Substituted tolyl fungicides and mixtures thereof

Abstract

Disclosed is a fungicidal composition comprising: (a) at least one compound selected from the group consisting of compounds of Formula 1 (including all geometric and stereoisomers), N-oxides, and salts thereof, wherein A, Q, R 1 , R 2 , R 3 , R 4 , W, and Y are as defined in the disclosure; and (b) at least one additional fungicidal compound. Also disclosed is a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or plant seed, a fungicidally effective amount of a compound of Formula 1, N-oxide, or salt thereof (e.g., as a component in the above composition). Also disclosed is a composition comprising: (a) at least one compound selected from the group consisting of compounds of Formula 1, N-oxides, and salts thereof described above; and at least one invertebrate pest control compound or agent.

Description

TECHNICAL FIELD

[0001] The present invention relates to certain tolyl derivatives, N-oxides, and salts thereof, and to mixtures and compositions comprising such tolyl derivatives and to methods of using such tolyl derivatives and mixtures and compositions thereof as fungicides. BACKGROUND

[0002] Controlling plant diseases caused by fungal plant pathogens is of utmost importance to achieve high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant yield loss and thus result in increased costs to the consumer. In addition to often being highly destructive, plant diseases can be difficult to control and can develop resistance to commercial fungicides. Numerous products are commercially available for these purposes, but there is a continuing need for new fungicidal compounds that are more effective, less costly, less toxic, more environmentally safe, or have different sites of action. In addition to the introduction of new fungicides, combinations of fungicides are often used to promote disease control, expand the spectrum of control, and delay the development of resistance. Furthermore, certain rare fungicide combinations exhibit more than additive (i.e., synergistic) action to provide commercially important levels of plant disease control. The advantages of particular fungicide combinations are recognized in the art to be different, depending on factors such as the particular plant species and plant disease to be treated, and whether the plant is treated before or after infection by the fungal plant pathogen. Thus, there is a need for new advantageous combinations to provide various options to best meet the particular plant disease control needs. Such combinations have now been discovered.

[0003] PCT patent publications WO 2008 / 124092, WO 2011 / 059619, WO 2014 / 066120, WO 2015 / 157005, and WO 2020 / 097012 disclose tolyl derivatives and methods of using such derivatives as fungicides. SUMMARY

[0004] The present invention relates to a fungicidal composition (i.e., combination, mixture) comprising

[0005] (a) at least one compound selected from the group consisting of compounds of Formula 1 (including all stereoisomers), N-oxides, and salts thereof,

[0006]

[0007] wherein

[0008] A is a group selected from the group consisting of:

[0009]

[0010] wherein the bond extending to the right is attached to the Q-containing ring and the bond extending to the left is attached to the Y-N(R 3 )C(=W)R 4 substituted phenyl ring;

[0011] Q is CR 6 or N;

[0012] Y is CR 7a R 7b , O or NR 8 ;

[0013] W is O or S;

[0014] R 1 and R 2 are each independently halogen, cyano, hydroxy, nitro, amino, Ci-C6alkyl, Ci-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C2-C6cyanoalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C4-C8cycloalkylalkyl, C2-C6alkoxyalkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, C2-C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyloxy, C2-C6haloalkynyloxy, C2-C6cyanoalkoxy, C3-C6cycloalkoxy, C4-C8cycloalkylalkoxy, C2-C6alkoxyalkoxy, Ci-C6alkylthio, Ci-C6haloalkylthio, Ci-C6alkylsulfinyl, Ci-C6haloalkylsulfinyl, Ci-C6alkylsulfonyl or Ci-C6haloalkylsulfonyl;

[0015] R 3 is H, Ci-C3alkyl, Ci-C3haloalkyl, cyclopropyl, C2-C4alkylcarbonyl, C2-C4haloalkylcarbonyl, C2-C4alkoxycarbonyl or C2-C4haloalkoxycarbonyl;

[0016] R 4 is Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylamino or C2-C4dialkylamino;

[0017] each R 5 is independently halogen, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy or Ci-C3haloalkoxy;

[0018] n is 0, 1 or 2;

[0019] R 6H, halogen, cyano, hydroxyl, nitro, amino, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C2-C6cyanoalkyl, C1-C6hydroxyalkyl, C2-C6alkoxyalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyloxy, C2-C6haloalkynyloxy, C2-C6cyanoalkoxy, C2-C6alkoxyalkoxy, C1-C6alkylamino, C1-C6haloalkylamino, C2-C6dialkylamino, C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkylsulfinyl, C1-C6haloalkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, -ZC(=O)V, CR 10a = NOR 10b , ON=CR 11a R 11b , CR 12a =NNR 12b R 12c or -L-J;

[0020] R 7a is H, hydroxyl, halogen, cyano, C1-C3alkyl, C1-C3haloalkyl, C2-C3alkoxyalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylsulfinyl, or C1-C3alkylsulfonyl;

[0021] R 7b is H, C1-C3alkyl, C1-C3haloalkyl, C2-C3alkoxyalkyl, C1-C3alkoxy, or C1-C3haloalkoxy;

[0022] R 8 is H, C1-C3alkyl, C1-C3haloalkyl, C2-C3alkylcarbonyl, or C2-C3haloalkylcarbonyl;

[0023] Z is a direct bond, O, S, or NH; or CH2optionally substituted with up to two substituents independently selected from halogen, methyl, or methoxy;

[0024] V is R 9 or OR 9 ;

[0025] R 9 , R 10b , R 11a , and R 12ceach independently H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C4-C8 cycloalkylalkyl;

[0026] R 10a , R 11b , R 12a , and R 12b each independently H, C1-C3 alkyl, or C1-C3 haloalkyl;

[0027] L is a direct bond, CH2, O, S, NR 13 , OCH2, CH2O, C(=O), S(=O), or S(=O)2;

[0028] J is a 3- to 6-membered non-aromatic carbocyclic ring, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), each ring being optionally substituted with up to 4 substituents independently selected from R 14 ; or

[0029] J is a 3- to 6-membered heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2 O atoms, up to 2 S atoms, and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), each ring being optionally substituted with up to 4 substituents independently selected from R 14 ;

[0030] R 13 is H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C3 alkylcarbonyl, or C2-C3 haloalkylcarbonyl;

[0031] each R 14 is independently halogen, hydroxyl, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C1-C4 alkoxy, C1-C4 haloalkoxy, or C(=O)OR 15 ; and

[0032] each R 15 is independently H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, or C3-C6 halocycloalkyl; and

[0033] (b) at least one additional fungicidal compound.

[0034] The present application also relates to a composition comprising: (a) at least one compound chosen from the compounds of Formula 1, N-oxides, and salts thereof described above; and at least one additional component chosen from the group consisting of a surfactant, a solid diluent, and a liquid diluent.

[0035] The present application also relates to a composition comprising one of the above compositions comprising component (a) and at least one additional component chosen from the group consisting of a surfactant, a solid diluent, and a liquid diluent.

[0036] The present application also relates to a method for controlling a plant disease caused by a fungal plant pathogen, the method comprising applying to the plant or portion thereof, or plant seed, a fungicidally effective amount of one of the above compositions.

[0037] The above method can also be described as a method for protecting a plant or plant seed from a disease caused by a fungal pathogen, the method comprising applying to the plant (or portion thereof) or plant seed a fungicidally effective amount of one of the above compositions (directly or through the environment of the plant or plant seed, e.g., the growth medium).

[0038] The present application also relates to a compound of Formula 1, N-oxides, or salts thereof described above. DETAILED DESCRIPTION

[0039] 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, a mixture, a process, a method, an article, or an apparatus that comprises a list of elements is not necessarily limited to only those elements but can include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus.

[0040] The conjunctive phrase "consisting of limits any unrecited elements, steps, or ingredients. If in a claim, this phrase will make the claim closed, excluding materials not stated in the claim, except for impurities ordinarily associated with the subject matter. When the phrase "consisting of appears in a clause of the body of the claim rather than immediately following the preamble, the phrase limits only the elements recited in that clause; in its entirety, the claim is not exclusive of other elements.

[0041] The transitional phrase "consisting essentially of limits the combination of materials, steps, features, components, or elements to those that do not materially affect the basic and novel characteristics of the claimed invention. The term "consisting essentially of is intermediate between "comprising" and "consisting of."

[0042] When the application or a portion thereof is defined by open terms such as "comprising," it should be readily understood (unless otherwise indicated) that the description is to be interpreted to also describe the application using the terms "consisting of or "consisting essentially of.

[0043] Furthermore, "or" is used herein in its inclusive sense, and not in its exclusive sense that means either whatsoever unless otherwise indicated (e.g., "comprises" or "comprising" means both "includes" and "including" but also "consists of" and "consisting of").

[0044] In addition, the indefinite articles "a" and "an" preceding an element or component of the application are intended to be non-limiting regarding the quantity of such element or component. As a result, the terms "a" and "an" should be interpreted to include one or at least one, and the singular word form "the" should be interpreted to include plural aspects, unless the context clearly indicates otherwise.

[0045] The term "agronomic" refers to the production of field crops such as those used for food and fiber, and includes the growth of maize or corn, soybeans and other legumes, rice, cereals (e.g., wheat, oats, barley, rye, and rice), leafy vegetables (e.g., lettuce, cabbage, and other brassica crops), fruiting vegetables (e.g., tomatoes, peppers, eggplants, crucifers, and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone, and citrus), small fruits (e.g., berries and cherries), and other specialty crops (e.g., canola, sunflower, and olives).

[0046] The term "non-agronomic" refers to applications that are not 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 farms, pastures, golf courses, lawns, athletic fields, etc.), wood products, stored products, forestry and vegetation management, public health (i.e., human) and animal health (e.g., domestic animals such as pets, livestock, and poultry, and non-domestic animals such as wildlife).

[0047] The term "crop vigor" refers to the rate of growth or biomass accumulation of a crop plant. An "increase in vigor" refers to an increase in growth or biomass accumulation of a crop plant relative to an untreated control crop plant. The term "crop yield" refers to the return in quantity and quality of crop material 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.

[0048] The term "biologically effective amount" refers to the amount of a biologically active compound (e.g., a compound of Formula 1) sufficient to effect a desired biological result when applied to (i.e., contacted with) a fungus to be controlled or its environment, or a plant, a seed from which the plant grows, or a locus of the plant (e.g., a growth medium) to protect the plant from damage by a fungal disease or for other desired effects (e.g., increasing plant vigor).

[0049] As referred to in the present disclosure and claims, "plants / plant" includes members of the plant kingdom at all life stages, particularly Spermatopsida, at all life stages including young plants (e.g., developing seedlings from germinated seeds) and mature, reproductive stages (e.g., flowering and seed-producing plants). Parts of a plant include both geotropic members such as roots, tubers, bulbs, and corms that typically grow below the surface of a growth medium (e.g., soil), and also members that grow above the growth medium such as leaves (including stems and foliage), flowers, fruits, and seeds.

[0050] As referred to herein, the term "seedling" used alone or in combination with the word "plant" refers to a young plant developed from the embryo of a seed.

[0051] As referred to herein, the term "broadleaf" used alone or in combination with a word such as "broadleaf crop" refers to a dicot or dicotyledon, a term used to describe a group of angiosperms characterized by embryos with two cotyledons.

[0052] As referred to in the present disclosure, the terms "fungal pathogen" and "fungal plant pathogen" include pathogens in the phyla Ascomycota, Basidiomycota, and Zygomycota, as well as the fungal-like Oomycota class, which are causative agents of a broad spectrum of economically important plant diseases affecting ornamental, turf, vegetable, field, cereal, and fruit crops. In the context of the present disclosure, "protecting a plant from disease" or "controlling a plant disease" includes prophylactic action (interrupting the cycle of infection, colonization, symptom development, and spore production of a fungus) and / or therapeutic action (inhibiting colonization of plant host tissues).

[0053] As used herein, the term "mode of action" (MOA) is as defined by the Fungicide Resistance Action Committee (FRAC) and is used to distinguish fungicides according to their biochemical mode of action in the biosynthetic pathway of the plant pathogen and their resistance risk. The FRAC-defined modes of action include (A) nucleic acid synthesis, (B) mitosis and cell division, (C) respiration, (D) amino acid and protein synthesis, (E) signal transduction, (F) lipid synthesis and membrane integrity, (G) sterol biosynthesis in the membrane, (H) cell wall biosynthesis, (I) melanin biosynthesis in the cell wall, (P) host plant defense induction, (U) unknown mode of action, (NC) not classified, (M) multi-site contact activity, and (BM) biological agents with multiple modes of action. Each mode of action (i.e., the letters A through BM) contains one or more subgroups (e.g., A includes subgroups Al, A2, A3, and A4) that are based on individually validated target sites of action, or in cases where the precise target site is not known, based on cross-resistance characteristics within or with other groups. Each of these subgroups (e.g., Al, A2, A3, and A4) is assigned a FRAC code (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, for example, a publicly available database maintained by FRAC.

[0054] As used herein, the term "cross-resistance" refers to the phenomenon that occurs when a pathogen becomes resistant to one fungicide and at the same time becomes resistant to one or more other fungicides. These other fungicides are typically, but not always, of the same chemical class or have the same target site of action, or can be detoxified by the same mechanism.

[0055] Generally, when a molecular fragment (i.e., a radical) is represented by a series of atomic symbols (e.g., C, H, N, O, and S), one or more points of attachment will be readily identified by one of skill in the art. In some instances herein, particularly where an alternative point of attachment is possible, one or more points of attachment can be represented by a hyphen (“-”). For example, “-NCS” indicates that the point of attachment is a nitrogen atom (i.e., isothiocyanato, rather than thiocyanato).

[0056] As used herein, the term “alkylating agent” refers to a compound in which a carbon- containing group is bonded to a leaving group such as a halide or sulfonate ester through a carbon atom, which can be displaced by the bonding of a nucleophile to the carbon atom. Unless otherwise specified, the term “alkylation” does not limit the carbon-containing group to an alkyl group; carbon-containing groups in alkylating agents include, for example, for R 1 and R 2 various carbon-bonded substituent groups as specified.

[0057] In the above detailed description, the term "alkyl", used alone or in a compound word such as "alkylthio" or "haloalkyl", includes straight-chain or branched-chain alkyl groups such as methyl, ethyl, n-propyl and i-propyl, or the various butyl, pentyl, or hexyl isomers. "Alkenyl" includes straight-chain or branched-chain alkenes such as ethenyl, 1- propenyl, 2-propenyl, and the various butenyl, pentenyl, and hexenyl isomers. "Alkenyl" also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched-chain alkynes such as ethynyl, 1-propynyl, 2-propynyl, and the various butynyl, pentynyl, and hexynyl isomers. "Alkynyl" can also include moieties composed of multiple triple bonds such as 2,5-hexadiynyl.

[0058] "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, i-propyloxy, and the various butyloxy, pentyloxy, and hexyloxy isomers. "Alkoxyalkyl" denotes alkoxy substitution on an alkyl group. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2, and CH3CH2OCH2CH2. "Alkenyloxy" includes straight-chain or branched-chain alkenyl groups attached to and linked by an oxygen atom. Examples of "alkenyloxy" include H2C=CHCH2O, (CH3)2C=CHCH2O, CH3CH=CHCH2O, CH3CH=C(CH3)CH2O, and CH2=CHCH2CH2O. "Alkynyloxy" includes straight-chain or branched-chain alkynyl groups attached to and linked by an oxygen atom. Examples of "alkynyloxy" include HC≡CCH2O, CH3C≡CCH2O, and CH3C≡CCH2CH2O. "Alkoxyalkyloxy" denotes alkoxy substitution on another alkoxy moiety. Examples of "alkoxyalkyloxy" include CH3OCH2O, CH3OCH2O, and CH3CH2OCH2O.

[0059] "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the various propylthio, butylthio, pentylthio, and hexylthio isomers. "Alkylsulfinyl" includes both enantiomers of alkylsulfinyl. Examples of "alkylsulfinyl" include CH3S(=O), CH3CH2S(=O), CH3CH2CH2S(=O), (CH3)2CHS(=O), and the various butylsulfinyl, pentylsulfinyl, and hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH3S(=O)2, CH3CH2S(=O)2, CH3CH2CH2S(=O)2, (CH3)2CHS(=O)2, and the various butylsulfonyl, pentylsulfonyl, and hexylsulfonyl isomers.

[0060] "Alkylamino" includes NH groups substituted with straight-chained or branched alkyl groups. Examples of "alkylamino" include CH3NH, CH3CH2NH, CH3CH2CH2NH, and (CH3)2CHNH. Examples of "dialkylamino" include (CH3)2N, (CH3CH2)2N, and CH3CH2(CH3)N.

[0061] The term "cycloalkyl" denotes a saturated carbocyclic ring consisting of between 3 and 6 carbon atoms connected to each other by single bonds. Examples of "cycloalkyl" include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl group. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chained or branched alkyl groups. The term "cycloalkoxy" denotes a cycloalkyl group attached to and linked by an oxygen atom, such as cyclopentoxy and cyclohexoxy. "Cycloalkylalkoxy" denotes cycloalkyl substitution on an alkoxy group. Examples of "cycloalkylalkoxy" include cyclopropylmethoxy, cyclopentylethoxy, and other cycloalkyl moieties bonded to straight-chained or branched alkoxy groups.

[0062] "Alkylcarbonyl" denotes straight-chained or branched alkyl groups bonded to a C(=O) moiety. Examples of "alkylcarbonyl" include CH3C(=O), CH3CH2CH2C(=O), and (CH3)2CHC(=O). Examples of "alkoxycarbonyl" include CH3OC(=O), CH3CH2OC(=O), CH3CH2CH2OC(=O), and (CH3)2CHOC(=O).

[0063] The term "halogen", either alone or in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted by halogen", includes fluorine, chlorine, bromine, or iodine. Furthermore, when used in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted by halogen", the alkyl group can be partially or completely substituted by halogen atoms, which can be the same or different. Examples of "haloalkyl" or "alkyl substituted by halogen" include F3C, CICH2, CF3CH2, and CF3CCl2. The term "haloalkoxy" and the like is defined similarly to the term "haloalkyl". Examples of "haloalkoxy" include CF3O, CCl3CH2O, F2CHCH2CH2O, and CF3CH2O.

[0064] "Cyanoalkyl" denotes an alkyl group substituted with one cyano group. Examples of "cyanoalkyl" include NCCH2, NCCH2CH2, and CH3CH(CN)CH2. The term "cyanoalkoxy" denotes an alkoxy group substituted with one cyano group. Examples of "cyanoalkoxy" include NCCH2O, NCCH2CH2O, and CH3CH(CN)CH2O. "Hydroxyalkyl" denotes an alkyl group substituted with one hydroxy group. Examples of "hydroxyalkyl" include HOCH2CH2, CH3CH2(OH)CH, and HOCH2CH2CH2CH2.

[0065] The total number of carbon atoms in a substituent group is designated by the prefix "C i -C j " where i and j are numbers from 1 to 6. For example, C1-C3 alkylsulfonyl denotes methylsulfonyl through propylsulfonyl; C2 alkoxyalkyl denotes CH3OCH2; C3 alkoxyalkyl denotes, for example, CH3OCH2CH2 or CH3CH2OCH2; and C4 alkoxyalkyl denotes the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2 and CH3CH2OCH2CH2.

[0066] The term "unsubstituted" in relation to a group such as a ring or ring system means that the group has no 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, an optionally substituted group can be substituted with as many optional substituents as the available carbon or nitrogen atoms will allow, by replacing a hydrogen atom with a non-hydrogen substituent. Typically, the number of optional substituents, when present, is in the range of 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."

[0067] The number of optional substituents can be subject to explicit limitations. For example, the phrase "optionally substituted with up to 4 substituents independently selected from R 14 " means that there can be 0, 1, 2, 3, or 4 substituents.

[0068] Unless otherwise indicated, when a compound is substituted with a substituent bearing a subscript that indicates that the number of said substituents can vary (e.g., (R 5 ) n where n is 0 to 2), then said substituents are independently selected from the group of substituents defined. When a variable group is shown as optionally attached to one position (e.g., (R 5 ) nWhen n can be 0), then hydrogen can be located at that position even though it is not mentioned in the definition of the variable group.

[0069] The nomenclature of substituents in this disclosure uses accepted terminology to provide conciseness to accurately convey chemical structures to those skilled in the art. Position descriptors can be omitted for the sake of brevity.

[0070] Unless otherwise indicated, a“ring” as a component in Formula 1 (e.g., J) is carbocyclic or heterocyclic. The term“ring member” refers to an atom (e.g., C, O, N, or S) or other moiety (e.g., C(=0) and C(=S)) that forms the backbone of a ring or ring system. The term“aromatic” indicates that each ring atom is essentially in the same plane and has a p-orbital perpendicular to the plane of the ring, and that (4n+2) pi electrons are associated with the ring to comply with Hückel’s rule (where n is a positive integer).

[0071] The term“carbocyclic ring” indicates a ring in which the atoms forming the ring backbone are selected from carbon only. 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 the ring is also referred to as an“aromatic ring.” A“saturated carbocyclic ring” refers to a ring having a backbone consisting of carbon atoms connected to each other by single bonds; unless otherwise indicated, the remaining carbon valences are occupied by hydrogen atoms.

[0072] As used herein, the term“partially unsaturated ring” or“partially unsaturated heterocycle” refers to a ring containing unsaturated ring atoms and one or more double bonds but is not aromatic.

[0073] The term“heterocyclic ring” or“heterocycle” indicates a ring in which at least one of the atoms forming the ring backbone is not carbon. Unless otherwise indicated, a heterocyclic ring can be saturated, partially unsaturated, or fully unsaturated. When a fully unsaturated heterocyclic ring satisfies Hückel’s rule, then the ring is also referred to as a“heteroaromatic ring” or aromatic heterocycle. A“saturated heterocyclic ring” refers to a heterocycle containing only single bonds between ring members.

[0074] Unless otherwise indicated, a heterocyclic ring is attached to the remainder of Formula 1 through any available carbon or nitrogen atom by replacing a hydrogen on the carbon or nitrogen atom.

[0075] The compounds of the present application can exist as one or more stereoisomers. Stereoisomers are isomers that have the same constitutional (atomic arrangement) but differ in the spatial arrangement of their atoms. Stereoisomers include enantiomers, diastereomers, cis- and trans-isomers (also known as E- and Z-isomers), and atropisomers. Atropisomers are stereoisomers that arise from hindered rotation about a single bond, where the rotational barrier is high enough to allow separation of the isomers. Those skilled in the art will appreciate that one stereoisomer can be more active and / or can exhibit a beneficial effect than one or more other stereoisomers. In addition, those skilled in the art will appreciate how to separate, enrich, and / or selectively prepare the stereoisomers. For a comprehensive discussion of stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.

[0076] The present application also includes compounds of Formula 1, wherein one stereoisomer is enriched relative to one or more other stereoisomers. For example, the ratio of (Z)- to (E)-isomers in any compound of Formula 1 can take on a wide range of values, whether stereoselectivity or non-stereoselectivity is produced. In addition, the present application includes compounds enriched compared to a racemic mixture of enantiomers of Formula 1. Also included are substantially pure enantiomers of compounds of Formula 1. When enriched enantiomerically, one enantiomer is present in greater amounts than the other, and the degree of enrichment can be defined by the expression enantiomeric excess ("ee") defined as (2x - 1) - 100%, where x is the mole fraction of the enantiomer that predominates in the mixture (e.g., 20% ee corresponds to a 60:40 ratio of enantiomers).

[0077] Preferably, the compositions of the present application have an enantiomeric excess of at least 50% of the more active isomer; more preferably an enantiomeric excess of at least 75%; still more preferably an enantiomeric excess of at least 90%; and most preferably an enantiomeric excess of at least 94%. Of particular note are embodiments that are enantiomerically pure of the more active isomer.

[0078] The compounds of the present application can exist as one or more conformers due to restricted rotation about the amide bond (e.g., C(=0)-N) in Formula 1. The present application includes mixtures of conformers. In addition, the present application includes compounds enriched in one conformer relative to other conformers.

[0079] The present application includes all stereoisomers, conformational isomers, and mixtures thereof in all proportions, and isotopic forms such as deuterated compounds.

[0080] Those skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides, as the nitrogen requires an available lone pair to oxidize to an oxide; those skilled in the art will recognize those nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also recognize that tertiary amines are capable of forming N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art, including the use of peroxy acids such as peroxyacetic acid and meta-chloroperoxybenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane to oxidize the heterocycle or tertiary amine. These methods for preparing N-oxides have been widely described and reviewed in the literature, see for example: T. L. Gilchrist, Comprehensive Organic Synthesis, Volume 7, pages 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik, Comprehensive Heterocyclic Chemistry, Volume 3, pages 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene, Advances in Heterocyclic Chemistry, Volume 43, pages 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik, Advances in Heterocyclic Chemistry, Volume 9, pages 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk, Advances in Heterocyclic Chemistry, Volume 22, pages 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.

[0081] Those skilled in the art recognize that salts share the biological utility of the non-salt forms of the compounds, since the salts of the compounds are in equilibrium with their corresponding non-salt forms in the environment and under physiological conditions. Thus, a variety of salts of the compounds of Formula 1 are useful for controlling plant diseases caused by fungal plant pathogens (i.e., are agriculturally suitable). 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 the compounds of Formula 1 contain 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. Thus, the present application includes compounds selected from Formula 1, N-oxides and agriculturally suitable salts and solvates thereof.

[0082] The compounds selected from Formula 1, stereoisomers, tautomers, N-oxides, and salts thereof typically exist in more than one form, and thus Formula 1 includes all crystalline and non-crystalline forms of the compounds represented by Formula 1. Non-crystalline forms include embodiments that are solids such as waxes and gums, and embodiments that are liquids such as solutions and melts. Crystalline forms include embodiments that represent a substantially single crystal type and embodiments that represent a mixture of polymorphs (i.e., different crystal types). The term “polymorph” refers to a specific crystalline form of a compound that can crystallize in different crystal forms having different molecular arrangements and / or conformations in the crystal lattice. While polymorphs can have the same chemical composition, they can also differ compositionally due to the presence or absence of co-crystallized water or other molecules that can be weakly or strongly bound within the crystal lattice. Polymorphs can differ in such chemical, physical, and biological properties, such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate, and bioavailability. Those skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitable for preparing useful formulations, improved biological performance) relative to another polymorph or mixture of polymorphs of the same compound represented by Formula 1. The 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 with selected solvents and temperatures. For a comprehensive discussion of polymorphism, see R. Hilfiker, ed., Polymorphism in the Pharmaceutical Industry, Wiley-VCH, Weinheim, 2006.

[0083] As described in the Summary, aspects of the present application relate to a composition comprising (a) at least one compound selected from Formula 1, N-oxides, and salts thereof, and (b) at least one additional fungicidal compound. More particularly, component (b) is selected from the group consisting of

[0084] (b1) a benzimidazole methylcarbamate (MBC) fungicide;

[0085] (b2) a dicarboximide fungicide;

[0086] (b3) a demethylation inhibitor (DMI) fungicide;

[0087] (b4) a phenylamide (PA) fungicide;

[0088] (b5) an amine / morpholine fungicide;

[0089] (b6) a phospholipid biosynthesis inhibitor fungicide;

[0090] (b7) a succinate dehydrogenase inhibitor (SDHI) fungicide;

[0091] (b8) a hydroxy(2-amino)pyrimidine fungicide;

[0092] (b9) an anilinopyrimidine (AP) fungicide;

[0093] (b10) an N-phenylcarbamate fungicide;

[0094] (b11) a quinone outside inhibitor (QoI) fungicide;

[0095] (b12) a phenylpyrrole (PP) fungicide;

[0096] (b13) an azanaphthaline fungicide;

[0097] (b14) a cell permeability inhibitor fungicide;

[0098] (b15) a melanin biosynthesis inhibitor-reductase (MBI-R) fungicide;

[0099] (b16a) a melanin biosynthesis inhibitor-dehydratase (MBI-D) fungicide;

[0100] (b16b) a melanin biosynthesis inhibitor-polyketide synthase (MBI-P) fungicide;

[0101] (b17) a ketolide reductase inhibitor (KRI) fungicide;

[0102] (b18) a squalene-epoxidase inhibitor fungicide;

[0103] (b19) polyoxin fungicides;

[0104] (b20) phenylurea fungicides;

[0105] (b21) quinone inside inhibitors (QiI) fungicides;

[0106] (b22) benzamide and thiazolecarboxamide fungicides;

[0107] (b23) enopyranuronic acid antibiotic fungicides;

[0108] (b24) hexopyranosyl antibiotic fungicides;

[0109] (b25) pyranoglycosyl antibiotic: protein synthesis fungicides;

[0110] (b26) pyranoglycosyl antibiotic fungicides;

[0111] (b27) cyanoacetamide-oxime fungicides;

[0112] (b28) carbamate fungicides;

[0113] (b29) oxidative phosphorylation uncouplers fungicides;

[0114] (b30) organotin fungicides;

[0115] (b31) carboxylic acid fungicides;

[0116] (b32) heteroaromatic fungicides;

[0117] (b33) phosphonate fungicides;

[0118] (b34) anthranilic acid fungicides;

[0119] (b35) benzotriazine fungicides;

[0120] (b36) benzene-sulfonamide fungicides;

[0121] (b37) pyridazinone fungicides;

[0122] (b38) thiophene-carboxamide fungicides;

[0123] (b39) complex I NADH oxidoreductase inhibitor fungicides;

[0124] (b40) carboxylic acid amide (CAA) fungicides;

[0125] (b41) tetracycline antibiotic fungicides;

[0126] (b42) thiocarbamate fungicides;

[0127] (b43) benzamide fungicides;

[0128] (b44) microbial fungicides;

[0129] (b45) quinone outside inhibitors, strobilurin binding (QoSI) fungicides;

[0130] (b46) plant extract fungicides;

[0131] (b47) cyanoacrylate fungicides;

[0132] (b48) polyene fungicides;

[0133] (b49) oxysteryl binding protein inhibitor (OSBPI) fungicides;

[0134] (b50) aryl-phenyl-ketone fungicides;

[0135] (b51) host plant defense inducer fungicides;

[0136] (b52) multi-site activity fungicides;

[0137] (b53) biologicals with multiple modes of action;

[0138] (b54) fungicides other than fungicides of component (a) and components (bl) through (b53); and

[0139] (b1) through (b54) of the compounds.

[0140] Of note are embodiments wherein component (b) comprises at least one fungicidal compound from each of two different groups selected from (bl) through (b54).

[0141] “benzimidazole methylcarbamate (MBC) fungicides (bl)” (FRAC code 1) inhibit mitosis by binding to beta-tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within cells, and cellular structure. Benzimidazole methylcarbamate fungicides include benzimidazoles and thiophanate fungicides. Benzimidazoles include benomyl, carbendazim, furan-based benzimidazoles, and thiabendazole. Thiophanate fungicides include thiophanate and thiophanate-methyl.

[0142] “dicarboximide fungicides (b2)” (FRAC code 2) inhibit mitogen-activated protein (MAP) / histidine kinase in osmotic signal transduction. Examples include iprodione, vinclozolin, iphencarbandazole, procymidone, and fenhexamid.

[0143] “Demethylation Inhibitor (DMI) fungicides (b3)” (FRAC code 3) (Sterol Biosynthesis Inhibitors (SBI): Class I) inhibit the C14-demethylase, which plays a role in sterol production. Sterols, such as ergosterol, are required for membrane structure and function, making them essential for the development of a functional cell wall. Thus, exposure to these fungicides results in abnormal growth and eventual death of susceptible fungi. DMI fungicides are divided into several chemical classes: piperazines, pyridines, pyrimidines, imidazoles, triazoles, and triazole thione. Piperazines include uniconazole-P. Pyridines include bithionol, fenodan, fenoxanil, and (aS)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4- isoxazolyl]-3-pyridinemethanol. Pyrimidines include chlorphenospiril, fluotrimazole, and pyrimethanil. Imidazoles include azaconazole, imazalil, oxpoconazole, peconazole, prochloraz, and triflumizole. Triazoles include bitertanol, bifenzthiazyl alcohol, bromocryptone, cyroconazole, cyprodinil, diniconazole (including diniconazole-M), fluquinconazole, etaconazole, fenbuconazole, fenhexamid, fenpiclonil, ferbam, flusilazole, flutriafol, hexaconazole, iminoctad, ipconazole, ipfentrifluconazole, metconazole, paclobutrazol, penconazole, propiconazole, quinconazole, silthiofam, tebuconazole, tetraconazole, triadimefon, triadimenol, tricyclazole, uniconazole, zeta-picox, a-(l-chlorocyclopropyl)-a-[2-(2,2-dichlorocyclopropyl)ethyl]-lH-l,2,4-triazole-l-ethanol, rac-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-lH-l,2,4-triazole, rac-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-l,2-dihydro-3H-l,2,4-triazole-3-thione, and rac-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-l-ylthio)-lH-l,2,4-triazole. Triazole thione includes prothioconazole. Biochemical studies have shown that all of the above 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.

[0144] “Phenylamide (PA) fungicides (b4)” (FRAC code 4) are specific inhibitors of RNA polymerase in fungi of the class Oomycetes. Susceptible fungi exposed to these fungicides show a reduced ability to incorporate uridine into rRNA. Growth and development of susceptible fungi is prevented by exposure to fungicides of this class. Phenylamide fungicides include acylalanine, oxazolidine, and butyrolactone fungicides. Acylalanines include benodanil, benodanil-M (also known as precise), furalaxyl, metalaxyl, and metalaxyl-M (also known as precise metalaxyl). Oxazolidines include oxadixyl. Butyrolactones include ofurace.

[0145] “Amines / morpholines fungicides (b5)” (FRAC code 5) (SBI: Class II) inhibit two target sites within the sterol biosynthetic pathway, Δ 8 → Δ 7 isomerase and Δ 14 reductase. Sterols, such as ergosterol, are required for membrane structure and function, making them essential for development of a functional cell wall. Exposure to these fungicides thus results in abnormal growth and eventual death of susceptible fungi. Amines / morpholines fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholines, piperidines, and spiro-lactone-amine fungicides. Morpholines include aldimorph, cycladiamorph, fenpropimorph, tridiamorph, and trimorphamide. Piperidines include fenpropidine and pyunicarb. Spiro-lactone-amine includes spiroxamine.

[0146] “Phospholipid biosynthesis inhibitor fungicides (b6)” (FRAC code 6) inhibit the growth of fungi by affecting phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phosphorothiolates and dithiolane fungicides. Phosphorothiolates include phosphorous acid, iprobenfos, and pyrazolynate. Dithiolanes include anilazin.

[0147] “succinate dehydrogenase inhibitor (SDHI) fungicides (b7)” (FRAC code 7) inhibit complex II fungal respiration by destroying a key enzyme in the Krebs cycle (TCA cycle) called succinate dehydrogenase. Inhibiting respiration prevents the fungus from producing ATP, and thus inhibits growth and reproduction. SDHI fungicides include phenylbenzamides, phenyl-oxo-ethylthiopheneamides, pyridyl-ethyl-benzamides, furancarboxamides, oxathiapiprolinamides, thiazolecarboxamides, pyrazole-4-carboxamides, N-cyclopropyl-N-benzyl-pyrazolecarboxamides, N-methoxy(phenylethyl)pyrazolecarboxamides, pyridinecarboxamides, and pyrazinecarboxamide fungicides. Phenylbenzamides include carboxin, flutolanil, and fenhexamid. Phenyl-oxo-ethylthiopheneamides include ethaboxam. Pyridyl-ethyl-benzamides include fluopyram. Furancarboxamides include fenfuram. Oxathiapiprolinamides include furalaxyl and oxycarboxin. Thiazolecarboxamides include ethaboxam. Pyrazole-4-carboxamides include benzovindiflucy, bixafen, fluopimida (provisional common name, reg. no. 1676101-39-5), fluindapyr, fluopyram, fenpyrazamine, inpyrfluxam, pyracolpyrun, pyrametostrobin, pyribencarb, pyrapropoyne (provisional common name, reg. no. 1803108-03-3), pyraqualmyl, and N-[2-(2,4-dichlorophenyl)-2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide. N-cyclopropyl-N-benzyl-pyrazolecarboxamides include isoflucypram. N-methoxy(phenylethyl)pyrazolecarboxamides include fluazinam. Pyridinecarboxamides include boscalid. Pyrazinecarboxamide includes bixafen.

[0148] “hydroxy(2-amino)pyrimidine fungicides (b8)” (FRAC code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, cyprodinil, and pyrimethanil.

[0149] “anilinopyrimidine (AP) fungicides (b9)” (FRAC code 9) are proposed to inhibit the biosynthesis of the amino acid methionine and to disrupt the secretion of hydrolytic enzymes that lyse plant cells during infection. Examples include cyprodinil, pyrimethanil, and pyrimethanil.

[0150] “N-phenylcarbamate fungicides (b10)” (FRAC code 10) inhibit mitosis by binding to beta-tubulin and disrupting microtubule assembly. Inhibiting microtubule assembly can disrupt cell division, transport within cells, and cell structure. An example includes diethofencarb.

[0151] “Quinone outside inhibitors (Qol) fungicides (bl l)” (FRAC code 11) inhibit complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the “quinone outside” (Qo) site of the cytochrome bcl complex located in the inner membrane of the mitochondria of fungi. Inhibition of mitochondrial respiration prevents normal fungal growth and development. Quinone outside inhibitor fungicides include the strobilurin fungicides (collectively known as the azoles) and the oxazolidinedione, imidazolinone, and benzyl-carbamate fungicides. The strobilurin fungicides include azoxystrobin, coumoxystrobin, enoxastrobin (also known as enstroburin), fluoxastrobin, picoxystrobin, and pyraclostrobin. The oxazolidinedione fungicide includes pyraclostrobin. The imidazolinone fungicide includes iminoctad. The benzyl-carbamate fungicide includes metominostrobin. The strobilurin fungicides include azoxystrobin, coumoxystrobin, enoxastrobin (also known as enstroburin), fluoxastrobin, picoxystrobin, and pyraclostrobin. The oxazolidinedione fungicide includes pyraclostrobin. The imidazolinone fungicide includes iminoctad. The benzyl-carbamate fungicide includes metominostrobin.

[0152] “Phenylpyrrole (PP) fungicides (b12)” (FRAC code 12) inhibit MAP / histidine kinases associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this class of fungicides.

[0153] “Phenylpyrrole (PP) fungicides (b12)” (FRAC code 12) inhibit MAP / histidine kinases associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this class of fungicides.

[0154] “Cellular respiration inhibitors fungicides (bl 4)” (FRAC code 14) are proposed to inhibit lipid peroxidation affecting membrane synthesis in fungi. Members of this class, such as etridiazole, can also affect other biological processes such as respiration and melanin biosynthesis. Cellular respiration fungicides include the arene and 1,2,4-thiadiazole fungicides. The arene fungicides include biphenyl, chloroneb, dicofol, quintozene, tecnazene, and toclofos-methyl. The 1,2,4-thiadiazole fungicide includes etridiazole.

[0155] “Melanin biosynthesis inhibitor-reductase (MBI-R) fungicides (b15)” (FRAC code 16.1) inhibit the naphthoquinone reductase step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor-reductase fungicides include isobenzofuranones, pyrroloquinolinones, and triazolobenzothiazole fungicides. Isobenzofuranones include tetrachlorophthalide. Pyrroloquinolinones include pyroquilon. Triazolobenzothiazoles include tricyclazole.

[0156] “Melanin biosynthesis inhibitor-dehydratase (MBI-D) fungicides (b16a)” (FRAC code 16.2) inhibit the scytalone dehydratase in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor-dehydratase fungicides include cyclopropane carboxamides, formamidines, and propionamides. Cyclopropane carboxamides include carpropamid. Formamidines include dichlofluanid. Propionamides include iprodione.

[0157] “Melanin biosynthesis inhibitor-polyketide synthase (MBI-P) fungicides (b16b)” (FRAC code 16.3) inhibit the polyketide synthase in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor-polyketide synthase fungicides include trifluoroethyl carbamates. Trifluoroethyl carbamates include toprocarb.

[0158] “Keto reductase inhibitor (KRI) fungicides (b17)” (FRAC code 17) inhibit the 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-pyrazolones. Hydroxyanilides include fenhexamid. Amino-pyrazolones include metrafenone. In addition, Quinofumelin (provisional common name, Reg. No. 861647-84-9) and ipflufenoquin (provisional common name, Reg. No. 1314008-27-9) are considered to be keto reductase inhibitor fungicides.

[0159] “Squalene-epoxidase inhibitor fungicides (b18)” (FRAC code 18) (SBI: class IV) inhibit squalene-epoxidase in the sterol biosynthesis pathway. Sterols, such as ergosterol, are required for membrane structure and function, making them essential for the development of a functional cell wall. Thus, exposure to these fungicides results in abnormal growth and eventual death of sensitive fungi. Squalene-epoxidase inhibitor fungicides include thio- carbamates and allylamine fungicides. Thio-carbamates include tiocarbazil. Allylamines include naftifine and terbinafine.

[0160] “Polyoxin fungicides (b19)” (FRAC code 19) inhibit chitin synthase. Examples include polyoxins.

[0161] “Phenylurea fungicides (b20)” (FRAC code 20) are proposed to affect cell division. Examples include pencycuron.

[0162] “Quinone inside inhibitors (QiI) fungicides (b21)” (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 bcl complex located in the inner membrane of the mitochondria of fungi. Inhibition of mitochondrial respiration prevents normal fungal growth and development. Quinone inside inhibitor fungicides include cyanoguanidines, sulfamoyl-triazoles, and pyridinamide fungicides. Cyanoguanidines include cyanamide. Sulfamoyl-triazoles include ethaboxam. Pyridinamide includes fenpicoxamid.

[0163] “Benzamide and thiazolecarboxamide fungicides (b22)” (FRAC code 22) inhibit mitosis by binding to beta-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, intracellular transport, and cell structure. Benzamides include toltrazamide, such as carpropamid. Thiazolecarboxamides include ethylamino-thiazolecarboxamides, such as thiazolylalanine.

[0164] “Enolpyranosidic acid antibiotic fungicides (b23)” (FRAC code 23) inhibit fungal growth by affecting protein biosynthesis. Examples include blasticidin-S.

[0165] “Hexopyranosyl antibiotic fungicides (b24)” (FRAC code 24) inhibit the growth of fungi by affecting protein biosynthesis. Examples include springomycin.

[0166] “Glucopyranosyl antibiotic: protein synthesis fungicides (b25)” (FRAC code 25) inhibit the growth of fungi by affecting protein biosynthesis. Examples include streptomycin.

[0167] “Glucopyranosyl antibiotic fungicides (b26)” (FRAC code U18, previously FRAC code 26 reclassified as U18) are proposed to inhibit trehalase and inositol biosynthesis. Examples include validamycin.

[0168] “Cyanoacetamide-oxime fungicides (b27)” (FRAC code 27) include cymoxanil.

[0169] “Carbamate fungicides (b28)” (FRAC code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in the cell membrane, which then disrupts cell membrane permeability. Iodocarb, Propamocarb, and Proquinazid are examples of this class of fungicides.

[0170] “Oxidative phosphorylation uncouplers (b29)” (FRAC code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development. This class includes dinitrophenyl crotonates such as Binapacryl, Dinobuton, and Dinocap, and 2,6-dinitroanilines such as Fluazinam.

[0171] “Organotin fungicides (b30)” (FRAC code 30) inhibit adenosine triphosphate (ATP) synthase in the oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride, and fentin hydroxide.

[0172] “Carboxylic acid fungicides (b31)” (FRAC code 31) inhibit fungal growth by affecting DNA topoisomerase type II (gyrase). An example includes Oxolinic acid.

[0173] “Heteroaromatic fungicides (b32)” (FRAC code 32) are proposed to affect DNA / RNA synthesis. Heteroaromatic fungicides include isoxazoles and isothiazolones. Isoxazoles include Hymexazol, and isothiazolones include Octhiozate.

[0174] “Phosphonate fungicides (b33)” (FRAC code P07, formerly FRAC code 33 reclassified as P07) include phosphorous acid and its various salts, including fosetyl-aluminum.

[0175] “Anthranilic diamide fungicides (b34)” (FRAC code 34) include iprodione.

[0176] “Benzotriazine fungicides (b35)” (FRAC code 35) include triforine.

[0177] “Benzene-sulfonamide fungicides (b36)” (FRAC code 36) include flusulfamide.

[0178] “Pyridazinone fungicides (b37)” (FRAC code 37) include diclomezine.

[0179] “Thiophene-carboxamide fungicides (b38)” (FRAC code 38) are proposed to affect ATP production. An example includes silthiofam.

[0180] “Complex INADH oxidoreductase inhibitor fungicides (b39)” (FRAC code 39) inhibit electron transport in mitochondria and include pyrimidine amines such as fluazinam, pyrazole-5-carboxamides such as pyridaben, and quinazolines such as chinomethionat.

[0181] “Carboxamide (CAA) fungicides (b40)” (FRAC code 40) inhibit cellulose synthase, which prevents target fungi from growing and causes target fungi to die. Carboxamide fungicides include cinnamic acid amides, valinamide carbamates, and mandelic acid amide fungicides. Cinnamic acid amides include dimethomorph, flumorph, and pyrimorph. Valinamide carbamates include ethaboxam, ethaboxam-isopropyl, iprovalicarb, and kiralate (also known as fluopimomide). Mandelic acid amides include mandipropamid, N-[2-[4-[[3-(4-chlorophenyl)-2- propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butanamide, and N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2- [(ethylsulfonyl)amino]butanamide.

[0182] “Tetracycline antibiotic fungicides (b41)” (FRAC code 41) inhibit the growth of fungi by affecting protein synthesis. Examples include oxytetracycline.

[0183] “Thioaminocarbamate fungicides (b42)” (FRAC code M12, formerly FRAC code 42 reclassified as M12) include ethaboxam.

[0184] “Benzamide fungicides (b43)” (FRAC code 43) inhibit fungal growth by delocalization of hemopexin-like proteins. Examples include pyridylmethyl benzamides such as fluopicolide and fluopimomide.

[0185] “Microbial fungicides (b44)” (FRAC code BM02, formerly FRAC code 44 reclassified as 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, FCC1256 (deposited as ATCC number PTA-122162, disclosed in PCT / US2019 / 053424), TJ100 (also known as strain 1BE; known from EP2962568), and the fungicidal lipopeptides they produce.

[0186] “Quinone outside inhibitors, stilbines binding (QoSI) fungicides (b45)” (FRAC code 45) inhibit complex III mitochondrial respiration in fungi by affecting the ubiquinol reductase at the “quinone outside” (Qo) site, stilbines binding sub-site of the cytochrome bc1 complex. Inhibition of mitochondrial respiration prevents normal fungal growth and development. QoSI fungicides include triazolo-pyrimidine amines such as ametoctradin.

[0187] “Plant extract fungicides (b46)” (FRAC code 46) cause cell membrane disruption. Plant extract fungicides include terpene hydrocarbons, terpene alcohols and terpene phenols such as extracts from Melaleuca alternifolia (tea tree) and plant oils (mixtures) such as eugenol, geraniol and thymol.

[0188] “Cyanoacrylate fungicides (b47)” (FRAC code 47) bind to the myosin motor domain and affect motility activity and actin assembly. Cyanoacrylates include fungicides such as cyenopyrafen.

[0189] “Polyene fungicides (b48)” (FRAC code 48) cause disruption of fungal cell membranes by binding to the major sterol, ergosterol, in the membrane. Examples include pimaricin (pimaracin).

[0190] “Oxidored al binding protein inhibitor (OSBPI) fungicides (b49)” (FRAC code 49) bind to the oxidored al binding protein in oomycetes, causing inhibition of zoospore release, zoospore motility and sporangium germination. Oxidored al binding fungicides include piperidinyl-thiazole-isoxazoline such as oxathiapiprolin and fluoxapiprolin.

[0191] “Aryl-phenyl-ketone fungicides (b50)” (FRAC code 50, previously FRAC code U8 reclassified as 50) inhibit growth of mycelium in fungi. Aryl-phenyl-ketone fungicides include benzophenones such as metrafenone, and benzoylpyridines such as pydiflumetofen.

[0192] “Host plant defense inducing fungicides (b51)” induce host plant defense mechanisms. Host plant defense inducing fungicides include benzothiadiazoles (FRAC code P01), benzoisothiazoles (FRAC code P02), thiazolidines (FRAC code P03), polysaccharides (FRAC code P04), plant extracts (FRAC code P05), microorganisms (FRAC code P06), and phosphonate fungicides (FRAC code P07, see (b33) above). Benzothiadiazoles include acibenzolar-S-methyl. Benzoisothiazoles include probenazole. Thiazolidines include tiadinil and isotianil. Polysaccharides include laminarin. Plant extracts include extracts from Reynoutria sachalinensis ( giant knotweed). Microorganisms include cells walls of Bacillus mycoides strain J and Saccharomyces cerevisiae strain LAS117.

[0193] "Multi-site active fungicides (b52)" inhibit fungal growth by multiple sites of action and have contact / preventive activity. Multi-site active fungicides include copper fungicides (FRAC code M01), sulphur fungicides (FRAC code M02), dithio carbamate fungicides (FRAC code M03), phthalimide fungicides (FRAC code M04), chloronitrile fungicides (FRAC code M05), sulphenamide fungicides (FRAC code M06), multi-site contact guanidine fungicides (FRAC code M07), triazine fungicides (FRAC code M08), quinone fungicides (FRAC code M09), quinoxaline fungicides (FRAC code M10), maleimide fungicides (FRAC code M11) and thiocarbamate (FRAC code M12, see (b42) above) fungicides. Copper fungicides are inorganic compounds containing copper, typically in the copper (II) oxidation state; examples include copper oxychloride, copper sulphate and copper hydroxide, including compositions such as Bordeaux mixture (termary copper sulphate). Sulphur fungicides are inorganic chemicals containing rings or chains of sulphur atoms; examples include elemental sulphur. Dithio carbamate fungicides contain a dithio carbamate molecular moiety; examples include ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, ziram and zolezimate. Phthalimide fungicides contain a phthalimide molecular moiety; examples include captan, folpet and diclomezine. Chloronitrile fungicides contain an aromatic ring substituted with chlorine and cyano groups; an example includes chlorothalonil. Sulphenamide fungicides include benfluralin and tolufluralin. Multi-site contact guanidine fungicides include salts of biguanides, salts of octhilinol and salts of iminoctadine. Triazine fungicides include anilazine. Quinone fungicides include dithianon. Quinoxaline fungicides include quinomethionate (also known as chinomethionat). Maleimide fungicides include fluoroimide.

[0194] "Biologicals with multiple modes of action (b53)" include agents from biological sources that show multiple mechanisms of action without evidence of a primary mode of action. Fungicides in this category include polypeptides (lectins), phenols, sesquiterpenes, triterpenes and coumarin fungicides (FRAC code BM01) such as extracts from Lupin seedlings. This category also includes microbial fungicides (FRAC code BM02, see (b44) above).

[0195] "Fungicides other than fungicides of component (a) and components (b1) to (b53); (b54)" include certain fungicides whose mode of action can not be known. 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-quinolinyl acetate fungicides" (FRAC code U16), (54.6) "tetrazole oxime fungicides" (FRAC code U17) and "glucopeptide antibiotic fungicides" (FRAC code U18, see (b26) above). Phenyl-acetamides include cyflufenamid. Guanidines include dodine. Thiazolidines include flutianil. Pyrimidinone-hydrazones include metrafenone. 4-Quinolinyl acetates include tebufloquin. Tetrazole oximes include picarbutrazox.

[0196] The (b54) class also includes bethoxazin, dichlobentiazox (provisional common name, registration number 957144-77-3), dipymetitrone (provisional common name, registration number 16114-35-5), flometoquin, fentin (ferric acetoarsenite), nitroquinox, ethaboxam (registration number 304911-98-6), N'-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylformamidine, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidineamine and N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamic acid 4-fluorophenyl ester.

[0197] Additional "fungicides other than fungicides of classes (1) to (54)" whose mode of action can not be known or can not yet be classified include fungicidal compounds selected from components (b54.7) to (b54.11) as shown below.

[0198] Component (54.7) relates to pyridylcarboxamide (provisional common name) (registration number 1961312-55-9, CAS name N-[[3-(acetyloxy)-4-methoxy-2-pyridinyl]carbonyl]-L-alanine (1S)-2,2-bis(4-fluorophenyl)-1-methylethyl ester) which is believed to be a quinone inside inhibitor (QiI) fungicide (FRAC code 21) that inhibits complex III mitochondrial respiration in fungi.

[0199] Component (54.8) relates to metyltetraprole (INN provisional) (Reg. No. 1472649-01-6, CAS name 1 -[2-[[[1 -(4-chlorophenyl)-1 H-pyrazol-3-yl]oxy]methyl]-3-methylphenyl]-1,4- dihydro-4-methyl-5H-tetrazol-5-one), which is considered a quinone outside inhibitor (QoI) fungicide (FRAC code 45) that inhibits complex III mitochondrial respiration in fungi, and is effective against QoI resistant strains.

[0200] Component (54.9) relates to 3-chloro-4-(2,6-difluorophenyl)-6-methyl-5- phenylpyridazine (INN provisional pyridachlometyl, Reg. No. 1358061-55-8), which is considered a promoter of microtubule polymerization, resulting in antifungal activity against fungal species belonging to the phyla Ascomycota and Basidiomycota.

[0201] Component (54.10) relates to aminopyrifen (INN provisional) (Reg. No. 1531626-08-0, CAS name 2-amino-6-methyl-pyridine-3-carboxylic acid (4-phenoxyphenyl) methyl ester), which is considered to inhibit the GWT-1 protein in the biosynthesis of glycosylphosphatidylinositol-anchors in Neurospora crassa.

[0202] Component (b54.11) relates to a compound of formula b54.11

[0203]

[0204] wherein

[0205] R b1 is

[0206]

[0207] R b3 is C2-C3alkoxycarbonyl or C2-C3haloalkylaminocarbonyl;

[0208] L is CH2or CH2O, wherein the atom on the right is attached to the phenyl ring in formula b54.11;

[0209] R b2 is

[0210] and

[0211] R b4 is C1-C3alkyl, wherein the wavy bond indicates that the adjacent double bond is in the (Z)- or (E)-configuration, or a mixture thereof.

[0212] Examples of compounds of Formula b54.11 include (b54.11a) N-(2,2,2-trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-4-oxazolecarboxamide, (b54.11b) 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenoxy]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester, (b54.11c) 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester, and (b54.11d) 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester. Compounds of Formula b54.11, their use as fungicides, and methods of preparation are generally known; see, for example, PCT Patent Publications WO 2018 / 187553 and WO 2020 / 056090.

[0213] Component (b54.12) relates to compounds of Formula b54.12

[0214]

[0215] wherein

[0216] R b7 , R b8 , and R b9 each independently is H, halogen, or cyano; and

[0217] R b10 , and R b11 each independently is H, halogen, C1-C3 alkyl, or C1-C3 methoxy.

[0218] Examples of compounds of Formula b54.12 include (b54.12a) 4-(2-chloro-4-fluorophenyl)-N-(2-fluoro-4-methyl-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (b54.12b) 4-(2-chloro-4-fluorophenyl)-N-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (b54.12c) 3,5-difluoro-4-[5-[(4-methoxy-2-nitrophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-benzonitrile, and (b54.12d) N-(2-chloro-4-fluoro-6-nitrophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine. Compounds of Formula b54.12, their use as fungicides, and methods of preparation are generally known; see, for example, PCT Patent Publication WO 2020 / 051402.

[0219] Embodiments of the present application as described in the SUMMARY include those described below. In the following embodiments, Formula 1 includes stereoisomers, N-oxides, and salts thereof, and reference to "a compound of Formula 1" includes the definitions of the substituents specified in the SUMMARY, unless further defined in the embodiments.

[0220] Embodiment 1. A composition comprising components (a) and (b) as described in the SUMMARY, wherein in Formula 1, A is A-1, A-3, or A-4.

[0221] Embodiment 2. The composition of Embodiment 1, wherein A is A-1 or A-3.

[0222] Embodiment 3. The composition of Embodiment 1, wherein A is A-1.

[0223] Embodiment 4. The composition of Embodiment 1, wherein A is A-3.

[0224] Embodiment 5. The composition of Embodiment 1, wherein A is A-4.

[0225] Embodiment 6. A composition comprising components (a) and (b) as described in the SUMMARY, wherein in Formula 1, A is A-2.

[0226] Embodiment 7. The composition comprising components (a) and (b) as described in the SUMMARY of any one of Embodiments 1 to 6, wherein in Formula 1, wherein Q is CR 6 .

[0227] Embodiment 8. The composition comprising components (a) and (b) as described in the SUMMARY of any one of Embodiments 1 to 6, wherein in Formula 1, Q is N.

[0228] Embodiment 9. The composition comprising components (a) and (b) as described in the SUMMARY of any one of Embodiments 1 to 8, wherein in Formula 1, Y is CR 7a R 7b or O.

[0229] Embodiment 10. The composition comprising components (a) and (b) as described in the SUMMARY of any one of Embodiments 1 to 8, wherein in Formula 1, Y is CR 7a R 7b or NR 8 .

[0230] Embodiment 11. The composition of Embodiment 9 or 10, wherein Y is CR 7a R 7b .

[0231] Example 12. The composition of Example 9, wherein Y is O.

[0232] Example 13. The composition of Example 10, wherein Y is NR 8 .

[0233] Example 14. The composition comprising components (a) and (b) as recited in the summary of the application in any one of Examples 1 to 13, wherein in Formula 1, W is O.

[0234] Example 15. The composition comprising components (a) and (b) as recited in the summary of the application in any one of Examples 1 to 13, wherein in Formula 1, W is S.

[0235] Example 16. The composition comprising components (a) and (b) as recited in the summary of the application in any one of Examples 1 to 15, wherein in Formula 1, R 1 and R 2 are each independently halogen, cyano, hydroxyl, nitro, amino, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C2-C4 haloalkynyl, C2-C4 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C6 cycloalkylalkyl, C2-C4 alkoxyalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C4 alkenyloxy, C2-C4 haloalkenyloxy, C2-C4 alkynyloxy, C2-C4 haloalkynyloxy, C2-C4 cyanoalkoxy, C3-C6 cycloalkoxy, C4-C6 cycloalkylalkoxy, C2-C4 alkoxyalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, or C1-C3 haloalkylsulfonyl.

[0236] Example 17. The composition of Example 16, wherein R 1 and R 2 are each independently halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 cyanoalkyl, C2-C4 alkoxyalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C4 alkenyloxy, C2-C4 haloalkenyloxy, C2-C4 cyanoalkoxy, C2-C4 alkoxyalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, or C1-C3 haloalkylsulfonyl.

[0237] Example 18. The composition of Example 17, wherein R 1and R 2 each independently is halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkoxyalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C4 alkenyloxy, C2-C4 haloalkenyloxy, C2-C4 alkoxyalkoxy, or C1-C3 alkylthio.

[0238] Embodiment 19. The composition of embodiment 18, wherein R 1 and R 2 each independently is halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or C1-C3 alkylthio.

[0239] Embodiment 20. The composition of embodiment 19, wherein R 1 and R 2 each independently is halogen, cyano, methyl, halomethyl, methoxy, or halomethoxy.

[0240] Embodiment 21. The composition of embodiment 20, wherein R 1 and R 2 each independently is Br, Cl, F, methyl, trifluoromethyl, methoxy, or trifluoromethoxy.

[0241] Embodiment 21a. The composition of embodiment 21, wherein R 1 and R 2 each independently is Br, Cl, F, methyl, or trifluoromethyl.

[0242] Embodiment 22. The composition of embodiment 21a, wherein R 1 and R 2 each independently is Cl, F, or methyl.

[0243] Embodiment 23. The composition of embodiment 22, wherein R 1 and R 2 each independently is Cl or F.

[0244] Embodiment 24. The composition of embodiment 23, wherein R 1 and R 2 each is F.

[0245] Embodiment 25. The composition comprising components (a) and (b) as recited in the Summary of the Invention of any one of embodiments 1 to 24, wherein in formula 1, R 3 is H, C1-C3 alkyl, C2-C4 alkylcarbonyl, or C2-C4 alkoxycarbonyl.

[0246] Embodiment 26. The compound of embodiment 25, wherein R3 is H, methyl, methylcarbonyl, or methoxycarbonyl.

[0247] Example 27. The composition of Example 26, wherein R 3 is H or methyl.

[0248] Example 28. The composition of Example 27, wherein R 3 is H.

[0249] Example 29. The composition comprising components (a) and (b) recited in the Summary of the Invention of any one of Examples 1 to 28, wherein in Formula 1, R 4 is methyl, methoxy, ethoxy, methylamino, or dimethylamino.

[0250] Example 30. The composition of Example 29, wherein R 4 is methyl, methoxy, or ethoxy.

[0251] Example 30a. The composition of Example 30, wherein R 4 is methoxy or ethoxy.

[0252] Example 31. The composition of Example 30a, wherein R 4 is methoxy.

[0253] Example 32. The composition comprising components (a) and (b) recited in the Summary of the Invention of any one of Examples 1 to 31, wherein in Formula 1, each R 5 is independently halogen, cyano, methyl, or methoxy.

[0254] Example 33. The composition of Example 32, wherein each R 5 is independently halogen or methyl.

[0255] Example 34. The composition of Example 33, wherein each R 5 is methyl.

[0256] Example 35. The composition comprising components (a) and (b) recited in the Summary of the Invention of any one of Examples 1 to 34, wherein in Formula 1, n is 0 or 1.

[0257] Example 36. The composition of Example 35, wherein n is 0.

[0258] Example 37. The composition comprising components (a) and (b) recited in the Summary of the Invention of any one of Examples 1 to 36, wherein in Formula 1, R 6H, halogen, cyano, nitro, amino, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C2-C6alkoxyalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyloxy, C2-C6haloalkynyloxy, C2-C6alkoxyalkoxy, C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkylsulfinyl, C1-C6haloalkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, -ZC(=O)V, CR 10a =NNR 10b , ON=CR 11a R 11b , CR 12a =NNR 12b R 12c or -L-J.

[0259] Embodiment 38. The composition of embodiment 37, wherein R 6 is H, halogen, cyano, nitro, amino, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C2-C6alkoxyalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyloxy, C2-C6haloalkynyloxy, C2-C6alkoxyalkoxy, C1-C6alkylthio, C1-C6haloalkylthio,

[0260] -ZC(=O)V, CR 10a =NNR 10b , CR 12a =NNR 12b R 12c or -L-J.

[0261] Embodiment 39. The composition of embodiment 38, wherein R 6 is H, halogen, cyano, nitro, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyloxy, C2-C6haloalkynyloxy, C1-C6alkylthio, C1-C6haloalkylthio, CR 10a =NNR 10b or -L-J.

[0262] Embodiment 40. The composition of embodiment 39, wherein R6 H, halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C4 alkynyloxy, CR 10a = NOR 10b or -L-J.

[0263] Embodiment 41. The composition of Embodiment 40, wherein R 6 H, halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C4 alkynyloxy, CR 10a = NOR 10b or -L-J.

[0264] Embodiment 42. The composition of Embodiment 41, wherein R 6 H, Br, Cl, methyl, propyl, isopropyl, CH2F, CHF2, trifluoromethyl, methoxy, ethoxy, isopropoxy, OCH2F, OCHF2, trifluoromethoxy, OCH2CºCH, CH=NOCH3, C(Me)=NOCH3, or -L-J.

[0265] Embodiment 43. The composition of Embodiment 42, wherein R 6 Br, Cl, methyl, isopropyl, CHF2, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, OCH2CºCH, C(Me)=NOCH3, or -L-J.

[0266] Embodiment 44. The composition of Embodiment 43, wherein R 6 Br, Cl, methyl, isopropyl, CHF2, trifluoromethyl, isopropoxy, C(CH3)=NOCH3, or -L-J.

[0267] Embodiment 45. The composition of Embodiment 44, wherein R 6 Br, Cl, methyl, isopropyl, trifluoromethyl, or -L-J.

[0268] Embodiment 46. The composition of Embodiment 45, wherein R 6 Br, Cl, isopropyl, trifluoromethyl, or -L-J.

[0269] Embodiment 47. The composition of Embodiment 46, wherein R 6 Cl, isopropyl, trifluoromethyl, or -L-J.

[0270] Example 48. The composition comprising components (a) and (b) as described in the summary of the application in any of examples 1 to 47, wherein in formula 1, R 7a is H, hydroxyl, halogen, cyano, methyl, halomethyl, methoxy, or halomethoxy.

[0271] Example 49. The composition of example 48, wherein R 7a is H, halogen, methyl, or methoxy.

[0272] Example 50. The composition of example 49, wherein R 7a is H or methyl.

[0273] Example 51. The composition of example 50, wherein R 7a is H.

[0274] Example 52. The composition comprising components (a) and (b) as described in the summary of the application in any of examples 1 to 51, wherein in formula 1, R 7b is H, methyl, halomethyl, methoxy, or halomethoxy.

[0275] Example 53. The composition of example 52, wherein R 7b is H, methyl, or methoxy.

[0276] Example 54. The composition of example 53, wherein R 7b is H or methyl.

[0277] Example 55. The composition of example 54, wherein R 7b is H.

[0278] Example 56. The composition comprising components (a) and (b) as described in the summary of the application in any of examples 1 to 55, wherein in formula 1, R 8 is H, methyl, halomethyl, or methylcarbonyl.

[0279] Example 57. The composition of example 56, wherein R 8 is H or methyl.

[0280] Example 58. The composition of example 57, wherein R 8 is H.

[0281] Example 59. The composition comprising components (a) and (b) as described in the summary of the application in any of examples 1 to 58, wherein in formula 1, Z is a direct bond, O, NH, CH2, or CH(OCH3).

[0282] Embodiment 60. The composition of Embodiment 59, wherein Z is a direct bond, O, or CH2.

[0283] Embodiment 61. The composition of Embodiment 60, wherein Z is a direct bond.

[0284] Embodiment 62. The composition of Embodiment 61, wherein Z is O.

[0285] Embodiment 63. The composition of Embodiment 62, wherein Z is CH2.

[0286] Embodiment 64. The composition comprising components (a) and (b) as recited in the Summary of the Invention of any one of Embodiments 1 to 63, wherein in Formula 1, R 9 , R 10b , R 11a , and R 12c are each H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, or C2-C4 alkynyl.

[0287] Embodiment 65. The composition of Embodiment 64, wherein R 9 , R 10b , R 11a , and R 12c are each H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, or C2-C4 haloalkenyl.

[0288] Embodiment 66. The composition of Embodiment 65, wherein R 9 , R 10b , R 11a , and R 12c are each H, methyl, ethyl, or C2-C4 alkenyl.

[0289] Embodiment 67. The composition of Embodiment 66, wherein R 9 , R 10b , R 11a , and R 12c are each H or methyl.

[0290] Embodiment 68. The composition of Embodiment 67, wherein R 9 , R 10b , R 11a , and R 12c are each H.

[0291] Embodiment 69. The composition of Embodiment 67, wherein R 9 , R 10b , R 11a , and R 12c are each methyl.

[0292] The composition comprising components (a) and (b) as described in the Summary of the Invention of any of embodiments 1 to 69, wherein in Formula 1, R 10a , R 11b , R 12a , and R 12b are each independently H, methyl, or halomethyl.

[0293] The composition of embodiment 71, wherein R 10a , R 11b , R 12a , and R 12b are each independently H or methyl.

[0294] The composition of embodiment 72, wherein R 10a , R 11b , R 12a , and R 12b are each H.

[0295] The composition of embodiment 73, wherein R 10a , R 11b , R 12a , and R 12b are each methyl.

[0296] The composition comprising components (a) and (b) as described in the Summary of the Invention of any of embodiments 1 to 73, wherein in Formula 1, L is a direct bond, CH2, O, S, NR 13 , OCH2, CH2O, or C(=O).

[0297] The composition of embodiment 75, wherein L is a direct bond, CH2, O, OCH2, CH2O, or C(=O).

[0298] The composition of embodiment 76, wherein L is a direct bond, CH2, O, OCH2, or CH2O.

[0299] The composition of embodiment 77, wherein L is a direct bond, O, or OCH2.

[0300] The composition of any of embodiments 74 to 77, wherein L is a direct bond or O.

[0301] The composition of embodiment 78, wherein L is a direct bond.

[0302] The composition of embodiment 79, wherein L is O.

[0303] Example 80. The composition of Example 76, wherein L is CH2.

[0304] Example 81. The composition of Example 76, wherein L is OCH2or CH2O.

[0305] Example 82. The composition comprising components (a) and (b) recited in the Summary of the Invention of any one of Examples 1 to 81, wherein in Formula 1, J is selected from J-1 to J-71, as described in Example A Example A

[0306]

[0307]

[0308]

[0309] wherein the float bonds are connected to L through any available carbon or nitrogen atom of the depicted ring; and x is 0, 1, 2, or 3.

[0310] Example 83. The composition of Example 82, wherein J is J-4, J-5, J-6, J-7, J-8, J-9, J-18, J-19, J-20, J-21, J-22, J-23, J-24, J-25, J-26, J-27, J-34, J-35, J-36, J-37, J-38, J-53, J-56, J-57, J-58, J-59, J-60, J-61, J-63, J-64, J-65, J-66, J-67, J-68, J-69, or J-70.

[0311] Example 84. The composition of Example 83, wherein J is J-4, J-5, J-6, J-22, J-23, J-24, J-35, J-36, J-37, J-38, J-53, J-57, J-58, J-59, J-60, J-63, J-64, J-65, J-66, J-67, J-68, J-69, or J-70.

[0312] Example 85. The composition of Example 84, wherein J is J-53, J-58, J-59, J-60, J-65, J-66, J-67, J-68, J-69, or J-70.

[0313] Example 86. The composition of Example 85, wherein J is J-53, J-58, J-59, J-60, J-65, J-66, J-67, or J-68.

[0314] Example 87. The composition of Example 86, wherein J is J-58, J-66, or J-67.

[0315] Example 88. The composition of Example 87, wherein J is J-66 or J-67.

[0316] Example 89. The composition of Example 87, wherein J is J-58.

[0317] Example 90. The composition of Example 87, wherein J is J-66.

[0318] Example 91. The composition of Example 87, wherein J is J-67.

[0319] Example 92. The composition of Example 91, wherein J is J-66 and x is 1 or 2.

[0320] Example 93. The composition of Example 92, wherein J is J-66 and x is 2.

[0321] Example 94. The composition of any one of Examples 82-93, wherein x is 0, 1, or 2.

[0322] Example 95. The composition of Example 94, wherein x is 2.

[0323] Example 95a. The composition of Example 94, wherein x is 1.

[0324] Example 96. The composition of Example 94, wherein x is 0.

[0325] Example 97. The composition of any one of Examples 1-96, comprising components (a) and (b), wherein in Formula 1 each R 14 is independently halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, or C(=O)OR 15 .

[0326] Example 98. The composition of Example 97, wherein each R 14 is independently halogen, cyano, methyl, halomethyl, methoxy, halomethoxy, or C(=O)OR 15 .

[0327] Example 99. The composition of Example 98, wherein each R 14 is independently halogen, methyl, methoxy, or C(=O)OR 15 .

[0328] Embodiment 100. The composition of Embodiment 99, wherein each R 14 is independently halogen, methyl, or C(=0)OR 15 .

[0329] Embodiment 101. The composition of Embodiment 100, wherein each R 14 is independently halogen or methyl.

[0330] Embodiment 102. The composition of Embodiment 101, wherein each R 14 is independently Br, CI, F, or methyl.

[0331] Embodiment 103. The composition comprising components (a) and (b) recited in the SUMMARY, wherein in Formula 1, each R 15 is independently C1-C3 alkyl, C1-C3 haloalkyl, or cyclopropyl.

[0332] Embodiment 104. The composition of Embodiment 103, wherein each R 15 is independently C1-C3 alkyl or C1-C3 haloalkyl.

[0333] Embodiment 105. The composition of Embodiment 104, wherein each R 15 is independently methyl or ethyl.

[0334] Embodiment 106. The composition of Embodiment 105, wherein each R 15 is methyl.

[0335] Embodiment 107. The composition comprising components (a) and (b) recited in the SUMMARY, wherein Embodiment 1 to 106, wherein component (a) does not comprise N-oxides of the compounds of Formula 1.

[0336] Embodiment 108. The composition comprising components (a) and (b) recited in the SUMMARY, wherein Embodiment 1 to 107, wherein component (a) comprises a compound selected from the group consisting of

[0337] methyl N-[[5-[l-(2,6-difluoro-4-nitrophenyl)-lH-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 1);

[0338] methyl N-[[5-[l-(2,6-difluoro-4-nitrophenyl)-lH-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 1);

[0339] Methyl N-[[5-[l-(2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 4);

[0340] Methyl N-[[5-[l-(4-amino-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 5);

[0341] Methyl N-[[5-[l-(4-chloro-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 6);

[0342] Methyl N-[[5-[l-(4-bromo-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 7);

[0343] Methyl N-[[5-[l-(2,6-difluoro-4-iodophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 8);

[0344] Methyl N-[[5-[l-(2,6-difluoro-4-hydroxyphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 10);

[0345] Methyl N-[[5-[l-(4-ethoxy-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 11);

[0346] Methyl N-[[5-[l-[4-(cyclobutyloxy)-2,6-difluorophenyl]-lH-pyrazol-3- yl]-2-methylphenyl]methyl]carbamate (Compound 13);

[0347] Methyl N-[[5-[l-[2,6-difluoro-4-(l-methylethoxy)phenyl]-lH-pyrazol-3- yl]-2-methylphenyl]methyl]carbamate (Compound 14);

[0348] Methyl N-[[5-[l-[4-(difluoromethoxy)-2,6-difluorophenyl]-lH-pyrazol-3- yl]-2-methylphenyl]methyl]carbamate (Compound 15);

[0349] Methyl N-[[5-[l-[2,6-difluoro-4-(2-propyn-l-yloxy)phenyl]-lH-pyrazol-3- yl]-2-methylphenyl]methyl]carbamate (Compound 30);

[0350] Methyl N-[[5-[l-(2,6-difluoro-4-methoxyphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 33);

[0351] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0352] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0353] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0354] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0355] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0356] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0357] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0358] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0359] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0360] Methyl N-[[5-[l-(4-cyclopropyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 41);

[0361] 3,5-difluoro-4-[3-[3-[[(methoxy carbonyl)amino]methyl]-4-methylphenyl]-1H- pyrazol-1-yl]benzoic acid methyl ester (Compound 70);

[0362] N-[[5-[1-[2,6-difluoro-4-(hydroxymethyl)phenyl]-1H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamic acid methyl ester (Compound 71);

[0363] N-[[5-[1-[2,6-difluoro-4-(trifluoromethoxy)phenyl]-1H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamic acid methyl ester (Compound 78);

[0364] (E)-N-[[5-[1-[2,6-difluoro-4-[1-(methoxyimino)ethyl]phenyl]-1H-pyrazol-3-yl]- 2-methylphenyl]methyl]carbamic acid methyl ester (Compound 83);

[0365] N-[[5-[1-[4-(difluoromethyl)-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamic acid methyl ester (Compound 87);

[0366] N-[[5-[1-[4-(2,2-difluorocyclopropyl)-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamic acid methyl ester (Compound 89);

[0367] N-[[5-[1-[4-[(1,1-dimethylethoxy)-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamic acid methyl ester (Compound 93);

[0368] (Z)-N-[[5-[1-[2,6-difluoro-4-[1-(methoxyimino)ethyl]phenyl]-1H-pyrazol-3-yl]- 2-methylphenyl]methyl]carbamic acid methyl ester (Compound 99);

[0369] N-[[5-[2-[2,6-difluoro-4-(1-methylethyl)phenyl]-2H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]carbamic acid methyl ester (Compound 108);

[0370] N-[[5-[2-[2,6-difluoro-4-methylphenyl]-2H-1,2,3-triazol-4-yl]-2-methylphenyl] methyl]carbamic acid methyl ester (Compound 111);

[0371] N-[[5-[2-[4-cyclopropyl-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 113);

[0372] N-[[5-[2-(4-amino-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 115);

[0373] N-[[5-[2-(4-chloro-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 117);

[0374] N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 118);

[0375] N-[[5-[1-(4-chloro-2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 121);

[0376] N-[[5-[1-(4-amino-2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 131);

[0377] N-[[5-[1-(2,6-difluoro-4-nitrophenyl)-1H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 132);

[0378] N-[[5-[1-[4-(1,3-dioxan-2-yl)-2,6-difluorophenyl)]-1H-pyrazol-3-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 134);

[0379] N-[[5-[1-[2,6-dichloro-4-(1,1-dimethylethyl)phenyl]-1H-pyrazol-3-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 135);

[0380] N-[[5-[2-[2,6-difluoro-4-(1-methylpropyl)phenyl]-2H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]methy lam inoacetate (Compound 139); and

[0381] (E)-N-[[5-[2-[2,6-difluoro-4-[1-(methoxyimino)ethyl]phenyl]-2H-1,2,3- triazol-4-yl]-2-methylphenyl]methyl]methy lam inic acid methyl ester (Compound 142).

[0382] Example 109. The composition of Example 108, wherein component (a) comprises a compound selected from the group consisting of Compound 3, 4, 6, 7, 11, 13, 14, 15, 30, 33, 41, 63, 64, 66, 78, 83, 87, 89, 93, 99, 108, 111, 113, 117, 134, 135, and 142.

[0383] Example 110. The composition of Example 109, wherein component (a) comprises a compound selected from the group consisting of Compound 3, 4, 6, 7, 11, 13, 14, 15, 30, 33, 41, 63, 64, 78, 99, 108, and 117.

[0384] Example 111. The composition of Example 110, wherein component (a) comprises a compound selected from the group consisting of Compound 3, 4, 6, 7, 11, 14, 15, 30, 33, 41, 63, 64, 78, and 99.

[0385] Example 112. The composition of Example 111, wherein component (a) comprises a compound selected from the group consisting of Compound 3, 4, 6, 15, 41, 63, and 64.

[0386] Example 113. The composition of Example 114, wherein component (a) comprises a compound selected from the group consisting of Compound 6, 41, 63, and 64.

[0387] Example 114. The composition of Example 113, wherein component (a) comprises Compound 6.

[0388] Example 115. The composition of Example 113, wherein component (a) comprises Compound 41.

[0389] Example 116. The composition of Example 113, wherein component (a) comprises Compound 63.

[0390] Example 117. The composition of Example 113, wherein component (a) comprises Compound 64.

[0391] Example 118. The composition of any one of examples 108-117, wherein component (b) comprises at least two fungicidal compounds selected from the group consisting of azoxystrobin, benzovindiflucy, bifenathi, chlorothalonil, copper sulfate, cyproconazole, difenconazole, fluquinconazole, fenpropimorph, pyridinamide, fluindapyr, flutriafol, fluazinam, iprovalicarb, isoflucypram, mancozeb, metconazole, pyxoxystrobin, prothioconazole, pyraclostrobin, triflumizole, and trifloxystrobin.

[0392] Embodiments of the present application, including embodiments 1-118 above as well as any other embodiments described herein, can be combined in any manner and the description of variables in the embodiments is not only with respect to compositions comprising a compound of Formula 1 in combination with at least one other fungicidal compound, but also with respect to compositions comprising a compound of Formula 1 in combination with at least one invertebrate pest control compound or agent, and also with respect to compounds of Formula 1 and compositions thereof, and also with respect to starting compounds and intermediate compounds useful in making compounds of Formula 1. Furthermore, embodiments of the present application, including embodiments 1-118 above as well as any other embodiments described herein, and any combinations thereof, are directed to the methods of the present application. Thus, as another embodiment, it is noted that the compositions disclosed above comprising (a) at least one compound selected from the group consisting of compounds of Formula 1, N-oxides, and salts thereof described above; and at least one invertebrate pest control compound or agent are of interest.

[0393] The combinations of embodiments 1-118 are shown below:

[0394] Example A. The composition described in the SUMMARY comprising components (a) and (b), wherein component (a) comprises a compound of Formula 1, or a salt thereof, wherein in Formula 1,

[0395] A is A-1, A-3, or A-4;

[0396] Q is CR 6 ;

[0397] Y is CR 7a R 7b ;

[0398] W is O;

[0399] R 1 and R 2 are each independently halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkoxyalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C4 alkenyloxy, C2-C4 haloalkenyloxy, C2-C4 alkoxyalkoxy, or C1-C3 alkylthio;

[0400] R 3 is H, methyl, methylcarbonyl or methoxycarbonyl;

[0401] R 4 is methyl, methoxy, ethoxy, methylamino or dimethylamino;

[0402] each R 5 is independently halogen or methyl;

[0403] R 6 is H, halogen, cyano, nitro, amino, Ci-C6-alkyl, Ci-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, C2-C6-haloalkynyl, C2-C6-alkoxyalkyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, C2-C6-alkenyloxy, C2-C6-haloalkenyloxy, C2-C6-alkynyloxy, C2-C6-haloalkynyloxy, C2-C6-alkoxyalkoxy, Ci-C6-alkylthio, Ci-C6-haloalkylthio, -ZC(=0)V, CR 10a = N OR 10b , CR 12a = N NR 12b R 12c or -L-J;

[0404] R 7a is H, halogen, methyl or methoxy;

[0405] R 7b is H or methyl;

[0406] Z is a direct bond, O, NH, CH2or CH(OCH3);

[0407] R 9 , R 10b and R 12c are each H, Ci-C3-alkyl, Ci-C3-haloalkyl, C2-C4-alkenyl or C2-C4-haloalkenyl;

[0408] R 10a , R 12a and R 12b are each independently H, methyl or halomethyl;

[0409] L is a direct bond, CH2, O, OCH2or CH2O;

[0410] J is selected from J-1 to J-71

[0411]

[0412]

[0413]

[0414] wherein the float key is attached to L through any available carbon or nitrogen atom of the depicted ring; and x is 0, 1, 2, or 3;

[0415] each R 14 is independently halogen, methyl, methoxy, or C(=O)OR 15 ; and

[0416] each R 15 is independently C1-C3 alkyl, C1-C3 haloalkyl, or cyclopropyl.

[0417] Embodiment AA. The composition of Embodiment A, wherein in Formula 1,

[0418] A is A-1;

[0419] R 1 and R 2 are each independently Br, Cl, F, methyl, or trifluoromethyl;

[0420] R 3 is H or methyl;

[0421] R 4 is methoxy or ethoxy;

[0422] n is 0;

[0423] R 7a is H;

[0424] R 7b is H;

[0425] R 9 , R 10b , and R 12c are each H or methyl;

[0426] R 10a , R 12a , and R 12b are each independently H or methyl;

[0427] L is a direct bond or O;

[0428] J is J-58, J-66, or J-67; and

[0429] each R 14 is independently halogen or methyl.

[0430] Embodiment B. The composition of Embodiment A, wherein in Formula 1,

[0431] A is A-1;

[0432] R 1 and R2 each independently is Br, CI, F, methyl, trifluoromethyl, methoxy, or trifluoromethoxy;

[0433] R 3 is H or methyl;

[0434] R 4 is methyl, methoxy, or ethoxy;

[0435] each R 5 is methyl;

[0436] R 6 is H, halogen, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, Ci-C3haloalkoxy, C2-C4alkenyloxy, C2-C4haloalkenyloxy, C2-C4alkynyloxy, CR 10a = NOR 10b or -L-J;

[0437] R 7a is H or methyl;

[0438] R 10b is H, methyl, ethyl, or C2-C4alkenyl;

[0439] R 10a is H or methyl;

[0440] L is a direct bond or O;

[0441] J is J-53, J-58, J-59, J-60, J-65, J-66, J-67, or J-68; and

[0442] each R 14 is independently halogen or methyl.

[0443] Embodiment C. The composition of Embodiment B, wherein in Formula 1,

[0444] R 1 and R 2 are each independently CI or F;

[0445] R 3 is H;

[0446] R 4 is methoxy;

[0447] n is 0;

[0448] R 6 is Br, CI, methyl, isopropyl, CHF2, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, OCH2CºCH, C(Me)=NOCH3, or -L-J;

[0449] R 7a is H;

[0450] R 7b is H;

[0451] L is a direct bond; and

[0452] J is J-58, J-66, or J-67.

[0453] In some embodiments, the composition comprises a compound of Formula 1, wherein:

[0454] R 1 and R 2 are each F;

[0455] R 6 is Br, Cl, methyl, isopropyl, CHF2, trifluoromethyl, isopropoxy, C(CH3)=NOCH3, or

[0456] -L-J;

[0457] J is J-66;

[0458] x is 0, 1, or 2; and

[0459] R 14 is Br, Cl, F, or methyl.

[0460] In some embodiments, the composition comprises a compound of Formula 1, wherein:

[0461] R 6 is Cl, isopropyl, trifluoromethyl, or -L-J; and

[0462] x is 0.

[0463] In some embodiments, the composition comprises a compound of Formula 1, wherein:

[0464] Example G. The composition of Example F, wherein component (a) comprises a compound selected from the group consisting of: Compound 3, Compound 4, Compound 6, Compound 7, Compound 11, Compound 14, Compound 15, Compound 30, Compound 33, Compound 41, Compound 63, Compound 64, Compound 78, and Compound 99.

[0465] Example H. The composition of Example G, wherein component (a) comprises a compound selected from the group consisting of: Compound 3, Compound 4, Compound 6, Compound 15, Compound 41, Compound 63, and Compound 64.

[0466] Example I. The composition of Example H, wherein component (a) comprises a compound selected from the group consisting of: Compound 6, Compound 41, Compound 63, and Compound 64.

[0467] Example J. The composition of Example I, wherein component (a) comprises Compound 63.

[0468] Example B1. The composition recited in the Summary (including but not limited to the composition of any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (bl) a benzimidazole methylcarbamate fungicide such as benomyl, carbendazim, furanilazole, thiabendazole, and thiophanate-methyl.

[0469] Example B2. The composition recited in the Summary (including but not limited to the composition of any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b2) a dithiocarbamate fungicide such as tecloftalam, dimethirimol, iprodione, procymidone, and vinclozolin.

[0470] Example B3. The composition recited in the Summary (including but not limited to the composition of any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b3) a demethylation inhibitor fungicide such as azaconazole, bitertanol, bromocryptone, bupirimate, cyproconazole, difenoconazole (including difenoconazole-M), diniconazole (including diniconazole-M), enilconazole, fluquinconazole, etaconazole, fenbuconazole, fenclorim, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipfenpyrazol, metconazole, myclobutanil, naftifime, oxpoconazole, pefurazoate, penconazole, pyrimethanil, prothioconazole, spicinazole, silthioconazole, simeconazole, tebufloquinazole, triflumizole, triforine, triticonazole, uniconazole, and uniconazole-P.

[0471] Example B4. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b4) phenylamide fungicides such as benodanil, benodanil-M, furalaxyl, metalaxyl, metalaxyl-M, ofurace, and oxadixyl.

[0472] Example B5. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b5) amine / morpholine fungicides such as 4-dodecyl-2,6-dimethylmorpholine, dodecylmorpholine, fenpropidin, fenpropimorph, fenpropidine, spiroxamine, tridemorph, and triforine.

[0473] Example B6. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b6) phospholipid biosynthesis inhibitor fungicides such as edifenphos, isinolin, isoprothiolane, and pyrazophos.

[0474] Example B7. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b7) succinate dehydrogenase inhibitor fungicides such as benodanil, benzovindiflucy, bixafen, carpropamid, chlorbenzole, fenhexamid, fluazinam, fluindapyr, fluopicolide, fluopyram, flutri- namide, furophanate, iprovalicarb, isoflucypram, isopyrazam, mepronil, oxycarboxin, penthi- azylfen, penthiopyrad, seda- pyr, spicamate, terarubin, and thifluzamide.

[0475] Example B8. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b8) hydroxy(2-amino)pyrimidine fungicides such as buefloxate, dimethirimol, and ethirimol.

[0476] Example B9. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b9) anilinopyrimidine fungicides such as cyprodinil, pyrimethanil, and pyriminom.

[0477] Example B10. A composition as described in the Summary herein (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b10) N-phenylcarbanilate fungicides such as diethofencarb.

[0478] Example B11. A composition as described in the Summary herein (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b11) fungicide quinone outside inhibitor fungicides such as azoxystrobin, boscalid, dimoxystrobin, enestrobin, famoxadone, fenamidone, fenoxystrobin, fluopimtrex, fluoxastrobin, kresoxim-methyl, mandaaromycin, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, pyrametostrobin, pyramoxystrobin, spicinomycin, zoxamid, and trifloxystrobin.

[0479] Example B12. A composition as described in the Summary herein (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b12) phenylpyrrole fungicide compounds such as fenpropimorph and fludioxonil.

[0480] Example B13. A composition as described in the Summary herein (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b13) naphthyl- azide fungicides such as quinoxyfen and proquinazid.

[0481] Example B14. A composition as described in the Summary herein (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b14) cell peroxidation inhibitor fungicides such as benthival, chloroneb, diclomezni, etridiazole quintozene, tecnazene, and tolclofos-methyl.

[0482] Example B15. A composition as described in the Summary herein (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b15) melanin biosynthesis inhibitor-reductase fungicides such as phthalide, pyroquilon, and tricyclazole.

[0483] Example B16a. A composition as described in the Summary herein (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b16a) melanin biosynthesis inhibitor-dehydratase fungicides such as carpropamid, diclocymet, and iprodione.

[0484] Example B16b. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b16b) a melanin biosynthesis inhibitor-polyketide synthase fungicide such as tolylfluralin.

[0485] Example B17. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b17) a ketolide reductase inhibitor fungicide such as cymoxanil, mandipropamid, fluazinam, and quinoxyfen.

[0486] Example B18. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b18) a squalene-epoxidase inhibitor fungicide such as naftifine, pyridone, and terbinafine.

[0487] Example B19. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b19) a polyoxin fungicide such as polyoxin.

[0488] Example B20. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b20) a phenylurea fungicide such as pencycuron.

[0489] Example B21. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b21) a quinone inside inhibitor fungicide such as indaziflam, cyazofamid, and fenpiclonil.

[0490] Example B22. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b22) a benzamide and thiazolecarboxamide fungicide such as ethaboxam and tiadinil.

[0491] Example B23. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b23) an enolpyranosyluronic acid antibiotic fungicide such as blasticidin-S.

[0492] Example B24. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b24) hexopyranosyl antibiotic fungicides such as springomycin.

[0493] Example B25. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b25) glucopyranosyl antibiotic: protein synthesis fungicides such as streptomycin.

[0494] Example B26. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides such as validamycin.

[0495] Example B27. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b27) cyanoacetamide-oxime fungicides such as cymoxanil.

[0496] Example B28. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b28) carbamate fungicides such as iodocarb, propamocarb and thiophanate-methyl.

[0497] Example B29. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b29) oxidative phosphorylation uncoupling fungicides such as binapacryl, dinocap, fluazinam and nitrothal-isopropyl.

[0498] Example B30. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b30) organotin fungicides such as fentin acetate, fentin chloride and fentin hydroxide.

[0499] Example B31. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b31) carboxylic acid fungicides such as oxolinic acid.

[0500] Example B32. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b32) a heteroaromatic fungicide such as hymexazol and cymoxanil.

[0501] Example B33. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b33) a phosphonate fungicide such as phosphorous acid and various salts thereof, including fosetyl-aluminum.

[0502] Example B34. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b34) an anthranilic acid fungicide such as phthalid.

[0503] Example B35. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b35) a benzotriazine fungicide such as metrafenone.

[0504] Example B36. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b36) a benzenesulfonamide fungicide such as fluazinam.

[0505] Example B37. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b37) a pyridazinone fungicide such as pyridazincarb.

[0506] Example B38. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b38) a thiophene-carboxamide fungicide such as silthiofam.

[0507] Example B39. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b39) a complex I NADH oxidoreductase inhibitor fungicide such as fenhexamid, quinalphos and formetanate.

[0508] Example B40. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b40) carboxamide fungicides such as benthiavalicarb, benthiavalicarb-isopropyl, dimoxystrobin, fluoxastrobin, iprovalicarb, mandipropamid, pyrisoxazole, and valifenalate.

[0509] Example B41. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b41) tetracycline antibiotic fungicides such as oxytetracycline.

[0510] Example B42. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b42) thiocarbamate fungicides such as flubenthiavalicarb.

[0511] Example B43. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b43) benzamide fungicides such as fluopicolide and fluopimide.

[0512] Example B44. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b44) microbial fungicides such as Bacillus amyloliquefaciens strains AP-136, AP-188, AP-218, AP-219, AP-295, D747, F727, FCC1256, FZB24, FZB42, MB1600, QST713, RTI301, RTI472, TJ100 (also known as strain 1BE; known from EP2962568), and the fungicidal lipopeptides they produce.

[0513] Example B45. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b45) quinone outside inhibitor, calmodulin binding fungicides such as fampronil.

[0514] Example B46. A composition as described in the Summary of the Invention (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b46) plant extract fungicides such as eugenol, geraniol, and thymol.

[0515] Example B47. A composition as described in the Summary (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b47) a cyanoacrylate fungicide such as fenhexamid.

[0516] Example B48. A composition as described in the Summary (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b48) a polyene fungicide such as natamycin.

[0517] Example B49. A composition as described in the Summary (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b49) an oxysterol binding protein inhibitor fungicide such as flutriafol and fengrile.

[0518] Example B50. A composition as described in the Summary (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b50) an aryl-phenyl-ketone fungicide such as metrafenone and spicamone.

[0519] Example B51. A composition as described in the Summary (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b51) a host plant defense inducer fungicide such as acibenzolar-S-methyl, thiabendazole, thiadicarbamide, isotianil, laminarin, extract from giant knotweed, and cell walls of Bacillus mycoides strain J and Saccharomyces cerevisiae strain LAS117.

[0520] Example B52. A composition as described in the Summary (including but not limited to a composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b52) a multisite activity fungicide such as copper oxychloride, copper sulfate, copper hydroxide, Bordeaux mixture (tribasic copper sulfate), elemental sulfur, ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, ziram, fomet, folpet, captan, dicofol, fluorofolpet, a bisguanide, a bisguanidinioxyalkylbenzenesulfonate, a bisguanidinioxyalkylamine triacetate, guazatine, dithianon, milneb, and flutolanil.

[0521] Example B53. The compositions described in the present invention (including, but not limited to, the compositions as described in Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b53) biological fungicides having multiple modes of action, such as extracts from the cotyledons of lupinus plantlets.

[0522] Example B54. The compositions described in the present invention (including, but not limited to, the compositions as described in Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b54) fungicides different from those of components (a) and (b1 to (b53), such as besoxazine, cycloflufenoxam, dichlorophenazine, dipyridone, doxycycline, pyrimethanil, flumethrin, flumethinazole, and fluthiazolinium. Nitriles, Tianan, Tetrazopyridine, Nitropyrrolizidine, Terfenoquinoline, Methanosulfanilamide, N'-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylformamidin, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine and N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate-4-fluorophenyl ester (XR-539).

[0523] Example B55. The compositions described in the present invention (including, but not limited to, the compositions as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises pyridoxine.

[0524] Example B56. The composition described in the summary of the invention (including, but not limited to, the composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises methyltetraproline.

[0525] Example B57. The composition described in the present invention (including, but not limited to, the composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises 3-chloro-4-(2,6-difluorophenyl)-6-methyl-5-phenylpyridazine (provisional generic name pyridinechloromethyl).

[0526] Example B58. The composition described in the present invention (including, but not limited to, the composition as described in any one of Examples 1 to 118 and A to J), wherein component (b) comprises aminopyrine.

[0527] Example B59. The compositions described in the invention (including, but not limited to, the compositions as described in Examples 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b54.11) (i.e., formula b54.11).

[0528]

[0529] wherein

[0530] R b1 is

[0531]

[0532] R b3 is C2-C3alkoxycarbonyl or C2-C3haloalkylaminocarbonyl;

[0533] L is CH2or CH2O, wherein the atom on the right is attached to the phenyl ring in formula b54.11;

[0534] R b2 is

[0535] and

[0536] R b4 is C1-C3alkyl, wherein the wavy bond indicates that the adjacent double bond is in the (Z)- or (E)-configuration, or a mixture thereof.

[0537] Embodiment B60. The composition of embodiment B59, wherein component (b) comprises at least one fungicidal compound selected from the group consisting of N-(2,2,2- trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-4- oxazolecarboxamide, 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenoxy]methyl]- 1H-pyrazole-4-carboxylic acid ethyl ester, 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1- propen-1-yl]oxy]phenyl]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester, and 1-[[4- [[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1H-pyrazole-4- carboxylic acid ethyl ester.

[0538] Embodiment B60a. The composition of embodiment B60, wherein component (b) comprises at least one fungicidal compound selected from the group consisting of 1-[[4- [[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methyl]-1H-pyrazole-4- carboxylic acid ethyl ester and 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy] phenyl]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester.

[0539] Embodiment B61. The composition recited in the Summary (including but not limited to the composition as described in any one of embodiments 1 to 118 and A to J), wherein component (b) comprises at least one compound selected from (b54.12) (i.e., formula b54.12)

[0540]

[0541] wherein

[0542] R b7 , R b8 and R b9 are each independently H, halogen, or cyano; and

[0543] R b10 and R b11 are each independently H, halogen, C1-C3 alkyl, or C1-C3 methoxy.

[0544] In some embodiments, the composition comprises at least one fungicidal compound selected from the group consisting of 4-(2-chloro-4-fluorophenyl)-N-(2-fluoro-4-methyl-6- nitrophenyl)-1,3-dimethyl-1 H-pyrazol-5-amine, 4-(2-chloro-4-fluorophenyl)-N-(2-fluoro-6- nitrophenyl)-1,3-dimethyl-1 H-pyrazol-5-amine, 3,5-difluoro-4-[5-[(4-methoxy-2-nitrophenyl)amino]- 1,3-dimethyl-1 H-pyrazol-4-yl]-benzonitrile, and N-(2-chloro-4-fluoro-6-nitrophenyl)-4-(2-chloro-4- fluorophenyl)-1,3-dimethyl-1 H-pyrazol-5-amine.

[0545] Example B63. The composition described in the Summary, including but not limited to the composition as described in any one of Examples 1 to 118 and A to J, wherein component (b) comprises at least one fungicidal compound (fungicide) selected from the group consisting of azoxystrobin, benzovindiflucy, boscalid, bifenazate, bromocryptone, carbendazim, chlorothalonil, copper sulfate, cyflufenamid, cyproconazole, difenacozon, dimoxystrobin, fluquinconazole, furametpyr, fenbuconazole, fenpropimorph, pyridinitrile, fluindapyr, flusilazole, flutriafol, fluxapyroxad, hexaconazole, ipfentrifluconazole, ipconazole, isoflucypram, mefenoxam, mancozeb, metominostrobin, metconazole, metiram, metrafenone, myclobutanil, pefurazoate, pencycuron, penthiopyrad, pyricarbate, prochloraz, propiconazole, proquinazid, prothioconazole, pyridinitrile, pyraclostrobin, pyrametostrobin, pyramoxystrobin, pyrisoxazole, quinofumelin, tebuconazole, trifloxystrobin, tridemorph, N-(2,2,2-trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-4-oxazolcarboxamide, 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenoxy]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester, 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester, and 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester.

[0546] Example B64. The composition of Example B63, wherein component (b) comprises at least one compound selected from the group consisting of azoxystrobin, benzovindiflupyr, bifenathi, chlorothalonil, copper sulfate, cyprodinil, cyproconazole, difenoconazole, dimoxystrobin, fluazinam, flutri- nazole, myclobutanil, fenpropidine, fenpropimorph, pyridinamide, fluindapyr, flusilazole, flutri- nafol, fluoxymetofen, mancozeb, maneb, metconazole, paclobutrazol, pyriofenone, spiroxa- din, tridymyl, prothioconazole, pyridylcarbanilide, pyraclostrobin, pyrametostrobin, pyra- metostrobin, pyramidaline, quinoxyfen, tebuconazole, triflumizole, 1 -[[4-[[(1 Z)-2-ethoxy-3,3,3- trifluoro-1 -propen-1 -yl]oxy]phenyl]methyl]-1 H-pyrazole-4-carboxylic acid ethyl ester, 1 -[[4- [[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1 H-pyrazole-4-carboxylic acid ethyl ester, and 1 -[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1 H- pyrazole-4-carboxylic acid ethyl ester.

[0547] Example B65. The composition of Example B64, wherein component (b) comprises at least one compound selected from the group consisting of azoxystrobin, benzovindiflupyr, bifenathi, chlorothalonil, copper sulfate, cyproconazole, difenoconazole, fluazinam, fenpropimorph, pyridinamide, fluindapyr, flutri- nafol, mancozeb, metconazole, pyriofenone, prothioconazole, pyridylcarbanilide, pyraclostrobin, tebuconazole, triflumizole, 1 -[[4-[[(1 Z)-2-ethoxy-3,3,3-trifluoro-1 -propen-1 -yl]oxy]phenyl]methyl]- 1 H-pyrazole-4-carboxylic acid ethyl ester, and 1 -[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1 H-pyrazole-4-carboxylic acid ethyl ester.

[0548] Example B66. The composition of Example B65, wherein component (b) comprises at least one compound selected from the group consisting of azoxystrobin, benzovindiflupyr, bifenathi, chlorothalonil, copper sulfate, cyproconazole, difenoconazole, fluazinam, fenpropimorph, pyridinamide, fluindapyr, flutri- nafol, mancozeb, metconazole, pyriofenone, prothioconazole, pyridylcarbanilide, pyraclostrobin, tebuconazole, and triflumizole.

[0549] Example B67. The composition of Example B66, wherein component (b) comprises at least one compound selected from the group consisting of azoxystrobin, benzovindiflupyr, chlorothalonil, cyprodinil, difenoconazole, fluquinconazole, fenpropimorph, fluindapyr, flutriafol, mancozeb, metconazole, picoxystrobin, prothioconazole, triflumizole, and trifloxystrobin.

[0550] It is noted that the composition of any of the embodiments described herein, including any of Examples 1-118, A-J, and B1-B67, wherein reference to Formula 1 includes salts thereof, but not N-oxides thereof; thus, the phrase "a compound of Formula 1" can be replaced with the phrase "a compound of Formula 1 or a salt thereof." In this noted composition, component (a) comprises a compound of Formula 1 or a salt thereof.

[0551] Also noted as an embodiment is a fungicidal composition of the present application comprising a fungicidally effective amount of the composition of any of Examples 1-118, A-J, and B1-B67, and at least one additional component selected from the group consisting of a surfactant, a solid diluent, and a liquid diluent.

[0552] Embodiments of the present application further include a method for controlling a plant disease caused by a fungal plant pathogen, the method comprising applying to a plant or portion thereof, or a plant seed or seedling, a fungicidally effective amount of the composition of any of Examples 1-118, A-J, and B1-B67 (e.g., as a composition comprising formulation ingredients as described herein). Embodiments of the present application also include a method for protecting a plant or plant seed from a disease caused by a fungal pathogen, the method comprising applying to the plant or plant seed a fungicidally effective amount of the composition of any of Examples 1-118, A-J, and B1-B67.

[0553] Some embodiments of the present application relate to controlling or protecting against plant diseases that primarily affect plant foliage or applying the compositions of the present application to plant foliage (i.e., to the plant, not the seed). Preferred methods of use include those involving the above preferred compositions; and diseases that are particularly effectively controlled include plant diseases caused by fungal plant pathogens. The combination of fungicides used according to the present application can facilitate disease control and delay the development of resistance.

[0554] Method embodiments further include:

[0555] Example C1. A method for protecting a plant from a disease selected from the group consisting of rust diseases, powdery mildew diseases, septoria diseases, and botrytis diseases, the method comprising applying to the plant a fungicidally effective amount of a composition comprising components (a) and (b) as described in the Summary of the application of any one of Examples 1 to 118.

[0556] Example C2. The method of Example C1, wherein the disease is a rust disease and component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of (b3) demethylation inhibitor (DMI) fungicides, (b5) amine / morpholine fungicides, (b7) succinate dehydrogenase inhibitor fungicides, (b11) quinone outside inhibitor (QoI) fungicides, (b13) benzimidazole carbamate fungicides, and (b52) multi-site activity fungicides.

[0557] Example C3. The method of Example C2, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of (b3) demethylation inhibitor (DMI) fungicides, (b7) succinate dehydrogenase inhibitor fungicides, (b11) quinone outside inhibitor (QoI) fungicides, and (b52) multi-site activity fungicides.

[0558] Example C4. The method of Example C3, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of (b3) demethylation inhibitor (DMI) fungicides, (b7) succinate dehydrogenase inhibitor fungicides, and (b11) quinone outside inhibitor (QoI).

[0559] Example C5. The method of any one of Examples C1 to C4, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of azoxystrobin, benzovindiflupyr, bixafen, cyprodinil, difenoconazole, epoxiconazole, fenpropimorph, fluopyram, fluindapyr, flutriafol, fluxapyroxad, ipfentrifluconazole, iphigen, isoflucypram, mancozeb, metconazole, pyrametostrobin, pydiflumetofen, prothioconazole, pyrisoxazole, triflumizole, and trifloxystrobin.

[0560] Example C6. The method of Example C5, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of azoxystrobin, benzovindiflupyr, cyprodinil, epoxiconazole, fenpropimorph, flutriafol, fluxapyroxad, pyrametostrobin, pydiflumetofen, prothioconazole, pyrisoxazole, triflumizole, and trifloxystrobin.

[0561] Example C7. The method of any one of Examples C2 to C6, wherein the disease is Asian Soybean Rust caused by Phakopsora pachyrhizi.

[0562] Example C8. The method of any one of Examples C2 to C6, wherein the disease is Leaf Rust of Wheat caused by Puccinia recondita.

[0563] Example C9. The method of Example C1, wherein the disease is Powdery Mildew and component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of (b3) a Demethylation Inhibitor (DMI) fungicide, (b11) a Quinone outside Inhibitor (QoI) fungicide, (b13) a Naphthalene fungicide, and (b52) a Multi-site Activity fungicide.

[0564] Example C10. The method of Example C9, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of (b3) a Demethylation Inhibitor (DMI) fungicide, (b11) a Quinone outside Inhibitor (QoI) fungicide, and (b52) a Multi-site Activity fungicide.

[0565] Example C11. The method of Examples C9 and C10, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of azoxystrobin, chlorothalonil, copper sulfate, cyproconazole, difenoconazole, fluquinconazole, flutriafol, mancozeb, metconazole, pyridinitr, picoxystrobin, prothioconazole, pyraclostrobin, tebuconazole, and trifloxystrobin.

[0566] Example C12. The method of Example C11, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of cyproconazole, difenoconazole, fluquinconazole, flutriafol, mancozeb, prothioconazole, tebuconazole, and trifloxystrobin.

[0567] Example C13. The method of Example C10, wherein component (b) of the composition comprises at least one fungicidal compound selected from (b3) a DMI fungicide.

[0568] Example C14. The method of Example C13, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of cyproconazole, difenoconazole, fluquinconazole, flutriafol, prothioconazole, and tebuconazole.

[0569] Example C15. The method of Example C10, wherein component (b) of the composition comprises at least one fungicidal compound selected from (b11) a QoI fungicide.

[0570] Example C16. The method of Example C15, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of azoxystrobin, picoxystrobin, pyraclostrobin, and trifloxystrobin.

[0571] Example C17. The method of any one of Examples C9-C16, wherein the disease is wheat powdery mildew caused by Erysiphe graminis.

[0572] Example C18. The method of Example C1, wherein the disease is a Pyrenophora disease and component (b) of the composition comprises at least one fungicidal compound selected from (b3) a demethylation inhibitor (DMI) fungicide and (b11) a quinone outside inhibitor (QoI) fungicide.

[0573] Example C19. The method of Example C18, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of azoxystrobin, cyproconazole, difenoconazole, epoxiconazole, fenpropimorph, pyridinylaminopyrimidines, flutriafol, metconazole, phytolacca, picoxystrobin, prothioconazole, pyraclostrobin, tebuconazole, and trifloxystrobin.

[0574] Example C20. The method of any one of Examples C18 and C19, wherein the disease is wheat leaf spot caused by Zymoseptoria tritici.

[0575] Example C21. The method of Example C1, wherein the disease is a Botrytis disease and component (b) of the composition comprises at least one fungicidal compound selected from (b11) a quinone outside inhibitor (QoI) fungicide and (b52) a multisite active fungicide.

[0576] Example C22. The method of Example C21, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of azoxystrobin, chlorothalonil, mancozeb, phytolacca, picoxystrobin, pyraclostrobin, and trifloxystrobin.

[0577] Example C23. The method of Example C22, wherein component (b) of the composition comprises at least one fungicidal compound selected from the group consisting of azoxystrobin mancozeb, and trifloxystrobin.

[0578] Example C24. The method of any one of Examples C1-C23, wherein components (a) and (b) are applied in a synergistically effective amount (and in a synergistically effective ratio relative to one another).

[0579] Of note are embodiments corresponding to embodiments C1-C24, which relate to a method for controlling a plant disease caused by a fungal plant pathogen, the method comprising applying to the plant or portion thereof a fungicidally effective amount of a fungicidal composition of the present application.

[0580] As noted in the SUMMARY, the present application also relates to a compound of Formula 1, or an N-oxide or salt thereof. It is also noted that embodiments of the present application, including embodiments 1-118, also relate to a compound of Formula 1.

[0581] The present application 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 are embodiments of such compositions that comprise a compound corresponding to any of the compound embodiments described above.

[0582] One or more of the following methods and variations as described in Schemes 1-12 can be used to prepare compounds of Formula 1. Unless otherwise noted, the definitions of A, Q, R 1 , R 2 , R 3 , R 4 , R 5 , W, Y, and n are as defined in the SUMMARY above. Unless otherwise noted, compounds of Formulas 1a-1d are subsets of Formula 1, and all substituents of Formulas 1a-1d are as defined above for Formula 1.

[0583] As shown in Scheme 1, compounds of Formula 1 can be prepared by reacting compounds of Formula 2 with compounds of Formula 3 under copper or palladium catalyzed cross-coupling conditions. For compounds of Formula 3 where X is halogen or triflate, Ullmann or Buchwald-Hartwig conditions can be used. For relevant references, see, for example, Chemical Reviews 2002, 102(5), 1359-1470; Angew. Chem. Int. Ed. Engl. 2008, 47(34), 6338-6361; and Chem. Sci. 2010, 1(1), 13-31; and PCT Patent Application WO 2014 / 066120. Example 1 of the present application also illustrates the method of Scheme 1. These reactions typically require the presence of a base such as a metal carbonate like potassium carbonate and a suitable catalyst and ligand such as copper (I) iodide and a ligand such as trans-1,2-diamino-N,N'-dimethylcyclohexane. The reaction is usually carried out in an aprotic solvent such as N,N-dimethylformamide, dioxane or toluene at a temperature between ambient temperature and the boiling point of the solvent. In cases where the compound of Formula 3 contains an electron withdrawing substituent (e.g., when R 1 2 and / or R 6 ​In the case where X is halo, direct nucleophilic substitution of X can be achieved by a compound of Formula 2 when Y is nitro, cyano, or ester (when Y is nitro, cyano, or ester) and X is halo. These reactions are carried out in the presence of a base such as an alkali metal carbonate, hydride, alkoxide, or trialkylamine, in a solvent such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, dioxane, tetrahydrofuran, or acetonitrile, at temperatures between about ambient temperature and 130 °C. For reaction conditions, see, Bioorganic & Medicinal Chemistry Letters 2014, 24(24), 5805-5813; Bioorganic & Medicinal Chemistry Letters 2010, 20(15), 4521-4525; and Journal of Materials Chemistry A: Materials for Energy and Sustainability 2014, 2(21), 7917-7926; and PCT Patent Application WO 2016 / 187667. In addition, Invention Examples 2, 7, and 11 illustrate the preparation of compounds of Formula 1 by direct nucleophilic substitution. For compounds of Formula 3 where X is boronic acid, Chan-Lam conditions can be used. These reactions are carried out in the presence of a suitable base such as pyridine or triethylamine and a catalyst such as copper(II) acetate. Typically, the reaction is carried out in an aprotic solvent like dichloromethane or chloroform, at temperatures between about ambient temperature and the boiling point of the solvent, and in the presence of oxygen. For primary references, see, for example, Tetrahedron 2018, 74(5), 606-617; and Tetrahedron Lett. 1998, 39(19), 2933-2936.

[0584] Scheme 1

[0585]

[0586] Compounds of Formula 3 are widely available from commercial sources and can be readily prepared using commercial precursors and known methods (see, for example, US2013 / 0158004 and WO 2018 / 011094).

[0587] In some cases, the method of Scheme 1 produces two regioisomers. For example, as shown in Scheme 2, the reaction of a compound of Formula 2a (i.e., Formula 2 where A is A-4) with a compound of Formula 3 typically provides an isomeric mixture of compounds of Formula la’ (i.e., Formula 1 where A is A-4) and Formula la” (i.e., Formula 1 where A is A-3). Purification of the regioisomers can be achieved using standard techniques such as column chromatography. For a related reference, see, for example, PCT Patent Publication WO 2009 / 013211. In addition, the method of Scheme 2 is illustrated in Example 18, Step F.

[0588] Scheme 2

[0589]

[0590] As shown in Scheme 3, a compound of Formula 2a (i.e., Formula 2 where A is A-4) can be prepared by reacting an alkyne of Formula 4 with a suitable source of azide ion in the presence of a copper (I) salt. Suitable sources of azide include, for example, azidotrimethylsilane and sodium azide. Suitable copper (I) salts include copper (I) iodide, copper (I) bromide, and copper (I) chloride. Alternatively, a copper (II) salt can be used in conjunction with a mild reducing agent, for example, copper (II) sulfate with sodium ascorbate. The reaction is typically carried out in a solvent such as N,N-dimethylformamide, tetrahydrofuran, methanol, t-butanol, dimethylsulfoxide (optionally containing water) at a temperature from about 25 °C to 100 °C. In some cases, the use of a lower boiling solvent can necessitate elevated pressure to facilitate the reaction at temperatures above the normal boiling point of the solvent. For primary references, see, for example, Organic Letters 2009, 11 (23), 5490-5493; European J. Organic Chem. 2004, (18), 3789-3791; Synlett 2005, (19), 2941-2947; and Tetrahedron Letters 2006, 47 (18), 3035-3038; and PCT Patent Publication WO 2004 / 072243. The method of Scheme 3 is also illustrated in Example 18, Step E of the present application.

[0591] Scheme 3

[0592]

[0593] Scheme 4 outlines two methods for preparing compounds of Formula 4. As shown in Method A, compounds of Formula 4 can be prepared from compounds of Formula 5 and alkynes of Formula 6 using Sonogashira reaction coupling conditions. Sonogashira couplings are well known in the literature. See, for example, Molecules 2010, 15, 9157-9173; Sonogashira, K. in Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E. Ed.; Wiley-Interscience: New York, 2002, pp. 493-529; Palladium in Heterocyclic Chemistry, A Guide for the Synthetic Chemist, Li, J.; Gribble, G. Eds., Tetrahedron Organic Series, Vol. 20; Pergamon Press: New York, 2000.

[0594] As shown in Method B, compounds of Formula 4 can be prepared by reacting compounds of Formula 5 with ethynyltrimethylsilane (Formula 7) in the presence of a suitable palladium catalyst such as tetrakis(triphenylphosphine)palladium or dichlorobis-(triphenylphosphine)- palladium(II) and a suitable copper catalyst such as copper(I) iodide. The reaction is preferably carried out in the presence of an amine base such as triethylamine, N,N- diisopropylethylamine, diethylamine, or piperidine. The reaction is typically carried out in a solvent such as tetrahydrofuran, toluene, or N,N-dimethylformamide; however, in some cases, the reaction can be carried out without a solvent other than the compound of Formula 5, ethynyltrimethylsilane, and the amine base. Removal of the trimethylsilyl group to obtain compounds of Formula 4 can be carried out using well known conditions such as treatment with an alkali metal hydroxide or carbonate such as potassium hydroxide, sodium hydroxide, or potassium carbonate in methanol or ethanol. The reaction is preferably carried out in a suitable organic solvent. Typically, the process is most satisfactorily conducted at temperatures ranging from about 0 °C to the reflux temperature of the solvent. For representative procedures, see JACS 2003, 125(38), 11545-11552 and Bioorganic & Medicinal Chemistry 2009, 17(24), 8149-8160. In addition, Invention Example 18, Steps A and B illustrate the method of Scheme 4.

[0595] Scheme 4

[0596]

[0597] As shown in Scheme 5, compounds of Formula 2 can also be prepared by a Suzuki coupling of a compound of Formula 5 with a boron intermediate of Formula 8, wherein A is bonded to boron through a carbon atom ring member and is unsubstituted on the N atom ring member (i.e., A is a 5-membered heteroaromatic ring comprising ring members -NH- and -(CB(OH)2)-). The reaction is carried out in the presence of a Pd(0) or Pd(II) salt, a suitable ligand, and a base. Suitable bases for this transformation are potassium carbonate or cesium carbonate, while Pd(II) salts such as Pd(OAc)2or PdCl2are used in conjunction with ligands such as triphenylphosphine or 1,1’-bis(diphenylphosphino) ferrocene (dppf). Conditions for Suzuki couplings are well documented in the literature; see, e.g., Angewandte Chemie International Edition 2006, 45(21), 3484-3488 and Tetrahedron Letters 2002, 43(16), 2885-2888. Boron intermediates of Formula 8 are commercially available and can be prepared from the corresponding halide or triflate by methods known in the literature; see, e.g., PCT Patent Publication WO 2007 / 043278; U.S. Patent No. 8080566; Organic Letters 2011, 13(6), 1366-1369; European Journal of Medicinal Chemistry 2014, 87, 529-539, and Organic Letters 2012, 14(2), 600-603.

[0598] Other coupling procedures provide a number of alternatives for introducing the heterocyclic A ring to Formula 5, including coupling methods disclosed by Heck, Stille, and Kumada. See also, e.g., Zificsak et al., Tetrahedron 2004, 60, 8991-9016.

[0599] Scheme 5

[0600]

[0601] As shown in Scheme 6, compounds of formula 5 can be prepared by reacting an amine of formula 9 with an acyl chloride of formula 10 in the presence of a base such as potassium carbonate, triethylamine or pyridine. The reaction can be carried out in the absence of a solvent other than the compounds of formula 9, 10 and the base, or in a solvent such as acetonitrile, dichloromethane, chloroform, diethyl ether or tetrahydrofuran at a temperature ranging from about 0 °C to 50 °C. For reaction conditions, see, for example, PCT Patent Publication WO 2004 / 037770 and European Patent EP 1586552. In addition, the method of Scheme 6 is illustrated in Example 18, Step D of the present application.

[0602] For the synthesis of compounds of formula 10, see Advanced Organic Synthesis, 4thEdition, Wiley & Sons 1992, 437, and references cited therein. Compounds of formula 9 are commercially available and can be readily synthesized by general methods known to one skilled in the art.

[0603] Scheme 6

[0604]

[0605] As shown in Scheme 7, compounds of formula 1 can also be prepared by reacting an acyl chloride of formula 10 with a compound of formula 11 in analogy to the method of Scheme 6. The method of Scheme 7 is illustrated in Example 17, Step F of the present application.

[0606] Scheme 7

[0607]

[0608] As shown in Scheme 8, compounds of formula 11 can be prepared from nitriles of formula 12 using an appropriate reducing agent such as lithium aluminum hydride or borane / tetrahydrofuran complex or tris(pentafluorophenyl)borane in an aprotic solvent such as tetrahydrofuran at a temperature between ambient temperature and the boiling point of the solvent. For related examples, see procedures and references contained in PCT Patent Applications WO 2011 / 079102 and WO 2011 / 073444. In addition, the method of Scheme 8 is illustrated in Example 17, Step E of the present application.

[0609] Nitriles of Formula 12 can also be converted to amines of Formula 11 by catalytic hydrogenation. These reactions are traditionally carried out in the presence of a transition metal catalyst such as palladium(0) on carbon, Raney nickel, or platinum oxide in a lower alcohol solvent such as methanol or ethanol under a hydrogen atmosphere at a temperature between ambient and 100 °C at a pressure between 1 and 7500 kPa. For related examples, see the procedures and references contained in PCT Patent Applications WO 2009 / 152868 and WO 2010 / 023161.

[0610] Scheme 8

[0611]

[0612] As shown in Scheme 9, compounds of Formula 12 can be prepared by coupling a compound of Formula 13, wherein A is not substituted on the N atom ring member (i.e., A is a 5-membered heteroaromatic ring containing the ring member -NH-), with a compound of Formula 3 using methods analogous to those of Scheme 1. Invention Example 17, Step A, illustrates the method of Scheme 9.

[0613] Scheme 9

[0614]

[0615] As shown in Scheme 10, compounds of Formula 13 can be prepared from compounds of Formula 14. In a typical procedure, compounds of Formula 14 are contacted with a cyanide salt such as copper(I) cyanide or zinc(II) cyanide in the presence of a suitable transition metal catalyst such as copper(I) iodide or tetrakis(triphenylphosphine)palladium(0) in a polar aprotic solvent such as N,N-dimethylformamide or dimethyl sulfoxide at a temperature between about 50 °C and 150 °C. For related procedures, see PCT Patent Applications WO 2012 / 032528 and WO 2011 / 133882 and references contained therein.

[0616] Scheme 10

[0617]

[0618] As shown in Scheme 11, compounds of Formula 14 can be prepared by first reacting a compound of Formula 15 with N,N-dimethylformamide dimethyl acetal (DMF-DMA) in a solvent such as toluene or benzene at a temperature between about 40 °C and 100 °C to provide an intermediate compound of Formula 16. In a subsequent step, the compound of Formula 16 is reacted with hydrazine or a hydrazine salt in a lower alcohol solvent such as methanol or ethanol to provide a compound of Formula 14.

[0619] Scheme 11

[0620]

[0621] The compounds of Formula 1 and intermediates thereto described herein can be subjected to various electrophilic, nucleophilic, organometallic, oxidative, and reductive reactions to add substituents or modify existing substituents, and thus provide other functionalized compounds of Formula 1. For example, as shown in Scheme 12, compounds of Formula 1c (i.e., where Q is CR 6 and R 6 is NH2can be prepared by reduction of the corresponding nitro compound of Formula 1 (i.e., where Q is CR 6 and R 6 is NO2using Fe, Zn, or SnCl2in acidic aqueous solution at temperatures ranging from ambient to reflux. Alcohol co-solvents such as methanol, ethanol, and isopropanol can also be used. In a subsequent reaction, the amino group of Formula 1c can be converted to halogen under diazotization conditions in the presence of a halogen source to provide compounds of Formula 1d (i.e., where Q is CR 6 and R 6 is halogen. A variety of halogen sources can be used in the method of Scheme 12. For example, addition of tert-butylnitrite to a solution of an amino compound of Formula 1c in a solvent such as acetonitrile in the presence of copper(II) bromide provides the corresponding bromide compound of Formula 1d; likewise, reaction with diiodomethane provides the corresponding iodo compound of Formula 1d. Compounds of Formula 1c can also be converted to diazonium salts and then to the corresponding compounds of Formula 1d by treatment with sodium nitrite in a solvent such as water, acetic acid, or trifluoroacetic acid in the presence of an inorganic acid containing the same halogen atom (such as aqueous HI) followed by treatment with the corresponding copper(I) or copper(II) salt according to general procedures well known to those skilled in the art. Many known reduction, diazotization, and halogenation methods can be readily adapted to prepare compounds of Formula 1c and 1d, for example, see the procedures and references contained in U.S. Patent Applications US2017 / 0121300, US2017 / 069105, and US2017 / 038909, and PCT Patent Application WO 2017 / 036357. In addition, the method of Scheme 12 is illustrated in Inventive Examples 3, 4, and 13. 6

[0622] Scheme 12

[0623]

[0624] ​The methods of Scheme 12 provide only two examples of techniques for adding substituents or modifying existing substituents in compounds of Formula 1. One skilled in the art will recognize that compounds of Formula 1 can also be subjected to a number of reactions to provide other functionalized compounds of Formula 1. For example, aromatic halides of Formula 1 (e.g., Formula 1d where the halogen is Br or I) can be reacted with alcohols or thiols under metal catalyzed conditions to provide compounds of Formula 1 containing alkoxy or alkyl thiol substituents (see Example 15 for conditions).

[0625] Compounds of Formula 1 and intermediates described in the above methods where W is O can be converted to the corresponding thiolate (where W is S) using a variety of standard sulfurizing reagents such as phosphorus pentasulfide or 2,4-bis(4-methoxyphenyl)-1,3- dithia-2,4-diphosphetane-2,4-disulfide (Lawesson's reagent). Such reactions 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.

[0626] It will be recognized that certain of the reagents and reaction conditions described above for preparing compounds of Formula 1 can not be compatible with certain functional groups present in the intermediates. In these cases, the incorporation of protection / deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired product. The use and choice of the protecting groups will be apparent to a person skilled in the art of chemical synthesis (see, for example, T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2ndedition; Wiley: New York, 1991). A person skilled in the art will recognize that in some cases, after the introduction of a given reagent as depicted in any individual scheme, it can be necessary to carry out additional routine synthetic steps not described in detail to complete the synthesis of a compound of Formula 1. A person skilled in the art will also recognize that it can be necessary to carry out combinations of the steps shown in the above schemes in a different order than the specific sequence presented for the preparation of compounds of Formula 1.

[0627] Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present application to its fullest extent. The following examples are, therefore, to be construed as merely illustrative, and not limitative of the disclosure in any way whatsoever. The procedures in the following examples show the procedures for each step in the overall synthetic transformation, and the starting material used for each step does not necessarily have to be prepared from the specific preparative experiment whose procedure is described in other examples or steps. Percentages are by weight, except for chromatographic solvent mixtures or where otherwise indicated. The parts and percentages of the chromatographic solvent mixtures are by volume, unless otherwise indicated. 1 H NMR spectra are reported in ppm from low field of tetramethylsilane; "s" means singlet, "d" means doublet, "t" means triplet, "m" means multiplet, "br s" means broad singlet and "dd" means doublet of doublets. Mass spectra are reported as the molecular weight of the highest isotopic abundance parent ion (M+1) formed by adding H + ) or electrospray ionization (ESI + ) observed by using a liquid chromatograph-mass spectrometer (LCMS) using atmospheric pressure chemical ionization (APCI + ) or electrospray ionization (ESI

[0628] Example 1

[0629] Methyl N-[[5-[l-(2,6-difluoro-4-methoxyphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate

[0630] Preparation of methyl N-[[5-[l-(2,6-difluoro-4-methoxyphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 3)

[0631] To a mixture of methyl N-[[2-methyl-5-(lH-pyrazol-3-yl)phenyl]methyl]carbamate (1.12 g, 4.57 mmol) (see PCT Patent Publication WO 2008124092 for preparation), copper (I) iodide (0.17 g, 0.914 mmol) and 2-bromo-l,3-difluoro-5-methoxy-benzene (1.32 g, 5.94 mmol) was added potassium carbonate (11.4 mmol) followed by N,N-dimethylformamide (8 mL). The reaction mixture was sparged with nitrogen for 30 minutes followed by the addition of trans-N,N'-dimethylcyclohexane-l,2-diamine (0.26 g, 1.83 mmol). The reaction mixture was heated at 80 °C overnight, cooled to room temperature and diluted with ethyl acetate. The resulting mixture was washed with saturated aqueous sodium chloride solution (4x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 20% to 80% ethyl acetate in hexanes to provide the title compound (compound of the invention) as a colourless oil (0.43 g).

[0632] 1 H NMR (CDCI3): δ 7.74 (d, 1 H), 7.67 (dd, 1 H), 7.59 (d, 1 H), 7.22 (d, 1 H), 6.74 (d, 1 H), 6.61 (d, 2 H), 4.87 (br s, 1 H), 4.41 (d, 2 H), 3.84 (s, 3 H), 3.69 (s, 3 H), 2.36 (s, 3 H). LCMS: m / z: 388 [M+H] +

[0633] Example 2

[0634] Methyl N-[[5-[l-(2,6-difluoro-4-nitrophenyl)-lH-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate

[0635] Preparation of (Compound 1)

[0636] To a stirred solution of methyl N-[[2-methyl-5-(1H-pyrazol-3-yl)phenyl]methyl]carbamate (0.45 g, 1.84 mmol) (see PCT Patent Publication WO 2008124092 for preparation method) in dimethyl sulfoxide (5 mL) was added potassium carbonate (762 mg, 5.52 mmol) and 1,2,3-trifluoro-5-nitrobenzene (0.235 mL, 2.02 mmol). The reaction mixture was stirred at room temperature overnight and diluted with ethyl acetate. The resulting mixture was washed with saturated aqueous sodium chloride solution (4x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography eluting with a gradient of 10% to 50% ethyl acetate in hexanes to provide the title compound (compound of the invention) as a yellow solid (0.44 g).

[0637] 1 H NMR (CDCI3): δ 8.02 (d, 2H), 7.79 (dd, 1H), 7.75 (d, 1H), 7.69 (dd, 1H), 7.25 (d, 1H), 6.85 (d, 1H), 4.86 (br s, 1H), 4.44 (d, 2H), 3.71 (s, 3H), 2.38 (s, 3H).

[0638] Example 3

[0639] Methyl N-[[5-[1-(4-amino-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate

[0640] Preparation of (Compound 5)

[0641] To a mixture of methyl N-[[5-[1-(2,6-difluoro-4-nitrophenyl)-1H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 2) (0.4 g, 0.995 mmol) and ammonium chloride (32 mg, 0.597 mmol) in ethanol / water (9:1, 20 mL) was added iron powder (555 mg, 9.95 mmol) in portions. The reaction mixture was heated at reflux for 1.5 h, and then cooled to room temperature and filtered through a pad of Celite, rinsing with ethyl acetate. The filtrate was washed with saturated aqueous sodium chloride solution (4x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 30% to 100% ethyl acetate in hexanes to provide the title compound (compound of the invention) as a light yellow solid (0.3 g).

[0642] 1 ​H NMR (CDCI3): δ 7.75 (d, 1H), 7.66 (dd, 1H), 7.56 (d, 1H), 7.21 (d, 1H), 6.72 (d, 1H), 6.31 (d, 2H), 4.82 (br s, 1H), 4.41 (d, 2H), 4.04 (br s, 2H), 3.69 (s, 3H), 2.36 (s, 3H).

[0643] Example 4

[0644] Preparation of methyl N-[[5-[l-(4-bromo-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 7)

[0645] To a mixture of methyl N-[[5-[l-(4-amino-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 3) (90 mg, 0.242 mmol) in acetonitrile (2 mL) was added copper(II) bromide (65 mg, 0.290 mmol). The reaction mixture was cooled to approximately 0 °C and n-butyl nitrite (0.043 mL, 0.363 mmol) was added. The reaction mixture was stirred at room temperature overnight, and then quenched with hydrochloric acid (1 N aqueous solution). The resulting mixture was extracted with ethyl acetate (2x) and the combined extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel eluting with a gradient of 10% to 40% ethyl acetate in hexanes. The resulting material was further purified by column chromatography eluting with a gradient of 0% to 10% ethyl acetate in dichloromethane to provide the title compound (a compound of the invention) as a yellow oil (49 mg).

[0646] 1 H NMR (CDCI3): δ 7.74 (d, 1H), 7.67-7.65 (m, 2H), 7.29 (d, 2H), 7.23 (d, 1H), 6.78 (d, 1H), 4.83 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 2.37 (s, 3H).

[0647] LCMS: m / z: 436 [M+H] +

[0648] Example 5

[0649] Preparation of methyl N-[[5-[l-(2,6-difluoro-4-hydroxyphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 10)

[0650] To a mixture of methyl N-[[5-[l-(2,6-difluoro-4-methoxyphenyl)-lH-pyrazol-3-yl]- 2-methylphenyl]methyl]carbamate (i.e. the product of Example 1) (1.20 g, 3.10 mmol) in dichloromethane (30 mL) at 0 °C was added boron tribromide (1 M solution in dichloromethane, 9.40 mL, 9.30 mmol) dropwise. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was quenched slowly with water (35 mL) followed by the dropwise addition of methanol (35 mL) and then stirred at room temperature for 1 h. The layers were separated and the aqueous layer was extracted with dichloromethane (2x). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 20% to 70% ethyl acetate in hexanes to afford the title compound (a compound of the invention) as a white solid (0.87 g).

[0651] 1 H NMR (CDCI3): δ 7.74 (br s, 1 H), 7.63 (dd, 1 H), 7.60 (d, 1 H), 7.24 (d, 1 H), 6.75 (d, 1 H), 6.46 (d, 2 H), 4.95 (br s, 1 H), 4.42 (d, 2 H), 3.69 (s, 3 H), 2.37 (s, 3 H).

[0652] Example 6

[0653] Preparation of methyl N-[[5-[l-[2,6-difluoro-4-(l-methylethoxy)phenyl]-lH-pyrazol-3- yl]-2-methylphenyl]methyl]carbamate (Compound 14)

[0654] To a mixture of methyl N-[[5-[l-(2,6-difluoro-4-hydroxyphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 5) (87 mg) in tetrahydrofuran (3 mL) was added triphenylphosphine (122 mg, 0.46 mmol) followed by 2-propanol (0.035 mL, 0.46 mmol) and diethyl azodicarboxylate (0.073 mL, 0.46 mmol). The reaction mixture was stirred at room temperature for 48 h and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 10% to 50% ethyl acetate in hexanes to afford the title compound (a compound of the invention) as a white solid (85 mg).

[0655] 1H NMR (CDCI3): δ 7.75 (d, 1 H), 7.67 (dd, 1 H), 7.59 (d, 1 H), 7.22 (d, 1 H), 6.74 (d, 1 H), 6.58 (d, 2 H), 4.54 (m, 1 H), 4.83 (br s, 1 H), 4.42 (d, 2 H), 3.70 (s, 3 H), 2.36 (s, 3 H), 1.37 (d, 6 H).

[0656] LCMS: m / z: 416 [M+H] +

[0657] Example 7

[0658] Preparation of methyl 3,5-difluoro-4-[3-[3-[[(methoxy carbonyl)amino]methyl]-4- methylphenyl]-1 H-pyrazol-1 -yl]benzoate (compound 70)

[0659] To a mixture of methyl N-[[2-methyl-5-(1 H-pyrazol-3-yl)phenyl]methyl]carbamate (2.58 g, 10.5 mmol) (for preparation see PCT Patent Publication WO 2008124092) and methyl 3,4,5-trifluorobenzoate (2.41 g, 12.6 mmol) in dimethyl sulfoxide (10 mL) was added potassium carbonate (4.35 g, 31.5 mmol). The reaction mixture was stirred at room temperature for 48 h and diluted with ethyl acetate. The resulting mixture was washed with saturated aqueous ammonium chloride solution (4x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography eluting with a gradient of 10% to 50% ethyl acetate in hexanes to provide the title compound (compound of the invention) (3.55 g) as a light pink solid.

[0660] 1 H NMR (CDCI3): δ 7.76 (d, 2 H), 7.74 (m, 2 H), 7.68 (d, 1 H), 7.24 (d, 1 H), 6.80 (d, 1 H), 4.87 (br s, 1 H), 4.42 (d, 2 H), 3.97 (s, 3 H), 3.70 (s, 3 H), 2.37 (s, 3 H).

[0661] Example 8

[0662] Preparation of methyl N-[[5-[1-[2,6-difluoro-4-(hydroxymethyl)phenyl]-1 H-pyrazol-3- yl]-2-methylphenyl]methyl]carbamate (compound 71 )

[0663] To a mixture of methyl 3,5-difluoro-4-[3-[3-[[(methoxy carbonyl)amino]methyl]-4- methylphenyl]-lH-pyrazol-l-yl]benzoate (i.e. the product of Example 7) (3.55 g, 8.55 mmol) in methanol (45 mL) was added sodium borohydride (1.94 g, 51.3 mmol) in portions. The reaction mixture was stirred at room temperature overnight, then quenched with hydrochloric acid (1 N aqueous solution) and filtered. The filtrate was extracted with ethyl acetate (3x) and the combined extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 20% to 100% ethyl acetate in hexanes to provide the title compound (a compound of the invention) as a white solid (2.52 g).

[0664] 1 H NMR (DMSO-d6): δ 8.11 (d, 1H), 7.73 (d, 1H), 7.65 (t, 1H), 7.62 (dd, 1H), 7.29 (d, 1H), 7.22 (d, 1H), 6.94 (d, 1H), 5.59 (t, 1H), 4.60 (d, 2H), 4.21 (d, 2H), 3.55 (s, 3H), 2.30 (s, 3H).

[0665] Example 9

[0666] Preparation of methyl N-[[5-[l-(2,6-difluoro-4-formylphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 67)

[0667] To a mixture of methyl N-[[5-[l-(2,6-difluoro-4-formylphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 8) (2.30 g, 5.94 mmol) in tetrahydrofuran (70 mL) was added Dess-Martin periodinane (2.52 g, 5.94 mmol) in portions. The reaction mixture was stirred at room temperature overnight, then quenched with aqueous sodium carbonate solution and extracted with ethyl acetate (2x). The combined extracts were filtered, rinsing with ethyl acetate. The filtrate was washed with saturated aqueous sodium bicarbonate solution (3x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 20% to 60% ethyl acetate in hexanes to provide the title compound (a compound of the invention) as a white solid (1.78 g).

[0668] 1H NMR (CDCI3): δ 9.98 (t, 1 H), 7.76 (m, 2H), 7.69 (dd, 1 H), 7.62 (d, 2H), 7.24 (d, 1 H), 6.83 (d, 1 H), 4.86 (br s, 1 H), 4.43 (d, 2H), 3.71 (s, 3H), 2.38 (s, 3H).

[0669] Example 10

[0670] Preparation of methyl N-[[5-[1 -(2,6-difluoro-4-formylphenyl)-1 H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 87)

[0671] To a mixture of methyl N-[[5-[1 -(2,6-difluoro-4-formylphenyl)-1 H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 9) (0.25 g, 0.65 mmol) in dichloromethane (10 mL) at about 0 °C was added dropwise (0.36 mL, 1.95 mmol) followed by ethanol (1 drop). The reaction mixture was stirred at room temperature overnight and then slowly poured into saturated aqueous sodium carbonate solution (200 mL). After 30 minutes, the layers were separated and the aqueous layer was extracted with dichloromethane (1 x). The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel eluting with a gradient of 10% to 50% ethyl acetate in hexanes to provide the title compound (a compound of the invention) as a colourless oil (0.23 g).

[0672] 1 H NMR (CDCI3): δ 9.98 (t, 1 H), 7.76 (m, 2H), 7.69 (dd, 1 H), 7.62 (d, 2H), 7.24 (d, 1 H), 6.83 (d, 1 H), 4.86 (br s, 1 H), 4.43 (d, 2H), 3.71 (s, 3H), 2.38 (s, 3H).

[0673] LCMS: m / z: 408 [M+H] +

[0674] Example 11

[0675] Methyl N-[[5-[1 -(4-acetyl-2,6-difluorophenyl)-1 H-pyrazol-3-yl]-2-methylphenyl]methyl] carbamate

[0676] Preparation of methyl N-[[5-[1 -(4-acetyl-2,6-difluorophenyl)-1 H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 68)

[0677] To a mixture of methyl N-[[2-methyl-5-(lH-pyrazol-3-yl)phenyl]methyl]carbamate (2.0 g, 8.16 mmol) (see PCT Patent Publication WO 2008124092 for preparation) and l-(3,4,5-trifluorophenyl)ethanone (2.0 g, 11.4 mmol) in dimethyl sulfoxide (9 mL) was added potassium carbonate (3.38 g, 24.5 mmol). The reaction mixture was stirred at room temperature overnight and then diluted with ethyl acetate. The resulting mixture was washed with saturated aqueous ammonium chloride solution (4x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 10% to 70% ethyl acetate in hexanes to provide the title compound (compound of the invention) (2.10 g) as a light orange solid.

[0678] 1 H NMR (CDCI3): δ 7.75 (m, 2H), 7.69 (dd, 1H), 7.67 (d, 2H), 7.24 (d, 1H), 6.81 (d, 1H), 4.87 (br s, 1H), 4.43 (d, 2H), 3.70 (s, 3H), 2.64 (s, 3H), 2.37 (s, 3H).

[0679] Example 12

[0680] (E)-N-[[5-[l-[2,6-difluoro-4-[l-(methoxyimino)ethyl]phenyl]-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamic acid methyl ester (compound 83)

[0681] Preparation of (E)-N-[[5-[l-[2,6-difluoro-4-[l-(methoxyimino)ethyl]phenyl]-lH-pyrazol-3- yl]-2-methylphenyl]methyl]carbamic acid methyl ester (compound 83)

[0682] A mixture of methyl N-[[5-[l-(4-acetyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 11) (0.24 g, 0.602 mmol), O-methylhydroxylamine hydrochloride (60.3 mg, 0.722 mmol) and sodium acetate (59.2 mg, 0.722 mmol) in ethanol was heated at reflux overnight. The reaction mixture was cooled to room temperature and diluted with water. The resulting mixture was extracted with ethyl acetate (2x) and the combined extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound (compound of the invention) (239 mg) as an amber solid.

[0683] 1H NMR (CDCI3): δ 7.75 (d, 1H), 7.68 (m, 2H), 7.41 (d, 2H), 7.23 (d, 1H), 6.78 (d, 1H), 4.85 (br s, 1H), 4.42 (d, 2H), 4.04 (s, 3H), 3.70 (s, 3H), 2.37 (s, 3H), 2.21 (s, 3H). LCMS: m / z: 429 [M+H] +

[0684] Example 13

[0685] Preparation of methyl N-[[5-[l-(2,6-difluoro-4-iodophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (Compound 8)

[0686] To a mixture of methyl N-[[5-[l-(4-amino-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 3) (2.38 g, 6.40 mmol) in acetonitrile (50 mL) was added diiodomethane (2.1 mL, 25.6 mmol). The reaction mixture was cooled to about 0 °C and then added dropwise tert-butylnitrite (0.84 mL, 7.04 mmol). The reaction mixture was stirred at room temperature for 5 h and then added more diiodomethane (12 mL, 150 mmol). After stirring overnight, the reaction mixture was diluted with ethyl acetate and washed with saturated sodium metabisulfite solution (3x), saturated sodium chloride solution (2x) and hydrochloric acid (1 N aqueous solution). The mixture was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 0% to 10% ethyl acetate in hexanes to provide the title compound (a compound of the invention) as an off-white solid (1.0 g).

[0687] 1 H NMR (CDCI3): δ 7.73 (d, 1H), 7.66-7.64 (m, 2H), 7.47 (d, 2H), 7.22 (d, 1H), 6.77 (d, 1H), 4.86 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 2.36 (s, 3H).

[0688] Example 14

[0689] Methyl N-[[5-[l-(4-ethynyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2-methylphenyl]methyl] carbamate

[0690] Preparation of methyl N-[[5-[l-(4-ethynyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]-2-methylphenyl]methyl] carbamate (Compound 53)

[0691] Step A: Preparation of methyl N-[[5-[l-(2,6-difluoro-4-iodophenyl)-lH-pyrazol-3-yl]- 2-methylphenyl]methyl]carbamate

[0692] To a mixture of methyl N-[[5-[l-(2,6-difluoro-4-iodophenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 13) (0.2 g, 0.414 mmol), copper (I) iodide (8 mg, 0.041 mmol), N,N-dimethylformamide (4 mL), ethynyltrimethylsilane (0.088 mL, 0.621 mmol) and dichlorobis(triphenylphosphine)palladium (29 mg, 0.041 mmol) was added triethylamine (0.063 mL, 0.455 mmol). The reaction mixture was stirred at room temperature overnight, then diluted with ethyl acetate, washed with saturated sodium chloride solution (4x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel (eluting with a gradient of 5% to 40% ethyl acetate in hexane) to afford the title compound as a light brown oil (0.17 g).

[0693] 1 H NMR (CDCI3): δ 7.74 (d, 1 H), 7.67 (m, 2H), 7.23 (d, 1 H), 7.16 (d, 2H), 6.77 (d, 1 H), 4.84 (br s, 1 H), 4.42 (d, 2H), 3.70 (s, 3H), 2.37 (s, 3H), 0.27 (s, 9H).

[0694] Step B: Preparation of methyl N-[[5-[l-(4-ethynyl-2,6-difluorophenyl)-lH-pyrazol-3-yl]- 2-methylphenyl]methyl]carbamate (Compound 53)

[0695] To a mixture of methyl N-[[5-[l-(2,6-difluorophenyl-4-(2- (trimethylsilyl)ethynyl)-lH-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (i.e. the product of Step A) (0.12 g, 0.265 mmol) in methanol (6 mL) was added potassium carbonate (44 mg, 0.318 mmol). The reaction mixture was stirred at room temperature for 1.5 h, then diluted with ethyl acetate and water and allowed to stand at room temperature overnight. The resulting mixture was washed with saturated sodium chloride solution (2x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel (eluting with a gradient of 10% to 50% ethyl acetate in hexane) to afford the title compound (a compound of the invention) as an amber oil (0.109 g).

[0696] 1 H NMR (CDCI3): δ 7.75 (d, 1 H), 7.68-7.66 (m, 2H), 7.23 (d, 1 H), 7.20 (d, 2H), 6.78 (d, 1 H), 4.84 (br s, 1 H), 4.42 (d, 2H), 3.70 (s, 3H), 3.24 (s, 1 H), 2.37 (s, 3H).

[0697] LCMS m / z: 382 [M+H] +

[0698] Example 15

[0699] Preparation of methyl N-[[5-[1-[4-[(1,1-dimethylethyl)thio]-2,6-difluorophenyl]- 1 H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 42)

[0700] A mixture of methyl N-[[5-[1 -(2,6-difluoro-4-iodophenyl)-1 H-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate (i.e. the product of Example 13) (0.217 g, 0.450 mmol) and N,N-dimethylformamide (2 mL) was purged with a stream of nitrogen for 10 to 15 minutes and then tetrakis(triphenylphosphine)palladium (52 mg, 0.045 mmol) was added, followed by 2-methyl-2-propanethiol (0.100 mL, 0.900 mmol) and triethylamine (0.20 mL, 1.35 mmol). The reaction mixture was heated at 70 °C for 1 h, then cooled to room temperature and diluted with ethyl acetate. The resulting mixture was washed with saturated sodium chloride solution (3x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel eluting with a gradient of 10 to 50% ethyl acetate in hexane to afford the title compound (a compound of the invention) as an orange oil (0.189 g). 1 H NMR (CDCI3): δ 7.75 (d, 1 H), 7.69-7.67 (m, 2H), 7.27 (d, 2H), 7.23 (d, 1 H), 6.79 (d, 1 H), 4.84 (br s, 1 H), 4.42 (d, 2H), 3.70 (s, 3H), 2.37 (s, 3H), 1.37 (s, 9H).

[0701] Example 16

[0702] Preparation of methyl N-[[5-[1-[4-[(difluoromethyl)thio]-2,6-difluorophenyl]-1 H- pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 43)

[0703] Step A: Preparation of methyl N-[[5-[l-(2,6-difluoro-4-mercaptophenyl)-lH- pyrazol-3-yl]-2-methylphenyl]methyl]carbamate

[0704] To a mixture of methyl N-[[5-[l-[4-[(l,l-dimethylethyl)thio]-2,6-difluorophenyl]- lH-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (the product of Example 15) (0.16 g, 0.360 mmol) in dichloromethane (5 mL) at about 0 °C was added boron tribromide (1 M solution in dichloromethane, 1.10 mL, 1.08 mmol) dropwise. The reaction mixture was stirred at room temperature overnight and quenched with water (6 mL) and methanol (6 mL). After stirring for 2 h, the layers were separated and the aqueous layer was extracted with dichloromethane (2x). The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 20% to 100% ethyl acetate in hexanes to provide the title compound as a solid (77 mg).

[0705] 1 H NMR (CDC13): δ 7.74 (d, 1H), 7.67 (dd, 1H), 7.62 (m, 1H), 7.22 (d, 1H), 6.98 (d, 2H), 6.75 (d, 1H), 4.83 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 2.36 (s, 3H).

[0706] Step B: Preparation of methyl N-[[5-[l-[4-[(difluoromethyl)thio]-2,6-difluorophenyl]- lH-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate

[0707] To a mixture of methyl N-[[5-[l-(2,6-difluoro-4-mercaptophenyl)-lH- pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (the product of Step A) (77 mg, 0.198 mmol) in acetonitrile and water (1:1, 2 mL) was added potassium hydroxide (222 mg, 3.96 mmol) followed by diethyl (bromodifluoromethyl)phosphonate (0.070 mL, 0.396 mmol). The reaction mixture was stirred at room temperature for 1.5 h, and then diluted with ethyl acetate. The resulting mixture was washed with saturated sodium chloride solution (2x), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 10% to 50% ethyl acetate in hexanes to provide the title compound (a compound of the invention) as an off-white solid (64 mg). 1H NMR (CDCI3): δ 7.75 (d, 1H), 7.70-7.68 (m, 2H), 7.34 (d, 2H), 7.24 (d, 1H), 7.02-6.80 (t, 1H), 6.80 (d, 1H), 4.84 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 2.37 (s, 3H). LCMS m / z: 440 [M+H] +

[0708] Example 17

[0709] Methyl N-[[5-[l-(2,6-dichloro-4-cyclopropylphenyl)-lH-pyrazol-3-yl]-2- methylphenyl]methyl]carbamate

[0710] Preparation of (Compound 65)

[0711] Step A: Preparation of 5-[l-(2,6-dichloro-4-nitrophenyl)-lH-pyrazol-3-yl]-2- methylbenzonitrile

[0712] A mixture of 2-methyl-5-(lH-pyrazol-3-yl)benzonitrile (3.0 g, 16.4 mmol) (for preparation see PCT Patent Publication WO 2014066120), 1,3-dichloro-2-fluoro-5- nitrobenzene (4.12 g, 19.6 mmol) and potassium carbonate (2.72 g, 19.6 mmol) in N,N- dimethylformamide (51 mL) was heated at 80 °C for 4 h and then stirred at room temperature overnight. The reaction mixture was diluted with water and the resulting precipitate was collected by filtration and rinsed with water. The solid precipitate was triturated in a mixture of hexanes / 1-chlorobutane, filtered and air dried to provide the title compound (3.59 g).

[0713] 1 H NMR (CDCI3): δ 8.37 (s, 2H), 8.11 (s, 1H), 7.96 (d, 1H), 7.64 (s, 1H), 7.38 (d, 1H), 6.87 (s, 1H), 2.60 (s, 3H).

[0714] Step B: Preparation of 5-[l-(4-amino-2,6-dichlorophenyl)-lH-pyrazol-3-yl]-2- methylbenzonitrile To a mixture of tin(II) chloride dihydrate (12.82 g, 56.82 mmol), acetic acid (51.78 mL), and concentrated hydrochloric acid (34.57 mL) was added 5-[l-(2,6-dichloro-4-nitrophenyl)-lH-pyrazol-3-yl]-2-methylbenzonitrile (i.e., the product of Step A) (6.07 g, 16.26 mmol) in portions while maintaining the reaction temperature at about 25 °C. The reaction mixture was stirred overnight, and then was slowly poured into a mixture of potassium hydroxide (200 g), water (200 g), and ice (400 g). The resulting solid precipitate was collected by filtration and dried to provide the title product (6.8 g).

[0715] 1 H NMR (CDC13): δ 8.22 (s, 1H), 7.98 (d, 1H), 7.55 (s, 1H), 7.35 (d, 1H), 6.76 (s, 1H), 6.71 (s, 2H), 4.06 (s, 2H), 2.57 (s, 3H).

[0716] Step C: Preparation of 5-[l-(4-bromo-2,6-dichlorophenyl)-lH-pyrazol-3-yl]-2- methylbenzonitrile

[0717] A mixture of 5-[l-(4-amino-2,6-dichlorophenyl)-lH-pyrazol-3-yl]-2-methylbenzonitrile (i.e., the product of Step B) (6.75 g, 18.67 mmol) and n-butyl nitrite (27.38 mL, 233.7 mmol) was heated at reflux overnight, then cooled to room temperature and concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel eluting with 20% ethyl acetate in hexanes to provide the title compound (4.3 g).

[0718] 1 H NMR (CDC13): δ 8.22 (s, 1H), 7.98 (d, 1H), 7.55 (s, 1H), 7.35 (d, 1H), 6.76 (s, 1H), 6.71 (s, 2H), 4.06 (s, 2H), 2.57 (s, 3H).

[0719] Step D: Preparation of 5-[l-(2,6-dichloro-4-cyclopropylphenyl)-lH-pyrazol-3-yl]-2- methylbenzonitrile To a mixture of 5-[l-(4-bromo-2,6-dichlorophenyl)-lH-pyrazol-3-yl]-2- methylbenzonitrile (i.e. the product of Step C) (2.19 g, 5.37 mmol), cyclopropylboronic acid (0.53 g, 6.31 mmol), sodium carbonate (1.99 g, 18.75 mmol), and bis(triphenylphosphine)palladium(II) dichloride (0.46 g, 0.66 mmol) in 1,2-dimethoxyethane (43.7 mL) and water (10.03 mL) was heated at 85 °C overnight. The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 0% to 10% ethyl acetate in hexanes to provide the title compound (0.90 g).

[0720] 1 H NMR (CDC13): δ 8.13 (s, 1H), 7.97 (d, 1H), 7.55 (s, 1H), 7.34 (d, 1H), 7.15 (s, 2H), 6.78 (s, 1H), 2.57 (s, 3H), 1.98-1.90 (m, 1H), 1.14-1.08 (m, 2H), 0.81-0.75 (m, 2H).

[0721] Step E: Preparation of 5-[l-(2,6-dichloro-4-cyclopropylphenyl)-lH-pyrazol-3-yl]-2- methylbenzylamine hydrochloride

[0722] To a mixture of 5-[l-(2,6-dichloro-4-cyclopropylphenyl)-lH-pyrazol-3-yl]-2- methylbenzonitrile (i.e. the product of Step D) (0.88 g, 2.39 mmol) in dichloromethane (5 mL) was added tris(2,3,4,5,6-pentafluorophenyl)borane (0.01 g, 0.07 mmol) followed by diethylsilane (0.53 g, 5.97 mmol). The reaction mixture was stirred at room temperature overnight, cooled to about 0-5 °C, and then hydrochloric acid (4N solution in dioxane, 2.02 mL) was added dropwise. The resulting precipitate was collected by filtration and air dried to provide the title compound as a solid (0.82 g).

[0723] 1H NMR (CDCI3): δ 8.30 (br s, 3H), 8.03 (s, 1H), 7.95 (s, 1H), 7.77 (d, 1H), 7.43 (s, 2H), 7.32 (d, 1H), 6.97 (s, 1H), 3.57 (s, 2H), 2.36 (s, 3H), 2.13-2.05 (m, 1H), 1.14-1.05 (m, 2H), 0.91-0.85 (m, 2H).

[0724] Step F: Preparation of methyl N-[[5-[l-(2,6-dichloro-4- cyclopropylphenyl)-lH-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate

[0725] To a mixture of 5-[l-(2,6-dichloro-4-cyclopropylphenyl)-lH-pyrazol-3-yl]-2- methylbenzylamine hydrochloride (i.e. the product of Step E) (0.82 g, 2.01 mmol) and potassium carbonate (0.83 g, 6.02 mmol) in acetonitrile (10 mL) at about 0-5 °C was added methyl chloroformate (0.21 g, 2.21 mmol). The reaction mixture was stirred at room temperature overnight and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with a gradient of 0% to 100% ethyl acetate in hexanes to provide the title compound (a compound of the invention) as a solid (0.87 g).

[0726] 1 H NMR (CDCI3): δ 7.78 (s, 1H), 7.70 (d, 1H), 7.63 (s, 1H), 7.22 (d, 1H), 7.15 (s, 2H), 6.76 (s, 1H), 4.82 (br s, 1H), 4.41 (br s, 2H), 3.70 (s, 3H), 2.37 (s, 3H), 1.95-1.88 (m, 1H), 1.12-1.08 (m, 2H), 0.80-0.72 (m, 2H).

[0727] LCMS: m / z 430 [M+H] +

[0728] Example 18

[0729] Preparation of methyl N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-l,2,3-triazol-4-yl]- 2-methylphenyl]methyl]carbamate (Compound 118) and methyl N-[[5-[l-(2,6-difluoro- 4-nitrophenyl)-lH-l,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 132)

[0730] Step A: Preparation of 2-methyl-5-[2-(trimethylsilyl)ethynyl]benzonitrile

[0731] To a mixture of 2-amino-5-bromobenzonitrile (50 g, 255 mmol) and ethynyltrimethylsilane (181 mL, 1275 mmol) in tetrahydrofuran (600 mL) was added bis(triphenylphosphine)palladium(II) chloride (26 g, 38 mmol), copper(I) iodide (14.5 g, 76.5 mmol), triphenylphosphine (20 g, 76.5 mmol) and triethylamine (600 mL). The reaction mixture was stirred at room temperature for 24 h and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with 5% ethyl acetate in petroleum ether to afford the title compound as a solid (45 g).

[0732] 1 H NMR (CDCI3): δ 7.68 (d, 1 H), 7.63 (dd, 1 H), 7.24 (s, 1 H), 2.53 (s, 3 H), 0.24 (s, 9 H). Step B: Preparation of 5-ethynyl-2-methylbenzonitrile

[0733] To a mixture of 2-methyl-5-[2-(trimethylsilyl)ethynyl]benzonitrile (i.e. the product of Step A) (40 g, 187.7 mmol) in methanol (800 mL) was added potassium hydroxide (67 mL, 1% in methanol). The reaction mixture was stirred at room temperature for 16 h and then distilled to remove the methanol. The resulting mixture was diluted with water (200 mL) and extracted with ethyl acetate. The combined organic extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography eluting with 12% ethyl acetate in petroleum ether to afford the title compound as a solid (15 g).

[0734] 1 H NMR (CDCI3): δ 7.70 (d, 1 H), 7.57 (dd, 1 H), 7.28 (d, 1 H), 3.12 (s, 1 H), 2.55 (s, 3 H). Step C: Preparation of 5-ethynyl-2-methylbenzylamine hydrochloride

[0735] To a mixture of diphenylsilane (81 mL, 443 mmol) in chloroform (250 mL) was added tris(2,3,4,5,6-pentafluorophenyl)borane (2.7 g, 5.3 mmol) followed by a solution of 5-ethynyl-2-methylbenzonitrile (i.e. the product of Step B) (25 g, 177.3 mmol) in chloroform. The reaction mixture was stirred at room temperature for 16 h and concentrated under reduced pressure. Hydrochloric acid (2N solution in diethyl ether) was added to the resulting material and the mixture was stirred for 1 h. The resulting solid precipitate was collected by filtration and dried to provide the title compound as a solid (30 g).

[0736] 1 H NMR (DMSO-d6): δ 8.26 (br s, 3H), 7.53 (s, 1H), 7.37-7.39 (m, 1H), 7.27-7.25 (m, 1H), 4.19 (s, 1H), 4.01 (s, 2H), 2.35 (s, 3H).

[0737] Step D: Preparation of methyl [(5-ethynyl-2-methylphenyl)methyl]carbamate

[0738] To a mixture of 5-ethynyl-2-methylbenzenamine hydrochloride (i.e. the product of Step C) (30 g, 165.7 mmol) and potassium carbonate (68.5 g, 497 mmol) in acetonitrile (330 mL) at 0 °C was added methyl chloroformate (23.3 g, 248.6 mmol) dropwise over 20 minutes. The reaction mixture was stirred at room temperature for 16 h, then diluted with water (200 mL) and extracted with ethyl acetate. The combined organic extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography (eluting with 30% ethyl acetate in petroleum ether) to provide the title compound as a solid (25 g). 1 H NMR (CDCI3): δ 7.38 (br s, 1H), 7.33-7.31 (m, 1H), 7.13-7.11 (m, 1H), 4.83 (br s, 1H) 4.34 (d, 2H), 3.71 (s, 3H), 3.04 (s, 1H), 2.32 (s, 3H).

[0739] Step E: Preparation of methyl N-[[5-(lH-l,2,3-triazol-4-yl)-2-methylphenyl]methyl]carbamate

[0740] To a mixture of methyl [(5-ethynyl-2-methylphenyl)methyl]carbamate (i.e. the product of Step D) (30 g, 165.7 mmol) in N,N-dimethylformamide (117 mL) was added methanol (12 mL), azidotrimethylsilane (11.7 mL, 88.6 mmol) and copper (I) iodide (0.56 g, 2.9 mmol). The reaction mixture was heated at 100 °C for 16 h, then diluted with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic extracts were washed with water and saturated sodium chloride solution, 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 afford the title compound (4 g) as a solid.

[0741] 1 H NMR (CDCI3): δ 11.8 (br s, 1 H), 7.94 (s, 1 H), 7.71 (s, 1 H), 7.64-7.61 (m, 1 H), 7.24 (s, 1 H), 4.93 (br s, 1 H), 4.43 (d, 2 H), 3.71 (s, 3 H), 2.37 (s, 3 H).

[0742] Step F: Preparation of methyl N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-1,2,3- triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 118) and methyl N-[[5-[1 -(2,6-difluoro-4-nitrophenyl)-1 H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 132)

[0743] To a mixture of methyl N-[[5-(1 H-1,2,3-triazol-4-yl)-2-methylphenyl]methyl]carbamate (i.e. the product of Step E) (4 g, 16.2 mmol) in dimethyl sulfoxide (40 mL) was added potassium carbonate (6.7 g, 48.6 mmol) followed by 1,2,3-trifluoro-5-nitrobenzene (3.1 g, 17.8 mmol). The reaction mixture was stirred at room temperature for 16 h, and then diluted with water (30 mL) and extracted with ethyl acetate. The combined organic extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography eluting with 20% ethyl acetate in petroleum ether to afford methyl N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 118) (a compound of the application) (2 g) as a solid.

[0744] 1H NMR (DMSO-d6): δ 8.77 (s, 1H), 8.45 (dd, 2H), 7.80 (s, 1H), 7.76-7.74 (m, 1H), 7.69-7.66 (m, 1H), 7.32 (d, 1H), 4.24 (d, 2H), 3.55 (s, 3H), 2.33 (s, 3H).

[0745] LCMS: m / z: 404 [M+H] + .

[0746] A solid comprising a mixture of methyl N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-1,2,3- triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 118) and methyl N-[[5-[1 -(2,6- difluoro-4-nitrophenyl)-1 H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 132) was also obtained. Further purification of the solid by silica gel chromatography provided methyl N-[[5-[1 -(2,6-difluoro-4-nitrophenyl)-1 H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]carbamate (Compound 132) as a solid (800 mg) (a compound of the application).

[0747] 1 H NMR (DMSO-d6): δ 9.08 (s, 1H), 8.50 (d, 2H), 7.83-7.82 (m, 2H), 7.71-7.67 (m, 2H), 7.29 (d, 1H), 4.24 (d, 2H), 3.57 (s, 3H), 2.32 (s, 3H).

[0748] LCMS: m / z: 404 [M+H] + .

[0749] Example 19

[0750] Preparation of methyl N-[[5-[2-(4-amino-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]carbamate (Compound 115)

[0751] To a mixture of methyl N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-1,2,3-triazol-4- yl]-2-methylphenyl]methyl]carbamate (i.e. the product from Example 18, Step F, Compound 118) (2 g, 4.9 mmol) in ethanol (18 mL) and water (2 mL) was added iron powder (2.7 g, 49.6 mmol) and ammonium chloride (0.16 g, 2.9 mmol). The reaction mixture was heated at reflux for 1.5 h, stirred at room temperature for 16 h, and then filtered through Celite (celite filter aid) rinsing with ethyl acetate (30 mL). The filtrate was diluted with water and extracted with ethyl acetate. The combined organics were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography eluting with 30% ethyl acetate in petroleum ether to provide the title compound (a compound of the invention) as a solid (1.6 g). The residue was diluted with water and extracted with ethyl acetate. The combined organics were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography eluting with 30% ethyl acetate in petroleum ether to provide the title compound (a compound of the invention) as a solid (1.6 g).

[0752] 1 H NMR (CDCI3): d 8.08 (s, 1 H), 7.74-7.73 (m, 1 H), 7.67-7.65 (m, 1 H), 7.24 (s, 1 H), 6.33-6.30 (m, 2H), 4.89 (br s, 1 H), 4.42 (d, 2H), 4.13 (s, 2H), 3.70 (s, 3H), 2.37 (s, 3H LCMS: m / z: 374 [M+H] + .

[0753] The following compounds were prepared in a similar manner to that in Example 19:

[0754] Methyl N-[[5-[1 -(4-amino-2,6-difluorophenyl)-1 H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]carbamate (Compound 131 ).

[0755] 1 H NMR (CDCI3): d 8.08 (s, 1 H), 7.74-7.73 (m, 1 H), 7.67-7.65 (m, 1 H), 7.24 (s, 1 H), 6.33-6.30 (m, 2H), 4.89 (br s, 1 H), 4.42 (d, 2H), 4.13 (s, 2H), 3.70 (s, 3H), 2.37 (s, 3H LCMS: m / z: 374 [M+H]

[0756] Example 20

[0757] Methyl N-[[5-[2-(4-chloro-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]carbamate

[0758] Preparation of (Compound 117)

[0759] To a mixture of methyl N-[[5-[2-(4-amino-2,6-difluorophenyl)-2H-1,2,3-triazol-4- yl]-2-methylphenyl]methyl]carbamate (i.e. the product of Example 19) (1 g, 2.68 mmol) in carbon tetrachloride (125 mL) was added n-butyl nitrite (3.3 g, 32.17 mmol). The reaction mixture was heated at reflux for 16 h and then filtered through a pad of celite (celite filter aid) rinsing with ethyl acetate (20 mL). The filtrate was diluted with water (60 mL) and extracted with ethyl acetate. The combined organics were washed with saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography eluting with 30% ethyl acetate in petroleum ether to afford the title compound (a compound of the invention) as a solid (0.12 g).

[0760] 1 H NMR (CDCI3): d 8.13 (s, 1 H), 7.74-7.73 (m, 1 H), 7.66 (dd, 1 H), 7.28 (s, 1 H), 7.19-7.15 (m, 2H), 4.90 (br s, 1 H), 4.43 (d, 2H), 4.71 (s, 3H), 2.38 (s, 3H).

[0761] LCMS: m / z: 393 [M+H] + .

[0762] The following compounds were prepared in a similar manner to that in Example 20:

[0763] Methyl N-[[5-[1 -(4-chloro-2,6-difluorophenyl)-1 H-1,2,3-triazol-4-yl]-2- methylphenyl]methyl]carbamate (Compound 121 ).

[0764] 1 H NMR (CDCI3): d 8.13 (s, 1 H), 7.74-7.73 (m, 1 H), 7.66 (dd, 1 H), 7.28 (s, 1 H), 7.19-7.15 (m, 2H), 4.90 (br s, 1 H), 4.43 (d, 2H), 4.71 (s, 3H), 2.38 (s, 3H).

[0765] LCMS: m / z: 393 [M+H] + .

[0766] ​The following compounds of Tables 1A-33D can be prepared by the procedures described herein and methods known in the art. The following abbreviations are used in the subsequent tables: n means normal, i means iso, c means cyclo, Me means methyl, Et means ethyl, Pr means propyl, MeO means methoxy, EOt means ethoxy, MeS means methylthio, EtS means ethylthio, -CN means cyano, and -NO2 means nitro.

[0767]

[0768] Table 1A R 1 and R 2 are F

[0769]

[0770] The present disclosure also includes Tables 2A-33A, each of which is constructed identically to Table 1A above, except that the row headings in Table 1A (i.e., “R 1 and R 2 are F”) are replaced by the corresponding row headings shown below. For example, in Table 2A the row headings are “R 1 and R 2 are Cl”, and R 6 is as defined in Table 1A above.

[0771]

[0772] Table 1B

[0773] Table 1B is identical to Table 1A except that the chemical structure in Table 1A is replaced by the following structure:

[0774]

[0775] Table 2B-33B

[0776] Tables 2B-33B are constructed in a similar manner to Tables 2A-33A.

[0777] Table 1C

[0778] Table 1C is identical to Table 1A except that the chemical structure in Table 1A is replaced by the following structure:

[0779]

[0780] Table 2C-33C

[0781] Tables 2C-33C are constructed in a similar manner to Tables 2A-33A.

[0782] Table 1D

[0783] Table 1D is the same as Table 1A except that the chemical structure in Table 1A is replaced by the following structure:

[0784]

[0785] Table 2D-33D

[0786] Tables 2D to 33D are constructed in a similar manner to Tables 2A to 33A.

[0787] Formulation / Utility

[0788] The compounds of the application having Formula 1 (including N-oxides and salts thereof) or mixtures (i.e., compositions) comprising the compounds with at least one additional fungicidal compound as described in the Summary will generally be used as the fungicidally active ingredient in a composition (i.e., formulation) wherein at least one additional component is selected from the group consisting of surfactants, solid diluents, and liquid diluents, serving as a carrier. The formulation or composition components are selected to be consistent with the physical characteristics of the active ingredient, the mode of application, and environmental factors such as soil type, moisture, and temperature.

[0789] Mixtures of component (a) (i.e., at least one compound of Formula 1, N-oxides, or salts thereof) with component (b) (e.g., selected from (b1) to (b54) as described above, and salts thereof) and / or one or more other biologically active compounds or agents (i.e., insecticides, other fungicides, nematicides, miticides, herbicides, and other biological agents) can be formulated in a variety of ways, including:

[0790] (i) Component (a), component (b), and / or one or more other biologically active compounds or agents can be formulated separately and applied separately or simultaneously, e.g., as a tank mix, in the appropriate weight ratios; or

[0791] (ii) Component (a), component (b), and / or one or more other biologically active compounds or agents can be formulated together in the appropriate weight ratios.

[0792] 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. General types of aqueous liquid compositions are soluble concentrates, suspension concentrates, capsule suspensions, concentrated emulsions, microemulsions, oil-in-water emulsions, flowable concentrates, and suspoemulsions. General types of non-aqueous liquid compositions are emulsifiable concentrates, microemulsifiable concentrates, dispersible concentrates, and oil dispersions.

[0793] The general types of solid compositions are dusts, powders, granules, pellets, prills, tablets, pellets, 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 treatments. The active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively, the entire formulation of the active ingredient can be encapsulated (or "coated"). Encapsulation can control or delay the release of the active ingredient. Emulsifiable granules combine the advantages of both emulsifiable concentrate formulations and dry granular formulations. High-strength compositions are primarily used as intermediates for further formulation.

[0794] Of note are composition embodiments wherein particles comprising a solid composition of a compound of Formula 1 (or an N-oxide or salt thereof) are mixed with particles comprising a solid composition of component (b). These mixtures can be further mixed with particles comprising additional agricultural protectants. Alternatively, two or more agricultural protectants (e.g., a compound of Formula 1 as component (a), a compound of component (b), an agricultural protectant different from component (a) or (b)) can be combined in a solid composition of one set of particles, which is then mixed with particles of one or more sets of solid compositions comprising one or more additional agricultural protectants. These particle mixtures can be according to the general particle mixture disclosure of PCT Patent Publication WO 94 / 24861, or more preferably the uniform particle mixture teachings of U.S. Patent 6,022,552.

[0795] Sprayable formulations are typically dispersed in a suitable medium prior to spraying. Such liquid and solid formulations are formulated to be readily dilutable in the spray medium, usually water, but occasionally another suitable medium like an aromatic or paraffinic hydrocarbon or a vegetable oil. The volume of spray can range from about one liter to several thousand liters per hectare, but more typically is in the range of from about ten to several hundred liters per hectare. The sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by air or ground application, or for application into the growth medium of the plant. Liquid and dry formulations can be metered directly into a drip irrigation system, or metered into a furrow during planting. Liquid and solid formulations can be applied to the seeds of the crop and other desired vegetation as a seed treatment prior to planting to protect the developing roots and other below-ground plant parts and / or the foliage by systemic uptake.

[0796] Formulations will typically contain up to 100 weight percent of an effective amount of active ingredient, diluent, and surfactant, in the approximate ranges below.

[0797]

[0798] 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, diatomite, urea, calcium carbonate, sodium and sodium 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.

[0799] Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidone), alkyl phosphates (e.g., triethyl phosphate), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oil, n-paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerol, glycerol triacetate, sorbitol, aromatic hydrocarbons, de-aromatized 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 gamma-butyrolactone, and alcohols which can be linear, branched, saturated, or unsaturated such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecanol, isooctadecanol, sperm whale alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol, methylphenyl carbinol, and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22) such as vegetable seed and fruit oils (e.g., olive oil, castor oil, linseed oil, sesame oil, corn oil (maize oil), peanut oil, sunflower seed oil, grape seed oil, safflower oil, cottonseed oil, soybean oil, rapeseed oil, coconut oil, and palm kernel oil), fats of animal origin (e.g., beef tallow, lard, hog fat, fish liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated (e.g., methylated, ethylated, butylated) fatty acids, where the fatty acids can be obtained by hydrolysis of glycerides from vegetable and animal sources and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd ed., Interscience, New York, 1950. 22 ) of saturated and unsaturated fatty acids (typically C6-C

[0800] The solid and liquid compositions of the present application generally comprise one or more surfactants. When added to a liquid, surfactants (also known as "surface-active agents") generally change, most often lower, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, surfactants can function as wetting agents, dispersants, emulsifiers, or defoamers.

[0801] Surfactants can be classified as nonionic, anionic, or cationic. Nonionic surfactants useful in the compositions of the present application include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols, which can be branched or straight chain, and prepared from alcohols and ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof; amine ethoxylates, alkanolamides, and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean oil, castor oil, and rapeseed oil; alkyl phenol alkoxylates such as octyl phenol ethoxylate, nonyl phenol ethoxylate, dinonyl phenol ethoxylate, and dodecyl phenol ethoxylate (prepared from phenol and ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers in which the terminal block is prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyryl phenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylated 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, alcohol acid peg (polyethylene glycol) resins, graft or comb polymers, and star polymers; polyethylene glycol (peg); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar derivatives such as sucrose esters, alkyl polyglycosides; alkyl polysaccharides; and glucamides such as a mixture of octyl-N-methyl glucamide and decyl-N-methyl glucamide (e.g., available from Clariant under the name Glucopon® 200XP). GA name available products).

[0802] Useful anionic surfactants include, but are not limited to, alkyl aryl sulfonic acids and their salts; carboxylated alcohols or alkyl phenol ethoxylates; diphenyl sulfonic acid ester 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 alkyl phenol alkoxylates, and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkyl phenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as N,N-alkyl taurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecyl benzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalenes; sulfonates of petroleum fractions; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinates.

[0803] Useful cationic surfactants include, but are not limited to, amides and ethoxylated amides; amines such as N-alkyl propylenediamines, tripropylenetriamine, and dipropylenetetraamine, and ethoxylated amines, ethoxylated diamines, and propoxylated amines (prepared from amines and ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); amine salts such as ammonium acetate and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts, and diquaternary salts; and amine oxides such as alkyl dimethyl amine oxides and bis-(2-hydroxyethyl)-alkyl amine oxides.

[0804] Also useful in the compositions of the present application 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 number of published references, including McCutcheon's Emulsifiers and Detergents, McCutcheon Division of The Manufacturing Confectioner Publishing Co., annual American and International Editions; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, 7th Ed., John Wiley and Sons, New York, 1987.

[0805] The compositions of the present application can also include formulation aids and additives known to those skilled in the art as adjuvants to the formulation (some of which can also be considered to act as solid diluents, liquid diluents, or surfactants). Such formulation aids and additives can control: pH (buffers), foaming during processing (antifoams such as polyorganosiloxanes), settling of active ingredients (suspending agents), viscosity (thixotropic thickening agents), microbial growth within the container (antimicrobials), product freeze (antifreeze agents), color (dye / pigment dispersions), elution (film formers or sticking agents), evaporation (evaporation retarders), and other formulation attributes. Film formers include, for example, polyvinyl acetate, polyvinyl acetate copolymer, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinyl alcohol copolymer, and waxes. Examples of formulation aids and additives include those listed in McCutcheon's Volume 2: Functional Materials, McCutcheon Division of The Manufacturing Confectioner Publishing Co., annual International and North American editions; and PCT publication WO 03 / 024222.

[0806] The compounds of Formula 1 and any additional active ingredients are incorporated into the compositions of the present application typically by dissolving the active ingredients 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 the liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifying agent is typically added to emulsify the solvent containing the active ingredients upon dilution with water. Active ingredient slurries having a particle size of up to 2,000 μm can be wet milled using a media mill to obtain particles having a mean particle size of less than 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations generally require a dry milling process, resulting in a mean particle size in the range of 2 to 10 μm. Dusts and powders can be prepared by blending and, usually, by grinding (for example, with a hammer mill or fluid energy mill). Granules and pellets can be prepared either by spraying the active material on preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp. 147-48; Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and beyond, 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.

[0807] One embodiment of the present application relates to a method for controlling a fungal pathogen comprising diluting a fungicidal composition of the present application (a compound of Formula 1 formulated with a surfactant, a solid diluent, and a liquid diluent, 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 the diluted composition.

[0808] While spray compositions formed by diluting a fungicidal composition of the present application to a sufficient concentration with water can provide adequate efficacy in controlling fungal pathogens, separately formulated adjuvant products can also be added to the spray tank mix. These additional adjuvants are commonly referred to as "spray adjuvants" or "tank mix adjuvants" and include any substance mixed in the spray tank to improve the performance of the pesticide or to alter the physical properties of the spray mixture. Adjuvants can be anionic or non-ionic surfactants, emulsifiers, petroleum-based crop oils, crop-derived seed oils, acidulants, buffers, thickeners, or antifoam agents. Adjuvants are used to enhance efficacy (e.g., bioavailability, adhesion, penetration, coverage uniformity, and protection durability), or to minimize or eliminate spray application problems associated with incompatibility, foaming, drift, evaporation, volatilization, and degradation. To achieve optimal performance, adjuvants are selected based on the properties of the active ingredient, the formulation, and the target (e.g., crop, insect pest).

[0809] The amount of adjuvant added to the spray mixture is typically in the range of about 0.1% to 2.5% by volume. The application rate of adjuvant added to the spray mixture is typically between about 1 and 5 L per hectare. Representative examples of spray adjuvants include: Adjuvant 47% methylated rapeseed oil in liquid hydrocarbon, Adjuvant II® (Syngenta) Adjuvant polyether-modified heptamethyltrisiloxane, Adjuvant 22® (Helena Chemical Company) Adjuvant 17% surfactant blend in 83% paraffinic mineral oil, Adjuvant 24® (BASF)

[0810] One method of seed treatment is by spraying or dusting the seed with a compound of the present application (i.e., as a formulated composition) prior to sowing the seed. Compositions formulated for seed treatment typically include a film-forming agent or a binder. Thus, typically, a seed coating composition of the present application includes a biologically effective amount of a compound of Formula 1 and a film-forming agent or a binder. Seed can be coated by spraying a flowable suspension directly onto a tumbling bed of seed and then drying the seed. Alternatively, other formulation types such as wettable powders, solutions, suspoemulsions, emulsifiable concentrates, and emulsions in water can be sprayed on the seed. This method is particularly useful for applying a film coating to the seed. Various coating machines and methods are available to the skilled artisan. Suitable methods include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Monograph No. 57, and references listed therein.

[0811] For further information on the field of formulation, see T.S. Woods, "The Formulator's Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T.R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, col. 6, line 16 to col. 7, line 19 and Examples 10-41; U.S. 3,309,192, col. 5, line 43 to 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 to 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.

[0812] In the following examples, all percentages are by weight, and all formulations are prepared in the conventional manner. Active ingredient refers to the compounds of the Index Tables A-F disclosed herein. Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present application. The following examples are provided by way of illustration and not by way of limitation.

[0813] Example A

[0814] High-strength concentrate

[0815] Compound 3 98.5%

[0816] Silica aerogel 0.5%

[0817] Synthetic amorphous fine silica 1.0%

[0818] Example B

[0819] Wettable powder

[0820]

[0821] Example C

[0822] Granule

[0823] Compound 6 10.0%

[0824] Attapulgite granules (low volatile, 0.71 / 0.30 90.0%

[0825] mm; U.S.S. No. 25-50 sieve)

[0826] Example D

[0827] Extruded pellet

[0828]

[0829] Example E

[0830] Emulsifiable concentrate

[0831] Compound 11 10.0%

[0832] Polyoxyethylene sorbitol hexaoleate 20.0%

[0833] C6-C 10 Fatty acid methyl esters 70.0%

[0834] Example F

[0835] Microemulsion

[0836]

[0837] Example G

[0838] Seed treatment

[0839]

[0840] Example H

[0841] Fertilizer rod

[0842]

[0843] Example I

[0844] Suspension

[0845]

[0846]

[0847] Example J Emulsion in water

[0848]

[0849] Example K Oil dispersion

[0850]

[0851] Example L Suspoemulsion

[0852]

[0853]

[0854] Water-soluble and water-dispersible formulations are typically diluted with water prior to application to form an aqueous composition. Aqueous compositions (e.g., spray tank compositions) that are applied directly to a plant or portion thereof typically contain at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of one or more compounds of the present application.

[0855] Seeds are typically treated at a rate from about 0.001 g (more typically about 0.1 g) to about 10 g per kg of seed (i.e., from about 0.0001% to 1% by weight of the seed prior to treatment). Flowable suspensions formulated for seed treatment typically comprise from about 0.5% to about 70% active ingredient, from about 0.5% to about 30% film-forming binder, from about 0.5% to about 20% dispersing agent, from 0% to about 5% thickening agent, from 0% to about 5% pigment and / or dye, from 0% to about 2% antifoam agent, from 0% to about 1% preservative, and from 0% to about 75% volatile liquid diluent.

[0856] The compositions of the invention can be used as plant disease control agents. Accordingly, the invention further includes a method for controlling plant diseases caused by fungal plant pathogens, the method comprising applying to the plant or portion thereof to be protected or to the seed of the plant 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 the invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the phyla 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, the name of the sexual / anamorphic / teleomorphic stage is listed, where known, along with the name of the asexual / anamorphic / teleomorphic stage (in parentheses). Synonyms for the pathogen are indicated by an equal sign. For example, the sexual / anamorphic / teleomorphic stage name Phaeosphaeria nodorum is followed by the corresponding asexual / anamorphic / teleomorphic stage name Stagnospora nodorum and the synonymous older name Septoria nodorum.

[0857] Table 1-1

[0858]

[0859]

[0860]

[0861] 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 compositions of the invention can be used to increase (i.e., increase) the ratio of beneficial microorganisms to harmful microorganisms in contact with or in the agronomic environment of a crop plant or propagule thereof (e.g., seed, corm, bulb, tuber, cutting).

[0862] The compositions of the present application can be used to treat all plants, plant parts, and seeds. Plant and seed varieties and cultivars can be obtained by conventional methods of breeding and selection 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 or seed genome. Transgenes defined by the specific location in the plant genome are referred to as transformation or transgenic events.

[0863] Genetically modified plant cultivars which can be treated according to the application include all plants which have been modified by the use of genetic engineering methods, including the expression of foreign or endogenous genes, and which have a modified genetic material. Genetically modified plants include plants whose genetic material has been recombined, i.e., has been manipulated by genetic engineering methods. Genetic recombination is to be understood as the deliberate modification of the genetic material, i.e., by the targeted introduction or removal of a foreign or endogenous gene or genes, or a targeted change in the genetic makeup of the organism. The genetic material can be DNA or RNA.

[0864] Genetically modified plant cultivars which can be treated according to the application include those that are resistant to one or more biotic stresses (pests such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (drought, cold, soil mineralization, etc.), or that comprise other desirable characteristics. Plants can be genetically modified to exhibit traits such as herbicide tolerance, insect resistance, modified oil profile, or drought tolerance.

[0865] Treatment of genetically modified plants and seeds with the compounds of the present application can result in over-additive or enhanced effects. For example, reduced application rates, expanded activity spectrum, increased tolerance to biotic / abiotic stress, or enhanced storage stability can be greater than expected from simply additive effects of applying the compounds of the present application on genetically modified plants and seeds.

[0866] The compounds and compositions of the present application are particularly useful in seed treatments for crops, including but not limited to maize (corn), soybean, cotton, cereals (for example, wheat, oats, barley, rye, and rice), potato, vegetables, and canola.

[0867] In addition, the compounds and compositions of the present application can be used to treat postharvest diseases of fruits and vegetables caused by fungi, oomycetes, and bacteria. These infections can occur before, during, and after harvest. For example, infection can occur before harvest and then remain dormant until some point during ripening (e.g., the host begins to undergo tissue changes in a manner that infection can proceed or conditions become conducive to disease development); infection can also result from surface wounding by mechanical or insect injury. In this regard, the compositions of the present application can reduce losses (i.e., losses resulting from quantity and quality) due to postharvest diseases that can occur at any time from harvest to consumption. Treatment of postharvest diseases with the compounds of the present application can increase the period of time during which perishable edible plant parts (e.g., fruits, seeds, leaves, stems, bulbs, tubers) can be stored after harvest, either refrigerated or unrefrigerated, and remain edible and free from significant or deleterious degradation or contamination by fungi or other microorganisms. Treatment of edible plant parts before or after harvest with the compounds of the present application can also reduce the formation of toxic metabolites of fungi or other microorganisms, e.g., mycotoxins such as aflatoxins.

[0868] Plant disease control is generally achieved by applying an effective amount of a compound of the present application to the parts of the plant to be protected, such as the roots, stems, leaves, fruits, seeds, tubers, or bulbs, or to the medium (soil or sand) in which the plant to be protected is growing, either before or after infection. The compounds can also be applied to the seed to protect the seed and the seedling that develops from the seed. The compounds can also be applied through irrigating water to treat the plant. Control of postharvest pathogens that infect preharvest produce is typically achieved by applying a compound of the present application in situ, and in cases where infection occurs after harvest, the compounds can be applied to the harvested crop as a dip, spray, fumigant, treatment wrap, and box liner.

[0869] The compounds and compositions of the present application can also be applied using unmanned aerial vehicles (UAVs) to disperse the compositions disclosed herein over a planted area. In some embodiments, the planted area is an area containing a crop. In some embodiments, the crop is selected from a monocot or a dicot. In some embodiments, the crop is selected from rice, corn, barley, soybean, wheat, vegetables, tobacco, tea, fruit trees, and sugar cane. In some embodiments, the compositions disclosed herein are formulated for application as an ultra-low volume spray. Products applied by drones can use water or oil as the spray carrier. Typical spray volumes (including product) for global drone applications. 5.0 liters / ha - 100 liters / ha (approximately 0.5 gpa - 10 gpa). This includes a range from ultra-low volume (ULV) to low volume (LV) spray. While not common, there can be instances where even lower spray volumes as low as 1.0 liter / ha (0.1 gpa) can be used.

[0870] Suitable application rates (e.g., fungicidally effective amounts) of component (a) (i.e., at least one compound selected from the group consisting of compounds of Formula 1, N-oxides, and salts thereof) and suitable application rates (e.g., biologically effective amounts, fungicidally effective amounts, or insecticidally effective amounts) of mixtures and compositions comprising component (a) according to the present application can be influenced by factors such as the plant disease to be controlled, the plant species to be protected, the population structure of the pathogen to be controlled, environmental humidity and temperature, and the like and should be determined under practical use conditions. One skilled in the art can readily determine the fungicidally effective amount needed to achieve the desired level of plant disease control through simple experimentation. Leaves can generally be protected when treated at a rate of from less than about 1 g / ha to about 5,000 g / ha of active ingredient. Seeds and seedlings can generally be protected when treated at a rate of from about 0.001 g (more typically about 0.1 g) to about 10 g per kg of seed. One skilled in the art can readily determine application rates of component (a) and mixtures and compositions thereof, containing the particular combination of active ingredients according to the present application needed to provide the spectrum of desired plant protection and control of plant diseases and, optionally, other plant pests, through simple experimentation.

[0871] The compounds and compositions of the present application can also be used to increase the vigor of a crop plant. This method comprises contacting a crop plant (e.g., a leaf, flower, fruit, or root) or a seed from which a crop plant grows with an amount (i.e., a biologically effective amount) of a composition comprising a compound of Formula 1 sufficient to achieve the desired vigor effect on the plant. Typically, the compound of Formula 1 is applied in a formulated composition. Although the compound of Formula 1 is typically applied directly to the crop plant or to a seed thereof, the compounds can also be applied to the locus of the crop plant, i.e., the environment of the crop plant, particularly in sufficient proximity to allow the compound of Formula 1 to migrate to the environment portion of the crop plant. The locus associated with this method most typically includes the growth medium (i.e., the medium that provides nutrients to the plant), typically soil in which the plant is growing. Thus, treatment of a crop plant to increase the vigor of the crop plant comprises contacting the crop plant, a seed from which the crop plant grows, or the locus of the crop plant with a biologically effective amount of a compound of Formula 1.

[0872] Increasing the vigor of a crop plant can result in one or more of the following observed effects: (a) optimal crop establishment as demonstrated by superior seed germination, crop emergence, and crop stand; (b) enhanced crop growth as demonstrated by rapid and robust leaf growth (e.g., as measured by leaf area index), plant height, tiller number (e.g., for rice), root mass, and total dry weight of the vegetative mass of the crop; (c) improved crop yield as demonstrated by flowering time, flowering duration, number of flowers, total biomass accumulation (i.e., yield), and / or fruit or grain product quality marketability (i.e., yield quality); (d) enhanced ability of the crop to tolerate or prevent infection by plant disease pathogens and arthropod, nematode, or mollusk pests; and (e) increased ability of the crop to tolerate environmental stress such as exposure to extreme heat, suboptimal moisture, or phytochemicals.

[0873] The compounds and compositions of the present application can increase the vigor of a treated plant by preventing and / or curing plant disease caused by fungal plant pathogens in the plant's environment, as compared to an untreated plant. In the absence of such control of plant disease, the disease reduces the vigor of the plant by consuming plant tissue or sap, or by spreading plant pathogens such as viruses. Even in the absence of fungal plant pathogens, the compounds of the present application can increase the vigor of a plant by altering the plant's metabolism. Generally, the vigor of a crop plant will be most significantly increased by treating the plant with the compounds of the present application if the plant is growing in a non-ideal environment, i.e., an environment that includes one or more aspects that are not conducive to the plant realizing its full genetic potential as it would perform in an ideal environment.

[0874] Of note are methods for increasing the vigor of a crop plant, wherein the crop plant is growing in an environment that includes plant disease caused by a fungal plant pathogen. Also of note are methods for increasing the vigor of a crop plant, wherein the crop plant is growing in an environment that does not include plant disease caused by a fungal plant pathogen. Also of note are methods for increasing the vigor of a crop plant, wherein the crop plant is growing in an environment that includes an amount of water that is less than an ideal amount of water to support the growth of the crop plant.

[0875] The compounds and compositions of the present application can also be mixed with one or more other biologically active compounds or agents to form a multi-component pesticidal agent to impart an even broader spectrum of agricultural protection, including fungicides, insecticides, nematicides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect ecdysis inhibitors and root growth stimulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, viruses or fungi. Accordingly, the present application is also directed to compositions 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 the composition can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compound or agent can be formulated into a composition comprising at least one of a surfactant, a solid or liquid diluent. For the mixtures of the present application, one or more other biologically active compounds or agents can be formulated together with the compound of Formula 1 to form a pre-mix, 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 (e.g., in a spray tank) prior to application, or alternatively, applied sequentially.

[0876] As mentioned in the SUMMARY, one aspect of the present application is a fungicidal composition comprising a compound of Formula 1, N-oxide, or salt thereof (i.e., component (a)) and at least one other fungicide (i.e., component (b)) (i.e., a mixture or combination thereof). Of note are such combinations where the other fungicidally active ingredient has a different site of action than the compound of Formula 1. In certain instances, combinations with at least one other fungicidally active ingredient having a similar control spectrum but a different site of action would be particularly advantageous for resistance management. Accordingly, the compositions of the present application can further comprise a fungicidally effective amount of at least one additional fungicidally active ingredient having a similar control spectrum but a different site of action.

[0877] Examples of fungicides in component (b) include aramid-type benzene-S-methyl, 4-dodecyl-2,6-dimethylmorpholine, azoxystrobin, indoxam, thiamethoxam, tebuconazole, pyraclostrobin, benzalkonium chloride (including benzalkonium chloride-M), cymoxanil, benomyl, benomyl, benomyl (including benomyl-isopropyl), benzovindiflubenzuron, besoxazin, chlorpyrifos, biphenyl, bifenthrin, bifenpyroxenamide, blastomycin-S, cyazofamid, furazolidone, bromelain, thiophanate-methyl, captan, carbendazim, carbendazim, cymoxanil, dimethomorph, chlorothalonil, ethoxysulfuron, clotrimazole, copper hydroxide, copper oxychloride, copper sulfate, eugenol, cyazofamid, cycloflubenzuron, cymoxanil, cyclooxygenated, pyraclostrobin, cymoxanil ... The following fungicides are listed: Pyridaben, Nitrosamine, Ethiocarb, Difenoconazole, Flupyraclostrobin, Mefenoxam, Dimethomorph, Ethiocarb, Tebuconazole (including Tebuconazole-M), Difenoconazole, Dithiocarbamate, Dithiocarbamate, Mothoxyfen, Polyoxin, Dipyridaben, Econazole, Chlorpyrifos, Enoxastrobin (also known as Enoxastrobin), Fluconazole, Ethiocarb, Thiazolamide, Ethiocarb, Tebuconazole, Oxafloxacin, Imidacloprid, Chlorpyrifos, Enoxastrobin, Cyproconazole, Mefenoxam, Cyclopyralid, Isoprothiolane, Seed dressing, Benzoic acid, Butylmorpholine, Amifenpyroxime, Triphenyltin acetate, Triphenyltin chloride, Triphenyltin hydroxide, Ferrous sulfate, Azoxystrobin, Flumetoquinone, Pyridabenamide, Fluazinam Fludioxonil, flufenoxuron, fludioxonil, flumorpholine, fluopyram, fluopyram, fluopyram, fluopyram, fluimide, flupyraclostrobin, fluquinazole, flusilazole, sulfadiazine, fluthiazolinone, fluamide, fenpyroximate, fluopyram, captan, tetrachlorophthalide, furazolidone, furazolidone, biguanide salt, hexaconazole, oxamyl, imazalil, amide, biguanide octylamine sulfonate, biguanide octylamine triacetate, iodopropynyl butylmethoate, styrazide, eprofen trifluconazole, isoprothiolane, iprodione, isoprothiolane, isoprothiolane, isoprothiolane, isoprothiolane, isoprothiolane, isoprothiolane, isoprothiolane, pyraclostrobin, isoprothiolane, mancozeb, mandepropamid, mandocycline Mancozeb, pyraclostrobin, cymoxanil, acaricide, metalaxyl (including metalaxyl-M / metalaxyl-M), chlorfluazuron, tebuconazole, sulfadiazine, mancozeb, fenoxyfen, benomyl, miconazole, cyproconazole, naftifine, tebuconazole, flufenoxuron, octazolone, furazolidone, oxadiazon, oxazolidinone, fluoxetine, oxaziclomefone, oxaziclomefone, oxaziclomefone, oxaziclomefone, oxaziclomefone, tetracycline, oxaziclomefone Isoprothiolane, pendimethalin, pendimethalin, fluopyram, pyraclostrobin, phosphite (including its salts, e.g., fosetyl-aluminum), tetrazolium pyraclostrobin, azoxystrobin, fenvalerate, polyoxin, thiamethoxam, prochloraz, iprodione, propiconazole, propineb, propineb, propineb, propoxyquin, thiophanate-methyl, prothioconazole, azoxystrobin, azoxystrobin, pyraclostrobin, pyraclostrobin, pyraclostrobin, barnyardgrass,Acetonide, pyrimethanil, pyridaben, pyraclostrobin, quinclorac, nitropyrrolizamide, quinazole, quinofolin (registration number 861647-84-9), fenpyroximate, quinoxal, pentachloronitrobenzene, fluoxastrobin, silthiamethoxam, siloxane, spirocycline, streptomycin, sulfur, tebuconazole, terfenadine, tebuconazole, thiamethoxam, thiamethoxam, thiamethoxam, methyl thiophanate, thiamethoxam, methyl thiophanate, mesotrione, topcocarb, toluenesulfonamide, triadimefon, triadimefon, pyraclostrobin, cymoxanil, copper sulfate, tricyclazole, chlorpyrifos, tridemorph, azoxystrobin, fluopyram, cymoxanil, cymoxanil-P, valerate Amines (also known as cymoxanil), vinclozolin, zineb, thiram, benzyl benzoate, N-[2-(1S,2R)-[1,1'-dicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, α-(1-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-isooxazolyl]-3-pyridinemethanol, meso-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxacyclopropyl]methyl]-1H-1,2,4-triazole Meso-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxetanepropyl]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-thione, Meso-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxetanepropyl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole, N-[2-[4-[[3-(4-chlorophenyl)-2-propynyl-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butyramide, N-[2-[4-[[3-(4-chlorophenyl)-2-propynyl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butyramide, N-[2-[4-[[3-(4-chlorophenyl)-2-propynyl] [-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butyramide, N'-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylformamidinium, 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-pyrazinamide, 3-(difluoromethyl)-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-1-methyl-1H-pyrazole-4-carboxamide,5,8-difluoro-N-[2-[3-methoxy-4-[[4-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]ethyl]-4- quinazolinamine, 1 -[4-[4-[5R-[(2,6-difluorophenoxy)methyl]-4,5-dihydro-3- isoxazolyl]-2-thiazolyl]-1 -piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 - yl]ethanone, 4-fluorophenyl N-[1 -[[[1 -(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl] carbamate, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine, alpha-(methoxyimino)-N- methyl-2-[[[1 -[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. Thus, of interest are fungicidal compositions 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.

[0878] Of particular note are compounds of Formula 1 (or N-oxides or salts thereof) (i.e., component (a) in the composition) in combination with a component (b) compound selected from the group consisting of aminophenylarsonic acid (Registry No. 1531626-08-0), azoxystrobin, benzovindiflucarb, bifenazate, captan, carpropamid, chlorothalonil, copper hydroxide, copper oxychloride, copper sulfate, cymoxanil, cyproconazole, cyprodinil, dichlorophenyl-dichloroazene (Registry No. 957144-77-3), diethofencarb, difenacozole, dimoxystrobin, dipyridyone, epoxiconazole, ethaboxam, fenbuconazole, fenpiclonil, fluazinam, fludioxonil, flufenoxystrobin, fluindapyr, fluopyram, flusilazole, flutianil, flutriafol, fluxapyroxad, folpet, fluquinconazole (Registry No. 1314008-27-9), iprodione, iprovalicarb, isoflucypram, isopyrazam, kresoxim-methyl, mancozeb, mandaraquin, meptyldinocap, metalaxyl (including metalaxyl-M / precis), metconazole, metrafenone, methyltetrahydropyridine (Registry No. 1472649-01-6), myclobutanil, nu-2-dihydro-3H-1,2,4-triazole-3-thione and meso-1 -[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4- difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-1 -ylthio)-1 H-1,2,4-triazole (i.e., as component (b) in the composition).

[0879] It is generally preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rates or a broader spectrum of controlled plant pathogens) or resistance management that the compound of Formula 1, N-oxide, or salt thereof be combined with a fungicidal compound selected from the group consisting of azoxystrobin, benzovindiflucy, bifenathi, boscalid, carbendazim, chlorothalonil, copper sulfate, cymoxanil, cyproconazole, difenoconazole, dimoxystrobin, enestrobin, ethaboxam, fluazinam, fludioxonil, flusilazole, fluopicolide, flusilazole, flutriafol, ipfenpyl, ipconazole, iprodione, irpemi, isoflucypram, mefenoxam, metconazole, metominostrobin, metalaxyl-M, monodig, myclobutanil, pefurazoate, picoxystrobin, prothioconazole, pyraclostrobin, pyrametostrobin, pyramut, pyridinitr, silthiofam, tebuconazole, thifluzamide, thiophanate-methyl, triflumizole, and triticonazole.

[0880] In the fungicidal compositions of the present application, component (a) (i.e., at least one compound selected from the group consisting of the compound of Formula 1, N-oxides, and salts thereof) and component (b) are present in fungicidally effective amounts. The weight ratio of component (a) to component (b) (i.e., one or more additional fungicidal compounds) is generally between about 1 :3000 to about 3000:1, and more typically between about 1 :500 to about 500:1. Of note are compositions wherein the weight ratio of component (a) to component (b) is from about 125:1 to about 1 :125. 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 readily determine the weight ratio and application rate of the fungicidal compounds necessary to achieve the desired spectrum of fungicidal protection and control by simple experimentation. It will be apparent that the inclusion of additional fungicidal compounds in component (b) can extend the spectrum of plant diseases controlled beyond that controlled by component (a) alone. Furthermore, Tables A1 to A27 and C1 to C27 exemplify the weight ratio combinations of the fungicidal compounds of the present application. Additionally, Table B1 lists the typical, more typical, and most typical ratio ranges for the particular fungicidal compounds involved in component (b).

[0881] Tables Al to A27 list particular mixtures of the application (the compound numbers refer to the compounds in the index tables A to L). In table Al, each row under the column headings "Component (a)" and "Component (b)" specifically discloses a mixture of component (a) (i.e. compound 3) with a component (b) fungicidal compound. The entries under the heading "Illustrative Ratios" disclose three specific weight ratios of component (a) to component (b) for the disclosed mixture. For example, the first row of table Al discloses a mixture of compound 3 with fenhexamid and lists weight ratios of compound 3 to fenhexamid of 1 : 1, 1 :4 or 1 : 18.

[0882] Table A1

[0883]

[0884]

[0885]

[0886]

[0887]

[0888]

[0889] (*) weight ratio of component (a) to component (b).

[0890] Tables A2 to A27 are each identically constructed to table Al above, except that the entries under the column heading "Component (a)" are replaced by the corresponding component (a) column entries shown below. Thus, for example, in table A2, the entries under the column heading "Component (a)" all recite "compound 4". Thus, the first entry in table A2 specifically discloses a mixture of compound 4 with fenhexamid. Tables A3 to A27 are similarly constructed.

[0891]

[0892]

[0893] Table B1 lists combinations of component (b) compounds with component (a) compounds to illustrate the mixtures, compositions, and methods of the application. The first column of Table B1 lists a particular component (b) compound (e.g., "acibenzolar-S-methyl" is the first entry). The second, third, and fourth columns of Table B1 list ranges of weight ratios relative to the rate at which the component (a) compound is typically applied to a field-grown crop. Thus, for example, the first row of Table B1 discloses that a combination of a component (a) compound with acibenzolar-S-methyl is typically applied at a weight ratio of component (a) to component (b) between 2: 1 and 1 : 180, more typically between 1 : 1 and 1 :60, and most typically between 1 : 1 and 1 : 18. The remaining rows of Table B1 will be similarly constructed. Of particular note are compositions comprising a mixture of any one of the compounds listed in Example 108 as component (a) with the compounds listed in the component (b) column of Table B1 according to the weight ratios disclosed in Table B1. Table B1 thus supplements the particular ratios disclosed in Tables A1-A27 with ranges of ratios for these combinations.

[0894] Table B1

[0895]

[0896]

[0897]

[0898]

[0899]

[0900]

[0901] As already noted, the application includes embodiments in which in the composition comprising components (a) and (b), in which component (b) comprises at least one fungicidal compound from each of two groups selected from (b1) to (b54). Tables C1 to C27 list specific mixtures to illustrate embodiments in which component (b) comprises at least one fungicidal compound from each of two groups selected from (b1) to (b54). Table C1 discloses mixtures of compound 3 of the application with at least two component (b) compounds. The entries under the heading "Illustrative Ratios" disclose three specific weight ratios of component (a) to each component (b) compound. For example, the first row discloses a mixture of compound 3 with cyproconazole and azoxystrobin and lists weight ratios of compound 3 to cyproconazole to azoxystrobin of 1 : 1 : 1, 2: 1 : 1, or 3: 1 : 1.

[0902] Table C1

[0903]

[0904]

[0905]

[0906] (*) The weight ratio of component (a) to component (b) in the order specified.

[0907] Tables C2 to C27 are each identically constructed as Table CI above, except that the entries under the heading "Component (a)" are replaced by the corresponding component (a) column entries shown below. Thus, for example, in Table C2, the entries under the heading "Component (a)" all recite "Compound 4". Thus, the first entry in Table C2 specifically discloses a mixture of Compound 4 with Cyazofyrn and Azoxystrobin, wherein the illustrative weight ratios of Compound 4 to Cyazofyrn to Azoxystrobin are 1 : 1 : 1, 2: 1 : 1, and 3: 1 : 1. Tables C3 to C27 are similarly constructed.

[0908]

[0909] It is noted that the compositions of the present application comprise a compound of Formula 1 (or an N-oxide or salt thereof) in combination with at least one other fungicidal compound having a different site of action than the compound of Formula 1. In certain cases, a combination with at least one other fungicidal compound having a similar control spectrum but a different site of action would be particularly advantageous for resistance management. Thus, the compositions of the present application can advantageously comprise at least one fungicidally active compound selected from the group consisting of (bl) to (b54) as described above, which have a similar control spectrum but a different site of action.

[0910] The component (a), or the combination of component (a) and component (b), can be further mixed with one or more other biologically active compounds or agents, including insecticides, nematicides, fungicides, acaricides, herbicides, herbicide safeners, growth regulators such as insect ecdysis inhibitors and root-stimulating agents, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, viruses or fungi, to form a multi-component pesticide, to impart an even broader spectrum of agricultural protection. Thus, the present application also relates to a composition comprising a fungicidally effective amount of component (a), or a mixture of component (a) and component (b), and a biologically effective amount of at least one additional biologically active compound or agent, and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compounds or agents can also be formulated separately into a composition comprising at least one of a surfactant, a solid or liquid diluent. For the compositions of the present application, one or more other biologically active compounds or agents can be formulated together with either or both of components (a) and (b) to form a pre-mix, or one or more other biologically active compounds or agents can be formulated separately from components (a) and (b) and the formulations combined together (e.g., in a spray tank) prior to application, or alternatively, applied sequentially.

[0911] Examples of such biologically active compounds or agents that can be formulated with component (a) or a combination of component (a) and component (b) are: insecticides such as abamectin, acephate, fenpyroxene, acetamiprid, flufenoxuron, acynonapyr, bispyribac-methyl, sulfadiazine, amitraz, avermectin, azadirachtin, methyl glutathione, carbofuran, sulfadiazine, benzpyrimoxan, bifenthrin, κ-bifenthrin, bifenazate, bispyribac-sodium, borate, broflanilide, thiamethoxam, thion, carbaryl, carbofuran, pyridaben, chlorantraniliprole, brofenoxuron, flufenoxuron, and dextrorotatory trans-chloropropargyl. Chlorpyrifos-e, chlorpyrifos-e, methyl chlorpyrifos, cyclophosphamide, tetradifon, dextrorotatory trans-chloropyrifos, thiamethoxam, bromocyanamide, cyclobromocyanamide, cypermethrin, cyclopyridaben, cypermethrin, cypermethrin, deltamethrin, cypermethrin, cypermethrin, cypermethrin, cis-cypermethrin, ζ-cypermethrin, cyromazine, deltamethrin, difenoconazole, diazinon, dichlorvos, dieldrin, diflubenzuron, tetrafluoromethrin, cartap, dimethoate, pymetrozine, dinotefuran, benzyl ether, methyl parathion Aminoaben, emamectin benzoate, endosulfan, cypermethrin, acetamiprid, permethrin, ε-methoxybenzylflupyr, etoxazole, fenbutatin, fenitrothion, fenthiocarb, fenoxycarb, cypermethrin, flufenoxuron, flumethrin, flumetsulam, trifluralin, flufenoxuron, flufenoxuron, flufenoxuron, flufenoxuron, flufenoxuron, flupyrazole, flufenoxuron, flupyrprole, flupyrflupyr, flupyriminin, lambda-cyhalothrin, t-flupyrflupyr, fluoxazolamide, terbufos, thiamethoxam, lambda-cyhalothrin, chlorantraniliprole, heptamethrin, flufenoxuron, thiamethoxam, flufenoxuron, imidacloprid, indoxacarb, chlorfenapyr Insect soap, isopropyl methamidophos, isoxaflutole, κ-heptafluthrin, lambda-cyhalothrin, lufenuron, malathion, cyfluthrin, cyfluthrin, metaldehyde, methamidophos, chlorpyrifos, thiamethoxam, methomyl, methoxyfenozide, methoxyfenozide, ε-methoxyfenozide, ε-cyhalothrin, monofluorothrin, nicotine, acetamiprid, nitenpyram, flufenoxuron, polyfluorourea, chlorpyrifos, oxazosulfyl, parathion, methyl parathion, permethrin, phorate, fenpyroxen, phosmet, phosmet, pirimicarb, profenofos, propargite, propargite, pyrimethanil, pymetrozine, pyridabenPyrethroids, pyridaben, acetamiprid, pyrimethanil, pyrazosulfuron, pyrazosulfuron, pyriproxyfen, rotenone, ranylamine, flusilazole, ethyl spinosad, spinosad, spirodiclofen, spirodiclofen, ethoxyfen, thiophanate-methyl, flonicamid, tebufenozide, pyridaben, flufenoxuron, heptafluthrin, κ-heptafluthrin, terbufos, tetrachlorfenapyr, chlorfenapyr, pyrethroid, tetrafluthrin, tetrachlorfenapyr, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, tetrabromopyrethrin, pymetrozine, trichlorfon, trifluralin, chlorfenapyr, tyclopyrazoflor, ζ-cypermethrin, Bacillus thuringiensis δ-endotoxin, entomopathogenic bacteria, entomopathogenic viruses, or entomopathogenic fungi.

[0912] One embodiment of a biological agent for mixing with the compounds disclosed herein includes entomopathogenic bacteria, such as Bacillus thuringiensis, and... Encapsulated δ-endotoxins of Bacillus thuringiensis prepared by process, such as and Biological insecticides ( and It is a trademark of Mycogen Corporation, Indianapolis, Indiana, USA; entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic (natural and genetically modified) viruses, including baculoviruses, nucleopolyhedroviruses (NPVs), such as the grain borer nucleopolyhedrovirus (HzNPV) and the celery borer nucleopolyhedrovirus (Anagrapha falcifera nucleopolyhedrovirus, AfNPV); and granuloviruses (GVs), such as the codling moth granulosisvirus (CpGV).

[0913] General references for these agricultural protectants (i.e., insecticides, fungicides, nematicides, miticides, herbicides, and biologicals) include The Pesticide Manual, 13thEdition, C. D. S. Tomlin, Editor, British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2ndEdition, L. G. Copping, Editor, British Crop Protection Council, Farnham, Surrey, U.K., 2001.

[0914] For embodiments in which one or more of the unsegmented pest control compounds are used, the weight ratio of these compounds (total amount) to the compound of component (a) is typically between about 1 :3000 and about 3000: 1. Ratios of about 1 :300 and about 300: 1 are of note (e.g., ratios of about 1 :30 and about 30: 1). One of skill in the art can readily determine the biologically effective amount of active ingredient needed to achieve the desired spectrum of biological activity through simple experimentation.

[0915] The compound of component (a) and / or its combination with the compound of component (b) and / or one or more other biologically active compounds or agents can be applied to plants that have been genetically transformed to express a protein toxic to unsegmented pests, such as Bacillus thuringiensis delta-endotoxin. The effect of the compound of component (a) of the present invention, alone or in combination with component (b), applied exogenously can be synergistic with the expressed toxin protein.

[0916] Of note are combinations or compositions comprising component (a) or components (a) and (b) as described in the SUMMARY, further comprising at least one unsegmented pest control compound or agent (e.g., an insecticide, a miticide). Of particular note are compositions comprising component (a) and at least one (i.e., one or more) unsegmented pest control compound or agent, which can then be subsequently combined with component (b) to provide a composition comprising components (a) and (b) and one or more unsegmented pest control compounds or agents. Alternatively, without first being mixed with component (b), a biologically effective amount of a composition comprising component (a) and at least one unsegmented pest control agent can be applied to a plant or plant seed (directly or through the environment of the plant or plant seed) to protect the plant or plant seed from disease caused by a fungal pathogen and injury caused by an unsegmented pest.

[0917] It is noteworthy that the compositions of the present invention, in addition to component (a) (alone or in combination with component (b)) of the compound, also contain at least one invertebrate pest control compound or agent selected from the group consisting of: abamectin, acetamiprid, flufenoxuron, acetamiprid, difenoconazole, amitraz, avermectin, azadirachtin, carbofuran, chlorantraniliprole, bifenthrin, thiamethoxam, brofenoxuron, thion, carbaryl, fenitrothion, chlorantraniliprole, d-trans-chlorpropamide, brofenoxuron, Chlorpyrifos, thiamethoxam, brofenac, cyclobromin, cypermethrin, deltamethrin, lambda-cyhalothrin, trifluralin, lambda-cyhalothrin, lambda-cyhalothrin, cypermethrin, cis-cypermethrin, ζ-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, benzyl ether, emamectin benzoate, endosulfan, ε-methoxybenzylflupyr, fenvalerate, acetamiprid, permethrin, etoxazole, fenitrothion, fenthion, fenoxycarb, cypermethrin, fipronil, flumethrin, flumethrin Flupyradifonamide, flufenoxuron, flufenoxuron sulfonate, flufenoxuron, flufenoxuron, sulfadiazine, tebufenozide, flupyrrolidone, flupyrflupyr, lambda-cyhalothrin, cypermethrin, thiamethoxam, lambda-cyhalothrin, heptamethrin, flufenoxuron, flufenoxuron, imidacloprid, indoxacarb, isoxaflutole, κ-heptamethrin, lambda-cyhalothrin, lufenuron, cyfluthrin, cyfluthrin, methiocarb, methomyl, tebufenozide, methoxyfenozide, methoxyfenozide, pyrethroid, acetamiprid, nitenpyram, flufenoxuron, The following are included: chlorfenapyr, pyrimethanil, pymetrozine, pyridaben, acetamiprid, pyrimethanil, pyriproxyfen, lanyl alkaloid, spinosad, spinosad, spirodiclofen, spirotetramat, spirotetramat, flupyridine, tebufenozide, pyrethroid, tetraflufenoxam, thiamethoxam, thiamethoxam, thiamethoxam, chlorpyrifos, tetrabromopyrethrin, pymetrozine, trifluralin, chlorfenapyr, pyrazosulfuron, zebufenozide, zebufenozide, Bacillus thuringiensis δ-endotoxin, all strains of Bacillus thuringiensis, and all strains of nucleopolyhedrovirus.

[0918] In certain circumstances, the combination of component (a) of the present invention (alone or in combination with component (b)) with other biologically active (particularly fungicidal) compounds or agents (i.e., active ingredients) can produce effects greater than additive (i.e., synergistic). Reducing the amount of active ingredient released into the environment while ensuring effective pest control has always been desirable. Such combinations can be advantageously used to reduce crop production costs and environmental impact when the application ratio of the fungicidal active ingredient produces a synergistic effect to achieve agronomically satisfactory levels of fungal control.

[0919] Table D1 lists specific combinations of an invertebrate pest control agent and Compound 3 (the compound number refers to the compound in Index Tables A through F) as the compound of component (a), illustrating mixtures and compositions comprising these active ingredients and methods of using them in accordance with the present application. The second column of Table D1 lists the specific invertebrate pest control agent (e.g., “abamectin” in the first row). The third column of Table D1 lists the mode of action (if known) or chemical class of the invertebrate pest control agent. The fourth column of Table D1 lists one or more embodiments of a range of weight ratios in which the invertebrate pest control agent is typically applied relative to Compound 32 alone or in combination with component (b) (e.g., abamectin is “50: 1 to 1 :50” by weight relative to Compound 32). Thus, for example, the first row of Table D1 specifically discloses a combination of Compound 3 and abamectin is typically applied in a weight ratio between 50: 1 and 1 :50. The remaining rows of Table D1 will be similarly constructed. Thus, for example, the first row of Table D1 specifically discloses a combination of Compound 3 and abamectin is typically applied in a weight ratio between 50: 1 and 1 :50. The remaining rows of Table D1 will be similarly constructed.

[0920] Table D1

[0921]

[0922]

[0923] Tables D2 through D27 are each similarly constructed as Table D1 above, except that the entries under the column heading “component (a)” are replaced by the corresponding component (a) column entries shown below. Thus, for example, in Table D2, the entries under the column heading “component (a)” all recite “Compound 4,” and the first row under the column heading in Table D2 specifically discloses a mixture of Compound 4 and abamectin. Tables D3 through D27 are similarly constructed.

[0924]

[0925]

[0926] Compositions comprising a compound of Formula 1 that can be used in seed treatments 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 dwelling animals such as nematodes. Bacteria that exhibit nematicidal properties can include, but are not limited to, Bacillus firmus, Bacillus cereus, Bacillus subtilis, and Pasteuria penetrans. A suitable Bacillus firmus strain is sold as BioNem TMThe commercially available strain CNCM 1-1582 (GB-126). A suitable Bacillus cereus strain is strain NCMM 1-1592. Both Bacillus strains are disclosed in US 6,406,690. Other suitable bacteria that exhibit nematicidal activity are Bacillus amyloliquefaciens IN937a and Bacillus subtilis strain GB03. Bacteria that exhibit fungicidal properties can include, but are not limited to, Bacillus pumilus strain GB34. Fungal species that exhibit nematicidal properties can include, but are not limited to, Myrothecium verrucaria, Paecilomyces lilacinus, and Purpureocillium lilacinum.

[0927] The seed treatment can also include one or more nematicides of natural origin, such as the elicitor protein known as harpin, which is isolated from certain bacterial plant pathogens such as Erwinia amylovora. An example is N-Hibit® as a seed treatment technology available from N-Tek®. TM Gold CST has a Harpin-N-Tek seed treatment technology available.

[0928] The seed treatment can also include one or more rhizobial species of the family Fabaceae, such as the microsymbiotic nitrogen-fixing bacterium Bradyrhizobium japonicum. These inoculants can optionally include one or more lipochitooligosaccharides (LCOs), which are nodulation (Nod) factors produced by rhizobial bacteria during the initiation of nodule formation on the roots of legumes. For example, InnoTech The brand BioN-Boost® seed treatment technology incorporates LCO primers in combination with inoculants TM .

[0929] The seed treatment can also include one or more isoflavones, which can increase the level of mycorrhizal fungal root colonization. Mycorrhizal fungi improve plant growth by enhancing root uptake of nutrients such as water, sulfate, nitrate, phosphate, and metals. Examples of isoflavones include, but are not limited to, genistein, biochanin A, formononetin, daidzein, glycitein, hesperetin, naringenin, and pratensein. Pratensein is available as a mycorrhizal inoculant product such as PHC AG has active ingredients available.

[0930] The seed treatment can also include one or more plant activators that elicit systemic acquired resistance in plants upon contact with a pathogen. An example of a plant activator that elicits such protective mechanisms is acibenzolar-S-methyl.

[0931] In the fungicidal compositions of the present application, the compound of formula 1 of component (a) can act synergistically with the additional fungicidal compound of component (b) to provide such beneficial results as an expanded spectrum of plant diseases controlled, an extended duration of preventive and curative protection, and inhibition of the proliferation of resistant fungal pathogens. In particular embodiments, compositions are provided according to the present application comprising component (a) and component (b) in proportions useful, inter alia, for the control of specific fungal diseases such as Alternaria solani, Erysiphe graminis, Botrytis cinerea, Puccinia recondita, Rhizoctonia solani, Ascochyta tritici, Septoria tritici.

[0932] Mixtures of fungicides can also provide better disease control than might be expected based on the activities of the individual components. Such synergism has been described as "the cooperative action of two components of a mixture so that the total effect is greater than, or more than the sum of the individual effects" (see P. M. L. Tames, Neth. J. Plant Pathology 1964, 70, 73-80). In a method of providing plant disease control, wherein synergism is exhibited from a combination of active ingredients (e.g., fungicidal compounds) applied to a plant or seed, the active ingredients are applied in synergistic weight ratios and in synergistic (i.e., synergistically effective) amounts. The measure of disease control, inhibition, and prevention cannot exceed 100%. Thus, the expression of substantial synergism typically requires the use of application rates of active ingredients, wherein the active ingredients alone provide far less than 100% of the effect, such that their additive effect is substantially less than 100%, to allow the possibility of increased effect due to synergism. On the other hand, application rates of active ingredients that are too low can show little activity in the mixture even with the benefit of synergism. One skilled in the art can readily determine and optimize the weight ratios and application rates (i.e., amounts) of fungicidal compounds that provide synergism through simple experimentation.

[0933] Synergistic effects between two active ingredients are determined by means of the Colby formula (see Colby, S. R. "Calculating Synergistic and Antagonistic Responses of Herbicide Combinations", Weeds, (1967), 15, 20-22):

[0934]

[0935] Synergistic interaction between two active ingredients is determined by first calculating the expected activity p of a mixture based on the activity of the two components applied separately using the Colby method. Synergy occurs if p is lower than the experimentally determined effect. In the above formula, A is the percent control of fungicidal activity of one component applied alone at rate x. Term B is the percent control of fungicidal activity of the second component applied at rate y. The formula estimates p, the expected fungicidal activity of a mixture of A at rate x and B at rate y, if their effects are strictly additive and no interaction occurs.

[0936] The following tests demonstrate the control efficacy of the compounds of the present application against specific pathogens. However, the pathogen control protection provided by the compounds is not limited to these species. See the Index Tables A-F below for compound descriptions. The following abbreviations are used in the Index Tables A-F: Me means methyl, n-Pr means normal propyl, i-Pr means isopropyl, c-Pr means cyclopropyl, i-Bu means isobutyl, c-Bu means cyclobutyl, t-Bu means tert-butyl and NO2 means nitro. The abbreviation "Cmpd." stands for "Compound" and the abbreviation "Ex." stands for "Example" and is followed by a number which indicates in which example the compound was prepared. The abbreviation "m.p." stands for melting point. The numbers reported in the column "MS (M+1)" are the molecular weights of the observed molecular ions formed by adding one hydrogen + (Molecular weight of 1) to the molecule with the greatest isotopic abundance (i.e., M) to form the observed molecular ion. The presence of molecular ions containing one or more higher atomic weight isotopes of lower abundance (e.g., C13, N15, O18, etc.) is not reported. The reported MS peaks were observed by mass spectrometry using either electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI). 37 Cl, 81 Br) are not reported. The reported MS peaks were observed by mass spectrometry using either electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI).

[0937] Index Table A

[0938]

[0939]

[0940]

[0941]

[0942]

[0943] * 1 H NMR data are found in Index Table G.

[0944] Index Table B

[0945]

[0946] Index Table C

[0947]

[0948] Index Table D

[0949]

[0950]

[0951] * 1 H NMR data see Index Table G.

[0952] Index Table E

[0953]

[0954] * 1 H NMR data see Index Table G.

[0955] Index Table F

[0956]

[0957] Index Table G

[0958]

[0959] a 1 H NMR data reported in ppm with low field of tetramethylsilane. Couplings are designated by (s) - singlet, (br s) - broad singlet, (d) - doublet, and (m) - multiplet.

[0960] Biological Examples of the Invention

[0961] General protocol for preparing test suspensions for tests A-F: The test compound is first dissolved in acetone in an amount equal to 3% of the final volume, and then suspended in acetone and purified water (50 / 50 mix by volume) containing 250 ppm of the surfactant PEG400 (polyol ester) at the desired concentration (in ppm). The resulting test suspension is then used for tests A-F.

[0962] Test A

[0963] Test solutions were sprayed to run-off on wheat seedlings. The next day, the seedlings were inoculated with a spore suspension of Zymoseptoria tritici (the causal agent of wheat brown leaf spot) and incubated for 48 h in a saturated atmosphere at 24°C and then moved to a growth chamber at 20°C for 17 days after which disease rating was performed.

[0964] Test B

[0965] Test solutions were sprayed to run-off on wheat seedlings. The next day, the seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated for 24 h in a saturated atmosphere at 20°C and then moved to a growth chamber at 20°C for 7 days after which disease rating was performed.

[0966] Test C

[0967] Test solutions were sprayed to run-off on wheat seedlings. The next 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 for 8 days in a growth chamber at 20°C after which visual disease rating was performed.

[0968] Test D

[0969] Test solutions were sprayed to run-off on soybean seedlings. The next day, the seedlings were inoculated with a spore suspension of Phakopsora pachyrhizi (the causal agent of Asian soybean rust) and incubated for 24 h in a saturated atmosphere at 22°C and then moved to a growth chamber at 22°C for 8 days after which visual disease rating was performed.

[0970] Test E

[0971] Test solutions were sprayed to run-off on tomato seedlings. The next day, the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of tomato gray mold) and incubated for 48 h in a saturated atmosphere at 20°C and then moved to a growth chamber at 24°C for 3 days after which visual disease rating was performed.

[0972] Test F

[0973] The test suspensions were sprayed to run-off on tomato seedlings. The next day, the seedlings were inoculated with a spore suspension of Alternaria solani, the causal agent of early blight of tomato, and incubated for 48 h in a saturated atmosphere at 27°C, and then moved to a growth chamber at 20°C for 3 days, after which visual disease ratings were performed.

[0974] The results of tests A-F for the compounds of formula 1 are given in Table A below. Rating 100 indicates 100% disease control and rating 0 indicates no disease control (relative to the control). A dash (-) indicates that the compound was not tested.

[0975] Table A

[0976]

[0977]

[0978]

[0979] The test results presented in Table A above for tests A to F for the compounds of formula 1 illustrate the fungicidal activity of component (a), which contributes to the plant disease control utility of the compositions comprising component (a) in combination with component (b) and optionally at least one additional fungicidal compound according to the present application.

[0980] Test G below demonstrates the control efficacy of the compositions of the present application on Asian Soybean Rust. The general protocol for preparing the test compositions for Test G is as follows: Compound 41, Compound 63, N-(2,2,2-trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-4-oxazolcarboxamide (b54.11a), 1-[[4-[[ (1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester (b54.11c), 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1H-pyrazole-4-carboxylic acid ethyl ester (b54.11d), azoxystrobin, benzovindiflucarb, bixafen, chlorothalonil, cyproconazole, epoxiconazole, fenpropidin, fenpropimorph, fluindapyr, flutriafol, fluoxymetofen, ipfentrifluconazole, iph- 137, metiram, myclobutanil, propineb, tebuconazole, and trifloxystrobin were obtained as unformulated, technical grade materials. Copper hydroxide and maneb were obtained as formulated products sold under the trademarks KOCIDE 3000 and MANZATE, respectively. The unformulated materials were first dissolved in acetone, and then suspended in acetone and surfactant-containing water at the desired concentrations (in ppm) to make the test solutions. The formulated materials were diluted in water at the desired concentrations (in ppm) to make the test solutions. The test solutions were sprayed to run-off on soybean seedlings. The next day, the seedlings were inoculated with a spore suspension of Phakopsora pachyrhizi, the causal agent of Asian Soybean Rust, and incubated for 48 h in a saturated atmosphere at 27°C, and then moved to a growth chamber at 20°C for 3 days, after which visual disease ratings were performed. 014purified water (50 / 50 mix by volume) of the polyol ester. The formulated material was dispersed in enough water to achieve the desired concentration and no organic solvent nor surfactant was added to the suspension. The resulting test mixture was then used in Test G. The test was conducted on four individual plants and the results are reported as the average of the four plants.

[0981] The presence of a synergistic interaction between two active ingredients was determined by means of the Colby formula (see Colby, S.R. "Calculating Synergistic and Antagonistic Responses of Herbicide Combinations", Weeds, (1967), 15, 20-22):

[0982]

[0983] The presence of a synergistic interaction between two active ingredients was determined using the Colby method by first calculating the expected activity p of a mixture based on the activity of the two components applied individually. Synergy occurs if p is lower than the experimentally determined effect. In the above formula, A is the percent control of fungicidal activity of one component applied individually at rate x. Term B is the percent control of fungicidal activity of the second component applied at rate y. The formula estimates p, the expected fungicidal activity of a mixture of A at rate x and B at rate y, if their effects are strictly additive and no interaction occurs.

[0984] Test G

[0985] The test mixtures were sprayed to runoff on soybean seedlings. The next day, the seedlings were inoculated with a spore suspension of Phakopsora pachyrhizi, the causal agent of Asian Soybean Rust, and incubated for 24 h under saturated atmosphere at 22°C and then moved to a growth chamber at 22°C for 8 days, after which visual disease ratings were performed.

[0986] The results of Test G are given below in Tables B-1 to J-1 for compound 41 and in Tables B-2 to J-2 for compound 63. Each table corresponds to a set of evaluations performed simultaneously together. In each table, rating 100 indicates 100% disease control and rating 0 indicates no disease control (relative to the control). The column labeled "Obsd" indicates the average of the results observed from the test performed on four individual plants. The column labeled "Exp" indicates the expected value for each treatment mixture using the Colby formula.

[0987] Table B-1

[0988] Observed and expected effects of the individual compound 41 and the mixture with N-(2,2,2-trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-4-oxazolecarboxamide (b54.11a), ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methyl]-1H-pyrazole-4-carboxylate (b54.11c), and ethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1H-pyrazole-4-carboxylate (b54.11d) in the control of Asian Soybean Rust

[0989]

[0990]

[0991] Table B-2

[0992] Observed and expected effects of the individual compound 63 and the mixture with ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methyl]-1H-pyrazole-4-carboxylate (b54.11c) and ethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]-1H-pyrazole-4-carboxylate (b54.11d) in the control of Asian Soybean Rust

[0993]

[0994] Table C-1

[0995] Observed and expected effects of the individual compound 41 and the mixture with bixafen, fluazinam, and zoxamide in the control of Asian Soybean Rust

[0996]

[0997] Table C-2

[0998] Observed and expected effects of the individual compound 63 and the mixture with bixafen, fluazinam, and zoxamide in the control of Asian Soybean Rust

[0999]

[1000]

[1001] Table D-1

[1002] Observed and expected effects of compound 41 alone and in mixture with mancozeb, fenpropimorph and tebuconazole in controlling Asian Soybean Rust

[1003]

[1004]

[1005] Table D-2

[1006] Observed and expected effects of compound 63 alone and in mixture with mancozeb, fenpropimorph and tebuconazole in controlling Asian Soybean Rust

[1007]

[1008] Table E-1

[1009] Observed and expected effects of compound 41 alone and in mixture with myclobutanil in controlling Asian Soybean Rust

[1010]

[1011] Table E-2

[1012] Observed and expected effects of compound 63 alone and in mixture with myclobutanil in controlling Asian Soybean Rust

[1013]

[1014] Table F-1

[1015] Observed and expected effects of compound 41 alone and in mixture with epoxiconazole and fluoxastrobin in controlling Asian Soybean Rust

[1016]

[1017]

[1018] Table F-2

[1019] Observed and expected effects of compound 63 alone and in mixture with epoxiconazole and fluoxastrobin in controlling Asian Soybean Rust

[1020]

[1021]

[1022] Table G-1

[1023] Observed and expected effects of compound 41 alone and in mixture with boscalid, prothioconazole, and chlorothalonil in controlling Asian Soybean Rust

[1024]

[1025] Table G-2

[1026] Observed and expected effects of compound 63 alone and in mixture with boscalid, prothioconazole, and chlorothalonil in controlling Asian Soybean Rust

[1027]

[1028] Table H-1

[1029] Observed and expected effects of compound 41 alone and in mixture with pyraclostrobin in controlling Asian Soybean Rust

[1030]

[1031]

[1032] Table H-2

[1033] Observed and expected effects of compound 63 alone and in mixture with pyraclostrobin in controlling Asian Soybean Rust

[1034]

[1035] Table I-1

[1036] Observed and expected effects of compound 41 alone and in mixture with copper hydroxide, flutriafol, fenpropidine, azoxystrobin, triflumizole, and enestrobin in controlling Asian Soybean Rust

[1037]

[1038]

[1039] Table I-2

[1040] Observed and expected effects of compound 63 alone and in mixture with copper hydroxide, flutriafol, fenpropidine, azoxystrobin, triflumizole, and enestrobin in controlling Asian Soybean Rust

[1041]

[1042]

[1043] Table J-1

[1044] Observed and expected effects of compound 41 alone and in mixture with ipfencarbazone in controlling asian soybean rust

[1045]

[1046]

[1047] Table J-2

[1048] Observed and expected effects of compound 63 alone and in mixture with ipfencarbazone in controlling asian soybean rust

[1049]

Claims

1. A fungicidal composition comprising: (a) a compound of Formula 1, and salts thereof, and (b) at least one additional fungicidal compound selected from the group consisting of: (b3) demethylation inhibitor fungicides selected from the group consisting of azaconazole, bitertanol, bromocryptone, bthothalonil, cyproconazole, difenoconazole, enilconazole, enilconazole-M, etaconazole, fluquinconazole, etaconazole, hymexazol, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, ipfentriazole, metconazole, myclobutanil, naftalate, nuconazole, prochloraz, propiconazole, prothioconazole, spicinazole, spiroxamine, quinazamyl, simeconazole, tebuconazole, tetraconazole, triticonazole, triflumizole, triforine, uniconazole, and uniconazole-P; (b5) amine / morpholine fungicides selected from the group consisting of 4-dodecyl-2,6-dimethylmorpholine, dodecylmorpholine, fenpropimorph, fenpropidin, fenpiclonil, spiroxamine, tridemorph, and zoxamide; (b7) succinate dehydrogenase inhibitor fungicides selected from the group consisting of benodanil, bixafen, bifenaptile, boscalid, carboxin, fenfuram, fluazinam, fluindapyr, fluopyram, flutianil, fluoroimide, furophanate, iphensudione, iprovalicarb, isoflucypram, isopyrazam, kresoxim-methyl, metaminostrobin, metiram, metrafenone, pencycuron, pencyval, picoxystrobin, pyraclostrobin, pyrametostrobin, pyramoxystrobin, pyribencarb, pyrisoxazole, and thifluzamide; (b9) anilino-pyrimidine fungicides selected from the group consisting of cyprodinil, pyrimethanil, and pyriminom. (b11) quinone outside inhibitor fungicides selected from the group consisting of azoxystrobin, coumoxystrobin, dimoxystrobin, enoxastrobin, famoxadone, fenamidone, fenaminstrobin, fluopimoxystrobin, fluoxastrobin, kresoxim-methyl, manumycin, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, pyrametostrobin, pyramoxystrobin, spicisoxystrobin, trifloxystrobin, and triflumizole; (b16b) melanin biosynthesis inhibitor-polyketide synthase fungicides selected from the group consisting of tolycloxystrobin; (b17) ketoreductase inhibitor fungicides selected from the group consisting of fenaminstrobin, mandipropamid, fluoroquinconazole, and quinoxyfen; (b21) quinone inside inhibitor fungicides selected from the group consisting of indoxacarb, cyazofamid, and fenpiclanil; (b43) benzamide fungicides selected from the group consisting of fluazinam and fluopimoxystrobin; (b49) oxysterol binding protein inhibitor fungicides selected from the group consisting of flutianil and flusulam; (b52) multi-site activity fungicides selected from the group consisting of copper oxychloride, copper sulfate, copper hydroxide, bordeaux mixture, elemental sulfur, ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, ziram, folpet, captan, dichlofluanid, tolylfluanid, bisguanide, bisguanidinocyanododecylbenzenesulfonate, bisguanidinoctylphenylsulfonate, bisguanylhydrazone triacetate, guazatine, dithianon, binamite, and flutolanil; (b54) a fungicide selected from the group consisting of aminophenylarsonic acid, bethoxochlor, cyflufamid, dichlorophenyl-diazone, dipyridyldiketone, dodine, ferimzone, fluazinam, pyridinamide, flusulfamide, methyltetrahydropyridine, nitrapyrin, nitrothalisulfuron, tecloftalam, and N-(2,2,2-trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-4-oxazolcarboxamide.

2. The composition of claim 1, wherein, Component (b) comprises at least one fungicidal compound selected from two different (b) groups.

3. The composition of claim 1, wherein, Component (b) comprises at least one compound selected from the group consisting of azoxystrobin, benzovindiflucy, bifenathi, chlorothalonil, cyproconazole, difenoconazole, etaconazole, fenpropimorph, fluindapyr, flutriafol, fluoxymetofen, pyraclostrobin, penthiopyrad, prothioconazole, pyracarbolid, tebuconazole, and trifloxystrobin.

4. The composition of claim 1, wherein, Component (b) comprises at least one compound selected from the group consisting of azoxystrobin, benzovindiflucy, boscalid, bifenathi, bromuconazole, chlorothalonil, copper sulfate, cyflufamid, cyproconazole, difenoconazole, dimethomorph, fenbuconazole, fenhexamid, fenpropimorph, fluazinam, flutriafol, fluoxymetofen, pyraclostrobin, hexaconazole, ipfentrifluconazole, ipconazole, isoflucypram, mefenoxam, metiram, myclobutanil, pefurazoate, picoxystrobin, prothioconazole, pyracarbolid, pyraclostrobin, pyrimethanil, spiroxamine, tebuconazole, trifloxystrobin, and triticonazole.

5. The composition of claim 1, wherein component (b) comprises one selected from the group consisting of azoxystrobin, benzovindiflucy, bifenathi, chlorothalonil, cyazofamid, cyproconazole, cyprodinil, difenoconazole, etaconazole, fenpropimorph, fluindapyr, fluopyram, flutriafol, ipfentrifluconazole, metiram, prothioconazole, pyracarbolid, pyraclostrobin, spiroxamine, tebuconazole, and trifloxystrobin.

6. The composition of claim 5, wherein component (b) comprises one selected from the group consisting of benzovindiflucy, bifenathi, difenoconazole, fluopyram, flutriafol, pyracarbolid, pyraclostrobin, prothioconazole, and tebuconazole.

7. The composition of claim 5, wherein component (b) comprises one selected from the group consisting of fenpropimorph, fluindapyr, prothioconazole, and tebuconazole.

8. The composition of claim 5, wherein component (b) comprises difenoconazole.

9. The composition of claim 5, wherein component (b) comprises fenpropimorph.

10. The composition of claim 5, wherein component (b) comprises prothioconazole.

11. The composition of claim 5, wherein component (b) comprises tebuconazole.

12. The composition of claim 1, wherein component (b) comprises N-(2,2,2- trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-4- oxalomal e.

13. A composition comprising the composition of any one of claims 1 to 12 and at least one additional component selected from the group consisting of a surfactant, a solid diluent, and a liquid diluent.

14. A method for protecting a plant from disease caused by a fungal pathogen, the method comprising applying to the plant a fungicidally effective amount of the composition of any one of claims 1 to 13.

15. A method for protecting a plant seed from disease caused by a fungal pathogen, the method comprising applying to the plant seed a fungicidally effective amount of the composition of any one of claims 1 to 13.

16. A method for protecting a plant from rust disease, the method comprising applying to the plant a fungicidally effective amount of the composition of any one of claims 1 to 13, wherein, Component (b) comprises at least one fungicidal compound selected from (b3) demethylation inhibitor fungicides, (b5) amine / morpholine fungicides, (b7) succinate dehydrogenase inhibitor fungicides, (b11) quinone outside inhibitor fungicides, and (b52) multi-site activity fungicides.

17. A method for protecting a plant seed from rust disease, the method comprising applying to the plant seed a fungicidally effective amount of the composition of any one of claims 1 to 13, wherein, Component (b) comprises at least one fungicidal compound selected from (b3) demethylation inhibitor fungicides, (b5) amine / morpholine fungicides, (b7) succinate dehydrogenase inhibitor fungicides, (b11) quinone outside inhibitor fungicides, and (b52) multi-site activity fungicides.

18. The composition of any one of claims 1 to 12, wherein the weight ratio of component (a) to component (b) is from 125: 1 to 1 :

125.

19. The composition of claim 18, wherein the weight ratio of component (a) to component (b) is from 25: 1 to 1 :

25.

20. The composition of claim 18, wherein the weight ratio of component (a) to component (b) is from 5: 1 to 1 :

5.

21. The method of claim 14 or 15, wherein the fungal pathogen is Phakopsora pachyrhizi.

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