 F-Bn, R1 is CI and R2 is CFH2.
Q is 4 F-Bn, R1 is Br and R2 is Me.
Q is 4 F-Bn, R1 is I and R2 is Me.
Q is 4 F-Bn, R1 is Me and R2 is Me.
Q is 4 F-Bn, R1 is Me and R2 is CI. Row Heading
Q is 4- F-Bn, R1 is Me and R2 is Br.
Q1 is 4- F-Bn, R1 is Me and R2 is I.
Q1 is 4- F-Bn, R1 is Br and R2 is Br.
Q1 is 4 F-Bn, R1 is Br and R2 is CI.
Q1 is 4 F-Bn, R1 is CI and R2 is Br.
Q1 is 4■F-Bn, R1 is CI and R2 is CI.
Q1 is 6 ■3-pyridinyl, R is CI and R2 is Me.
Q1 is 6 ■3-pyridinyl, R is CI and R2 is CFH2.
Q1 is 6 ■3-pyridinyl, R is Br and R" is Me.
Q1 is 6 ■3-pyridinyl, R is I and R" is Me.
Q1 is 6 ■3-pyridinyl, R is Me and R2 is Me.
Q1 is 6 ■3-pyridinyl, R is Me and R2 is CI.
Q1 is 6 ■3-pyridinyl, R is Me and R2 is Br.
Q1 is 6 ■3-pyridinyl, R is Me and R2 is I.
Q1 is 6 ■3-pyridinyl, R is Me and R2 is MeO.
Q1 is 6 ■3-pyridinyl, R is MeO and R2 is Me.
Q1 is 6 ■3-pyridinyl, R is Br and R" is Br.
Q1 is 6 ■3-pyridinyl, R is Br and R2 is CI.
Q1 is 6 ■3-pyridinyl, R is CI and R2 is Br.
Q1 is 6 ■3-pyridinyl, R is CI and R2 is CI.
Q1 is 6 ■3-pyridinyl, R is Me and R2 is MeS.
Q1 is 6 ■3-pyridinyl, R is MeS and R2 is Me.
Q1 is 6 ■3-pyridinyl, R is Et and R" is Br.
Q1 is 6 ■3-pyridinyl, R is Et and R" is CI.
Q1 is 6 -3-pyridinyl, R is Et and R2 is Me.
Q1 is 6 -3-pyridinyl, R is Me and R2 is Et.
Q1 is 6 -3-pyridinyl, R is CI and R2 is Et.
Q1 is 6 -3-pyridinyl, R is Me and R2 is CN.
Q1 is 6 Me-3-pyridinyl, R1 is CI and R2 is Me.
Q1 is 6 Me-3-pyridinyl, R1 is CI and R2 is CFH2.
Q1 is 6 Me-3-pyridinyl, R1 is Br and R^ is Me.
Q1 is 6 Me-3-pyridinyl, R^ is I and R2 is Me.
Q1 is 6 Me-3-pyridinyl, R^ is Me and R2 is Me.
Q1 is 6 Me-3-pyridinyl, R1 is Me and R2 is CI.
Q1 is 6 Me -3-pyridinyl, R^ is Me and R2 is Br.
Q1 is 6 Me -3-pyridinyl, R^ is Me and R2 is I.
1
Q1 is 6 Me -3-pyridinyl, R1 is Br and R^ is Br. Row Heading
Q is 6-Me-3-pyridinyl, R1 is Br and R~ is CI. Q is 6-Me-3-pyridinyl, R^ is CI and R2 is Br. Q is 6-Me-3-pyridinyl, R1 is CI and R2 is CI. Q is 6-MeO-3-pyridinyl, R1 is CI and R2 is Me. Q is 6-MeO-3-pyridinyl, R1 is CI and R2 is CFH2. Q is 6-MeO-3-pyridinyl, R^ is Br and R2 is Me. Q is 6-MeO-3-pyridinyl, R^ is I and R2 is Me. Q is 6-MeO-3-pyridinyl, R1 is Me and R2 is Me. Q is 6-MeO-3-pyridinyl, R1 is Me and R2 is CI. Q is 6-MeO-3-pyridinyl, R^ is Me and R2 is Br. Q is 6-MeO-3-pyridinyl, R^ is Me and R2 is I. Q is 6-MeO-3-pyridinyl, R^ is Br and R2 is Br. Q is 6-MeO-3-pyridinyl, R1 is Br and R2 is CI. Q is 6-MeO-3-pyridinyl, R1 is CI and R2 is Br. Q is 6-MeO-3-pyridinyl, R1 is CI and R2 is CI. Q is 6-CF3-3-pyridinyl, R is CI and R2 is Me. Q is 6-CF3-3-pyridinyl, R is CI and R2 is CFH2 Q is 6-CF3-3-pyridinyl, R is Br and R2 is Me. Q is 6-CF3-3-pyridinyl, R is I and R2 is Me. Q is 6-CF3-3-pyridinyl, R is Me and R2 is Me. Q is 6-CF3-3-pyridinyl, R is Me and R2 is CI. Q is 6-CF3-3-pyridinyl, R is Me and R2 is Br. Q is 6-CF3-3-pyridinyl, R is Me and R2 is I. Q is 6-CF3-3-pyridinyl, R is Br and R2 is Br. Q is 6-CF3-3-pyridinyl, R is Br and R2 is CI. Q is 6-CF3-3-pyridinyl, R is CI and R2 is Br. Q is 6-CF3-3-pyridinyl, R is CI and R2 is CI. Q is 6-Br-3-pyridinyl, R is CI and R2 is Me. Q is 6-Br-3-pyridinyl, R is CI and R2 is CFH2. Q is 6-Br-3-pyridinyl, R is Br and R2 is Me. Q is 6-Br-3-pyridinyl, R is I and R2 is Me. Q is 6-Br-3-pyridinyl, R is Me and R2 is Me. Q is 6-Br-3-pyridinyl, R is Me and R2 is CI. Q is 6-Br-3-pyridinyl, R is Me and R2 is Br. Q is 6-Br-3-pyridinyl, R is Me and R2 is I. Q is 6-Br-3-pyridinyl, R is Br and R2 is Br. Q is 6-Br-3-pyridinyl, R is Br and R2 is CI. Row Heading
Q is 6-Br-3-pyridinyl, R1 is CI and is Br.
Q is 6-Br-3-pyridinyl, R^ is CI and R2 is CI.
Q is 6-F-3-pyridinyl, R^ is CI and R2 is Me.
Q is 6-F-3-pyridinyl, R^ is CI and R2 is CFH2.
Q is 6-F-3-pyridinyl, R^ is Br and R2 is Me.
Q is 6-F-3-pyridinyl, R^ is I and R2 is Me.
Q is 6-F-3-pyridinyl, R^ is Me and R2 is Me.
Q is 6-F-3-pyridinyl, R^ is Me and R2 is CI.
Q is 6-F-3-pyridinyl, R^ is Me and R2 is Br.
Q is 6-F-3-pyridinyl, R^ is Me and R2 is I.
Q is 6-F-3-pyridinyl, R^ is Br and R2 is Br.
Q is 6-F-3-pyridinyl, R^ is Br and R2 is CI.
Q is 6-F-3-pyridinyl, R^ is CI and R2 is Br.
Q is 6-F-3-pyridinyl, R^ is CI and R2 is CI.
Q is 2-Cl, 6-Me-4-pyridinyl, R1 is CI and R2 is Me. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is CI and R2 is CFH2. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is Br and R2 is Me. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is I and R2 is Me. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is Me and R2 is Me. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is Me and R2 is CI. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is Me and R2 is Br. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is Me and R2 is I. Q is 2-Cl. 6-Me-4-pyridinyl, R^ is Br and R2 is Br. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is Br and R2 is CI. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is CI and R2 is Br. Q is 2-Cl. 6-Me-4-pyridinyl, R1 is CI and R2 is CI. Q is 2-Cl 6-MeO-3-pyridinyl, R is CI and R2 is Me. Q is 2-Cl 6-MeO-3-pyridinyl, R is CI and R2 is CFH2. Q is 2-Cl 6-MeO-3-pyridinyl, R is Br and R2 is Me. Q is 2-Cl 6-MeO-3-pyridinyl, R is I and R2 is Me. Q is 2-Cl 6-MeO-3-pyridinyl, R is Me and R2 is Me. Q is 2-Cl 6-MeO-3-pyridinyl, R is Me and R2 is CI. Q is 2-Cl 6-MeO-3-pyridinyl, R is Me and R2 is Br. Q is 2-Cl 6-MeO-3-pyridinyl, R is Me and R2 is I. Q is 2-Cl 6-MeO-3-pyridinyl, R is Br and R2 is Br. Q is 2-Cl 6-MeO-3-pyridinyl, R is Br and R2 is CI. Q is 2-Cl, 6-MeO-3-pyridinyl, R is CI and R2 is Br.
Figure imgf000098_0001
Row Heading
Q is 5-Me-3-pyridinyl, R is CI and R2 is Me.
Q is 5-Me-3-pyridinyl, R is CI and R2 is CFH2.
Q is 5-Me-3-pyridinyl, R is Br and R2 is Me.
Q is 5-Me-3-pyridinyl, R is I and R2 is Me.
Q is 5-Me-3-pyridinyl, R is Me and R2 is Me.
Q is 5-Me-3-pyridinyl, R is Me and R2 is CI.
Q is 5-Me-3-pyridinyl, R is Me and R2 is Br.
Q is 5-Me-3-pyridinyl, R is Me and R2 is I.
Q is 5-Me-3-pyridinyl, R is Br and R2 is Br.
Q is 5-Me-3-pyridinyl, R is Br and R2 is CI.
Q is 5-Me-3-pyridinyl, R is CI and R2 is Br.
Q is 5-Me-3-pyridinyl, R is CI and R2 is CI.
Q is 5-MeO-3-pyridinyl, R is CI and R2 is Me.
Q is 5-MeO-3-pyridinyl, R is CI and R2 is CFH2 Q is 5-MeO-3-pyridinyl, R is Br and R2 is Me.
Q is 5-MeO-3-pyridinyl, R is I and R2 is Me.
Q is 5-MeO-3-pyridinyl, R is Me and R2 is Me.
Q is 5-MeO-3-pyridinyl, R is Me and R2 is CI.
Q is 5-MeO-3-pyridinyl, R is Me and R2 is Br.
Q is 5-MeO-3-pyridinyl, R is Me and R2 is I.
Q is 5-MeO-3-pyridinyl, R is Br and R2 is Br.
Q is 5-MeO-3-pyridinyl, R is Br and R2 is CI.
Q 5-MeO-3-pyridinyl, R1 is C and R^- is Br.
Q 5- MeO-3-pyridinyl, R1 is C and R2 is CI.
Q 6- Cl, 5-MeO-3-pyridinyl, R is CI and R2 is Me. Q 6-Cl, 5-MeO-3-pyridinyl, R is CI and R2 is CFH2. Q 6-Cl, 5-MeO-3-pyridinyl, R is Br and R2 is Me. Q 6-Cl, 5-MeO-3-pyridinyl, R is I and R2 is Me. Q 6-Cl, 5-MeO-3-pyridinyl, R is Me and R2 is Me. Q 6-Cl, 5-MeO-3-pyridinyl, R is Me and R2 is CI. Q 6-Cl, 5-MeO-3-pyridinyl, R is Me and R2 is Br. Q 6-Cl, 5-MeO-3-pyridinyl, R is Me and R2 is I. Q 6-Cl, 5-MeO-3-pyridinyl, R is Br and R2 is Br. Q 6-Cl, 5-MeO-3-pyridinyl, R is Br and R2 is CI. Q 6-Cl, 5-MeO-3-pyridinyl, R is CI and R2 is Br. Q 6-Cl, 5-MeO-3-pyridinyl, R is CI and R2 is CI. Q is 6-Cl-3-pyridazinyl, R^ is CI and R2 is Me. Row Heading
Q is 6-Cl-3-pyridazinyl, R1 is CI and z is CFH2. Q is 6-Cl-3-pyridazinyl, R^ is Br and R2 is Me. Q is 6-Cl-3-pyridazinyl, R^ is I and R2 is Me. Q is 6-Cl-3-pyridazinyl, R^ is Me and R2 is Me. Q is 6-Cl-3-pyridazinyl, R^ is Me and R2 is CI. Q is 6-Cl-3-pyridazinyl, R^ is Me and R2 is Br. Q is 6-Cl-3-pyridazinyl, R^ is Me and R2 is I. Q is 6-Cl-3-pyridazinyl, R^ is Br and R2 is Br. Q is 6-Cl-3-pyridazinyl, R^ is Br and R2 is CI. Q is 6-Cl-3-pyridazinyl, R^ is CI and R2 is Br. Q is 6-Cl-3-pyridazinyl, R^ is CI and R2 is CI. Q is 6-Me-3-pyridazinyl, R^ is CI and R2 is Me. Q is 6-Me-3-pyridazinyl, R^ is CI and R2 is CFH2. Q is 6-Me-3-pyridazinyl, R^ is Br and R2 is Me. Q is 6-Me-3-pyridazinyl, R^ is I and R2 is Me. Q is 6-Me-3-pyridazinyl, R^ is Me and R2 is Me. Q is 6-Me-3-pyridazinyl, R^ is Me and R2 is CI. Q is 6-Me-3-pyridazinyl, R^ is Me and R2 is Br. Q is 6-Me-3-pyridazinyl, R^ is Me and R2 is I. Q is 6-Me-3-pyridazinyl, R^ is Br and R2 is Br. Q is 6-Me-3-pyridazinyl, R^ is Br and R2 is CI. Q is 6-Me-3-pyridazinyl, R^ is CI and R2 is Br. Q is 6-Me-3-pyridazinyl, R^ is CI and R2 is CI. Q is 6-MeO-3-pyridazinyl, R1 is CI and R2 is Me. Q is 6-MeO-3-pyridazinyl, R^ is CI and R2 is CFH2. Q is 6-MeO-3-pyridazinyl, R^ is Br and Rz is Me. Q is 6-MeO-3-pyridazinyl, R^ is I and R2 is Me. Q is 6-MeO-3-pyridazinyl, R^ is Me and R2 is Me, Q is 6-MeO-3-pyridazinyl, R^ is Me and R2 is CI. Q is 6-MeO-3-pyridazinyl, R^ is Me and R2 is Br. Q is 6-MeO-3-pyridazinyl, R^ is Me and R2 is I. Q is 6-MeO-3-pyridazinyl, R^ is Br and R2 is Br. Q is 6-MeO-3-pyridazinyl, R^ is Br and R2 is CI. Q is 6-MeO-3-pyridazinyl, R^ is CI and R2 is Br. Q is 6-MeO-3-pyridazinyl, R^ is CI and R2 is CI. Q is 6-CF3-3-pyridazinyl, R^ is CI and Rz is Me. Q is 6-CF3-3-pyridazinyl, R^ is CI and R2 is CFH2. Table Row Heading
442B Q1 is 6-CF3-3-pyridazinyl, R^ is Br and R2 is Me.
443B Q1 is 6-CF3-3-pyridazinyl, R^ is I and R2 is Me.
444B Q1 is 6-CF3-3-pyridazinyl, R^ is Me and R2 is Me.
445B Q1 is 6-CF3-3-pyridazinyl, R^ is Me and R2 is CI.
446B Q1 is 6-CF3-3-pyridazinyl, R^ is Me and R2 is Br.
447B Q1 is 6-CF3-3-pyridazinyl, R^ is Me and R2 is I.
448B Q1 is 6-CF3-3-pyridazinyl, R^ is Br and R2 is Br.
449B Q1 is 6-CF3-3-pyridazinyl, R^ is Br and R2 is CI.
450B Q1 is 6-CF3-3-pyridazinyl, R^ is CI and R2 is Br.
451B Q1 is 6-CF3-3-pyridazinyl, R^ is CI and R2 is CI.
452B Q1 is 5-Cl-3-pyridazinyl, R^ is CI and R2 is Me.
453B Q1 is 5-Cl-3-pyridazinyl, R1 is CI and R2 is CFH2.
454B Q1 is 5-Cl-3-pyridazinyl, R^ is Br and R2 is Me.
455B Q1 is 5-Cl-3-pyridazinyl, R^ is I and R2 is Me.
456B Q1 is 5-Cl-3-pyridazinyl, R^ is Me and R2 is Me.
457B Q1 is 5-Cl-3-pyridazinyl, R^ is Me and R2 is CI.
458B Q1 is 5-Cl-3-pyridazinyl, R^ is Me and R2 is Br.
459B Q1 is 5-Cl-3-pyridazinyl, R^ is Me and R2 is I.
460B Q1 is 5-Cl-3-pyridazinyl, R^ is Br and R2 is Br.
461B Q1 is 5-Cl-3-pyridazinyl, R^ is Br and R2 is CI.
462B Q1 is 5-Cl-3-pyridazinyl, R^ is CI and R2 is Br.
463B Q1 is 5-Cl-3-pyridazinyl, R^ is CI and R2 is CI.
464B Q1 is 5-F-3-pyridazinyl, R^ is CI and R2 is Me.
465B Q1 is 5-F-3-pyridazinyl, R^ is CI and R2 is CFH2.
466B Q1 is 5-F-3-pyridazinyl, R^ is Br and R2 is Me.
467B Q1 is 5-F-3-pyridazinyl, R^ is I and R2 is Me.
468B Q1 is 5-F-3-pyridazinyl, R^ is Me and R2 is Me.
469B Q1 is 5-F-3-pyridazinyl, R^ is Me and R2 is CI.
470B Q1 is 5-F-3-pyridazinyl, R^ is Me and R2 is Br.
471B Q1 is 5-F-3-pyridazinyl, R^ is Me and R2 is I.
472B Q1 is 5-F-3-pyridazinyl, R^ is Br and R2 is Br.
473B Q1 is 5-F-3-pyridazinyl, R^ is Br and R2 is CI.
474B Q1 is 5-F-3-pyridazinyl, R^ is CI and R2 is Br.
475B Q1 is 5-F-3-pyridazinyl, R^ is CI and R2 is CI.
476B Q1 is 5-MeO-3-pyridazinyl, R^ is CI and R2 is Me.
477B Q1 is 5-MeO-3-pyridazinyl, R1 is CI and R2 is CFH2.
478B Q1 is 5-MeO-3-pyridazinyl, R^ is Br and R2 is Me. Row Heading
Q is 5-MeO-3-pyridazinyl, R1 is I and R~ is Me. Q is 5-MeO-3-pyridazinyl, R^ is Me and R2 is Me, Q is 5-MeO-3-pyridazinyl, R1 is Me and R2 is CI. Q is 5-MeO-3-pyridazinyl, R^ is Me and R2 is Br. Q is 5-MeO-3-pyridazinyl, R^ is Me and R2 is I. Q is 5-MeO-3-pyridazinyl, R^ is Br and R2 is Br. Q is 5-MeO-3-pyridazinyl, R^ is Br and R2 is CI. Q is 5-MeO-3-pyridazinyl, R^ is CI and R2 is Br. Q is 5-MeO-3-pyridazinyl, R1 is CI and R2 is CI. Q is 2-Cl-5-pyrimidinyl, R is CI and R2 is Me. Q is 2-Cl-5-pyrimidinyl, R is CI and R2 is CFH2. Q is 2-Cl-5-pyrimidinyl, R is Br and R2 is Me. Q is 2-Cl-5-pyrimidinyl, R is I and R2 is Me. Q is 2-Cl-5-pyrimidinyl, R is Me and R2 is Me. Q is 2-C1-5 pyrimidinyl, R is Me and R2 is CI. Q is 2-Cl-5-pyrimidinyl, R is Me and R2 is Br. Q is 2-Cl-5-pyrimidinyl, R is Me and R2 is I. Q is 2-Cl-5-pyrimidinyl, R is Br and R2 is Br. Q is 2-Cl-5-pyrimidinyl, R is Br and R2 is CI. Q is 2-Cl-5-pyrimidinyl, R is CI and R2 is Br. Q is 2-Cl-5-pyrimidinyl, R is CI and R2 is CI. Q is 2-Me-5-pyrimidinyl, R1 is CI and R^ is Me. Q is 2-Me-5-pyrimidinyl, R1 is CI and R2 is CFH2. Q is 2-Me-5-pyrimidinyl, R^ is Br and R2 is Me. Q is 2-Me-5-pyrimidinyl, R^ is I and R2 is Me. Q is 2-Me-5-pyrimidinyl, R^ is Me and R2 is Me. Q is 2-Me-5-pyrimidinyl, R^ is Me and R2 is CI. Q is 2-Me-5-pyrimidinyl, R^ is Me and R2 is Br. Q is 2-Me-5-pyrimidinyl, R^ is Me and R2 is I. Q is 2-Me-5-pyrimidinyl, R^ is Br and R2 is Br. Q is 2-Me-5-pyrimidinyl, R^ is Br and R2 is CI. Q is 2-Me-5-pyrimidinyl, R^ is CI and R2 is Br. Q is 2-Me-5-pyrimidinyl, R^ is CI and R2 is CI. Q is 2-MeO-5-pyrimidinyl, R1 is CI and R2 is Me. Q is 2-MeO-5-pyrimidinyl, R1 is CI and R2 is CFH2. Q is 2-MeO-5-pyrimidinyl, R^ is Br and R2 is Me. Q is 2-MeO-5-pyrimidinyl, R^ is I and R2 is Me. Row Heading
2-MeO-5-pyrimidinyl, R1 is Me and R2 is Me. 2-MeO-5-pyrimidinyl, R1 is Me and R2 is CI. 2-MeO-5-pyrimidinyl, R1 is Me and R"- is Br. 2-MeO-5-pyrimidinyl, R^ is Me and R2 is I. 2-MeO-5 pyrimidinyl, R^ is Br and R2 is Br. 2-MeO-5-pyrimidinyl, R^ is Br and R2 is CI.
Q1 2-MeO-5-pyrimidinyl, R^ is CI and R2 is Br.
2 -MeO-5 -pyrimidinyl, R1 is CI and R2 is CI.
2-CF3-5-pyrimidinyl, R is CI and R2 is Me. 2-CF3-5-pyrimidinyl, R is CI and R2 is CFH2.
-CF3-5-pyrimidinyl, R is Br and R2 is Me. -CF3-5-pyrimidinyl, R is I and R2 is Me.
QJ -CF3-5-pyrimidinyl, R is Me and Rz is Me. Q1 -CF3-5-pyrimidinyl, R is Me and R2 is CI.
-CF3-5-pyrimidinyl, R is Me and R2 is Br. -CF3-5-pyrimidinyl, R is Me and R2 is I. -CF3-5-pyrimidinyl, R is Br and R"- is Br. -CF3-5-pyrimidinyl, R is Br and R2 is CI. -CF3-5-pyrimidinyl, R is CI and R2 is Br.
Q -CF3-5-pyrimidinyl, R is CI and R2 is CI.
Q1 s 5-C1-2 -pyrimidinyl, R is CI and R2 is Me.
Q1 s 5-C1-2 -pyrimidinyl, R is CI and R2 is CFH2. s 5-C1-2 -pyrimidinyl, R is Br and R"- is Me. s 5-C1-2 -pyrimidinyl, R is I and R"- is Me. s 5-Cl-2-pyrimidinyl, R is Me and R2 is Me. s 5-C1-2 -pyrimidinyl, R is Me and R2 is CI.
Q s 5-C1-2 -pyrimidinyl, R is Me and R2 is Br.
Q1 s 5-C1-2 -pyrimidinyl, R is Me and R2 is I.
Q1 s 5-C1-2 -pyrimidinyl, R is Br and R2 is Br. s 5-C1-2 -pyrimidinyl, R is Br and R2 is CI. s 5-C1-2 -pyrimidinyl, R is CI and R"- is Br. s 5-Cl-2-pyrimidinyl, R is CI and R2 is CI. s 5-Me -2 -pyrimidinyl, R^ is CI and R2 is Me. s 5-Me -2 -pyrimidinyl, R1 is CI and R2 is CFH2.
Q s 5-Me -2 -pyrimidinyl, R^ is Br and R2 is Me. Q1 s 5-Me -2 -pyrimidinyl, R^ is I and R2 is Me. s 5-Me -2 -pyrimidinyl, R^ is Me and R2 is Me.
Figure imgf000104_0001
Row Heading
Q s 5-CF3-2-pyrimidinyl, R1 is Me and R is Br. s 5-CF3-2-pyrimidinyl, ^ is Me and R2 is I. s 5-CF3-2-pyrimidinyl, R1 is Br and R"- is Br. s 5-CF3-2-pyrimidinyl, R^ is Br and R2 is CI. s 5-CF3-2-pyrimidinyl, is CI and R2 is Br.
Q s 5-CF3-2-pyrimidinyl, R^ is CI and R2 is CI. s 5-Me-2-thienyl, R is CI and R2 is Me. s 5-Me-2-thienyl, R is CI and R2 is CFFK s 5-Me-2-thienyl, R is Br and Rz is Me. s 5-Me-2-thienyl, R is I and R2 is Me.
s 5-Me-2-thienyl, R is Me and R2 is Me. s 5-Me-2-thienyl, R is Me and R2 is CI.
»1 s 5-Me-2-thienyl, R is Me and R2 is Br.
»1 s 5-Me-2-thienyl, R is Me and R2 is I.
s 5-Me-2-thienyl, R is Br and R2 is Br. s 5-Me-2-thienyl, R is Br and R2 is CI. s 5-Me-2-thienyl, R is CI and R2 is Br. s 5-Me-2-thienyl, R is CI and R2 is CI.
5 -Cl-2-thienyl, R1 is CI and R2 is Me.
Q 5 -Cl-2-thienyl, R1 is CI and R2 is CFH2.
5 -Cl-2-thienyl, R1 is Br and R2 is Me.
5 -Cl-2-thienyl, R1 is I and R2 is Me.
5 -Cl-2-thienyl, R1 is Me and R2 is Me.
5 -Cl-2-thienyl, R1 is Me and R2 is CI.
5 -Cl-2-thienyl, R1 is Me and R2 is Br.
5 -Cl-2-thienyl, R1 is Me and R2 is I.
5 -Cl-2-thienyl, R1 is Br and R2 is Br.
5 -Cl-2-thienyl, R1 is Br and R2 is CI.
5 -Cl-2-thienyl, R1 is CI and R2 is Br.
5 -Cl-2-thienyl, R1 is CI and R2 is CI.
5-F-2-thienyl, R1 is CI and z is Me.
5-F-2-thienyl, R1 is CI and R2 is CFH2. 5-F-2-thienyl, R1 is Br and R2 is Me.
5-F-2-thienyl, R1 is I and R2 is Me.
5-F-2-thienyl, R1 is Me and R2 is Me. 5-F-2-thienyl, R1 is Me and R2 is CI.
5-F-2-thienyl, R1 is Me and R2 is Br. Row Heading
Q1 is 5-F-2-thienyl, R1 is Me and R1 is I. Q1 is 5-F-2-thienyl, R1 is Br and R2 is Br. Q1 is 5-F-2-thienyl, R1 is Br and R2 is CI. Q1 is 5-F-2-thienyl, R1 is CI and R2 is Br. Q1 is 5-F-2-thienyl, R1 is CI and R2 is CI. Q1 is 5-Me-3-thienyl, R1 is CI and R2 is Me. Q1 is 5-Me-3-thienyl, R1 is CI and R2 is CFH2. Q1 is 5-Me-3-thienyl, R1 is Br and R2 is Me. Q1 is 5-Me-3-thienyl, R1 is I and R2 is Me. Q1 is 5-Me-3-thienyl, R1 is Me and R2 is Me. Q1 is 5-Me-3-thienyl, R1 is Me and R2 is CI. Q1 is 5-Me-3-thienyl, R1 is Me and R2 is Br. Q1 is 5-Me-3-thienyl, R1 is Me and R2 is I. Q1 is 5-Me-3-thienyl, R1 is Br and R2 is Br. Q1 is 5-Me-3-thienyl, R1 is Br and R2 is CI. Q1 is 5-Me-3-thienyl, R1 is CI and R2 is Br. Q1 is 5-Me-3-thienyl, R1 is CI and R2 is CI. Q1 is 5-Cl-3-thienyl, R1 is CI and R2 is Me. Q1 is 5-Cl-3-thienyl, R1 is CI and R2 is CFH2. Q1 is 5-Cl-3-thienyl, R1 is Br and R2 is Me. Q1 is 5-Cl-3-thienyl, R1 is I and R2 is Me. Q1 is 5-Cl-3-thienyl, R1 is Me and R2 is Me. Q1 is 5-Cl-3-thienyl, R1 is Me and R2 is CI. Q1 is 5-Cl-3-thienyl, R1 is Me and R2 is Br. Q1 is 5-Cl-3-thienyl, R1 is Me and R2 is I. Q1 is 5-Cl-3-thienyl, R1 is Br and R2 is Br. Q1 is 5-Cl-3-thienyl, R1 is Br and R2 is CI. Q1 is 5-Cl-3-thienyl, R1 is CI and R2 is Br. Q1 is 5-Cl-3-thienyl, R1 is CI and R2 is CI. Q1 is 5-F-3-thienyl, R1 is CI and R2 is Me. Q1 is 5-F-3-thienyl, R1 is CI and R2 is CFH2. Q1 is 5-F-3-thienyl, R1 is Br and R2 is Me. Q1 is 5-F-3-thienyl, R1 is I and R2 is Me. Q1 is 5-F-3-thienyl, R1 is Me and R2 is Me. Q1 is 5-F-3-thienyl, R1 is Me and R2 is CI. Q1 is 5-F-3-thienyl, R1 is Me and R2 is Br. Q1 is 5-F-3-thienyl, R1 is Me and R2 is I. Table Row Heading
664B Q1 is 5 -F-3 -thienyl, R^ is Br and R2 is Br.
665B Q1 is 5 -F-3 -thienyl, R1 is Br and R2 is CI.
666B Q1 is 5 -F-3 -thienyl, R1 is CI and R2 is Br.
667B Q1 is 5 -F-3 -thienyl, R1 is CI and R2 is CI.
668B Q1 is 1 -Me l /-pyrazol-3-yl, R1 is CI and R2 is Me.
669B Q1 is 1 -Me l /-pyrazol-3-yl, R1 is CI and R2 is CFH2.
670B Q1 is 1 -Me l /-pyrazol-3-yl, R^ is Br and R2 is Me.
671B Q1 is 1 -Me l /-pyrazol-3-yl, R^ is I and R2 is Me.
672B Q1 is 1 -Me l /-pyrazol-3-yl, R^ is Me and R2 is Me.
673B Q1 is 1 -Me l//-pyrazol-3-yl, R1 is Me and R2 is CI.
674B Q1 is 1 -Me l /-pyrazol-3-yl, R^ is Me and R2 is Br.
675B Q1 is 1 -Me l /-pyrazol-3-yl, R^ is Me and R2 is I.
676B Q1 is 1 -Me l /-pyrazol-3-yl, R^ is Br and R2 is Br.
677B Q1 is 1 -Me l /-pyrazol-3-yl, R^ is Br and R2 is CI.
678B Q1 is 1 -Me l /-pyrazol-3-yl, R^ is CI and R2 is Br.
679B Q1 is 1 -Me l//-pyrazol-3-yl, R1 is CI and R2 is CI.
680B Q1 is 1 -Me l//-pyrazol-4-yl, R1 is CI and R2 is Me.
681B Q1 is 1 -Me l /-pyrazol-4-yl, R1 is CI and R2 is CFH2.
682B Q1 is 1 -Me l /-pyrazol-4-yl, R^ is Br and R2 is Me.
683B Q1 is 1 -Me l /-pyrazol-4-yl, R^ is I and R2 is Me.
684B Q1 is 1 -Me l//-pyrazol-4-yl, R1 is Me and R2 is Me.
685B Q1 is 1 -Me l//-pyrazol-4-yl, R1 is Me and R2 is CI.
686B Q1 is 1 -Me l /-pyrazol-4-yl, R^ is Me and R2 is Br.
687B Q1 is 1 -Me l /-pyrazol-4-yl, R^ is Me and R2 is I.
688B Q1 is 1 -Me l /-pyrazol-4-yl, R^ is Br and R2 is Br.
689B Q1 is 1 -Me l /-pyrazol-4-yl, R^ is Br and R2 is CI.
690B Q1 is 1 -Me l /-pyrazol-4-yl, R^ is CI and R2 is Br.
691B Q1 is 1 -Me l /-pyrazol-4-yl, R1 is CI and R2 is CI.
692B Q1 is 2 -Me 5-thiazolyl, R1 is CI and R2 is Me.
693B Q1 is 2 -Me 5-thiazolyl, R1 is CI and R2 is CFH2.
694B Q1 is 2 -Me 5-thiazolyl, R^ is Br and R2 is Me.
695B Q1 is 2 -Me 5-thiazolyl, R^ is I and R2 is Me.
696B Q1 is 2 -Me 5-thiazolyl, R1 is Me and R2 is Me.
697B Q1 is 2 -Me 5-thiazolyl, R1 is Me and R2 is CI.
698B Q1 is 2 -Me 5-thiazolyl, R^ is Me and R2 is Br.
699B Q1 is 2 -Me 5-thiazolyl, R^ is Me and R2 is I.
700B Q1 is 2 -Me 5-thiazolyl, R^ is Br and R2 is Br. Table Row Heading
701B Q1 is 2-Me-5-thiazolyl, R1 is Br and z is CI.
702B Q1 is 2-Me-5-thiazolyl, R1 is CI and R2 is Br.
703B Q1 is 2-Me-5-thiazolyl, R1 is CI and R2 is CI.
704B Q1 is 2-Cl-5-thiazolyl, R1 is CI and R2 is Me.
705B Q1 is 2-Cl-5-thiazolyl, R1 is CI and R2 is CFH2
706B Q1 is 2-Cl-5-thiazolyl, R1 is Br and R2 is Me.
707B Q1 is 2-Cl-5-thiazolyl, R1 is I and R2 is Me.
708B Q1 is 2-Cl-5-thiazolyl, R1 is Me and R2 is Me.
709B Q1 is 2-Cl-5-thiazolyl, R1 is Me and R2 is CI.
710B Q1 is 2-Cl-5-thiazolyl, R1 is Me and R2 is Br.
711B Q1 is 2-Cl-5-thiazolyl, R1 is Me and R2 is I.
712B Q1 is 2-Cl-5-thiazolyl, R1 is Br and R2 is Br.
713B Q1 is 2-Cl-5-thiazolyl, R1 is Br and R2 is CI.
714B Q1 is 2-Cl-5-thiazolyl, R1 is CI and R2 is Br.
715B Q1 is 2-Cl-5-thiazolyl, R1 is CI and R2 is CI.
Table 3
Figure imgf000108_0001
R1 is CI, R2 is Me and (R3)m is 2,6-di-F, 4-MeNH(CH2)30.
Figure imgf000108_0002
The present disclosure also includes Tables 1C through 62C, each of which is constructed the same as Table 3 above except that the row heading in Table 3 (i.e. "R1 is CI, R2 is Me and (R3)m is 2,6-di-F, 4-MeNH(CH2)30") is replaced with the respective row heading shown below. Thus, for example, in Table 1C the row heading is "R1 is CI, R2 is CI and (R3)m is 2,6-di-F, 4-MeNH(CH2)30", and Q2 is as defined in Table 3 above. Tables 2C through 62C are constructed similarly.
Table Number Row Heading
is CI, R2 is CI and (R3)m is 2,6-di-F, 4-MeNH(CH2)30.
is CI, R2 is Br and (R3)m is 2,6-di-F, 4-MeNH(CH2)30.
is Br, R2 is Me and (R3)m is 2,6-di-F, 4-MeNH(CH2)30.
is Br, R2 is CI and (R3)m is 2,6-di-F, 4-MeNH(CH2)30.
is Me, R2 is Me and (R3)m is 2,6-di-F, 4-MeNH(CH2)30.
is Br, R2 is Br and (R3)m is 2,6-di-F, 4-MeNH(CH2)30.
is CI, R2 is Me and (R3)m is 2,6-di-F, 4-Me2N(CH2)30.
is CI, R2 is CI and (R3)m is 2,6-di-F, 4-Me2N(CH2)30.
is CI, R2 is Br and (R3)m is 2,6-di-F, 4-Me2N(CH2)30.
is Br, R2 is Me and (R3)m is 2,6-di-F, 4-Me2N(CH2)30.
is Br, R2 is CI and (R3)m is 2,6-di-F, 4-Me2N(CH2)30.
is Me, R2 is Me and (R3)m is 2,6-di-F, 4-Me2N(CH2)30.
is Br, R2 is Br and (R3)m is 2,6-di-F, 4-Me2N(CH2)30.
is CI, R2 is Me, and (R3)m is 2,6-di-F, 4-MeO(CH2)30.
is CI, R2 is CI and (R3)m is 2,6-di-F, 4-MeO(CH2)30.
is CI, R2 is Br and (R3)m is 2,6-di-F, 4-MeO(CH2)30.
is Br, R2 is Me and (R3)m is 2,6-di-F, 4-MeO(CH2)30.
is Br, R2 is CI and (R3)m is 2,6-di-F, 4-MeO(CH2)30.
is Me, R2 is Me and (R3)m is 2,6-di-F, 4-MeO(CH2)30.
is Br, R2 is Br and (R3)m is 2,6-di-F, 4-MeO(CH2)30.
is CI, R2 is Me and (R3)m is 2-C1-6-F, 4-MeNH(CH2)30.
is CI, R2 is CI and (R3)m is 2-C1-6-F, 4-MeNH(CH2)30.
is CI, R2 is Br and (R3)m is 2-C1-6-F, 4-MeNH(CH2)30.
is Br, R2 is Me and (R3)m is 2-C1-6-F, 4-MeNH(CH2)30.
is Br, R2 is CI and (R3)m is 2-C1-6-F, 4-MeNH(CH2)30.
is Me, R2 is Me and (R3)m is 2-C1-6-F, 4-MeNH(CH2)30,
is Br, R2 is Br and (R3)m is 2-C1-6-F, 4-MeNH(CH2)30.
is CI, R2 is Me and (R3)m is 2,6-di-F, 3-MeNH(CH2)30.
is CI, R2 is CI and (R3)m is 2,6-di-F, 3-MeNH(CH2)30.
is CI, R2 is Br and (R3)m is 2,6-di-F, 3-MeNH(CH2)30.
is Br, R2 is Me and (R3)m is 2,6-di-F, 3-MeNH(CH2)30.
is Br, R2 is CI and (R3)m is 2,6-di-F, 3-MeNH(CH2)30.
is Me, R2 is Me and (R3)m is 2,6-di-F, 3-MeNH(CH2)30.
is Br, R2 is Br and (R3)m is 2,6-di-F, 3-MeNH(CH2)30. Table Number Row Heading
is CI, R2 is Me and (R3)m is 2,6-di-F, 3-Me2N(CH2)30. is CI, R2 is CI and (R3)m is 2,6-di-F, 3-Me2N(CH2)30. is CI, R2 is Br and (R3)m is 2,6-di-F, 3-Me2N(CH2)30. is Br, R2 is Me and (R3)m is 2,6-di-F, 3-Me2N(CH2)30. is Br, R2 is CI and (R3)m is 2,6-di-F, 3-Me2N(CH2)30. is Me, R2 is Me and (R3)m is 2,6-di-F, 3-Me2N(CH2)30. is Br, R2 is Br and (R3)m is 2,6-di-F, 3-Me2N(CH2)30. is CI, R2 is Me, and (R3)m is 2,6-di-F, 3-MeO(CH2)30. is CI, R2 is CI and (R3)m is 2,6-di-F, 3-MeO(CH2)30. is CI, R2 is Br and (R3)m is 2,6-di-F, 3-MeO(CH2)30. is Br, R2 is Me and (R3)m is 2,6-di-F, 3-MeO(CH2)30. is Br, R2 is CI and (R3)m is 2,6-di-F, 3-MeO(CH2)30. is Me, R2 is Me and (R3)m is 2,6-di-F, 3-MeO(CH2)30. is Br, R2 is Br and (R3)m is 2,6-di-F, 3-MeO(CH2)30. is CI, R2 is Me and (R3)m is 2-C1-6-F, 3-MeNH(CH2)30. is CI, R2 is CI and (R3)m is 2-C1-6-F, 3-MeNH(CH2)30. is CI, R2 is Br and (R3)m is 2-C1-6-F, 3-MeNH(CH2)30. is Br, R2 is Me and (R3)m is 2-C1-6-F, 3-MeNH(CH2)30. is Br, R2 is CI and (R3)m is 2-C1-6-F, 3-MeNH(CH2)30. is Me, R2 is Me and (R3)m is 6-C1-6-F, 3-MeNH(CH2)30. is Br, R2 is Br and (R3)m is 2-C1-6-F, 3-MeNH(CH2)30. is CI, R2 is Me and (R3)m is 6-C1-2-F, 3-MeNH(CH2)30. is CI, R2 is CI and (R3)m is 6-C1-2-F, 3-MeNH(CH2)30. is CI, R2 is Br and (R3)m is 6-C1-2-F, 3-MeNH(CH2)30. is Br, R2 is Me and (R3)m is 6-C1-2-F, 3-MeNH(CH2)30. is Br, R2 is CI and (R3)m is 6-C1-2-F, 3-MeNH(CH2)30. is Me, R2 is Me and (R3)m is 6-C1-2-F, 3-MeNH(CH2)30. is Br, R2 is Br and (R3)m is 6-C1-2-F, 3-MeNH(CH2)30.
Figure imgf000111_0001
R1 is CI, R2 is Me and (R5)n is 2,6-di-F, 4-MeNH(CH2)30.
Figure imgf000111_0002
The present disclosure also includes Tables ID through 62D, each of which is constructed the same as Table 4 above except that the row heading in Table 4 (i.e. "R1 is CI, R2 is Me and (R5)n is 2,6-di-F, 4-MeNH(CH2)30") is replaced with the respective row heading shown below. Thus, for example, in Table ID the row heading is "R1 is CI, R2 is CI and (R5)n is 2,6-di-F, 4-MeNH(CH2)30", and Q1 is as defined in Table 4 above. Tables 2D through 62D are constructed similarly.
Table Number Row Heading
ID R1 is CI, R2 is CI and (R5)n is 2,6-di-F, 4-MeNH(CH2)30.
2D R1 is CI, R2 is Br and (R5)n is 2,6-di-F, 4-MeNH(CH2)30.
3D R1 is Br, R2 is Me and (R5)n is 2,6-di-F, 4-MeNH(CH2)30.
4D R1 is Br, R2 is CI and (R5)n is 2,6-di-F, 4-MeNH(CH2)30.
5D R1 is Me, R2 is Me and (R5)n is 2,6-di-F, 4-MeNH(CH2)30.
6D R1 is Br, R2 is Br and (R5)n is 2,6-di-F, 4-MeNH(CH2)30.
7D R1 is CI, R2 is Me and (R5)n is 2,6-di-F, 4-Me2N(CH2)30.
8D R1 is CI, R2 is CI and (R5)n is 2,6-di-F, 4-Me2N(CH2)30.
9D R1 is CI, R2 is Br and (R5)n is 2,6-di-F, 4-Me2N(CH2)30.
10D R1 is Br, R2 is Me and (R5)n is 2,6-di-F, 4-Me2N(CH2)30.
11D R1 is Br, R2 is CI and (R5)n is 2,6-di-F, 4-Me2N(CH2)30. Table Number Row Heading
R1 is Me, R2 is Me and (R5)n is 2,6-di-F, 4-Me2N(CH2)30. R1 is Br, R2 is Br and (R5)n is 2,6-di-F, 4-Me2N(CH2)30. R1 is CI, R2 is Me, and (R5)n is 2,6-di-F, 4-MeO(CH2)30. R1 is CI, R2 is CI and (R5)n is 2,6-di-F, 4-MeO(CH2)30. R1 is CI, R2 is Br and (R5)n is 2,6-di-F, 4-MeO(CH2)30. R1 is Br, R2 is Me and (R5)n is 2,6-di-F, 4-MeO(CH2)30. R1 is Br, R2 is CI and (R5)n is 2,6-di-F, 4-MeO(CH2)30. R1 is Me, R2 is Me and (R5)n is 2,6-di-F, 4-MeO(CH2)30. R1 is Br, R2 is Br and (R5)n is 2,6-di-F, 4-MeO(CH2)30. R1 is CI, R2 is Me and (R5)n is 2-C1-6-F, 4-MeNH(CH2)30. R1 is CI, R2 is CI and (R5)n is 2-C1-6-F, 4-MeNH(CH2)30. R1 is CI, R2 is Br and (R5)n is 2-C1-6-F, 4-MeNH(CH2)30. R1 is Br, R2 is Me and (R5)n is 2-C1-6-F, 4-MeNH(CH2)30. R1 is Br, R2 is CI and (R5)n is 2-C1-6-F, 4-MeNH(CH2)30. R1 is Me, R2 is Me and (R5)n is 2-C1-6-F, 4-MeNH(CH2)30. R1 is Br, R2 is Br and (R5)n is 2-C1-6-F, 4-MeNH(CH2)30. R1 is CI, R2 is Me and (R5)n is 2,6-di-F, 3-MeNH(CH2)30. R1 is CI, R2 is CI and (R5)n is 2,6-di-F, 3-MeNH(CH2)30. R1 is CI, R2 is Br and (R5)n is 2,6-di-F, 3-MeNH(CH2)30. R1 is Br, R2 is Me and (R5)n is 2,6-di-F, 3-MeNH(CH2)30. R1 is Br, R2 is CI and (R5)n is 2,6-di-F, 3-MeNH(CH2)30. R1 is Me, R2 is Me and (R5)n is 2,6-di-F, 3-MeNH(CH2)30. R1 is Br, R2 is Br and (R5)n is 2,6-di-F, 3-MeNH(CH2)30. R1 is CI, R2 is Me and (R5)n is 2,6-di-F, 3-Me2N(CH2)30. R1 is CI, R2 is CI and (R5)n is 2,6-di-F, 3-Me2N(CH2)30. R1 is CI, R2 is Br and (R5)n is 2,6-di-F, 3-Me2N(CH2)30. R1 is Br, R2 is Me and (R5)n is 2,6-di-F, 3-Me2N(CH2)30. R1 is Br, R2 is CI and (R5)n is 2,6-di-F, 3-Me2N(CH2)30. R1 is Me, R2 is Me and (R5)n is 2,6-di-F, 3-Me2N(CH2)30. R1 is Br, R2 is Br and (R5)n is 2,6-di-F, 3-Me2N(CH2)30. R1 is CI, R2 is Me, and (R5)n is 2,6-di-F, 3-MeO(CH2)30. R1 is CI, R2 is CI and (R5)n is 2,6-di-F, 3-MeO(CH2)30. R1 is CI, R2 is Br and (R5)n is 2,6-di-F, 3-MeO(CH2)30. R1 is Br, R2 is Me and (R5)n is 2,6-di-F, 3-MeO(CH2)30. R1 is Br, R2 is CI and (R5)n is 2,6-di-F, 3-MeO(CH2)30. R1 is Me, R2 is Me and (R5)n is 2,6-di-F, 3-MeO(CH2)30. R1 is Br, R2 is Br and (R5)n is 2,6-di-F, 3-MeO(CH2)30. Table Number Row Heading
49D Rl is CI, R2 is Me and (R5)n is 2-C1-6-F, 3-MeNH(CH2)30.
50D R1 is CI, R2 is CI and (R5)n is 2-C1-6-F, 3-MeNH(CH2)30.
51D Rl is CI, R2 is Br and (R5)n is 2-C1-6-F, 3-MeNH(CH2)30.
52D Rl is Br, R2 is Me and (R5)n is 2-C1-6-F, 3-MeNH(CH2)30.
53D Rl is Br, R2 is CI and (R5)n is 2-C1-6-F, 3-MeNH(CH2)30.
54D Rl is Me, R - is Me and (R5)n is 6-C1-6-F, 3-MeNH(CH2)30.
55D Rl is Br, R2 is Br and (R5)n is 2-C1-6-F, 3-MeNH(CH2)30.
56D Rl is CI, R2 is Me and (R5)n is 6-C1-2-F, 3-MeNH(CH2)30.
57D Rl is CI, R2 is CI and (R5)n is 6-C1-2-F, 3-MeNH(CH2)30.
58D Rl is CI, R2 is Br and (R5)n is 6-C1-2-F, 3-MeNH(CH2)30.
59D Rl is Br, R2 is Me and (R5)n is 6-C1-2-F, 3-MeNH(CH2)30.
60D Rl is Br, R2 is CI and (R5)n is 6-C1-2-F, 3-MeNH(CH2)30.
61D Rl is Me, R - is Me and (R5)n is 6-C1-2-F, 3-MeNH(CH2)30.
62D Rl is Br, R2 is Br and (R5)n is 6-C1-2-F, 3-MeNH(CH2)30.
Formulation/Utility
A compound selected from compounds of Formula 1, N-oxides, and salts thereof, or a mixture (i.e. composition) comprising the compound with at least one additional fungicidal compound (i.e. fungicide) as described in the Summary of the Invention, will generally be used to provide fungicidal active ingredients in further compositions, i.e. formulations, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredients, mode of application and environmental factors such as soil type, moisture and temperature.
The mixtures of component (a) (i.e. at least one compound of Formula 1, N-oxides, or salts thereof) with component (b) (e.g., selected from (bl) to (b46) and salts thereof as described above) and/or one or more other biologically active compound or agent (i.e. insecticides, other fungicides, nematocides, acaricides, herbicides and other biological agents) can be formulated in a number of ways, including:
(i) component (a), component (b) and/or one or more other biologically active compound or agent can be formulated separately and applied separately or applied simultaneously in an appropriate weight ratio, e.g., as a tank mix; or
(ii) component (a), component (b) and/or one or more other biologically active compound or agent can be formulated together in the proper weight ratio.
Useful formulations include both liquid and solid compositions. Liquid compositions include 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 emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation.
Of note is a composition embodiment wherein granules of a solid composition comprising a compound of Formula 1 (or an N-oxide or salt thereof) is mixed with granules of a solid composition comprising component (b). These mixtures can be further mixed with granules comprising additional agricultural protectants. Alternatively, two or more agricultural protectants (e.g., a component (a) (Formula 1) compound, a component (b) compound, an agricultural protectant other than component (a) or (b)) can be combined in the solid composition of one set of granules, which is then mixed with one or more sets of granules of solid compositions comprising one or more additional agricultural protectants. These granule mixtures can be in accordance with the general granule mixture disclosure of PCT Patent Publication WO 94/24861 or more preferably the homogeneous granule mixture teaching of U.S. Patent 6,022,552.
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 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
Active
Ingredient Diluent Surfactant
Water-Dispersible and Water- 0.001-90 0-99.999 0-15
soluble 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, N,N-dimethylalkanamides (e.g.,
N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-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 isobornyl 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, n-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 C6-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.
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 lignosulfonates; 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 N,N-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 N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, 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 diquaternary 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 compounds 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 μιη can be wet milled using media mills to obtain particles with average diameters below 3 μιη. 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 um 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; Klmgman, 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 Table A. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated. Example A
High Strength Concentrate
Compound 517 49.3% penthiopyrad 49.2% silica aerogel 0.5%> synthetic amorphous fine silica 1.0%
Example B
Wettable Powder
Compound 536 43.0% quinoxyfen 22.0% dodecylphenol polyethylene glycol ether 2.0%> sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0%> montmorillonite (calcined) 23.0%
Example C
Granule
Compound 525 7.5% epoxiconazole 2.5% attapulgite granules (low volatile matter,
0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0%
Example D
Extruded Pellet
Compound 529 8.0% spiroxamine 17.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0%> sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%
Example E
Emulsifiable Concentrate
Compound 520 5.0% azoxystrobin 5.0% polyoxyethylene sorbitol hexoleate 20.0%
C6-C10 fatty acid methyl ester 70.0% Example F
Microemulsion
Compound 516 3.3% picoxystrobin 1.7% polyvinylpyrrolidone-vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0%> glyceryl monooleate 15.0% water 20.0%
Example G
Seed Treatment
Compound 526 4.00% iprodione 16.00%) 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%
Formulations such as those in the Formulation Table are typically diluted with water to form aqueous compositions before application. Aqueous compositions for direct applications to the plant or portion thereof (e.g., spray tank compositions) typically comprise at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of fungicidally active compounds according to the present invention.
Examples of component (b) fungicidal compounds (i.e. fungicides) include acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl, benalaxyl-M, benodanil, benomyl, benthiavalicarb, benthiavalicarb- isopropyl, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper salts such as Bordeaux mixture (tribasic copper sulfate), copper hydroxide and copper oxychloride, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, dithianon, dodemorph, dodine, edifenphos, enestroburin, epoxiconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin chloride, fentin hydroxide, ferbam, ferimzone, fiuazinam, fiudioxonil, flumetover, flumorph, fluopicolide (also known as picobenzamid), fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil (2-[[2-fluoro-5- (trifluoromethyl)phenyl]thio] -2- [3 -(2-methoxyphenyl)-2-thiazolidinylidene] acetonitrile), fiutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminum, fuberidazole, furalaxyl, furametpyr, hexaconazole, hymexazol, guazatine, imazalil, imibenconazole, iminoctadine, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mepronil, meptyldinocap, metalaxyl, metalaxyl-M, metconazole, methasulfocarb, metiram, metominostrobin, mepanipyrim, metrafenone, myclobutanil, naftifine, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, penconazole, pencycuron, penflufen (N-[2- (l,3-dimethylbutyl)phenyl]-5-fluoro-l,3-dimethyl-lH-pyrazol-4-carboxamide),
penthiopyrad, pefurazoate, phosphorous acid and salts, phthalide, picoxystrobin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyrrolnitrin, quinomethionate, quinoxyfen, quintozene, sedaxane, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, tecloftalam, tecnazene, terbinafme, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, triflumizole, tricyclazole, trifloxystrobin, triforine, trimorphamide, triticonazole, uniconazole, validamycin, valifenalate (valiphenal), vinclozolin, zineb, ziram, zoxamide, N'-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5- dimethylphenyl]-N-ethyl-N-methylmethanimidamide, 5-chloro-6-(2,4,6-trifluorophenyl)-7- (4-methylpiperidin- 1 -yl)[ 1 ,2,4]triazolo[ 1 ,5-a]pyrimidine (BAS600), N-[2-[4-[[3-(4- chlorophenyl)-2-propyn- 1 -yl]oxy] -3 -methoxyphenyl] ethyl] -3 -methy 1-2- [(methylsulfonyl)- amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]- ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide, 2-butoxy-6-iodo-3-propyl-4H-l- benzopyran-4-one, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine, 4-fluoro- phenyl N-[l-[[[l-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, N-[[(cyclopropyl- methoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, a-(methoxyimino)-N-methyl-2- [[ [ 1 -[3 -(trifluoromethyl)phenyl] ethoxy]imino]methyl] - benzeneacetamide, N- [4- [4-chloro-3 -(trifluoromethyl)phenoxy] -2,5 -dimethylphenyl]-N- ethyl-N-methylmethanimidamide, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzene- sulfonamide, 2-[[[[3-(2,6-dichlorophenyl)-l-methyl-2-propen-l-ylidene]amino]oxy]methyl]- a-(methoxyimino)-N-methylbenzeneacetamide, l-[(2-propenylthio)carbonyl]-2-(l -methyl- ethyl)-4-(2-methylphenyl)-5-amino-lH-pyrazol-3-one, ethyl-6-octyl-[l,2,4]triazolo[l,5- a]pyrimidin-7-ylamine, pentyl N-[4-[[[[(l -methyl- lH-tetrazol-5-yl)phenylmethylene]- amino]oxy]methyl]-2-thiazolyl]carbamate and pentyl N-[6-[[[[(l-methyl-lH-tetrazol-5-yl)- phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate. Of note is the aforedescribed list excluding fenpyrazamine, fluxapyroxad, pyrametostrobin, pyraoxystrobin, pyriofenone, tebufloquin and valifenalate.
Of note as fungicidal compounds in component (b) of the present composition are azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, pyrametostrobin, pyraoxystrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, pyriofenone, cyflufenamid, fenpropidin, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, fluxapyroxad, hexaconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, famoxadone, prochloraz, penthiopyrad and boscalid (nicobifen). Of further note is the aforedescribed list excluding pyrametostrobin, pyraoxystrobin, pyriofenone and fluxapyroxad.
Generally preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of Formula 1, an N-oxide, or salt thereof, with a fungicidal compound selected from the group: azoxystrobin, kresoxim- methyl, trifloxystrobin, pyraclostrobin, pyrametostrobin, pyraoxystrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidin, fenpropimorph, cyproconazole, difenoconazole, epoxiconazole, flusilazole, metconazole, myclobutanil, propiconazole, proquinazid, prothioconazole, pyriofenone, tebuconazole, triticonazole, famoxadone and penthiopyrad. Of note is the aforedescribed list excluding pyrametostrobin, pyraoxystrobin and pyriofenone.
In the fungicidal compositions of the present invention, component (a) (i.e. at least one compound selected from compounds of Formula 1, N-oxides, and salts thereof) and component (b) are present in fungicidally effective amounts. The weight ratio of component (b) (i.e. one or more additional fungicidal compounds) to component (a) is generally between about 1 :3000 to about 3000: 1, and more typically between about 1 :500 and about 500: 1. Table Bl lists typical, more typical and most typical ranges of ratios involving particular fungicidal compounds of component (b). Tables Al through A27 and CI through C27 exemplify weight ratios for particular combinations of fungicidal compounds. Of note are compositions where in the weight ratio of component (a) to component (b) is from about 125:1 to about 1 : 125. With many fungicidal compounds of component (b), these compositions are particularly effective for controlling plant diseases caused by fungal plant pathogens. Of particular note are compositions wherein the weight ratio of component (a) to component (b) is from about 25:1 to about 1:25, or from about 5:1 to about 1:5. One skilled in the art can easily determine through simple experimentation the weight ratios and application rates of fungicidal compounds necessary for the desired spectrum of fungicidal protection and control. It will be evident that including additional fungicidal compounds in component (b) may expand the spectrum of plant diseases controlled beyond the spectrum controlled by component (a) alone.
Specific mixtures (compound numbers refer to compounds in Index Table A) are listed in Tables Al through A27. In Table Al, each line below the column headings "Component (a)" and "Component (b)" specifically discloses a mixture of Component (a), which is Compound 181, with a Component (b) fungicidal compound. The entries under the heading "Illustrative Ratios" disclose three specific weight ratios of Component (b) to Component (a) for the disclosed mixture. For example, the first line of Table Al discloses a mixture of Compound 181 with acibenzolar-S-methyl and lists weight ratios of acibenzolar-S-methyl to Compound 181 of 1:1 , 1:4 or 1:18.
Table Al
Component (a) Component (b) Illustrative Ratios(*)
Compound 181 acibenzolar-iS-methyl 1:1 1:4 1:18
Compound 181 aldimorph 7:1 3:1 1:1
Compound 181 ametoctradin 3:1 1:1 1:3
Compound 181 amisulbrom 1:1 1:2 1:6
Compound 181 anilazine 22:1 8:1 4:1
Compound 181 azaconazole 2:1 1:2 1:4
Compound 181 azoxystrobin 3:1 1:1 1:3
Compound 181 benalaxyl 1:1 1:2 1:6
Compound 181 benalaxyl-M 1:1 1:3 1:8
Compound 181 benodanil 4:1 2:1 1:2
Compound 181 benomyl 11:1 4:1 1:1
Compound 181 benthiavalicarb 1:1 1:4 1:12
Compound 181 benthiavalicarb-isopropyl 1:1 1:4 1:12
Compound 181 bethoxazin 15:1 5:1 2:1
Compound 181 binapacryl 15:1 5:1 2:1
Compound 181 biphenyl 15:1 5:1 2:1
Compound 181 bitertanol 3:1 1:1 1:2
Compound 181 bixafen 2:1 1:1 1:3
Compound 181 blasticidin-S 1:4 1:12 1:30
Compound 181 Bordeaux mixture (tribasic copper sulfate) 45:1 15:1 5:1
Compound 181 boscalid 4:1 2:1 1:2
Compound 181 bromuconazole 3:1 1:1 1:3 Compound 18! bupirimate 1:3 1: 10 1:30
Compound 18! captafol 15: 1 5:1 2:1
Compound 18 captan 15: 1 5:1 2:1
Compound 18! carbendazim 11:1 4:1 2:1
Compound 18! carboxin 4:1 2:1 1:2
Compound 18! carpropamid 3:1 1:1 1:3
Compound 18! chloroneb 100:1 35:1 14:1
Compound 18! chlorothalonil 15: 1 5:1 2:1
Compound 18! chlozolinate 11: 1 4:1 2:1
Compound 18! clotrimazole 3:1 1:1 1:3
Compound 18! copper hydroxide 45: 1 15: 1 5:1
Compound 18! copper oxychloride 45: 1 15: 1 5:1
Compound 18! cyazofamid 1: 1 1:2 1:6
Compound 18! cyflufenamid 1:2 1:6 1:24
Compound 18! cymoxanil 1:1 1:2 1:5
Compound 18! cyproconazole 1:1 1:2 1:6
Compound 18! cyprodinil 4:1 2:1 1:2
Compound 18! dichloiluanid 15:1 5:1 2:1
Compound 18! diclocymet 15: 1 5:1 2:1
Compound 18! diclomezine 3: 1 1:1 1:3
Compound 18! dicloran 15:1 5:1 2:1
Compound 18! diethofencarb 7:1 2:1 1:2
Compound 18! difenoconazole 1:1 1:3 1: 12
Compound 18! diflumetorim 15:1 5:1 2:1
Compound 18! dimethirimol 1:3 1:8 1:30
Compound 18! dimethomorph 3:1 1:1 1:2
Compound 18! dimoxystrobin 2:1 1:1 1:4
Compound 18! diniconazole 1:1 1:3 1:8
Compound 18! diniconazole-M 1:1 1:3 1: 12
Compound 18! dinocap 2:1 1:1 1:3
Compound 18! dithianon 5:1 2:1 1:2
Compound 18! dodemorph 7:1 3:1 1:1
Compound 18! dodine 10:1 4:1 2:1
Compound 18! edifenphos 3:1 1:1 1:3
Compound 18! enestroburin 2: 1 1:1 1:4
Compound 18! epoxiconazole 1:1 1:3 1:7
Compound 18! ethaboxam 2:1 1:1 1:3
Compound 18! ethirimol 7:1 3:1 1:1 Compound 18! etridiazole 7:1 2:1 1:2
Compound 18 famoxadone 2:1 1:1 1:4
Compound 18 fenamidone 2:1 1:1 1:4
Compound 18! fenarimol 1:2 1:7 1:24
Compound 18! fenbuconazole 1:1 1:3 1: 10
Compound 18! fenfuram 4:1 1:1 1:2
Compound 18! fenhexamid 10: 1 4:1 2:1
Compound 18! fenoxanil 15:1 4:1 1:1
Compound 18! fenpiclonil 15: 1 5:1 2:1
Compound 18! fenpropidin 7:1 2:1 1:1
Compound 18! fenpropimorph 7:1 2:1 1:1
Compound 18! fenpyrazamine 3: 1 1: 1 1:3
Compound 18! fentin salt such as fentin acetate, fentin chloride or fentin 3:1 1:1 1:3 hydroxide
Compound 18! ferbam 30: 1 10: 1 4:1
Compound 18! ferimzone 7:1 2:1 1:2
Compound 18! fluazinam 3:1 1:1 1:2
Compound 18! fludioxonil 2:1 1:1 1:4
Compound 18! flumetover 3:1 1:1 1:2
Compound 18! flumorph 3:1 1:1 1:3
Compound 18! fluopicolide 1:1 1:2 1:6
Compound 18! fluopyram 3:1 1:1 1:3
Compound 18! iluoroimide 37:1 14:1 5:1
Compound 18! fluoxastrobin 1:1 1:2 1:6
Compound 18! fluquinconazole 1:1 1:2 1:4
Compound 18! flusilazole 3:1 1:1 1:3
Compound 18! ilusulfamide 15: 1 5:1 2:1
Compound 18! flutianil 1:1 1:2 1:6
Compound 18! flutolanil 4:1 1:1 1:2
Compound 18! flutriafol 1:1 1:2 1:4
Compound 18! fluxapyroxad 2:1 1:1 1:3
Compound 18! folpet 15:1 5:1 2:1
Compound 18! fosetyl-aluminum 30: 1 12: 1 5:1
Compound 18! fuberidazole 11:1 4: 1 2:1
Compound 18! furalaxyl 1:1 1:2 1:6
Compound 18! furametpyr 15: 1 5:1 2:1
Compound 18! guazatine 15: 1 5:1 2:1
Compound 18! hexaconazole 1: 1 1:2 1:5 Compound 18 hymexazol 75: 1 25: 1 9:1
Compound 18 imazalil 1: 1 1:2 1:5
Compound 18 imibenconazole 1: 1 1:2 1:5
Compound 18 iminoctadine 15: 1 4:1 1:1
Compound 18 iodocarb 15: 1 5:1 2:1
Compound 18 ipconazole 1:1 1:2 1:5
Compound 18 iprobenfos 15:1 5:1 2:1
Compound 18 iprodione 15: 1 5:1 2:1
Compound 18 iprovalicarb 2:1 1:1 1:3
Compound 18 isoprothiolane 45:1 15:1 5:1
Compound 18 isopyrazam 2:1 1:1 1:3
Compound 18 isotianil 2:1 1:1 1:3
Compound 18 kasugamycin 1:2 1:7 1:24
Compound 18 kre soxim-methyl 2:1 1:1 1:4
Compound 18 mancozeb 22: 1 7:1 3:1
Compound 18 mandipropamid 2:1 1:1 1:4
Compound 18 maneb 22: 1 7:1 3:1
Compound 18 mepanipyrim 6:1 2:1 1:1
Compound 18 mepronil 1:1 1:2 1:6
Compound 18 meptyldinocap 2:1 1:1 1:3
Compound 18 metalaxyl 1:1 1:2 1:6
Compound 18 metalaxyl-M 1:1 1:4 1: 12
Compound 18 metconazole 1:1 1:2 1:6
Compound 18 methasulfocarb 15: 1 5:1 2:1
Compound 18 metiram 15:1 5:1 2:1
Compound 18 metominostrobin 3:1 1:1 1:3
Compound 18 metrafenone 2:1 1:1 1:4
Compound 18 myclobutanil 1:1 1:3 1:8
Compound 18 naftifine 15: 1 5:1 2:1
Compound 18 neo-asozin (ferric methanearsonate) 15:1 5:1 2:1
Compound 18 nuarimol 3:1 1:1 1:3
Compound 18 octhilinone 15:1 4: 1 1: 1
Compound 18 ofurace 1:1 1:2 1:6
Compound 18 orysastrobin 3:1 1:1 1:3
Compound 18 oxadixyl 1:1 1:2 1:6
Compound 18 oxolinic acid 7:1 2:1 1:2
Compound 18 oxpoconazole 1:1 1:2 1:5
Compound 18 oxycarboxin 4:1 1:1 1:2 Compound 18 oxytetracycline 3: 1 1:1 1:3
Compound 18 pefurazoate 15: 1 5:1 2:1
Compound 18 penconazole 1:2 1:6 1: 15
Compound 18 pencycuron 11: 1 4:1 2:1
Compound 18 penflufen (TV- [2-( 1 , 3 -dimethylbutyl)phenyl] -5 -fluoro- 1,3- 2:1 1:1 1:3 dimethyl-lii-pyrazol-4-carboxamide)
Compound 18 penthiopyrad 2:1 1:1 1:3
Compound 18 phosphorous acid or a salt thereof 15: 1 6:1 2:1
Compound 18 phthalide 15: 1 6:1 2:1
Compound 18 picoxystrobin 1:1 1:2 1:5
Compound 18 piperalin 3:1 1:1 1:3
Compound 18 polyoxin 3:1 1:1 1:3
Compound 18 probenazole 3:1 1:1 1:3
Compound 18 prochloraz 7:1 2:1 1:2
Compound 18 procymidone 11: 1 4:1 2:1
Compound 18 propamocarb or propamocarb-hydrochloride 10:1 4:1 2:1
Compound 18 propiconazole 1:1 1:2 1:5
Compound 18 propineb 11:1 4:1 2:1
Compound 18 proquinazid 1:1 1:3 1: 12
Compound 18 prothiocarb 3:1 1:1 1:3
Compound 18 prothioconazole 1:1 1:2 1:5
Compound 18 pyraclostrobin 2:1 1:1 1:4
Compound 18 pyrametostrobin 2:1 1:1 1:4
Compound 18 pyraoxystrobin 2:1 1:1 1:4
Compound 18 pyrazophos 15: 1 4:1 1:1
Compound 18 pyribencarb 4:1 1:1 1:2
Compound 18 pyributicarb 15: 1 4:1 1:1
Compound 18 pyrifenox 3:1 1:1 1:3
Compound 18 pyrimethanil 3:1 1:1 1:2
Compound 18 pyriofenone 2:1 1:1 1:4
Compound 18 pyroquilon 3:1 1:1 1:3
Compound 18 pyrrolnitrin 15:1 5:1 2:1
Compound 18 quinomethionate 15: 1 5:1 2:1
Compound 18 quinoxyfen 1:1 1:2 1:6
Compound 18 quintozene 15: 1 5:1 2:1
Compound 18 silthiofam 2:1 1:1 1:4
Compound 18 simeconazole 1: 1 1:2 1:5
Compound 18 spiroxamine 5:1 2:1 1:2 Compound 181 streptomycin 3:1 1:1 1:3
Compound 181 sulfur 75:1 25:1 9:1
Compound 181 tebuconazole 1:1 1:2 1:5
Compound 181 tebufloquin 3:1 1:1 1:3
Compound 181 tecloftalam 15:1 5:1 2:1
Compound 181 tecnazene 15:1 5:1 2:1
Compound 181 terbinafine 15:1 5:1 2:1
Compound 181 tetraconazole 1:1 1:2 1:5
Compound 181 thiabendazole 11:1 4:1 2:1
Compound 181 thifluzamide 3:1 1:1 1:3
Compound 181 thiophanate 11:1 4:1 2:1
Compound 181 thiophanate -methyl 11:1 4:1 2:1
Compound 181 thiram 37:1 14:1 5:1
Compound 181 tiadinil 2:1 1:1 1:3
Compound 181 tolclofos-methyl 37:1 14:1 5:1
Compound 181 tolylfluanid 15:1 5:1 2:1
Compound 181 triadimefon 1:1 1:2 1:5
Compound 181 triadimenol 1:1 1:2 1:5
Compound 181 triazoxide 15:1 5:1 2:1
Compound 181 tricyclazole 3:1 1:1 1:3
Compound 181 tridemorph 7:1 2:1 1:1
Compound 181 trifloxystrobin 2:1 1:1 1:4
Compound 181 triflumizole 3:1 1:1 1:3
Compound 181 triforine 3:1 1:1 1:3
Compound 181 trimo hamide 7:1 2:1 1:2
Compound 181 triticonazole 1:1 1:2 1:5
Compound 181 uniconazole 1:1 1:2 1:5
Compound 181 validamycin 3:1 1:1 1:3
Compound 181 valifenalate (valiphenal) 2:1 1:1 1:4
Compound 181 vinclozolin 15:1 6:1 2:1
Compound 181 zineb 37:1 14:1 5:1
Compound 181 ziram 37:1 14:1 5:1
Compound 181 zoxamide 2:1 1:1 1:4
Compound 181 5 - chloro- 6 - (2 ,4 , 6 -trifluorophenyl) - 7 - (4 -methylpiperidin- 1:1 1:2 1:6
1 -yl)[ 1 ,2,4]triazolo[l ,5-a]pyrimidine
Compound 181 N-[2-[4-[[3-(4- chlorophenyl) -2 -propyn- 1 -yl] oxy ] -3 -methoxy- 2:1 1:1 1:4 phenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]- butanamide Compound 181 ^-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3-methoxy- phenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide
Compound 181 2-butoxy-6-iodo-3-propyl-4 /-l-benzopyran-4-one
Compound 181 3 - [ 5 - (4 - chlorophenyl) -2,3 -dimethyl- 3 -isoxazolidinyl] - pyridine
Compound 181 4 -fluorophenyl N-[l-[[[l-(4-cyanophenyl)ethyl]sulfonyl]- methyl]propyl]carbamate
Compound 181 A^-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-
2,3-difluorophenyl]methylene]benzeneacetamide
Compound 181 c - [methoxyimino] -N-methyl-2- [ [ [ 1 - [3 -(trifluoromethyl)- phenyl] ethoxy ] imino] methyl] benzene acetamide
Compound 181 A^-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5- dimethylphenyl]-A^-ethyl-A^-methylmethanimidamide
Compound 181 A^-(4-chloro-2-nitrophenyl)-A^-ethyl-4-methylbenzene- sulfonamide
Compound 181 2-[[[3 -(2,6-dichlorophenyl)- 1 -methyl-2-propen- 1 -ylidene] - amino] oxy ] methyl] - a- (methoxyimino) - V-methylbenzene - acetamide
Compound 181 pentyl N-[4-[[[[(l -methyl- l#-tetrazol-5-yl)phenyl- methylene] amino]oxy]methyl] -2-thiazolyl] carbamate
Compound 181 pentyl N-[6-[[[[(l -methyl- l /-tetrazol-5-yl)phenyl- methylene]amino]oxy]methyl]-2-pyridinyl]carbamate
(*) Ratios of Component (b) relative to Component (a) by weight.
Tables A2 through A27 are each constructed the same as Table Al above except that entries below the "Component (a)" column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table A2 the entries below the "Component (a)" column heading all recite "Compound 292", and the first line below the column headings in Table A2 specifically discloses a mixture of Compound 292 with acibenzolar-S-methyl. Tables A3 throug A27 are constructed similarly.
Table Number Component (a) Column Entries Table Number Component (a) Column Entries
A2 Compound 292 A15 Compound 524
A3 Compound 469 A16 Compound 525
A4 Compound 513 A17 Compound 526
A5 Compound 514 A18 Compound 527
A6 Compound 515 A19 Compound 528
A7 Compound 516 A20 Compound 529
A8 Compound 517 A21 Compound 530
A9 Compound 518
Figure imgf000129_0001
A22 Compound 531 A10 Compound 519 A23 Compound 532 All Compound 520 A24 Compound 533 A12 Compound 521 A25 Compound 534 A13 Compound 522 A26 Compound 535 A14 Compound 523 A27 Compound 536
Table B 1 lists specific combinations of a Component (b) compound with Component (a) illustrative of the mixtures, compositions and methods of the present invention. The first column of Table Bl lists the specific Component (b) compound (e.g., "acibenzolar-S- methyl" in the first line). The second, third and fourth columns of Table Bl lists ranges of weight ratios for rates at which the Component (b) compound is typically applied to a field- grown crop relative to Component (a) (e.g., "2:1 to 1:180" of acibenzolar-S-methyl relative to Component (a) by weight). Thus, for example, the first line of Table Bl specifically discloses the combination of acibenzolar-S-methyl with Component (a) is typically applied in a weight ratio between 2:1 to 1:180. The remaining lines of Table Bl are to be construed similarly. Of particular note is a composition comprising a mixture of any one of the compounds listed in Embodiment 38 as Component (a) with a compound listed in the Component (b) column of Table Bl according to the weight ratios disclosed in Table Bl. Table Bl thus supplements the specific ratios disclosed in Tables Al through A27 with ranges of ratios for these combinations.
Table Bl
Component (b) Typical More Typical Most Typical
Weight Ratio Weight Ratio Weight Ratio acibenzolar-iS-methyl 2:1 to 1:180 1:1 to 1:60 1:1 to 1:18 aldimorph 30:1 to 1:3 10:1 to 1:1 7:1 to 1:1 ametoctradin 9:1 to 1:18 3:1 to 1:6 3:1 to 1:3 amisulbrom 6:1 to 1:18 2:1 to 1:6 1:1 to 1:6 anilazine 90:1 to 2:1 30:1 to 4:1 22:1 to 4:1 azaconazole 7:1 to 1:18 2:1 to 1:6 2:1 to 1:4 azoxystrobin 9:1 to 1:12 3:1 to 1:4 3:1 to 1:3 benalaxyl 4:1 to 1:18 1:1 to 1:6 1:1 to 1:6 benalaxyl-M 4:1 to 1:36 1:1 to 1:12 1:1 to 1:8 benodanil 18:1 to 1:6 6:1 to 1:2 4:1 to 1:2 benomyl 45:1 to 1:4 15:1 to 1:1 11:1 to 1:1 benthiavalicarb or benthiavalicarb-
2:1 to 1:36 1:1 to 1:12 1:1 to 1:12 isopropyl
bethoxazin 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 binapacryl 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 Component (b) Typical More Typical Most Typical
Weight Ratio Weight Ratio Weight Ratio biphenyl 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 bitertanol 15:1 to 1:5 5:1 to 1:2 3:1 to 1:2 bixafen 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3 blasticidin-S 3:1 to 1:90 1:1 to 1:30 1:4 to 1:30 boscalid 18:1 to 1:6 6:1 to 1:2 4:1 to 1:2 bromuconazole 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 bupirimate 3:1 to 1:90 1:1 to 1:30 1:3 to 1:30 captafol 90:1 to 1:4 30:1 to 1:2 15:1 to 2:1 captan 90:1 to 1:4 30:1 to 1:2 15:1 to 2:1 carbendazim 45:1 to 1:4 15:1 to 1:2 11:1 to 2:1 carboxin 18:1 to 1:6 6:1 to 1:2 4:1 to 1:2 carpropamid 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 chloroneb 300:1 to 2:1 100:1 to 4:1 100:1 to 14:1 chlorothalonil 90:1 to 1:4 30:1 to 1:2 15:1 to 2:1 chlozolinate 45:1 to 1:2 15:1 to 2:1 11:1 to 2:1 clotrimazole 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 copper salts such as Bordeaux mixture
(tribasic copper sulfate), copper
450:1 to 1:1 150:1 to 4:1 45:1 to 5:1 oxychloride, copper sulfate and copper
hydroxide
cyazofamid 4:1 to 1:18 1:1 to 1:6 1:1 to 1:6 cyflufenamid 1:1 to 1:90 1:2 to 1:30 1:2 to 1:24 cymoxanil 6:1 to 1:18 2:1 to 1:6 1:1 to 1:5 cyproconazole 4:1 to 1:18 1:1 to 1:6 1:1 to 1:6 cyprodinil 22:1 to 1:9 7:1 to 1:3 4:1 to 1:2 dichlofluanid 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 diclocymet 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 diclomezine 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 dicloran 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 diethofencarb 22:1 to 1:9 7:1 to 1:3 7:1 to 1:2 difenoconazole 4:1 to 1:36 1:1 to 1:12 1:1 to 1:12 diflumetorim 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 dimethirimol 3:1 to 1:90 1:1 to 1:30 1:3 to 1:30 dimethomorph 9:1 to 1:6 3:1 to 1:2 3:1 to 1:2 dimoxystrobin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4 Component (b) Typical More Typical Most Typical
Weight Ratio Weight Ratio Weight Ratio diniconazole 3:1 to 1:36 1:1 to 1:12 1:1 to 1:8 diniconazole M 3:1 to 1:90 1:1 to 1:30 1:1 to 1:12 dinocap 7:1 to 1:9 2:1 to 1:3 2:1 to 1:3 dithianon 15:1 to 1:4 5:1 to 1:2 5:1 to 1:2 dodemorph 30:1 to 1:3 10:1 to 1:1 7:1 to 1:1 dodine 30:1 to 1:2 10:1 to 2:1 10:1 to 2:1 edifenphos 30:1 to 1:9 10:1 to 1:3 3:1 to 1:3 enestroburin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4 epoxiconazole 3:1 to 1:36 1:1 to 1:12 1:1 to 1:7 ethaboxam 7:1 to 1:9 2:1 to 1:3 2:1 to 1:3 ethirimol 30:1 to 1:3 10:1 to 1:1 7:1 to 1:1 etridiazole 30:1 to 1:9 10:1 to 1:3 7:1 to 1:2 famoxadone 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4 fenamidone 6:1 to 1:18 2:1 to 1:6 2:1 to 1:4 fenarimol 3:1 to 1:90 1:1 to 1:30 1:2 to 1:24 fenbuconazole 3:1 to 1:30 1:1 to 1:10 1:1 to 1:10 fenfuram 18:1 to 1:6 6:1 to 1:2 4:1 to 1:2 fenhexamid 30:1 to 1:2 10:1 to 2:1 10:1 to 2:1 fenoxanil 150:1 to 1:36 50:1 to 1:12 15:1 to 1:1 fenpiclonil 75:1 to 1:9 25:1 to 1:3 15:1 to 2:1 fenpropidin 30:1 to 1:3 10:1 to 1:1 7:1 to 1:1 fenpropimorph 30:1 to 1:3 10:1 to 1:1 7:1 to 1:1 fentin salt such as the acetate, chloride or
15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 hydroxide
ferbam 300:1 to 1:2 100:1 to 2:1 30:1 to 4:1 ferimzone 30:1 to 1:5 10:1 to 1:2 7:1 to 1:2 fluazinam 22:1 to 1:5 7:1 to 1:2 3:1 to 1:2 fludioxonil 7:1 to 1:12 2:1 to 1:4 2:1 to 1:4 flumetover 9:1 to 1:6 3:1 to 1:2 3:1 to 1:2 flumorph 9:1 to 1:18 3:1 to 1:6 3:1 to 1:3 fluopicolide 3:1 to 1:18 1:1 to 1:6 1:1 to 1:6 fluopyram 15:1 to 1:90 5:1 to 1:30 3:1 to 1:3 fluoromide 150:1 to 2:1 50:1 to 4:1 37:1 to 5:1 fluoxastrobin 4:1 to 1:18 1:1 to 1:6 1:1 to 1:6 fluquinconazole 4:1 to 1:12 1:1 to 1:4 1:1 to 1:4 Component (b) Typical More Typical Most Typical Weight Ratio Weight Ratio Weight Ratio flusilazole 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 flusulfamide 90:1 to 1:2 30:1 to 2:1 15:1 to 2:1 flutianil 7:1 to 1:36 2:1 to 1:12 1:1 to 1:6 flutolanil 18:1 to 1:6 6:1 to 1:2 4:1 to 1:2 flutriafol 4:1 to 1:12 1:1 to 1:4 1:1 to 1:4 iluxapyroxad 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3 folpet 90:1 to 1:4 30:1 to 1:2 15:1 to 2:1 fosetyl-aluminum 225:1 to 2:1 75:1 to 5:1 30:1 to 5:1 fuberidazole 45:1 to 1:4 15:1 to 1:2 11:1 to 2:1 furalaxyl 15:1 to 1:45 5:1 to 1:15 1:1 to 1:6 furametpyr 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 guazatine or iminoctadine 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 hexaconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 hymexazol 225:1 to 2:1 75:1 to 4:1 75:1 to 9:1 imazalil 7:1 to 1:18 2:1 to 1:6 1:1 to 1:5 imibenconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 iodocarb 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 ipconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 iprobenfos 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 iprodione 120:1 to 1:2 40:1 to 2:1 15:1 to 2:1 iprovalicarb 9:1 to 1:9 3:1 to 1:3 2:1 to 1:3 isoprothiolane 150:1 to 2:1 50:1 to 4:1 45:1 to 5:1 isopyrazam 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3 isotianil 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3 kasugamycin 7:1 to 1:90 2:1 to 1:30 1:2 to 1:24 kresoxim-methyl 7:1 to 1:18 2:1 to 1:6 2:1 to 1:4 mancozeb 180:1 to 1:3 60:1 to 2:1 22:1 to 3:1 mandipropamid 6:1 to 1:18 2:1 to 1:6 2:1 to 1:4 maneb 180:1 to 1:3 60:1 to 2:1 22:1 to 3:1 mepanipyrim 18:1 to 1:3 6:1 to 1:1 6:1 to 1:1 mepronil 7:1 to 1:36 2:1 to 1:12 1:1 to 1:6 meptyldinocap 7:1 to 1:9 2:1 to 1:3 2:1 to 1:3 metalaxyl 15:1 to 1:45 5:1 to 1:15 1:1 to 1:6 metalaxyl-M 7:1 to 1:90 2:1 to 1:30 1:1 to 1:12 metconazole 3:1 to 1:18 1:1 to 1:6 1:1 to 1:6 Component (b) Typical More Typical Most Typical
Weight Ratio Weight Ratio Weight Ratio methasulfocarb 150:1 to 1:36 50:1 to 1:12 15:1 to 1:1 metiram 150:1 to 1:36 50:1 to 1:12 15:1 to 1:1 metominostrobin 9:1 to 1:12 3:1 to 1:4 3:1 to 1:3 metrafenone 6:1 to 1:12 2:1 to 1:4 2:1 to 1:4 myclobutanil 5:1 to 1:26 1:1 to 1:9 1:1 to 1:8 naftifine 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 neo-asozin (ferric methanearsonate) 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 nuarimol 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 octhilinone 150:1 to 1:36 50:1 to 1:12 15:1 to 1:1 ofurace 15:1 to 1:45 5:1 to 1:15 1:1 to 1:6 orysastrobin 9:1 to 1:12 3:1 to 1:4 3:1 to 1:3 oxadixyl 15:1 to 1:45 5:1 to 1:15 1:1 to 1:6 oxolinic acid 30:1 to 1:9 10:1 to 1:3 7:1 to 1:2 oxpoconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 oxycarboxin 18:1 to 1:6 6:1 to 1:2 4:1 to 1:2 oxytetracycline 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 pefurazoate 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 penconazole 1:1 to 1:45 1:2 to 1:15 1:2 to 1:15 pencycuron 150:1 to 1:2 50:1 to 2:1 11:1 to 2:1 penflufen (N-[2-(l,3-dimethylbutyl)- phenyl] -5-fluoro- 1 ,3 -dimethyl- l /-pyrazol- 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3
4-carboxamide)
penthiopyrad 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3 phosphorous acid and salts thereof 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 phthalide 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 picoxystrobin 7:1 to 1:18 2:1 to 1:6 1:1 to 1:5 piperalin 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 polyoxin 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 probenazole 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 prochloraz 22:1 to 1:4 7:1 to 1:1 7:1 to 1:2 procymidone 45:1 to 1:3 15:1 to 1:1 11:1 to 2:1 propamocarb or propamocarb-
30:1 to 1:2 10:1 to 2:1 10:1 to 2:1 hydrochloride
propiconazole 4:1 to 1:18 1:1 to 1:6 1:1 to 1:5 propineb 45:1 to 1:2 15:1 to 2:1 11:1 to 2:1 Component (b) Typical More Typical Most Typical Weight Ratio Weight Ratio Weight Ratio proquinazid 3:1 to 1:36 1:1 to 1:12 1:1 to 1:12 prothiocarb 9:1 to 1:18 3:1 to 1:6 3:1 to 1:3 prothioconazole 6:1 to 1:18 2:1 to 1:6 1:1 to 1:5 pyraclostrobin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4 pyrametostrobin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4 pyraoxystrobin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4 pyrazophos 150:1 to 1:36 50:1 to 1:12 15:1 to 1:1 pyribencarb 15:1 to 1:6 5:1 to 1:2 4:1 to 1:2 pyrifenox 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 pyrimethanil 30:1 to 1:6 10:1 to 1:2 3:1 to 1:2 pyriofenone 6:1 to 1:12 2:1 to 1:4 2:1 to 1:4 pyroquilon 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 pyrrolnitrin 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 quinmethionate 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 quinoxyfen 4:1 to 1:18 1:1 to 1:6 1:1 to 1:6 quintozene 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 silthiofam 7:1 to 1:18 2:1 to 1:6 2:1 to 1:4 simeconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 spiroxamine 22:1 to 1:4 7:1 to 1:2 5:1 to 1:2 streptomycin 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 sulfur 300:1 to 3:1 100:1 to 9:1 75:1 to 9:1 tebuconazole 7:1 to 1:18 2:1 to 1:6 1:1 to 1:5 tebufloquin 100:1 to 1:100 10:1 to 1:10 3:1 to 1:3 tecloftalam 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 tecnazene 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 terbinafine 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 tetraconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 thiabendazole 45:1 to 1:4 15:1 to 1:2 11:1 to 2:1 thifluzamide 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 thiophanate 45:1 to 1:3 15:1 to 2:1 11:1 to 2:1 thiophanate -methyl 45:1 to 1:3 15:1 to 2:1 11:1 to 2:1 thiram 150:1 to 1:2 50:1 to 2:1 37:1 to 5:1 tiadinil 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3 tolclofos-methyl 150:1 to 1:2 50:1 to 2:1 37:1 to 5:1 tolylfluanid 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 Component (b) Typical More Typical Most Typical
Weight Ratio Weight Ratio Weight Ratio triadimefon 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 triadimenol 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 triazoxide 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1 tricyclazole 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 tridemorph 30:1 to 1:3 10:1 to 1:1 7:1 to 1:1 trifloxystrobin 6:1 to 1:18 2:1 to 1:6 2:1 to 1:4 triflumizole 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 triforine 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 trimo hamide 45:1 to 1:9 15:1 to 1:3 7:1 to 1:2 triticonazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 uniconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5 validamycin 150:1 to 1:36 50:1 to 1:12 3:1 to 1:3 valifenalate (valiphenal) 6:1 to 1:18 2:1 to 1:6 2:1 to 1:4 vinclozolin 120:1 to 1:2 40:1 to 2:1 15:1 to 2:1 zineb 150:1 to 1:2 50:1 to 2:1 37:1 to 5:1 ziram 150:1 to 1:2 50:1 to 2:1 37:1 to 5:1 zoxamide 6:1 to 1:18 2:1 to 1:6 2:1 to 1:4
5-chloro-6-(2,4,6-trifluorophenyl)- 7-(4-methylpiperidin- 1 -yl)[ 1 ,2,4]triazolo- 15:1 to 1:36 5:1 to 1:12 1:1 to 1:6
[l,5-a]pyrimidine
N- [2 - [4 - [ [ 3 - (4 - chlorophenyl) -2 -propyn- 1 -yl] oxy] -3 -methoxyphenyl] ethyl] -
6:1 to 1:18 2:1 to 1:6 2:1 to 1:4 3-methyl-2-[(methylsulfonyl)amino]- butanamide
A-[2-[4-[[3-(4-chlorophenyl)-2-propyn- 1 - yl] oxy ] - 3 -methoxyphenyl] ethyl] - 3 -methyl- 6:1 to 1:18 2:1 to 1:6 2:1 to 1:4 2 - [ (ethylsulfonyl) amino] butanamide
2-butoxy-6-iodo-3 -propyl-4 /- 1 -
3:1 to 1:36 1:1 to 1:12 1:1 to 1:12 benzopyran-4-one
3 - [ 5 - (4 - chlorophenyl) -2,3 -dimethyl- 3 -
15:1 to 1:9 5:1 to 1:3 3:1 to 1:3 isoxazolidinyl]pyridine
4-fluorophenyl N-[ 1 -[[[ 1 -(4-cyanophenyl)-
6:1 to 1:18 2:1 to 1:6 2:1 to 1:4 ethyl]sulfonyl]methyl]propyl]carbamate
N- [ [ (cy clopropylmethoxy) amino] [ 6 - (difluoromethoxy)-2,3-difluorophenyl]- 1:1 to 1:90 1:2 to 1:30 1:2 to 1:24 methylene]benzeneacetamide Component (b) Typical More Typical Most Typical
Weight Ratio Weight Ratio Weight Ratio a- [methoxyimino] -N-methyl-2- [ [ [ 1 - [3 - (trifluoromethyl)phenyl]ethoxy]imino]- 9:1 to 1:18 3:1 to 1:6 3:1 to 1:3 methyl] benzene acetamide
A"-[4-[4-chloro-3-(trifluoromethyl)- phenoxy] -2,5-dimethylphenyl] -N-ethyl- 15:1 to 1:18 5:1 to 1:6 3:1 to 1:3 A-methylmethanimidamide
A-(4-chloro-2-nitrophenyl)-A-ethyl-
15:1 to 1:18 5:1 to 1:6 3:1 to 1:3 4-methylbenzenesulfonamide
2-[[[3-(2,6-dichlorophenyl)- 1 -methyl- 2-propen- 1 -ylidene] amino]oxy]methyl] -
9:1 to 1:18 3:1 to 1:6 3:1 to 1:3 a - (methoxyimino) - A-methylbenzeneacetamide
pentyl N-[4-[[[[(l -methyl- l /-tetrazol- 5 -yl)phenylmethylene] amino] oxy]methyl] - 9:1 to 1:18 3:1 to 1:6 3:1 to 1:3 2-thiazolyl] carbamate
pentyl N-[6-[[[[(l -methyl- l /-tetrazol- 5 -yl)phenylmethylene] amino] oxy]methyl] - 9:1 to 1:18 3:1 to 1:6 3:1 to 1:3 2-pyridinyl] carbamate
As already noted, the present invention includes embodiments wherein in the composition comprising components (a) and (b), component (b) comprises at least one fungicide from each of two groups selected from (bl) through (b46). Tables CI through C27 list specific mixtures (compound numbers refer to compounds in Index Table A) to illustrate embodiments wherein component (b) includes at least one fungicide from each of two groups selected from (bl) through (b46). In Table CI, each line below the column headings "Component (a)" and "Component (b)" specifically discloses a mixture of Component (a), which is Compound 181, with at least two Component (b) fungicides. The entries under the heading "Illustrative Ratios" disclose three specific weight ratios of Component (a) to each Component (b) fungicide in sequence for the disclosed mixture. For example, the first line discloses a mixture of Compound 181 with cyproconazole and azoxystrobin and lists weight ratios of Compound 181 to cyproconazole to azoxystrobin of 1:1:1 ,2:1:1 or 3:1:1.
Table CI
Component (a) Component (b) Illustrative Ratios(*)
Compound 181 cyproconazole azoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 cyproconazole kresoxim-methyl 1:1:1 2:1:1 3:1:1
Compound 181 cyproconazole picoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 cyproconazole pyraclostrobin 1:1:1 2:1:1 3:1:1 Component (a) Component (b) Illustrative Ratios(*)
Compound 181 cyproconazole pyrametostrobin 1:1:1 2:1:1 3:1:1
Compound 181 cyproconazole pyraoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 cyproconazole trifloxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 cyproconazole bixafen 1:1:2 2:1:2 3:1:2
Compound 181 cyproconazole boscalid 1:1:2 2:1:2 3:1:2
Compound 181 cyproconazole cyflufenamid 1:2:1 2:2:1 3:2:1
Compound 181 cyproconazole fluopyram 1:1:2 2:1:2 3:1:2
Compound 181 cyproconazole isopyrazam 1:1:2 2:1:2 3:1:2
Compound 181 cyproconazole metrafenone 1:1:2 2:1:2 3:1:2
Compound 181 cyproconazole penthiopyrad 1:1:2 2:1:2 3:1:2
Compound 181 cyproconazole proquinazid 1:1:1 2:1:1 3:1:1
Compound 181 cyproconazole pyriofenone 1:1:2 2:1:2 3:1:2
Compound 181 cyproconazole quinoxyfen 1:1:1 2:1:1 3:1:1
Compound 181 cyproconazole sedaxane 1:1:2 2:1:2 3:1:2
Compound 181 cyproconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 cyproconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 difenconazole azoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole kre soxim-methyl 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole picoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole pyraclostrobin 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole pyrametostrobin 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole pyraoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole trifloxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole bixafen 1:1:2 2:1:2 3:1:2
Compound 181 difenconazole boscalid 1:1:2 2:1:2 3:1:2
Compound 181 difenconazole cyflufenamid 1:2:1 2:2:1 3:2:1
Compound 181 difenconazole fluopyram 1:1:2 2:1:2 3:1:2
Compound 181 difenconazole isopyrazam 1:1:2 2:1:2 3:1:2
Compound 181 difenconazole metrafenone 1:1:2 2:1:2 3:1:2
Compound 181 difenconazole penthiopyrad 1:1:2 2:1:2 3:1:2
Compound 181 difenconazole proquinazid 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole pyriofenone 1:1:2 2:1:2 3:1:2
Compound 181 difenconazole quinoxyfen 1:1:1 2:1:1 3:1:1
Compound 181 difenconazole sedaxane 1:1:2 2:1:2 3:1:2
Compound 181 difenconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 difenconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Component (a) Component (b) Illustrative Ratios(*)
Compound 181 epoxiconazole azoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole kre soxim-methyl 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole picoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole pyraclostrobin 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole pyrametostrobin 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole pyraoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole trifloxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole bixafen 1:1:2 2:1:2 3:1:2
Compound 181 epoxiconazole boscalid 1:1:2 2:1:2 3:1:2
Compound 181 epoxiconazole cyflufenamid 1:2:1 2:2:1 3:2:1
Compound 181 epoxiconazole fluopyram 1:1:2 2:1:2 3:1:2
Compound 181 epoxiconazole isopyrazam 1:1:2 2:1:2 3:1:2
Compound 181 epoxiconazole metrafenone 1:1:2 2:1:2 3:1:2
Compound 181 epoxiconazole penthiopyrad 1:1:2 2:1:2 3:1:2
Compound 181 epoxiconazole proquinazid 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole pyriofenone 1:1:2 2:1:2 3:1:2
Compound 181 epoxiconazole quinoxyfen 1:1:1 2:1:1 3:1:1
Compound 181 epoxiconazole sedaxane 1:1:2 2:1:2 3:1:2
Compound 181 epoxiconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 epoxiconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 metconazole azoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 metconazole kre soxim-methyl 1:1:1 2:1:1 3:1:1
Compound 181 metconazole picoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 metconazole pyraclostrobin 1:1:1 2:1:1 3:1:1
Compound 181 metconazole pyrametostrobin 1:1:1 2:1:1 3:1:1
Compound 181 metconazole pyraoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 metconazole trifloxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 metconazole bixafen 1:1:2 2:1:2 3:1:2
Compound 181 metconazole boscalid 1:1:2 2:1:2 3:1:2
Compound 181 metconazole cyflufenamid 1:2:1 2:2:1 3:2:1
Compound 181 metconazole fluopyram 1:1:2 2:1:2 3:1:2
Compound 181 metconazole isopyrazam 1:1:2 2:1:2 3:1:2
Compound 181 metconazole metrafenone 1:1:2 2:1:2 3:1:2
Compound 181 metconazole penthiopyrad 1:1:2 2:1:2 3:1:2
Compound 181 metconazole proquinazid 1:1:1 2:1:1 3:1:1
Compound 181 metconazole pyriofenone 1:1:2 2:1:2 3:1:2 Component (a) Component (b) Illustrative Ratios(*)
Compound 181 metconazole quinoxyfen 1:1:1 2:1:1 3:1:1
Compound 181 metconazole sedaxane 1:1:2 2:1:2 3:1:2
Compound 181 metconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 metconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 myclobutanil azoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil kre soxim-methyl 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil picoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil pyraclostrobin 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil pyrametostrobin 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil pyraoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil trifloxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil bixafen 1:1:2 2:1:2 3:1:2
Compound 181 myclobutanil boscalid 1:1:2 2:1:2 3:1:2
Compound 181 myclobutanil cyflufenamid 1:2:1 2:2:1 3:2:1
Compound 181 myclobutanil fluopyram 1:1:2 2:1:2 3:1:2
Compound 181 myclobutanil isopyrazam 1:1:2 2:1:2 3:1:2
Compound 181 myclobutanil metrafenone 1:1:2 2:1:2 3:1:2
Compound 181 myclobutanil penthiopyrad 1:1:2 2:1:2 3:1:2
Compound 181 myclobutanil proquinazid 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil pyriofenone 1:1:2 2:1:2 3:1:2
Compound 181 myclobutanil quinoxyfen 1:1:1 2:1:1 3:1:1
Compound 181 myclobutanil sedaxane 1:1:2 2:1:2 3:1:2
Compound 181 myclobutanil picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 myclobutanil trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 prothioconazole azoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole kre soxim-methyl 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole picoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole pyraclostrobin 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole pyrametostrobin 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole pyraoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole trifloxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole bixafen 1:1:2 2:1:2 3:1:2
Compound 181 prothioconazole boscalid 1:1:2 2:1:2 3:1:2
Compound 181 prothioconazole cyflufenamid 1:2:1 2:2:1 3:2:1
Compound 181 prothioconazole fluopyram 1:1:2 2:1:2 3:1:2
Compound 181 prothioconazole isopyrazam 1:1:2 2:1:2 3:1:2 Component (a) Component (b) Illustrative Ratios(*)
Compound 181 prothioconazole metrafenone 1:1:2 2:1:2 3:1:2
Compound 181 prothioconazole penthiopyrad 1:1:2 2:1:2 3:1:2
Compound 181 prothioconazole proquinazid 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole pyriofenone 1:1:2 2:1:2 3:1:2
Compound 181 prothioconazole quinoxyfen 1:1:1 2:1:1 3:1:1
Compound 181 prothioconazole sedaxane 1:1:2 2:1:2 3:1:2
Compound 181 prothioconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 prothioconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 tebuconazole azoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole kre soxim-methyl 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole picoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole pyraclostrobin 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole pyrametostrobin 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole pyraoxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole trifloxystrobin 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole bixafen 1:1:2 2:1:2 3:1:2
Compound 181 tebuconazole boscalid 1:1:2 2:1:2 3:1:2
Compound 181 tebuconazole cyflufenamid 1:2:1 2:2:1 3:2:1
Compound 181 tebuconazole fluopyram 1:1:2 2:1:2 3:1:2
Compound 181 tebuconazole isopyrazam 1:1:2 2:1:2 3:1:2
Compound 181 tebuconazole metrafenone 1:1:2 2:1:2 3:1:2
Compound 181 tebuconazole penthiopyrad 1:1:2 2:1:2 3:1:2
Compound 181 tebuconazole proquinazid 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole pyriofenone 1:1:2 2:1:2 3:1:2
Compound 181 tebuconazole quinoxyfen 1:1:1 2:1:1 3:1:1
Compound 181 tebuconazole sedaxane 1:1:2 2:1:2 3:1:2
Compound 181 tebuconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 181 tebuconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
(*) Ratios of Component (a) relative to Component (b) in sequence, by weight.
Tables C2 through C27 are each constructed the same as Table CI above except that entries below the "Component (a)" column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table C2 the entries below the "Component (a)" column heading all recite "Compound 292", and the first line in below the column headings in Table C2 specifically discloses a mixture of Compound 292 with cyproconazole and azoxystrobin, and the illustrative weight ratios of 1:1:1, 2:1:1 and 3:1 : 1 of Compound 292:cyproconazole:azoxystrobin. Tables C3 through C27 are constructed similarly.
Table Number Component (a) Column Entries Table Number Component (a) Column Entries
C2 Compound 292 C15 Compound 524
C3 Compound 469 C16 Compound 525
C4 Compound 513 C17 Compound 526
C5 Compound 514 C18 Compound 527
C6 Compound 515 C19 Compound 528
C7 Compound 516 C20 Compound 529
C8 Compound 517 C21 Compound 530
C9 Compound 518 C22 Compound 531
CIO Compound 519 C23 Compound 532
Cl l Compound 520 C24 Compound 533
C12 Compound 521 C25 Compound 534
C13 Compound 522 C26 Compound 535
C14 Compound 523
Figure imgf000142_0001
C27 Compound 536
Of note is a composition of the present invention comprising a compound of Formula 1 (or an N-oxide or salt thereof) with at least one other fungicidal compound that has a different site of action from the compound of Formula 1. In certain instances, a combination with at least one other fungicidal compound 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 advantageously comprise at least one fungicidal active compound selected from the group consisting of (bl) through (b46) as described above, having a similar spectrum of control but a different site of action.
Compositions of component (a) with component (b) can be further mixed with one or more other biologically active compounds or agents including insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Thus the present invention also pertains to a composition comprising a fungicidally effective amount of a mixture of component (a) with component (b) and a biologically effective amount of at least one additional biologically active compound or agent and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compounds or agents can also be separately formulated in compositions comprising at least one of a surfactant, solid or liquid diluent. For compositions of the present invention, one or more other biologically active compounds or agents can be formulated together with one or both of components (a) and (b) to form a premix, or one or more other biologically active compounds or agents can be formulated separately from components (a) and (b) and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
Examples of such biologically active compounds or agents with which compositions of component (a) with component (b) can be formulated are: insecticides such as 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, cyantraniliprole (3-bromo-l-(3- chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-lH-pyrazole- 5-carboxamide), 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, meperfluthrin, 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, prothiocarb, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen, spirotetramat, sulfoxaflor, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron; nematocides such as aldicarb, imicyafos, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyenopyrafen, 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 HzNPV, AfNPV; and granulosis virus (GV) such as CpGV.
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, Farnham, Surrey, U.K., 2001.
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 mixture of component (a) with component (b) is generally between about 1 :3000 and about 3000: 1. Of note are weight ratios between about 1 :100 and about 3000: 1, or between about 1 :30 and about 300:1 (for example ratios between about 1 : 1 and about 30: 1). It will be evident that including these additional components may expand the spectrum of diseases controlled beyond the spectrum controlled by a mixture of component (a) with component (b).
Component (a) compounds and/or combinations thereof with component (b) compounds and/or one or more other biologically active compounds or agents 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 present component (a) alone or in combination with component (b) may be synergistic with the expressed toxin proteins.
Of note is the combination of the composition comprising components (a) and (b) as described in the Summary of the Invention further comprising at least one invertebrate pest control compound or agent (e.g., insecticide, acaricide). Of particular note is a composition comprising component (a) and at least one (i.e. one or more) invertebrate pest control compound or agent, which then can be subsequently combined with component (b) to provide a composition comprising components (a) and (b) and the one or more invertebrate pest control compounds or agents. Alternatively without first mixing with component (b), a biologically effective amount of the composition comprising component (a) with at least one invertebrate pest control agent can be applied to a plant or plant seed (directly or through the environment of the plant or plant seed) to protect the plant or plant seed from diseases caused by fungal pathogens and injury caused by invertebrate pests.
For embodiments where one or more of invertebrate pest control compounds are used, the weight ratio of these compounds (in total) to the component (a) compounds 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. Of note is a composition of the present invention which comprises in addition to a component (a) compound, alone or in combination with component (b), at least one invertebrate pest control compound or agent 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, cyantraniliprole, 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, meperfluthrin, 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, sulfoxaflor, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethylfluthin, 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. Of note is the aforedescribed list excluding meperflutrin, sulfoxaflor and tetramethylfluthrin.
In certain instances, combinations of a component (a) compound, alone or in mixture with component (b), 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. Table Dl lists specific combinations of invertebrate pest control agents with Compound 181 (identified in Index Table A) as a component (a) compound illustrative of mixtures and compositions comprising these active ingredients and methods using them according to the present invention. The second column of Table Dl lists the specific invertebrate pest control agents (e.g., "Abamectin" in the first line). The third column of Table Dl lists the mode of action (if known) or chemical class of the invertebrate pest control agents. The fourth column of Table Dl lists embodiment(s) of ranges of weight ratios for rates at which the invertebrate pest control agent is typically applied relative to Compound 181 alone or in combination with component (b) (e.g., "50: 1 to 1 :50" of abamectin relative to a Compound 181 by weight). Thus, for example, the first line of Table Dl specifically discloses the combination of Compound 181 with abamectin is typically applied in a weight ratio between 50: 1 to 1 :50. The remaining lines of Table Dl are to be construed similarly.
Table Dl
Component (a) Invertebrate Pest Control Mode of Action or Chemical Typical
Agent Class Weight Ratio
Compound 181 Abamectin macrocyclic lactones 50:1 to 1:50
Compound 181 Acetamiprid neonicotinoids 150:1 to 1:200
Compound 181 Amitraz octopamine receptor ligands 200: 1 to 1:100
Compound 181 Avermectin macrocyclic lactones 50:1 to 1:50
Compound 181 Azadirachtin ecdysone agonists 100:1 to 1: 120
Compound 181 Beta-cyf uthrin sodium channel modulators 150: 1 to 1:200
Compound 181 Bifenthrin sodium channel modulators 100: 1 to 1:10
Compound 181 Buprofezin chitin synthesis inhibitors 500:1 to 1:50
Compound 181 Cartap nereistoxin analogs 100:1 to 1:200
Compound 181 Chlorantraniliprole ryanodine receptor ligands 100:1 to 1:120 mitochondrial electron transport
Compound 181 Chlorfenapyr 300:1 to 1:200 inhibitors
Compound 181 Chlorpyrifos cholinesterase inhibitors 500:1 to 1:200
Compound 181 Clothianidin neonicotinoids 100:1 to 1:400
Compound 181 Cyantraniliprole ryanodine receptor ligands 100:1 to 1: 120
Compound 181 Cyfluthrin sodium channel modulators 150: 1 to 1:200
Compound 181 Cyhalothrin sodium channel modulators 150: 1 to 1:200
Compound 181 Cypermethrin sodium channel modulators 150: 1 to 1:200
Compound 181 Cyromazine chitin synthesis inhibitors 400: 1 to 1:50
Compound 181 Deltamethrin sodium channel modulators 50: 1 to 1:400
Compound 181 Dieldrin cyclodiene insecticides 200:1 to 1: 100
Compound 181 Dinotefuran neonicotinoids 150:1 to 1:200 Component (a) Invertebrate Pest Control Mode of Action or Chemical Typical
Agent Class Weight Ratio
Compound 181 Diofenolan molting inhibitor 150:1 to 1:200
Compound 181 Emamectin macrocyclic lactones 50:1 to 1: 10
Compound 181 Endosulfan cyclodiene insecticides 200:1 to 1: 100
Compound 181 Esfenvalerate sodium channel modulators 100: 1 to 1:400
GABA-regulated chloride channel
Compound 181 Ethiprole 200:1 to 1: 100 blockers
Compound 181 Fenothiocarb 150:1 to 1:200
Compound 181 Fenoxycarb juvenile hormone mimics 500:1 to 1: 100
Compound 181 Fenvalerate sodium channel modulators 150: 1 to 1:200
GABA-regulated chloride channel
Compound 181 Fipronil 150:1 to 1: 100 blockers
Compound 181 Flonicamid 200:1 to 1: 100
Compound 181 Flubendiamide ryanodine receptor ligands 100: 1 to 1:120
Compound 181 Flufenoxuron chitin synthesis inhibitors 200:1 to 1: 100
Compound 181 Hexaflumuron chitin synthesis inhibitors 300:1 to 1:50 mitochondrial electron transport
Compound 181 Hydramethylnon 150:1 to 1:250 inhibitors
Compound 181 Imidacloprid neonicotinoids 1000:1 to 1: 1000
Compound 181 Indoxacarb sodium channel modulators 200: 1 to 1:50
Compound 181 Lambda-cyhalothrin sodium channel modulators 50:1 to 1:250
Compound 181 Lufenuron chitin synthesis inhibitors 500:1 to 1:250
Compound 181 Meperfluthrin sodium channel modulators 100: 1 to 1:400
Compound 181 Metaflumizone 200:1 to 1:200
Compound 181 Methomyl cholinesterase inhibitors 500:1 to 1: 100
Compound 181 Methoprene juvenile hormone mimics 500:1 to 1:100
Compound 181 Methoxyfenozide ecdysone agonists 50:1 to 1:50
Compound 181 Nitenpyram neonicotinoids 150:1 to 1:200
Compound 181 Nithiazine neonicotinoids 150:1 to 1:200
Compound 181 Novaluron chitin synthesis inhibitors 500:1 to 1:150
Compound 181 Oxamyl cholinesterase inhibitors 200:1 to 1:200
Compound 181 Pymetrozine 200:1 to 1: 100
Compound 181 Pyrethrin sodium channel modulators 100: 1 to 1: 10 mitochondrial electron transport
Compound 181 Pyridaben 200:1 to 1: 100 inhibitors
Compound 181 Pyridalyl 200:1 to 1: 100 Component (a) Invertebrate Pest Control Mode of Action or Chemical Typical
Agent Class Weight Ratio
Compound 181 Pyriproxyfen juvenile hormone mimics 500:1 to 1:100
Compound 181 Ryanodine ryanodine receptor ligands 100:1 to 1:120
Compound 181 Spinetoram macrocyclic lactones 150:1 to 1:100
Compound 181 Spinosad macrocyclic lactones 500:1 to 1:10
Compound 181 Spirodiclofen lipid biosynthesis inhibitors 200:1 to 1:200
Compound 181 Spiromesifen lipid biosynthesis inhibitors 200:1 to 1:200
Compound 181 Tebufenozide ecdysone agonists 500:1 to 1:250
Compound 181 Tetramethylfluthrin sodium channel modulators 100:1 to 1:40
Compound 181 Thiacloprid neonicotinoids 100:1 to 1:200
Compound 181 Thiamethoxam neonicotinoids 1250:1 to 1:1000
Compound 181 Thiodicarb choline sterase inhibitors 500:1 to 1:400
Compound 181 Thiosultap-sodium 150:1 to 1:100
Compound 181 Tralomethrin sodium channel modulators 150:1 to 1:200
Compound 181 Triazamate choline sterase inhibitors 250:1 to 1:100
Compound 181 Triflumuron chitin synthesis inhibitors 200:1 to 1:100
Compound 181 Bacillus thuringiensis biological agents 50:1 to 1:10
Bacillus thuringiensis delta-
Compound 181 biological agents 50:1 to 1:10 endotoxin
Compound 181 NPV (e.g., Gemstar) biological agents 50:1 to 1:10
Tables D2 through D27 are each constructed the same as Table Dl above except that entries below the "Component (a)" column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table D2 the entries below the "Component (a)" column heading all recite "Compound 292", and the first line in below the column headings in Table D2 specifically discloses a mixture of Compound 292 with abamectin. Tables D3 through D27 are c nstructed similarly.
Table Number Component (a) Column Entries Table Number Component (a) Column Entries
D2 Compound 292 D15 Compound 524
D3 Compound 469 D16 Compound 525
D4 Compound 513 D17 Compound 526
D5 Compound 514 D18 Compound 527
D6 Compound 515 D19 Compound 528
D7 Compound 516 D20 Compound 529
D8 Compound 517 D21 Compound 530
D9 Compound 518 D22 Compound 531
D10 Compound 519
Figure imgf000148_0001
D23 Compound 532 Dl l Compound 520 D24 Compound 533
D12 Compound 521 D25 Compound 534
D13 Compound 522 D26 Compound 535
D14 Compound 523 D27 Compound 536
One embodiment of invertebrate pest control agents (e.g., insecticides and acaricides) for mixing with compounds of component (a) include sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, meperfluthrin, metofluthrin, profluthrin, pyrethrin, tetramethylfluthrin 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, cyantraniliprole and flubendiamide; 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 component (a) 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 a composition comprising component (a) and at least one additional biologically active compound or agent selected from the Invertebrate Pest Control Agents listed in Table Dl above.
The compositions of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or vegetative propagation unit to be protected, an effective amount of a composition of the invention (e.g., a composition comprising components (a) and (b)). This aspect of the present invention can also be described as a method for protecting a plant or plant seed from diseases caused by fungal pathogens comprising applying a fungicidally effective amount of a composition of the invention to the plant (or portion thereof) or plant seed (directly or through the environment (e.g., growing medium) of the plant or plant seed).
Plant disease control is ordinarily accomplished by applying an effective amount of a composition of the invention (e.g., comprising a mixture of components (a) and (b)), typically as a formulated composition, either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The mixtures can also be applied to seeds to protect the seeds and seedlings developing from the seeds. The mixtures can also be applied through irrigation water to treat plants.
Suitable rates of application (e.g., biologically effective amounts, fungicidally effective amounts or insecticidally effective amounts) for the mixtures and compositions of this invention can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active ingredients. Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.1 to about 10 g per kilogram of seed; and vegetative propagation units (e.g., cuttings and tubers) can normally be protected when propagation unit is treated at a rate of from about 0.1 to about 10 g per kilogram of propagation unit. One skilled in the art can easily determine through simple experimentation the application rates of mixtures and compositions containing particular combinations of active ingredients according to this invention needed to provide the desired spectrum of plant protection and control of plant diseases and optionally other plant pests.
The compounds of Formula 1, N-oxides, and salts thereof, are particularly efficacious for controlling plant diseases caused by fungal pathogens. Combining these compounds with other fungicidal compounds can provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. Accordingly, mixtures and compositions described herein can control a broad spectrum of plant diseases, foliar pathogens of crops including: cereal grain crops such as wheat, barley, oats, rye, triticale, rice, maize, sorghum and millet; vine crops such as table and wine grapes; field crops such as oilseed rape (canola), sunflower; sugar beets, sugar cane, soybean, peanuts (groundnut), tobacco, alfafa, clover, lespedeza, trefoil and vetch; pome fruits such as apple, pear, crabapple, loquat, mayhaw and quince; stone fruits such as peaches, cherries, plums, apricots, nectarines and almonds; citrus fruits such as lemons, limes, oranges, grapefruit, mandarin (tangerines) and kumquat; root and tuber vegetables and field crops (and their foliage) such as artichoke, garden and sugar beet, carrot, cassava, ginger, ginseng, horseradish, parsnip, potato, radish, rutabaga, sweet potato, turnip and yam; bulb vegetables such as garlic, leek, onion and shallot; leafy vegetables such as arugula (roquette), celery, celery, cress, endive (escarole), fennel, head and leaf lettuce, parsley, radicchio (red chicory), rhubarb, spinach and Swiss chard; brassica (cole) leafy vegetables such as broccoli, broccoli raab (rapini), Brussels sprouts, cabbage, bok choy, cauliflower, collards, kale, kohlrabi, mustard and greens; legume vegetables (succulent or dried) such as lupin, bean (Phaseolus spp.) (including field bean, kidney bean, lima bean, navy bean, pinto bean, runner bean, snap bean, tepary bean and wax bean), bean (Vigna spp.) (including adzuki bean, asparagus bean, blackeyed pea, catjang, Chinese longbean, cowpea, crowder pea, moth bean, mung bean, rice bean, southern pea, urd bean and yardlong bean), broad bean (fava), chickpea (garbanzo), guar, jackbean, lablab bean, lentil and pea (Pisum spp.) (including dwarf pea, edible -podded pea, English pea, field pea, garden pea, green pea, snowpea, sugar snap pea, pigeon pea and soybean); fruiting vegetables such as eggplant, groundcherry (Physalis spp.), pepino and pepper (including bell pepper, chili pepper, cooking pepper, pimento, sweet pepper; tomatillo and tomato); cucurbit vegetables such as Chayote (fruit), Chinese waxgourd (Chinese preserving melon), citron melon, cucumber, gherkin, edible gourd (including hyotan, cucuzza, hechima, and Chinese okra), Momordica spp. (including balsam apple, balsam pear, bittermelon and Chinese cucumber), muskmelon (including cantaloupe and pumpkin), summer and winter squash (including butternut squash, calabaza, hubbard squash, acorn squash, spaghetti squash) and watermelon; berries such as blackberry (including bingleberry, boysenberry, dewberry, lowberry, marionberry, olallieberry and youngberry), blueberry, cranberry, currant, elderberry, gooseberry, huckleberry, loganberry, raspberry and strawberry; tree nuts such as almond, beech nut, Brazil nut, butternut, cashew, chestnut, chinquapin, filbert (hazelnut), hickory nut, macadamia nut, pecan and walnut; tropical fruits and other crops such as bananas, plantains, mangos, coconuts, papaya, guava, avocado, lichee, agave, coffee, cacao, sugar cane, oil palm, sesame, rubber and spices; fiber crops such as cotton, flax and hemp; turfgrasses (including warm- and cool-season turfgrasses) such as bentgrass, Kentucky bluegrass, St. Augustine grass, tall fescue and Bermuda grass.
These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes, including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwelli, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici, powdery mildew diseases such as Blumeria spp. (including Blumeria graminis) and Erysiphe spp. (including Erysiphe polygoni), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare), and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rhizoctonia spp. (such as Rhizoctonia solani and Rhizoctonia oryzae); Fusarium diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; Rutstroemia floccosum (also known as Sclerontina homoeocarpa); and other genera and species closely related to these pathogens. Certain fungicidal compounds are also bactericidal, and therefore in addition to their fungicidal activity, the compositions or combinations can also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.
In the present fungicidal compositions, the Formula 1 compounds of component (a) can work synergically with the additional fungicidal compounds of component (b) to provide such beneficial results as broadening the spectrum of plant diseases controlled, extending duration of preventative and curative protection, and suppressing proliferation of resistant fungal pathogens. In particular embodiments, compositions are provided in accordance with this invention that comprise proportions of component (a) and component (b) that are especially useful for controlling particular fungal diseases (such as Alternaria solani, Blumeria graminis f. sp. tritici, Botrytis cinerea, Puccinia recondita f. sp. tritici, Rhizoctonia solani, Septoria nodorum, Septoria tritici).
Mixtures of fungicides may also provide significantly better disease control than could be predicted based on the activity of the individual components. This synergism has been described as "the cooperative action of two components of a mixture, such that the total effect is greater or more prolonged than the sum of the effects of the two (or more) taken independently" (see P. M. L. Tames, Neth. J. Plant Pathology 1964, 70, 73-80). In methods providing plant disease control in which synergy is exhibited from a combination of active ingredients (e.g., fungicidal compounds) applied to the plant or seed, the active ingredients are applied in a synergistic weight ratio and synergistic (i.e. synergistically effective) amounts. One skilled in the art can easily identify and optimize through simple experimentation the weight ratios and application rates (i.e. amounts) of fungicidal compounds providing synergy. The following Tests include tests demonstrating the efficacy that the present compounds can provide to fungicidal mixtures for controlling specific pathogens. The following Tests also include tests demonstrating the control efficacy of the mixtures of this invention on specific pathogens. The disease control afforded by the present compounds alone or in mixtures is not limited, however, to the pathogenic fungi species exemplified.
See Index Table A for compound descriptions. See Index Table B for Ipl NMR data. The following abbreviations are used in the Index Tables which follow: i means iso, Me is methyl, Et is ethyl, Ph is phenyl, Bn is benzyl, MeO is methoxy, EtO is ethoxy, MeS is methylthio, CN is cyano and NCS is thiocyano (i.e. -SCN). In the Index Tables when an instance of Q1 or Q2 comprises a phenyl ring attached through the linker CH2 (i.e. benzyl) to the remainder of Formula 1, locant numbers of the ring are relative to the connection of the ring to the linker CH2. The abbreviation "Cmpd." stands for "Compound", and the abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared. The abbreviation "m.p." stands for melting point. In Index Table A the numerical value reported in the column "MS (M+l)" is the molecular weight of the observed molecular ion formed by addition of H+ (molecular weight of 1) to the molecule having the greatest isotopic abundance (i.e. M). The reported M+l peaks were observed by mass spectrometry using atmospheric pressure chemical ionization (APCI) or electrospray ionization (ESI). The presence of molecular ions containing one or more higher atomic weight isotopes of lower abundance (e.g., 37C1, 81Br) is not reported.
Figure imgf000153_0001
Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
1 (Ex. 4) 2,6-di-F-Ph 4-Cl-Ph CI Me
2 (Ex. 3) 2,6-di-F-Ph 4-Cl-Ph CI CI
3 (Ex. 6) 4-F-Ph 4-Cl-Ph CI Me
4 (Ex. 2) 2,4,6-tri-F-Ph 4-Cl-Ph CI CI
5 4-Cl-Ph 2-Cl, 4-F-Ph CI CI 129-131
6 2,6-di-F-Ph Ph CI Br 371
7 2,4,6-tri-F-Ph 4-Cl-Ph CI Br 139-141
8 2,4,6-tri-F-Ph 4-Cl-Ph CI Me 148-150
9 2,6-di-F-Ph Ph CI I 417
10 2,6-di-F-Ph Ph CI Me 305 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
11 2,6-di-F-Ph 3-F-Ph CI CI 131-134
12 2,4,6-tri-F-Ph 4-Cl-Ph Br Br 145-148
13 2,6-di-F-Ph 3-F-Ph CI Br 120-122
14 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph CI Br 135-137
15 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph CI CI 397
16 2,6-di-F-Ph 3-F-Ph CI Me 323
17 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph CI Me 375
18 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph CI Br ** **
19 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph CI Me 387
20 2,6-di-F-Ph 4-Cl-Ph CI Br 124-126
21 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Br Br 144-146
22 2,6-di-F, 4-MeO-Ph 4-Cl-Ph CI Me 146-148
23 2,6-di-F, 4-MeO-Ph 4-Cl-Ph CI Br 152-153
24 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Me Me 355
25 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Br Br 166-168
26 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Br Br 495
27 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Me Me 367
28 2,4,6-tri-F-Ph 4-Cl-Ph Me Me ** ** (Ex. 14) 2,6-di-F-Ph 3-F-Ph CI CH≡C 333
30 2,3,6-tri-F-Ph 4-Cl-Ph CI Me 357
31 2-Cl, 4-F-Ph 4-Cl-Ph CI Me 357
32 2,3,6-tri-F-Ph 4-Cl-Ph CI Br 124-127
33 2-Cl, 4-F-Ph 4-Cl-Ph CI Br 117-120
34 2-Cl, 6-F-Ph 4-Cl-Ph CI Br 174-177
35 2-Cl, 6-F-Ph 4-Cl-Ph CI Me 357
36 2,6-di-F-Ph 3,5-di-F-Ph CI Br 407
37 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Me Me 105-108
(Ex. 13) 2,3,6-tri-F-Ph 4-Cl-Ph CI CN 147-149
39 2,6-di-F-Ph 2-F-Ph CI Br 113-115
40 2,6-di-F, 4-MeO, 3-Me-Ph 4-Cl-Ph Br Me 143-147
41 2,6-di-F-Ph 2-F-Ph CI Me 323
42 2,6-di-F-Ph 4-CFsO-Ph CI Br 355
43 2,6-di-F-Ph 4-Br-Ph CI Br 143-145
44 2,6-di-F-Ph 4-F-Ph CI Br 389
45 2,6-di-F-Ph 3,5-di-F-Ph CI Me 341
46 2-Cl, 3,6-di-F-Ph 4-Cl-Ph CI Br 439
47 2-Cl, 3,6-di-F-Ph 4-Cl-Ph CI Me 373 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
48 2,6-di-F-Ph 4-CF3O-PI1 CI Me 389
49 2,6-di-F-Ph 4-Me-Ph CI Me 319
50 2,6-di-F-Ph 4-F-Ph CI Me 323
51 2,6-di-F-Ph 4-CF3-Ph CI Br 117-120
52 2,5-di-F-Ph 4-Cl-Ph CI Br 114-117
53 2-CF3, 6-F-Ph 4-Cl-Ph CI Br 455
54 2-Cl, 6-F-Ph 4-Cl-Ph CI CF3 409
55 3 -Br, 2,6-di-F-Ph 4-Cl-Ph CI Me 419
56 2,6-di-F-Ph 4-CF3-Ph CI Me 373
57 2,5-di-F-Ph 4-Cl-Ph CI Me 339
58 2-CF3, 6-F-Ph 4-Cl-Ph CI Me 389
59 2,6-di-F-Ph Bn CI Br 85-87
60 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Br MeO 141-144
61 3 -CI, 2, 6-di-F-Ph 4-Cl-Ph CI Br 439
62 2,6-di-F-Ph 3-Cl-Bn CI Br 419
63 2,6-di-F-Ph 4-Cl, 3-F-Bn CI Br 437
64 2,6-di-F-Ph 4-Cl-Bn CI Br 419
65 2,6-di-F, 3-Me-Ph 4-Cl-Ph CI Br 419
66 2,6-di-F, 3-Me-Ph 4-Cl-Ph CI Me 353
67 2,6-di-F-Ph 4-Cl-Ph CI Et 125-126
68 3 -Br, 2-F, 4-MeO-Ph 4-Cl-Ph CI Br 498
69 2-F, 4-MeO-Ph 4-Cl-Ph CI Br 417
70 2-F, 4-MeO-Ph 4-Cl-Ph CI Me 351
71 2-F, 4-MeO, 3-Me-Ph 4-Cl-Ph CI Me 365
72 2,6-di-F-Ph 4-Cl-Ph CI z-Pr 106-108
73 2,6-di-F, 3-MeO-Ph 4-Cl-Ph CI Br 435
74 2,6-di-F-Ph Bn CI Me 319
75 2,6-di-F, 4-HO-Ph 4-Cl-Ph CI Me 355
76 2,6-di-F-Ph 4-Cl, 3-F-Bn CI Me 371
77 2,6-di-F, 3-MeO-Ph 4-Cl-Ph CI Me 369
78 2,6-di-F-Ph 3-Cl-Bn CI Me 353
79 3 -CI, 2,6-di-F-Ph 4-Cl-Ph CI Me 375
80 2,6-di-F-Ph 4-Cl-Bn CI Me 353
81 2,3,6-tri-F-Ph 4-F-Ph CI CI 361
82 2,3,6-tri-F-Ph 4-Me-Ph CI CI 357
83 4-Cl-Ph 2,4,6-tri-F-Ph CI Br 117-118
84 2,3,6-tri-F-Ph 4-F-Ph CI Br 407 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
85 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph CI CI 395
86 4-Cl, 2-F, 6-MeO-Ph 4-Cl-Ph CI Br 451
87 2,3,6-tri-F-Ph 4-Me-Ph CI Br 403
88 2,6-di-F, 4-MeO-Ph 4-F-Ph CI CI 373
89 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph CI Br 441
90 2,6-di-F, 4-MeO-Ph 4-F-Ph CI Br 419
91 2,3,6-tri-F-Ph 4-F-Ph CI Me 341
92 2,6-di-F, 4-MeO-Ph 4-Me-Ph CI CI 369
93 2,4,6-tri-F-Ph 4-F-Ph CI CI 361
94 2,6-di-F, 4-MeO-Ph 4-Me-Ph CI Br 415
95 4-Cl, 2-F, 6-MeO-Ph 4-Cl-Ph CI Me 387
96 4-Cl-Ph 2,6-di-F-Ph CI CI 123-126
97 2,6-di-F-Ph 4-Cl-Ph Me Me 146-148
98 2,4,6-tri-F-Ph 4-F-Ph CI Br 407
99 2,4,6-tri-F-Ph 4-Me-Ph CI Br 403
100 2,4,6-tri-F-Ph 4-Me-Ph CI CI 357
101 2,3,6-tri-F-Ph 4-Me-Ph CI Me 337
102 4-EtO, 2,6-di-F-Ph 4-Cl-Ph CI Me 383
103 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph CI Me 375
104 2,6-di-F, 4-MeO-Ph 4-F-Ph CI Me 353
105 2,6-di-F, 4-MeO-Ph 4-Me-Ph CI Me 349
106 4-Cl-Ph 2,6-di-F-Ph Br Br 156-158
107 4-Cl-Ph 2,6-di-F-Ph CI Br 148-150
108 2,4,6-tri-F-Ph 4-F-Ph CI Me 341
109 2,4,6-tri-F-Ph 4-Me-Ph CI Me 337
110 2,6-di-F-Ph 3,4-di-F-Ph CI Br 407
111 2,6-di-F-Ph 3-F, 4-Me-Ph CI Br 403
112 2-Cl, 6-F, 4-MeO-Ph 4-Cl-Ph CI Br 451
113 2-Cl, 6-F, 4-MeO-Ph 4-Cl-Ph CI Me 385
114 2,6-di-F-Ph 3,4-di-F-Ph CI Me 341
115 2,6-di-F-Ph 3-F, 4-Me-Ph CI Me 337
116 2-Cl, 4-F-Ph 4-F-Ph CI Br 111-112
117 2-Cl, 4-F-Ph 4-F-Ph CI CI 359
118 2-Cl, 4-F-Ph 4-Me-Ph CI Br 127-128
119 2-Cl, 6-F-Ph 4-F-Ph CI Br 95-97
120 2-Cl, 6-F-Ph 4-Me-Ph CI Br 147-148
121 2-Cl, 4-F-Ph 4-F-Ph CI Me 101-106 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
122 2-Cl, 4-F-Ph 4-Me-Ph CI Me 148-149
123 2-Cl, 6-F-Ph 4-F-Ph CI Me 122-123
124 2-Cl, 6-F-Ph 4-Me-Ph CI Me 158-162
125 2-Cl, 3,6-di-F-Ph 4-F-Ph CI Br 423
126 2-Cl, 3,6-di-F-Ph 4-F-Ph CI CI 378
127 2-Cl, 3,6-di-F-Ph 4-Me-Ph CI Br 419
128 2-Cl, 3,6-di-F-Ph 4-Me-Ph CI CI 374
129 2,6-di-F-Ph 3-quinolinyl CI Me 158-160
130 4-CN, 2,6-di-F-Ph 4-Cl-Ph CI Br 429
131 2-Cl, 4-F-Ph 4-Cl, 3-F-Ph CI Br 103-104
132 2-Cl, 6-F-Ph 4-Cl, 3-F-Ph CI Br 80-84
133 4-Cl-Ph 2,4,6-tri-F-Ph CI CI 76-78
134 4-CN, 2,6-di-F-Ph 4-Cl-Ph CI Me 429
135 2-Cl, 3,6-di-F-Ph 4-F-Ph CI Me 429
136 2-Cl, 3,6-di-F-Ph 4-Me-Ph CI Me 429
137 2,6-di-F-Ph 3 -CI, 4-MeO-Bn CI CI 405
138 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Br CI 119-122
139 4-Cl-Ph 2,6-di-F-Ph Me Br 156-158
140 2,6-di-F-Ph 4-Cl-Ph H2C=CH Me 141-143
141 4-Cl-Ph 2,4,6-tri-F-Ph Br Br 130-131
142 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph CI Br 457
143 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph CI CI 413
144 2,6-di-F-Ph 3-Cl-Ph CI Br 405
145 2,6-di-F-Ph 3-Cl-Ph CI CI 361
146 2,6-di-F-Ph 4-Cl, 3-F-Ph CI Br 423
147 2,3,6-tri-F-Ph 3,4-di-Me-Ph CI Br 417
148 2,6-di-F-Ph 4-Cl, 3-F-Ph CI CI 379
149 2,3,6-tri-F-Ph 3,4-di-Me-Ph CI CI 371
150 2-Cl, 6-F-Ph 4-Me-Ph CI CI 142-143
151 2-Cl, 6-F-Ph 4-F-Ph CI CI 102-103
152 2-Cl, 4-F-Ph 4-Cl, 3-F-Ph CI CI 116-117
153 2-Cl, 6-F-Ph 4-Cl, 3-F-Ph CI CI 66-67
154 2,6-di-F, 3-MeS-Ph 4-Cl-Ph CI Br 451
155 4-Cl-Ph 2,4,6-tri-F-Ph Br CI 111-112
156 2,3,6-tri-F-Ph 3,4-di-Cl-Ph CI CI 413
157 2,6-di-F, 3-MeS-Ph 4-Cl-Ph CI Me 385
158 2,6-di-F-Ph 3-Cl-Ph CI Me 339 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
159 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph CI Me 393
160 2,3,6-tri-F-Ph 3,4-di-Me-Ph CI Me 351
161 2,6-di-F, 4-MeO-Ph 4-Cl-Ph CI CI 391
162 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph CI CI 407
163 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph CI I 499
164 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Br Br 137-139
165 2-Cl, 4-F-Ph 4-Cl, 3-F-Ph CI Me 89-91
166 2-Cl, 6-F-Ph 4-Cl, 3-F-Ph CI Me 140-142
167 2,6-di-F, 4-MeO-Ph 4-Cl-Ph CI I 481
168 2,6-di-F-Ph 4-Cl, 3-F-Ph CI Me 358
169 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Me Me 105-108
170 (Ex. 8) 2,6-di-F, 4-MeO-Ph 3-F-Ph CI Br 418
171 2,6-di-F, 4-MeO-Ph 3-F-Ph CI CI 373
172 2,6-di-F-Bn 4-Cl-Ph CI Me 353
173 2-F-Ph 4-Cl, 3-F-Ph C1CH2 CI 373
174 2-F-Ph 4-Cl, 3-F-Ph Me CI 339
175 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Me CI 387
176 3,5-di-Cl-4-pyridinyl 4-Cl, 3-F-Ph Me CI 390
177 2,6-di-F, 4-MeO-Ph 6-Cl-3-pyridinyl Me CI 370
178 2-pyridinyl 4-Cl, 3-F-Ph Me CI 322
179 2,6-di-F, 3-MeO-Ph 3-F-Ph CI Br 419
180 2,6-di-F, 3-MeO-Ph 3-F-Ph CI CI 373
181 (Ex. 9) 2,6-di-F, 4-MeO-Ph 3-F-Ph CI Me 354
182 2,6-di-F, 3-MeO-Ph 4-Me-Ph CI Br 415
183 2-Cl, 4-F-Ph 4-Me-Ph CI CI 72-73
184 2,6-di-F, 4-MeO-Ph 4-Cl-Bn CI Br 139-140
185 2,6-di-F, 4-MeO-Ph 4-Cl-Bn CI CI 123-124
186 2,3,6-tri-F-Ph 4-Cl-Bn CI CI ** **
187 2,3,6-tri-F-Ph 4-Cl-Bn CI Br 87-88
188 2,6-di-F, 4-MeO-Ph 4-Cl-Bn CI Me 116-117
189 2,6-di-F, 3-MeO-Ph 4-Cl-Bn CI CI ** **
190 2,6-di-F, 3-MeO-Ph 4-Cl-Bn CI Br 449
191 4-Cl-Ph 3-Cl-Bn CI Br 108-109
192 2,6-di-F, 4-MeO-Ph 4-Me-Bn CI CI 383
193 2,6-di-F, 4-MeO-Ph 4-Me-Bn CI Br 104-105
194 2,3,6-tri-F-Ph 4-Cl-Bn CI Me 371
195 2,6-di-F, 3-MeO-Ph 4-Cl-Bn CI Me 384 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M
196 4-Cl-Ph 3-Cl-Bn CI Me 113-114
197 2,6-di-F, 4-MeO-Ph 4-Me-Bn CI Me 363
198 4-Cl-Ph 2,6-di-F, 4-MeO-Ph CI CI 117-118
199 (Ex.
2,6-di-F, 4-MeO-Ph 4-F-Ph CI HOCH2 *** *** 15)
200 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Br Br 104-106
201 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph CI CI 120-122
202 2,6-di-F-Ph 4-Cl-Ph Et Me 122-124
203 4-Cl-Ph 2-Cl, 4-F-Ph Br Br 114-116
204 4-Cl-Ph 2-Cl, 4-F-Ph Me Me 336
205 4-Cl-Ph 2,4,6-tri-F-Ph Me Me 90-92
206 2,6-di-F, 3-MeO-Ph 4-Cl-Ph CI CI 391
207 2,6-di-F, 3-MeO-Ph 4-Me-Ph CI CI 369
208 2,6-di-F, 3-MeO-Ph 4-F-Ph CI Br 419
209 2,6-di-F, 3-MeO-Ph 3-F-Ph CI Me 353
210 2,6-di-F, 3-MeO-Ph 3-Me-Ph CI Br 414
211 2,6-di-F, 3-MeO-Ph 4-Cl, 3-F-Ph CI Br 453
212 2,6-di-F-Ph 5-Cl-2-pyridinyl Me CI ** **
213 2-F-4-pyridinyl 4-Cl, 3-F-Ph C1CH2 CI ** **
214 2-F-4-pyridinyl 4-Cl, 3-F-Ph Me CI ** **
215 4-Cl-Ph 2-Cl, 4-F-Ph Br CI 106-109
216 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Me Br 105-107
217 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Br CI 116-118
218 2,6-di-F-Ph 6-quinolinyl CI Br 176-180
219 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph CI Br 120-122
220 4-Cl-Ph 2-Cl, 4-F-Ph CI Br 113-116
221 (Ex.
2,6-di-F, 4-MeO-Ph 4-F-Ph CI FC¾ *** *** 16)
222 2,6-di-F, 3-MeO-Ph 4-Me-Ph CI Me 349
223 2,6-di-F, 3-MeO-Ph 4-F-Ph CI Me 353
224 2,6-di-F, 3-MeO-Ph 3-Me-Ph CI Me 113-117
225 4-Cl-Ph 2-Cl, 4-F-Ph Br Me 127-131
226 4-Cl-Ph 2-Cl, 4-F-Ph Me Br 146-150
227 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Br Me 125-127
228 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Br CI ** **
229 2,3,6-tri-F-Ph 4-Cl-Ph Br CI ** **
230 2,3,6-tri-F-Ph 4-F-Ph Br CI ** ** Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
231 2-Br-4-pyridinyl 4-Cl, 3-F-Ph C1CH2 CI 434
232 2-Br-4-pyridinyl 4-Cl, 3-F-Ph Me CI 400
233 5-Br-3-pyridinyl 4-Cl, 3-F-Ph C1CH2 CI 434
234 5-Br-3-pyridinyl 4-Cl, 3-F-Ph Me CI 400
235 5-Br-2-pyridinyl 4-Cl, 3-F-Ph C1CH2 CI ** **
236 5-Br-2-pyridinyl 4-Cl, 3-F-Ph Me CI 400
237 2-Cl-3-pyridinyl 4-Cl, 3-F-Ph C1CH2 CI 390
238 2-Cl-3-pyridinyl 4-Cl, 3-F-Ph Me CI 356
239 4-Cl-Ph 3-Cl-Bn CI CI 107-109
240 2,4,6-tri-F-Ph 3-F-Ph CI CI 78-81
241 2,3,6-tri-F-Ph 3-F-Ph CI CI 143-145
242 2,4,6-tri-F-Ph 3-F-Ph CI Br 130-132
243 2,3,6-tri-F-Ph 3-F-Ph CI Br 137-138
244 2,3,6-tri-F-Ph 3-F-Ph CI Me 146-147
245 2,4,6-tri-F-Ph 3-F-Ph CI Me 150-152
4,5-di-Br, I-Me-IH-
246 4-Cl-Ph Br Br 496 imidazol-2-yl
4,5-di-Br, I-Me-IH-
247 4-Cl-Ph Br Br 575 imidazol-2-yl
248 4-Cl-Ph 2,6-di-F, 4-MeO-Ph CI Br 1 18-125
249 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Br Br ** **
250 6-Me-2-pyridinyl 4-Cl, 3-F-Ph Me CI ** **
251 6-Me-2-pyridinyl 4-Cl, 3-F-Ph C1CH2 CI ** **
252 4-Cl-5-thiazolyl 4-Cl, 3-F-Ph Me CI ** **
253 2,4-di-Cl-5-thiazolyl 4-Cl, 3-F-Ph Me CI ** **
254 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Br Br ** **
255 2,3,6-tri-F-Ph 4-Cl-Ph Br Br 467
256 2,3,6-tri-F-Ph 4-F-Ph Br Br 449
257 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Br CI 439
258 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Me Me 353
259 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Me CI ** **
260 2,6-di-F, 3-MeO-Ph 4-F-Ph CI CI 374
261 2,6-di-F, 3-MeO-Ph 3-Me-Ph CI CI 133-136
262 2,6-di-F, 3-MeO-Ph 4-Cl, 3-F-Ph CI CI 84-86
263 2,6-di-F, 3-MeO-Ph 4-Cl, 3-F-Ph CI Me 387
264 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Me CI 104-106
265 4-Cl-Ph 2,6-di-F, 4-MeO-Ph C1CH2 CI 127-129 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
266 2,6-di-F, 3-MeO-Ph 3-Et-Ph CI Br 429
267 2,6-di-F, 3-MeO-Ph 4-Cl, 3-Me-Ph CI CI 403
268 2,6-di-F, 3-MeO-Ph 3-F2CHO-Ph CI CI 100-102
269 2,6-di-F, 3-MeO-Ph 4-Cl, 3-Me-Ph CI Br 449
270 2,6-di-F, 3-MeO-Ph 3-F2CHO-Ph CI Br 109-111
271 2,4-di-F-Bn 4-Cl-Ph Br Me 399
272 3-Cl, 2,6-di-F, 4-MeO-Ph 4-Me-Ph CI CI ** **
273 2,6-di-F, 4-MeO-Ph 6-C1-3 -pyridinyl CI CI 390
274 3-CN, 2,6-di-F-Ph 4-Cl-Ph CI CI 386
275 4-Br, 5-MeS-2-thienyl 4-Cl-Ph Br Br 545
276 2,3,6-tri-F-Ph 4-Cl-Ph Me CI ** **
277 2,3,6-tri-F-Ph 4-F-Ph Me CI ** **
278 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Me CI ** **
279 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Me Me ** **
280 2,3,6-tri-F-Ph 4-Cl-Ph Me Me ** **
281 2,3,6-tri-F-Ph 4-F-Ph Me Me ** **
282 2,6-di-F, 3-MeO-Ph 3-Et-Ph CI Me 364
283 (Ex.
3-CN, 2,6-di-F-Ph 4-Cl-Ph CI Br 430 18)
284 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph CI Me 108-110
285 4-Cl-Ph 2-Cl, 4-F-Ph CI Me 135-137
286 4-Cl-Ph 2,6-di-F, 4-MeO-Ph CI Me 108-110
287 2,6-di-F, 3-MeO-Ph 4-Cl, 3-Me-Ph CI Me 383
288 2,6-di-F, 3-MeO-Ph 3-F2CHO-Ph CI Me 401
289 2,6-di-F, 3-MeO-Ph 3-Et-Ph CI CI 93-95
290 3-Cl, 2,6-di-F, 4-MeO-Ph Ph CI CI 391
291 3-Br, 2,6-di-F, 4-MeO-Ph Ph CI Br 479
292 (Ex.
3-CN, 2,6-di-F-Ph 4-Cl-Ph CI Me 364 19)
293 6-Br-2-pyridinyl 4-Cl, 3-F-Ph CI CI 420
294 6-MeO-3 -pyridinyl 4-Cl, 3-F-Ph CI CI ** **
295 3-F, 5-MeO-4-pyridinyl 4-Cl, 3-F-Ph CI CI 390
296 3-quinolinyl 4-Cl, 3-F-Ph CI CI 392
297 2,6-di-Cl, 4-MeO-Ph 4-Cl, 3-F-Ph CI CI ** **
298 2,4-di-Cl, 6-MeO-Ph 4-Cl, 3-F-Ph CI CI ** **
299 2,6-di-F, 4-MeO, 3-Me-Ph Ph CI Me 349
300 2,3,6-tri-F-Ph 3,4-di-Cl-Ph CI Br 457 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
301 2,6-di-F, 3-MeO-Ph 4-Et-Ph CI Br 429
302 2,6-di-F, 3-MeO-Ph 4-Et-Ph CI CI 383
303 2,6-di-F, 3-MeO-Ph 4-I-Ph CI Br 134-138
304 2,6-di-F, 3-MeO-Ph 4-I-Ph CI CI 481
305 4-Cl-Ph 2,4,6-tri-F-Ph Me Br 123-125
306 4-Cl-Ph 2,4,6-tri-F-Ph Me CI 86-88
307 4-Cl-Ph 2,4,6-tri-F-Ph Me H 110-112
308 2,6-di-F, 4-MeO-Ph 3-Cl-Ph CI CI ** **
309 2,6-di-F, 4-MeO-Ph 3,4-di-F-Ph CI CI 391
310 3-F-4-pyridinyl 4-Cl, 3-F-Ph CI CI 360
311 4-Cl, 2-MeO-5-thiazolyl 4-Cl, 3-F-Ph CI CI 412
312 4-Cl-5-thiazolyl 4-Cl, 3-F-Ph CI CI 482
313 2-Cl-3-pyridinyl 4-Cl, 3-F-Ph CI CI 376
314 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Br Br ** **
315 2-Cl, 3,6-di-F-Ph 4-Me-Ph Br Br ** **
316 2,3,6-tri-F-Ph 4-Me-Ph Br Br ** **
317 2,4,6-tri-F-Ph 4-F-Ph Br Br ** **
318 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Br CI ** **
319 2-Cl, 3,6-di-F-Ph 4-Me-Ph Br CI ** **
320 2,3,6-tri-F-Ph 4-Me-Ph Br CI ** **
321 4-Cl-Ph 2,6-di-F-Ph Me CI 127-129
MeO-
322 4-Cl-Ph 2,6-di-F-Ph CI 95-97
CH2
323 2,6-di-F-Ph 6-quinolinyl CI Me 210-215
324 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Br Br ** **
325 2,6-di-F, 3-MeO-Ph 4-F-Ph Br CI 417
326 (Ex.
2,6-di-F-Ph 4-Cl-Ph Br BrCH2 463 17)
2,6-di-Br, 3,5-di-
327 2,4-di-F-Bn Br Me 582
MeO-Ph
328 2,6-di-F, 3-MeO-Ph 4-Et-Ph CI Me 364
329 2,3,6-tri-F-Ph 3,4-di-Cl-Ph CI Me 391
330 2-Cl, 6-F, 3-MeO-Ph 4-Cl-Ph CI CI 407
331 2,6-di-F, 4-MeO-Ph 3-Cl-Ph CI Br 435
332 2,6-di-F, 4-MeO-Ph 3,4-di-F-Ph CI Br 437
333 2-Br-4-pyridinyl 4-Cl, 3-F-Ph CI CI 420
334 5-Br-3-pyridinyl 4-Cl, 3-F-Ph CI CI 420 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
335 5-Br-2-pyridinyl 4-Cl, 3-F-Ph CI CI ** **
336 2,6-di-F, 4-MeO-Ph 6-CF3 -3 -pyridinyl CI CI ** **
337 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Me Me ** **
338 2,3,6-tri-F-Ph 4-Me-Ph Me Me ** **
339 2,4,6-tri-F-Ph 4-F-Ph Me Me ** **
340 2,4,6-tri-F-Ph 4-F-Ph Me CI ** **
341 2-Cl, 3,6-di-F-Ph 4-Me-Ph Me Me ** **
342 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Me CI ** **
343 2-Cl, 3,6-di-F-Ph 4-Me-Ph Me CI ** **
344 2,3,6-tri-F-Ph 4-Me-Ph Me CI ** **
345 2,6-di-F, 4-MeO-Ph 3,4-di-F-Ph CI Me 169-170
346 2,6-di-F, 4-MeO-Ph 3-Cl-Ph CI Me 173-174
347 2-Cl, 6-F, 3-MeO-Ph 4-Cl-Ph CI Br 154-156
348 2,6-di-F, 4-MeO-Ph 3 -CI, 4-Me-Ph CI CI 143-145
349 4-Cl-Ph 2-Cl, 4-F-Ph Me CI 123-127
350 (Ex.
2,6-di-F, 3-MeO-Ph 4-F-Ph Br Br 134-136 10)
351 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Br CI ** **
352 2,6-di-F, 3-MeO-Ph 4-Me-Ph Br Br 459
353 2-Cl, 6-F, 5-MeO-Ph 4-Cl-Ph CI Br 451
354 2,6-di-F, 4-MeO-Ph 2-C1-3 -pyridinyl CI CI 390
6-Cl, 2-MeO-3-
355 2,6-di-F, 4-MeO-Ph CI CI ** **
pyridinyl
2-Cl, 6-MeO-3-
356 2,6-di-F, 4-MeO-Ph CI CI 420 pyridinyl
357 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl CI CI 386
358 2,6-di-F, 3-MeO-Ph 4-Me-Ph Br CI 415
359 2-Cl, 6-F, 5-MeO-Ph 4-Cl-Ph CI CI 407
360 2-Cl, 6-F, 3-MeO-Ph 4-Cl-Ph CI Me 387
361 2,6-di-F, 4-MeO-Ph 4-Me-Ph Me Me ** **
362 2,6-di-F, 4-MeO-Ph 4-F-Ph Me Me ** **
363 2,6-di-F, 4-MeO-Ph 4-F-Ph Br Br ** **
364 2,6-di-F, 4-MeO-Ph 4-Me-Ph Br Br ** **
365 4-Me-Ph 2,6-di-F, 4-MeO-Ph Me Br 128-129
366 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Me CI 369
367 2,6-di-F-Ph 4-ClCH2S-Ph CI Me 386
368 2,4,6-tri-F-Bn 4-Cl-Ph H Me 338 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M-
369 2,4,6-tri-F-Bn 4-Cl-Ph CI Me 372
370 2,4,6-tri-F-Bn 4-Cl-Ph Br Me 417
371 2,4,6-tri-F-Bn 3,5-di-MeO-Ph CI Me 398
372 2,4,6-tri-F-Bn 3,5-di-MeO-Ph Br Me 442
373 2,4,6-tri-F-Bn 2,6-di-Cl-Ph CI Me 407
374 2,4,6-tri-F-Bn 2,6-di-Cl-Ph Br Me 451
375 2,4,6-tri-F-Bn 3,5-di-Cl-Ph CI Me 407
376 2,4,6-tri-F-Bn 3,5-di-Cl-Ph Br Me 451
377 2,6-di-F, 4-MeO-Ph 3 -CI, 4-Me-Ph CI Br 161-163
378 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Me Me 354
379 2,6-di-F, 4-MeO-Ph 3-F2CHO-Ph CI Br 467
380 2,6-di-F, 4-MeO-Ph 4-F2CHO-Ph CI Br 467
381 2,6-di-F, 4-MeO-Ph 3-CF3O-PI1 CI Br 485
382 2,6-di-F, 4-MeO-Ph 4-CF3O-PI1 CI Br 80-82
383 (Ex.
2,6-di-F, 3-MeO-Ph 4-F-Ph Me Me 333 11)
384 2-Cl, 6-F, 5-MeO-Ph 4-Cl-Ph CI Me 387
385 2,6-di-F, 3-MeO-Ph 3-F, 4-Me-Ph CI Br 432
386 2,6-di-F, 3-MeO-Ph 4-CN-Ph CI CI 191-193
387 2,6-di-F, 4-MeO-Ph 6-Me-3 -pyridinyl CI CI 370
388 2,6-di-F, 4-MeO-Ph 6-Me-3 -pyridinyl Br Br 458
389 2,6-di-F, 3-MeO-Ph 3-F, 4-Me-Ph CI CI 387
390 2,6-di-F, 3-MeO-Ph 4-Br-Ph CI CI 435
391 2,6-di-F, 3-MeO-Ph 4-Br-Ph CI Br 479
392 4-Me-Ph 2,6-di-F, 4-MeO-Ph Me CI 121-122
393 2,6-di-F, 4-MeO-Ph 3-F2CHO-Ph CI CI 68-70
394 2,6-di-F, 4-MeO-Ph 4-F2CHO-Ph CI CI 421
395 2,6-di-F, 4-MeO-Ph 3-CF30-Ph CI CI 94-95
396 2,6-di-F, 4-MeO-Ph 4-CF30-Ph CI CI 90-91
397 2,6-di-F, 4-MeO-Ph 4-F2CHO-Ph CI Me 401
398 2,6-di-F, 4-MeO-Ph 3-CN, 4-Me-Ph CI CI 141-143
399 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Me CI 106-109
400 2,6-di-Cl, 4-MeO-Ph 4-Cl, 3-F-Ph CI Br ** **
401 4-CN, 2-F, 6-MeO-Ph 4-Cl, 3-F-Ph CI CI ** **
402 2,6-di-F, 4-MeO-Ph 2-Br-3 -pyridinyl CI CI ** **
403 2,6-di-F-Ph 5-Me-2-pyridinyl CI CI ** **
404 4-Me-Ph 2,6-di-F, 4-MeO-Ph C1CH2 CI ** ** Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M-
405 2,6-di-F, 3-MeO-Ph 4-Br-Ph CI Me 415
406 (Ex.
2,6-di-F, 3-MeO-Ph 3-F2CHO-Ph CI H2C=CH 413
12)
407 2,6-di-F, 4-MeO-Ph 3-F2CHO-Ph CI Me 401
408 2,6-di-F, 4-MeO-Ph 3-CF30-Ph CI Me 419
409 2,6-di-F, 3-MeO-Ph 3-F, 4-Me-Ph CI Me 367
410 2,6-di-F-Ph Ph CI CI 325
411 2,6-di-F-Ph 6-Cl-3-pyridinyl CI CI ** **
412 3,5-di-F-4-pyridinyl 4-Cl, 3-F-Ph CI CI ** **
413 2,6-di-F, 3-MeO-Ph 4-CN-Ph CI Br 426
414 2,4,6-tri-F-Ph 3-F2CHO-Ph CI CI 82-83
415 2,4,6-tri-F-Ph 4-F2CHO-Ph CI CI 91-92
416 2,4,6-tri-F-Ph 3-CF30-Ph CI CI 76-77
417 2,4,6-tri-F-Ph 4-CF30-Ph CI CI 75-76
418 2,6-di-F, 4-MeO-Ph 3 -CI, 4-Me-Ph CI Me 143-145
419 2,4,6-tri-F-Ph 3-CF2HO-Ph CI Br 89-90
420 2,4,6-tri-F-Ph 4-F2CHO-Ph CI Br 94-95
421 2,4,6-tri-F-Ph 3-CF30-Ph CI Br 80-81
422 2,4,6-tri-F-Ph 4-CF30-Ph CI Br 87-88
423 2,6-di-F, 4-MeO-Ph 3-CN, 4-Me-Ph CI Br 145-147
424 2,4,6-tri-F-Ph 3-F2CHO-Ph CI Me 389
425 2,4,6-tri-F-Ph 4-F2CHO Ph CI Me 96-97
426 2,4,6-tri-F-Ph 3-CF30-Ph CI Me 93-94
427 2,4,6-tri-F-Ph 4-CF30-Ph CI Me 81-82
428 2,6-di-F, 4-MeO-Ph 3-CN, 4-Me-Ph CI Me 123-125
429 2,6-di-F, 3-MeO-Ph 4-CN-Ph CI Me 360
430 2,6-di-F-Ph 2-MeO-3 -pyridinyl CI CI ** **
431 2,6-di-F-Ph 2-Cl-3-pyridinyl CI CI 360
432 2,6-di-F-Ph 2-C1-3 -pyridinyl Br Br 448
6-Cl, 2-MeO-3-
433 2,6-di-F-Ph CI CI 390 pyridinyl
2-Cl, 6-MeO-3-
434 2,6-di-F-Ph CI CI 390 pyridinyl
435 2,6-di-F-Ph 6-MeO-3 -pyridinyl CI CI 356
436 2,6-di-F-Ph 6-MeO-3 -pyridinyl Br Br 444
437 (Ex.
2,6-di-F, 4-HO-Ph 4-Me-Ph CI Me 335 20) Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l
438 2,6-di-F, 4-F2CHO-Ph 4-Me-Ph CI Me 385
4-CH3C(=0)NH, 3-
439 2,6-di-F-Ph CI CI 171-172
Cl-Ph
440 2,6-di-F-Ph 4-CH3C(=0)NH-Ph CI CI 191-195
441 2,6-di-F-Ph 4-CH3C(=0)NH-Ph CI Br 224-225
442 2,6-di-F, 4-MeO-Ph 3 -CI, 4-MeO-Ph CI Br 126-128
443 2,6-di-F, 4-MeO-Ph 3 -CI, 4-MeO-Ph CI CI 113-115
444 2,6-di-F, 4-MeO-Ph 3-1, 4-Me-Ph CI CI 105-107
445 2,6-di-F-Ph 4-MeOC(=0)-Ph CI CI 173-174
446 3,5-di-MeO-Ph 2,6-di-F, 4-N02-Ph Br Me 456
447 2,6-di-F, 4-MeO-Ph 2-F, 4-Me-Ph CI CI 120-122
448 2,6-di-F, 4-MeO-Ph 2-F, 4-Me-Ph CI Br 144-146
449 2,6-di-F, 4-MeO-Ph 3-1, 4-Me-Ph CI Br 127-129
450 2,6-di-F, 4-MeO-Ph 3,5-di-MeO-Ph Me Br 441
2,6-di-Br, 3,5-di-
451 2,6-di-F, 4-MeO-Ph Me Br 599
MeO-Ph
452 3-EtO, 2,6-di-F-Ph 4-Cl-Ph CI Br 449
453 3-EtO, 2,6-di-F-Ph 3-F-Ph CI Br 433
454 3-EtO, 2,6-di-F-Ph 4-Cl-Ph CI CI 403
455 3-EtO, 2,6-di-F-Ph 3-F-Ph CI CI 487
456 2,6-di-F-Ph 6-Cl-3-pyridinyl CI Me 341
6-CH3C(=0)NH-3-
457 2,6-di-F, 4-MeO-Ph CI CI 413 pyridinyl
458 2,6-di-F, 4-MeO-Ph 2,6-di-Cl-3-pyridinyl CI CI 424
459 2,6-di-F, 4-MeO-Ph 2 -Me - 3 -pyridinyl CI CI 370
460 2,6-di-F, 4-MeO-Ph 2-MeO-3 -pyridinyl CI CI 386
2-Cl, 5-Me-3-
461 2,6-di-F, 4-MeO-Ph CI CI 404 pyridinyl
462 2,6-di-F, 4-MeO-Ph 5 -Br-3 -pyridinyl CI CI 434
463 3-CN, 2,6-di-F-Ph 4-F-Ph CI CI 368
464 3-CN, 2,6-di-F-Ph 4-Me-Ph CI CI 364
465 3-CN, 2,6-di-F-Ph 3-F-Ph CI CI 368
466 2,6-di-F-Ph 6-C1-3 -pyridinyl Me Br 386
467 3-EtO, 2,6-di-F-Ph 4-Cl-Ph CI Me 383
468 3-F-Ph 2,6-di-F, 4-MeO-Ph Me CI ** **
469 3-F-Ph 2,6-di-F, 4-MeO-Ph Me Br 113-114
470 2,6-di-F-Ph 4-MeOC(=0)-Ph CI Br 186-187 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
471 3-CN, 2,6-di-F-Ph 6-Cl-3-pyridinyl CI CI 387
472 2,6-di-F-Ph 6-Cl-3-pyridinyl Me CI 341
473 (Ex. 7) 2,6-di-F, 4-MeO-Ph 3,5-di-MeO-Ph Me CI
474 2,6-di-F, 4-MeO-Ph 4-Me-Ph CI MeS 381
475 (Ex.
6-Cl-3-pyridinyl 2,6-di-F, 4-MeO-Ph Me CI 94-95 24)
476 3-CN, 2,6-di-F-Ph 6-Cl-3-pyridinyl H CI 351
477 4-MeO-Ph 2,4-di-Cl-Ph CI CI 389
478 3-CN, 2,6-di-F-Ph 6-Cl-3-pyridinyl CI Br 429
479 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl CI Br 432
480 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl Br CI 470
481 (Ex.
2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl CI Br 470
22)
482 4-Cl-Ph 2,6-di-F, 4-N02-Ph CI Me 384
483 2,6-di-F, 3-MeO-Ph 6-C1-3 -pyridinyl CI CI 392
484 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Br CI 432
485 2,6-di-F-Ph 6-C1-3 -pyridinyl CI Br 406
486 3-F-Ph 2,6-di-F, 4-MeO-Ph C1CH2 CI ** **
487 (Ex.
2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl CI Me 404
23)
488 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl CI Me 366
489 3-CN, 2,6-di-F-Ph 6-C1-3 -pyridinyl Me Br 409
490 3-CN, 2,6-di-F-Ph 6-C1-3 -pyridinyl Me CI 365
491 3-CN, 2,6-di-F-Ph 6-C1-3 -pyridinyl C1CH2 CI 401
492 2,6-di-F-Ph 6-MeO-3 -pyridinyl Me CI 337
493 2,6-di-F-Ph 6-MeO-3 -pyridinyl Me Br 381
494 3-EtO, 2,6-di-F-Ph 3-F-Ph CI Me 367
495 2-Cl, 4-MeO-Ph 4-F-Ph CI Br 115-118
497 2,6-di-F, 4-MeO-Ph 5-F-3-pyridinyl CI CI 374
498 2,6-di-F, 4-MeO-Ph 6-C1-3 -pyridinyl CI Br 434
499 2,6-di-F, 3-MeO-Ph 6-C1-3 -pyridinyl CI Br 436
500 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl Me Br 450
501 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl Me CI 404
502 2,6-di-F, 3-MeO-Ph 6-C1-3 -pyridinyl Me CI 370
503* 2,6-di-F, 4-
4-Me-Ph CI Me 406 (Ex. 21) (MeNHCH2CH2CH2)-Ph
504 2,6-di-F, 3-MeO-Ph 6-C1-3 -pyridinyl Me Br 416 Cmpd. Q1 Q2 Rl R2 m.p. (°C) MS (M+l)
505 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Me Br 412
506 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Me CI 366
507 2,6-di-F, 3-MeO-Ph 6-C1-3 -pyridinyl CI Me 370
508 2,6-di-F, 4-MeO-Ph 6-C1-3 -pyridinyl CI Me 370
509 (Ex. 5) 2,6-di-F-Ph 4-Cl-Ph Br Me
510 (Ex.
2,6-di-F, 4-MeO-Ph 4-NCS-Ph CI Me
25)
511 2,6-di-F, 4-HO-Ph 3-F-Ph CI Me 339
512
2,6-di-F, 4-(NCCH20)-Ph 3-F-Ph CI Me
(Ex. 26)
513 4-CN, 2,6-di-F-Ph 6-C1-3 -pyridinyl Me CI ** **
514 4-EtO, 2,6-di-F-Ph 3-F-Ph CI Br ** **
515 4-EtO, 2,6-di-F-Ph 4-Me-Ph CI Me 150-156
516 4-EtO, 2,6-di-F-Ph 4-F-Ph CI Me 167-171
517 4-EtO, 2,6-di-F-Ph 3-F-Ph CI Me 136-140
518 4-EtO, 2,6-di-F-Ph 3-CF2HO-Ph CI Br 109-119
519 4-EtO, 2,6-di-F-Ph 3-CF2HO-Ph CI CI 100-104
520 4-CN, 2,6-di-F-Ph 6-MeO-3 -pyridinyl Me CI 361
521 4-CN, 2,6-di-F-Ph 6-MeO-3 -pyridinyl Me Br 405
522 4-CN, 2,6-di-F-Ph 4-Me-Ph CI Br 409
523 4-EtO, 2,6-di-F-Ph 3-CF2HO-Ph CI Me 116-120
524 4-CN, 2,6-di-F-Ph 3-F-Ph CI Br 413
525 4-CN, 2,6-di-F-Ph 3,4-di-F-Ph CI Me 366
526 4-CN, 2,6-di-F-Ph 3-F-Ph CI Me 348
527 4-CN, 2,6-di-F-Ph 4-F-Ph CI Br 413
528 2,6-di-F, 4-MeO-Ph 4-CF2HO-Ph Me CI 401
529 4-CN, 2,6-di-F-Ph 4-Cl-Ph Me CI 365
530 4-CN, 2,6-di-F-Ph 3-F-Ph Me CI 348
531 4-CN, 2,6-di-F-Ph 2,4-di-F-Ph CI Me 366
532 4-CN, 2,6-di-F-Ph 3-CF2HO-Ph Me CI 396
533 4-CN, 2,6-di-F-Ph 4-CF2HO-Ph CI CI 416
534 4-CN, 2,6-di-F-Ph 2-F, 4-Me-Ph CI Me 362
535 4-CN, 2,6-di-F-Ph 2-F, 4-Me-Ph Br Me 407
536 4-CN, 2,6-di-F-Ph 3-F-Ph Br Br 458
* HC1 salt.
** See Index Table B for lR NMR data.
*** See synthesis example for NMR data. INDEX TABLE B
Cmpd. NMR Data (CDCI3 solution unless indicated otherwise)a
18 δ 7.43 (t, IH), 7.03 (dd, IH), 6.95 (d, IH), 6.43 (d, 2H), 3.78 (s, 3H).
28 δ 7.36-7.30 (m, 2H), 7.08-7.01 (m, 2H), 6.66-6.57 (m, 2H), 2.30 (s, 3H), 2.14 (s, 3H).
186 δ 7.34-7.20 (m, 3H), 6.96-6.88 (m, IH), 6.80 (m, 2H), 5.00 (s, 2H).
189 δ 7.20 (d, 2H), 6.99-7.08 (m, IH), 6.93-6.80 (m, 3H), 4.99 (s, 2H), 3.88 (s, 3H).
212 δ 8.34 (m, IH), 7.74 (d, IH), 7.29 (m, 2H), 6.84 (t, 2H), 2.17 (s, 3H).
213 δ 8.50 (d, IH), 8.45 (s, IH), 7.44 (t, IH), 7.30 (t, IH), 7.04 (dd, IH), 4.50 (s, 2H).
214 δ 8.45 (s, IH), 8.38 (d, IH), 7.42 (t, IH), 7.02 (m, 2H), 6.88 (d, IH), 2.23 (s, 3H).
228 δ 7.46-7.42 (t, J = 8.0 Hz, IH), 7.24 (m, IH), 7.06-7.03 (dd, J= 8.0, 4.0 Hz, IH), 6.96-6.94 (d, J =
8.0 Hz, IH), 6.85 (m, IH).
229 δ 7.38 (d, J= 8.0 Hz, 2H), 7.23-7.15 (m, IH), 7.13 (d, J= 8.0 Hz, 2H), 6.86-6.81 (m, IH).
230 δ 7.20-7.10 (m, 3H), 7.11-7.07 (t, J= 8.0 Hz, 2H), 6.85-6.80 (m, IH).
235 δ 8.54 (d, IH), 7.82 (dd, IH), 7.46 (t, IH), 7.21 (d, IH), 7.10 (dd, IH), 6.97 (m, IH), 4.70 (s, 2H).
249 δ 7.36 (d, J= 8.0 Hz, 2H), 7.17-7.13 (m, 3H), 6.97-6.93 (m, IH).
250 δ 7.51 (t, IH), 7.40 (t, IH), 7.08 (dd, IH), 6.96 (m, 3H), 2.39 (s, 3H), 2.33 (s, 3H).
251 δ 7.57 (t, IH), 7.44 (t, IH), 7.11 (m, 2H), 7.05 (d, IH), 7.00 (m, IH), 4.73 (s, 2H), 2.37 (s, 3H).
252 δ 8.75 (s, IH), 7.45 (t, IH), 7.03 (dd, IH), 6.93 (m, IH), 2.22 (s, 3H).
253 δ 7.50 (t, IH), 7.05 (dd, IH), 6.95 (m, IH), 2.24 (s, 3H).
254 δ 7.46-7.42 (t, J= 8.0 Hz, IH), 7.22 (m, IH), 7.06-7.03 (dd, J= 8.0, 4.0 Hz, IH), 6.97-6.94 (dd, J =
8.0, 4.0 Hz, IH), 6.88-6.85 (m, IH).
259 δ 7.22-7.18 (m, 3H), 7.09-7.07 (t, J= 8.0 Hz, 2H), 6.84-6.79 (m, IH).
272 δ 7.19 (d, 2H), 7.06 (d, 2H), 7.04 (m, IH), 3.87 (s, 3H), 2.35 (s, 3H).
276 δ 7.34 (d, J= 8.0 Hz, 2H), 7.18-7.13 (m, IH), 7.11 (d, J= 8.0 Hz, 2H), 6.82-6.77 (m, IH), 2.81 (s,
3H).
277 δ 7.17-7.03 (m, 5H), 6.82-6.77 (m, IH), 2.18 (s, 3 H).
278 δ 7.32 (d, J= 8.0 Hz, 2H), 7.17-7.12 (m, IH), 7.10 (d, J= 8.0 Hz, 2H), 6.94-6.89 (m, IH), 2.13 (s,
3H).
279 δ 7.42-7.40 (t, J = 8.0 Hz, IH), 7.14-7.12 (m, IH), 6.97-6.95 (d, J= 8.0 Hz, IH), 6.89-6.87 (d, J =
8.0 Hz, IH), 6.80 (m, IH), 2.33 (s, 3H), 2.16 (s, 3H).
280 δ 7.19 (d, J= 8.0 Hz, 2H), 7.02-6.97 (m, IH), 6.91 (d, J= 8.0 Hz, 2H), 6.67-6.63 (m, 1 H), 1.97 (s,
3H), 1.88 (s, 3H).
281 δ 7.11-7.03 (m, 5H), 6.79-6.76 (m, IH), 2.32 (s, 3H), 2.17 (s, 3H).
294 δ 8.00 (d, IH), 7.48 (t, IH), 7.34 (dd, IH), 7.03 (dd, IH), 6.95 (m, IH), 6.70 (d, IH), 3.92 (s, 3H).
297 δ 7.47 (t, IH), 7.10 (dd, IH), 7.01 (m, IH), 6.87 (s, 2H), 3.80 (s, 3H).
298 δ 7.39 (t, IH), 7.06 (d, IH), 7.02 (dd, IH), 6.92 (m, IH), 6.74 (d, IH), 3.70 (s, 3H).
308 δ 7.43-7.20 (m, 3H), 7.09 (d, IH), 6.42 (d, 2H), 3.78 (s, 3H).
314 δ 7.44-7.40 (t, J= 8.0 Hz, IH), 7.25-7.16 (m, IH), 7.05 (d, J= 8.0 Hz, IH), 6.97-6.95 (m, 2H).
315 δ 7.16 (d, J = 8.0 Hz, 2H), 7.15-7.12 (m, IH), 7.06 (d, J= 8.0 Hz, 2H), 6.93-6.92 (m, IH), 2.34 (s, Cmpd. NMR Data (CDCI3 solution unless indicated otherwise)a
3H).
316 δ 7.17 (d, J = 8.0 Hz, 2H), 7.15-7.10 (m, IH), 7.05 (d, J = 8.0 Hz, 2H), 6.82-6.78 (m, IH), 2.36 (s,
3H).
317 δ 7.19-7.16 (m, 2H), 7.11-7.07 (t, J= 8.0 Hz, 2H), 6.67-6.63 (t, J= 8.0 Hz, 2H).
318 δ 7.45-7.40 (t, J= 8.0 Hz, IH), 7.21-7.06 (m, IH), 7.05 (d, J= 8.0 Hz, IH), 6.96-6.94 (m, 2H).
319 δ 7.16 (d, J= 8.0 Hz, 2 H,), 7.15-7.10 (m, IH), 7.06 (d, J= 8.0 Hz, 2H), 6.95-6.92 (m, IH), 2.34 (s,
3H).
320 δ 7.18 (d, J = 8.0 Hz, 2H), 7.15-7.10 (m, IH), 7.05 (d, J = 8.0 Hz, 2H), 6.81-6.78 (m, IH), 2.36 (s,
3H).
324 δ 7.35 (d, 2 H), 7.14 (d, 2 H), 6.95 (m, 1 H), 6.79 (m, 1 H), 3.83 (s, 3 H).
335 δ 8.40 (m, IH), 7.85 (dd, IH), 7.61 (d, IH), 7.45 (t, IH), 7.08 (dd, IH), 6.97 (m, IH).
336 δ 8.57 (br s, IH), 7.77 (m, 2H), 6.44 (d, 2H), 3.79 (s, 3H).
337 δ 7.39-7.35 (t, J = 8.0 Hz, IH), 7.12-7.08 (m, 2H), 6.95-6.91 (m, IH), 6.86-6.79 (d, J = 8.0 Hz,
IH), 2.33 (s, 3H), 2.11 (s, 3H).
338 δ 7.14-7.12 (d, J = 8.0 Hz, 2H), 7.11-7.02 (m, IH), 6.99-6.97 (d, J = 8.0 Hz, 2H), 6.77-6.72 (m,
2H), 2.34 (s, 3H), 2.16 (s, 3H).
339 δ 7.11-7.02 (m, 4 H), 6.62-6.50 (t, J= 8.0 Hz, 2H), 2.28 (s, 3H), 2.13 (s, 3H).
340 δ 7.15-7.13 (m, 2H), 7.05-7.03 (t, J= 8.0 Hz, 2H), 6.61-6.64 (t, J= 8.0 Hz, 2H), 2.15 (s, 3H).
341 δ 7.11-7.09 (d, J = 8.0 Hz, 2H), 7.14-7.01 (m, IH), 6.99-6.97 (d, J = 8.0 Hz, 2H), 6.88-6.83 (m,
IH), 2.32 (s, 3H), 2.12 (s, 3H).
342 δ 7.40-7.36 (t, J = 8.0 Hz, IH), 7.19 (m, 2H), 7.01 (d, J = 8.0 Hz, IH), 6.98-6.90 (m, 2H), 2.13 (s,
3H).
343 δ 7.12 (d, J = 8.0 Hz, 2H), 7.10-7.05 (m, IH), 7.03 (d, J = 8.0 Hz, 2H), 6.91-6.87 (m, IH), 2.33 (s,
3H), 2.13 (s, 3H).
344 δ 7.15 (d, J = 8.0 Hz, 2H), 7.13-7.05 (m, IH), 7.03 (d, J = 8.0 Hz, 2H), 6.80-6.75 (m, IH), 2.35 (s,
3H), 2.17 (s, 3H).
351 δ 7.35 (d, 2 H), 7.14 (d, 2 H), 6.95 (m, 1 H), 6.80 (m, 1 H), 3.84 (s, 3 H).
355 δ 7.46 (d, IH), 6.96 (d, IH), 6.41 (m, 2H), 3.85 (s, 3H), 3.78 (s, 3H).
361 δ 7.12 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.36 (d, J = 8.0 Hz, 2H), 3.74 (s, 3H), 2.27 (s,
3H), 2.13 (s, 3H).
362 δ 7.11-7.00 (m, 4H), 6.37 (d, J= 8.0 Hz, 2H), 3.75 (s, 3H), 2.28 (s, 3H), 2.13 (s, 3H).
363 δ 7.19-7.17 (m, 2H), 7.05-7.09 (t, J= 8.0 Hz, 2H), 6.40 (d, J= 8.0 Hz, 2H), 3.71 (s, 3H).
364 δ 7.16 (d, J = 8.0 Hz, 2H,), 7.05 (d, J = 8.0 Hz, 2H), 6.39 (d, J = 8.0 Hz, 2H), 3.76 (s, 3H), 2.36 (s,
3H).
400 δ 7.41 (t, IH), 7.11 (dd, IH), 7.01 (m, IH), 6.86 (s, 2H), 3.80 (s, 3H).
401 δ 7.42 (t, IH), 7.01 (m, 2H), 6.90 (m, 2H), 3.75 (s, 3H).
402 δ 8.46 (m, IH), 7.73 (m, IH), 7.39 (m, IH), 6.48 (m, IH), 6.34 (m, IH), 3.77 (s, 3H).
403 δ 8.25 (s, IH), 7.59 (d, IH), 7.32 (m, IH), 7.19 (d, IH), 6.86 (t, 2H), 2.36 (s, 3H). Cmpd. iH NMR Data (CDCI3 solution unless indicated otherwise)a
404 δ 7.15-7.10 (m, 4H), 6.53-6.47 (m, 2H), 4.54 (s, 2H), 3.80 (s, 3H), 2.33 (s, 3H).
411 δ 8.24 (s, 1H), 7.54 (d, 1H), 7.39 (m, 2H), 6.91 (t, 2H).
412 δ 8.39 (s, 2H), 7.46 (t, 1H), 7.07 (dd, 1H), 6.94 (d, 1H).
430 δ 8.20 (dd, 1H), 7.54 (m, 1H), 7.31 (m, 1H), 6.93 (m, 2H), 6.81 (t, 1H), 3.81 (s, 3H).
468 δ 7.35-7.29 (m, 1H), 7.08-6.92 (m, 3H), 6.56-6.50 (m, 2H), 4.54 (s, 2H), 3.82 (s, 3H).
486 δ 7.36-7.28 (m, 1H), 7.08-7.02 (m, 2H), 6.98-6.92 (m, 1H), 6.53 (d, 2H), 4.54 (s, 2H), 3.82 (s, 3H).
513 δ 8.18 (m, 1H), 7.54-7.52 (m, 1H), 7.41-7.39 (m, 1H), 7.23-7.21 (m, 2H), 2.19 (s, 3H).
514 δ 7.4 (m, 1H), 7.1 (m, 1H), 6.9 (m, 2H), 6.4 (d, 2H), 4.0 (q, 2H), 1.4 (t, 3H).
a NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (q)-quartet, (m) -multiple t, (dd)-doublet of doublets, (br s)-broad singlet.
BIOLOGICAL EXAMPLES OF THE INVENTION
General protocol for preparing test suspensions for Tests A-J: The test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-J. Each test was conducted in triplicate, and the results were averaged. Spraying a 200 ppm test suspension to the point of run-off on the test plants was the equivalent of a rate of about 800 g/ha. (An asterisk "*" next to the rating value indicates a 40 ppm test suspension.)
TEST A
Grape seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20 °C for 24 h. After a short drying period, the grape seedlings were sprayed with the test suspension to the point of run-off and then moved to a growth chamber at 20 °C for 5 days, after which time the grape seedlings were placed back into a saturated atmosphere at 20 °C for 24 h. Upon removal, visual disease ratings were made.
TEST B
The test suspension was sprayed to the point of run-off on bentgrass (Agrostis sp.) seedlings. The following day the seedlings were inoculated with a bran and mycelial slurry of Rhizoctonia solani (the causal agent of turf brown patch) and incubated in a saturated atmosphere at 27 °C for 48 h, and then moved to a growth chamber at 27 °C for 6 days, after which time visual disease ratings were made.
TEST C
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of tomato Botrytis) and incubated in saturated atmosphere at 20 °C for 48 h, and then moved to a growth chamber at 24 °C for 3 days, after which time visual disease ratings were made.
TEST D
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Alternaria solani (the causal agent of tomato early blight) and incubated in a saturated atmosphere at 27 °C for 48 h, and then moved to a growth chamber at 20 °C for 5 days, after which time visual disease ratings were made.
TEST E
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of tomato late blight) and incubated in a saturated atmosphere at 20 °C for 24 h, and then moved to a growth chamber at 20 °C for 5 days, after which time visual disease ratings were made.
TEST F
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria nodorum (the causal agent of wheat glume blotch) and incubated in a saturated atmosphere at 24 °C for 48 h, and then moved to a growth chamber at 20 °C for 6 days, after which time visual disease ratings were made.
TEST G
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria tritici (the causal agent of wheat leaf blotch) and incubated in saturated atmosphere at 24 °C for 48 h, and then moved to a growth chamber at 20 °C for 19 days, after which time visual disease ratings were made.
TEST H
Wheat seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20 °C for 24 h, and then moved to a growth chamber at 20 °C for 2 days. At the end of this time the test suspension was sprayed to the point of run-off on the wheat seedlings, then the seedlings were moved to a growth chamber at 20 °C for 6 days, after which time visual disease ratings were made. TEST I
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20 °C for 24 h, and then moved to a growth chamber at 20 °C for 7 days, after which time visual disease ratings were made.
TEST J
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Blumeria graminis f. sp. tritici (also known as Erysiphe graminis f. sp. tritici, the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20 °C for 8 days, after which time visual disease ratings were made.
Results for Tests A- J are given in Table A. In the Table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates no test results. All results are for 200 ppm except where followed by "*", which indicates 40 ppm.
TABLE A
mpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
1 0 65 99 100 0 100 100 0* 100 100
2 0 99 99 100 0 99 100 - 99 100
3 0 38 98 99 0 0 100 - 88 99
4 0 99 99 100 0 95 100 - 100 100
5 0 81 100 100 0 0 99 - 98 99
6 - - 99* 99* - 0* 94* - 97* 100*
7 6 99 100 100 0 99 99 - 100 100
8 20 99 87* 100* 0 94* 96* - 99* 100*
9 - - 0 - 0 97 - 99 90
10 - - 98* 100* - 0* 84* - 97* 95*
11 - - 99 99 - 0 88 - 100 95
12 13 100 99 100 0 100 100 - 99 100
13 - - 93 100 - 0 91 - 100 100
14 - - 99 100 - - 88 - 100 99
15 - - 97 100 - 51 95 - 100 100
16 - - 99 100 - 74 91 - 100 100
17 - - 99* 100* - 0* 94* - 100* 100*
18 - - 99 100 - 100 95 - 100 100
19 99* 100* 99* 90* 91* 100* 100* Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
20 20 100 100 100 0 100 100 - 100 100
21 - - 99 100 - 99 92 - 100 100
22 - - 99* 100* - 100* 92* - 100* 100*
23 - - 99* 100* - 99* 95* - 98* 100*
24 - - 99 100 - 64 94 - 99 98
25 - - 99* 100* - 99* 93* - 91 * 100*
26 - - 98* 100* - 97* 96* - 97* 99*
27 - - 99* 100* - 40* 92* - 99* 98*
28 - - 100 98 - 100 100 99 100 100
29 - - 94 42 - 0 77 - 54 93
30 - - 99 100 - 100 94 - 100 100
31 - - 98 100 - 100 94 - 99 99
32 - - 98 100 - 100 92 - 100 100
33 - - 94 100 - 100 94 - 97 99
34 - - 84 100 - 0 97 - 99 100
35 - - 89 100 - 0 95 - 100 99
36 - - 92 24 - 0 87 - 99 91
37 - - 94* 100* - 98* 93* - 99* 100*
38 - - 84 99 - 0 87 - 96 100
39 - - 98 100 - 51 79 - 99 100
40 - - 93* 100* - 82* 97* - 86* 97*
41 - - 99 100 - 95 95 - 100 96
42 - - 0 100 - 0 95 - 41 95
43 - - 99 100 - 99 94 - 99 99
44 - - 96 100 - 92 97 - 99 100
45 - - 100 100 - 60 87 - 100 100
46 - - 37 99 - 60 97 - 99 100
47 - - 90 100 - 100 98 - 100 100
48 - - 81 100 - 69 93 - 98 100
49 - - 90 100 - 100 91 - 99 100
50 - - 97 100 - 99 98 - 100 100
51 - - 0 99 - 0 88 - 91 99
52 - - 73 100 - 11 98 - 96 100
53 - - 0 0 - 0 93 - 27 99
54 - - 0 0 - 0 0 - 54 0
55 - - 98 100 - 100 99 - 96 100
56 76 100 0 98 89 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
57 - - 97 100 - 100 99 - 98 100
58 - - 56 53 - 0 95 - 99 100
59 - - 96 97 - 95 95 - 100 100
60 - - 98* 100* - 97* 97* - 97* 99*
61 - - 97 93 - 99 97 - 98 99
62 - - 88 0 - 0 97 - 100 99
63 - - 98 0 - 55 97 - 99 99
64 - - 79 92 - 90 98 - 100 99
65 - - 98 99 - 94 94 - 99 100
66 - - 96 100 - 100 96 - 100 100
67 - - 100* 100* - 0* 74* - 98* 99*
68 - - 94 57 - 0 94 - 68 63
69 - - 94 99 - 100 95 - 97 96
70 - - 98 99 - 97 95 - 97 97
71 - - 93 0 - 0 95 - 41 72
72 - - 0* 0* - 0* 0* - 0* 0*
73 - - 96 100 - 99 97 - 99 100
74 - - 99 100 - 60 94 - 99 100
75 - - 96 80 - 40 91 - 80 0
76 - - 98 0 - 0 96 - 90 92
77 - - 98 100 - 100 96 - 100 100
78 - - 97 99 - 69 96 - 99 99
79 - - 99 100 - 98 95 - 100 100
80 - - 97 96 - 96 93 - 97 100
81 - - 99 100 - 0 89 - 74 95
82 - - 98 100 - 0 85 - 99 96
83 - - 90* 99* - 0* 85* - 0* 48*
84 - - 97 100 - 99 93 - 99 100
85 - - 99 100 - 0 93 - 100 100
86 - - 0 0 - 0 93 - 55 39
87 - - 99 100 - 0 91 - 99 100
88 - - 99 100 - 97 94 - 100 100
89 - - 99 100 - 100 100 - 100 100
90 - - 100 100 - 100 100 - 100 100
91 - - 99 100 - 100 100 - 100 100
92 - - 99 100 - 100 100 - 100 100
93 - - 91 100 82 100 100 99 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
94 - - 99 100 - 99 100 - 100 100
95 - - 53 0 - 98 96 - 95 95
96 - - 99 100 - 60 98 - 97 100
97 - - 97* 100* - 69* 99* - 89* 96*
98 - - 99 99 - 69 96 - 89 99
99 - - 98 100 - 69 96 - 99 100
100 - - 99 100 - 0 93 - 86 99
101 - - 99 100 - 87 95 - 99 100
102 - - 98* 100* - 99* 97* - 97* 99*
103 - - 97 99 - 98 97 - 100 100
104 - - 99 100 - 96 97 - 100 100
105 - - 99 100 - 99 97 - 100 100
106 - - 88* 97* - 0* 93* - 23* 94*
107 - - 91* 88* - 0* 96* - 19* 94*
108 - - 99* 100* - 0* 95* - 0* 98*
109 - - 97 99 - 84 98 - 100 100
110 - - 99 100 - 40 96 - 88 99
111 - - 97 98 - 0 95 - 99 99
112 - - 99 100 - 100 98 - 98 99
113 - - 99 99 - 100 98 - 99 99
114 - - 98 99 - 82 98 - 100 100
115 - - 97 97 - 82 98 - 100 99
116 - - 99 100 - 73 96 - 97 99
117 - - 99* 91 * - 0* 85* - 66* 48*
118 - - 99 100 - 0 97 - 100 100
119 - - 99 100 - 78 94 - 100 99
120 - - 98 88 - 0 97 - 100 100
121 - - 99 100 - 94 97 - 100 100
122 - - 98 100 - 0 97 - 100 99
123 - - 98 100 - 51 97 - 100 99
124 - - 97 100 - 0 93 - 100 100
125 - - 99 100 - 64 94 - 100 94
126 - - 99 100 - 0 92 - 100 97
127 - - 99 99 - 0 93 - 100 100
128 - - 98 99 - 0 90 - 100 95
129 - - 92 100 - 100 96 - 98 95
130 99 100 100 98 96 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
131 - - 91 61 - 98 97 - 98 100
132 - - 87 98 - 87 97 - 100 99
133 - - 90* 91 * - 0* 90* - 18* 26*
134 - - 99 100 - 100 98 - 100 100
135 - - 95 99 - 0 98 - 100 99
136 - - 93 99 - 80 98 - 100 99
137 - - 63 0 - 0 96 - 100 42
138 - - 100* 99* - 97* 94* - 97* 98*
139 - - 99* 100* - 0* 96* - 93* 94*
140 - - 33* 57* - 0* 13* - 0* 0*
141 - - 99* 99* - 0* 91* - 80* 73*
142 33 99 98 97 0 51 96 - 99 99
143 82 99 98 99 0 0 97 - 99 100
144 - - 99 99 - 0 95 - 97 98
145 - - 99 99 - 0 99 - 97 98
146 - - 99 100 - 60 98 - 99 100
147 - - 93 51 - 0 90 - 80 98
148 - - 96 100 - 0 98 - 99 100
149 - - 76 67 - 0 88 - 0 95
150 - - 98 96 - 0 94 - 99 99
151 - - 96 99 - 0 98 - 94 99
152 - - 98 99 - 0 98 - 89 91
153 - - 99 97 - 0 99 - 94 99
154 - - 87 61 - 100 99 - 96 98
155 - - 96* 88* - 0* 95* - 41 * 94*
156 - - 95 99 - 0 98 - 55 98
157 - - 99 99 - 92 99 - 97 99
158 - - 100 100 - 99 96 - 100 100
159 - - 100 100 - 100 98 - 100 100
160 - - 99 99 - 0 93 - 96 100
161 - - 100 100 - 100 96 - 99 100
162 - - 100 100 - 100 97 - 100 100
163 - - 100 100 - 100 96 - 96 93
164 - - 99* 95* - 51 * 95* - 89* 92*
165 - - 99 100 - 98 99 - 100 98
166 - - 100 100 - 99 96 - 99 100
167 100 99 100 97 95 99 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
168 - - 100 100 - 100 97 - 100 100
169 - - 100* 99* - 73* 93* - 74* 81 *
170 - - 100 100 - 100 97 100 100 99
171 - - 100 100 - 99 95 - 100 100
172 - - 99 0 - 42 87 - 97 78
173 - - 99 16 - 0 63 - 82 93
174 - - 100 95 - 0 92 - 94 99
175 - - 99 100 - 100 95 - 100 100
176 - - 99 99 - 69 96 - 100 100
177 - - 99 100 - 100 95 - 100 100
178 - - 99 88 - 0 95 - 98 99
179 - - 99 100 - 100 95 - 100 100
180 - - 100 100 - 100 93 - 100 100
181 - - 100 100 - 100 95 - 100 100
182 - - 100 100 - 97 96 - 100 100
183 - - 99 99 - 0 93 65 99 100
184 - - 100 98 - 0 93 0 93 99
185 - - 100 99 - 92 95 6 99 100
186 - - 99 85 - 83 94 98 100 100
187 - - 99 96 - 79 95 64 99 100
188 - - 100 100 - 99 95 17 100 99
189 - - 100 91 - 73 94 32 96 99
190 - - 100 96 - 0 94 11 94 97
191 - - 95 0 - 0 85 11 19 0
192 - - 99 80 - 0 94 6 98 94
193 - - 99 98 - 69 93 11 99 99
194 - - 99 91 - 0 95 6 99 100
195 - - 99 100 - 98 96 11 98 97
196 - - 99 0 - 0 94 0 80 0
197 - - 100 96 - 86 96 17 99 97
198 - - 99* 100* - 99* 94* - 99* 100*
199 - - 100 100 - 0 96 0 98 0
200 - - 100 94 - 0 95 6 91 96
201 - - 100 100 - 0 94 17 98 100
202 - - 63* 0* - 0* 23* 11* 0* 0*
203 - - 99 96 - 0 94 6 91 99
204 100 99 0 97 11 97 99 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
205 - - 99* 100* - 0* 88* 11* 41 * 0*
206 - - 100 100 - 100 97 11 100 100
207 - - 99 100 - 99 96 61 100 100
208 - - 99 100 - 100 93 32 100 100
209 - - 99 100 - 100 95 86 100 100
210 - - 99 99 - 95 93 6 99 100
211 - - 100 100 - 100 95 17 99 100
212 - - 100 100 - 100 100 83 100 100
213 - - 62* 0* - 0* 0* 63* 28* 0*
214 - - 100 99 - 0 100 70 100 99
215 - - 99 99 - 82 93 9 97 99
216 - - 94 91 - 51 96 0 97 99
217 - - 100 100 - 51 96 67 98 100
218 - - 99* 98* - 0* 94* 0* 86* 0*
219 - - 100 98 - 0 95 9 94 98
220 - - 99 99 - 0 94 0 90 99
221 - - 100 100 - 99 95 85 100 100
222 - - 100* 100* - 99* 91* 0* 100* 100*
223 - - 100* 100* - 90* 93* 0* 100* 100*
224 - - 100* 100* - 82* 91* 0* 99* 99*
225 - - 100 100 - 80 93 0 99 99
226 - - 100 99 - 78 95 0 96 96
227 - - 99 98 - 0 92 0 94 95
228 - - 99 100 - 82 91 0 99 100
229 - - 100 100 - 99 93 54 100 100
230 - - 100 100 - 87 92 18 97 77
231 - - 0 0 - 0 8 0 41 0
232 - - 100 99 - 0 93 0 98 97
233 - - 0 0 - 0 3 0 28 0
234 - - 98 57 - 0 72 17 0 0
235 - - 63 0 - 100 50 0 55 0
236 - - 99 0 - 0 90 0 41 0
237 - - 98 0 - 0 35 0 80 0
238 - - 100 99 - 0 95 9 99 98
239 - - 99 0 - 0 93 9 74 80
240 - - 100 100 - 40 91 54 99 96
241 100 100 64 91 41 99 97 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
242 - - 99 100 - 89 90 9 98 97
243 - - 99 100 - 0 92 0 99 96
244 - - 99 100 - 98 92 74 99 99
245 - - 99 100 - 87 89 100 100 100
246 - - 31 * 0* - 0* 48* 0* 0* 0*
247 - - 99 0 - 0 91 0 74 0
248 - - 99* 98* - 60* 92* 0* 95* 99*
249 - - 99 99 - 0 94 0 90 98
250 - - 100 0 - 0 93 0 74 75
251 - - 99 0 - 0 86 0 27 0
252 - - 100 91 - 0 91 0 99 99
253 - - 94 0 - 0 78 0 0 0
254 - - 100* 99* - 0* 96* 0* 95* 97*
255 - - 100* 99* - 35* 96* 0* 91 * 98*
256 - - 100* 99* - 0* 95* 0* 67* 95*
257 - - 99* 99* - 0* 95* 0* 95* 99*
258 - - 99 100 - 60 99 - 100 100
259 - - 98 100 - 0 91 - 99 98
260 - - 100 100 - 99 95 18 100 100
261 - - 100 99 - 0 94 0 99 100
262 - - 100 100 - 100 97 60 99 100
263 - - 99 100 - 99 95 79 99 100
264 - - 100* 100* - 99* 93* 0* 100* 99*
265 - - 100* 98* - 0* 94* 0* 88* 13*
266 - - 100 80 - 79 96 0 79 100
267 - - 100 99 - 82 96 0 82 100
268 - - 100 100 - 99 94 0 99 100
269 - - 99 100 - 0 96 0 73 100
270 - - 100 100 - 99 96 0 94 99
271 - - 100 0 - 0 99 0 97 98
272 - - 99 98 - 0 100 0 98 99
273 - - 100 100 - 100 93 100 100 100
274 - - 100 0 - 92 96 0 97 98
275 - - 0* 0* - 0* 3* 0* 0* 0*
276 - - 100* 100* - 0* 99* 0* 74* 99*
277 - - 100* 99* - 0* 14* 9* 0* 0*
278 99* 99* 0* 96* 0* 93* 100* Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
279 - - 100* 100* - 0* 99* 0* 94* 98*
280 - - 100* 100* - 0* 97* 0* 26* 99*
281 - - 100* 99* - 0* 89* 9* 9* 94*
282 - - 100 100 - 99 100 0 97 100
283 - - 100 100 - 100 100 0 97 99
284 - - 100 98 - 0 100 0 100 100
285 - - 100 100 - 60 100 0 99 100
286 - - 100* 0* - 69* 94* 0* 91 * 99*
287 - - 100 100 - 100 100 0 96 100
288 - - 100 100 - 100 100 27 100 100
289 - - 100 100 - 99 100 0 93 100
290 - - 100 100 - 0 99 0 100 100
291 - - 99 77 - 0 99 0 98 98
292 - - 100 100 - 100 100 0 100 100
293 - - 50 0 - 0 92 0 0 0
294 - - 96 9 - 0 99 0 68 76
295 - - 99 24 - 0 99 0 68 0
296 - - 87 98 - 0 81 0 0 0
297 - - 99 80 - 60 100 0 98 98
298 - - 0 0 - 0 86 0 0 0
299 - - 97 100 - 95 94 - 100 100
300 - - 99 100 - 98 95 - 98 99
301 - - 97 99 - 0 97 - 97 99
302 - - 99 99 - 0 95 - 99 100
303 - - 99 99 - 99 97 - 89 100
304 - - 99 100 - 100 98 - 95 99
305 - - 97* 100* - 92* 95 - 97* 98*
306 - - 96* 100* - 0* 95* - 68* 91 *
307 - - 94 80 - 0 30 - 0 81
308 - - 99 100 - 90* 93 - 100 100
309 - - 77 100 - 33 93 - 100 100
310 - - 99 95 - 0 95 - 99 68
311 - - 0 0 - 0 88 - 0 43
312 - - 85 0 - 0 91 - 97 97
313 - - 96 16 - 0 92 - 95 89
314 - - 99* 63* - 0* 95* 9* 98* 98*
315 99* 85* 0* 97* 0* 93* 96* Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
316 - - 99* 99* - 0* 94* 0* 97* 98*
317 - - 100* 100* - 0* 96* 0* 78* 99*
318 - - 99* 99* - 0* 95* 0* 100* 99*
319 - - 99* 89* - 0* 72* 0* 99* 100*
320 - - 100* 99* - 0* 88* 0* 99* 99*
321 - - 99* 100* - 0* 82* 0* 93* 100*
322 - - 94* 0* - 0* 32* 0* 71 * 96*
323 - - 99* 99* - 0* 96* 0* 91 * 58*
324 - - 100 100 - 100 97 0 98 100
325 - - 100 100 - 100 96 80 100 100
326 - - 98 26 - 0 92 0 87 42
327 - - 9 0 - 0 0 0 75 0
328 - - 100 100 - 95 94 0 99 100
329 - - 100 100 - 95 96 0 99 100
330 - - 100 100 - 99 95 0 97 100
331 - - 100 99 - 0 94 32 98 100
332 - - 100 100 - 89 95 28 100 100
333 - - 96 88 - 0 95 0 98 98
334 - - 66 0 - 0 0 0 14 0
335 - - 96 0 - 0 88 0 78 0
336 - - 99 100 - 100 93 41 100 100
337 - - 96* 98* - 0* 93* 0* 100* 100*
338 - - 97* 99* - 0* 87* 0* 76* 100*
339 - - 92* 99* - 0* 91* 0* 0* 0*
340 - - 94* 100* - 0* 82* 0* 0* 0*
341 - - 96* 99* - 0* 93* 0* 97* 99*
342 - - 89* 99* - 0* 89* 0* 99* 99*
343 - - 97* 99* - 0* 31* 0* 99* 100*
344 - - 93* 99* - 0* 6* 0* 0* 97*
345 - - 99 100 - 100 93 100 100 100
346 - - 98 100 - 100 94 98 100 100
347 - - 98 99 - 98 95 0 67 99
348 - - 90* 92* - 60* 93* 0* 98* 100*
349 - - 99 99 - 99 96 0 100 100
350 - - 99 100 - 100 97 0 99 100
351 - - 99 100 - 100 99 9 98 100
352 99 99 99 99 0 99 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
353 - - 97 98 - 0 98 40 79 99
354 - - 99 100 - 100 100 100 100 100
355 - - 99 99 - 73 100 0 93 99
356 - - 97 99 - 0 100 100 100 100
357 - - 97 100 - 100 100 100 100 100
358 - - 100 100 - 96 98 0 99 100
359 - - 100 99 - 99 98 0 98 100
360 - - 100 100 - 100 97 0 100 100
361 - - 99* 99* - 0* 98* 0* 98* 90*
362 - - 100* 100* - 0* 98* 0* 99* 96*
363 - - 100* 100* - 0* 98* 0* 99* 97*
364 - - 99* 100* - 60* 98* 85* 99* 97
365 - - 100* 100* - 80* 98* 68* 100* 98*
366 - - 100 100 - 100 99 0 100 100
367 - - 0 0 - 0 82 9 48 0
368 - - 0 0 - 0 58 0 88 71
369 - - 100 0 - 0 99 41 99 95
370 - - 97 0 - 0 99 0 99 91
371 - - 38 0 - 0 2 0 0 0
372 - - 0 0 - 0 2 0 0 0
373 - - 99 76 - 60 97 9 100 99
374 - - 99 0 - 0 99 27 100 100
375 - - 15 0 - 0 3 0 0 21
376 - - 0 0 - 0 0 0 0 0
377 - - 99* 96* - 0* 97* 0* 98* 89*
378 - - 99* 60* - 0* 97* 0* 95* 0*
379 - - 100 100 - 98 99 27 100 99
380 - - 100 100 - 99 98 0 100 100
381 - - 99 88 - 60 97 0 99 100
382 - - 98 100 - 94 96 0 99 100
383 - - 100 100 - 99 98 0 100 100
384 - - 100 100 - 100 97 0 99 100
385 - - 100 100 - 96 98 0 100 100
386 - - 99 100 - 0 96 0 46 98
387 - - 100 100 - 100 99 100 100 100
388 - - 100 100 - 100 99 100 100 100
389 99 100 97 100 9 100 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
390 - - 100 100 - 99 100 0 99 100
391 - - 100 100 - 100 100 0 94 100
392 - - 99* 100* - 64* 99* 66* 100* 100*
393 - - 100 100 - 100 96 97 100 100
394 - - 100 100 - 100 97 97 100 100
395 - - 99 67 - 0 94 7 99 100
396 - - 99 100 - 98 94 72 100 100
397 - - 100 100 - 100 97 84 100 99
398 - - 100* 99* - 92* 95* 0* 99* 71 *
399 - - 100 100 - 0 96 22 100 99
400 - - 100 0 - 60 100 0 98 97
401 - - 96 0 - 0 73 0 76 72
402 - - 100 99 - 100 100 100 100 99
403 - - 100 100 - 87 100 97 100 100
404 - - 99* 33* - 0* 96* 84* 98* 21 *
405 - - 100 100 - 99 97 15 99 100
406 - - 99 97 - 0 94 0 85 83
407 - - 100 100 - 100 97 100 100 100
408 - - 100 99 - 98 98 97 100 100
409 - - 100* 100* - 94* 96* 7* 100* 100*
410 - - 100 100 - 0 97 96 98 98
411 - - 100 100 - 100 96 100 100 100
412 - - 100 100 - 99 96 99 100 100
413 - - 94 73 - 0 98 0 74 97
414 - - 100 100 - 97 98 99 - 100
415 - - 100 100 - 100 99 99 100 100
416 - - 26 0 - 0 9 0 0 0
417 - - 86 100 - 0 94 7 0 99
418 - - 99* 98* - 87* 99* 7* 97* 97*
419 - - 99 100 - 99 99 98 100 100
420 - - 99 100 - 100 99 97 100 100
421 - - 19 0 - 0 73 0 0 94
422 - - 99 100 - 0 99 0 28 100
423 - - 100* 96* - 31 * 99* 7* 86* 82*
424 - - 99 100 - 100 99 100 100 100
425 - - 99 100 - 99 99 100 100 100
426 91 66 0 81 0 16 57 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
427 - - 99 100 - 60 96 0 8 100
428 - - 99* 100* - 64* 99* 15* 97* 21 *
429 - - 100 100 - 0 100 0 99 100
430 - - 100 0 - 0 99 0 98 99
431 - - 99 99 - 0 100 100 100 99
432 - - 98 85 - 0 98 99 99 97
433 - - 99 53 - 0 96 51 98 99
434 - - 100 99 - 90 98 100 100 99
435 - - 100 100 - 99 98 100 100 100
436 - - 100 100 - 99 99 100 100 100
437 - - 99 64 - 0 94 0 99 90
438 - - 99 99 - 0 100 40 99 100
439 - - 90* 24* - 0* 95* 0* 52* 0*
440 - - 97* 0* - 0* 92* 0* 65* 0*
441 - - 0* 0* - 0* 87* 0* 52* 0*
442 - - 99* 17* - 0* 95* 0* 83* 35*
443 - - 93* 47* - 0* 97* 0* 92* 35*
444 - - 0* 0* - 0* 95 0* 0* 69*
445 - - 0* 0* - 0* 97* 0* 61 * 0*
446 - - 97 0 - 60 97 0 95 79
447 - - 99* 99* - 78* 100* 99* 100* 99*
448 - - 100* 99* - 91 * 98* 100* 99* 100*
449 - - 8* 0* - 0* 97* 49* 9* 0*
450 - - 99* 99* - 99* 99* 100* 100* 96*
451 - - 0 0 - 0 55 0 61 61
452 - - 100 99 - 100 99 0 98 100
453 - - 100 99 - 99 99 54 99 100
454 - - 100 99 - 96 99 46 97 100
455 - - 100 99 - 99 99 54 99 100
456 - - 100 100 - 99 99 100 100 100
457 - - 99 100 - 99 99 9 100 90
458 - - 99 93 - 98 99 98 100 94
459 - - 100 100 - 99 98 100 100 100
460 - - 100 99 - 99 99 99 100 98
461 - - 100 100 - 100 99 100 100 100
462 - - 100 100 - 100 99 100 100 100
463 100 100 99 99 18 100 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
464 - - 99 100 - 98 100 0 100 100
465 - - 99 100 - 98 99 0 99 100
466 - - 100 100 - 99 100 97 100 100
467 - - 100 100 - 100 99 53 99 100
468 - - 100* 100* - 82* 98* 98* 99* 98*
469 - - 100* 100* - 99* 98* 100* 100* 100*
470 - - 78 0 - 0 98 0 74 81
471 - - 99* 99* - 51 * 95* 39* 82* 64*
472 - - 100 100 - 99 99 100 100 100
473 - - 100* 100* - 99* 98* 0* 99* 98*
474 - - 100 99 - 97 99 97 99 96
475 - - 100* 100* - 100* 99* 99* 99* 100*
476 - - 100 91 - 0 98 8 19 93
477 - - 99 0 - 0 99 0 83 56
478 - - 100 100 - 91 99 7 100 95
479 - - 99 100 - 99 99 100 100 100
480 - - 57 100 - 0 99 25 86 100
481 - - 100 100 - 100 99 67 100 100
482 - - 100 0 - 82 99 7 80 89
483 - - 100 100 - 100 99 100 100 100
484 - - 100 100 - 100 98 99 100 98
485 - - 100 100 - 99 99 98 99 99
486 - - 100* 57* - 0* 95 7* 86* 61 *
487 - - 100 100 - 100 100 78 100 100
488 - - 100 100 - 100 99 100 100 100
489 - - 100 100 - 78 99 0 99 73
490 - - 100 100 - 95 100 - 99 99
491 - - 100 100 - 0 99 0 96 79
492 - - 100 100 - 97 100 99 100 100
493 - - 99 100 - 98 99 99 100 100
494 - - 100 100 - 97 98 0 100 99
495 - - 100 99 - 73 99 15 91 98
497 - - 100 100 - 100 99 100 100 100
498 - - 100 100 - 99 99 - 100 100
499 - - 100 100 - 99 100 9 99 100
500 - - 99 100 - 99 100 0 99 100
501 100 100 100 99 0 99 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
502 - - 100 100 - 100 100 41 100 100
503 - - 100 99 - 99 99 41 100 95
504 - - 100 100 - 99 100 9 100 100
505 - - 99 100 - 97 100 99 100 100
506 - - 100 100 - 100 100 100 100 100
507 - - 100 100 - 100 100 96 100 100
508 - - 100 100 - 100 100 100 100 100
509 37 99 100 100 0 100 100 - 100 100
510 - - 100 99 - 92 98 0 99 72
511 - - 100 99 - 0 97 0 98 72
512 - - 100 100 - 100 99 41 100 100
513 - - 100 100 - 100 100 41 99 99
514 - - 99 99 - 100 99 89 97 100
515 - - 99 99 - 100 98 95 99 99
516 - - 100 100 - 99 100 98 99 100
517 - - 100 100 - 100 100 100 100 100
518 - - 100 97 - 90 100 90 98 99
519 - - 100 100 - 99 99 96 99 99
520 - - 99 99 - 100 100 98 100 100
521 - - 100 100 - 87 100 32 100 100
522 - - 100 100 - 98 99 0 99 99
523 - - 100 100 - 100 100 100 10 99
524 - - 100 100 - 99 99 0 98 100
525 - - 99 99 - 99 100 0 99 100
526 - - 100 100 - 99 99 97 100 100
527 - - 99 99 - 100 100 18 100 100
528 - - 98 97 - 97 99 0 100 100
529 - - 100 100 - 100 98 0 99 100
530 - - 100 100 - 100 100 99 100 100
531 - - 100 99 - 100 100 100 100 100
532 - - 99 99 - 90 100 0 98 97
533 - - 100* 100* - 99* 100* 0* 92* 100*
534 - - 99* 100* - 90* 100* 8* 100* 100*
535 - - 99* 100 - 95* 100* 0* 100* 100*
536 99 100 98 100 0 99 100 The general protocol for preparing test compositions for Tests K, L and M was as follows. Compound 181, bixafen, 5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin- l-yl)[l,2,4]triazolo[l,5-a]pyrimidine (BAS600), cyproconazole, isopyrazam, penthiopyrad, probenazole, quinoxyfen and spiroxamine were obtained as unformulated, technical-grade materials. Azoxystrobin, boscalid, chlorothalonil, copper hydroxide, cymoxanil, difenoconazole, dimethomorph, epoxiconazole, fenpropimorph, fluazinam, fludioxonil, folpet, iprodione, iprovalicarb, mancozeb, mefenoxam (also known as metalaxyl-M), myclobutanil, picoxystrobin, proquinazid, prothioconazole, pyraclostrobin, tetraconazole and tricyclozole were obtained as formulated products marketed under the trademarks AMISTAR, ENDURA, BRAVO, KOCIDE, CURZATE, SCORE, ACROBAT, OPUS, CORBEL, OMEGA, MAXIM, PHALTAN, ROVRAL, MELODY, MANZATE, RIDOMIL GOLD, NOVA, ACANTO, TALIUS, PROLINE, HEADLINE, DOMARK and BEAM, respectively. Unformulated materials were first dissolved in acetone and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix by volume) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). Formulated materials were dispersed in sufficient water to give the desired concentration, and neither organic solvent nor surfactant was added to the suspension. The resulting test mixtures were then used in Tests K, L and M. Spraying a 200 ppm test suspension to the point of run-off on the test plants was the equivalent of a rate of about 800 g/ha. The tests were replicated three times and the results reported as the mean average of the three replicates.
The presence of a synergistic effect between two active ingredients was established with the aid of the Colby equation (see Colby, S. R. "Calculating Synergistic and Antagonistic Responses of Herbicide Combinations", Weeds, (1967), 15, 20-22):
Figure imgf000188_0001
Using the method of Colby, the presence of a synergistic interaction between two active ingredients is established by first calculating the predicted activity, p, of the mixture based on activities of the two components applied alone. If p is lower than the experimentally established effect, synergism has occurred. In the equation above, A is the fungicidal activity in percentage control of one component applied alone at rate x. The B term is the fungicidal activity in percentage control of the second component applied at rate y. The equation estimates p, the expected fungicidal activity of the mixture of A at rate x with B at rate y if their effects are strictly additive and no interaction has occurred.
TEST K (i.e. Tests Kl. 2. K4. K5. K6. K7. K8)
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Blumeria graminis f. sp. tritici, (also known as Erisyphe graminis f. sp. tritici, the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20 °C for 7 days, after which time visual disease ratings were made.
TEST L (i.e. Tests LI. L2. L3. L4. L6. L7
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20 °C for 24 h, and then moved to a growth chamber at 20 °C for 6 days, after which time visual disease ratings were made.
TEST M (i.e. Tests Ml. M2. M3. M4. M5. M7
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria tritici (the causal agent of wheat leaf blotch) and incubated in saturated atmosphere at 24 °C for 48 h. and then the seedlings moved to a growth chamber at 20 °C for 19 additional days, after which time visual disease ratings were made.
Results for Tests K-M are presented in the following Tables B through I. A rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates no test results. Columns labeled "Obsd" indicate the average of results observed from three replications. Columns labeled "Exp" indicate the expected effect for each treatment mixture calculated using the Colby Equation.
TABLE B
Observed and Expected Effects of Compound 181 Alone and Mixtures with Probenazole, Mancozeb, Iprodione, Boscalid, Copper hydroxide, Cymoxanil or Chlorothalonil for Control of Wheat Powdery Mildew, Leaf Rust and Leaf Blotch
Application Application Test Kl Test LI Test Ml Rate (ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0 None 0 0 0 0
0.01 None 0 0 0 0
0.1 None 0 21 18 22
1 None 0 91 82 94
10 None 0 100 100 98
0 probenazole 10 0 0 0
0 probenazole 40 0 27 0
0 probenazole 200 76 41 10
0.1 probenazole 10 0 21 9 18 0 22
0.1 probenazole 40 21 21 18 41 0 22 Application Application Test Kl Test LI Test Ml
Rate (ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0.1 probenazole 200 21 81 69 52 20 30
1 probenazole 10 91 91 74 82 96 94
1 probenazole 40 98 91 88 87 94 94
1 probenazole 200 97 98 95 90 96 95
0 mancozeb 10 0 55 0
0 mancozeb 40 0 96 0
0 mancozeb 200 0 99 84
0.1 mancozeb 10 0 21 68 63 0 22
0.1 mancozeb 40 0 21 96 97 61 22
0.1 mancozeb 200 21 21 99 99 77 88
1 mancozeb 10 50 91 91 92 80 94
1 mancozeb 40 71 91 98 99 83 94
1 mancozeb 200 96 91 100 100 96 99
0 iprodione 10 0 0 0
0 iprodione 40 0 0 0
0 iprodione 200 0 18 8
0.1 iprodione 10 0 21 0 18 0 22
0.1 iprodione 40 0 21 9 18 0 22
0.1 iprodione 200 0 21 27 33 0 28
1 iprodione 10 64 91 68 82 77 94
1 iprodione 40 76 91 74 82 90 94
1 iprodione 200 96 91 85 86 91 95
0 boscalid 10 0 9 70
0 boscalid 40 0 91 90
0 boscalid 200 74 100 97
0.1 boscalid 10 64 21 55 26 66 77
0.1 boscalid 40 0 21 97 93 99 92
0.1 boscalid 200 0 79 99 100 99 97
1 boscalid 10 97 91 80 84 97 98
1 boscalid 40 91 91 99 98 100 99
1 boscalid 200 98 98 99 100 99 100
0 copper hydroxide 10 0 0
0 copper hydroxide 40 0 0
0 copper hydroxide 200 0 0 82 Application Application Test Kl Test LI Test Ml
Rate (ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0.1 copper hydroxide 10 0 21 0 22
0.1 copper hydroxide 40 0 21 0 0 22
0.1 copper hydroxide 200 0 21 0 18 77 86
1 copper hydroxide 10 71 91 27 88 94
1 copper hydroxide 40 0 91 41 87 94
1 copper hydroxide 200 0 91 55 82 98 99
0 cymoxanil 10 0 0 0
0 cymoxanil 40 0 0 0
0 cymoxanil 200 0 9 0
0.1 cymoxanil 10 0 21 0 18 0 22
0.1 cymoxanil 40 0 21 0 18 0 22
0.1 cymoxanil 200 0 21 0 26 0 22
1 cymoxanil 10 95 91 55 82 65 94
1 cymoxanil 40 81 91 68 82 70 94
1 cymoxanil 200 84 91 80 84 78 94
0 chlorothalanil 10 0 27 0
0 chlorothalanil 40 0 74 68
0 chlorothalanil 200 0 98 96
0.1 chlorothalanil 10 0 21 27 41 0 22
0.1 chlorothalanil 40 0 21 74 79 55 75
0.1 chlorothalanil 200 72 21 93 98 99 97
1 chlorothalanil 10 76 91 27 87 70 94
1 chlorothalanil 40 96 91 74 95 81 98
1 chlorothalanil 200 96 91 97 100 100 100
TABLE C
Observed and Expected Effects of Compound 181 Alone and Mixtures with Tricyclozole, Fluazinam, Dimethomorph, Iprovalicarb, Fludioxonil, Mefenoxam, Folpet or Myclobutanil for Control of Wheat Powdery Mildew, Leaf Rust and Leaf Blotch
Application Rate Application Test K2 Test L2 Test M2
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0 None 0 71 0 0
0.01 None 0 56 0 0 Application Rate Application Test K2 Test L2 Test M2
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0.1 None 0 76 41 67
1 None 0 98 95 99
10 None 0 100 100 100
0 tricyclazole 10 0 9 0
0 tricyclazole 40 64 9 0
0 tricyclazole 200 56 9 0
0.1 tricyclazole 10 64 76 18 46 0 67
0.1 tricyclazole 40 56 91 18 46 25 67
0.1 tricyclazole 200 0 89 27 46 0 67
1 tricyclazole 10 95 98 27 95 84 99
1 tricyclazole 40 98 99 68 95 95 99
1 tricyclazole 200 99 99 74 95 71 99
0 fluazinam 10 0 27 0
0 fluazinam 40 96 68 87
0 fluazinam 200 100 88 99
0.1 fluazinam 10 0 76 27 57 74 67
0.1 fluazinam 40 65 99 68 81 89 96
0.1 fluazinam 200 96 100 88 93 100 100
1 fluazinam 10 92 98 54 96 99 99
1 fluazinam 40 99 100 80 98 97 100
1 fluazinam 200 99 100 88 99 100 100
0 dimethomorph 10 0 0 0
0 dimethomorph 40 0 0 0
0 dimethomorph 200 0 0 0
0.1 dimethomorph 10 0 76 0 41 0 67
0.1 dimethomorph 40 42 76 0 41 0 67
0.1 dimethomorph 200 0 76 9 41 32 67
1 dimethomorph 10 84 98 54 95 95 99
1 dimethomorph 40 95 98 91 95 94 99
1 dimethomorph 200 95 98 88 95 94 99
0 iprovalicarb 10 0 0 0
0 iprovalicarb 40 0 0 0
0 iprovalicarb 200 0 0 0
0.1 iprovalicarb 10 0 76 0 41 0 67 Application Rate Application Test K2 Test L2 Test M2
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0.1 iprovalicarb 40 0 76 9 41 38 67
0.1 iprovalicarb 200 0 76 9 41 27 67
1 iprovalicarb 10 93 98 41 95 93 99
1 iprovalicarb 40 96 98 27 95 94 99
1 iprovalicarb 200 98 98 74 95 95 99
0 fludioxonil 10 84 0
0 fludioxonil 40 63 0
0 fludioxonil 200 34 54
0.1 fludioxonil 10 13 96 0 41
0.1 fludioxonil 40 68 91 27 41
0.1 fludioxonil 200 81 84 54 73
1 fludioxonil 10 94 100 68 95
1 fludioxonil 40 100 99 95 95
1 fludioxonil 200 98 99 98 98
0 mefenoxam 10 0 0 0
0 mefenoxam 40 0 0 0
0 mefenoxam 200 64 0 0
0.1 mefenoxam 10 0 76 0 41 38 67
0.1 mefenoxam 40 0 76 0 41 0 67
0.1 mefenoxam 200 0 91 0 41 32 67
1 mefenoxam 10 89 98 18 95 77 99
1 mefenoxam 40 95 98 41 95 90 99
1 mefenoxam 200 98 99 80 95 86 99
0 folpet 10 0 0 0
0 folpet 40 0 9 83
0 folpet 200 0 54 98
0.1 folpet 10 0 76 27 41 21 67
0.1 folpet 40 0 76 47 46 90 94
0.1 folpet 200 48 76 85 73 95 99
1 folpet 10 95 98 68 95 90 99
1 folpet 40 96 98 74 95 99 100
1 folpet 200 98 98 88 98 98 100
0 myclobutanil 10 0
0 myclobutanil 40 25 Application Rate Application Test K2 Test L2 Test M2
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0 myclobutanil 200 90
0.1 myclobutanil 10 0 67
0.1 myclobutanil 40 12 75
0.1 myclobutanil 200 91 97
1 myclobutanil 10 80 99
1 myclobutanil 40 98 99
1 myclobutanil 200 98 100
TABLE D
Observed and Expected Effects of Compound 181 Alone and Mixtures with Quinoxyfen, Pyraclostrobin, Azoxystrobin, Picoxystrobin, Tetraconazole, Spiroxamine, Fenpropimorph or Proquinazid for Control of Wheat Leaf Rust and Leaf Blotch
Application Rate Application Rate Test L3 Test M3
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0 None 0 0 0
0.01 None 0 0 0
0.1 None 0 9 0
1 None 0 68 74
10 None 0 98 98
0 quinoxyfen 10 41 0
0 quinoxyfen 40 18 0
0 quinoxyfen 200 18 0
0.1 quinoxyfen 10 9 46 58 0
0.1 quinoxyfen 40 9 26 38 0
0.1 quinoxyfen 200 18 26 0 0
1 quinoxyfen 10 55 81 45 74
1 quinoxyfen 40 55 74 88 74
1 quinoxyfen 200 74 74 82 74
0 pyraclostrobin 10 0
0 pyraclostrobin 40 42
0 pyraclostrobin 200 92
0.1 pyraclostrobin 10 0 0
0.1 pyraclostrobin 40 0 42 Application Rate Application Rate Test L3 Test M3
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0.1 pyraclostrobin 200 84 92
1 pyraclostrobin 10 65 74
1 pyraclostrobin 40 88 85
1 pyraclostrobin 200 95 98
0 azoxystrobin 10 0
0 azoxystrobin 40 0
0 azoxystrobin 200 27
0.1 azoxystrobin 10 0 0
0.1 azoxystrobin 40 12 0
0.1 azoxystrobin 200 79 27
1 azoxystrobin 10 91 74
1 azoxystrobin 40 92 74
1 azoxystrobin 200 92 81
0 picoxystrobin 10 0
0 picoxystrobin 40 0
0 picoxystrobin 200 0
0.1 picoxystrobin 10 0 0
0.1 picoxystrobin 40 0 0
0.1 picoxystrobin 200 17 0
1 picoxystrobin 10 70 74
1 picoxystrobin 40 93 74
1 picoxystrobin 200 91 74
0 tetraconazole 10 0
0 tetraconazole 40 0
0 tetraconazole 200 94
0.1 tetraconazole 10 30 0
0.1 tetraconazole 40 63 0
0.1 tetraconazole 200 98 94
1 tetraconazole 10 89 74
1 tetraconazole 40 97 74
1 tetraconazole 200 99 99
0 spiroxamine 10 0
0 spiroxamine 40 0
0 spiroxamine 200 0 Application Rate Application Rate Test L3 Test M3
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0.1 spiroxamine 10 20 0
0.1 spiroxamine 40 17 0
0.1 spiroxamine 200 37 0
1 spiroxamine 10 92 74
1 spiroxamine 40 94 74
1 spiroxamine 200 95 74
0 fenpropimorph 10 0 0
0 fenpropimorph 40 0 0
0 fenpropimorph 200 87 0
0.1 fenpropimorph 10 0 9 30 0
0.1 fenpropimorph 40 0 9 0 0
0.1 fenpropimorph 200 41 88 17 0
1 fenpropimorph 10 41 68 94 74
1 fenpropimorph 40 68 68 93 74
1 fenpropimorph 200 80 96 94 74
0 proquinazid 10 0 0
0 proquinazid 40 0 0
0 proquinazid 200 0 13
0.1 proquinazid 10 0 9 0 0
0.1 proquinazid 40 9 9 0 0
0.1 proquinazid 200 9 9 20 13
1 proquinazid 10 27 68 28 74
1 proquinazid 40 68 68 0 74
1 proquinazid 200 68 68 85 78
TABLE E
Observed and Expected Effects of Compound 181 Alone and Mixtures with Cyproconazole, Epoxiconazole, Prothioconazole, Difenconazole, Myclobutanil or Spiroamine for Control of
Wheat Powdery Mildew, Leaf Rust and Leaf Blotch
Application Rate Application Test K4 Test L4 Test M4
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0 None 0 0 0 0
0.01 None 0 21 0 0 Application Rate Application Test K4 Test L4 Test M4
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0.1 None 0 0 9 47
1 None 0 99 80 93
10 None 0 100 100 99
0 cyproconazole 0.4 0
0 cyproconazole 2 0
0 cyproconazole 10 68
0 cyproconazole 40 94
0.1 cyproconazole 0.4 51 47
0.1 cyproconazole 2 68 47
0.1 cyproconazole 10 72 83
0.1 cyproconazole 40 95 97
1 cyproconazole 0.4 93 93
1 cyproconazole 2 95 93
1 cyproconazole 10 99 98
1 cyproconazole 40 96 100
0 epoxiconazole 0.4 0
0 epoxiconazole 2 0
0 epoxiconazole 10 86
0 epoxiconazole 40 97
0.1 epoxiconazole 0.4 0 47
0.1 epoxiconazole 2 17 47
0.1 epoxiconazole 10 91 93
0.1 epoxiconazole 40 98 99
1 epoxiconazole 0.4 95 93
1 epoxiconazole 2 96 93
1 epoxiconazole 10 99 99
1 epoxiconazole 40 99 100
0 prothioconazole 0.4 0
0 prothioconazole 2 0
0 prothioconazole 10 58
0 prothioconazole 40 98
0.1 prothioconazole 0.4 0 47
0.1 prothioconazole 2 64 47
0.1 prothioconazole 10 71 78 Application Rate Application Test K4 Test L4 Test M4
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0.1 prothioconazole 40 96 99
1 prothioconazole 0.4 89 93
1 prothioconazole 2 94 93
1 prothioconazole 10 95 97
1 prothioconazole 40 99 100
0 difenoconazole 0.4 0
0 difenoconazole 2 25
0 difenoconazole 10 75
0 difenoconazole 40 96
0.1 difenoconazole 0.4 0 47
0.1 difenoconazole 2 47 60
0.1 difenoconazole 10 82 87
0.1 difenoconazole 40 99 98
1 difenoconazole 0.4 93 93
1 difenoconazole 2 96 95
1 difenoconazole 10 96 98
1 difenoconazole 40 99 100
0 myclobutanil 0.4 21 0
0 myclobutanil 2 81 0
0 myclobutanil 10 98 60
0 myclobutanil 40 100 100
0.1 myclobutanil 0.4 42 21 9 9
0.1 myclobutanil 2 84 81 9 9
0.1 myclobutanil 10 99 98 92 64
0.1 myclobutanil 40 100 100 100 100
1 myclobutanil 0.4 98 99 55 80
1 myclobutanil 2 99 100 55 80
1 myclobutanil 10 100 100 98 92
1 myclobutanil 40 100 100 100 100
0 spiroxamine 0.4 9
0 spiroxamine 2 0
0 spiroxamine 10 0
0 spiroxamine 40 0
0.1 spiroxamine 0.4 0 17 Application Rate Application Test K4 Test L4 Test M4
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0.1 spiroxamine 2 0 9
0.1 spiroxamine 10 0 9
0.1 spiroxamine 40 9 9
1 spiroxamine 0.4 68 82
1 spiroxamine 2 68 80
1 spiroxamine 10 74 80
1 spiroxamine 40 80 80
TABLE F
Observed and Expected Effects of Compound 181 Alone and Mixtures with Bixafen, Penthiopyrad, Isopyrazam, Fludioxonil, Fenpropimorph, Difenoconazole, Azoxystrobin or
Spiroxamine for Control of Wheat Powdery Mildew and Leaf Blotch
Application Rate Application Rate Test K5 Test M5
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0 None 0 0 0
0.01 None 0 0 0
0.1 None 0 0 82
1 None 0 91 93
10 None 0 100 100
0 bixafen 0.08 0 0
0 bixafen 0.4 0 62
0 bixafen 2 60 98
0 bixafen 10 96 99
0.1 bixafen 0.08 0 0 0 82
0.1 bixafen 0.4 0 0 69 93
0.1 bixafen 2 64 60 97 100
0.1 bixafen 10 95 96 100 100
1 bixafen 0.08 89 91 92 93
1 bixafen 0.4 74 91 89 97
1 bixafen 2 94 97 99 100
1 bixafen 10 98 100 99 100
0 penthiopyrad 0.08 0 0
0 penthiopyrad 0.4 0 0 Application Rate Application Rate Test K5 Test M5
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0 penthiopyrad 2 68 89
0 penthiopyrad 10 99 99
0.1 penthiopyrad 0.08 0 0 0 82
0.1 penthiopyrad 0.4 0 0 62 82
0.1 penthiopyrad 2 47 68 86 98
0.1 penthiopyrad 10 99 99 98 100
1 penthiopyrad 0.08 95 91 93 93
1 penthiopyrad 0.4 87 91 92 93
1 penthiopyrad 2 84 97 97 99
1 penthiopyrad 10 100 100 96 100
0 isopyrazam 0.08 0 0
0 isopyrazam 0.4 21 73
0 isopyrazam 2 82 93
0 isopyrazam 10 99 99
0.1 isopyrazam 0.08 0 0 68 82
0.1 isopyrazam 0.4 0 21 67 95
0.1 isopyrazam 2 95 82 97 99
0.1 isopyrazam 10 100 99 99 100
1 isopyrazam 0.08 83 91 93 93
1 isopyrazam 0.4 91 93 98 98
1 isopyrazam 2 98 98 99 100
1 isopyrazam 10 100 100 100 100
0 fludioxonil 0.08 0
0 fludioxonil 0.4 68
0 fludioxonil 2 96
0 fludioxonil 10 97
0.1 fludioxonil 0.08 43 82
0.1 fludioxonil 0.4 84 94
0.1 fludioxonil 2 93 99
0.1 fludioxonil 10 99 99
1 fludioxonil 0.08 88 93
1 fludioxonil 0.4 96 98
1 fludioxonil 2 100 100
1 fludioxonil 10 100 100 Application Rate Application Rate Test K5 Test M5
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0 fenpropimorph 0.08 0
0 fenpropimorph 0.4 0
0 fenpropimorph 2 0
0 fenpropimorph 10 64
0.1 fenpropimorph 0.08 0 0
0.1 fenpropimorph 0.4 0 0
0.1 fenpropimorph 2 0 0
0.1 fenpropimorph 10 63 64
1 fenpropimorph 0.08 98 91
1 fenpropimorph 0.4 100 91
1 fenpropimorph 2 100 91
1 fenpropimorph 10 100 97
0 difenoconazole 0.08 0
0 difenoconazole 0.4 0
0 difenoconazole 2 63
0 difenoconazole 10 100
0.1 difenoconazole 0.08 0 0
0.1 difenoconazole 0.4 0 0
0.1 difenoconazole 2 65 63
0.1 difenoconazole 10 99 100
1 difenoconazole 0.08 99 91
1 difenoconazole 0.4 98 91
1 difenoconazole 2 100 97
1 difenoconazole 10 100 100
0 azoxystrobin 0.08 0
0 azoxystrobin 0.4 0
0 azoxystrobin 2 0
0 azoxystrobin 10 50
0.1 azoxystrobin 0.08 0 0
0.1 azoxystrobin 0.4 0 0
0.1 azoxystrobin 2 0 0
0.1 azoxystrobin 10 71 50
1 azoxystrobin 0.08 96 91 —
1 azoxystrobin 0.4 99 91 Application Rate Application Rate Test K5 Test M5
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
1 azoxystrobin 2 98 91
1 azoxystrobin 10 100 96
0 spiroxamine 0.08 0
0 spiroxamine 0.4 0
0 spiroxamine 2 0
0 spiroxamine 10 0
0.1 spiroxamine 0.08 0 0
0.1 spiroxamine 0.4 0 0
0.1 spiroxamine 2 0 0
0.1 spiroxamine 10 29 0
1 spiroxamine 0.08 98 91
1 spiroxamine 0.4 93 91
1 spiroxamine 2 97 91
1 spiroxamine 10 100 91
TABLE G
Observed and expected effects of Compound 181 Alone and Mixtures with BAS600, Bixafen, Cyproconazole, Epoxiconazole, Prothioconazole, Pyraclostrobin, Tetraconazole or
Picoxystrobin for Control of Wheat Powdery Mildew and Leaf Rust
Application Rate Application Test K6 Test L6
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0 None 0 0 5
0.01 None 0 87 5
0.1 None 0 89 16
1 None 0 98 97
10 None 0 100 100
0 BAS600 0.08 73
0 BAS600 0.4 93
0 BAS600 2 98
0 BAS600 10 100
0.1 BAS600 0.08 76 97
0.1 BAS600 0.4 76 99
0.1 BAS600 2 98 100 Application Rate Application Test K6 Test L6
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0.1 BAS600 10 100 100
1 BAS600 0.08 98 99
1 BAS600 0.4 99 100
1 BAS600 2 99 100
1 BAS600 10 100 100
0 bixafen 0.08 0
0 bixafen 0.4 76
0 bixafen 2 100
0 bixafen 10 100
0.1 bixafen 0.08 0 0
0.1 bixafen 0.4 83 76
0.1 bixafen 2 100 100
0.1 bixafen 10 100 100
1 bixafen 0.08 91 76
1 bixafen 0.4 93 94
1 bixafen 2 100 100
1 bixafen 10 100 100
0 cyproconazole 0.08 68 71
0 cyproconazole 0.4 97 99
0 cyproconazole 2 99 100
0 cyproconazole 10 100 100
0.1 cyproconazole 0.08 20 96 97 71
0.1 cyproconazole 0.4 98 100 99 99
0.1 cyproconazole 2 100 100 100 100
0.1 cyproconazole 10 100 100 100 100
1 cyproconazole 0.08 92 99 100 93
1 cyproconazole 0.4 100 100 100 100
1 cyproconazole 2 100 100 100 100
1 cyproconazole 10 100 100 100 100
0 epoxiconazole 0.08 0 10
0 epoxiconazole 0.4 97 100
0 epoxiconazole 2 100 100
0 epoxiconazole 10 100 100
0.1 epoxiconazole 0.08 83 89 99 10 Application Rate Application Test K6 Test L6
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0.1 epoxiconazole 0.4 99 100 100 100
0.1 epoxiconazole 2 100 100 100 100
0.1 epoxiconazole 10 100 100 100 100
1 epoxiconazole 0.08 100 98 100 79
1 epoxiconazole 0.4 100 100 100 100
1 epoxiconazole 2 100 100 100 100
1 epoxiconazole 10 100 100 100 100
0 prothioconazole 0.08 59 31
0 prothioconazole 0.4 65 5
0 prothioconazole 2 68 10
0 prothioconazole 10 100 89
0.1 prothioconazole 0.08 59 96 5 31
0.1 prothioconazole 0.4 96 96 10 5
0.1 prothioconazole 2 98 96 5 10
0.1 prothioconazole 10 100 100 70 89
1 prothioconazole 0.08 100 99 63 84
1 prothioconazole 0.4 100 99 83 78
1 prothioconazole 2 100 99 76 79
1 prothioconazole 10 100 100 94 98
0 pyraclostrobin 0.08 11 31
0 pyraclostrobin 0.4 89 86
0 pyraclostrobin 2 97 100
0 pyraclostrobin 10 100 100
0.1 pyraclostrobin 0.08 65 90 10 31
0.1 pyraclostrobin 0.4 39 99 95 86
0.1 pyraclostrobin 2 99 100 100 100
0.1 pyraclostrobin 10 100 100 100 100
1 pyraclostrobin 0.08 98 98 84 84
1 pyraclostrobin 0.4 98 100 97 97
1 pyraclostrobin 2 100 100 100 100
1 pyraclostrobin 10 100 100 100 100
0 tetraconazole 0.08 59 5
0 tetraconazole 0.4 65 0
0 tetraconazole 2 99 70 Application Rate Application Test K6 Test L6
(ppm) of Rate (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp
0 tetraconazole 10 100 100
0.1 tetraconazole 0.08 59 96 0 5
0.1 tetraconazole 0.4 84 96 0 0
0.1 tetraconazole 2 98 100 86 70
0.1 tetraconazole 10 100 100 100 100
1 tetraconazole 0.08 99 99 76 78
1 tetraconazole 0.4 100 99 89 76
1 tetraconazole 2 100 100 100 93
1 tetraconazole 10 100 100 100 100
0 picoxystrobin 0.08 70 0
0 picoxystrobin 0.4 95 0
0 picoxystrobin 2 100 97
0 picoxystrobin 10 100 100
0.1 picoxystrobin 0.08 71 97 0 0
0.1 picoxystrobin 0.4 93 99 10 0
0.1 picoxystrobin 2 100 100 91 97
0.1 picoxystrobin 10 100 100 100 100
1 picoxystrobin 0.08 100 99 83 76
1 picoxystrobin 0.4 100 100 76 76
1 picoxystrobin 2 100 100 93 99
1 picoxystrobin 10 100 100 100 100
TABLE H
Observed and Expected Effects of Compound 181 Alone and Mixtures with xyfen, BAS600, Penthiopyrad, Isopyrazam, Difenoconazole or Azoxystrobin for Control of Wheat Powdery Mildew, Leaf Rust and Leaf Blotch
Application Rate Application Rate Test K7 Test L7 Test M7
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0 None 0 71 0 0
0.01 None 0 64 0 0
0.1 None 0 63 37 32
1 None 0 96 94 94
10 None 0 100 100 99 Application Rate Application Rate Test K7 Test L7 Test M7
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
0 quinoxyfen 0.016 0
0 quinoxyfen 0.08 21
0 quinoxyfen 0.4 81
0 quinoxyfen 2 96
0.1 quinoxyfen 0.016 56 63
0.1 quinoxyfen 0.08 21 71
0.1 quinoxyfen 0.4 64 93
0.1 quinoxyfen 2 95 99
1 quinoxyfen 0.016 98 96
1 quinoxyfen 0.08 99 97
1 quinoxyfen 0.4 99 99
1 quinoxyfen 2 99 100
0 BAS600 0.016 30 0
0 BAS600 0.08 37 91
0 BAS600 0.4 85 98
0 BAS600 2 100 100
0.1 BAS600 0.016 8 56 8 32
0.1 BAS600 0.08 43 61 66 94
0.1 BAS600 0.4 78 90 99 99
0.1 BAS600 2 100 100 99 100
1 BAS600 0.016 87 96 97 94
1 BAS600 0.08 92 97 93 99
1 BAS600 0.4 96 99 98 100
1 BAS600 2 100 100 100 100
0 penthiopyrad 0.016 8
0 penthiopyrad 0.08 23
0 penthiopyrad 0.4 72
0 penthiopyrad 2 100
0.1 penthiopyrad 0.016 0 42
0.1 penthiopyrad 0.08 23 52
0.1 penthiopyrad 0.4 72 83
0.1 penthiopyrad 2 100 100
1 penthiopyrad 0.016 64 95
1 penthiopyrad 0.08 87 96 Application Rate Application Rate Test K7 Test L7 Test M7
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
1 penthiopyrad 0.4 92 98
1 penthiopyrad 2 100 100
0 isopyrazam 0.016 81
0 isopyrazam 0.08 99
0 isopyrazam 0.4 100
0 isopyrazam 2 100
0.1 isopyrazam 0.016 89 88
0.1 isopyrazam 0.08 98 99
0.1 isopyrazam 0.4 100 100
0.1 isopyrazam 2 100 100
1 isopyrazam 0.016 98 99
1 isopyrazam 0.08 99 100
1 isopyrazam 0.4 100 100
1 isopyrazam 2 100 100
0 difenoconazole 0.016 0
0 difenoconazole 0.08 37
0 difenoconazole 0.4 100
0 difenoconazole 2 100
0.1 difenoconazole 0.016 8 37
0.1 difenoconazole 0.08 92 61
0.1 difenoconazole 0.4 100 100
0.1 difenoconazole 2 100 100
1 difenoconazole 0.016 87 94
1 difenoconazole 0.08 99 97
1 difenoconazole 0.4 100 100
1 difenoconazole 2 100 100
0 azoxystrobin 0.016 8
0 azoxystrobin 0.08 98
0 azoxystrobin 0.4 100
0 azoxystrobin 2 100
0.1 azoxystrobin 0.016 22 42
0.1 azoxystrobin 0.08 99 98
0.1 azoxystrobin 0.4 100 100
0.1 azoxystrobin 2 100 100 Application Rate Application Rate Test K7 Test L7 Test M7
(ppm) of (ppm) of
Compound 181 Component (b) Component (b) Obsd Exp Obsd Exp Obsd Exp
1 azoxystrobin 0.016 81 95
1 azoxystrobin 0.08 100 100
1 azoxystrobin 0.4 100 100
1 azoxystrobin 2 100 100
TABLE I
Observed and Expected Effects of Compound 181 Alone and Mixtures with
Proquinazid for Control of Wheat Powdery Mildew
Figure imgf000208_0001
Tables B through I show compositions of the present invention comprising mixtures of a representative Formula 1 compound with a variety of component (b) compounds demonstrating, in some instances, synergistic control of wheat powdery mildew, leaf rust, and particularly leaf blotch. As control cannot exceed 100%, increased activity above expected fungicidal activity was not always observed in mixtures but more likely observed when the separate active ingredient components alone were at application rates providing considerably less than 100% control. Synergy may not be evident at low application rates where the individual active ingredient components alone have little activity. However, in some instances greater activity was observed for combinations wherein individual active ingredients alone at the same application rates had little or no activity. As demonstrated above, this invention provides a method for controlling powdery mildew (Blumeria graminis f. sp. tritici), leaf rust (Puccinia recondita f. sp. tritici), and wheat leaf blotch (Septoria tritici).

Claims

CLAIMS What is claimed is:
1. A fungicidal composition comprising:
(a) at least one compound selected from the compounds of Formula 1, N-oxides, and salts thereof:
Figure imgf000210_0001
1
wherein
Q1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl,
pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 4 substituents independently selected from R3 on carbon atom ring members and R4 on nitrogen atom ring members;
Q2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl,
pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 4 substituents independently selected from R5 on carbon atom ring members and R6 on nitrogen atom ring members;
R1 and R2 are independently halogen, cyano, nitro, -C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, -C3 haloalkyl, C2-C3 haloalkenyl, -C3 alkoxy, C1-C3 haloalkoxy, C 1 -C3 alkylthio, C1 -C3 haloalkylthio or C 1 -C7 hydroxyalkyl;
each R3 and R5 is independently halogen, cyano, hydroxy, nitro, C -C alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C2-C7 cyanoalkyl, Ci -C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, Cg-C^ cycloalkylcycloalkyl, C3-C7 cycloalkoxy, C3-C7 halocycloalkoxy, C1 -C7 alkoxy, C2-C7 cyanoalkoxy, C 1 -C7 haloalkoxy, Ci -Cg alkylthio, C1 -C7 haloalkylthio, C1 -C7 alkylsulfinyl, C 1 -C7 alkylsulfonyl, C 1 -C7 haloalkylsulfinyl, C1 -C7 haloalkylsulfonyl, C1 -C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, aminocarbonyl, C2-C7 alkylaminocarbonyl, C3-C7 dialkylaminocarbonyl, C2-C7
alkylcarbonylamino, C3-C10 trialkylsilyl, -SCN, C(=S)NH2 or -X-U-Z; each R4 and R6 is independently cyano, Ci -Cg alkyl, C3-C6 alkenyl, C3-C6 alkynyl, Ci -Cg haloalkyl, C3-C6 cycloalkyl, Ci -Cg alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl or C3-C6 dialkylaminoalkyl; each X is independently O, S(=0)n, NR7 or a direct bond;
each U is independently Cj-Cg alkylene, C2-C6 alkenylene, C3-C6 alkynylene, C3-C6 cycloalkylene or C3-Cg cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(=0), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, Cj-Cg alkyl, C^-Cg haloalkyl, C^-Cg alkoxy and C^-Cg haloalkoxy;
each Z is independently NR8aR8b, OR9 or S(=0)nR10;
each R7 is independently H, Cj-Cg alkyl, Cj-Cg haloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl);
each R8a and R8b is independently H, Cj-Cg alkyl, Cj-Cg haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8
(cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl);
each R9 and R10 is independently H, Cj-Cg alkyl, -Cg haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8
(cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl);
each n is independently 0, 1 or 2; and
(b) at least one additional fungicidal compound.
2. The composition of Claim 1 wherein component (a) comprises a compound of Formula 1 or salt thereof, wherein in Formula 1,
Q1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl,
pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R3 on carbon atom ring members and R4 on nitrogen atom ring members;
Q2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl,
pyrimidinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R5 on carbon atom ring members and R6 on nitrogen atom ring members; and
R1 and R2 are independently halogen, cyano, ethenyl, ethynyl, methoxy or methylthio; or methyl optionally substituted with one substituent selected from halogen, -OH and methyl.
3. The composition of Claim 2 wherein in Formula 1,
Q1 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R3 on carbon atom ring members;
Q2 is phenyl, pyridinyl or benzyl, each optionally substituted with up to 3 substituents independently selected from R5 on carbon atom ring members; and
each R3 and R5 is independently halogen, cyano, Ci-C^ alkyl, C2-C3 alkenyl, C2-C3 alkynyl, Ci-C^ haloalkyl, cyclopropyl, Ci-C^ alkoxy, Ci-C^ haloalkoxy, Ci-C^ alkylthio, C1 -C3 alkylamino, C2-C4 dialkylamino, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl or C2-C4 alkylcarbonylamino.
4. The composition of Claim 3 wherein in Formula 1,
Q1 is a phenyl or 3 -pyridinyl ring optionally substituted with up to 3 substituents
independently selected from R3 on carbon atom ring members; and
Q2 is a phenyl or 3 -pyridinyl ring optionally substituted with up to 3 substituents
independently selected from R5 on carbon atom ring members.
5. The composition of Claim 4 wherein in Formula 1,
R1 and R2 are independently halogen, cyano or methoxy; or methyl optionally
substituted with one substituent selected from F, CI or methyl; and
each R3 and R5 is independently halogen, cyano, Ci-C^ alkyl, C2-C3 alkenyl, Ci-C^ haloalkyl, C1-C3 alkoxy, C1 -C3 haloalkoxy, C1 -C3 alkylthio or C1-C3 alkylamino.
6. The composition of Claim 5 wherein in Formula 1,
R1 and R2 are independently CI, Br, I or Ci-C2 alkyl;
each R3 and R5 is independently F, CI, Br, cyano, Ci -C2 alkyl, Ci~C2 haloalkyl, Ci-C2 alkoxy or i~C2 haloalkoxy; and
the ring of one of Q1 and Q2 is substituted with 2 or 3 substituents and the ring of the other of Q1 and Q2 is substituted with 1 or 2 substituents.
7. The composition of Claim 6 wherein in Formula 1,
R1 and R2 are independently CI, Br or methyl;
the ring of one of Q1 and Q2 is a phenyl or 3 -pyridinyl ring substituted at a meta or para position with one substituent selected from F, CI, methyl, methoxy and fluoromethoxy, and optionally substituted with one F at a remaining position; and
the ring of the other of Q1 and Q2 is a phenyl ring substituted at both ortho positions with F and substituted at a meta or para position with a substituent selected from cyano and Ci~C2 alkoxy.
8. The composition of Claim 1 wherein component (a) comprises a compound selected from the group consisting of
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)-2-methyl- lH-imidazole,
3-[4-chloro- 1 -(4-chlorophenyl)-2-methyl- lH-imidazol-5-yl]-2,4-difluorobenzonitrile,
2-bromo-l-(2,6-difluoro-4-methoxyphenyl)-5-(3-fluorophenyl)-4-methyl- lH-imidazole,
4-[2-chloro-l-(6-chloro-3-pyridinyl)-4-methyl-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile,
2-bromo-4-chloro-5-(4-ethoxy-2,6-difluorophenyl)-l-(3-fluorophenyl)-lH-imidazole, 4-chloro-5-(4-ethoxy-2,6-difluorophenyl)-2-methyl- 1 -(4-methylphenyl)- lH-imidazole, 4-chloro-5-(4-ethoxy-2,6-difluorophenyl)-l-(4-fluorophenyl)-2-methyl-lH-imidazole, 4-chloro-5-(4-ethoxy-2,6-difluorophenyl)-l-(3-fluorophenyl)-2-methyl-lH-imidazole, 2-bromo-4-chloro-l-[3-(difluoromethoxy)phenyl]-5-(4-ethoxy-2,6-difluorophenyl)- lH-imidazole,
2,4-dichloro-l-[3-(difluoromethoxy)phenyl]-5-(4-ethoxy-2,6-difluorophenyl)- lH-imidazole,
4-[2-chloro-l-(6-methoxy-3-pyridinyl)-4-methyl-lH-imidazol-5-yl]-
3,5-difluorobenzonitrile,
4-[2-bromo-l-(6-methoxy-3-pyridinyl)-4-methyl-lH-imidazol-5-yl]-
3,5-difluorobenzonitrile,
4-[2-bromo-4-chloro-l -(4-methylphenyl)- lH-imidazol-5-yl]-3,5-difluorobenzonitrile, 4-chloro-l-[3-(difluoromethoxy)phenyl]-5-(4-ethoxy-2,6-difluorophenyl)-2-methyl- lH-imidazole,
4-[2-bromo-4-chloro-l-(3-fluorophenyl)-lH-imidazol-5-yl]-3,5-difluorobenzonitrile, 4-[4-chloro-l-(3,4-difluorophenyl)-2-methyl-lH-imidazol-5-yl]-
3,5-difluorobenzonitrile,
4- [4-chloro- 1 -(3 -fluorophenyl)-2 -methyl- lH-imidazol-5 -yl] -3 ,5 -difluorobenzonitrile, 4-[2-bromo-4-chloro-l-(4-fluorophenyl)-lH-imidazol-5-yl]-3,5-difluorobenzonitrile, 2-chloro- l-[4-(difluoromethoxy)phenyl]-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl- lH-imidazole,
4-[2-chloro-l-(4-chlorophenyl)-4-methyl-lH-imidazol-5-yl]-3,5-difluorobenzonitrile, 4- [2-chloro- 1 -(3 -fluorophenyl)-4-methyl- lH-imidazol-5 -yl] -3 ,5 -difluorobenzonitrile, 4-[4-chloro-l-(2,4-difluorophenyl)-2-methyl-lH-imidazol-5-yl]- 3,5-difluorobenzonitrile,
4- [2-chloro- 1 - [3 -(difluoromethoxy)phenyl] -4-methyl- lH-imidazol-5 -yl]- 3,5-difluorobenzonitrile, 4-[2,4-dichloro- 1 -[4-(difluoromethoxy)phenyl]- lH-imidazol-5-yl]-
3,5-difluorobenzonitrile,
4-[4-chloro-l-(2-fluoro-4-methylphenyl)-2-methyl-lH-imidazol-5-yl]-
3,5-difluorobenzonitrile,
4-[4-bromo-l-(2-fluoro-4-methylphenyl)-2-methyl-lH-imidazol-5-yl]-
3,5-difluorobenzonitrile, and
4-[2,4-dibromo-l-(3-fluorophenyl)-lH-imidazol-5-yl]-3,5-difluorobenzonitrile.
9. The composition of any one of Claims 1 through 8 wherein component (b) includes at least one fungicide selected from the group consisting of:
(bl) methyl benzimidazole carbamate fungicides;
(b2) dicarboximide fungicides;
(b3) demethylation inhibitor fungicides;
(b4) phenylamide fungicides;
(b5) amine/morpholine fungicides;
(b6) phospholipid biosynthesis inhibitor fungicides;
(b7) carboxamide fungicides;
(b8) hydroxy(2-amino-)pyrimidine fungicides;
(b9) anilinopyrimidine fungicides;
(blO) N-phenyl carbamate fungicides;
(bl 1) quinone outside inhibitor fungicides;
(bl2) phenylpyrrole fungicides;
(bl3) quinoline fungicides;
(bl4) lipid peroxidation inhibitor fungicides;
(bl5) melanin biosynthesis inhibitors-reductase fungicides;
(bl6) melanin biosynthesis inhibitors-dehydratase fungicides;
(bl7) hydroxyanilide fungicides;
(bl8) squalene-epoxidase inhibitor fungicides;
(bl9) polyoxin fungicides;
(b20) phenylurea fungicides;
(b21) quinone inside inhibitor fungicides;
(b22) benzamide fungicides;
(b23) enopyranuronic acid antibiotic fungicides;
(b24) hexopyranosyl antibiotic fungicides;
(b25) glucopyranosyl antibiotic: protein synthesis fungicides;
(b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides;
(b27) cyanoacetamideoxime fungicides;
(b28) carbamate fungicides;
(b29) oxidative phosphorylation uncoupling fungicides; (b30) organo tin fungicides;
(b31) carboxylic acid fungicides;
(b32) heteroaromatic fungicides;
(b33) phosphonate fungicides;
(b34) phthalamic acid fungicides;
(b35) benzotriazine fungicides;
(b36) benzene-sulfonamide fungicides;
(b37) pyridazinone fungicides;
(b38) thiophene-carboxamide fungicides;
(b39) pyrimidinamide fungicides;
(b40) carboxylic acid amide fungicides;
(b41) tetracycline antibiotic fungicides;
(b42) thiocarbamate fungicides;
(b43) benzamide fungicides;
(b44) host plant defense induction fungicides;
(b45) multi-site contact activity fungicides;
(b46) fungicides other than fungicides of component (a) and components (bl) through (b45); and salts of compounds of (bl) through (b46).
10. The composition of Claim 9 wherein component (b) comprises at least one fungicide from each of two different groups selected from (bl) through (b46).
11. The composition of Claim 1 wherein component (b) includes at least one compound selected from acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl, benalaxyl-M, benodanil, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper salts, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim,
dimethirimol, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, dithianon, dodemorph, dodine, edifenphos, enestroburin, epoxiconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin chloride, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl- aluminum, fuberidazole, furalaxyl, furametpyr, hexaconazole, hymexazol, guazatine, imazalil, imibenconazole, iminoctadine, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mepronil, meptyldinocap, metalaxyl, metalaxyl-M, metconazole, methasulfocarb, metiram, metominostrobin, mepanipyrim, metrafenone, myclobutanil, naftifme, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, penconazole, pencycuron, penflufen, penthiopyrad, pefurazoate, phosphorous acid and salts, phthalide, picoxystrobin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothiocarb, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyrrolnitrin, quinomethionate, quinoxyfen, quintozene, sedaxane, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, tecloftalam, tecnazene, terbinafme, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, triflumizole, tricyclazole, trifloxystrobin, triforine, trimorphamide, triticonazole,
uniconazole, validamycin, valifenalate, vinclozolin, zineb, ziram, zoxamide, N"-[4-[4-chloro- 3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide,
5- chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-l-yl)[l,2,4]triazolo[l,5-a]- pyrimidine, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3-methoxyphenyl]ethyl]- 3 -methyl-2- [(methylsulfonyl)amino]butanamide, N-[2- [4- [ [3 -(4-chlorophenyl)-2-propyn-
1 -yl]oxy] -3 -methoxyphenyl] ethyl] -3 -methyl-2- [(ethylsulfonyl)amino]butanamide, 2-butoxy-
6- iodo-3-propyl-4H- 1 -benzopyran-4-one, 3-[5-(4-chlorophenyl)-2,3-dimethyl- 3-isoxazolidinyl]pyridine, 4-fluorophenyl N-[ 1 -[[[ 1 -(4-cyanophenyl)ethyl]sulfonyl]- methy ljpropyl] carbamate, N- [ [(cyclopropylmethoxy)amino] [6-(difluoromethoxy)- 2,3-difluorophenyl]methylene]benzeneacetamide, a-(methoxyimino)-N-methyl-2-[[[ 1 -[3- (trifluoromethyl)phenyl]ethoxy]imino]methyl]benzeneacetamide, N"-[4-[4-chloro- 3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide, 2-[[[[3-(2,6- dichlorophenyl)- 1 -methyl-2-propen- 1 -ylidene]amino]oxy]methyl]-a-(methoxyimino)- N-methylbenzeneacetamide, l-[(2-propenylthio)carbonyl]-2-(l-methylethyl)-4-(2-methyl- phenyl)-5-amino-lH-pyrazol-3-one, 5-ethyl-6-octyl-[l ,2,4]triazolo[l ,5-a]pyrimidin-
7- ylamine, pentyl N-[4-[[[[(l -methyl- lH-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]- 2-thiazolyl]carbamate and pentyl N-[6-[[[[(l-methyl-lH-tetrazol-5-yl)phenyl- methylene]amino]oxy]methyl]-2-pyridinyl]carbamate.
12. A composition comprising:
(a) at least one compound selected from the compounds of Formula 1 as defined in Claim 1 , N-oxides, and salts thereof; and at least one invertebrate pest control compound or agent.
13. A composition comprising the composition of any one of Claims 1 through 12 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
14. A method for protecting a plant or plant seed from diseases caused by fungal pathogens comprising applying a fungicidally effective amount of the composition of any one of Claims 1 through 13 to the plant or plant seed.
15. A method for protecting a plant from a Septoria disease comprising applying to the plant a fungicidally effective amount of the composition of any one of Claims 1 through 8 wherein component (b) includes at least one fungicidal compound selected from (b5) amine/morpholine fungicides.
16. A compound selected from the compounds of Formula 1 as defined in Claim 1 , N-oxides, and salts thereof; provided that
when Q1 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each optionally substituted with up to 4 substituents independently selected from R3a on carbon atom ring members and R4a on nitrogen atom ring members; wherein
each R3a is independently halogen, cyano, hydroxy, nitro, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C^-C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C3-C7 cycloalkoxy, C3-C7 halocycloalkoxy, Ci-C alkoxy, C^-C7 haloalkoxy, C^-Cg alkylthio, C^-C7 haloalkylthio, C^-C7 alkylsulfinyl, Ci-C alkylsulfonyl, Ci-C haloalkylsulfinyl, Ci-C haloalkylsulfonyl, C^-C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylcarbonylamino, C3-CIQ trialkylsilyl, -SCN, C(=S)NH2 or -X-U-Z; and
each R4a is independently cyano, Cj-Cg alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, Cj-Cg alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2- Cg alkoxycarbonyl, C2-Cg alkylaminoalkyl or C3-Cg dialkylaminoalkyl;
then Q2 is phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl or benzyl, each substituted with 1 to 4 substituents independently selected from R5 on carbon atom ring members and R6 on nitrogen atom ring members; provided that least one substituent is C2-C7 cyanoalkyl, C2-C7 cyanoalkoxy, aminocarbonyl, C2-C7 alkylaminocarbonyl or C3-C7 dialkylaminocarbonyl on a carbon atom ring member, or C^-Cg haloalkyl on a nitrogen atom ring member.
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