Fungicidal substituted azoles

Abstract

Disclosed are compounds of Formula 1 and Formula 6 including all geometric and stereoisomers, tautomers, N‑oxides, and salts thereof, or wherein R1, R2, R3, R4, Q, Y, W, A and Z are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.

Description

[0001] TITLE

[0002] FUNGICIDAL SUBSTITUTED AZOLES

[0003] FIELD OF THE INVENTION

[0004] This invention relates to certain substituted azoles, their N-oxides, salts and compositions, and methods of using them as fungicides.

[0005] BACKGROUND OF THE INVENTION

[0006] 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. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different sites of action.

[0007] PCT Patent Publications WO 2023 / 012044, WO 2022 / 253645 and WO 2023 / 110869 disclose pyrazole derivatives and their use as fungicides.

[0008] SUMMARY OF THE INVENTION

[0009] This invention is directed to compounds of Formula 1 (including all stereoisomers), N-oxides, and salts thereof, compositions containing them and their use as fungicides: wherein

[0010] Q is selected from

[0011] wherein the bond extending to the right is attached to CR1Y; and m is 0, 1 or 2;

[0012] R1is H, cyano, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy or C1-C4haloalkoxy;

[0013] Y is selected from wherein the floating bond is attached to Formula 1 through any available carbon atom that is adjacent to any nitrogen atom of the depicted ring; and n is 0, 1, 2 or 3;

[0014] R2and R3are each independently H or C1-C4alkyl;

[0015] R4is H, amino, C2-C4alkenyl, C3-C6cycloalkyl, CH(=O), S(=O)2OM, S(=O)uR7, (C=O)R8or OR9; or C1-C3alkyl or C1-C3haloalkyl, each optionally substituted with up to 1 substituent selected from R4a; M is K or Na; u is 0, 1 or 2;

[0016] R4ais cyano, C3-C6cycloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkyl sulfinyl or C1-C3alkyl sulfonyl;

[0017] W is 0 or S; A is A1or A2; A1is selected from: wherein the bond extending to the left is attached to C=W , and the bond extending to the right is attached to Z; and q is 0, 1 or 2;

[0018] A2is a 6-membered nonaromatic ring, each ring containing ring members selected from carbon atoms and optionally up to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N atoms, wherein up to 2 ring members are independently selected from C(=O), C(=S), S(=O) and S(=O)2, each ring optionally substituted with up to 3 substituents independently selected from R11;

[0019] A2is a 6-membered heteroaromatic ring, each ring optionally substituted with up to 3 substituents independently selected from R11;

[0020] Z is phenyl optionally substituted with up to 4 substituents independently selected from R12; or a 5- to 6-membered heteroaromatic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, each ring optionally substituted with up to 4 substituents independently selected from R12; or a 5- to 6-membered nonaromatic ring, each ring containing ring members selected from carbon atoms and optionally up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 2 ring members are independently selected from C(=O), C(=S), S(=O) and S(=O)2, each ring optionally substituted with up to 4 substituents independently selected from R12; each R5ais independently halogen, cyano, hydroxy, nitro, C4-C4alkyl, C4-C4haloalkyl, C2-C4alkenyl, C2-C4alkynyl, C3-C4cycloalkyl, C3-C4alkoxy, C4-C4haloalkoxy, C2-C4alkenyloxy, C2-C4alkynyloxy, C1-C4alkylthio, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl, C2-C4alkylcarbonyl or C2-C4alkoxycarbonyl;

[0021] R5bis H, C1-C4alkyl, C1-C4haloalkyl, C2-C4alkenyl, C2-C4alkynyl or cyclopropyl; each R6is independently halogen, cyano, amino, hydroxy, nitro, CH(=O), C(=O)OH,

[0022] NR13aR13b, C(=O)NR13aR13b, C(R14)=NR15, -U-V-T or C3-C15trialkylsilyl; or C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkoxy, C2-C6alkenyloxy, C2-C6alkynyloxy, C3-C6cycloalkoxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6alkylaminosulfinyl, C2-C6dialkylaminosulfinyl, C1-C6alkyl sulfonyloxy, C1-C6alkylsulfonylamino, C2-C6alkylcarbonyl, C2-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, C2-C6alkylcarbonyloxy, C2-C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy or C2-C6alkylaminocarbonylamino, each optionally substituted with up to 3 substituents independently selected from R16;

[0023] R7is C1-C3alkyl or C1-C3alkoxy;

[0024] R8is C1-C3alkyl, C1-C3alkoxy or C1-C3alkylthio;

[0025] R9is H, CH(=O), C1-C3alkyl, C1-C3haloalkyl, C3-C6cycloalkyl or S(=O)2OM; each R10is independently halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy or C1-C3haloalkoxy; each R11is independently halogen, cyano, C1-C3alkyl, C1-C3haloalkyl, C2-C3alkenyl,

[0026] C2-C3haloalkenyl, C1-C3alkoxy or C1-C3haloalkoxy; each R12is independently halogen, cyano, hydroxy, nitro, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylthio, C1-C6alkyl sulfinyl, C1-C6alkylsulfonyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6alkenyl oxy, C2-C6alkynyloxy, C1-C6alkylsulfinyloxy, C1-C6alkylsulfonyloxy, C2-C6alkylcarbonyl or C2-C6alkoxycarbonyl; each R13ais independently H, C1-C3alkyl, C2-C4alkenyl, C2-C4alkylcarbonyl or C2-C4alkoxy carbonyl; each R13bis independently H, cyano, hydroxy, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6, alkoxyalkyl, C2-C6alkylcarbonyl, C2-C6haloalkylcarbonyl or C2-C6alkoxycarbonyl; each R14is independently H, cyano, halogen, C1-C2alkyl or C1-C2alkoxy; each R15is independently hydroxy, C1-C4alkyl, C1-C4alkoxy, C2-C4alkenyloxy, C2-C4alkynyloxy, C2-C4alkylcarbonyloxy or C2-C4alkoxycarbonyloxy; each U is independently a direct bond, C(=O)O or C(=O)NH, wherein the atom to the left is attached to Formula 1, and the atom to the right is connected to V; each V is independently a direct bond, C1-C3alkylene, C2-C3alkenylene, C3-C3alkynylene, C3-C6cycloalkylene or C3-C6cycloalkenylene; each T is independently phenyl optionally substituted with up to 3 substituents independently selected from R17; or each T is independently a 5- to 6-membered heteroaromatic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N atoms, each ring optionally substituted with up to 2 substituents independently selected from R17; or each T is independently a 3- to 6-membered nonaromatic heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N atoms, wherein up to 2 ring members are independently selected from C(=O), C(=S), S(=O) and S(=O)2, each ring optionally substituted with up to 2 substituents independently selected from R17; each R16is independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl, C3-C6cycloalkyl, C1-C2alkoxy, C1-C2haloalkoxy, C2-C3alkylcarbonyl, C2-C3haloalkylcarbonyl, C2-C3alkoxycarbonyl, C2-C3haloalkoxycarbonyl or C3-C15trialkylsilyl; and each R17is independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl or C1-C2alkoxy.

[0027] More particularly, this invention pertains to a compound of Formula 1 (including all stereoisomers), an N-oxide or a salt thereof.

[0028] This invention also relates to a fungicidal composition comprising (a) a compound of the invention (i.e. in a fungicidally effective amount); and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.

[0029] This invention also relates to a fungicidal composition comprising (a) a compound of the invention; and (b) at least one other fungicide (e.g., at least one other fungicide having a different site of action).

[0030] 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 of the invention (e.g., as a composition described herein). This invention also relates to a composition comprising a compound of Formula 1, an

[0031] N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent.

[0032] This invention further relates to compounds of Formula 6 (including all stereoisomers),

[0033] N-oxides, and salts thereof: wherein

[0034] R1and Q are as defined above for Formula 1.

[0035] Compounds of Formula 6 can be used as process intermediates to prepare compounds of Formula 1.

[0036] DETAILS OF THE INVENTION

[0037] 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, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus.

[0038] 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.

[0039] The transitional phrase “consisting essentially of” is used to define a composition, method or apparatus 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”.

[0040] 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.”

[0041] 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).

[0042] 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.

[0043] The term “agronomic” refers to the production of field crops such as for food and fiber and includes the growth of maize or corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye and rice), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (e.g., berries and cherries) and other specialty crops (e.g., canola, sunflower and olives).

[0044] The term “nonagronomic” refers to other than field crops, such as horticultural crops (e.g., greenhouse, nursery or ornamental plants not grown in a field), residential, agricultural, commercial and industrial structures, turf (e.g., sod farm, pasture, golf course, lawn, sports field, etc.), wood products, stored product, agro-forestry and vegetation management, public health (i.e. human) and animal health (e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife) applications.

[0045] The term “crop vigor” refers to rate of growth or biomass accumulation of a crop plant. An “increase in vigor” refers to an increase in growth or biomass accumulation in a crop plant relative to an untreated control crop plant. The term “crop yield” refers to the return on crop material, in terms of both quantity and quality, obtained after harvesting a crop plant. An “increase in crop yield” refers to an increase in crop yield relative to an untreated control crop plant.

[0046] The term “biologically effective amount” refers to the amount of a biologically active compound (e.g., a compound of Formula 1 or a mixture with at least one other fungicidal compound) sufficient to produce the desired biological effect when applied to (i.e. contacted with) a fungus to be controlled or its environment, or to a plant, the seed from which the plant is grown, or the locus of the plant (e.g., growth medium) to protect the plant from injury by the fungal disease or for other desired effect (e.g., increasing plant vigor).

[0047] 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.

[0048] 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.

[0049] As referred to herein, the term “broadleaf” used either alone or in words such as “broadleaf crop” means dicot or dicotyledon, a term used to describe a group of angiosperms characterized by embryos having two cotyledons.

[0050] As referred to in this disclosure, the terms “fungal pathogen” and “fungal plant pathogen” include pathogens in the Ascomycota, Basidiomycota and Zygomycota phyla, and the fungal-like Oomycota class that are the causal agents of a broad spectrum of plant diseases of economic importance, affecting ornamental, turf, vegetable, field, cereal and fruit crops. In the context of this disclosure, “protecting a plant from disease” or “control of a plant disease” includes preventative action (interruption of the fungal cycle of infection, colonization, symptom development and spore production) and / or curative action (inhibition of colonization of plant host tissues).

[0051] As used herein, the term “mode of action” (MOA) is as define by the Fungicide Resistance Action Committee (FRAC), and is used to distinguish fungicides according to their biochemical mode of action in the biosynthetic pathways of plant pathogens, and their resistance risk. FRAC-defined modes of actions include (A) nucleic acids metabolism, (B) cytoskeleton and motor protein, (C) respiration, (D) amino acids and protein synthesis, (E) signal transduction, (F) lipid synthesis or transport and membrane integrity or function, (G) sterol biosynthesis in membranes, (H) cell wall biosynthesis, (I) melanin synthesis in cell wall, (P) host plant defense induction, (U) unknown mode of action, (M) chemicals with multi-site activity and (BM) biologicals with multiple modes of action. Each mode of action (i.e. letters A through BM) contain one or more subgroups (e.g., A includes subgroups A1, A2, A3 and A4) based either on individual validated target sites of action, or in cases where the precise target site is unknown, based on cross resistance profiles within a group or in relation to other groups. Each of these subgroups (e.g., A1, A2, A3 and A4) is assigned a FRAC code which is a number and / or letter. For example, the FRAC code for subgroup Al is 4. Additional information on target sites and FRAC codes can be obtained from publicly available databases maintained, for example, by FRAC.

[0052] As used herein, the term “cross resistance” refers to the phenomenon that occurs when a pathogen develops resistance to one fungicide and simultaneously becomes resistant to one or more other fungicides. These other fungicides are typically, but not always, in the same chemical class or have the same target site of action, or can be detoxified by the same mechanism.

[0053] In the above recitations, the term “alkyl”, used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain and branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, and the different butyl, pentyl and hexyl isomers. “Alkenyl” includes straightchain and branched alkenes such as ethenyl, 1 -propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. “Alkenyl” also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. “Alkynyl” includes straight-chain and branched alkynes such as ethynyl, 1-propynyl, 2-propynyl, and the different butynyl, pentynyl and hexynyl isomers. “Alkynyl” can also include moieties comprised of multiple triple bonds such as 2, 5 -hexadiynyl. “Alkylene” denotes a straight-chain or branched alkanediyl. Examples of “alkylene” include CH2, CH2CH2, CH(CH3), CH2CH2CH2, CH2CH(CH3), and the different propylene isomers. “Alkenylene” denotes a straight-chain or branched alkenediyl containing one olefinic bond. Examples of “alkenylene” include CH=CH, CH2CH=CH, CH=C(CH3) and the different propylene isomers. “Alkynylene” denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of “alkynylene” include CH2C≡C, C≡CCH2. The term “cycloalkylene” denotes a cycloalkanediyl ring. Examples of “cycloalkylene” include cyclobutanediyl, cyclopentanediyl and cyclohexanediyl. The term “cycloalkenylene” denotes a cycloalkenediyl ring containing one olefinic bond. Examples of “cycloalkenylene” include cyclopropenediyl and cyclopentenediyl.

[0054] “Alkoxy” includes, for example, methoxy, ethoxy, n-propyloxy, z-propyloxy, and the different butoxy, pentoxy and hexyloxy isomers. “Alkenyloxy” includes straight-chain and branched alkenyl attached to and linked through an oxygen atom. Examples of “alkenyloxy” include H2C=CHCH2O and CH3CH=CHCH2O. “Alkynyloxy” includes straight-chain and branched alkynyl attached to and linked through an oxygen atom. Examples of “alkynyloxy” include HC≡CCH2O and CH3C≡CCH2O.

[0055] The term “alkylthio” includes straight-chain and branched alkylthio moieties such as methylthio, ethylthio, and the different propylthio and butylthio isomers. “Alkylsulfinyl” includes both enantiomers of an alkylsulfinyl group. Examples of “alkylsulfinyl” include CH3S(=O), CH3CH2S(=O), CH3CH2CH2S(=O), (CH3)2CHS(=O), and the different butylsulfinyl isomers. Examples of “alkylsulfonyl” include CH3S(=O)2, CH3CH2S(=O)2, CH3CH2CH2S(=O)2, (CH3)2CHS(=O)2, and the different butylsulfonyl isomers.

[0056] “Alkylamino” includes an NH radical substituted with a straight-chain or branched alkyl group. Examples of “alkylamino” include CH3CH2NH, CH3CH2CH2NH, and (CH3)2CHCH2NH. Examples of “dialkylamino” include (CH3)2N, (CH3CH2CH2)2N and CH3CH2(CH3)N.

[0057] “Alkylcarbonyl” denotes a straight-chain or branched alkyl group bonded to a C(=O) moiety. Examples of “alkylcarbonyl” include CH3C(=O), CH3CH2CH2C(=O) and (CH3)2CHC(=O). “Alkoxycarbonyl” includes a C(=O) moiety substituted with a straight-chain or branched alkoxy group. Examples of “alkoxycarbonyl” include CH3OC(=O), CH3CH2OC(=O), CH3CH2CH2OC(=O), (CH3)2CHOC(=O). The terms “alkenyloxycarbonyl” and “alkynyloxycarbonyl” are likewise defined. Examples of “alkenyloxycarbonyl” include H2C=CHCH2OC(=O) and CH3CH2CH=CHOC(=O). Examples of “alkynyloxycarbonyl” include HC≡CCH2OC(=O) and CH3C≡CCH2OC(=O).

[0058] The term “alkylaminocarbonylamino” denotes a straight-chain or branched alkyl group bonded to a NHC(=O)NH moiety. Examples of “alkylaminocarbonylamino” include CH3CH2NHC(=O)NH and (CH3CH2)2CH2NHC(=O)NH.

[0059] “Alkylsulfonylamino” denotes an NH radical substituted with alkylsulfonyl. Examples of “alkylsulfonylamino” include CH3CH2S(=O)2NH and (CH3)2CHS(=O)2NH. The term “alkylsulfonyloxy” denotes an alkylsulfonyl group bonded to an oxygen atom. Examples of “alkylsulfonyloxy” include CH3S(=O)2O, CH3CH2S(=O)2O, CH3CH2CH2S(=O)2O, (CH3)2CHS(=O)2O, and the different butylsulfonyloxy, pentylsulfonyloxy and hexylsulfonyloxy isomers.

[0060] “Alkoxyalkyl” denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2OCH2and CH3CH2OCH2CH2. “Alkoxyalkoxy” denotes alkoxy substitution on another alkoxy moiety.

[0061] The term “alkylcarbonyloxy” denotes a straight-chain or branched alkyl bonded to a C(=O)O moiety. Examples of “alkylcarbonyloxy” include CH3CH2C(=O)O and (CH3)2CHC(=O)O. The term “alkoxycarbonyloxy” denotes a straight-chain or branched alkoxy bonded to a C(=O)O moiety. Examples of “alkoxy carbonyloxy” include CH3CH2CH2OC(=O)O and (CH3)2CHOC(=O)O. The term “alkylaminocarbonyloxy” denotes a straight-chain or branched alkylaminocarbonyl attached to and linked through an oxygen atom. Examples of “alkylaminocarbonyloxy” include (CH3)2CHCH2NHC(=O)O and CH3CH2NHC(=O)O.

[0062] The term “cycloalkyl” refers to a saturated monocyclic group having at least 3, and at most 6 carbon atoms. Examples of “cycloalkyl” include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term “cycloalkoxy” denotes cycloalkyl attached to and linked through an oxygen atom including, for example, cyclopentyloxy and cyclohexyloxy.

[0063] 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 CF3, ClCH2, CF3CH2and CF3CCl2. The terms “haloalkenyl”, “haloalkynyl” “haloalkoxy”, “haloalkylcarbonyl”, “haloalkoxycarbonyl”, and the like, are defined analogously to the term “haloalkyl”. Examples of “haloalkenyl” include Cl2C=CHCH2and CF3CH2CH=CHCH2. Examples of “haloalkynyl” include HC≡CCHCl, CF3C≡C, CCl3C≡C and FCH2C≡CCH2. Examples of “haloalkoxy” include CF3O, CCl3CH2O, F2CHCH2CH2O and CF3CH2O. Examples of “haloalkylcarbonyl” include CF3C(=O), CH3CCl2CH2C(=O) and (CF3)2CHC(=O). Examples of “haloalkoxycarbonyl” include CF3OC(=O), CH3CCl2OC(=O), CH3CBr2CH2OC(=O), (CF3)2CHOC(=O).

[0064] “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 “halotrialkylsilyl” is likewise defined.

[0065] The total number of carbon atoms in a substituent group is indicated by the “Ci-Cj” prefix where i and j are numbers from 1 to 15. For example, C1-C4alkylsulfonyl designates methyl sulfonyl through butylsulfonyl; C2alkoxyalkyl designates CH3OCH2; C3alkoxyalkyl designates, for example, CH3CH(OCH3), CH3OCH2CH2or CH3CH2OCH2; and C4alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2and CH3CH2OCH2CH2.

[0066] Generally when a molecular fragment (i.e. radical) is denoted by a series of atom symbols (e.g., C, H, N, 0 and S) the implicit point or points of attachment will be easily recognized by those skilled in the art. In some instances herein, particularly when alternative points of attachment are possible, the point or points of attachment may be explicitly indicated by a hyphen ("-").

[0067] 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. Commonly, the number of optional substituents (when present) ranges from 1 to 3. As used herein, the term “optionally substituted” is used interchangeably with the phrase “substituted or unsubstituted” or with the term “(un)substituted.”

[0068] The number of optional substituents may be restricted by an expressed limitation. For example, the phrase “optionally substituted with up to 3 substituents independently selected from R11” means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows). When a range specified for the number of substituents (e.g., x being an integer from 0 to 3 in Exhibit B) exceeds the number of positions available for substituents on a ring (e.g., 1 position available for (R12)xon Z-10 in Exhibit B), the actual higher end of the range is recognized to be the number of available positions.

[0069] When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can vary (e.g., (R12)xin Exhibit B wherein x is 1 to 3), then said substituents are independently selected from the group of defined substituents, unless otherwise indicated. When a variable group is shown to be optionally attached to a position, for example (R12)xin Exhibit B wherein x may be 0, then hydrogen may be at the position even if not recited in the definition of the variable group.

[0070] Naming of substituents in the present disclosure uses recognized terminology providing conciseness in precisely conveying to those skilled in the art the chemical structure. For sake of conciseness, locant descriptors may be omitted.

[0071] Unless otherwise indicated, a “ring” as a component of Formula 1 (e.g., Z) is carbocyclic or heterocyclic.

[0072] The term “ring member” refers to an atom (e.g., C, 0, N or S) or other moiety (e.g., C(=O), C(=S), S(=O) and S(=O)2) forming the backbone of a ring or ring system. The term “aromatic” indicates that each of the ring atoms is essentially in the same plane and has a p-orbital perpendicular to the ring plane, and that (4n + 2) π electrons, where n is a positive integer, are associated with the ring to comply with Hückel’s rule.

[0073] The term “carbocyclic ring” denotes a ring wherein the atoms forming the ring backbone are selected only from carbon. Unless otherwise indicated, a carbocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated carbocyclic ring satisfies Hückel’s rule, then said ring is also called an “aromatic ring”. “Saturated carbocyclic” refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.

[0074] As used herein, the term “partially unsaturated ring" or "partially unsaturated heterocycle” refers to a ring which contains unsaturated ring atoms and one or more double bonds but is not aromatic.

[0075] The terms “heterocyclic ring” or “heterocycle” denotes a ring wherein at least one of the atoms forming the ring backbone is other than carbon. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated heterocyclic ring satisfies Hückel’s rule, then said ring is also called a “heteroaromatic ring” or aromatic heterocyclic ring. “Saturated heterocyclic ring” refers to a heterocyclic ring containing only single bonds between ring members.

[0076] Unless otherwise indicated, heterocyclic rings are attached to the remainder of Formula 1 through any available carbon or nitrogen atom by replacement of a hydrogen on said carbon or nitrogen atom.

[0077] Compounds of this invention can exist as one or more stereoisomers. Stereoisomers are isomers of identical constitution but differing in the arrangement of their atoms in space and include enantiomers, diastereomers, cis- and trans-i somers (also known as geometric isomers) and atropisomers. Atropisomers result from restricted rotation about single bonds where the rotational barrier is high enough to permit isolation of the isomeric species. One skilled in the art will appreciate that one stereoisomer may be more active and / or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and / or to selectively prepare said stereoisomers. For a comprehensive discussion of all aspects of stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.

[0078] The term “isomers” means compounds having identical molecular formulae but differing in the nature or sequence of bonding of their atoms or in the arrangement of their atoms in space. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers.” Stereoisomers that are not mirror images of one another are termed “diastereomers” and stereoisomers that are nonsuperimposable mirror images are termed “enantiomers” or “optical isomers.” Compounds of this invention can exist as one or more stereoisomers, including enantiomers, diastereomers, cis- and trans-i somers (also known as geometric isomers) and atropisomers. Atropisomers result from restricted rotation about single bonds where the rotational barrier is high enough to permit isolation of the isomeric species. One skilled in the art will appreciate that one stereoisomer may be more active and / or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and / or to selectively prepare said stereoisomers. For a comprehensive discussion of all aspects of stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.

[0079] A carbon atom bonded to four nonidentical substituents is termed a “chiral center.” A compound with one chiral center has two enantiomeric forms of opposite chirality. A mixture of the two enantiomeric forms is termed a “racemic mixture.” A compound that has more than one chiral center has 2nenantiomeric pairs, where n is the number of chiral centers. Compounds with more than one chiral center may exist as an individual diastereomer or as a mixture of diastereomers, termed a “diastereomeric mixture.” When a chiral center is present a stereoisomer may be characterized by the absolute configuration of that chiral center. Absolute configuration refers to the arrangement in space of the substituents attached to the chiral center and is described by the R- and S-sequencing rules of Cahn, Ingold and Prelog. Conventions for stereochemical nomenclature, methods for the determination of stereochemistry and the separation of stereoisomers are well known in the art (e.g., see “Advanced Organic Chemistry”, 4th edition, March, Jerry, John Wiley & Sons, New York, 1992).

[0080] Compounds of this invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form. Unless the structural formula or the language of this application specifically designate a particular cis- or trans-isomer, or a configuration of a chiral center, the scope of the present invention is intended to cover all such isomers per se, as well as mixtures of cis- and trans-isomers, mixtures of diastereomers and racemic mixtures of enantiomers (optical isomers) as well. Molecular depictions drawn herein follow standard conventions for depicting stereochemistry.

[0081] Compounds of Formula 1 according to the present invention comprise chiral centers at least at the positions designated with an asterisk (*) in the structure shown below, depending on the meanings of Q, R1, Y, R2and R3.

[0082] Accordingly, compounds of Formula 1 which exhibit two asymmetric carbon atoms have four enantiomers which are depicted below as Formulae lathrough ldwherein the chiral centers are identified with an asterisk (*).

[0083]

[0084] When enantiomerically enriched, one enantiomer is present in greater amounts than the other, and the extent of enrichment can be defined by an expression of enantiomeric excess (“ee”), which is defined as (2x-1)· 100%, where x is the mole fraction of the dominant enantiomer in the mixture (e.g., an ee of 20% corresponds to a 60:40 ratio of enantiomers).

[0085] In a preferred embodiment the compositions of this invention have at least a 50% enantiomeric excess; more preferably at least a 75% enantiomeric excess; still more preferably at least a 90% enantiomeric excess; and the most preferably at least a 95% enantiomeric excess of the more active isomer. Of note are enantiomerically pure embodiments of the more active isomer. In a preferred embodiment of the present invention, compounds of Formula 1 exhibit only one asymmetric carbon at the atom to which the substituents Q, R1and Y are attached.

[0086] Compounds of this invention can exist as one or more conformational isomers due to restricted rotation about an amide bond (e.g., C(=O)-N) in Formula 1. This invention comprises mixtures of conformational isomers. In addition, this invention includes compounds that are enriched in one conformer relative to others.

[0087] This invention comprises all stereoisomers, conformational isomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.

[0088] One skilled in the art will appreciate that not all nitrogen containing heterocycles can form Y-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 A -oxi des. 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

[0089] 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

[0090] 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.

[0091] 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 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. When a compound of Formula 1 contains an acidic moiety such as a carboxylic acid, salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium. Accordingly, the present invention comprises compounds selected from Formula 1, N-oxides, and agriculturally suitable salts, and solvates thereof.

[0092] Compounds selected from Formula 1, stereoisomers, tautomers, N-oxides, and salts thereof, typically exist in more than one form, and Formula 1 thus includes all crystalline and noncrystalline 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 to 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. For a comprehensive discussion of polymorphism see R. Hilfiker, Ed., Polymorphism in the Pharmaceutical Industry, Wiley -VCH, Weinheim, 2006.

[0093] Embodiments of the present invention as described in the Summary of the Invention include those described below. In the following Embodiments, Formula 1 includes stereoisomers,

[0094] 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.

[0095] Embodiment 1. A compound of Formula 1 wherein Q is Q-1, Q-2, Q-5, Q-6, Q-7, Q-9, Q-11 or Q-13.

[0096] Embodiment 2. A compound of Embodiment 1 wherein Q is Q-1, Q-5, Q-9 or Q-11.

[0097] Embodiment 3. A compound of Embodiment 2 wherein Q is Q-1, Q-5 or Q-11.

[0098] Embodiment 3a. A compound of Embodiment 3 wherein Q is Q-1 or Q-5.

[0099] Embodiment 4. A compound of Embodiment 3 wherein Q is Q-1.

[0100] Embodiment 5. A compound of Embodiment 3 wherein Q is Q-5.

[0101] Embodiment 6. A compound of Embodiment 3 wherein Q is Q-11.

[0102] Embodiment 7. A compound of Embodiment 2 wherein Q is Q-9.

[0103] Embodiment 8. A compound of Formula 1 wherein Q is Q-1, Q-5, Q-8, Q-9, Q-11 or Q-14.

[0104] Embodiment 9. A compound of Embodiment 8 wherein Q is Q-1, Q-5 or Q-14.

[0105] Embodiment 9a. A compound of Embodiment 9 wherein Q is Q-5 or Q-14.

[0106] Embodiment 10.. A compound of Embodiment 9 wherein Q is Q-14.

[0107] Embodiment 11. A compound of Formula 1 or any one of Embodiments 1 through 10 wherein m is 0 or 1.

[0108] Embodiment 12. A compound of Embodiment 11 wherein m is 0.

[0109] Embodiment 13. A compound of Formula 1 or any one of Embodiments 1 through 10 wherein when Q is Q-9, Q-10, Q-11, Q-12 or Q-13, then m is 1. Embodiment 14. A compound of Formula 1 or any one of Embodiments 1 through 10 wherein when Q is Q-9 or Q-11 , then m is 1.

[0110] Embodiment 15. A compound of Formula 1 or any one of Embodiments 1 through 14 wherein R1is H, cyano, C1-C2alkyl, C1-C2haloalkyl or C1-C2alkoxy.

[0111] Embodiment 16. A compound of Embodiment 15 wherein R1is H.

[0112] Embodiment 17. A compound of Embodiment 15 wherein R1is C1-C2alkyl or C1-C2haloalkyl.

[0113] Embodiment 18. A compound of Embodiment 17 wherein R1is C1-C2alkyl.

[0114] Embodiment 19. A compound of Embodiment 18 wherein R1is methyl.

[0115] Embodiment 20. A compound of Formula 1 or any one of Embodiments 1 through 14 wherein R1is H, methyl or ethyl.

[0116] Embodiment 20a. A compound of Embodiment 20 wherein R1is methyl or ethyl.

[0117] Embodiment 21. A compound of Formula 1 or any one of Embodiments 1 through 20a wherein Y is Y-1, Y-3 or Y-4.

[0118] Embodiment 22. A compound of Embodiment 21 wherein Y is Y-1.

[0119] Embodiment 22a. A compound of Embodiment 22 wherein Y is Y-1 attached to Formula 1 at the 2-position.

[0120] Embodiment 23. A compound of Embodiment 21 wherein Y is Y-3.

[0121] Embodiment 24. A compound of Embodiment 21 wherein Y is Y-4.

[0122] Embodiment 25. A compound of Formula 1 or any one of Embodiments 1 through 20a wherein Y is Y-1 or Y-5.

[0123] Embodiment 26. A compound of Formula 1 or any one of Embodiments 1 through 25 wherein n is 0, 1 or 2.

[0124] Embodiment 27. A compound of Embodiment 26 wherein n is 0 or 1.

[0125] Embodiment 28. A compound of Embodiment 26 wherein n is 1 or 2.

[0126] Embodiment 29. A compound of Embodiment 28 wherein n is 1.

[0127] Embodiment 30. A compound of Embodiment 28 wherein n is 2.

[0128] Embodiment 31. A compound of Embodiment 27 wherein n is 0.

[0129] Embodiment 32. A compound of Formula 1 or any one of Embodiments 1 through 31 wherein R2and R3are each independently H or methyl.

[0130] Embodiment 33. A compound of Embodiment 32 wherein R2and R3are each H.

[0131] Embodiment 34. A compound of Formula 1 or any one of Embodiments 1 through 33 wherein R4is H, amino, cyclopropyl, CH(=O), S(=O)uR7, (C=O)R8or OR9; or C1-C3alkyl or C1-C3haloalkyl, each optionally substituted with up to 1 substituent selected from R4a. Embodiment 35. A compound of Embodiment 34 wherein R4is H, amino, cyclopropyl, CH(=O), S(=O)uR7, (C=O)R8, OR9, C1-C3alkyl or C1-C3haloalkyl.

[0132] Embodiment 36. A compound of Embodiment 35 wherein R4is H, amino, cyclopropyl,

[0133] CH(=O), S(=O)uR7, (C=O)R8, OR9, methyl or halomethyl.

[0134] Embodiment 37. A compound of Embodiment 36 wherein R4is H, CH(=O), S(=O)uR7, (C=O)R8, OR9, methyl or halomethyl.

[0135] Embodiment 38. A compound of Embodiment 34 wherein R4is H, methyl or ethyl.

[0136] Embodiment 39. A compound of Embodiment 38 wherein R4is H or methyl.

[0137] Embodiment 40. A compound of Embodiment 39 wherein R4is H.

[0138] Embodiment 41. A compound of Formula 1 or any one of Embodiments 1 through 37 wherein u is 0 or 2.

[0139] Embodiment 42. A compound of Embodiment 41 wherein u is 2.

[0140] Embodiment 43. A compound of Formula 1 or any one of Embodiments 1 through 42 wherein R4ais cyano, cyclopropyl, C1-C2alkoxy, C1-C2haloalkoxy or C1-C2alkyl sulfonyl.

[0141] Embodiment 44. A compound of Embodiment 43 wherein R4ais cyano, methoxy, halomethoxy or methyl sulfonyl.

[0142] Embodiment 45. A compound of Formula 1 or any one of Embodiments 1 through 44 wherein W is O.

[0143] Embodiment 46. A compound of Formula 1 or any one of Embodiments 1 through 45 wherein A is A1.

[0144] Embodiment 47. A compound of Formula 1 or any one of Embodiments 1 through 45 wherein A is A2.

[0145] Embodiment 48. A compound of Formula 1 or any one of Embodiments 1 through 46 wherein A1is A1-1, A1-2, A1-6, A1-8 or A1-10.

[0146] Embodiment 49. A compound of Embodiment 48 wherein A1is A1-1, A1-2 or A1-1O.

[0147] Embodiment 50. A compound of Embodiment 49 wherein A1is A1- 1 or A1-10.

[0148] Embodiment 51. A compound of Embodiment 49 wherein A1is A1-1.

[0149] Embodiment 52. A compound of Embodiment 49 wherein A1is A1-1O

[0150] Embodiment 53. A compound of Embodiment 48 wherein A1is A1-2.

[0151] Embodiment 54. A compound of Embodiment 48 wherein A1is A1-6.

[0152] Embodiment 55. A compound of Embodiment 48 wherein A1is A1-8.

[0153] Embodiment 56. A compound of Formula 1 or any one of Embodiments 1 through 47 wherein A1is A1-1, A1-3, A1-4, A1-5, A1-6, A1-8 or A1-10. Embodiment 57. A compound of Embodiment 56 wherein A1is A1-1, A1-4, A1-6 or A1-10.

[0154] Embodiment 57a. A compound of Embodiment 57 wherein A1is A1-4.

[0155] Embodiment 57b. A compound of Embodiment 57 wherein A1is, A1-6. Embodiment 58. A compound of Embodiment 57 wherein A1is A1- 1 or A1-10.

[0156] Embodiment 58a. A compound of Embodiment 58 wherein A1is A1-10.

[0157] Embodiment 59. A compound of Formula 1 or any one of Embodiments 1 through 58a wherein q is 0 or 1.

[0158] Embodiment 60. A compound of Embodiment 59 wherein q is 0. Embodiment 61. A compound of Formula 1 or any one of Embodiments 1 through 60 wherein A2is selected from A2-1 through A2-20 as shown in Exhibit A. wherein the bond extending to the left is attached to C=O, and the bond extending to the right is attached to Z; and y is 0, 1, 2 or 3.

[0159] Embodiment 62. A compound of Embodiment 61 wherein A2is A2-1, A2-2, A2-3, A2-4, A2-6, A2-10, A2-14, A2-15 or A2-17.

[0160] Embodiment 63. A compound of Embodiment 62 wherein A2is A2-4, A2-6, A2-10, A2-14, A2-15 or A2-17.

[0161] Embodiment 64. A compound of Embodiment 63 wherein A2is A2-4, A2-6, A2-14 or A2-17.

[0162] Embodiment 65. A compound of Embodiment 64 wherein A2is A2-4, A2-6 or A2-17.

[0163] Embodiment 66. A compound of any one of Embodiments 61 through 65 wherein y is 0, 1 or 2.

[0164] Embodiment 67. A compound of Embodiment 66 wherein y is 1 or 2.

[0165] Embodiment 68. A compound of Embodiment 67 wherein y is 1.

[0166] Embodiment 69. A compound of Embodiment 66 wherein y is 0.

[0167] Embodiment 70. A compound of Formula 1 or any one of Embodiments 1 through 69 wherein Z is selected from Z-1 through Z-60 as shown in Exhibit B.

[0168] wherein the floating bond is connected to A in Formula 1 through any available carbon or nitrogen atom of the depicted ring; and x is 0, 1, 2 or 3.

[0169] Embodiment 71. A compound of Embodiment 70 wherein Z is Z-40 through Z-44, Z-48 or Z-50. Embodiment 72. A compound of Embodiment 70 wherein Z is Z-4 or Z-40 through Z-44. Embodiment 72a. A compound of Embodiment 72 wherein Z is Z-40 through Z-44. Embodiment 73. A compound of Embodiment 72 wherein Z is Z-40, Z-41, Z-43 or Z-44. Embodiment 74. A compound of Embodiment 73 wherein Z is Z-40, Z-43 or Z-44. Embodiment 75. A compound of Embodiment 74 wherein Z is Z-40, or Z-41. Embodiment 76. A compound of Embodiment 75 wherein Z is Z-40. Embodiment 77. A compound of Embodiment 75 wherein Z is Z-41.

[0170] Embodiment 78. A compound of Embodiment 70 wherein Z is Z-4.

[0171] Embodiment 79. A compound of any one of Embodiments 70 through 78 wherein x is 1, 2 or 3.

[0172] Embodiment 80. A compound of Embodiment 79 wherein x is 1 or 2.

[0173] Embodiment 81. A compound of Embodiment 80 wherein x is 2.

[0174] Embodiment 82. A compound of Embodiment 80 wherein x is 1.

[0175] Embodiment 83. A compound of any one of Embodiments 70 through 78 wherein x is 0.

[0176] Embodiment 84. A compound of Formula 1 or any one of Embodiments 1 through 83 wherein each R5ais independently halogen, cyano, hydroxy, nitro, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkylthio or C2-C4alkylcarbonyl.

[0177] Embodiment 85. A compound of Embodiment 84 wherein each R5ais independently halogen, cyano, hydroxy, nitro, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy.

[0178] Embodiment 86. A compound of Embodiment 85 wherein each R5ais independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl or C1-C2alkoxy.

[0179] Embodiment 87. A compound of Embodiment 86 wherein each R5ais independently halogen, cyano or C1-C2alkyl.

[0180] Embodiment 88. A compound of Embodiment 87 wherein each R5ais independently halogen or methyl.

[0181] Embodiment 89. A compound of Formula 1 or any one of Embodiments 1 through 83 wherein each R5ais independently halogen, cyano, methyl, ethyl or C3-C4cycloalkyl.

[0182] Embodiment 89a. A compound of Embodiment 89 wherein each R5ais independently methyl, ethyl or cyclopropyl.

[0183] Embodiment 90. A compound of Embodiment 88 wherein each R5ais methyl.

[0184] Embodiment 91. A compound of Formula 1 or any one of Embodiments 1 through 90 wherein R5bis H, C1-C4alkyl, C1-C4haloalkyl or cyclopropyl.

[0185] Embodiment 92. A compound of Embodiment 91 wherein R5bis H.

[0186] Embodiment 93. A compound of Embodiment 91 wherein R5bis C1-C2alkyl, C1-C2haloalkyl or cyclopropyl.

[0187] Embodiment 94. A compound of Embodiment 93 wherein R5bis C1-C2alkyl.

[0188] Embodiment 95. A compound of Embodiment 94 wherein R5bis methyl.

[0189] Embodiment 96. A compound of Formula 1 or any one of Embodiments 1 through 95 wherein each R6is independently halogen, cyano, nitro, NR13aR13b, C(=O)NR13aR13b, C(R14)=NR15or -U-V-T; or C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C2-C6alkenyloxy, C1-C6alkylthio, C1-C6alkylsulfonyl, C1-C6alkylsulfonyloxy, C1-C6alkylsulfonylamino, C2-C6alkylcarbonyl, C2-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C2-C6alkylcarbonyloxy or C2-C6alkoxycarbonyloxy, each optionally substituted with up to 3 substituents independently selected from R16.

[0190] Embodiment 97. A compound of Embodiment 96 wherein each R6is independently -U-V-T.

[0191] Embodiment 98. A compound of Embodiment 96 wherein each R6is independently halogen, cyano, NR13aR13b, C(=O)NR13aR13b; or C1-C6alkyl, C2-C6alkenyl, C1-C6alkoxy, C2-C6alkenyloxy, C1-C6alkylthio, C1-C6alkyl sulfonyl, C1-C6alkylsulfonylamino, C2-C6alkylcarbonyl or C2-C6alkoxycarbonyl, each optionally substituted with up to 3 substituents independently selected from R16.

[0192] Embodiment 99. A compound of Embodiment 98 wherein each R6is independently halogen, cyano, NR13aR13b, C(=O)NR13aR13b; or C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6alkylsulfonyl, C2-C6alkylcarbonyl or C2-C6alkoxy carbonyl, each optionally substituted with up to 3 substituents independently selected from R16.

[0193] Embodiment 100. A compound of Embodiment 99 wherein each R6is independently halogen or cyano; or C1-C6alkyl, C1-C6alkoxy, C1-C6alkyl sulfonyl, C2-C6alkylcarbonyl or C2-C6alkoxycarbonyl, each optionally substituted with up to 3 substituents independently selected from R16.

[0194] Embodiment 101. A compound of Embodiment 100 wherein each R6is independently halogen or cyano; or C1-C3alkyl or C1-C3alkoxy, each optionally substituted with up to 3 substituents independently selected from R16.

[0195] Embodiment 102. A compound of Embodiment 101 wherein each R6is independently halogen or cyano; or C1-C3alkyl or C1-C3alkoxy, each optionally substituted with up to 1 substituent selected from R16.

[0196] Embodiment 103. A compound of Embodiment 102 wherein each R6is independently halogen, cyano, C1-C2alkyl or C1-C2alkoxy.

[0197] Embodiment 104. A compound of Embodiment 103 wherein each R6is independently halogen, cyano, methyl or methoxy.

[0198] Embodiment 105. A compound of Embodiment 104 wherein each R6is independently halogen, cyano or methyl.

[0199] Embodiment 106. A compound of Embodiment 105 wherein each R6is independently halogen. Embodiment 107. A compound of Embodiment 106 wherein each R6is independently Br,

[0200] Cl or F.

[0201] Embodiment 108. A compound of Embodiment 107 wherein each R6is Cl or F.

[0202] Embodiment 109. A compound of Embodiment 108 wherein each R6is Cl.

[0203] Embodiment 110. A compound of Embodiment 108 wherein each R6is F.

[0204] Embodiment 111. A compound of Formula 1 or any one of Embodiments 1 through 95 wherein each R6is independently halogen, cyano; or C1-C3alkyl, C2-C4alkenyl,

[0205] C2-C4alkynyl, C3-C5cycloalkyl or C1-C3alkoxy, each optionally substituted with up to 3 substituents independently selected from R16.

[0206] Embodiment I l la. A compound of Embodiment 111 wherein each R6is independently halogen, cyano; or C1-C2alkyl, C2-C3alkenyl, C2-C3alkynyl, cyclopropyl or C1-C2alkoxy, each optionally substituted with up to 3 substituents independently selected from R16.

[0207] Embodiment 112. A compound of Embodiment I l la wherein each R6is independently halogen, cyano; or methyl, C2-C3alkynyl or methoxy, each optionally substituted with up to 3 substituents independently selected from R16.

[0208] Embodiment 113. A compound of Embodiment 112 wherein each R6is independently halogen, cyano, methyl, trifluoromethyl or methoxy.

[0209] Embodiment 114. A compound of Embodiment 113 wherein each R6is independently Cl, Br, cyano, methyl, trifluoromethyl or methoxy.

[0210] Embodiment 115. A compound of Embodiment 114 wherein each R6is independently Br, Cl, methyl, trifluoromethyl or methoxy.

[0211] Embodiment 116. A compound of Embodiment 115 wherein each R6is independently Cl or methyl.

[0212] Embodiment 117. A compound of Formula 1 or any one of Embodiments 1 through 116 wherein R7is methyl or methoxy.

[0213] Embodiment 118. A compound of Embodiment 117 wherein R7is methyl.

[0214] Embodiment 119. A compound of Formula 1 or any one of Embodiments 1 through 118 wherein R8is methyl, methoxy or methylthio.

[0215] Embodiment 120. A compound of Embodiment 119 wherein R8is methyl.

[0216] Embodiment 121. A compound of Formula 1 or any one of Embodiments 1 through 120 wherein R9is H, methyl, halomethyl or S(=O)2OM.

[0217] Embodiment 122. A compound of Embodiment 121 wherein R9is H, methyl or trifluoromethyl. Embodiment 123. A compound of Formula 1 or any one of Embodiments 1 through 122 wherein each R10is independently halogen, methyl, halomethyl or methoxy.

[0218] Embodiment 124. A compound of Embodiment 123 wherein each R10is independently halogen, methyl, trifluoromethyl or methoxy.

[0219] Embodiment 125. A compound of Embodiment 124 wherein each R10is independently halogen or methyl.

[0220] Embodiment 126. A compound of Formula 1 or any one of Embodiments 1 through 125 wherein each R11is independently halogen, cyano, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy or C1-C3haloalkoxy.

[0221] Embodiment 127. A compound of Embodiment 126 wherein each R11is independently halogen, methyl or methoxy.

[0222] Embodiment 128. A compound of Embodiment 127 wherein each R11is independently halogen or methyl.

[0223] Embodiment 129. A compound of Formula 1 or any one of Embodiments 1 through 128 wherein each R12is independently halogen, cyano, C1-C3alkyl, C1-C3haloalkyl,

[0224] C2-C3alkenyl, C1-C3alkylthio, C1-C3alkyl sulfonyl, C1-C3alkoxy, C1-C3haloalkoxy, C2-C4alkylcarbonyl or C2-C4alkoxy carbonyl.

[0225] Embodiment 130. A compound of Embodiment 129 wherein each R12is independently halogen, cyano, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy or

[0226] C2-C4alkylcarbonyl.

[0227] Embodiment 131. A compound of Embodiment 130 wherein each R12is independently halogen, C1-C3alkyl, C1-C3haloalkyl or C1-C3alkoxy.

[0228] Embodiment 132. A compound of Embodiment 131 wherein each R12is independently halogen, methyl, trifluoromethyl or methoxy.

[0229] Embodiment 133. A compound of Embodiment 132 wherein each R12is independently halogen, methyl or methoxy.

[0230] Embodiment 134. A compound of Embodiment 133 wherein each R12is independently halogen or methoxy.

[0231] Embodiment 135. A compound of Embodiment 134 wherein each R12is independently halogen.

[0232] Embodiment 136. A compound of Embodiment 135 wherein each R12is independently Cl or F.

[0233] Embodiment 137. A compound of Embodiment 136 wherein each R12is F. Embodiment 138. A compound of Formula 1 or any one of Embodiments 1 through 137 wherein each R13ais independently H, C1-C3alkyl, C2-C4alkylcarbonyl or C2-C4alkoxy carbonyl.

[0234] Embodiment 139. A compound of Embodiment 138 wherein each R13ais independently H, C1-C3alkyl or C2-C4alkyl carbonyl.

[0235] Embodiment 140. A compound of Embodiment 139 wherein each R13ais independently H or C1-C3alkyl.

[0236] Embodiment 141. A compound of Embodiment 140 wherein each R13ais independently H or methyl.

[0237] Embodiment 142. A compound of Embodiment 141 wherein each R13ais H.

[0238] Embodiment 143. A compound of Embodiment 142 wherein each R13ais methyl.

[0239] Embodiment 144. A compound of Formula 1 or any one of Embodiments 1 through 143 wherein each R13bis independently H, cyano, hydroxy, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C2-C6alkylcarbonyl or C2-C6haloalkylcarbonyl.

[0240] Embodiment 145. A compound of Embodiment 144 wherein each R13bis independently H, cyano, hydroxy, C1-C6alkyl, C1-C6haloalkyl or C1-C6alkoxy.

[0241] Embodiment 146. A compound of Embodiment 145 wherein each R13bis independently H, cyano, hydroxy, C1-C6alkyl or C1-C6alkoxy.

[0242] Embodiment 147. A compound of Embodiment 146 wherein each R13bis independently H, cyano, hydroxy, methyl or methoxy.

[0243] Embodiment 148. A compound of Embodiment 147 wherein each R13bis independently H, methyl or methoxy.

[0244] Embodiment 149. A compound of Embodiment 148 wherein each R13bis independently H, or methyl.

[0245] Embodiment 150. A compound of Embodiment 149 wherein each R13bis methyl.

[0246] Embodiment 151. A compound of Formula 1 or any one of Embodiments 1 through 150 wherein each R14is independently H, cyano, halogen, methyl or methoxy.

[0247] Embodiment 152. A compound of Embodiment 151 wherein each R14is independently H, cyano, methyl or methoxy.

[0248] Embodiment 153. A compound of Embodiment 152 wherein each R14is independently H, methyl or methoxy.

[0249] Embodiment 154. A compound of Embodiment 153 wherein each R14is independently H, or methyl. Embodiment 155. A compound of Formula 1 or any one of Embodiments 1 through 154 wherein each R15is independently hydroxy, C1-C4alkoxy, C2-C4alkenyloxy or

[0250] C2-C4alkylcarbonyloxy.

[0251] Embodiment 156. A compound of Embodiments 155 wherein each R15is independently hydroxy or C1-C4alkoxy.

[0252] Embodiment 157. A compound of Embodiments 156 wherein each R15is independently hydroxy or methoxy.

[0253] Embodiment 158. A compound of Embodiments 157 wherein each R15is methoxy.

[0254] Embodiment 159. A compound of Formula 1 or any one of Embodiments 1 through 158 wherein each U is independently a direct bond or C(=O)O.

[0255] Embodiment 160. A compound of Embodiment 159 wherein each U is direct bond.

[0256] Embodiment 161. A compound of Formula 1 or any one of Embodiments 1 through 158 wherein each U is C(=O)NH.

[0257] Embodiment 162. A compound of Formula 1 or any one of Embodiments 1 through 161 wherein each V is independently a direct bond or C1-C3alkylene.

[0258] Embodiment 163. A compound of Embodiment 162 wherein each V is independently a direct bond or CH2.

[0259] Embodiment 164. A compound of Embodiment 163 wherein each V is a direct bond.

[0260] Embodiment 165. A compound of Embodiment 163 wherein each V is CH2.

[0261] Embodiment 166. A compound of Formula 1 or any one of Embodiments 1 through 165 wherein each T is independently phenyl optionally substituted with up to 3 substituents independently selected from R17; or pyridinyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, thienyl, piperidinyl, morpholinyl or piperazinyl, each optionally substituted with up to 3 substituents independently selected from R18.

[0262] Embodiment 167. A compound of Embodiment 166 wherein each T is independently phenyl optionally substituted with up to 2 substituents independently selected from R18; or pyridinyl or pyrazolyl, each optionally substituted with up to 2 substituents independently selected from R18.

[0263] Embodiment 168. A compound of Embodiment 167 wherein each T is phenyl optionally substituted with up to 2 substituents independently selected from R18.

[0264] Embodiment 169. A compound of Formula 1 or any one of Embodiments 1 through 168 wherein each R16is independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl, cyclopropyl, C1-C2alkoxy, C1-C2haloalkoxy, C2-C3alkylcarbonyl, C2-C3haloalkylcarbonyl or C2-C3alkoxycarbonyl. Embodiment 170. A compound of Embodiment 169 wherein each R16is independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl, C1-C2alkoxy, C1-C2haloalkoxy,

[0265] C2-C3alkylcarbonyl or C2-C3alkoxy carbonyl.

[0266] Embodiment 171. A compound of Embodiment 170 wherein each R16is independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl, C1-C2alkoxy or C1-C2haloalkoxy.

[0267] Embodiment 172. A compound of Embodiment 171 wherein each R16is independently halogen, C1-C2alkyl, C1-C2haloalkyl or C1-C2alkoxy.

[0268] Embodiment 173. A compound of Embodiment 172 wherein each R16is independently halogen, methyl, halomethyl or methoxy.

[0269] Embodiment 174. A compound of Embodiment 173 wherein each R16is independently halogen or methyl.

[0270] Embodiment 175. A compound of Embodiment 174 wherein each R16is independently halogen.

[0271] Embodiment 176. A compound of Embodiment 175 wherein each R16is F.

[0272] Embodiment 177. A compound of Formula 1 or any one of Embodiments 1 through 168 wherein each R16is independently C3-C15trialkylsilyl.

[0273] Embodiment 178. A compound of Embodiment 178 wherein each R16is trimethyl silyl.

[0274] Embodiment 179. A compound of Formula 1 or any one of Embodiments 1 through 178 wherein each R17is independently halogen, cyano, methyl, halomethyl or methoxy.

[0275] Embodiment 180. A compound of Embodiment 179 wherein each R17is independently halogen, cyano, methyl or methoxy.

[0276] Embodiment 181. A compound of Embodiment 180 wherein each R17is independently halogen or methyl.

[0277] Embodiment 182. A compound of Embodiment 181 wherein each R17is independently halogen.

[0278] Embodiment 183. A compound of Formula 1 or any one of Embodiments 1 through 182 wherein Y is Y-1 attached to Formula 1 at the 2-position and substituted with one R6attached at the 6-position.

[0279] Embodiment 184. A compound of Formula 1 or any one of Embodiments 1 through 182 wherein Y is Y-5 attached to Formula 1 at the 2-position and substituted with one R6attached at the 4-position.

[0280] Embodiment 185. A compound of Formula 1 or any one of Embodiments 1 through 184 wherein Z is Z-40 substituted with 1 R12group attached at the 2-position (ortho) or attached at the 4-position (para), or Z is Z-40 substituted with 2 R12groups attached at the 2- and 4- positions (ortho and para). Embodiment 186. A compound of Embodiment 185 wherein Z is Z-40 substituted with 2 R12groups attached at the 2- and 4- positions (ortho and para).

[0281] Embodiments of this invention, including Embodiments 1-186 above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds (e.g. compounds of Formula 6) useful for preparing the compounds of Formula 1. In addition, embodiments of this invention, including Embodiments 1- 186 above, as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.

[0282] Combinations of Embodiments 1-186 are illustrated by:

[0283] Embodiment A. A compound of Formula 1 wherein

[0284] Q is Q-1, Q-2, Q-5, Q-6, Q-7, Q-9, Q-11 or Q-13;

[0285] R1is C1-C2alkyl;

[0286] Y is Y-1, Y-3 or Y-4;

[0287] R2and R3are each independently H or methyl;

[0288] R4is H, amino, cyclopropyl, CH(=O), S(=O)uR7, (C=O)R8, OR9, C1-C3alkyl or C1-C3haloalkyl;

[0289] W is O;

[0290] A1is A1-1, A1-2, A1-6, A1-8 or A1-10; q is 0 or 1; A2is selected from

[0291] wherein the bond extending to the left is attached to C=O, and the bond extending to the right is attached to Z; and y is 0, 1, 2 or 3;

[0292] Z is selected from

[0293] wherein the floating bond is connected to A in Formula 1 through any available carbon or nitrogen atom of the depicted ring; and x is 0, 1, 2 or 3; each R5ais independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl or C1-C2alkoxy; R5bis H or C1-C2alkyl; each R6is independently halogen, cyano, NR13aR13b, C(=O)NR13aR13b; or C1-C6alkyl, C2-C6alkenyl, C1-C6alkoxy, C2-C6alkenyloxy, C , -C6alkylthio, C1-C6alkylsulfonyl, C1-C6alkylsulfonylamino, C2-C6alkylcarbonyl or C2-C6alkoxycarbonyl, each optionally substituted with up to 3 substituents independently selected from R16; R7is methyl or methoxy;

[0294] R8is methyl, methoxy or methylthio;

[0295] R9is H, methyl, halomethyl or S(=O)2OM; each R10is halogen, methyl, halomethyl or methoxy; each R11is independently halogen, cyano, C1-C3, alkyl, C1-C3haloalkyl, C1-C3alkoxy or C1-C3haloalkoxy; each R12is independently halogen, cyano, C1-C3alkyl, C1-C3haloalkyl, C2-C3alkenyl, C1-C3alkylthio, C1-C3alkylsulfonyl, C1-C3alkoxy, C1-C3haloalkoxy, C2-C4alkylcarbonyl or C2-C4alkoxycarbonyl; each R13ais independently H, C1-C3alkyl, C2-C4alkylcarbonyl or C2-C4alkoxy carbonyl; each R13bis independently H, cyano, hydroxy, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C2-C6alkylcarbonyl or C2-C6haloalkylcarbonyl; each R14is independently H, cyano, halogen, methyl or methoxy; each R15is independently hydroxy, C1-C4alkoxy, C2-C4alkenyloxy or C2-C4alkylcarbonyloxy; each R16is independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl, cyclopropyl, C1-C2alkoxy, C1-C2haloalkoxy, C2-C3alkylcarbonyl, C2-C3haloalkylcarbonyl or

[0296] C2-C3alkoxy carbonyl.

[0297] Embodiment B. A compound of Embodiment A wherein

[0298] Q is Q-1, Q-5, Q-9 or Q-11; m is 0 or 1;

[0299] R1is methyl;

[0300] Y is Y-1; n is 1 or 2;

[0301] R2and R3are each H;

[0302] R4is H;

[0303] A1is A1-1, A1-2 or A1-10; q is 0;

[0304] Z is Z-40, Z-43 or Z-44; x is 1 or 2;

[0305] R5ais halogen or methyl;

[0306] R5bis C1-C2alkyl; each R6is independently halogen or cyano; or C1-C3alkyl or C1-C3alkoxy, each optionally substituted with up to 1 substituent selected from R16; each R12is independently halogen, C1-C3alkyl, C1-C3haloalkyl or C1-C3alkoxy; and each R16is independently halogen, methyl, halomethyl or methoxy.

[0307] Embodiment C. A compound of Embodiment B wherein

[0308] Q is Q-1, Q-5 or Q-11; n is 1; A1is A1-1 or A1-10;

[0309] Z is Z-40;

[0310] R5ais methyl;

[0311] R5bis methyl;

[0312] R6is halogen, cyano, methyl or methoxy; and each R12is independently halogen, methyl or methoxy.

[0313] Embodiment D. A compound of Embodiment C wherein

[0314] Q is Q-1 or Q-5; m is 0;

[0315] A1is A1-1,

[0316] R6is halogen; and each R12is independently halogen.

[0317] Embodiment E. A compound of Embodiment D wherein

[0318] Q is Q-5;

[0319] R6is Cl or F; and each R12is independently Cl or F.

[0320] Embodiment F. A compound of Formula 1 wherein

[0321] Q is Q-1, Q-2, Q-5, Q-6, Q-7, Q-9, Q-11 or Q-13; m is 0 or 1;

[0322] R1is C1-C2alkyl;

[0323] Y is Y-1; n is 0, 1 or 2;

[0324] R2and R3are each H;

[0325] R4is H;

[0326] W is O;

[0327] A1is A1-1, A1-2, A1-6, A1-8 or A1-10; q is 0 or 1;

[0328] Z is Z-40, Z-43 or Z-44; x is 1 or 2;

[0329] R5ais halogen, cyano or C1-C2alkyl;

[0330] R5bis C1-C2alkyl; each R6is independently halogen, cyano, methyl or methoxy; and

[0331] R10is independently halogen or methyl; each R12is independently halogen.

[0332] Embodiment G. A compound of Embodiment F wherein Q is Q-1, Q-5, Q-9 or Q-11;

[0333] R1is methyl; n is 1;

[0334] A1is A1-1, A1-2 or A1-10; q is 0;

[0335] Z is Z-40;

[0336] R5ais methyl;

[0337] R5bis methyl; and

[0338] R6is halogen, cyano or methyl.

[0339] Embodiment H. A compound of Embodiment G wherein

[0340] Q is Q-5; m is 0;

[0341] A1is A1-1, q is 0;

[0342] R6is halogen; and each R12is independently Cl or F.

[0343] Embodiment I. A compound of Formula 1 or any one of Embodiments A through H wherein Y is wherein the bond extending to the right is attached to Formula 1; and R6is halogen, cyano, methyl or methoxy.

[0344] Embodiment J. A compound of Formula 1 wherein

[0345] Q is Q-1, Q-5, Q-8, Q-9, Q-11 or Q-14; m is 0 or 1;

[0346] R1is H, methyl or ethyl;

[0347] Y is Y-1 or Y-5; n is 0 or 1;

[0348] R2and R3are each H;

[0349] R4is H, methyl or ethyl;

[0350] W is O;

[0351] A is A1; A1is A1-1, A1-3, A1-4 A1-5, A1-6, A1-8 or A1-10; q is 0;

[0352] Z is selected from wherein the floating bond is connected to A in Formula 1 through any available carbon of the depicted ring; and x is 0, 1, 2 or 3; each R5ais independently halogen, cyano, methyl, ethyl or C3-C4cycloalkyl;

[0353] R5bis C1-C2alkyl; each R6is independently halogen, cyano; or C1-C3alkyl, C2-C4alkenyl, C2-C4alkynyl, C3-C5cycloalkyl or C1-C3alkoxy, each optionally substituted with up to 3 substituents independently selected from R16; each R12is independently halogen, cyano, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy or C2-C4alkyl carbonyl; and each R16is independently halogen, C1-C2alkyl, C1-C2haloalkyl, C1-C2alkoxy or trimethyl silyl.

[0354] Embodiment K. A compound of Embodiment J wherein

[0355] Q is Q-1, Q-5 or Q-14;

[0356] R1is methyl or ethyl;

[0357] Y is Y-1; n is 1;

[0358] R4is H;

[0359] A1is A1-1, A1-4, A1-6, A1-8 or A1-10;

[0360] Z is Z-40 or Z-41; x is 1 or 2; each R5ais independently methyl, ethyl or cyclopropyl;

[0361] R5bis methyl; each R6is independently halogen, cyano; or C1-C2alkyl, C2-C3alkenyl, C2-C3alkynyl, cyclopropyl or C1-C2alkoxy, each optionally substituted with up to 3 substituents independently selected from R16; each R12is independently halogen or methoxy; and each R16is independently halogen.

[0362] Embodiment L. A compound of Embodiment K wherein

[0363] Q is Q-5 or Q-14;

[0364] R1is methyl;

[0365] A1is A1-1 or A1-10;

[0366] Z is Z-40; each R5ais methyl; each R6is independently Cl, Br, cyano, methyl, trifluoromethyl or methoxy; and each R12is independently Cl or F.

[0367] Embodiment LI . A compound of Embodiment K wherein

[0368] Q is Q-5 or Q-14;

[0369] R1is methyl;

[0370] A1is A1-1 or A1-10;

[0371] Z is Z-40 or Z-41; each R5ais methyl; each R6is independently Cl, Br, cyano, methyl, trifluoromethyl or methoxy; and each R12is independently Cl or F.

[0372] Embodiment M. A compound of Embodiments L or LI wherein

[0373] A1is A1-1, m is 0; and each R6is independently Cl or methyl.

[0374] Embodiment N. A compound of Embodiment M wherein

[0375] Q is Q-14;

[0376] Embodiment 0. A compound of Formula 1 or any one of Embodiments A through N wherein Y is wherein the bond extending to the right is attached to Formula 1; and R6is Cl, Br, cyano, methyl, trifluoromethyl or methoxy.

[0377] Specific embodiments include compounds of Formula 1 selected from the group consisting of:

[0378] N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-5-(2,4-difluorophenyl)-

[0379] 3-isoxazolecarboxamide (Compound 1);

[0380] 5-(2,4-difluorophenyl)-N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4- yl)propyl]-3-isoxazolecarboxamide (Compound 24);

[0381] 2-(2,4-difluorophenyl)-iV-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4- yl)propyl]-2H-tetrazole-5-carboxamide (Compound 41);

[0382] N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-5-(2,4-difluorophenyl)-

[0383] 1.2.4-oxadiazole-3 -carboxamide (Compound 45);

[0384] N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-2-(2,4-difluorophenyl)-

[0385] 2H-tetrazole-5-carboxamide (Compound 46);

[0386] N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-3-(2,4-difluorophenyl)-

[0387] 1.2.4-oxadiazole-5-carboxamide (Compound 47);

[0388] N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-1-(2,4-difluorophenyl)-

[0389] 1H- 1 ,2,3-triazole-4-carboxamide (Compound 48);

[0390] N-[2-(6-chloro-2-pyridinyl)-2-(l-methyl-1H-1,2,4-triazol-3-yl)propyl]-5-(2,4-difluorophenyl)-

[0391] 3-isoxazolecarboxamide (Compound 77);

[0392] N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(2,4-difluorophenyl)-3- isoxazolecarboxamide (Compound 79);

[0393] N-[2-(6-chloro-2-pyridinyl)-2-(l-methyl-1H-1,2,3-triazol-4-yl)propyl]-5-(2,4-difluorophenyl)-

[0394] 3-isoxazolecarboxamide (Compound 82);

[0395] N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(2,4-difluorophenyl)-

[0396] 1.3.4-thiadiazolecarboxamide (Compound 90);

[0397] N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(2,4-difluorophenyl)-

[0398] 1,3,4-thiadiazolecarboxamide (Compound 92);

[0399] N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-5-(3,5-difluoro-2- pyridinyl)-3-isoxazolecarboxamide (Compound 94); and

[0400] N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(3,5-difluoro-2- pyridinyl)-3-isoxazolecarboxamide (Compound 95).

[0401] Specific embodiments also include compounds of Formula 1 selected from the group consisting of:

[0402]

[0403] As noted in the Summary of the Invention, this invention also relates to a compound of Formula 6, or an N-oxide or salt thereof Also noted is that the embodiments of this invention, including Embodiments 1-186 above, relate also to compounds of Formula 6. Accordingly, combinations of Embodiments 1-186 are further illustrated by:

[0404] Embodiment B 1. A compound of Formula 6, or an N-oxide or salt thereof, wherein

[0405] Q is Q-1, Q-5, Q-8, Q-9, Q-11 or Q-14; m is 0 or 1;

[0406] R1is H, methyl or ethyl;

[0407] R5ais halogen or methyl; and

[0408] R5bis C1-C2alkyl.

[0409] Embodiment B2. A compound of Embodiment Bl wherein

[0410] Q is Q-1, Q-5 or Q- 14; and m is 0;

[0411] R1is methyl or ethyl; and

[0412] R5bis methyl.

[0413] Embodiment B3. A compound of Embodiment B2 wherein

[0414] Q is Q-5 or Q-14; and

[0415] R1is methyl.

[0416] In addition to the embodiments described above, this invention also provides a fungicidal composition comprising a compound of Formula 1 (including all stereoisomers, N-oxides, and salts thereof), and at least one other fungicide. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.

[0417] This invention also provides a fungicidal composition comprising a compound of Formula 1 (including all stereoisomers, N-oxides, and salts thereof) (i.e. in a fungicidally effective amount), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.

[0418] This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to a plant seed, a fungicidally effective amount of a compound of Formula 1 (including all stereoisomers, N-oxides, and salts thereof). Of note as embodiments of such methods are methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments described above. Of particular note are embodiments where the compounds are applied as compositions of this invention.

[0419] One or more of the following methods and variations as described in Schemes 1-18 can be used to prepare the compounds of Formula 1. The definitions of R1, R2, R3, R4, R6, Q, Y, W, A and Z in the compounds of Formulae 1-25 below are as defined above in the Summary of the Invention unless otherwise noted. Compounds of Formulae la-1b are various subsets of Formula 1, and all substituents for Formulae la-1b are as defined above for Formula 1 unless otherwise noted. As shown in Scheme 1, compounds of Formula la (Formula 1 wherein W is 0 and is H) can be prepared by coupling an amine of Formula 3 (or its acid salt) with a carboxylic acid of Formula 2 in the presence of a dehydrative coupling reagent such as 1- [bis(dimethylamino)m ethylene]- 1H- 1,2, 3 -triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU), O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU), 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide (T3P, also known as propanephosphonic acid anhydride), l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 1- ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC HCl), 1,1'- carbonyldiimidazole (CDI), N,N-diisopropylcarbodiimide (DIC), 1 -hydroxybenzotriazole (HOBt) or N,N-dicyclohexylcarbodiimide (DCC). In certain instances it can be advantageous to use polymer-supported coupling reagents, such as polymer-bound cyclohexylcarbodiimide derivatives. The reaction is typically run in an aprotic solvent such as dichloromethane, tetrahydrofuran, N,N-dimethylformamide, acetonitrile or ethyl acetate and in the presence of a base such as tri ethylamine, pyridine or AA'-diisopropylethylamine. Useful reaction temperatures typically range from about room temperature to the reflux temperature of the solvent. For conditions and variations of this reaction see, for example, Organic Process Research & Development 2016, 20, 140-177. Also, the method of Scheme 1 is demonstrated in Example 1 (Step D), Example 2 (Step D), Example 3, Example 4 (Step C), Example 5 (Step B), Example 6 (Step D), Example 7 (Step F), Example 8 (Step D), Example 9 (Step C) and Example 11 (Step F).

[0420] Scheme 1

[0421] Alternatively, compounds of Formula la (Formula 1 wherein W is 0 and R4is H) can be prepared as shown in Scheme 2. In this method, a carboxylic acid of Formula 2 is first converted to a compound of Formula 4 wherein L1is a suitable leaving group, such as a halogen (e g., Br, Cl) or sulfonate (e.g., mesylate, triflate,p-toluenesulfonate). Particularly useful in the method of Scheme 2 are compounds of Formula 4 wherein L1is chloro (i.e. acid chlorides). Subsequent coupling of compounds of Formula 4 with compounds of Formula 3 provides the desired compounds of Formula la. The coupling reaction can be carried out in a wide variety of solvents including tetrahydrofuran, diethyl ether, and dichloromethane, typically in the presence of an amine base such as triethylamine, pyridine and N,N-diisopropylethylamine. In certain instances, it can be useful to use polymer-supported bases such as polymer-bound N,N- diisopropylethylamine and polymer-bound 4-(dimethylamino)pyridine. Acid salts of the Formula 3 amines can also be used in this reaction, provided that at least 2 equivalents of the base is present. Typical acids used to form salts with amines include hydrochloric acid, oxalic acid and trifluoroacetic acid. Conditions for converting carboxylic acids of Formula 2 to a compound of Formula 4 are well-known in the published chemistry literature. For example, acid chlorides of Formula 4 are readily obtained by treating corresponding acids of Formula 2 with thionyl chloride, oxalyl chloride, phosphorus trichloride, phosphorus oxychloride or phosphorus pentachloride in a solvent such as dichloromethane or toluene and optionally in the presence of a catalytic amount of N,N-dimethylformamide. Sulfonates of Formula 4 can be obtained by treating acids of Formula 2 with alkyl or aryl sulfonyl chlorides or sulfonic anhydrides to form the sulfonates.

[0422] Intermediate compounds of Formula ! are commercially available and can be prepared by methods documented in the chemistry literature. For example, see J. Med. Chem. 2020, 63, 15864-15882; J. Med. Chem. 2022, 65, 8843-8854; Organic Process Research & Development 2020, 24, 228-234; Letters in Organic Chemistry 2010, 7, 32-38; WO 2022 / 256419; WO 2023 / 166190; WO 2014 / 069554; EP 3786163, WO 2021 / 094434, WO 2018 / 019929 and WO 2024 / 156886.

[0423] Scheme 2

[0424] As shown in Scheme 3, compounds of Formula la (Formula 1 wherein W is 0 and R4is H) can be converted to compounds of Formula lb (Formula 1 wherein W is 0 and R4is alkyl, and the like) by reaction with compounds of formula R4-L1wherein L1is a suitable leaving group, such as a halogen (e.g., Br, Cl) or sulfonate (e.g., mesylate, triflate, p-toluenesulfonate), preferably in the presence of a base such as potassium carbonate, sodium hydride or potassium tert-butoxide, and in a solvent such as N,N-dimethylformamide, tetrahydrofuran or toluene. General procedures for reactions of this type are well-known in the art and can be readily adapted to prepare compounds of the present invention. Particularly useful reagents for preparing compounds of Formula lb wherein R4is methyl include diazomethane and iodomethane using general procedures known in the art, such as those described in Canada Journal of Chemistry 1986, 64, 2211-2219 and Heterocycles 2000, 53(12), 2775-2780. Also, the method of Scheme 3 is demonstrated in Example 10.

[0425] Scheme 3

[0426] As shown in Scheme 4, compounds of Formula 3 wherein R2and R3are H can be prepared from nitriles of Formula 5. In Method A, compounds of Formula 5 are treated with an appropriate reducing agent such as borane-tetrahydrofuran, borane dimethyl sulfide or lithium aluminum hydride in an aprotic solvent such as tetrahydrofuran at a temperature between ambient and the boiling point of the solvent. This type of reduction is well-known in the art; for references see, for example, Chem. Rev. 2006, 106, 2617-2650; J. Org. Chem. 1982, 47, 3153-3163 and J. Am. Chem. Soc. 1951, 73(1), 242-244. Also, the method of Scheme 4 using borane tetrahydrofuran as the reducing agent is illustrated in present Example 1 (Step C) and Example 4 (Step B); and the method of Scheme 4 using borane dimethyl sulfide is illustrated in Example 11 (Step E). Other reducing agents may also be used in Method A of Scheme 4, such as sodium borohydride in the presence of cobalt chloride as described in J. Am. Chem. Soc. 1982, 104, 6801-6802; and as illustrated in present Example 5 (Step A), Example 6 (Step C) and Example 7 (Step E). Other reduction methods known in the art may also be employed, such as catalytic hydrogenation as shown in Method B of Scheme 4. Typical reaction conditions involve exposing a compound of Formula 5 to hydrogen gas at a pressure of about 100 to 500 kPa, in the presence of a metal catalyst such as palladium or ruthenium supported on an inert carrier such as activated carbon, in a solvent such as ethanol at about 20 °C. This type of reduction is well-known; see, for example, Catalytic Hydrogenation, L. Cerveny, Ed., Elsevier Science, Amsterdam, 1986; Journal of Catalysis 2021, 404, 475-492 and WO 2005 / 094514. One skilled in the art will recognize that certain other functionalities that may be present in compounds of Formula 5 can also be reduced under catalytic hydrogenation conditions, thus requiring a suitable choice of catalyst and reaction conditions. In some cases, the presence of a chiral diamine ligand having at least one N-H bond results in higher chemoselectivity of the desired compound (i.e. the nitrile moiety is selectively reduced over certain other functionalities that may be present in compounds of Formula 5).

[0427] Scheme 4

[0428] As shown in Scheme 5, compounds of Formula 3 where in R2is C1-C4alkyl and R3is H can be prepared by reaction of an organometallic reagent of formula R2-M with nitriles of Formula 5. In this method compounds of formula R2-M are alkyl Grignard reagents (i.e. M is MgBr or MgCl, for example, methylmagnesium bromide or chloride) or alkyl lithium reagents (i.e. M is Li, for example, methyllithium or tert-butyl lithium). The addition product formed by reaction of the organometallic reagent with the nitrile of Formula 5 can be reduced in-situ either by sodium borohydride or lithium aluminum hydride. Depending on the reactants and reaction conditions, Grignard and lithium reagents can add twice to nitriles of Formula 5 to provide compounds of Formula 3 wherein R2and R3are both C1-C4alkyl. Double addition of the same or different organometallic reagent is possible, leading to symmetric or asymmetric amines of Formula 3. Alternatively, compounds of Formula 3 wherein R2and R3are C1-C4alkyl can be obtained by double addition of an alkyl cerium reagent to nitriles of Formula 5. The presence of a Lewis acid such as titanium(IV) isopropoxide can be advantageous. For representative procedures describing single and double addition of organometallics to nitriles see Advanced Synthesis & Catalysis 2017, 359, 179-201; J. Org. Chem. 1992, 57, 4521-4527; J. Org. Chem. 1986, 57, 5338-5341; Journal of the American Chemical Society, 1953, 75(23), 5898-5899; WO 2005 / 094514 (Example 9) WO 2014 / 184275 and U.S. 5,306,821. Scheme 5

[0429] As shown in Scheme 6, compounds of Formula 5 can be prepared by deprotonation of nitriles of Formula 6 with a strong base such as sodium hydride, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium tert-butoxide or an alkyl lithium base such as n-butyl lithium, in an inert solvent such as tetrahydrofuran, 2-methyltetrahydrofuran, toluene, or mixtures thereof, at temperatures ranging from -78 °C to the reflux temperature of the solvent, followed by treatment with an appropriate reagent of Formula 7 wherein L2is a leaving group such as a halogen. For typical reaction conditions see, for example U.S. 3,755,412. Also, the method of Scheme 6 is illustrated in Example 1 (Step B), Example 6 (Step B), Example 11 (Step D) and Example 12 (Step D).

[0430] Scheme 6

[0431] Compounds of Formula 6 wherein Q is a carbon linked ring (i.e. Q is Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7 and Q-8, and R5battached to Q is other than H) can be prepared by alkylation of compounds of Formula 8 as illustrated in Scheme 7. Alkylation is achieved by reacting a compound of Formula 8 with a metalating agent, followed by an alkylating agent of Formula 9 wherein L1is a leaving group such as halogen (e.g., Cl, Br, I) or a sulfonate (e.g., p- toluenesulfonate, methanesulfonate or trifluoromethanesulfonate). Suitable metalating agents include, for example, n-butyl lithium, lithium diisopropylamide or sodium hydride. For reaction conditions see Journal of Medicinal Chemistry 2003, 46(16), 3463-3475 and Heterocycles 1997, 44, 67-70. Also, the method of Scheme 1 is illustrated in Example 1 (Step A). Scheme 7

[0432] The starting acetonitrile of Formula 8 are commercially available and can easily be prepared using commercial precursors and known methods. For example, as illustrated in Scheme 8, reaction of a compound of Formula 10 with a cyanating reagent such as sodium cyanide, potassium cyanide or potassium hexacyanoferrate(II) provides compounds of Formula 8 wherein Q is a carbon link ring (i.e. Q is Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7 and Q-8). There are a variety of conditions published in the chemistry literature which can be used for converting a halide to a nitrile, including copper-catalyzed conditions involving the use of a suitable copper source (e.g., copper(I) iodide), an amine ligand (e.g., N,N -dimethylethylenediamine) and an iodide salt (e.g., copper(I) iodide, sodium iodide, potassium iodide or zinc iodide). For references see, for example, Journal of the American Chemical Society 2003, 125, 2890-2891; Synlett 2007, 4, 555-558 and Chem. Eur. J. 2007, 13, 6249-6254.

[0433] Chlorides of Formula 10 are easily prepared from the corresponding alcohols by treatment with a chlorinating reagent such as oxalyl chloride or thionyl chloride in a solvent such as dichloromethane or toluene and optionally in the presence of a catalytic amount of N, N- dimethylformamide.

[0434] Scheme 8

[0435] Compounds of Formula 6 wherein Q is a nitrogen linked ring (i.e. Q is Q-9, Q-10, Q-11, Q-12, and Q-13) can be prepared by displacement of an appropriate leaving group L1of compounds of Formula 12 with nitrogen-containing heterocycles of Formula 11 in the presence of a base as depicted in Scheme 9. Suitable bases include inorganic bases such as alkali or alkaline earth metal (e.g., lithium, sodium, potassium and cesium) hydrides, alkoxides, carbonates, phosphates and hydroxides. A variety of solvents are suitable for the reaction including, for example, N,N-dimethylformamide, N,N-di methyl acetamide, N-methylpyrrolidinone, acetonitrile and acetone. Suitable leaving groups in the compounds of Formula 12 include halogen (e.g., Cl, Br, I) or a sulfonate (e.g., p-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate). Particularly useful reaction conditions include using cesium carbonate as the base, chlorine as the leaving group and acetonitrile or N,N-dimethylformamide as the solvent at temperatures ranging between about room temperature to 100 °C. In some cases (depending on the Q ring), the method of Scheme 9 results in two regioisomers. Purification of the regioisomers can be achieved using standard techniques such as column chromatography. The method of Scheme 9 is illustrated in present Example 6 (Step A).

[0436] Scheme 9

[0437] An alternative method for the preparation of intermediates of Formula 3 involves reduction of nitro precursors of Formula 13 to form the corresponding amines as shown in Scheme 10. The reduction can be carried out by use of a metal such as iron or zinc in the presence of an acidic medium such as acetic acid under such conditions as described in Berichte der Deutschen Chemischen Gesellschaft 1904, 37, 3520-3525, or by treatment with SnCl2as described in Chemische Berichte 1955, 88, 1577-1585. The reduction can also be done via hydrogenation in the presence of a metal catalyst such as palladium supported on an inert carrier such as activated carbon or nickel under such conditions as described in Chemische Berichte 1955, 88, 866-874. One skilled in the art will recognize that certain functionalities that may be present in compounds of Formula 13 can also be reduced under catalytic hydrogenation conditions, thus requiring a suitable choice of catalyst and conditions. The synthetic literature includes many general methods for the reduction of nitro groups to amines; see, for example, J. Labelled Compounds & Radiopharmaceuticals, 2011, 54(5), 239; Comprehensive Organic Name Reactions Reagents, Z. Wang, Ed.; Wiley- VCH: Weinheim, Germany 2010, 2244; ARKIVOC 2005, (3), 179-191; Journal of Heterocyclic Chemistry 2001, 38(5), 1065-1069; Bioorganic & Medicinal Chemistry Letters 2006, 76(14), 3713-3718; Journal of Pharmacy and Pharmacology 2006, 58(3), 393-401; and WO 2021 / 021953.

[0438] Scheme 10

[0439] As shown in Scheme 11, compounds of Formula 13a (Formula 13 wherein R1and R3are H) wherein X is halogen (e.g., Br or I) can be prepared under halogen-metal exchange reaction conditions. For example, a compound of Formula 15 can first be treated with a metalating agent such as an alkyl lithium base (e.g., n-butyllithium, s-butyllithium or lithium diisopropylamide) or a Grignard reagent in a solvent such as toluene, ethyl ether, tetrahydrofuran or dimethoxymethane at temperatures ranging from about -78 °C to ambient temperature. Anions of Formula 15 are then contacted with a compound of Formula 14 to provide compounds of Formula 13a. There are a wide-variety of general methods described in the synthetic literature for metalation / alkylation reactions which can be readily adapted to prepare compounds of the present invention; see, for example, RSC Adv. 2021, 11, 1783-1793; J. Org. Chem. 2010, 75, 984-987 ; Journal of Medicinal Chemistry 1980, 23(12), 1398-1405; US2006 / 0287292; and WO 2021 / 021953.

[0440] Scheme 11

[0441] As shown in Scheme 12, compounds of Formula 14 can be accessed by coupling nitroalkanes of Formula 17 and aldehydes of Formula 16 in the presence of a suitable base to provide compounds of Formula 18. Subsequent dehydration with an anhydride such as trifluoroacetic acid anhydride or acetic anhydride in an inert solvent such as dichloromethane and in the presence of a base such as triethyl amine or 4-(dimethylamino)pyridine, or by heating in the presence of a mild acid such as ammonium acetate provides compounds of Formula 14. Such transformations commonly known as Henry reactions are well documented in the chemical literature under a variety of conditions, for example, Tetrahedron 2001, 57, 915-945; J. Med. Chem. 2020, 63, 542-568; U.S. 2006 / 0025468; and WO 2023 / 115165.

[0442] Scheme 12

[0443] As shown in Scheme 13, the compounds of Formula 5a (Formula 5 wherein Q is Q-14 and R5bis other than H) can be prepared by alkylation of corresponding compounds of Formula 5b (Formula 5 wherein Q is Q-14 and R5bis H). Alkylation is achieved by reacting a compound of Formula 5b with a base such as potassium carbonate, lithium diisopropylamide or sodium hydride, followed by an alkylating agent of Formula 19 wherein L2is a leaving group such as halogen (e.g., Cl, Br, I). Particularly useful as an alkylating agent for preparing compounds of Formula 5a wherein R1is methyl is iodomethane using general procedures known in the art, such as those described in Journal of Heterocyclic Chemistry 1988, 1307-1310. For other general alkylation conditions see Journal of Medicinal Chemistry 2003, 46(16), 3463-3475; Heterocycles 1997, 44, 67-70 and WO 2019 / 121885. Also, the method of Scheme 13 is illustrated in Example 7 (Step D)

[0444] Scheme 13

[0445] As shown in Scheme 14, compounds of Formula 5b (Formula 5 wherein Q is Q-14 and R5bis H) can be prepared from nitriles of Formula 20 by treatment with trimethyl silyl azide, typically in the presence of a metal catalyst. Common conditions involve using a dialkyltin oxide or copper catalyst in conjunction with trimethyl silyl azide. The reaction is typically run in a solvent such as toluene, N,N-dimethylformamide, tetrahydrofuran, methanol, dimethyl sulfoxide (optionally comprising water), at temperatures from about 25 to 100 °C. For references see, for example, Journal of Organic Chemistry 1993, 58, 4139-4141; Tetrahedron Letters 2008, 49(17), 2824- 2827; and WO 2010 / 011302. Also, the method of Scheme 14 is illustrated in Example 7 (Step C).

[0446] Scheme 14

[0447] As shown in Scheme 15, compounds of Formula 20 can be prepared by alkylation of compounds of Formula 21 using procedures analogous to those described for the method of Scheme 7. Present Example 7 (Step B) illustrates the method of Scheme 15.

[0448] Scheme 15

[0449] As shown in Scheme 16, compounds of Formula 21 can be prepared by deprotonation of malononitrile (Formula 22) with a base such as sodium hydride, potassium carbonate or cesium carbonate, in an inert solvent such as tetrahydrofuran, 2-methyltetrahydrofuran, toluene, or mixtures thereof, at temperatures ranging from -78 °C to the reflux temperature of the solvent, followed by treatment with an appropriate reagent of Formula 7 wherein L2is a leaving group such as a halogen (e.g., Cl, Br, I). For typical reaction conditions see, for example WO 2022 / 253334. Also, the method of Scheme 16 is illustrated in Example 7 (Step A). Scheme 16

[0450] Intermediate compounds of Formula 6 whose preparations are described in Scheme 9 above can alternatively be prepared as shown in Scheme 17. In this method, compounds of Formula 23 are reacted with tosylmethyl isocyanide to provide compounds of Formula 6 The reaction is typically carried out in a solvent such as dimethyl ether or a mixture of 1,2-dimethoxy ethane (DME) and ethanol and in the presence of a strong base such as potassium tert-butoxide. For references see, for example, Journal of Organic Chemistry 1977, 42 (19), 3114-3118; Reaction Chemistry & Engineering 2024, 9, 349-354; Bioorganic & Medicinal Chemistry Letters 2010, 20, 3565-3568 and Organic Reactions, 2001, 57, 417. Also, the method of Scheme 17 is illustrated in Example 11 (Step B) and Example 12 (Step C).

[0451] Scheme 17

[0452] One skilled in the art will recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents. In some instances, incorporation of a protection / functional group interconversion / deprotection sequence into the synthesis will aid in obtaining the desired products. In particular, certain R6substituents attached to the Y ring may be obtained via functional group interconversion reactions. For example, as shown in Scheme 18, intermediate compounds of Formula 3a-1 (i.e. Formula 3 wherein Y is Y-1 substituted with an R6substituent at the 6-position) wherein R6is alkyl, alkenyl, alkynyl, and the like, can be prepared from corresponding compounds of Formula 3a-2 wherein R6is halogen or haloalkyl sulfonyl (e.g., triflate). Compounds of Formula 3a-2 are first

[0453] N-protected with a protecting group PG. A wide array of amine protecting groups are suitable for the method of Scheme 18 (see, for example, T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). Particularly useful are tert-butoxycarbonyl or benzyloxycarbonyl to afford compounds of Formula 24 (for reaction conditions, see Example 2 (Step A)).

[0454] Transformation of compounds of Formula 24 to compounds of Formula 25 can be carried out under classic transition-metal-catalyzed cross-coupling reaction conditions, in the presence of a suitable palladium, copper or nickel catalyst. In this step compounds of formula R6-M are organoboronic acids (e.g., M is B(OH)2), organoboronic esters (e.g., M is B(-OC(CH2)3O-), organotrifluoroborates (e.g., M is BF3K), organotin reagents (e.g., M is Sn(n-Bu)3, Sn(Me)3), Grignard reagents (e.g., M is MgBr or MgCl) or organozinc reagents (e.g., M is ZnBr or ZnCl). Suitable metal catalysts include, but are not limited to, palladium(II) acetate, palladium(II) chloride, tetrakis(triphenylphosphine)palladium(0), bis(triphenylphosphine)palladium(II) dichloride, dichloro[l, r-bis(diphenylphosphino)ferrocene]palladium(II), bis(triphenyl- phosphine)dichloronickel(II) and copper(I) salts (e.g., copper(I) iodide, copper(I) bromide, copper(I) chloride, copper(I) cyanide or copper(I) triflate). Optimal conditions will depend on the catalyst used and the counterion attached to the compound of formula R6-M (i.e. M), as is understood by one skilled in the art. In some cases, the addition of a ligand such as a substituted phosphine or a substituted bisphosphinoalkane promotes reactivity. Also, the presence of a base such as an alkali carbonate, tertiary amine or alkali fluoride may be necessary for some reactions involving organoboron reagents of the formula R6-M. The reaction is typically carried out at temperatures ranging between about ambient and the boiling point of the solvent. The reaction can also be carried out at temperatures above the solvent boiling point by using a pressurized vessel, such as a microwave reactor or Fisher-Porter tube. For reviews of this type of reaction see: E. Negishi, Handbook of Organopalladium Chemistry for Organic Synthesis, John Wiley and Sons, Inc., New York, 2002; N. Miyaura, Cross-Coupling Reactions: A Practical Guide, Springer, New York, 2002; H. C. Brown et al., Organic Synthesis via Boranes, Vol. 3, Aldrich Chemical Co., Milwaukee, WI, 2002; Chemical Review 1995, 95, 2457-2483 and Accounts of Chemical Research 2007, 40, 275-286. Also, Example 2 (Step B) and Example 9 (Step A) illustrate the method of Scheme 18 for the preparation of compounds of Formula 25 wherein R6is a methyl and trimethylsilylethynyl group, respectively.

[0455] In the final step, compounds of Formula 3a- 1 are obtained by deprotection of corresponding

[0456] N-protected compounds of Formula 25. Methods for deprotection can be found in Greene, Protective Groups in Organic Synthesis, John Wiley and Sons, New York, 1981. Particularly useful conditions include hydrochloride acid in as solvent such as 1,4-di oxane. After deprotection, the compounds of Formula 3a-1 can be isolated as an acid salt or free amine by general methods known in the art. For conditions, see Example 2 (Step C) and Example 9 (Step B). Scheme 18

[0457] Compounds of Formula 1 and intermediates described in the above methods wherein W is 0 can be converted to the corresponding thiolates wherein W is S using a variety of standard thiating reagents such as phosphorus pentasulfide or 2,4-bis(4-methoxyphenyl)-1,3-dithia- 2,4-diphosphetane-2,4-disulfide (Lawesson’ s reagent). Reactions of this type are well-known see, for example, Heterocycles 1995, 40, 271-278; Journal of Medicinal Chemistry 2008, 51, 8124- 8134; Journal of Medicinal Chemistry 1990, 33, 2697-706; Synthesis 1989, (5), 396-3977; J. Chem. Soc., Perkin Trans. 1, 1988, 1663-1668; Tetrahedron 1988 44, 3025-3036 and Journal ' of Organic Chemistry 1988 53(6), 1323-1326.

[0458] 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, T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nded.; 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.

[0459] 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. Ambient or room temperature is defined as about 20-25 °C. Unless otherwise indicated, the following examples are conducted under a nitrogen atmosphere with stirring. 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. MPLC refers to medium pressure liquid chromatography on silica gel.1H NMR spectra are reported in ppm downfield from tetramethylsilane; “s” means singlet, “d” means doublet, “t” means triplet, “q” means quartet, “m” means multiplet, “br s” means broad singlet, “br d” means broad doublet, “dd” means doublet of doublets, “ddd” means doublet of doublet of doublets, “br t" means triplet and “td” means triplet of doublets. Mass spectra (MS) are reported as the molecular weight of the highest isotopic abundance parent ion (M+1) formed by addition of H+(molecular weight of 1) to the molecule, or (M-1) formed by the loss of H+(molecular weight of 1) from the molecule, observed by using liquid chromatography coupled to a mass spectrometer (LCMS) using either atmospheric pressure chemical ionization (AP+) or electrospray ionization (ESI+).

[0460] In the following examples, molecules with one chiral center, unless otherwise noted, exist as a racemic mixture. Those molecules with two or more chiral centers, unless otherwise noted, exist as a racemic mixture of diastereomers. Separation of single enantiomers / diastereomers can be achieved by methods known to those skilled in the art.

[0461] EXAMPLE 1

[0462] Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-5- (2,4-difluorophenyl)-3-isoxazolecarboxamide (Compound 1)

[0463] Step A: Preparation of α,2-dimethyl-2H-1,2,3-triazole-4-acetonitrile

[0464] To a mixture of 2-methyl-2H-1,2,3-triazole-4-acetonitrile (12.53 g, 102.595 mmol, 1 equiv.) in tetrahydrofuran (393 mL) at -78 °C was added dropwise n-butyllithium (2.5 M in hexanes) (6.572 g, 41.038 mL, 102.595 mmol, 1 equiv.). The reaction mixture was stirred for 30 minutes at -78 °C, and then iodomethane (14.562 g, 6.387 mL, 102.595 mmol, 1 equiv.) was added dropwise. After 10 minutes, the reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. The reaction mixture was poured into water and extracted with ethyl acetate. The organic extracts were concentrated under reduced pressure and the resulting material was purified by MPLC (eluting with a gradient of 0-100% ethyl acetate in hexanes) to provide the title compound (11.13 g).

[0465] 1H NMR (CDCl3): δ 7.56 (s, 1H), 4.18 (s, 3H), 4.07 (q, 1H), 1.70 (d, 3H). Step B: Preparation of 6-chloro-α-methyl-α-(2-methyl-2H-1,2,3-triazol-4-yl)-2- pyridineacetonitrile

[0466] To a mixture of α,2-dimethyl-2H- 1,2,3-triazole-4-acetonitrile (i.e. the product of Step A) (2 g, 14.689 mmol, 1 equiv.) in tetrahydrofuran (60 mL) at -78 °C was added dropwise n-butyllithium (2.5 M in hexanes) (0.941 g, 14.689 mmol, 1 equiv.). The reaction mixture was stirred for 10 minutes at -78 °C and then 2,6-dichloropyridine (2.174 g, 14.689 mmol, 1 equiv.) was added portionwise. After 10 minutes, the reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. The reaction mixture was poured into water and extracted with ethyl acetate. The organic extracts were concentrated under reduced pressure and the resulting material was purified by MPLC (eluting with a gradient of 0-60% ethyl acetate in hexanes) to provide the title compound (2.18 g).

[0467] 1H NMR (CDCl3): δ 7.72-7.66 (m, 1H), 7.57 (s, 1H), 7.56-7.51 (m, 1H), 7.30 (dd, 1H), 4.18 (s, 3H), 2.18 (s, 3H).

[0468] Step C: Preparation of 6-chloro-β-methyl-β-(2-methyl-2H- 1,2,3 -triazol-4-yl)-2- pyridineethanamine

[0469] To a mixture of 6-chloro-α-methyl-α-(2-methyl-2H- 1,2, 3 -triazol -4-yl)-2- pyridineacetonitrile (i.e. the product of Step B) (2.18 g, 8.801 mmol, 1 equiv.) in tetrahydrofuran (25 mL) was added borane tetrahydrofuran complex solution (1 M in tetrahydrofuran) (2.269 g, 26.404 mL, 26.404 mmol, 3 equiv.). The reaction mixture was heated at 65 °C for 16 h, then cooled to 0 °C and concentrated hydrochloric acid (10.6 mL) was added dropwise. The reaction was heated at 50 °C for 1.5 h and then cooled to 0 °C and concentrated under reduced pressure. The resulting material was diluted with water and then basified to approximately pH 13 with the addition of aqueous sodium hydroxide (6 N). The aqueous layer was extracted with di chloromethane. The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-100% ethyl acetate in hexanes, and then 20% methanol in ethyl acetate) to provide the title compound (1.75 g).

[0470] MS: 252 (M+1).

[0471] Step D: Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4- yl)propyl]-5-(2,4-difluorophenyl)-3-isoxazolecarboxamide

[0472] To a mixture of 6-chloro-β-methyl-β-(2-methyl-2H- 1,2, 3 -triazol -4-yl)-2- pyridineethanamine (i.e. the product of Step C) (1.2 g, 4.767 mmol, 1 equiv.) in N,N-dimethylformamide (62 mL) was added l-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) (2.175 g, 5.721 mmol, 1.2 equiv.), 5-(2,4-difluorophenyl)-3-isoxazolecarboxylic acid (1.073 g, 4.767 mmol, 1 equiv.) and N,N-di isopropyl ethyl ami ne (1.848 g, 2.491 mL, 14.302 mmol, 3 equiv.). After 16 hours, the reaction mixture was diluted with diethyl ether and washed with saturated aqueous ammonium chloride. The aqueous layer was extracted with diethyl ether and the combined organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-60% ethyl acetate in hexanes), and then with reverse phase MPLC (eluting with a gradient of 10-100% acetonitrile in water) to provide the title compound (0.83 g).

[0473] 1H NMR. (CDCl3): δ 7.99 (br t, 1H), 7.96-7.90 (m, 1H), 7.57 (t, 1H), 7.43 (s, 1H), 7.25-7.20 (m, 1H), 7.07 (d, 1H), 7.06-6.95 (m, 3H), 4.24-4.12 (m, 5H), 1.80 (s, 3H).

[0474] MS: 459 (M+1).

[0475] EXAMPLE 2

[0476] Preparation of 5-(2,4-difluorophenyl)-N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H- l,2,3-triazol-4-yl)propyl]-3-isoxazolecarboxamide (Compound 24)

[0477] Step A: Preparation of 1 , 1 -dimethylethyl N-[2-(6-bromo-2-pyridinyl)-2-(2-methyl-2H- l,2,3-triazol-4-yl)propyl]carbamate

[0478] To a mixture of 6-bromo-β-methyl-β-(2-methyl-2H- 1,2, 3 -triazol -4-yl)-2-pyridine- ethanamine (prepared in an analogous manner to Example 1, Steps A through B) (8.75 g, 29.544 mmol, 1 equiv.) in dichloromethane (219 mL) at 0 °C was added dropwise triethylamine (3.587 g, 5.125 mL, 35.452 mmol, 1.2 equiv.), followed by di- tert-butyl dicarbonate (7.093 g, 7.466 mL, 32.498 mmol, 1.1 equiv.). The reaction mixture was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was diluted with water and then extracted with dichloromethane and the organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-50% ethyl acetate in hexanes) to provide the title compound (8.68 g).

[0479] 1H NMR (CDCl3): δ 7.51-7.38 (m, 2H), 7.37-7.30 (m, 1H), 7.07 (d, 1H), 5.26 (br s, lH), 4.16 (s, 3H), 3.90-3.76 (m, 2H), 1.71 (s, 3H), 1.40 (s, 9H).

[0480] MS: 298 (M+1).

[0481] Step B : Preparation of 1 , 1 -dimethylethyl N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H- l,2,3-triazol-4-yl)propyl]carbamate

[0482] To a mixture of 1,1 -dimethylethyl N-[2-(6-bromo-2-pyridinyl)-2-(2-methyl-2H- 1,2,3 - triazol-4-yl)propyl]carbamate (i.e. the product of Step A) (2.8 g, 7.066 mmol, 1 equiv.) in dioxane (60 mL) was added 2,4,6-trimethylboroxin (0.887 g, 0.997 mL, 7.066 mmol, 1 equiv.) and potassium carbonate (3.906 g, 28.262 mmol, 4 equiv.). Nitrogen gas was streamed into the reaction mixture for 10 minutes, and then tetrakis(triphenylphosphine)palladium(0) (0.816 g, 0.707 mmol, 0.1 equiv.) was added. The reaction was heated at reflux for 48 h and then allowed to cool to room temperature. Nitrogen gas was again streamed into the reaction mixture for 15 minutes and then more tetrakis(triphenylphosphine)palladium(0) (0.816 g, 0.707 mmol, 0.1 equiv.) was added. The reaction mixture was heated at reflux for 16 h, then allowed to cool to room temperature and diluted with water. The aqueous layer was extracted with ethyl acetate and the organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-40% ethyl acetate in hexanes) to provide the title compound (1.92 g).

[0483] 1H NMR (CDCl3): δ 7.46 (t, 1H), 7.37 (s, 1 H), 6.99 (d, 1H), 6.87 (br d, 1H), 5.63 (br s, 1H), 4.16 (s, 3H), 3.96-3.75 (m, 2H), 2.55 (s, 3H), 1.71 (s, 3H), 1.41 (s, 9H).

[0484] MS: 332 (M+1).

[0485] Step C: Preparation of P,6-dimethyl-β-(2-methyl-2H-1,2,3-triazol-4-yl)-2- pyridineethanamine hydrochloride (1: 1)

[0486] To a mixture of 1,1 -dimethylethyl N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-1,2,3- triazol-4-yl)propyl]carbamate (i.e. the product of Step B) (1.92 g, 5.793 mmol, 1 equiv.) in 1,4 dioxane (28 mL) was added hydrochloric acid (4 M in 1,4-dioxane) (1.056 g, 7.242 mL, 28.966 mmol, 5 equiv.). The reaction mixture was stirred for 1 h and then concentrated under reduced pressure to provide the title compound (1.58 g).

[0487] 1H NMR (CDCl3): δ 8.87-8.59 (m, 3H), 8.25 (br t, 1H), 7.79-7.65 (m, 1H), 7.62 (s, 1 H), 7.32- 7.28 (m, 1H), 4.62 (br d, 1H), 4.29 (s, 3H), 3.91 (br d, 1H), 3.15 (s, 3H), 2.21 (s, 3H).

[0488] Step D: Preparation of 5-(2,4-difluorophenyl)-N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-

[0489] 2H-1,2,3-triazol-4-yl)propyl]-3-isoxazolecarboxamide

[0490] To a mixture of P,6-dimethyl-β-(2-methyl-2H-1,2,3-triazol-4-yl)-2-pyridineethanamine hydrochloride (1 :1) (i.e. the product of Step C) (0.177 g, 0.66 mmol, 1 equiv.) in N,N-dimethylformamide (9 mL) was added l-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) (0.301 g, 0.792 mmol, 1.2 equiv.), 5-(2,4-difluorophenyl)-3-isoxazolecarboxylic acid (0.149 g, 0.66 mmol, 1 equiv.) and N,N-diisopropylethylamine (0.299 g, 0.403 mL, 2.311 mmol, 3.5 equiv.). After 16 h, the reaction mixture was diluted with diethyl ether and washed with saturated aqueous ammonium chloride solution The aqueous layer was extracted with diethyl ether and the combined organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-60% ethyl acetate in hexanes) to provide the title compound (0.15 g).

[0491] 1H NMR (CDCl3): δ 8.87 (br t, 1H), 7.94 (td, 1H), 7.50 (t, 1H), 7.39 (s, 1H), 7.10-6.95 (m, 4H), 6.87 (d, 1H), 4.17 (s, 3H), 4.17-4.08 (m, 2H) 2.65 (s, 3H), 1.79 (s, 3H).

[0492] MS: 439 (M+1). EXAMPLE 3

[0493] Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-2-(2,4- difluorophenyl)-2H-tetrazole-5-carboxamide (Compound 46)

[0494] To a mixture of 2-(2,4-difluorophenyl)-2H-tetrazole-5 -carboxylic acid (prepared from 2,4-difluoroaniline and p-toluenesulfonyl hydrazide analogous to the method described in Scheme 6 of WO2022 / 256419) (0.119 g, 0.524 mmol, 1.1 equiv.) and 6-chloro-β-methyl-β-(2-methyl-2H- l,2,3-triazol-4-yl)-2-pyridineethanamine (i.e. the product of Example 1, Step C) (0.12 g, 0.477 mmol, 1 equiv.) in ethyl acetate (2 mL) was added N,N-diisopropylethylamine (0.185 g, 0.249 mL, 1.43 mmol, 3 equiv.) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6- trioxide (T3P®) (50% solution in ethyl acetate) 0.84 mL). The reaction was stirred for 1.5 h and then partitioned between water and ethyl acetate. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0- 80% ethyl acetate in hexanes) to provide the title compound (0.13 g).

[0495] 1H NMR (CDCl3): δ 8.56 (br t, 1H), 7.89 (td, 1H), 7.59 (t, 1H), 7.45 (s, 1H), 7.25-7.22 (m, 1H), 7.16-7.08 (m, 2H), 7.06 (dd, 1H), 4.29-4.19 (m, 2H), 4.19 (s, 3H), 1.82 (s, 3H).

[0496] MS: 461 (M+1).

[0497] EXAMPLE 4

[0498] Preparation of 5-(2,4-difluorophenyl)-N-[2-(6-methoxy-2-pyridinyl)-2-(2-methyl-2H- l,2,3-triazol-4-yl)propyl]-3-isoxazolecarboxamide (Compound 14)

[0499] Step A: Preparation of 6-methoxy-α-methyl-α-(2-methyl-2H-1,2,3-triazol-4-yl)-2- pyridineacetonitrile

[0500] To a solution of sodium methoxide (25% in methanol, 5.889 g, 23.556 mL, 109.007 mmol, 10 equiv.) was added to 6-chloro-α-methyl-α-(2-methyl-2H- 1,2, 3 -triazol -4-yl)-2- pyridineacetonitrile (i.e. the product of Example 1, Step B) (2.7 g, 10.901 mmol, 1 equiv.). The reaction mixture was heated at 70 °C for 16 h and then diluted with water and extracted with ethyl acetate. The organic extracts were concentrated under reduced pressure and the resulting material was purified by MPLC (eluting with a gradient of 0-50% ethyl acetate in hexanes) to provide the title compound (2.03 g).

[0501] 1H NMR (CDCl3): δ 7.58 (dd, 1H), 7.56-7.55 (m, 1H), 7.07 (d, 1H), 6.69 (d, 1H), 4.19 (s, 3 H), 3.92 (s, 3H), 2.16 (s, 3H).

[0502] MS: 244 (M+1). Step B: Preparation of 6-methoxy-β-methyl-β-(2-methyl-2H- l ,2,3-triazol-4-yl)-2- pyridineethanamine

[0503] The title compound (1.68 g) was prepared from 6-methoxy-α-methyl-α-(2-methyl-2H- l,2,3-triazol-4-yl)-2-pyridineacetonitrile (i.e. the product of Step A) (2.03 g, 8.345 mmol, 1 equiv.) analogous to the method described in Example 1 of Step C.

[0504] 1H NMR (CDCl3): δ 7.50-7.45 (m, 1H), 7.43 (s, 1H), 6.64 (d, 1H), 6.58 (d, 1H), 4.18 (s, 3H), 3.92 (s, 3H), 3.38 (d, 1H), 3.31-3.24 (m, 1H), 1.71 (s, 3H), 1.53-1.36 (m, 2H).

[0505] MS: 248 (M+1).

[0506] Step C: Preparation of 5-(2,4-difluorophenyl)-N-[2-(6-methoxy-2-pyridinyl)-2-(2-methyl-

[0507] 2H-1,2,3-triazol-4-yl)propyl]-3-isoxazolecarboxamide

[0508] The title compound (0.38 g) was prepared from 6-methoxy-β-methyl-β-(2-methyl-2H- l,2,3-triazol-4-yl)-2-pyridineethanamine (i.e. the product of Step B) (0.22 g, 0.89 mmol, 1 equiv.) and 5-(2,4-difluorophenyl)-3-isoxazolecarboxylic acid (0.2 g, 0.89 mmol, 1 equiv.) analogous to the method described in Example 1 of Step D.

[0509] 1H NMR (CDCl3): δ 8.18 (brt, 1H), 7.92 (td, 1H), 7.49 (dd, 1H), 7.42 (s, 1H), 7.07 (d, 1H), 7.05- 7.01 (m, 1H), 6.97 (ddd, 1H), 6.64 (dd, 2H), 4.24-4.10 (m, 5H), 4.04 (s, 3H), 1.79 (s, 3H).

[0510] MS: 455 (M+1).

[0511] EXAMPLE 5

[0512] Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(l-methyl-1H-pyrazol-3-yl)propyl]-5-(2,4- difluorophenyl)-3-isoxazolecarboxamide (Compound 50)

[0513] Step A: Preparation of 6-chloro-β-methyl-β-(l-methyl-1H-pyrazol-3-yl)-2- pyridineethanamine

[0514] To a mixture of 6-chloro-α-methyl-α-(l-methyl-1H-pyrazol-3-yl)-2-pyridineacetonitrile (prepared from 1 -methyl- lH-pyrazole-3 -acetonitrile and 2,6-dichloropyridine analogous to the method described in Example 1 of Steps A through B) (1.4 g, 5.675 mmol, 1 equiv.) and cobalt chloride (0.737 g, 0.219 mL, 5.675 mmol, 1 equiv.) in methanol (14 mL) at 0 °C was added sodium borohydride (0.482 g, 12.74 mmol, 2.245 equiv.) portionwise. The reaction mixture was stirred for 1.5 h at 0 °C and then partitioned between saturated aqueous bicarbonate solution and tetrahydrofuran / ethyl acetate (1: 1). The resulting mixture was extracted with tetrahydrofuran / ethyl acetate (1: 1) and the combined organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0- 100% ethyl acetate in hexanes and then 20% methanol in ethyl acetate) to provide the title compound (0.36 g).1H NMR (CDCl3): δ 7.59 (t, 1H), 7.35 (d, 1H), 7.27-7.19 (m, 1H), 7.09-6.92 (m, 1H), 6.23-6.07 (m, 1H), 3.87 (s, 3H), 3.83-3.76 (m, 1H), 3.59-3.49 (m, 1H), 1.76 (s, 3H).

[0515] MS: 251 (M+1).

[0516] Step B: Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(l-methyl-1H-pyrazol-3-yl)propyl]-

[0517] 5-(2,4-difluorophenyl)-3-isoxazolecarboxamide

[0518] To a mixture of 6-chloro-β-methyl-β-(l-methyl-1H-pyrazol-3-yl)-2-pyridineethanamine (i.e. the product of Step A) (0.18 g, 0.718 mmol, 1 equiv.) in N,N-dimethylformamide (9 mL) was added l-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluoro- phosphate (HATU) (0.328 g, 0.861 mmol, 1.2 equiv.), 5-(2,4-difluorophenyl)-3- isoxazolecarboxylic acid (0.162 g, 0.718 mmol, 1 equiv.) and N,N-diisopropylethylamine (0.186 g, 0.25 mL, 1.436 mmol, 2 equiv.). After 16 h, the reaction mixture was diluted with diethyl ether and washed with saturated aqueous ammonium chloride solution. The aqueous layer was extracted with diethyl ether and the combined organic extracts were concentrated under reduced pressure. The resulting material was purified by reverse phase MPLC (eluting with a gradient of 65-80% acetonitrile in water) to provide the title compound (0.074 g).

[0519] 1H NMR (CDCl3): δ 8.19 (br t, 1H), 7.93 (m, 1H), 7.50 (t, 1H), 7.32 (d, 1H), 7.16 (dd, 1H), 7.08- 7.01 (m, 3H), 6.97 (m, 1H), 6.08 (d, 1H), 4.19 (dd, 1H), 4.16-4.08 (m, 1H), 3.91 (s, 3H), 1.76 (s, 3H).

[0520] MS: 458 (M+1).

[0521] EXAMPLE 6

[0522] Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(4-methyl-1H-pyrazol-1-yl)propyl]-5-(2,4- difluorophenyl)-3-isoxazolecarboxamide (Compound 54)

[0523] Step A: Preparation of α,4-dimethyl- 1H-pyrazole- 1 -acetonitrile

[0524] A mixture of 4-methylpyrazole (0.27 mL, 3.26 mmol), 2-chloropropanenitrile, (0.35 mL, 3.91 mmol) and cesium carbonate (1.59 g, 4.88 mmol) in acetonitrile (4.2 mL) was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was diluted with water and 2-methoxy-2-methylpropane. The layers were separated, and the aqueous layer was extracted with 2-methoxy-2-methylpropane. The combined organic extracts were washed with water and saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound (450 mg).

[0525] 1H NMR (CDCl3): δ 7.39-7.38 (m, 1H), 7.34-7.33 (m, 1H), 5.27-5.22 (m, 1H), 2.09 (s, 3H), 1.89- 1.88 (m, 3H). Step B : Preparation of 6-chloro-α-methyl-α-(4-methyl- 1 H-pyrazol - 1 -yl)-2- pyridineacetonitrile

[0526] To an ice-cooled solution of α,4-dimethyl-1H-pyrazole-1 -acetonitrile (i.e. the product of Step A) (3.4 g, 23.9 mmol) in tetrahydrofuran (35 mL) was added dropwise lithium bis(trimethylsilyl)amide (IM solution in tetrahydrofuran, 35.8 mL). The reaction mixture was allowed to gradually warm to room temperature and stirred for 15 minutes, and then 2,6- dichloropyridine (3.9 g, 26.5 mmol) was added. The reaction mixture was heated at 40 °C for 24 h, then diluted with saturated aqueous ammonium chloride, and extracted with ethyl acetate. The combined extracts were washed with water and saturated aqueous sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-30% ethyl acetate in heptane) to provide the title compound (2.3 g).

[0527] 1H NMR (CDCl3): δ 7.68-7.65 (m, 1H), 7.48-7.47 (m, 1H), 7.45-7.44 (m, 1H), 7.34-7.33 (m, 1H), 7.00-6.99 (m, 1H) 2.40 (s, 3H), 2.10 (s, 3H).

[0528] MS: 247 (M+1).

[0529] Step C : Preparation of 6-chloro-β-methyl-β-(4-m ethyl- 1 H-pyrazol- 1 -yl)-2- pyridineethanamine

[0530] To an ice-cooled mixture of 6-chloro-α-methyl-α-(4-methyl-1H-pyrazol-1-yl)-2- pyridineacetonitrile (i.e. the product of Step B) (2.36 g, 8.13 mmol) and cobalt chloride (5.28 g, 40.66 mmol) in methanol (45 mL) was added portionwise sodium borohydride (0.92 g, 24.39 mol). The reaction mixture was allowed to gradually warm to room temperature and stirred for 1 h, and then cobalt chloride (2.11 g, 16.23 mmol) and sodium borohydride (0.92 g, 24.39 mol) were added. After 1 h, the reaction mixture was diluted with water and concentrated under reduced pressure to remove the methanol. The resulting material was extracted with ethyl acetate, washed with aqueous ammonium hydroxide solution (6 N), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with 10% methanol in ethyl acetate) to provide the title compound (1.27 g).

[0531] 1H NMR (CDCl3): δ 7.52-7.49 (m, 1H), 7.45-7.42 (m, 1H), 7.41-7.37 (m, 1H), 7.19-7.17 (m, 1H), 6.36-6.35 (m, 1H), 3.70- 3.68 (m, 1H), 3.44-3.41 (m, 1H), 2.13 (m, 3H), 1.93 (m, 3H), 1.51 (br, s, 2H).

[0532] MS: 251 (M+1).

[0533] Step D: Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(4-methyl-1H-pyrazol-1-yl)propyl]-

[0534] 5-(2,4-difluorophenyl)-3-isoxazolecarboxamide

[0535] To an ice-cooled mixture of 5-(2,4-difluorophenyl)-3-isoxazole carboxylic acid (87.4 mg, 0.39 mmol) and 6-chloro-β-methyl-β-(4-methyl-1H-pyrazol-1-yl)-2-pyridineethanamine (i.e. the product of Step C) (107.9 mg, 0.43 mmol) in N,N-dimethylformamide (1.4 mL) was added 1- ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC HCl) (111.6 mg, 0.58 mmol), 1 -hydroxybenzotriazole hydrate (89.1 mg, 0.58 mmol) and triethylamine (113.6 pL, 0.81 mmol). The reaction mixture was stirred at room temperature overnight, and then diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0- 60% ethyl acetate in heptane) to provide the title compound (137.9 mg).

[0536] 1H NMR (CDCl3): δ 7.95-7.86 (m, 2H), 7.53-7.49 (m, 2H), 7.37-7.36 (m, 1H), 7.23-7.21 (m, 1H), 7.08-7.07 (m, 1H), 7.06-7.02 (m, 1H), 7.00-6.96 (m, 1H), 6.43-6.41 (m, 1H), 4.46-4.42 (m, 1H), 4.37-4.33 (m, 1H), 2.13 (s, 3 H), 2.00 (s, 3H).

[0537] MS: 459 (M+1).

[0538] EXAMPLE 7

[0539] Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(2,4- difluorophenyl)-3-isoxazolecarboxamide (Compound 78)

[0540] Step A: Preparation of 2-(3-bromo-6-chloro-2-pyridinyl)propanedinitrile

[0541] To a mixture of 2-chloro-6-fluoropyridine (1 g, 7.603 mmol, 1 equiv.) and malononitrile (0.753 g, 11.404 mmol, 1.5 equiv.) in N,N-dimethylformamide (10 mL) was added potassium carbonate (2.627 g, 19.007 mmol, 2.5 equiv.). The reaction mixture was heated at 80 °C for approximately 24 h, then allowed to cool to room temperature and diluted with aqueous hydrochloric acid (2 N). The solid precipitate which formed was collected by filtration and dried under reduced pressure to provide the title compound (1 g).

[0542] 1H NMR (DMSO-d6): δ 9.50 (br s, 1), 7.33 (t, 1H), 6.64 (d, 1H), 6.50 (d, 1H).

[0543] Step B : Preparation of 6-chloro-α,α-dimethyl-2-pyridineacetonitrile

[0544] To a mixture of 2-(3-bromo-6-chloro-2-pyridinyl)propanedinitrile (i.e. the product of Step A) (1 g, 5.631 mmol, 1 equiv.) and potassium carbonate (1.946 g, 14.077 mmol, 2.5 equiv.) in acetonitrile (20 mL) was added dropwise iodomethane (0.911 mL, 14.64 mmol, 2.6 equiv.). The reaction mixture was heated at 40 °C for approximately 24 h, then allowed to cool to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting material was purified by MPLC (eluting with a gradient of 0-40% ethyl acetate in hexanes) to provide the title compound (1 g).

[0545] 1H NMR (CDCl3): δ 7.84 (t, 1H), 7.67 (d, 1H), 7.47 (d, 1H), 2.21 (s, 3H). Step C: Preparation of 6-chloro-α-methyl-α-2H-tetrazol-5-yl-2-pyridineacetonitrile

[0546] To a mixture of 6-chloro-α,α-dimethyl-2-pyridineacetonitrile (i.e. the product of Step B) (1.1 g, 5.741 mmol, 1 equiv.) and trimethylsilyl azide (0.755 ml, 5.741 mmol, 1 equiv.) in toluene (11 mL) was added dropwise dibutyltin oxide (0.0.48 mL, 0.287 mmol, 0.05 equiv.). The reaction mixture was heated at 80 °C for 2 h, then allowed to cool to room temperature and concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-10% methanol in di chloromethane) to provide the title compound (700 mg).

[0547] 1H NMR (DMSO-d6): δ 8.01 (t, 1H), 7.63 (d, 1H), 7.58 (d, 1H), 2.24 (s, 3H).

[0548] Step D: Preparation of 6-chloro-α-methyl-α-(2-methyl-2H-tetrazol-5-yl)-2- pyridineacetonitrile

[0549] To a mixture of 6-chloro-α-methyl-α-2H-tetrazol-5-yl-2-pyridineacetonitrile (i.e. the product of Step C) (0.7 g, 2.983 mmol, 1 equiv.) and potassium carbonate (0.412 g, 2.983 mmol, 1 equiv.) in acetonitrile (20 mL) was added dropwise iodomethane (0.911 mL, 14.64 mmol, 2.6 equiv.). The reaction mixture was heated at 60 °C for 1 h, then allowed to cool to room temperature and filtered. The filtrate was concentrated under reduced pressure. The resulting mixture was purified by MPLC (eluting with a gradient of 0-60% ethyl acetate in hexanes) to provide the title compound (350 mg).

[0550] 1H NMR (CDCl3): δ 7.74 (t, 1H), 7.62 (d, 1H), 7.34 (d, 1H), 4.37 (s, 3H), 2.32 (s, 3H).

[0551] Step E: Preparation of 6-chloro-β-methyl-β-(2-methyl-2H-tetrazol-5-yl)-2- pyridineethanamine

[0552] To a mixture of 6-chloro-α-methyl-α-(2-methyl-2H-tetrazol-5-yl )-2-pyridineacetonitrile (i.e. the product of Step D) (0.35 g, 1.4 mmol, 1 equiv.) in methanol (7 ml) at 0 °C was added cobalt chloride hexahydrate (0.67 g, 2.815 mmol, 2 equiv.), followed by sodium borohydride (0.213 g, 55.63 mmol, 4 equiv.). The reaction mixture was allowed to warm to room temperature and stirred for 3 h. The reaction was slowly diluted with ice water and ethyl acetate. The resulting mixture was filtered through a bed of Celite® and the filtrate was concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-10% methanol in dichloromethane) to provide the title compound (140 mg).

[0553] 1H NMR (CDCl3): δ 7.56 (t, 1H), 7.2 (d, 1H), 7.0 (d, 1H), 4.36 (s, 3H), 3.55 (d, 1H), 3.40 (d, 1H), 1.83 (s, 3H).

[0554] Step F : Preparation of N-[2-(6-chloro-2-pyridinyl )-2-(2-methyl-2H-tetrazol-5-yl )propyl]-

[0555] 5-(2,4-difluorophenyl)-3-isoxazolecarboxamide

[0556] To a mixture of 6-chloro-p-methyl-β-(2-methyl-2H-tetrazol-5-yl)-2-pyridineethanamine (i.e. the product of Step E) (0.14 g, 0.555 mmol, 1 equiv.) and 5-(2,4-difluorophenyl)-1,2- oxazole-3 -carboxylic acid (125 mg, 0.555 mmol, 1 equiv.) in dichloromethane (5 mL) was added ethyl dimethylaminopropyl carbodiimide (EDC) (0.16 g, 0.833 mmol, 1.5 equiv.), 1 -hydroxybenzotriazole (HOBt) (0.113 g, 0.833 mmol) and N,N-diisopropylethylamine (0.359 g, 2.776 mmol, 5 equiv.). The reaction mixture was stirred for 16 h and then concentrated under reduced pressure. The resulting mixture was purified by MPLC (eluting with a gradient of 0-60% ethyl acetate in hexanes) to provide the title compound (165 mg).

[0557] 1H NMR (CDCl3): δ 7.99 (t, 1H), 7.93 (t, 1H), 7.59 (t, 1H), 7.23 (d, 1H), 6.96-7.10 (m, 4H) 4.36 (s, 3H), 4.26-4.33 (m, 2H), 1.91 (s, 3H).

[0558] EXAMPLE 8

[0559] Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-5- (3,5-difluoro-2-pyridinyl)-3-isoxazolecarboxamide (Compound 94)

[0560] Step A: Preparation of ethyl 5-(3,5-difluoro-2-pyridinyl)-4,5-dihydro-5-hydroxy-3- isoxazolecarboxylate

[0561] To a mixture of l-(3,5-difluoro-2-pyridinyl)-ethanone (3.16 g, 20.112 mmol, 1 equiv.) and diethyl oxalate (16.166 g, 15.024 mL, 110.616 mmol, 5.5 equiv.) in toluene (63 mL) at -78 °C was added portionwise potassium tert-butoxide (2.257 g, 20.112 mmol, 1 equiv.). The reaction mixture was warmed to room temperature and stirred for 20 minutes and then cooled to 0 °C and hydroxylamine hydrochloride (2.795 g, 40.224 mmol, 2 equiv.) and acetic acid (3.623 g, 3.451 mL, 60.336 mmol, 3 equiv.) were added. The reaction mixture was warmed to room temperature and stirred approximately 24 h, and then poured into water, extracted with ethyl acetate. The organic extract was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure to provide the title compound (5.48 g).

[0562] MS: 273 (M+1).

[0563] Step B: Preparation of ethyl 5-(3,5-difluoro-2-pyridinyl)-3-isoxazolecarboxylate

[0564] To a mixture of ethyl 5-(3,5-difluoro-2-pyridinyl)-4,5-dihydro-5-hydroxy-3- isoxazolecarboxylate (i.e. the product of Step A) (5.48 g, 20.132 mmol, 1 equiv.) in toluene (110mL) was added p-toluenesulfonic acid monohydrate (3.829 g, 3.088 mL, 20.132 mmol, 1 equiv.). The reaction mixture was heated at 90 °C for approximately 24 h and then cooled to 0 °C and saturated aqueous sodium bicarbonate was slowly added. The aqueous layer was extracted with ethyl acetate and the organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-50% ethyl acetate in hexanes). The resulting material was further purified by reverse phase MPLC (eluting with a gradient of 10-100% acetonitrile in water) to provide the title compound (0.34 g). MS: 255 (M+1).

[0565] Step C : Preparation of 5-(3,5-difluoro-2-pyridinyl)-3-isoxazolecarboxylic acid

[0566] To a mixture of ethyl 5-(3,5-difluoro-2-pyridinyl)-3-isoxazolecarboxylate (i.e. the product of Step B) (0.35 g, 1.377 mmol, 1 equiv.) in tetrahydrofuran (1 mL) and water (0.4 mL) was added lithium hydroxide monohydrate (0.116 g, 0.077 mL, 2.754 mmol, 2 equiv.). The reaction mixture was stirred at room temperature for 2 h and then diluted with aqueous hydrochloric acid (2N). The solid precipitate was collected by vacuum filtration and air dry to obtain the title compound (030 g).

[0567] MS: 227 (M+1).

[0568] Step D: Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4- yl])propyl]-5-(3,5-difluoro-2-pyridinyl)-3-isoxazolecarboxamide

[0569] To a mixture of 6-chloro-β-methyl-β-(2-methyl-2H- 1,2, 3 -triazol -4-yl)-2- pyridineethanamine (0.22 g, 0.874 mmol, 1 equiv.) in N,N-dimethylformamide (11 mL) was added l-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (0.399 g, 1.049 mmol, 1.2. equiv.), 5-(3,5-difluoro-2-pyridinyl)-3- isoxazolecarboxylic acid (i.e. the product of Step C) (0.198 g, 0.874 mmol, 1 equiv.) and N,N- diisopropylethylamine (0.339 g, 0.457 mL, 2.622 mmol, 3 equiv ). The reaction mixture was stirred at room temperature for approximately 24 h, then diluted with diethyl ether and the resulting mixture was washed with saturated aqueous ammonium chloride. The aqueous layer was extracted with diethyl ether and the combined organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0- 80% ethyl acetate in hexanes) to provide the title compound (0.35 g).

[0570] 1H NMR (CDCl3): δ 8.51 (d, J=2.29 Hz, 1H), 8.08 (br t, J=6.26 Hz, 1H), 7.57 (t, J=7.78 Hz, 1H), 7.43 (s, 1H), 7.42-7.37 (m, 1H), 7.26 (d, J=3.05 Hz, 1H), 7.25-7.19 (m, 1H) 7.04 (dd, J=7.78, 0.61 Hz, 1H), 4.22-4.12 (m, 5H), 1.80 (s, 3H).

[0571] MS: 460 (M+1).

[0572] EXAMPLE 9

[0573] Preparation of 5-(2,4-difluorophenyl)-N-[2-(2-methyl-2H-1,2,3-triazol-4-yl)-2-[6-[2- (trimethylsilyl)ethynyl]-2-pyridinyl]propyl]-3-isoxazolecarboxamide (Compound 66) Step A: Preparation of 1,1 -dimethylethyl N-[2-(2-methyl-2H-1,2,3-triazol-4-yl])-2-[6-[2-

[0574] (trimethylsilyl)ethynyl]-2-pyridinyl]propyl]carbamate

[0575] A mixture of 1,1 -dimethylethyl N-[2-(6-bromo-2-pyridinyl)-2-(2-methyl-2H- 1,2,3 - triazol-4-yl)propyl]carbamate (i.e. the product of Example 2, Step A) (1.06 g, 2.675 mmol, 1 equiv.) and triethylamine (13 mL) was degassed with nitrogen gas for 10 minutes followed by the addition of trimethylsilylacetylene (0.315 g, 0.454 mL, 3.21 mmol, 1.2 equiv.), copper(I) iodide (0.051 g, 0.267 mmol, 0.1 equiv.) and bis(triphenylphosphine)palladium(II) di chloride (0.188 g, 0.267 mmol, 0.1 equiv.). The reaction mixture was again degassed with nitrogen gas for 10 minutes and stirred at room temperature for approximately 24 h. The reaction mixture was partitioned between water and ethyl acetate, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-40% ethyl acetate in hexanes) to provide the title compound (0.82 g).

[0576] MS: 414 (M+1).

[0577] Step B : Preparation of β-methyl-β-(2-methyl-2H-1,2,3-triazol-4-yl)-6-[2-

[0578] (trimethylsilyl)ethynyl]-2-pyridineethanamine hydrochloride (1 :1)

[0579] To a mixture of 1,1 -dimethylethyl N-[2-(2-methyl-2H-1,2,3-triazol-4-yl])-2-[6-[2- (trimethylsilyl)ethynyl]-2-pyridinyl]propyl]carbamate (i.e. the product of Step A) (0.82 g, 1.983 mmol) and dioxanes (20 mL) was added dropwise hydrochloric acid (4M in 1,4-dioxane, 0.361 g, 2.478 mL, 9.913 mmol). The reaction mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure to provide the title compound (0.69 g).

[0580] MS: 314 (M+1), free amine.

[0581] Step C: Preparation of 5-(2,4-difluorophenyl)-N-[2-(2-methyl-2H-1,2,3-triazol-4-yl)-2-

[0582] [6-[2-(trimethylsilyl)ethynyl]-2-pyridinyl]propyl]-3-isoxazolecarboxamide

[0583] To a mixture of β-methyl-β-(2-methyl-2H- 1,2,3 -triazol -4-yl)-6-[2-

[0584] (trimethylsilyl)ethynyl]-2-pyridineethanamine hydrochloride (1 : 1) (i.e. the product of Step B) (0.2 g, 0.572 mmol, 1 equiv.) in A.N-dimethylformamide (10 mL) was added 1- [bis(dimethylamino)m ethylene]- 1H- 1,2, 3 -triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (0.261 g, 0.686 mmol, 1.2 equiv.), 5-(2,4-difluorophenyl)-1,2- oxazole-3 -carboxylic acid (0.129 g, 0.572 mmol, 1 equiv.) and A,A-diisopropylethylamine (0.222 g, 0.299 mL, 1.715 mmol, 3 equiv.). After 16 h, the reaction mixture was diluted with diethyl ether and washed with saturated aqueous ammonium chloride. The aqueous layer was extracted with diethyl ether and the combined organic extracts were concentrated under reduced pressure. The resulting material was purified by MPLC (eluting with a gradient of 0-40% ethyl acetate in hexanes) to provide the title compound (0.067 g).

[0585] 1H NMR (CDCl3): δ 8.39 (s, 1H), 7.91 (br d, J=6.10 Hz, 1H), 7.56 (t, J=7.86 Hz, 1H), 7.39 (s, 1H), 7.35 (dd, J=7.63, 0.92 Hz, 1H), 7.07 (d, J=3.66 Hz, 1H), 7.05-6.95 (m, 3H), 4.13-4.21 (m, 5H), 1.79 (s, 3H), 0.33 (s, 9H).

[0586] MS: 521 (M+1). EXAMPLE 10

[0587] Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2A-1,2,3-triazol-4-yl)propyl]-5-(2,4- difluorophenyl)-N-methyl-3-isoxazolecarboxamide (Compound 63)

[0588] To a mixture of N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2A-1,2,3-triazol-4-yl)propyl]-5- (2,4-difluorophenyl)-3-isoxazolecarboxamide (i.e. the product of Example 1) (0.20 g, 0.436 mmol, 1 equiv.) in N,N-dimethylformamide (2 mL) at 0 °C was added portionwise sodium hydride (60 % dispersion in mineral oil, 0.035 g, 0.872 mmol, 2 equiv.). The reaction mixture was stirred for 15 minutes and then iodomethane (0.093 g, 0.041 mL, 0.654 mmol, 1.5 equiv.) was added dropwise. After 1.5 h, the reaction mixture was allowed to warm to room temperature and diluted with water and then partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were concentrated under reduced pressure and the resulting mixture was purified by MPLC (eluting with a gradient of 0-60% ethyl acetate in hexanes). The resulting material was further purified with reverse phase MPLC (eluting with a gradient of 10-100% acetonitrile in water) to provide the title compound (0.066 g).

[0589] 1H NMR (CDCl3): δ 7.99-7.89 (m, 1H), 7.65-7.35 (m, 2H), 7.24-6.93 (m, 4H), 6.79 (d, J=1.00 Hz, 1H), 4.60 (dd, J=1.00 Hz, 2H), 4.15 (s, 3H), 2.82 (s, 3H), 1.80 (s, 3H).

[0590] MS: 473 (M+1).

[0591] EXAMPLE 11

[0592] Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(5-cyclopropyl-2-methyl-2A-1,2,3-triazol- 4-yl)propyl]-5-(2,4-difluorophenyl)-3-isoxazolecarboxamide (Compound 70)

[0593] Step A: Preparation of l-(5-bromo-2-methyl-2A- 1,2, 3 -triazol -4-yl)ethanone

[0594] To a mixture of 4,5-dibromo-2-methyl-2A-1,2,3-triazole (500 g, 2.07 mol) in tetrahydrofuran (10 L) at -78 °C was added dropwise n-butyl lithium (2.5M in hexane) (1079 mL, 2.70 mol). The reaction mixture was stirred at -78 °C for 30 minutes and then N-methoxy-N- methyl acetamide (485 mL, 4.57 mol) was added. Stirring was continued at -78 °C for another 30 minutes and then the reaction mixture was diluted with ice-cooled water and acidified with the addition of aqueous hydrochloric acid (1 N). The resulting mixture was extracted with ethyl acetate (3x), dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was triturated with petroleum ether to provide the title compound (217 g).

[0595] 1H NMR (CDCl3): δ 4.23 (s, 3H), 2 60 (s, 3H) Step B: Preparation of α,2-dimethyl-5-bromo-2H- l ,2,3-triazole-4-acetonitrile

[0596] To a mixture of potassium tert-butoxide (35.86 g, 0.32 mol) in 1,2-dimethoxy ethane (400 mL) at -78 °C was added dropwise a mixture of p-toluenesulfonylmethyl isocyanide (39 g, 0.20 mol) in 1,2-dimethoxy ethane (25 mL), followed by the dropwise addition of a mixture of 1- (5-bromo-2-methyl-2H-1,2,3-triazol-4-yl)ethanone (i.e. the product of Step A) (20 g, 0.13 mol) in 1,2-dimethoxy ethane (25 mL). The reaction mixture was stirred at -78 °C for 1 h and then methanol (200 mL) was added. The reaction mixture was allowed to warm to room temperature and then heated at 85 °C for 1 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure, diluted with water and extracted with ethyl acetate (3x). The combined organic extracts were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was purified on silica gel column chromatography (eluting with 10-20% ethyl acetate in petroleum ether) to provide the title compound (8 g).

[0597] 1H NMR (CDCl3): δ 4.17 (s, 3H), 4.03 (q, J=7.5 Hz,lH), 1.70 (d, J=7.5 Hz, 3H).

[0598] Step C: Preparation of α,2-dimethyl-5-cyclopropyl-2H-1,2,3-triazole-4-acetonitrile

[0599] To a mixture of α,2-dimethyl-5-bromo-2H-1,2,3-triazole-4-acetonitrile (i.e. the product of Step B) (3 g, 13.95 mmol, 1 equiv.) in 1,4-dioxane (30 mL) was added cyclopropylboronic acid (4.79 g, 55.80 mmol, 4 equiv.) and potassium carbonate (5.78 g, 41.85 mmol, 3 equiv.). The reaction mixture was degassed with nitrogen gas for 20 minutes and then [1,1 - bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.51 g, 0.69 mmol, 0.05 equiv.) was added. The reaction mixture was heated at 100 °C for 4 h, cooled to room temperature and filtered through a bed of Celite®. The filtrate was concentrated under reduced pressure and the resulting material was purified by silica gel column chromatography (eluting with 5-7% ethyl acetate in petroleum ether) to provide the title compound (1.7 g).

[0600] 1H NMR (CDCl3): δ 4.10-4.06 (m, 4H), 1.84-1.77 (m, 1H), 1.71 (d, J=7.2 Hz, 3H), 1.01-0.97 (m, 2H), 0.90-0.88 (m, 2H).

[0601] MS: 177 (M+1).

[0602] Step D: Preparation of 6-chloro-α-(5-cyclopropyl-2-methyl-2H-1,2,3-triazol-4-yl)-α- methyl-2-pyridineacetonitrile

[0603] To a mixture of α,2-dimethyl-5-cyclopropyl-2H-1,2,3-triazole-4-acetonitrile (i.e. the product of Step C) (500 mg, 2.837 mmol, 1 equiv.) and 2,6-dichloropyridine (419.894 mg, 2.837 mmol, 1 equiv.) in tetrahydrofuran (15 mL) at 0 °C was added potassium bis(trimethylsilyl)amide solution (1 M in tetrahydrofuran) (3.4 mL, 3.4 mmol, 1.2 equiv.). The reaction mixture was stirred at 0 °C for 1 h and then diluted with ice-cooled water and extracted with ethyl acetate (2x). The combined organic extracts were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 15% ethyl acetate in petroleum ether) to provide the title compound (0.5 g).

[0604] 1H NMR. (CDCl3): δ 7.69-7.65 (m, 1H), 7.39 (d, J= 7.6 Hz, 1H), 7.30-7.26 (m, 1H), 4.08 (s, 3H), 2.21 (s, 3H), 1.56-1.50 (m, 1H), 0.86-0.81 (m, 2H), 0.68-0.66 (m, 2H).

[0605] MS: 288 (M+1).

[0606] Step E: Preparation of 6-chloro-β-(5-cyclopropyl-2-methyl-2H-1,2,3-triazol-4-yl)-β- methyl-2-pyridineethanamine

[0607] To a mixture of 6-chloro-α-(5-cyclopropyl-2-methyl-2H-1,2,3-triazol-4-yl)-α-methyl-2- pyridineacetonitrile (i.e. the product of Step D) (300 mg, 1.04 mmol, 1 equiv.) in tetrahydrofuran (10 mL) at 0 °C was added dropwise borane dimethyl sulfide complex solution (2 M in tetrahydrofuran) (1.56 mL, 3.13 mmol, 3 equiv.). The reaction mixture was heated at 75 °C for 4 h and then cooled to 0 °C and concentrated hydrochloric acid (1 mL, 4.17 mmol, 4 equiv.) was added dropwise over a period of 5 minutes. The reaction mixture was heated to 50 °C for 1 h and then cooled to 0 °C and adjusted to approximately pH 10 with the addition of aqueous sodium hydroxide solution (30%). The resulting mixture was extracted with ethyl acetate (2x) and the combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to provide the title compound (0.32 g).

[0608] MS: 292 (M+1).

[0609] Step F: Preparation of N-[2-(6-chloro-2-pyridinyl)-2-(5-cyclopropyl-2-methyl-2H-1,2,3- triazol-4-yl)propyl]-5-(2,4-difluorophenyl)-3-isoxazolecarboxamide

[0610] To a mixture of 6-chloro-β-(5-cyclopropyl-2-methyl-2H-1,2,3-triazol-4-yl)-β-methyl-2- pyridineethanamine (i.e. the product of Step E) (150 mg, 0.514 mmol, 1 equiv.) and 5-(2,4- difluorophenyl)-3-isoxazolecarboxylic acid (173.618 mg, 0.771 mmol, 1.5 equiv.) in N,N-dimethylformamide (10 mL) at 0 °C was added l-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (586.422 mg, 1.542 mmol, 3 equiv.) and N,N-diisopropylethylamine (0.269 mL, 1.542 mmol, 3 equiv.). The reaction mixture was warmed to room temperature and stirred for 5 h and then diluted with ice-cooled water and extracted with ethyl acetate (2x). The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 20% ethyl acetate in petroleum ether) to provide the title compound (0.09 g).1H NMR (CDCl3): δ 8.03 (t, J = 8 Hz, 1H), 7.96-7.90 (m, 1H), 7.55 (t, J = 8 Hz, 1H), 7.21 (d, J = 8 Hz, 1H), 7.06-6.94 (m, 4H), 4.17-4.14 (m, 2H), 4.10 (s, 3H), 1.84 (s, 3H), 1.12-1.05 (m, 1H), 0.70-0.65 (m, 4H).

[0611] MS: 499 (M+1).

[0612] EXAMPLE 12

[0613] Preparation of 2-(2,4-difluorophenyl)-N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H- l,2,3-triazol-4-yl)propyl]-2H-tetrazole-5-carboxamide (Compound 41)

[0614] Step A: Preparation of l-(5-bromo-2-methyl-2H- 1,2, 3 -triazol -4-yl)ethanone

[0615] To a mixture of 4,5-dibromo-2-methyl-2H-1,2,3-triazole (500 g, 2.07 mol) in tetrahydrofuran (10 L) at -78 °C. was added dropwise n-butyllithium (2.5 M in hexane) (1079.3 mL, 2.7 mol). The reaction mixture was stirred at -78 °C for 30 minutes and then N- methoxy-N-methyl acetamide (485.4 mL, 4.56 mol) was added. Stirring was continued at -78 °C for another 30 minutes, then the reaction mixture was diluted with ice-cooled water (5000 mL) and acidified by the addition of hydrochloric acid (1 N) (3000 mL). The resulting mixture was extracted with ethyl acetate (2500 mL x 3), dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was triturated with petroleum ether to provide the title compound as a solid (217 g).

[0616] 1H NMR (CDCl3): δ 4.23 (s, 3H), 2.60 (s, 3H).

[0617] MS: 203 (M+1).

[0618] Step B: Preparation of l-(2-methyl-2H-1,2,3-triazol-4-yl)ethanone

[0619] A mixture of l-(5-bromo-2-methyl-2H-1,2,3-triazol-4-yl)ethanone (i.e. the product of Step A) (150 g, 0.73 mol) in ethanol (3 L) was degassed with nitrogen gas for 5 minutes, then 10% palladium on carbon (50% wet with water, 75 g, 98 mmol) was added. The reaction mixture was stirred at room temperature in an autoclave under hydrogen atmosphere pressure of 65 psi (448 kPa) for 16 h. The reaction mixture was filtered through a bed of Celite®, washed with ethyl acetate (3000 mL), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 10% ethyl acetate in petroleum ether) to provide the title compound as an off-white solid (70 g).

[0620] 1H NMR (CDCl3): δ 8.01 (s, 1H), 4.25 (s, 3H), 2.59 (s, 3H).

[0621] MS: 125 (M+1).

[0622] Step C: Preparation of α,2-dimethyl-2H-1,2,3-triazole-4-acetonitrile

[0623] To a mixture of potassium tert-butoxide (182.9 g, 1.63 mol) in 1,2-dimethoxy ethane (1275 mL) at -78 °C was added dropwise a solution of p-toluenesulfonylmethyl isocyanide (198.9 g, 1.01 mol) in 1,2-dimethoxy ethane (425 mL), and then a solution of l-(2-methyl-2H- l,2,3-triazol-4-yl)ethanone (i.e. the product of Step B) (85 g, 0.68 mol) in dimethyl ether (425 mL) was added dropwise. The reaction mixture was stirred at -78 °C for 1 h, and then methanol (850 mL) was added, and the mixture was allowed to warm to room temperature. The reaction mixture was heated at 85 °C for 1 h, cooled and concentrated under reduced pressure. The resulting material was diluted with water (930 mL) and extracted with ethyl acetate (1000 mL x 3). The combined organic extracts were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 20% ethyl acetate in petroleum ether) to provide the title compound as a colorless oil (74 g).

[0624] 1H NMR (CDCl3): δ 7.56 (s, 1H), 4.19 (s, 3H), 4.06 (q, J=7.2 Hz,lH), 1.70 (d, J=7.2 Hz,3H). MS: 136 (M+1).

[0625] Step D: Preparation of 6-chloro-α-(2-methyl-2H-1,2,3-triazol-4-yl)-α-methyl-2- pyridineacetonitrile

[0626] A mixture of α,2-dimethyl-2H-1,2,3-triazole-4-acetonitrile (i.e. the product of Step C) (90 g, 0.661 mol, 1 equiv.) and 2,6-dichloropyridine (97.82 g, 0.661 mol, 1 equiv.) in tetrahydrofuran (2 L) at -78 °C was degassed with nitrogen gas for 10 minutes and then potassium tert-butoxide (96.42 g, 859.296 mmol, 1.3 equiv.) was added. The reaction mixture was stirred at -78 °C for 20 minutes, warm to 0 °C and stirred for 2 h and then diluted with ice-cooled water and extracted with ethyl acetate (1 L x 2). The combined organic extracts were washed with water and saturated aqueous sodium chloride solution (1 L), dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 20% ethyl acetate in petroleum ether) to provide the title compound (105 g) as a white solid.

[0627] 1H NMR (CDCl3): δ 7.69 (t, J = 7.6 Hz, 1H), 7.57 (s, 1H), 7.53 (dd, J = 8 Hz, 0.8 Hz, 1H), 7.31 (dd, J = 8 Hz, 0.8 Hz, 1H), 4.18 (s, 3H), 2.18 (s, 3H).

[0628] MS: 248 (M+1).

[0629] Step E: Preparation of 6-methyl-α-(2-methyl-2H-1,2,3-triazol-4-yl)-α-methyl-2- pyridineacetonitrile

[0630] To a mixture of 6-chloro-α-(2-methyl-2H- 1,2, 3 -triazol -4-yl)-α-methyl-2- pyridineacetonitrile (i.e. the product of Step D) (115 g, 0.46 mol, 1 equiv.) and methylboronic acid (277.92 g, 4.64 mol, 10 equiv.) in 1,4-dioxane (1200 ml) was added a solution of cesium carbonate (302.55 g, 0.93 mol, 2 equiv.) in water (34 mL). The reaction mixture was degassed with nitrogen gas for 10 minutes and then 1, 1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (16.97 g, 23.21 mmol, 0.05 equiv.) was added. The reaction mixture was heated at 120 °C for 2 h, cooled to room temperature and then filtered through a bed of Celite®. The filtrate was diluted with water and extracted with ethyl acetate (350 mL x 3). The combined organic extracts were washed with water and saturated aqueous sodium chloride solution (250 mL), dried over sodium sulphate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 1% ethyl acetate in dichloromethane) to provide the title compound (90 g) as an off-white solid.

[0631] 1H NMR. (CDCl3): δ 7.58 (t, J= 7.5 Hz, 1H), 7.52 (s, 1H), 7.32 (d, 7.5 Hz, 1H), 7.10 (d, J =

[0632] 7.5 Hz, 1H), 4.18 (s, 3H), 2.54 (s, 3H), 2.16 (s.3H).

[0633] MS: 228 (M+1).

[0634] Step F: Preparation of 6-methyl-β-methyl-β-(2-methyl-2H-1,2,3-triazol-4-yl)-2- pyridineethanamine

[0635] To a mixture of 6-m ethyl -α-(2-m ethyl -2H- 1,2, 3 -triazol -4-yl)-a-methyl-2- pyridineacetonitrile (i.e. the product of Step E) (35 g, 0.154 mol, 1 equiv.) in tetrahydrofuran (350 mL) at 0 °C was added borane dimethyl sulfide complex (2 M solution in tetrahydrofuran) (231 mL, 0.46 mol, 3 equiv.). The reaction mixture was heated at 85 °C for 3 h, then cooled to 0 °C and concentrated hydrochloric acid (87.73 mL, 0.770 mol, 5 equiv.) was added. After 30 minutes, the reaction mixture was diluted with water and extracted with ethyl acetate (150 mL). The aqueous layer was basified to approximately pH 12 with the addition of sodium hydroxide (4 N) and then extracted with ethyl acetate (250 mL x 3). The combined organic extracts were washed with water and saturated aqueous sodium chloride solution (150 mL), dried over sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to provide the title compound (30 g) as a solid.

[0636] 1H NMR (DMSO-d6): δ 7.56-7.53 (m, 2H), 7.06 (d, J = 7.6 Hz, 1H), 6.91 (d, J = 7.6 Hz, 1H), 4.08 (s, 3H), 3.15 (m, 2H), 2.45 (s, 3H), 1.64 (s, 3H).

[0637] MS: 232 (M+1).

[0638] Step G: Preparation of 2-(2,4-difluorophenyl)-N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-

[0639] 2H- l ,2,3-triazol-4-yl)propyl]-2H-tetrazole-5-carboxamide

[0640] To a mixture of 2-(2,4-difluorophenyl)-2H-tetrazole-5-carboxylic acid (i.e. the product of Example 13 below) (43 g, 0.19 mol, 1 equiv.) in dichloromethane (500 mL) at 0 °C was added N, A-di methyl form am ide (5 mL) and oxalyl chloride (49.25 mL, 0.57 mol, 3 equiv.). The reaction mixture was stirred at 0 °C for 1 h and then concentrated under reduced pressure to provide the acid chloride (i.e. 2-(2,4-difluorophenyl)-2H-tetrazole-5-carbonyl chloride).

[0641] A solution of the acid chloride in tetrahydrofuran (250 mL) was added dropwise to a mixture of 6-methyl-β-methyl-β-(2-methyl-2H-1,2,3-triazol-4-yl)-2-pyridineethanamine (i.e. the product of Step F) (43.98 g, 190.145 mmol., 1 equiv.) and N, N-di isopropyl ethyl amine (166.056 mL, 950.726 mmol, 5 equiv.) in tetrahydrofuran (250 mL) at 0 °C. The reaction mixture was allowed to warm to room temperature and stirred for 1 h, and then diluted with ice-cooled water and extracted with ethyl acetate (250 mL x 2). The combined organic extracts were washed with water and saturated aqueous sodium chloride solution (250 mL), dried over sodium sulphate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 50% ethyl acetate in petroleum ether) to provide the title compound (60 g) as a white solid.

[0642] 1H NMR (DMSO-d6): δ 9.18 (t, J= 6.4 Hz, 1H), 8.11-8.05 (m, 1H), 7.83-7.77 (m, 1H), 7.65-7.61 (m, 2H), 7.48-7.43 (m, 1H), 7.16 (d, .7=7.6 Hz, 1H), 6.97 (d, J=8 Hz, 1H), 4.17-3.99 (m, 5H), 2.54 (s, 3H), 1.71 (s, 3H).;

[0643] MS: 440 (M+1).

[0644] EXAMPLE 13

[0645] Preparation of 2-(2,4-difluorophenyl)-2H-tetrazole-5-carboxylic acid

[0646] Step A: Preparation of ethyl (2E)-2-[2-[(4-methylphenyl)sulfonyl]hydrazinylidene]- acetate

[0647] To a mixture 4-methylbenzenesulfonohydrazide (100 g, 0.53 mol, 1 equiv.) in ethanol (1.5 L) was added dropwise ethyl 2-oxoacetate (131.56 mL, 0.64 mol, 1.2 equiv.). The reaction mixture was stirred at room temperature for 1 h and then concentrated under reduced pressure to provide the title compound (145 g) as a colorless oil.

[0648] 1H NMR (CDCl3): δ 12.11 (s, 1H), 7.83 (d, J = 8 Hz, 2H), 7.34 (d, .7=8 Hz, 2H), 6.81 (s, 1H), 4.27-4.22 (m, 2H), 2.43 (s, 3H), 1.34-1.26 (m, 3H).

[0649] Step B : Preparation ethyl 2-(2,4-difluorophenyl)-2H-tetrazole-5-carboxylate

[0650] A mixture of 2,4-difluoroaniline (6.5 g, 50.345 mmol, 1 equiv.) in hydrochloric acid (6 M) (40 mL) and ethanol (32.5 mL) was cooled to 0 °C and then a solution of sodium nitrite solution in water (40 mL) (4.16 g) was added dropwise. The reaction mixture was stirred at 0 °C for 1 hour.

[0651] To a mixture of ethyl (2E)-2-[2-[(4-methylphenyl)sulfonyl]hydrazinylidene]acetate (i.e. the product of Step A) (14.969 g, 55.39 mmol, 1.1 equiv.) in pyridine (150 mL) at -20 °C was added dropwise the 2,4-dichlorobenzenediazonium solution prepared above. The reaction mixture was stirred at room temperature for 5 h and then hydrochloric acid solution (1 N) (1 L) was added. The resulting mixture was extracted with ethyl acetate (250 mL x 2) and the combined extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 15% ethyl acetate in petroleum ether to provide the title compound (5 g).

[0652] 1H NMR (CDCl3): δ 7.90-7.86 (m, 1H), 7.17-7.10 (m, 2H), 4.58 (q, J=7 Hz, 2H), 1.49 (t, J= 7 Hz, 3H).

[0653] MS: 255 (M+1).

[0654] Step C : Preparation of 2-(2,4-difluorophenyl)-2H-tetrazole-5-carboxylic acid

[0655] To a mixture of ethyl 2-(2,4-difluorophenyl)-2H-tetrazole-5-carboxylate (i.e. the product of Step B) (75 g, 0.296 mol, 1 equiv.) in tetrahydrofuran (750 mL) and water (250 mL) was added lithium hydroxide monohydrate (49.52 g, 1.18 mol, 4 equiv.). After 1 h, the reaction mixture was cooled to 15 °C and then acidified to approximately pH 2 by the addition of hydrochloric acid (IN) solution. The resulting mixture was extracted with ethyl acetate (2 L x 2) and the combined extracts were washed with water and saturated aqueous sodium chloride solution. The organic layer was dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting material was triturated with ethyl acetate / petroleum ether (10%, 1 L), filtered and dried under vacuum to provide the title compound (65 g).

[0656] 1H NMR (DMSO-d6): δ 14.68 (br s, 1H), 8.12-8.06 (m, 1H), 7.83-7.77 (m, 1H), 7.48-7.43 (m, 1H).

[0657] MS: 225 (M+1).

[0658] By the procedures described above, together with methods known in the art, the following compounds can be prepared:

[0659] Table 1 R6is Cl and m is 0. R6is Cl and m is 0.

[0660] The present disclosure also includes Tables 1-1 through 1-36, each of which is constructed the same as Table 1 above, except that the row heading in Table 1 (i.e. “R6is Cl and m is 0”) is replaced with the respective row headings shown below.

[0661] Table 2 R6is Cl and m is 0. R6is Cl and m is 0.

[0662] The present disclosure also includes Tables 2-1 through 2-12, each of which is constructed the same as Table 2 above, except that the row heading in Table 2 (i.e. “R6is Cl and m is 0”) is replaced with the respective row headings shown below. Table 3 R6is Cl and m is 0. R6is Cl and m is 0.

[0663] The present disclosure also includes Tables 3-1 through 3-12, each of which is constructed the same as Table 3 above, except that the row heading in Table 3 (i.e. “R6is Cl and m is 0”) is replaced with the respective row headings shown below.

[0664] Table 4 R6is Cl and m is 0. R6is Cl and m is 0.

[0665] The present disclosure also includes Tables 4-1 through 4-36, each of which is constructed the same as Table 4 above, except that the row heading in Table 4 (i.e. “R6is Cl and m is 0”) is replaced with the respective row headings shown below.

[0666] Table 5 R6is Cl and m is 0. R6is Cl and m is 0.

[0667] The present disclosure also includes Tables 5-1 through 5-36, each of which is constructed the same as Table 5 above, except that the row heading in Table 5 (i.e. “R6is Cl and m is 0”) is replaced with the respective row headings shown below. R6is Cl and m is 0. R6is Cl and m is 0.

[0668] The present disclosure also includes Tables 6-1 through 6-36, each of which is constructed the same as Table 6 above, except that the row heading in Table 6 (i.e. “R6is Cl and m is 0”) is replaced with the respective row headings shown below.

[0669] Table 7 discloses specific compounds of Formula 6 which are useful as process intermediates for preparing compounds of Formula 1.

[0670] TABLE 7 A dash in the R5acolumn means no R5asubstituent is present, and the remaining carbon valence is occupied by a hydrogen atom.

[0671] F ormulation / Utility

[0672] A compound of Formula 1 of this invention (including N-oxides and salts thereof), or a mixture (i.e. composition) comprising the compound with at least one additional fungicidal compound as described in the Summary of the Invention, will generally be used as a fungicidal active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serve as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.

[0673] A compound of Formula 1, or mixture thereof, can be formulated in a number of ways, including:

[0674] (i) the compound of Formula 1 and optionally one or more other biologically active compounds or agents can be formulated separately and applied separately or applied simultaneously in an appropriate weight ratio, e.g., as a tank mix; or

[0675] (ii) the compound of Formula 1 and optionally one or more other biologically active compounds or agents can be formulated together in the proper weight ratio.

[0676] Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions, oil-in-water emulsions, flowable concentrates 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, oil-in-water emulsion, flowable concentrate and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.

[0677] 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.

[0678] 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, but occasionally another suitable medium like an aromatic or paraffinic hydrocarbon or vegetable oil. Spray volumes can range from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and / or foliage through systemic uptake.

[0679] 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.

[0680] 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.

[0681] Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g., N,N- dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N- methylpyrrolidinone), alkyl phosphates (e.g., tri ethyl phosphate), ethylene glycol, tri ethylene 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, 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, alkyl and aryl benzoates and y- 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, cresol 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.

[0682] 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.

[0683] 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 tri styrylphenol (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.

[0684] 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 diquatemary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

[0685] 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.

[0686] 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.

[0687] The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 pm can be wet milled using media mills to obtain particles with average diameters below 3 pm. 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 pm 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, pp 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.

[0688] One embodiment of the present invention relates to a method for controlling fungal pathogens, comprising diluting the fungicidal composition of the present invention (a compound of Formula 1 formulated with surfactants, solid diluents and liquid diluents or a formulated mixture of a compound of Formula 1 and at least one other fungicide) with water, and optionally adding an adjuvant to form a diluted composition, and contacting the fungal pathogen or its environment with an effective amount of said diluted composition.

[0689] Although a spray composition formed by diluting with water a sufficient concentration of the present fungicidal composition can provide sufficient efficacy for controlling fungal pathogens, separately formulated adjuvant products can also be added to spray tank mixtures. These additional adjuvants are commonly known as “spray adjuvants” or “tank-mix adjuvants”, and include any substance mixed in a spray tank to improve the performance of a pesticide or alter the physical properties of the spray mixture. Adjuvants can be anionic or nonionic surfactants, emulsifying agents, petroleum-based crop oils, crop-derived seed oils, acidifiers, buffers, thickeners or defoaming agents. Adjuvants are used to enhancing efficacy (e.g., biological availability, adhesion, penetration, uniformity of coverage and durability of protection), or minimizing or eliminating spray application problems associated with incompatibility, foaming, drift, evaporation, volatilization and degradation. To obtain optimal performance, adjuvants are selected with regard to the properties of the active ingredient, formulation and target (e.g., crops, insect pests).

[0690] The amount of adjuvants added to spray mixtures is generally in the range of about 0.1% to 2.5% by volume. The application rates of adjuvants added to spray mixtures are typically between about 1 to 5 L per hectare. Representative examples of spray adjuvants include: Adigor® (Syngenta) 47% methylated rapeseed oil in liquid hydrocarbons, Silwet® (Helena Chemical Company) polyalkyleneoxide modified heptamethyltrisiloxane and Assist® (BASF) 17% surfactant blend in 83% paraffin based mineral oil.

[0691] One method of seed treatment is by spraying or dusting the seed with a compound of the invention (i.e. as a formulated composition) before sowing the seeds. Compositions formulated for seed treatment generally comprise a film former or adhesive agent. Therefore typically a seed coating composition of the present invention comprises a biologically effective amount of a compound of Formula 1 and a film former or adhesive agent. Seeds can be coated by spraying a flowable suspension concentrate directly into a tumbling bed of seeds and then drying the seeds. Alternatively, other formulation types such as wetted powders, solutions, suspoemulsions, emulsifiable concentrates and emulsions in water can be sprayed on the seed. This process is particularly useful for applying film coatings on seeds. Various coating machines and processes are available to one skilled in the art. Suitable processes include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and references listed therein.

[0692] For further information regarding the art of formulation, see T. S. Woods, “The Formulator’s Toolbox - Product Forms for Modem 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. Also see U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.

[0693] In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Active ingredient refers to the compounds in Index Table A disclosed herein. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be constructed as merely illustrative, and not limiting of the disclosure in any way whatsoever.

[0694] Example A

[0695] High Strength Concentrate

[0696] Compound 1 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%

[0697] Example B

[0698] Wettable Powder

[0699] Compound 14 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%

[0700] Example C Granule

[0701] Compound 19 10.0% attapulgite granules (low volatile matter, 0.71 / 0.30 mm; 90.0%

[0702] U.S.S. No. 25-50 sieves)

[0703] Example D Extruded Pellet

[0704] Compound 29 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium / magnesium bentonite 59.0%

[0705] Example E Emulsifiable Concentrate Compound 41 10.0% polyoxyethylene sorbitol hexoleate 20.0%

[0706] C6-C10fatty acid methyl ester 70.0%

[0707] Example F Microemulsion

[0708] Compound 50 5.0% polyvinylpyrrolidone-vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%

[0709] Example G Seed Treatment

[0710] Compound 52 20.00% polyvinylpyrrolidone-vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% poly oxy ethylene / polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%

[0711] Example H

[0712] Fertilizer Stick Compound 1 2.50% pyrrolidone-styrene copolymer 4.80% tristyrylphenyl 16-ethoxylate 2.30% talc 0.80% com starch 5.00% slow-release fertilizer 36.00% kaolin 38.00% water 10.60%

[0713] Example I

[0714] Suspension Concentrate Compound 14 35% butyl polyoxyethylene / polypropylene block copolymer 4.0% stearic acid / polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1% l,2-benzisothiazolin-3-one 0.1% water 53.7%

[0715] Example J

[0716] Emulsion in Water

[0717] Compound 19 10.0% butyl polyoxyethylene / polypropylene block copolymer 4.0% stearic acid / polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1% l,2-benzisothiazolin-3-one 0.1% aromatic petroleum based hydrocarbon 20.0 water 58.7%

[0718] Example K

[0719] Oil Dispersion Compound 29 25% polyoxyethylene sorbitol hexaoleate 15% organically modified bentonite clay 2.5% fatty acid methyl ester 57.5%

[0720] Example L

[0721] Suspoemulsion Compound 41 10.0% imidacloprid 5.0% butyl polyoxyethylene / polypropylene block copolymer 4.0% stearic acid / polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1% l,2-benzisothiazolin-3-one 0.1% aromatic petroleum based hydrocarbon 20.0% water 53.7%

[0722] Water-soluble and water-dispersible formulations 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 contain at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of the compound(s) of this invention.

[0723] Seed is normally treated at a rate of from about 0.001 g (more typically about 0.1 g) to about 10 g per kilogram of seed (i.e. from about 0.0001 to 1% by weight of the seed before treatment). A flowable suspension formulated for seed treatment typically comprises from about 0.5 to about 70% of the active ingredient, from about 0.5 to about 30% of a film-forming adhesive, from about 0.5 to about 20% of a dispersing agent, from 0 to about 5% of a thickener, from 0 to about 5% of a pigment and / or dye, from 0 to about 2% of an antifoaming agent, from 0 to about 1% of a preservative, and from 0 to about 75% of a volatile liquid diluent.

[0724] The compounds of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound. The compounds and / or compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Ascomycota, Basidiomycota, Zygomycota phyla, and the fungal-like Oomycota class. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops. These pathogens include but are not limited to those listed in Table 1-1. For Ascomycetes and Basidiomycetes, names for both the sexual / teleomorph / perfect stage as well as names for the asexual / anamorph / imperfect stage (in parentheses) are listed where known. Synonymous names for pathogens are indicated by an equal sign. For example, the sexual / teleomorph / perfect stage name Phaeosphaeria nodorum is followed by the corresponding asexual / anamorph / imperfect stage name Stagnospora nodorum and the synonymous older name Septoria nodorum.

[0725] Table 1-1

[0726] In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species. By controlling harmful microorganisms, the compounds of the invention are useful for improving (i.e. increasing) the ratio of beneficial to harmful microorganisms in contact with crop plants or their propagules (e.g., seeds, corms, bulbs, tubers, cuttings) or in the agronomic environment of the crop plants or their propagules.

[0727] Compounds of the invention are useful in treating all plants, plant parts and seeds. Plant and seed varieties and cultivars can be obtained by conventional propagation and breeding methods or by genetic engineering methods. Genetically modified plants or seeds (transgenic plants or seeds) are those in which a heterologous gene (transgene) has been stably integrated into the plant's or seed’s genome. A transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.

[0728] Genetically modified plant cultivars which can be treated according to the invention include those that are resistant against one or more biotic stresses (pests such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (drought, cold temperature, soil salinity, etc.), or that contain other desirable characteristics. Plants can be genetically modified to exhibit traits of, for example, herbicide tolerance, insect-resistance, modified oil profiles or drought tolerance.

[0729] Treatment of genetically modified plants and seeds with compounds of the invention may result in super-additive or enhanced effects. For example, reduction in application rates, broadening of the activity spectrum, increased tolerance to biotic / abiotic stresses or enhanced storage stability may be greater than expected from just simple additive effects of the application of compounds of the invention on genetically modified plants and seeds.

[0730] Compounds of this invention are useful in seed treatments for protecting seeds from plant diseases. In the context of the present disclosure and claims, treating a seed means contacting the seed with a biologically effective amount of a compound of this invention, which is typically formulated as a composition of the invention. This seed treatment protects the seed from soil- borne disease pathogens and generally can also protect roots and other plant parts in contact with the soil of the seedling developing from the germinating seed. The seed treatment may also provide protection of foliage by translocation of the compound of this invention or a second active ingredient within the developing plant. Seed treatments can be applied to all types of seeds, including those from which plants genetically transformed to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxin or those expressing herbicide resistance such as glyphosate acetyltransferase, which provides resistance to glyphosate. Seed treatments with compounds of this invention can also increase vigor of plants growing from the seed.

[0731] Compounds of this invention and their compositions, both alone and in combination with other fungicides, nematicides and insecticides, are particularly useful in seed treatment for crops including, but not limited to, maize or corn, soybeans, cotton, cereal (e.g., wheat, oats, barley, rye and rice), potatoes, vegetables and oilseed rape.

[0732] Furthermore, the compounds of this invention are useful in treating postharvest diseases of fruits and vegetables caused by fungi, oomycetes and bacteria. These infections can occur before, during and after harvest. For example, infections can occur before harvest and then remain dormant until some point during ripening (e.g., host begins tissue changes in such a way that infection can progress or conditions become conducive for disease development); also infections can arise from surface wounds created by mechanical or insect injury. In this respect, the compounds of this invention can reduce losses (i.e. losses resulting from quantity and quality) due to postharvest diseases which may occur at any time from harvest to consumption. Treatment of postharvest diseases with compounds of the invention can increase the period of time during which perishable edible plant parts (e.g., fruits, seeds, foliage, stems, bulbs, tubers) can be stored refrigerated or un-refrigerated after harvest, and remain edible and free from noticeable or harmful degradation or contamination by fungi or other microorganisms. Treatment of edible plant parts before or after harvest with compounds of the invention can also decrease the formation of toxic metabolites of fungi or other microorganisms, for example, mycotoxins such as aflatoxins.

[0733] Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruits, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to seeds to protect the seeds and seedlings developing from the seeds. The compounds can also be applied through irrigation water to treat plants. Control of postharvest pathogens which infect the produce before harvest is typically accomplished by field application of a compound of this invention, and in cases where infection occurs after harvest the compounds can be applied to the harvested crop as dips, sprays, fumigants, treated wraps and box liners.

[0734] The compounds can also be applied using an unmanned aerial vehicle (UAV) for the dispension of the compositions disclosed herein over a planted area. In some embodiments the planted area is a crop-containing area. In some embodiments, the crop is selected from a monocot or dicot. In some embodiments, the crop is selected form rice, corn, barley, sobean, wheat, vegetable, tobacco, tea tree, fruit tree and sugar cane. In some embodiments, the compositions disclosed herein are formulated for spraying at an ultra-low volume. Products applied by drones may use water or oil as the spray carrier. Typical spray volume (including product) used for drone applications globally is 5.0 liters / ha - 100 liters / ha (approximately 0.5-10 gpa). This includes the range of ultra low spray volume (ULV) to low spray volume (LV). Although not common there may be situations where even lower spray volumes could be used as low as 1.0 liter / ha (0.1 gpa).

[0735] Suitable rates of application for the compounds of this invention (i.e. a fungicidally effective amount) can be influenced by factors such as the plant diseases to be controlled, the plant species to be protected, the population structure of the pathogen to be controlled, ambient moisture and temperature and should be determined under actual use conditions. One skilled in the art can easily determine through simple experimentation the fungicidally effective amount necessary for the desired level of plant disease control. 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 ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.001 g (more typically about 0.1 g) to about 10 g per kilogram of seed. One skilled in the art can easily determine through simple experimentation the application rates for the compounds of this invention, and compositions thereof, needed to provide the desired spectrum of plant protection and control of plant diseases and optionally other plant pests.

[0736] Compounds of the present invention may also be useful for increasing vigor of a crop plant. This method comprises contacting the crop plant (e.g., foliage, flowers, fruit or roots) or the seed from which the crop plant is grown with a compound of Formula 1 in amount sufficient to achieve the desired plant vigor effect (i.e. biologically effective amount). Typically the compound of Formula 1 is applied in a formulated composition. Although the compound of Formula 1 is often applied directly to the crop plant or its seed, it can also be applied to the locus of the crop plant, i.e. the environment of the crop plant, particularly the portion of the environment in close enough proximity to allow the compound of Formula 1 to migrate to the crop plant. The locus relevant to this method most commonly comprises the growth medium (i.e. medium providing nutrients to the plant), typically soil in which the plant is grown. Treatment of a crop plant to increase vigor of the crop plant thus comprises contacting the crop plant, the seed from which the crop plant is grown or the locus of the crop plant with a biologically effective amount of a compound of Formula 1.

[0737] Increased crop vigor can result in one or more of the following observed effects: (a) optimal crop establishment as demonstrated by excellent seed germination, crop emergence and crop stand; (b) enhanced crop growth as demonstrated by rapid and robust leaf growth (e.g., measured by leaf area index), plant height, number of tillers (e.g., for rice), root mass and overall dry weight of vegetative mass of the crop; (c) improved crop yields, as demonstrated by time to flowering, duration of flowering, number of flowers, total biomass accumulation (i.e. yield quantity) and / or fruit or grain grade marketability of produce (i.e. yield quality); (d) enhanced ability of the crop to withstand or prevent plant disease infections and arthropod, nematode or mollusk pest infestations; and (e) increased ability of the crop to withstand environmental stresses such as exposure to thermal extremes, suboptimal moisture or phytotoxic chemicals.

[0738] The compounds of the present invention may increase the vigor of treated plants compared to untreated plants by preventing and / or curing plant diseases caused by fungal plant pathogens in the environment of the plants. In the absence of such control of plant diseases, the diseases reduce plant vigor by consuming plant tissues or sap, or transmiting plant pathogens such as viruses. Even in the absence of fungal plant pathogens, the compounds of the invention may increase plant vigor by modifying metabolism of plants. Generally, the vigor of a crop plant will be most significantly increased by treating the plant with a compound of the invention if the plant is grown in a nonideal environment, i.e. an environment comprising one or more aspects adverse to the plant achieving the full genetic potential it would exhibit in an ideal environment.

[0739] Of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment comprising plant diseases caused by fungal plant pathogens. Also of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment not comprising plant diseases caused by fungal plant pathogens. Also of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment comprising an amount of moisture less than ideal for supporting growth of the crop plant.

[0740] Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including fungicides, insecticides, nematicides, 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 compound of Formula 1 (in a fungicidally effective amount) and at least one additional biologically active compound or agent (in a biologically effective amount) 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 be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent. For mixtures of the present invention, one or more other biologically active compounds or agents can be formulated together with a compound of Formula 1, to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1, and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.

[0741] As mentioned in the Summary of the Invention, one aspect of the present invention is a fungicidal composition comprising (i.e. a mixture or combination of) a compound of Formula 1, an N-oxide, or a salt thereof (i.e. component a), and at least one other fungicide (i.e. component b). Of note is such a combination where the other fungicidal active ingredient has different site of action from the compound of Formula 1. In certain instances, a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise a fungicidally effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.

[0742] Of note is a composition which in addition to the Formula 1 compound of component (a), includes as component (b) at least one fungicidal compound selected from the group consisting of the FRAC-defined mode of action (MO A) classes, including (A) nucleic acids metabolism, (B) cytoskeleton and motor protein, (C) respiration, (D) amino acids and protein synthesis, (E) signal transduction, (F) lipid synthesis or transport and membrane integrity or function, (G) sterol biosynthesis in membranes, (H) cell wall biosynthesis, (I) melanin synthesis in cell wall, (P) host plant defense induction, (U) unknown mode of action, (M) chemicals with multi-site activity and (BM) biologicals with multiple modes of action.

[0743] FRAC -recognized or proposed target sites of action along with their FRAC target site codes belonging to the above MOA classes are (A1) RNA polymerase I, (A2) adenosine deaminase, (A3) DNA / RNA synthesis (proposed), (A4) DNA topoisomerase type II (gyrase), (A5) inhibition of dihydroorotate dehydrogenase within de novo pyrimidine biosynthesis, (B1)-(B3) tubulin polymerization, (B4) cell division (unknown site), (B5) delocalization of spectrin-like proteins, (B6) actin / myosin / fimbrin function, (B7) tubulin dynamics modulator, (Cl) complex I NADH odxido-reductase, (C2) complex II: succinate dehydrogenase, (C3) complex III: cytochrome bc1 (ubiquinol oxidase) at Qo site, (C4) complex III: cytochrome bc1 (ubiquinone reductase) at Qi site, (C5) uncouplers of oxidative phosphorylation, (C6) inhibitors of oxidative phosphorylation, ATP synthase, (C7) ATP production (proposed), (C8) complex III: cytochrome bc1 (ubiquinone reductase) at Qi and Qo site (stigmatellin binding mode), (D1) methionine biosynthesis (proposed), (D2) protein synthesis (ribosome, termination step), (D3) protein synthesis (ribosome, initiation step), (D4) protein synthesis (ribosome, initiation step), (D5) protein synthesis (ribosome, elongation step), (D6) leucyl-tRNA synthetase (LeuRS), (El) signal transduction (mechanism unknown), (E2) MAP / histidine kinase in osmotic signal transduction (os-2, HOG1), (E3) MAP / histidine kinase in osmotic signal transduction (os-1, Dafl), (F2) phospholipid biosynthesis, methyl transferase, (F3) cell peroxidation (proposed), (F4) cell membrane permeability, fatty acids (proposed), (F6) microbial disrupters of pathogen cell membranes, (F7) cell membrane disruption, (F8) ergosterol binding, (F9) lipid homeostasis and transfer / storage, (F10) interaction with lipid fraction of the cell membrane, with multiple effects on cell membrane integrity, (Gl) C14-demethylase in sterol biosynthesis (erg11 / cyp51), (G2) A14-reductase and Δ8→Δ7-isom erase in sterol biosynthesis (erg24, erg2), (G3) 3-keto reductase, C4-demethylation (erg27), C4-demethylation, (G4) squalene epoxidase in sterol biosynthesis (ergl), (H4) chitin synthase, (H5) cellulose synthase, (II) reductase in melanin biosynthesis, (12) dehydratase in melanin biosynthesis, (13) polyketide synthase in melanin biosynthesis, (P1)-(P3) salicylate- related, (P4) polysaccharide elicitors, (P5) anthraquinone elicitors, (P6) microbial elicitors, (P7) phosphonates, (P7) phosphonates, (P8) salicylate-related, (P9) peptide elicitors, (PIO) defense priming agents, (M01)-(M12) multi-site contact activity, (BM01) biologicals with multiple modes of action (plant extract), (BM02) biologicals with multiple modes of action (microbial, living microbes or extracts from microbes or metabolites), and (BM03) purified metabolites from plant or microbial sources or synthetic versions of these metabolites.

[0744] Of note is a composition which in addition to the Formula 1 compound of component (a), includes as component (b) at least one fungicidal compound selected from the group consisting of the classes (bl) methyl benzimidazole carbamate (MBC) fungicides; (b2) dicarboximide fungicides; (b3) demethylation inhibitor (DMI) fungicides (SBI Class I); (b4) phenylamide (PA) fungicides; (b5) amine / morpholine fungicides (SBI Class II); (b6) phospholipid biosynthesis inhibitor fungicides; (b7) succinate dehydrogenase inhibitor (SDHI) fungicides; (b8) hydroxy(2- amino-)pyrimidine fungicides; (b9) anilinopyrimidine (AP) fungicides; (blO) N-phenyl carbamate fungicides; (bl 1) quinone outside inhibitor (Qol) fungicides; (bl lA) quinone outside inhibitor (Qol) subgroup A fungicides; (bl2) phenylpyrrole (PP) fungicides; (bl3) azanaphthalene fungicides; (bl4) aromatic hydrocarbon and heteroaromatic (AH) fungicides; (bl6.1) melanin biosynthesis inhibitor-reductase (MBI-R) fungicides; (b16.2) melanin biosynthesis inhibitor- dehydratase (MBI-D) fungicides; (bl6.3) melanin biosynthesis inhibitor-polyketide synthase (MBI-P) fungicides; (b17) keto reductase inhibitor (KRI) fungicides (SBI Class III); (bl 8) sterol biosynthesis inhibitor (SBI class IV) fungicides; (bl 9) poly oxin fungicides; (b20) phenylurea fungicides; (b21) quinone inside inhibitor (Qil) fungicides; (b22) benzamide and thiazole carboxamide fungicides; (b23) enopyranuronic acid antibiotic fungicides; (b24) hexopyranosyl antibiotic fungicides; (b25) glucopyranosyl antibiotic fungicides; (b26) formerly glucopyranosyl antibiotic (validamycin) fungicides, reclassified to U18; (b27) cyanoacetamideoxime fungicides; (b28) carbamate fungicides; (b29) oxidative phosphorylation uncoupling fungicides; (b30) organo tin fungicides; (b31) carboxylic acid fungicides; (b32) heteroaromatic fungicides; (b33) formerly phosphonate fungicides, reclassified to P07; (b34) phthalamic acid fungicides; (b35) benzotriazine fungicides; (b36) benzene-sulfonamide fungicides; (b37) pyridazinone fungicides; (b38) thiophene-carboxamide fungicides; (b39) complex I NADH oxido-reductase inhibitor fungicides; (b40) carboxylic acid amide (CAA) fungicides; (b41) tetracycline antibiotic fungicides; (b42) formerly methasulfocarb fungicides, reclassified to M12; (b43) benzamide fungicides; (b44) formerly bacillus amyloliquefaciens strain fungicides, reclassified to BM02; (b45) quinone inside and outside inhibitor, stigmatellin binding (QioSI) fungicides; (b46) formerly extract from melaleuca altemifolia (tea tree oil) and plant oil fungicides, reclassified to BM01; (b47) cyanoacrylate fungicides; (b48) polyene fungicides; (b49) oxy sterol binding protein inhibitor (OSBPI) fungicides; (b50) aryl -phenyl -ketone fungicides; (b51) protein fragment (interaction with lipid fraction of the cell membrane) fungicides; (b52) dihydroorotate dehydrogenase inhibitor (DHODHI) fungicides; (b53) pyridazine fungicides; (b54) benzoxaborole fungicides; and (b55) fungicides other than fungicides of component (a) and components (bl) through (b54); and salts of compounds of (bl) through (b55).

[0745] Further of note is a composition which in addition to the Formula 1 compound of component (a), includes as component (b) at least one fungicidal compound selected from the group consisting of the classes (POI)-(PIO) host plant defense induction fungicides; (M01)-(M12) multisite activity fungicides; and (BM01)-(BM03) biologicals with multiple modes of action.

[0746] Also of note are embodiments wherein component (b) comprises at least one fungicidal compound from each of two different groups selected from (bl) through (b55).

[0747] Further descriptions of groups (bl) through (b55), (POI)-(PIO), (M01)-(M12) and (BM01)- (BM03) are as follows.

[0748] (bl) “Methyl benzimidazole carbamate (MBC) fungicides” (FRAC 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-methyl.

[0749] (b2) “Dicarboximide fungicides” (FRAC code 2) inhibit a mitogen-activated protein (MAP) / histidine kinase in osmotic signal transduction. Examples include chlozolinate, dimethachlone, iprodione, procymidone and vinclozolin.

[0750] (b3) “Demethylation inhibitor (DMI) fungicides” (FRAC code 3) (Sterol Biosynthesis Inhibitors (SBI): Class I) 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 results in abnormal growth and eventually death of sensitive fungi. DMI fungicides are divided between several chemical classes: piperazines, pyridines, pyrimidines, imidazoles, triazoles and triazolinthiones. The piperazines include triforine. The pyridines include buthiobate, pyrifenox, and pyrisoxazole. The pyrimidines include fenarimol and nuarimol. The imidazoles include econazole, imazalil, oxpoconazole, pefurazoate, prochloraz and triflumizole. The triazoles include azaconazole, bitertanol, bromuconazole, cy proconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, ipfentrifluconazole, mefentrifluconazole, metconazole, myclobutanil, penconazole, propiconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, uniconazole, uniconazole-P and methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(l,2,4-triazol- l-yl)propanoate. The triazolinthiones include prothioconazole and fluoxytioconazole. 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.

[0751] (b4) “Phenylamide fungicides” (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 (also known as kiralaxyl), furalaxyl, metalaxyl and metalaxyl-M (also known as mefenoxam). The oxazolidinones include oxadixyl. The butyrolactones include ofurace.

[0752] (b5) “Amine / morpholine fungicides” (FRAC code 5) (SBI: Class II) inhibit two target sites within the sterol biosynthetic pathway, Δ8→Δ7isomerase and A14reductase. 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 morpholines include aldimorph, dodemorph, fenpropimorph and tridemorph. The piperidines include fenpropidin and piperalin. The spiroketal-amines include spiroxamine.

[0753] (b6) “Phospholipid biosynthesis inhibitor fungicides” (FRAC code 6) inhibit growth of fungi by affecting phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phophorothiolate and dithiolane fungicides. The phosphorothiolates include edifenphos, iprobenfos and pyrazophos. The dithiolanes include isoprothiolane. (b7) “Succinate dehydrogenase inhibitor (SDHI) fungicides” (FRAC code 7) inhibit complex II 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. SDHI fungicides include phenylbenzamide, phenyl oxoethylthiophene amide, pyridinylmethyl-benzamide, phenylcyclobutyl-pyridineamide, furan carboxamide, oxathiin carboxamide, thiazole carboxamide, pyrazole-4-carboxamide, N- cyclopropyl-N-benzyl-pyrazole carboxamide, N-methoxy-(phenyl-ethyl)-pyrazole carboxamide, pyridine carboxamide and pyrazine carboxamide fungicides. The phenylbenzamides include benodanil, flutolanil and mepronil. The phenyloxoethyl-thiophene amides include isofetamid. The pyridinylmethyl-benzamides include fluopyram. The phenylcyclobutyl-pyridineamide include cyclobutrifluram. The furan carboxamides include fenfuram. The oxathiin carboxamides include carboxin and oxycarboxin. The thiazole carboxamides include thifluzamide. The pyrazole-4-carboxamides include benzovindiflupyr, bixafen, fluindapyr, flubeneteram, fluxapyroxad, furametpyr, inpyrfluxam, isopyrazam, penflufen, penthiopyrad, pyrapropoyne and sedaxane. The N-cyclopropyl-N-benzyl-pyrazole carboxamides include isoflucypram. The N- methoxy-(phenyl-ethyl)-pyrazole carboxamides include pydiflumetofen. The pyridine carboxamides include boscalid. The pyrazine carboxamides include pyraziflumid.

[0754] (b8) “Hydroxy-(2-amino-)pyrimidine fungicides” (FRAC code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol, ethirimol and triarimol (8).

[0755] (b9) “Anilinopyrimidine fungicides” (FRAC code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydrolytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.

[0756] (b10) “N-Phenyl carbamate fungicides” (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 di ethofencarb.

[0757] (b11) “Quinone outside inhibitor (Qol) fungicides” (FRAC code 11) inhibit complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the “quinone outside” (Qo) site of the cytochrome b(\ 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, methoxyacetamide, methoxycarbamate, oximinoacetate, oximinoacetamide, dihydrodioxazine, and benzyl-carbamates fungicides (collectively also known as strobilurin fungicides), and oxazolidinedione, imidazolinone and benzyl carb am ate fungicides. The methoxyacrylates include azoxystrobin, bifemetstrobin, coumoxystrobin, enoxastrobin (also known as enestroburin), flufenoxystrobin, picoxystrobin and pyraoxystrobin. The methoxyacetamides include mandestrobin. The methoxycarbamates include pyraclostrobin, pyrametostrobin and triclopyricarb. The oximinoacetates include kresoxim-methyl and trifl oxy strobin. The oximinoacetamides include dimoxystrobin, fenaminstrobin, metominostrobin and orysastrobin. The dihydrodioxazines include fluoxastrobin. The oxazolidinediones include famoxadone. The imidazolinones include fenamidone. The benzylcarbamates include pyribencarb.

[0758] (b11A) “Quinone outside inhibitor (Qol) (subgroup A) fungicides” (FRAC code 11A) inhibit fungal respiration the same as FRAC group 11, but subgroup 11A contains fungicides with slightly different binding properties within that site. FRAC code 11 A fungicides are not crossresistant with FRAC code 11 fungicides on pathogens that have developed the G143A mutation. Examples include tetrazolinones such as metyltetraprole

[0759] (b12) “Phenylpyrrole fungicides” (FRAC code 12) inhibit a MAP / histidine kinase associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.

[0760] (b13) “Azanaphthalene fungicides” (FRAC code 13) are proposed to inhibit signal transduction by a mechanism which is as yet unknown. They have been shown to interfere with germination and / or appressorium formation in fungi that cause powdery mildew diseases. Azanaphthalene fungicides include aryloxyquinolines and quinazolinones. The aryloxyquinolines include quinoxyfen. The quinazolinones include proquinazid.

[0761] (b14) “Aromatic hydrocarbon and heteroaromatic (AH) fungicides” (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. Cell peroxidation fungicides include aromatic hydrocarbon and 1,2,4- thiadiazole fungicides. The aromatic hydrocarboncarbon fungicides include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos-methyl. The 1,2,4-thiadiazoles include etridiazole.

[0762] (b 16.1) “Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides” (FRAC code 16.1) inhibit the naphthal reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor-reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. The isobenzofuranones include fthalide. The pyrroloquinolinones include pyroquilon. The triazolobenzothiazoles include tricyclazole.

[0763] (b16.2) “Melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides” (FRAC code 16.2) inhibit scytalone dehydratase in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides. The cyclopropanecarboxamides include carpropamid. The carboxamides include diclocymet. The propionamides include fenoxanil.

[0764] (b16.3) “Melanin biosynthesis inhibitor-polyketide synthase (MBI-P) fungicides” (FRAC code 16.3) inhibit polyketide synthase in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor-polyketide synthase fungicides include trifluoroethylcarbamate fungicides. The trifluoroethylcarbamates include tolprocarb.

[0765] (b17) “Keto reductase inhibitor (KRI) fungicides (SBI Class III)” (FRAC code 17) inhibit 3-keto reductase during C4-demethylation in sterol production. Keto reductase inhibitor fungicides (also known as Sterol Biosynthesis Inhibitors (SBI): Class III) include hydroxyanilides and amino-pyrazolinones. Hydroxyanilides include fenhexamid. Amino-pyrazolinones include fenpyrazamine.

[0766] (b18) “Sterol biosynthesis inhibitor fungicides” (FRAC code 18) (SBI: Class IV) inhibit squalene-epoxidase in the sterol 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 results in abnormal growth and eventually death of sensitive fungi. Sterol biosynthesis inhibitor fungicides include thiocarbamate and allylamine fungicides. The thiocarbamates include pyributicarb. The allylamines include naftifine and terbinafine.

[0767] (b19) “Poly oxin fungicides” (FRAC code 19) inhibit chitin synthase. Examples include polyoxin.

[0768] (b20) “Phenylurea fungicides” (FRAC code 20) are proposed to affect cell division. Examples include pencycuron.

[0769] (b21) “Quinone inside inhibitor (Qil) fungicides” (FRAC code 21) inhibit complex III mitochondrial respiration in fungi by affecting ubiquinone reductase. Reduction of ubiquinone is blocked at the “quinone inside” (Qi) 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, sulfamoyltriazole and picolinamide fungicides. The cyanoimidazoles include cyazofamid. The sulfamoyltriazoles include amisulbrom. The picolinamides include fenpicoxamid, florylpicoxamid, and metarylpicoxamid.

[0770] (b22) “Benzamide and thiazole carboxamide fungicides” (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. The benzamides include toluamides such as zoxamide. The thiazole carboxamides include ethylaminothiazole carboxamides such as ethaboxam. (b23) “Enopyranuronic acid antibiotic fungicides” (FRAC code 23) inhibit growth of fungi by affecting protein biosynthesis. Examples include blasticidin-S.

[0771] (b24) “Hexopyranosyl antibiotic fungicides” (FRAC code 24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin.

[0772] (b25) “Glucopyranosyl antibiotic fungicides” (FRAC code 25) inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.

[0773] (b26) “Glucopyranosyl antibiotic fungicides” (FRAC code U18, previously FRAC code 26 reclassified to U18) are proposed to inhibit trehalase and inositol biosynthesis. Examples include validamycin.

[0774] (b27) “Cyanoacetamideoxime fungicides (FRAC code 27) include cymoxanil.

[0775] (b28) “Carbamate fungicides” (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. lodocarb, propamacarb and prothiocarb are examples of this fungicide class.

[0776] (b29) “Oxidative phosphorylation uncoupling fungicides” (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, and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.

[0777] (b30) “Organo tin fungicides” (FRAC code 30) inhibit adenosine triphosphate (ATP) synthase in oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride and fentin hydroxide.

[0778] (b31) “Carboxylic acid fungicides” (FRAC code 31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.

[0779] (b32) “Heteroaromatic fungicides” (FRAC code 32) are proposed to affect DNA / ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides include isoxazoles, isothiazolones, imino-tosyl pyrimidinones. The isoxazoles include hymexazole, the isothiazolones include octhilinone and imino-tosyl pyrimidinones include flumetylsulforim.

[0780] (b33) “Phosphonate fungicides” (FRAC code P07, previously FRAC code 33 reclassified to P07) include phosphorous acid and its various salts, including fosetyl-aluminum.

[0781] (b34) “Phthalamic acid fungicides” (FRAC code 34) include teclofthalam.

[0782] (b35) “Benzotriazine fungicides” (FRAC code 35) include tri azoxi de.

[0783] (b36) “Benzene-sulfonamide fungicides” (FRAC code 36) include flusulfamide.

[0784] (b37) “Pyridazinone fungicides” (FRAC code 37) include diclomezine.

[0785] (b38) “Thiophene-carboxamide fungicides” (FRAC code 38) are proposed to affect ATP production. Examples include silthiofam. (b39) “Complex I NADH oxidoreductase inhibitor fungicides” (FRAC code 39) inhibit electron transport in mitochondria and include pyrimidinamines such as diflumetorim, pyrazole- 5-carboxamides such as tolfenpyrad and quinazoline such as fenazaquin.

[0786] (b40) “Carboxylic acid amide (CAA) fungicides” (FRAC code 40) inhibit cellulose synthase which 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, flumorph and pyrimorph. The valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valifenalate (also known as valiphenal). The mandelic acid amides include mandipropamid. Carboxylic acid amide fungicides also include trimorphamide.

[0787] (b41) “Tetracycline antibiotic fungicides” (FRAC code 41) inhibit growth of fungi by affecting protein synthesis. Examples include oxytetracy cline.

[0788] (b42) “Thiocarbamate fungicides” (FRAC code 42 reclassified to M12) includes methasulfocarb.

[0789] (b43) “Benzamide fungicides” (FRAC code 43) inhibit growth of fungi by delocalization of spectrin-like proteins. Examples include pyridinylmethyl benzamides such as fluopicolide and fluopimomide.

[0790] (b44) “Bacillus amyloliquefaciens strain fungicides” (FRAC code 44 reclassified to BM02) disrupt fungal pathogen cell membranes. Microbial fungicides include Bacillus species such as Bacillus amyloliquefaciens strains AP-136, AP-188, AP-218, AP-219, AP-295, QST713, FZB24, F727, MB1600, D747, TJ100 (also called strain 1 BE; known from EP2962568), and the fungicidal lipopeptides which they produce.

[0791] (b45) “Quinone inside and outside inhibitor, stigmatellin binding mode (QioSI) fungicides” (FRAC code 45) inhibit complex III mitochondrial respiration in fungi by affecting ubiquinone reductase at the stigmatellin binding sub-site, of the cytochrome bc\ complex. Inhibiting mitochondrial respiration prevents normal fungal growth and development. QioSI fungicides include triazolopyrimidylamines such as ametoctradin.

[0792] (b46) “Plant extract fungicides” (FRAC code 46 reclassified to BM01) cause cell membrane disruption. Plant extract fungicides include terpene hydrocarbons, terpene alcohols and terpen phenols such as the extract from Melaleuca alternifolia (tea tree) and plant oils (mixtures) such as eugenol, geraniol and thymol.

[0793] (b47) “Cyanoacrylate fungicides” (FRAC code 47) bind to the myosin motor domain and effect motor activity and actin assembly. Cyanoacrylates include fungicides such as phenamacril. (b48) “Polyene fungicides” (FRAC code 48) cause disruption of the fungal cell membrane by binding to ergosterol, the main sterol in the membrane. Examples include natamycin (pimaricin).

[0794] (b49) “Oxysterol binding protein inhibitor (OSBPI) fungicides” (FRAC code 49) bind to the oxysterol-binding protein in oomycetes causing inhibition of zoospore release, zoospore motility and sporangia germination. Oxysterol binding fungicides include piperdinyl-thiazole- isoxazolines such as oxathiapiprolin and fluoxapiprolin.

[0795] (b50) “Aryl-phenyl-ketone fungicides” (FRAC code 50, previously FRAC code U8 reclassified to 50) inhibit the growth of mycelium in fungi. Aryl-phenyl ketone fungicides include benzophenones such as metrafenone, and benzoylpyridines such as pyriofenone.

[0796] (b51) “Protein fragment fungicides” induce host plant defense mechanisms. Host plant defense induction fungicides include polypeptide.

[0797] (b52) “Dihydroorotate dehydrogenase inhibitor (DHODHI) fungicides” inhibit dihydroorotate dehydrogenase enzyme within de novo pyrimidine biosynthesis. The DHODH enzyme is crucial for pyrimidine biosynthesis in fungi. By disrupting this pathway, DHODH inhibitors prevent the production of essential nucleotides, ultimately inhibiting fungal growth and proliferation. Dihydroorotate dehydrogenase fungicides include phenyl-propanol such as ipflufenoquin, and dihydroisoquinoline such as quinofumelin.

[0798] (b53) “Pyridazine fungicides” target tubulin dynamics and are considered to have a high risk of resistance development. Pyridazine fungicides include pyridachlometyl.

[0799] (b54) “Benzoxaborole fungicides” inhibitors of leucyl-tRNA synthetase (LeuRS), an enzyme essential for protein synthesis. Benzoxaborole fungicides include tavaborole.

[0800] (P01)-(P10) “Host plant defense induction fungicides” include benzothiadiazole (FRAC code P01), benzisothiazole (FRAC code P02), thiadiazole carboxamide (FRAC code P03), polysaccharide (FRAC code P04), plant extract (FRAC code P05), microbial (FRAC code P06), phosphonate fungicides (FRAC code P07), isothiazolylmethyl ether fungicides (P08), flagellin peptide fungicides (P09) and ascaroside fungicide (PIO). The benzothiadiazoles include acibenzolar-S-methyl. The benzisothiazoles include probenazole. The thiadiazole carboxamides include tiadinil and isotianil. The polysaccharides include laminarin. The plant extracts include extract from Reynoutrici sachalinensis (giant knotweed). The microbials include Bacillus mycoides isolate J and cell walls of Saccharomyces cerevisiae strain LAS117. The phosphonates include fosetyl-Al and phosphorous acid and salts. The isothiazolylmethyl ethers include dichlobentiazox. The flagellin peptides include Flg22-Bt peptide. The ascarosides ascr#18.

[0801] (M01)-(M12) “Multi-site activity fungicides” inhibit fungal growth through multiple sites of action and have contact / preventive activity. Multi-site activity fungicides include copper fungicides (FRAC code M01), sulfur fungicides (FRAC code M02), dithiocarbamate fungicides (FRAC code M03), phthalimide fungicides (FRAC code M04), chloronitrile fungicides (FRAC code M05), sulfamide fungicides (FRAC code M06), multi-site contact guanidine fungicides (FRAC code M07), triazine fungicides (FRAC code M08), quinone fungicides (FRAC codeM09), quinoxaline fungicides (FRAC code MIO), maleimide fungicides (FRAC code M11) and thiocarbamate (FRAC code M12) fungicides. 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 amobam, ferbam, mancozeb, maneb, metiram, propineb, thiram, zinc thiazole, 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 tolyfluanid. Multi-site contact guanidine fungicides include, guazatine, iminoctadine albesilate and iminoctadine triacetate. Triazine fungicides include anilazine. Quinone fungicides include dithianon. Quinoxaline fungicides include quinomethionate (also known as chinomethionate). Maleimide fungicides include fluoroimide. The thiocarbamate fungicides include methasulfocarb.

[0802] (BM01)-(BM03) “Biologicals with multiple modes of action” include agents from biological origins showing multiple mechanisms of action without evidence of a dominating mode of action. This class of fungicides includes polypeptide (lectin), phenol, sesquiterpene, tritepenoid and coumarin fungicides (FRAC code BM01) such as extract from the cotyledons of lupine plantlets. This class also includes momicrobial fungicides (FRAC code BM02), and purified metabolites from plant or microbial sources, or synthetic versions of these metabolite (FRAC code BM03), such as cinnamaldehyde.

[0803] (b55) “Fungicides other than fungicides of component (a) and components (b1) through (b54)”; include certain fungicides whose mode of action may be unknown. These include: (b54.1) “phenyl-acetamide fungicides” (FRAC code U06), (b54.2) “guanidine fungicides” (FRAC code U12), (b54.3) “thiazolidine fungicides” (FRAC code U13), (b54.4) “pyrimidinone-hydrazone fungicides” (FRAC code U14), (b54.5) “4-quinolylacetate fungicides” (FRAC code U16), (54.6) “tetrazolyloxime fungicides” (FRAC code U17) and “glucopyranosyl antibiotic fungicides” (FRAC code U18, see (b26) above). The phenyl-acetamides include cyflufenamid. The guanidines include dodine. The thiazolidines include flutianil. The pyrimidinonehydrazones include ferimzone. The 4-quinolylacetates include tebufloquin. The tetrazolyloximes include picarbutrazox.

[0804] The (b55) class also includes bethoxazin, dichlobentiazox, dipymetitrone, flometoquin, neo- asozin (ferric methanearsonate), flumetylsulforim, pyrrolnitrin, tolnifanide and flufenoxadiazam (HD AC inhibitor), N'-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N- methylmethanimidamide, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine, and 4- fluorophenyl N-[l-[[[l-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate.

[0805] Additional “Fungicides other than fungicides of classes (bl) through (b55)” whose mode of action may be unknown, or may not yet be classified include a fungicidal compound selected from components (b55.7) through (b55.12), as shown below.

[0806] Component (54.7) relates to bifemetstrobin, and component (54.8) relates metcyclofenstrobin which are believed to be a quinone outside inhibitor (Qol) fungicides inhibiting the Complex III mitochondrial respiration in fungi, and is effective against Qol resistant strains.

[0807] Component (54.10) relates to aminopyrifen which is believed to inhibit GWT-1 protein in glycosylphosphatidylinositol-anchor biosynthesis in Neurospora crassa.

[0808] Component (b54.11) relates a compound of Formula b54.11 wherein

[0809] Rb1and Rb3are each independently halogen; and

[0810] Rb2is H, halogen, C1-Cg alkyl, C1-C3haloalkyl or C3-C6cycloalkyl.

[0811] Examples of compounds of Formula b54.11 include (b54.1 la) methyl N-[[5-[l -(2, 6-difluoro-4- formylphenyl)-1H-pyrazol-3-yl]-2-methylphenyl] methyl]carbamate, (b54.1 lb) methyl N-[[5-[l- (4-cyclopropyl-2,6-dichlorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate, (b54.11c) methyl N-[ [5-[l -(4-chl oro-2,6-di fluorophenyl )-1 H-pyrazol -3 -yl]-2-m ethylphenyl ]- methyl]carbamate, (b54.11d)d methyl .N-[[5-[l -(4-cyclopropyl-2,6-difluorophenyl)-1H-pyrazol-3- yl]-2-methylphenyl]methyl]carbamate, (b54.11e) methyl N-[[5-[l-[2,6-difluoro-4-(l- methylethyl)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate and (b54.11f) methyl

[0812] N-[[5-[l-[2,6-difluoro-4-(trifluoromethyl)phenyl]-1H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate. Compounds of Formula b54.11, their use as fungicides and methods of preparation are generally known; see, for example, PCT Patent Publications WO 2008 / 124092, WO 2014 / 066120 and WO 2020 / 097012.

[0813] Component (b54.12) relates to a compound of Formula b54.12 wherein

[0814] Rb4is

[0815] Rb6is C2-C4alkoxycarbonyl or C2-C4haloalkylaminocarbonyl;

[0816] L is CH2or CH2O, wherein the atom to the right is connected to the phenyl ring in Formula b54.12;

[0817] Rb5is

[0818] Rb7is C1-C3alkyl, wherein the wavy bond indicates the adjacent double bond is either (Z)- or (E)-configuration, or a mixture thereof.

[0819] Examples of compounds of Formula b54.12 include (b54.12a) N-(2,2,2-trifluoroethyl)-2-[[4-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-4-oxazolecarboxamide, (b54.12b) ethyl l-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenoxy]methyl]-1H-pyrazole-4-carboxylate, (b54.12c) ethyl l-[[4-[[(lZ)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methyl]-1H- pyrazole-4-carboxylate and (b54.12d) ethyl l-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2- yl]methoxy]phenyl]methyl]-1H-pyrazole-4-carboxylate. Compounds of Formula b54.12, their use as fungicides and methods of preparation are generally known; see, for example, PCT Patent Publications WO 2008 / 187553 and WO 2020 / 056090.

[0820] Therefore, of note is a mixture (i.e. composition) comprising a compound of Formula 1 and at least one fungicidal compound selected from the group consisting of the aforedescribed classes (b1) through (b54), including (b54.7) through (b54.12). Also of note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of particular note is a mixture (i.e. composition) comprising a compound of Formula 1 and at least one fungicidal compound selected from the group of specific compounds listed above in connection with classes (bl) through (b54). Also of particular note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid diluents and liquid diluents.

[0821] Examples of component (b) fungicides include acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl (including benalaxyl- M), benodanil, benomyl, benthiavalicarb (including benthiavalicarb-isopropyl), benzovindiflupyr, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, buthiobate, captafol, captan, carbendazim, carboxin, carpropamid, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper hydroxide, copper oxychloride, copper sulfate, coumoxystrobin, cyazofamid, cyflufenamid, cymoxanil, cy proconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole (including diniconazole-M), dinocap, dithianon, dithiolanes, dodemorph, dodine, dipymetitrone, econazole, edifenphos, enoxastrobin (also known as enestroburin), epoxiconazole, etaconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenaminstrobin, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin chloride, fentin hydroxide, ferbam, ferimzone, flometoquin, florylpicoxamid, fluazinam, fludioxonil, flufenoxystrobin, fluindapyr, flumorph, fluopicolide, fluopimomide, fluopyram, flouroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, fthalide, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hymexazole, imazalil, imibenconazole, iminoctadine albesilate, iminoctadine triacetate, iodocarb, ipconazole, ipfentrifluconazole, iprobenfos, iprodione, iprovalicarb, isoconazole, isofetamid, isoprothiolane, isoflucypram, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandepropamid, mandestrobin, maneb, mepanipyrim, mepronil, meptyldinocap, metalaxyl (including metalaxyl-M / mefenoxam), mefentrifluconazole, metconazole, methasulfocarb, metiram, metominostrobin, metrafenone, miconazole, myclobutanil, naftifine, neo-asozin, nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxathiapiprolin, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, pefurazoate, penconazole, pencycuron, penflufen, penthiopyrad, phosphorous acid (including salts thereof, e.g., fosetyl-aluminum), picarbutrazox, picoxystrobin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamacarb, propi conazole, propineb, proquinazid, prothiocarb, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyrisoxazole, pyroquilon, pyrrolnitrin, quinconazole, quinofumelin, quinomethionate, quinoxyfen, quintozene, sedaxane, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, teclofthalam, tecnazene, terbinafine, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate- methyl, thiram, tiadinil, tolclofos-methyl, tolnifanide, tolprocarb, tolyfluanid, triadimefon, triadimenol, triarimol, triticonazole, triazoxide, tribasic copper sulfate, tricyclazole, triclopyricarb, tridemorph, trifloxystrobin, triflumizole, triforine, trimorphamide, uniconazole, uniconazole-P, validamycin, valifenalate (also known as valiphenal), vinclozolin, zineb, ziram, zoxamide, N-[2-(1S,2R)-[1, 1'-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H- pyrazole-4-carboxamide, α-(l -chlorocyclopropyl)-α-[2-(2,2-dichlorocyclopropyl)ethyl]-1H- 1,2,4-triazole-1 -ethanol, (αS)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]- 3-pyridinemethanol, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]- methyl]-1H-1,2,4-triazole, rel-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2- oxiranyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2- (2,4-difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole, N-[2-[4-[[3-(4- chlorophenyl)-2-propyn-1-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, N'-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5- dimethylphenyl]-N-ethyl- N-methylmethanimidamide, N-[[(cyclopropylmethoxy)amino][6- (difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, N-[2-(2,4-dichlorophenyl)- 2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, N-(3',4'- difluoro[1, 1'-biphenyl]-2-yl)-3-(trifluoromethyl)-2-pyrazinecarboxamide, 3-(difluoromethyl)-N- (2,3 -dihydro- 1 , 1 ,3 -trimethyl- lH-inden-4-yl)- 1 -methyl- lH-pyrazole-4-carboxamide, 5,8-di- fluoro- N-[2-[3-methoxy-4-[[4-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]ethyl]-4-quinazo- linamine, l-[4-[4-[5R-[(2,6-difluorophenoxy)methyl]-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1- piperdinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, 4-fluorophenyl N-[1- [[[l-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, 5-fluoro-2-[(4-fluorophenyl)- m ethoxy ]-4-pyrimidinamine, α-(methoxyimino)- N-methyl-2-[[[l-[3-(trifluoromethyl)phenyl]- ethoxy]imino]methyl]benzeneacetamide, and [[4-methoxy-2-[[[(3S,7R,8R,9S)-9-methyl-8-(2- methyl-1-oxopropoxy)-2,6-dioxo-7-(phenylmethyl)-1,5-dioxonan-3-yl]amino]carbonyl]-3- pyridinyl]oxy]methyl 2-methylpropanoate. Therefore of note is a fungicidal composition comprising as component (a) a compound of Formula 1 (or an N-oxide or salt thereof) and as component (b) at least one fungicide selected from the preceding list.

[0822] Of particular note are combinations of compounds of Formula 1 (or an N-oxide or salt thereof) (i.e. Component (a) in compositions) with aminopyrifen, azoxy strobin, benzovindiflupyr, bixafen, captan, carpropamid, chlorothalonil, copper hydroxide, copper oxychloride, copper sulfate, cymoxanil, cy proconazole, cyprodinil, dichlobentiazox, diethofencarb, difenoconazole, dimethomorph, dipymetitrone, epoxiconazole, ethaboxam, fenarimol, fenhexamid, fluazinam, fludioxonil, fluindapyr, fluopyram, flusilazole, flutianil, flutriafol, fluxapyroxad, folpet, ipflufenoquin, iprodione, isofetamid, isoflucypram, isopyrazam, kresoxim-methyl, mancozeb, mandestrobin, meptyldinocap, metalaxyl (including metalaxyl-M / mefenoxam), mefentrifluconazole, metconazole, metrafenone, myclobutanil, oxathiapiprolin, penflufen, penthiopyrad, phosphorous acid (including salts thereof, e.g., fosetyl-aluminum), picoxystrobin, propiconazole, proquinazid, prothioconazole, pyridachlometyl, pyraclostrobin, pyrapropoyne, pyrimethanil, sedaxane spiroxamine, sulfur, tebuconazole, thiophanate-methyl, trifloxystrobin, zoxamide, α-(l-chlorocyclopropyl)-a-[2-(2,2-dichlorocyclopropyl)ethyl]-1H-1,2,4-triazole-1- ethanol, N-[2-(2,4-dichlorophenyl)-2-m ethoxy- 1 -methylethyl]-3-(difluorom ethyl)- 1 -methyl- 1H- pyrazole-4-carboxamide, 3 -(difluoromethyl)-N-(2, 3 -dihydro- 1,1, 3 -trimethyl- lH-inden-4-yl)-1 - methyl-1H-pyrazole-4-carboxamide, l-[4-[4-[5 / ?-(2,6-difluorophenyl)-4,5-dihydro-3-isox- azolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, 1,1 -dimethylethyl N-[6-[[[[(l-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2- pyridinyl]carbamate, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine, (αS)-[3-(4- chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]-3-pyridinemethanol, rel-1- [[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1H-1,2,4-triazole, rel- 2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1,2-dihydro-3H- l,2,4-triazole-3-thione, and rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiran- yl]methyl]-5-(2-propen- l -ylthio)- lH- L2.4-tri azole (i.e. as Component (b) in compositons).

[0823] 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 A -oxide, or salt thereof, with a fungicidal compound selected from the group: amisulbrom, azoxystrobin, boscalid, carbendazim, carboxin, cymoxanil, cyproconazole, difenoconazole, dimethomorph, dimoxystrobin, fenpropimorph, florylpicoxamid, fluazinam, fludioxonil, flufenoxystrobin, fluindapyr, fluquinconazole, fluopicolide, fluoxastrobin, flutriafol, fluxapyroxad, ipconazole, ipfentrifluconazole, iprodione, kresoxim-methyl, metalaxyl, mefenoxam, mefentrifluconazole, metconazole, metominostrobin, myclobutanil, paclobutrazole, penflufen, picoxystrobin, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyriofenone, sedaxane, silthiofam, tebuconazole, thiabendazole, thiophanate-methyl, thiram, trifloxystrobin and triticonazole.

[0824] Examples of other biologically active compounds or agents with which compounds of this invention can be formulated are: invertebrate pest control compounds or agents such as abamectin, acephate, acetamiprid, acrinathrin, afidopyropen, amidoflumet (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyantraniliprole (3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2- methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide), cyclaniliprole (3- bromo-N-[2-bromo-4-chloro-6-[[(l-cyclopropylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2- pyridinyl)-1H-pyrazole-5-carboxamide), cycloxaprid ((5S,8R)-1-[(6-chloro-3-pyridinyl)methyl]- 2,3,5,6,7,8-hexahydro-9-nitro-5,8-epoxy-1H-imidazo[l,2-rz]azepine), cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflub enzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, flufenoxystrobin (methyl (αE)-2-[[2-chloro-4-(trifluoromethyl)phenoxy]methyl]-α-(methoxymethylene)benzene- acetate), fluensulfone (5-chloro-2-[(3,4,4-trifluoro-3-buten-1-yl)sulfonyl]thiazole), flupiprole (1- [2, 6-dichloro-4-(trifluoromethyl)phenyl]-5-[(2-methyl-2-propen-1-yl)amino]-4-[(tri fluoro- methyl)sulfinyl]- lH-pyrazole-3 -carbonitrile), flupyradifurone (4-[[(6-chloro-3-pyridinyl)- methyl](2,2-difluoroethyl)amino]-2(5H)-furanone), tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, fonophos, halofenozide, heptafluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)- phenyl]methyl 2,2-dimethyl-3-[(lZ)-3,3,3-trifluoro-1-propen-1-yl]cyclopropanecarboxylate), hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, meperfluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl (1R,3S)-3-(2,2-dichloro- ethenyl)-2,2-dimethylcyclopropanecarboxylate), metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxy fenozi de, metofluthrin, milbemycin oxime, momfluorothrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl-3-(2- cyano- 1 -propen- 1 -yl)-2,2-dimethylcyclopropanecarboxylate), monocrotophos, nicotine, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, pyflubumide (l,3,5-trimethyl-N-(2- m ethyl- 1 -oxopropyl)-N-[3 -(2-methylpropyl)-4-[2,2,2-trifluoro- 1 -methoxy- 1 -(trifluoromethyl)- ethyl]phenyl]- 1H-pyrazole-4-carboxamide), parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, pymetrozine, pyrafluprole, pyrethrin, pyridalyl, pyrifluquinazon, pyriminostrobin, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfoxaflor, sulprofos, tebufenozide, teflub enzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon and triflumuron; 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.

[0825] One embodiment of biological agents for mixing with compounds of this disclosure include entomopathogenic bacteria such as Bacillus thuringiensis, and the encapsulated delta-endotoxins of Bacillus thuringiensis such as MVP® and MVPII® bioinsecticides prepared by the CellCap® process (CellCap®, MVP® and MVPII® are trademarks of My cogen Corporation, Indianapolis, Indiana, USA); entomopathogenic fungi such as green muscardine fungus; and entomopathogenic (both naturally occurring and genetically modified) viruses including baculovirus, nucleopolyhedro virus (NPV) such as Helicoverpa zea nucleopolyhedrovirus (HzNPV), Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus (GV) such as Cydia pomonella granulosis virus (CpGV).

[0826] 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.

[0827] For embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound of Formula 1 is typically between about 1 :3000 to about 3000: 1, and more typically between about 1 :500 and about 500: 1. 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.

[0828] In certain instances, combinations of a compound of this invention with other biologically active (particularly fungicidal) 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 fungicidal active ingredients occurs at application rates giving agronomically satisfactory levels of fungal control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.

[0829] Also in certain instances, combinations of a compound of the invention with other biologically active compounds or agents can result in a less-than-additive (i.e. safening) effect on organisms beneficial to the agronomic environment. For example, a compound of the invention may safen a herbicide on crop plants or protect a beneficial insect species (e.g., insect predators, pollinators such as bees) from an insecticide.

[0830] Fungicides of note for formulation with compounds of Formula 1 to provide mixtures useful in seed treatment include but are not limited to amisulbrom, azoxystrobin, boscalid, carbendazim, carboxin, cymoxanil, cyproconazole, difenoconazole, dimethomorph, florylpicoxamid, fluazinam, fludioxonil, flufenoxystrobin, fluquinconazole, fluopicolide, fluoxastrobin, flutriafol, fluxapyroxad, ipconazole, iprodione, metalaxyl, mefenoxam, mefentrifluconazole, metconazole, myclobutanil, paclobutrazole, penflufen, picoxystrobin, prothioconazole, pyraclostrobin, sedaxane, silthiofam, tebuconazole, thiabendazole, thiophanate-methyl, thiram, trifloxystrobin and triticonazole.

[0831] Invertebrate pest control compounds or agents with which compounds of Formula 1 can be formulated to provide mixtures useful in seed treatment include but are not limited to abamectin, acetamiprid, acrinathrin, afidopyropen, amitraz, avermectin, azadirachtin, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyclaniliprole, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta- cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, flubendiamide, fluensulfone, flufenoxuron, flufiprole, flupyradifurone, fluvalinate, formetanate, fosthiazate, heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, meperfluthrin, metaflumizone, methiocarb, methomyl, methoprene, methoxyfenozide, momfluorothrin, nitenpyram, nithiazine, novaluron, oxamyl, pyflubumide, pymetrozine, pyrethrin, pyridaben, pyriminostrobin, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, strains of Bacillus thuringiensis and strains of Nucleo polyhydrosis viruses.

[0832] Compositions comprising compounds of Formula 1 useful for seed treatment can further comprise bacteria and fungi that have the ability to provide protection from the harmful effects of plant pathogenic fungi or bacteria and / or soil born animals such as nematodes. Bacteria exhibiting nematicidal properties may include but are not limited to Bacillus firmus, Bacillus cereus, Bacillius subtiliis and Pasteuria penetrans. A suitable Bacillus firmus strain is strain CNCM I- 1582 (GB-126) which is commercially available as BioNem™. A suitable Bacillus cereus strain is strain NCMM 1-1592. Both Bacillus strains are disclosed in US 6,406,690. Other suitable bacteria exhibiting nematicidal activity are B. amyloliquefaciens IN937a and B. subtilis strain GB03. Bacteria exhibiting fungicidal properties may include but are not limited to B. pumilus strain GB34. Fungal species exhibiting nematicidal properties may include but are not limited to Myrothecium verrucaria. Paecilomyces lilacinus and Purpureocillium lilacinum.

[0833] Seed treatments can also include one or more nematicidal agents of natural origin such as the elicitor protein called harpin which is isolated from certain bacterial plant pathogens such as Erwinia amylovora. An example is the Harpin-N-Tek seed treatment technology available as N- Hibit™ Gold CST.

[0834] Seed treatments can also include one or more species of legume-root nodulating bacteria such as the microsymbiotic nitrogen-fixing bacteria Bradyrhizobium japonicum. These inocculants can optionally include one or more lipo-chitooligosaccharides (LCOs), which are nodulation (Nod) factors produced by rhizobia bacteria during the initiation of nodule formation on the roots of legumes. For example, the Optimize® brand seed treatment technology incorporates LCO Promoter Technology™ in combination with an inocculant.

[0835] Seed treatments can also include one or more isoflavones which can increase the level of root colonization by mycorrhizal fungi. Mycorrhizal fungi improve plant growth by enhancing the root uptake of nutrients such as water, sulfates, nitrates, phosphates and metals. Examples of isoflavones include, but are not limited to, genistein, biochanin A, formononetin, daidzein, glycitein, hesperetin, naringenin and pratensein. Formononetin is available as an active ingredient in mycorrhizal inocculant products such as PHC Colonize® AG.

[0836] Seed treatments can also include one or more plant activators that induce systemic acquired resistance in plants following contact by a pathogen. An example of a plant activator which induces such protective mechanisms is acibenzolar-S'-methyl.

[0837] The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Tables A through E below for compound descriptions. The following abbreviations are used in the Index Tables: Me means methyl and c-Pr means cyclopropyl. 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 numerical value reported in the column “MS” is the molecular weight of the highest isotopic abundance positively charged parent ion (M+1) formed by addition of H+ (molecular weight of 1) to the molecule having the highest isotopic abundance, or the highest isotopic abundance negatively charged ion (M-l) formed by loss of H+ (molecular weight of 1). The reported MS peaks were observed by mass spectrometry using electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI).

[0838] For the structures in column A, the bond extending to the left is attached to C=O, and the bond extending to the right is attached to the phenyl ring. A dash "-" in the R5column means that no substituent is present, and the remaining valence is occupied by hydrogen. INDEX TABLE C

[0839] INDEX TABLED

[0840] INDEX TABLE F

[0841] BIOLOGICAL EXAMPLES OF THE INVENTION

[0842] General protocol for preparing test suspensions for Tests A-E: 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 by volume) containing 250 ppm of the surfactant PEG400 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-E.

[0843] TEST A

[0844] The test solution was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septaria tritici (the causal agent of wheat leaf blotch) and incubated in a saturated atmosphere at 24 °C for 48 h, and then moved to a growth chamber at 20 °C for 19 days, after which time disease ratings were made.

[0845] TEST B

[0846] 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 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.

[0847] TEST C

[0848] 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 a 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.

[0849] TEST D

[0850] 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 3 days, after which time visual disease ratings were made.

[0851] TEST E

[0852] The test solution was sprayed to the point of run-off on grape seedlings. The following day the seedlings were inoculated with a spore suspension of Plasmopara viticoki (the causal agent of grape downy mildew) 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 disease ratings were made.

[0853] Results for Tests A-E are given in Table A below. A rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates the compound was not tested at the rate listed. TABLE A

Claims

CLAIMSWhat is claimed is:

1. A compound selected from Formula 1, tautomers, N-oxides. and salts thereof,whereinQ is selected fromwherein the bond extending to the right is attached to CR1Y; and m is 0, 1 or 2;R1is H, cyano, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy or C1-C4haloalkoxy;Y is selected fromwherein the floating bond is attached to Formula 1 through any available carbon atom that is adjacent to any nitrogen atom of the depicted ring; and n is 0, 1, 2 or 3;R2and R3are each independently H or C1-C4alkyl;R4is H, amino, C2-C4alkenyl, C3-C6cycloalkyl, CH(=O), S(=O)2OM, S(=O)uR7, (C=O)R8or OR9; or C1-C3alkyl or C1-C3haloalkyl, each optionally substituted with up to 1 substituent selected from R4a;M is K or Na; u is 0, 1 or 2;R4ais cyano, C3-C6cycloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl or C1-C3alkylsulfonyl;W is 0 or S;A is A1or A2;wherein the bond extending to the left is attached to C=W , and the bond extending to the right is attached to Z; and q is 0, 1 or 2;A2is a 6-membered nonaromatic ring, each ring containing ring members selected from carbon atoms and optionally up to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N atoms, wherein up to 2 ring members are independently selected from C(=O), C(=S), S(=O) and S(=O)2, each ring optionally substituted with up to 3 substituents independently selected from R11;A2is a 6-membered heteroaromatic ring, each ring optionally substituted with up to 3 substituents independently selected from R11;Z is phenyl optionally substituted with up to 4 substituents independently selected from R12; or a 5- to 6-membered heteroaromatic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N atoms, each ring optionally substituted with up to 4 substituents independently selected from R12; or a 5- to 6-membered nonaromatic ring, each ring containing ring members selected from carbon atoms and optionally up to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N atoms, wherein up to 2 ring members are independently selected from C(=O), C(=S), S(=O) and S(=O)2, each ring optionally substituted with up to 4 substituents independently selected from R12; each R5ais independently halogen, cyano, hydroxy, nitro, C1-C4alkyl, C1-C4haloalkyl, C2-C4alkenyl, C2-C4alkynyl, C3-C4cycloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C2-C4alkenyloxy, C2-C4alkynyloxy, C1-C4alkylthio, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl, C2-C4alkylcarbonyl or C2-C4alkoxy carbonyl;R5bis H, C1-C4alkyl, C1-C4haloalkyl, C2-C4alkenyl, C2-C4alkynyl or cyclopropyl; each R6is independently halogen, cyano, amino, hydroxy, nitro, CH(=O), C(=O)0H, NR13aR13b, c(=O)NR13aR13b, C(R14)=NR15, -U-V-T or C3-C15trialkylsilyl; or C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkoxy, C2-C6alkenyloxy, C2-C6alkynyloxy, C3-C6cycloalkoxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6alkylaminosulfmyl, C2-C6dialkylaminosulfinyl, C1-C6alkylsulfonyloxy, C1-C6alkylsulfonylamino, C2-C6alkylcarbonyl, C2-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, C2-C6alkylcarbonyloxy, C2-C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy or C2-C6alkylaminocarbonylamino, each optionally substituted with up to 3 substituents independently selected from R16;R7is C1-C3alkyl or C1-C3alkoxy;R8is C1-C3alkyl, C1-C3alkoxy or C1-C3alkylthio;R9is H, CH(=O), C1-C3alkyl, C1-C3haloalkyl, C3-C6cycloalkyl or S(=O)2OM; each R10is independently halogen, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy or C1-C3haloalkoxy; each R11is independently halogen, cyano, C1-C3alkyl, C1-C3haloalkyl, C2-C3alkenyl, C2-C3haloalkenyl, C1-C3alkoxy or C1-C3haloalkoxy; each R12is independently halogen, cyano, hydroxy, nitro, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6alkenyloxy, C2-C6alkynyloxy, C1-C6alkylsulfinyloxy, C1-C6alkylsulfonyloxy, C2-C6alkylcarbonyl or C2-C6alkoxy carbonyl;each R13ais independently H, C1-C3alkyl, C2-C4alkenyl, C2-C4alkylcarbonyl or C2-C4alkoxycarbonyl; each R13bis independently H, cyano, hydroxy, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6alkoxyalkyl, C2-C6alkylcarbonyl, C2-C6haloalkylcarbonyl or C2-C6alkoxycarbonyl; each R14is independently H, cyano, halogen, C1-C2alkyl or C1-C2alkoxy; each R15is independently hydroxy, C1-C4alkyd, C1-C4alkoxy, C2-C4alkenyloxy, C2-C4alkynyloxy, C2-C4alkylcarbonyloxy or C2-C4alkoxycarbonyloxy; each U is independently a direct bond, C(=O)O or C(=O)NH, wherein the atom to the left is attached to Formula 1, and the atom to the right is connected to V; each V is independently a direct bond, C1-C3alkylene, C2-C3alkenylene, C3-C3alkynylene, C3-C6cycloalkylene or C3-C6cycloalkenylene; each T is independently phenyl optionally substituted with up to 3 substituents independently selected from R17; or each T is independently a 5- to 6-membered heteroaromatic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N atoms, each ring optionally substituted with up to 2 substituents independently selected from R17; or each T is independently a 3- to 6-membered nonaromatic heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N atoms, wherein up to 2 ring members are independently selected from C(=O), C(=S), S(=O) and S(=O)2, each ring optionally substituted with up to 2 substituents independently selected from R17; each R16is independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl, C3-C6cycloalkyl, C1-C2alkoxy, C1-C2haloalkoxy, C2-C3alkylcarbonyl, C2-C3haloalkylcarbonyl, C2-C3alkoxy carbonyl, C2-C3haloalkoxy carbonyl or C3-C15trialkylsilyl; and each R17is independently halogen, cyano, C1-C2alkyl, C1-C2haloalkyl or C1-C2alkoxy.

2. A compound Claim 1 whereinQ is Q-1, Q-5, Q-9 or Q-11; m is 0 or 1;R1is methyl;Y is Y-1; n is 1 or 2;R2and R3are each H;R4is H;W is 0;A is A1;A1is A1-1, A1-2 or A1-10; q is 0;Z is selected fromwherein the floating bond is connected to A in Formula 1 through any available carbon atom of the depicted ring; and x is 1 or 2;R5ais halogen or methyl;R5bis C1-C2alkyl; each R6is independently halogen or cyano; or C1-C3alkyl or C1-C3alkoxy, each optionally substituted with up to 1 substituent selected from R16; each R12is independently halogen, C1-C3alkyl, C1-C3haloalkyl or C1-C3alkoxy; and each R16is independently halogen, methyl, halomethyl or methoxy.

3. A compound Claim 2 whereinQ is Q-1, Q-5 or Q-11; n is 1;A1is A1-1 or A1-10;Z is Z-40;R5ais methyl;R5bis methyl;R6is halogen, cyano, methyl or methoxy; and each R12is independently halogen, methyl or methoxy.

4. A compound Claim 3 whereinQ is Q-1 or Q-5; m is 0;A1is A1-1;R6is halogen; and each R12is independently halogen.

5. A compound Claim 4 whereinQ is Q-5;R6is Cl or F; and each R12is independently Cl or F.

6. A compound Claim 1 whereinQ is Q-1, Q-5, Q-8, Q-9, Q-11 or Q-14; m is 0 or 1;R1is H, methyl or ethyl;Y is Y-1 or Y-5; n is 0 or 1;R2and R3are each H;R4is H, methyl or ethyl;W is 0;A is A1;A1is A1-1, A1-3, A1-4, A1-5, A1-6, A1-8 or A1-10; q is 0;Z is selected fromwherein the floating bond is connected to A in Formula 1 through any available carbon atom of the depicted ring; and x is 0, 1, 2 or 3; each R5ais independently halogen, cyano, methyl, ethyl or C3-C4cycloalkyl;R5bis C1-C2alkyl; each R6is independently halogen, cyano; or C1-C3alkyl, C2-C4alkenyl, C2-C4alkynyl, C3-C6cycloalkyl or C1-C3alkoxy, each optionally substituted with up to 3 substituents independently selected from R16; each R12is independently halogen, cyano, C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy or C2-C4alkylcarbonyl; and each R16is independently halogen, C1-C2alkyl, C1-C2haloalkyl, C1-C2alkoxy or trimethyl silyl.

7. A compound Claim 6 whereinQ is Q-1, Q-5 or Q-14;R1is methyl or ethyl;Y is Y-1; n is 1;R4is H;A1is A1-1, A1-4, A1-6, A1-8 or A1-10;Z IS Z-40 or Z-41; x is 1 or 2; each R5ais independently methyl, ethyl or cyclopropyl;R5bis methyl; each R6is independently halogen, cyano; or C1-C2alkyl, C2-C3alkenyl, C2-C3alkynyl, cyclopropyl or C1-C2alkoxy, each optionally substituted with up to 3 substituents independently selected from R16; each R12is independently halogen or methoxy; and each R16is independently halogen.

8. A compound Claim 7 whereinQ is Q-5 or Q-14;R1is methyl;A1is A1-1 or A1-10;Z is Z-40; each R5ais methyl; each R6is independently Cl, Br, cyano, methyl, trifluoromethyl or methoxy; and each R12is independently Cl or F.

9. A compound Claim 8 whereinA1is A1-1; m is 0; and each R6is independently Cl or methyl.

10. A compound of Claim 1 which is selected from the group:N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-5-(2,4- difluorophenyl)-3-isoxazolecarboxamide;5-(2,4-difluorophenyl)-N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4- yl)propyl]-3-isoxazolecarboxamide;2-(2,4-difluorophenyl)-N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4- yl)propyl]-2H-tetrazole-5-carboxamide;N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-5-(2,4- difluorophenyl)-1,2,4-oxadiazole-3-carboxamide;N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-2-(2,4- difluorophenyl)-2H-tetrazole-5-carboxamide;N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-3-(2,4- difluorophenyl)-1,2,4-oxadiazole-5-carboxamide;N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-1-(2,4- difluorophenyl)-1H-1,2,3-triazole-4-carboxamide;N-[2-(6-chloro-2-pyridinyl)-2-(l-methyl-1H-1,2,4-triazol-3-yl)propyl]-5-(2,4- difluorophenyl)-3-isoxazolecarboxamide;N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(2,4-di fluorophenyl)- 3-isoxazolecarboxamide;N-[2-(6-chloro-2-pyridinyl)-2-(l-methyl-1H-1,2,3-triazol-4-yl)propyl]-5-(2,4- difluorophenyl)-3-isoxazolecarboxamide;N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(2.4-difluorophenyl)-1,3,4-thiadiazolecarboxamide;N-[2-(6-methyl-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(2,4-di fluorophenyl)- 1,3,4-thiadiazolecarboxamide;N-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-1,2,3-triazol-4-yl)propyl]-5-(3,5-difluoro-2- pyridinyl)-3-isoxazolecarboxamide; andN-[2-(6-chloro-2-pyridinyl)-2-(2-methyl-2H-tetrazol-5-yl)propyl]-5-(3,5-difluoro-2- pyridinyl)-3-isoxazolecarboxamide.

11. A fungicidal composition comprising (a) a compound of Claim 1 ; and (b) at least one other fungicide.

12. A fungicidal composition comprising (a) a compound of Claim 1; and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.

13. 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 Claim 1.

14. A compound selected from Formula 6, N-oxides. and salts thereof,whereinQ is Q-1, Q-5, Q-8, Q-9, Q-11 or Q-14; m is 0 or 1;R1is H, methyl or ethyl; R5ais halogen or methyl; andR5bis C1-C2alkyl.

Images