Substituted tolyls as fungicides.

Abstract

To provide specific tolyl fungicides, their N-oxides, salts and compositions, and methods for using them as fungicides.SOLUTION: Disclosed are compounds of Formula (1), including all geometric and stereoisomers, tautomers, N-oxides, and salts thereof. Also disclosed are compositions containing the compounds of Formula (1), and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.SELECTED DRAWING: None

Description

Technical Field

[0001] Field of the Invention The present invention relates to certain triazole fungicides, their N-oxides, salts, and compositions, and methods of using them as fungicides.

Background Art

[0002] Background of the Invention The control of plant diseases caused by fungal plant pathogens is very important in achieving high harvest efficiency. Plant diseases that damage ornamental plants, vegetables, crops, grains, and fruit crops can cause a significant reduction in productivity and thereby result in increased costs to consumers. Many products are commercially available for these purposes, but there remains a need for new compounds that are more efficient, less costly, less toxic, safer for the environment, or have different sites of action.

[0003] Patent Documents 1, 2, 3, and 4 disclose triazole fungicides and their use in agriculture.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Means for Solving the Problems

[0005] Gist of the Invention The present invention provides Formula 1: [Chemical formula] [wherein, A is [Chemical formula] a radical selected from the group consisting of here, the bond extending to the right is bonded to the ring containing Q, and the bond extending to the left is Y-N(R 3 )C(=W)R 4 bonded to a phenyl ring having a substituent; Q is CR 6 or N; Y is CR 7a R 7b , O or NR 8 ; W is O or S; R 1 and R 2 are each independently halogen, cyano, hydroxy, nitro, amino, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C8 cycloalkylalkyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 cyanoalkoxy, C3-C6 cycloalkoxy, C4-C8 cycloalkylalkoxy, C2-C6 alkoxyalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl or C1-C6 haloalkylsulfonyl; R 3is H, C1-C3 alkyl, C1-C3 haloalkyl, cyclopropyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C4 alkoxycarbonyl or C2-C4 haloalkoxycarbonyl; R 4 is C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylamino or C2-C4 dialkylamino; Each R 5 is independently halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy; n is 0, 1 or 2; R 6 is H, halogen, cyano, hydroxy, nitro, amino, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 cyanoalkoxy, C2-C6 alkoxyalkoxy, C1-C6 alkylamino, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, -ZC(=O)V, CR 10a =NOR 10b 、ON=CR 11a R 11b 、CR 12a =NNR 12b R 12c or -L-J; R 7a is H, hydroxy, halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C2-C3 alkoxyalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; R7b is H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C3 alkoxyalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy; R 8 is H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C3 alkylcarbonyl or C2-C3 haloalkylcarbonyl; Z is a direct bond, O, S or NH; or CH2 optionally substituted with up to two substituents independently selected from halogen, methyl or methoxy; V is R 9 or OR 9 ; R 9 R 10b R 11a and R 12c are each 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; R 10a R 11b R 12a and R 12b are each independently H, C1-C3 al kyl or C1-C3 haloalkyl; L is a direct bond, CH2, O, S, NR 13 , OCH2, CH2O, C(=O), S(=O) or S(=O)2; J is a 3- to 6-membered non-aromatic carbocyclic ring, where up to three carbon atoms in the ring are independently selected from C(=O) and C(=S), and each ring is optionally substituted with up to four substituents independently selected from R 14 ; or 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 two O atoms, up to two S atoms and up to four N atoms, where up to three carbon atoms in the ring are independently selected from C(=O) and C(=S), and each ring is R 14optionally substituted with up to four substituents independently selected therefrom; R 13 is H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C3 alkylcarbonyl or C2-C3 haloalkylcarbonyl; each R 14 is independently halogen, hydroxy, 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 wherein; and 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) relates to compounds (including all stereoisomers) thereof, their N-oxides, and salts, agricultural compositions containing them, and their use as fungicides.

[0006] More particularly, the present invention relates to compounds (including all stereoisomers) of formula 1, their N-oxides or salts.

[0007] The present invention also relates to a fungicidal composition comprising (a) a compound of the present invention (i.e., in a fungicidally effective amount); and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.

[0008] The present invention also relates to a fungicidal composition comprising (a) a compound of the present invention; and (b) at least one other fungicide (e.g., at least one other fungicide having a different site of action).

[0009] The present invention further relates to a method for controlling plant diseases caused by fungal plant pathogens, which comprises applying to a plant or a part thereof, or to a plant seed, a fungicidally effective amount of a compound of the present invention (e.g., as a composition described herein).

[0010] The present invention also relates to a composition comprising a compound of formula 1, its N-oxide, or a salt, and at least one pest control compound or agent.

Mode for Carrying Out the Invention

[0011] Details of the Invention As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", "contains", "containing", "characterized by", or any variation thereof are intended to cover a non-exclusive inclusion under any explicitly stated limitation. For example, a composition, mixture, process, method, article, or apparatus that includes a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus.

[0012] The transitional phrase "consisting of" excludes any unrecited element, step, or ingredient. In the case of a claim, the phrase will close the claim against the inclusion of materials other than those recited, except for impurities ordinarily associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim rather than immediately following the preamble, it limits only the elements recited in that clause; other elements are not excluded from the claim as a whole.

[0013] The transitional phrase "consisting essentially of" is used to define a composition, method, or apparatus that includes materials, steps, features, components, or elements in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristics of the claimed invention. The term "consisting essentially of" lies midway between "comprising" and "consisting of".

[0014] When the applicant defines the present invention or a part thereof using non-limiting terms such as "comprising", it is of course to be construed that the description (in the absence of other statements) also describes inventions using the terms "consisting essentially of" or "consisting of". Unless explicitly stated to the contrary, "or" refers to an inclusive or and not an exclusive or. For example, the condition A or B is satisfied by any one of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0015] Also, the indefinite articles "a" and "an" preceding an element or component of the present invention are intended to be non-limiting with respect to the number of instances (i.e., occurrences) of that element or component. Accordingly, "a" or "an" is to be read as including one or at least one, and the singular word form of an element or component includes the plural unless the number is clearly meant to be singular.

[0016] As referred to in the present disclosure and the claims, "plant" includes members of the plant kingdom at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature reproductive stages (e.g., plants producing flowers and seeds), particularly including spermatopsida. Plant parts also include geotropic members, such as roots, tubers, bulbs and corms, which typically grow below the surface of the growth medium (e.g., soil), as well as members growing above the growth medium, such as foliage (including stems and leaves), flowers, fruits and seeds.

[0017] As referred to herein, the term "seedling" used either alone or in any combination of words means a young plant developing from the embryo of a seed.

[0018] As referred to herein, the term "broadleaf", used alone or in conjunction with terms such as "broadleaf crops", means dicotyledonous plants or dicots, which is a term used to describe a group of angiosperms characterized by embryos having two cotyledons.

[0019] As referred to in the present disclosure, the terms "fungal pathogen" and "fungal plant pathogen" include pathogens in the Ascomycota, Basidiomycota, and Zygomycota, as well as the fungus-like oomycetes, which are the causative agents of a wide range of economically important plant diseases that affect foliage plants, turfgrass, vegetables, arenas, cereal grains, and fruit crops. In the context of the present disclosure, "protecting a plant from a disease" or "controlling a plant disease" includes preventive actions (interfering with the fungal cycle of infection, establishment, symptom development, and spore production) and / or therapeutic actions (inhibiting the establishment of the plant host tissue).

[0020] As used herein, the term "mode of action" (MOA) refers to the Fungicide Resistance Action Committee It is as defined by (FRAC), and is used to identify fungicides according to their biochemical mechanisms of action in the biosynthetic pathways of phytopathogens and their resistance risks. The mechanisms of action defined by FRAC are: (A) nucleic acid synthesis, (B) mitosis and cell division, (C) respiration, (D) amino acid and protein synthesis, (E) signal transduction, (F) lipid synthesis and cell membrane integrity, (G) sterol biosynthesis of the cell membrane, (H) cell wall biosynthesis, (I) melanin synthesis of the cell wall, (P) induction of host plant defense, (U) unknown mechanism of action, (NC) not classified, (M) multi-site contact activity, and (BM) biopesticides having multiple mechanisms of action. Each mechanism of action (i.e., letters A to BM) is based on any of the individual effective target sites, or, when the exact target site is unknown, on the cross-resistance profile within the group or in relation to other groups, and contains one or more subgroups (e.g., A has subgroups A1, A2, A3, and A4). Each of these subgroups (e.g., A1, A2, A3, and A4) is assigned a FRAC code (number and / or letter). For example, the FRAC code for subgroup A1 is 4. Further information regarding the target sites and FRAC codes can be obtained from publicly available databases maintained, for example, by FRAC.

[0021] As used herein, the term "cross-resistance" refers to the phenomenon that occurs when a pathogen develops resistance to one fungicide and simultaneously becomes resistant to one or more other fungicides. These other fungicides are typically, but not always, of the same chemical class or have the same target site of action or can be detoxified by the same mechanism.

[0022] 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), the potential points of attachment or bonding sites are readily recognizable by those skilled in the art. In some examples herein, particularly when alternative bonding sites are possible, the bonding site may be explicitly indicated by a hyphen ("-"). For example, "-NCS" indicates that the bonding site is the nitrogen atom (i.e., isothiocyanato rather than thiocyanato).

[0023] As used herein, the term "alkylating agent" refers to a chemical compound in which a carbon-containing radical is bonded through a carbon atom to a leaving group such as a halide or a sulfonate, and this leaving group is replaceable by the bonding of a nucleophile to the said carbon atom. Unless otherwise indicated, the term "alkylation" does not limit the carbon-containing radical to an alkyl; the carbon-containing radical in the alkylating agent may include, for example, R 1 and R 2 and various carbon-bonded substituent radicals specified with respect thereto.

[0024] In the above description, the term "alkyl", used either alone or in a compound word such as "alkylthio" or "haloalkyl", includes straight-chain or branched alkyls such as methyl, ethyl, n-propyl, and i-propyl, or the various butyl, pentyl, or hexyl isomers. "Alkenyl" includes straight-chain or branched 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 alkynes such as ethynyl, 1-propynyl, 2-propynyl, and the various butynyl, pentynyl, and hexynyl isomers. "Alkynyl" may also include moieties composed of multiple triple bonds such as 2,5-hexadiynyl.

[0025] "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, i-propyloxy and various butoxy, pentyloxy and hexyloxy isomers. "Alkoxyalkyl" indicates an alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. "Alkenyloxy" includes a straight-chain or branched alkenyl bonded to an oxygen atom and linked through the oxygen atom. Examples of "alkenyloxy" include H2C=CHCH2O, (CH3)2C=CHCH2O, CH3CH=CHCH2O, CH3CH=C(CH3)CH2O and CH2=CHCH2CH2O. "Alkynyloxy" includes a straight-chain or branched alkynyl bonded to an oxygen atom and linked through the oxygen atom. Examples of "alkynyloxy" include HC≡CCH2O, CH3C≡CCH2O and CH3C≡CCH2CH2O. "Alkoxyalkoxy" indicates an alkoxy substituent on another alkoxy moiety. Examples of "alkoxyalkoxy" include CH3OCH2O, CH3OCH2O and CH3CH2OCH2O.

[0026] "Alkylthio" includes a branched or straight-chain alkylthio moiety, for example, methylthio, ethylthio and various propyl, butyl, pentyl and hexylthio isomers. "Alkylsulfinyl" includes both enantiomers of the alkylsulfinyl group. Examples of "alkylsulfinyl" include CH3S(=O), CH3CH2S(=O), CH3CH2CH2S(=O), (CH3)2CHS(=O) and various butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH3S(=O)2, CH3CH2S(=O)2, CH3CH2CH2S(=O)2, (CH3)2CHS(=O)2 and various butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers.

[0027] "Alkylamino" includes an NH radical substituted with a straight-chain or branched alkyl. Examples of "alkylamino" include CH3NH, CH3CH2NH, CH3CH2CH2NH, and (CH3)2CHNH. Examples of "dialkylamino" include (CH3)2N, (CH3CH2)2N, and CH3CH2(CH3)N.

[0028] The term "cycloalkyl" refers to a saturated carbocyclic ring consisting of 3 to 6 carbon atoms linked to each other by single bonds. Examples of "cycloalkyl" include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "cycloalkylalkyl" refers to a cycloalkyl substitution on an alkyl group. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyls bonded to a straight-chain or branched alkyl group. The term "cycloalkoxy" refers to a cycloalkyl bonded to an oxygen atom and linked through the oxygen atom, such as cyclopentyloxy and cyclohexyloxy. "Cycloalkylalkoxy" refers to a cycloalkyl substitution on an alkoxy group. Examples of "cycloalkylalkoxy" include cyclopropylmethoxy, cyclopentylethoxy, and other cycloalkyl moieties bonded to a straight-chain or branched alkoxy group.

[0029] "Alkylcarbonyl" refers to a straight-chain or branched alkyl group bonded to a C(=O) moiety. Examples of "alkylcarbonyl" include CH3C(=O), CH3CH2CH2C(=O), and (CH3)2CHC(=O). Examples of "alkoxycarbonyl" include CH3OC(=O), CH3CH2OC(=O), CH3CH2CH2OC(=O), and (CH3)2CHOC(=O).

[0030] The term "halogen", when used alone or in any compound word such as "haloalkyl", or in a description such as "alkyl substituted with halogen", includes fluorine, chlorine, bromine or iodine. Further, when used in a compound word such as "haloalkyl", or in a description such as "alkyl substituted with halogen", the alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" or "alkyl substituted with halogen" include F3C, ClCH2, CF3CH2 and CF3CCl2. Terms such as "haloalkoxy" are defined in the same manner as "haloalkyl". Examples of "haloalkoxy" include CF3O, CCl3CH2O, F2CHCH2CH2O and CF3CH2O. Examples of "haloalkyl" or "alkyl substituted with halogen" include F3C, ClCH2, CF3CH2 and CF3CCl2. Terms such as "haloalkoxy" are defined in the same manner as "haloalkyl". Examples of "haloalkoxy" include CF3O, CCl3CH2O, F2CHCH2CH2O and CF3CH2O.

[0031] "Cyanoalkyl" refers to an alkyl group substituted with one cyano group. Examples of "cyanoalkyl" include NCCH2, NCCH2CH2 and CH3CH(CN)CH2. The term "cyanoalkoxy" refers to an alkyloxy group substituted with one cyano group. Examples of "cyanoalkoxy" include NCCH2O, NCCH2CH2O and CH3CH(CN)CH2O. "Hydroxyalkyl" refers to an alkyl group substituted with one hydroxy group. Examples of "hydroxyalkyl" include HOCH2CH2, CH3CH2(OH)CH and HOCH2CH2CH2CH2.

[0032] The total number of carbon atoms in a substituent is "C" i -C jis indicated by the prefix, where i and j are numbers from 1 to 6. For example, C1-C3 alkylsulfonyl designates from methylsulfonyl to propylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, CH3OCH2CH2 or CH3CH2OCH2; and C4 alkoxyalkyl designates various isomers of an alkyl group substituted with an alkoxy group containing a total of 4 carbon atoms, examples of which include CH3CH2CH2OCH2 and CH3CH2OCH2CH2.

[0033] The term "unsubstituted" in relation to a group such as a ring means that the group has no substituents other than one or more of its bonds to the remainder of Formula 1. The term "optionally substituted" means that the number of substituents may be zero. Unless otherwise indicated, an optionally substituted group may be substituted with as many optional substituents as can be accommodated by replacing hydrogen atoms with non-hydrogen substituents on any available carbon or nitrogen atom. Generally, the number of any substituents (when present) ranges from 1 to 3. As used herein, the term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or the term "(un)substituted".

[0034] The number of any substituents may be limited by the indicated limitations. For example, the phrase "optionally substituted with up to 4 substituents independently selected from 14 means that there may be 0, 1, 2, 3, or 4 substituents present.

[0035] When a compound is substituted with a substituent having a subscript indicating that the number of that substituent can vary (e.g., (R 5 ) n ) in Formula 1 where n is from 0 to 2, the substituent is independently selected from the defined group of substituents unless otherwise indicated. When a position with a variable group is indicated as optionally substituted, e.g., (R 5 ) n, Hydrogen may be present at that position even if it is not described in the definition of the variable group.

[0036] The nomenclature of substituents in the present disclosure uses recognized terms that provide brevity in accurately communicating the chemical structure to those skilled in the art. For the sake of brevity, locant descriptors may be omitted.

[0037] Unless otherwise indicated, a "ring" (e.g., J) as a component of Formula 1 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(=O) and C(=S)) that forms the backbone of the ring or relationship. The term "aromatic" indicates that the ring atoms are each essentially in the same plane, and the p-orbitals are perpendicular to the ring plane, and that (4n + 2) π electrons [where n is a positive integer] are associated with the ring such that Hückel's rule is satisfied.

[0038] The term "carbocyclic ring" means a ring in which the atoms forming the ring backbone are selected only from carbon. Unless otherwise indicated, a carbocyclic ring may be a saturated ring, a partially unsaturated ring, or a fully unsaturated ring. If a fully unsaturated carbocyclic ring satisfies Hückel's rule, the ring is also referred to as an "aromatic ring". "Saturated carbocyclic" refers to a ring having a backbone consisting of carbon atoms linked to each other by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.

[0039] As used herein, the term "partially unsaturated ring" or "partially unsaturated heterocycle" refers to a ring that contains unsaturated ring atoms and one or more double bonds but is not aromatic.

[0040] The term "heterocyclic ring" or "heterocycle" means a ring in which at least one of the atoms forming the ring backbone is other than carbon. Unless otherwise indicated, a heterocyclic ring may be a saturated, partially unsaturated, or fully unsaturated ring. If a fully unsaturated heterocyclic ring satisfies Hückel's rule, the ring is also referred to as a "heteroaromatic ring" or an aromatic heterocyclic ring. "Saturated heterocyclic ring" refers to a heterocyclic ring that contains only single bonds between ring members.

[0041] In the absence of other instructions, the heterocyclic ring is attached to the remainder of Formula 1 by replacing the hydrogen on its carbon or nitrogen atom via any available carbon or nitrogen atom.

[0042] The compounds of the present invention may exist as one or more stereoisomers. Stereoisomers are isomers that have the same constitution but differ in the spatial arrangement of their atoms, and these include enantiomers, diastereomers, cis- and trans-isomers (also known as geometric isomers), and atropisomers. Atropisomers result from restricted rotation around a single bond when the rotational barrier is high enough to permit isolation of the isomeric species. It will be appreciated by those skilled in the art that one stereoisomer may be more active and / or exhibit beneficial effects when enriched compared to other stereoisomers or when separated from other stereoisomers. Further, methods for separating, enriching, and / or selectively producing the above stereoisomers are known to those skilled in the art. For a comprehensive discussion of all aspects of stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.

[0043] The compounds of the present invention may exist as one or more conformational isomers due to restricted rotation around the amide bond (e.g., C(=O)-N) in Formula 1. The present invention includes mixtures of conformational isomers. Further, the present invention includes compounds in which one conformational isomer is enriched compared to the other.

[0044] The present invention includes all stereoisomers, conformational isomers, and mixtures of all their ratios, as well as isotopic forms such as deuterated compounds.

[0045] It is a matter of course for those skilled in the art that since nitrogen requires lone pairs of electrons available for oxidation to oxides, not all nitrogen-containing heterocycles can form N-oxides; those skilled in the art will know the nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also know that tertiary amines can form N-oxides. Synthetic methods for the preparation of N-oxides of heterocycles and tertiary amines are well-known to those skilled in the art, and these include peroxyacids such as peracetic acid and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane for the oxidation of heterocycles and tertiary amines. These methods for the preparation of N-oxides have been widely described and reexamined in the literature, for example: see T.L. Gilchrist, Comprehensive Organic Synthesis, Volume 7, pages 748 - 750, edited by S.V. Ley, Pergamon Press; M. Tisler and B. Stanovnik, Comprehensive Heterocyclic Chemistry, Volume 3, pages 18 - 20, edited by A.J. Boulton and A. McKillop, Pergamon Press; M.R. Grimmett and B.R.T. Keene, Advances in Heterocyclic Chemistry, Volume 43, pages 149 - 161, edited by A.R. Katritzky, Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, Volume 9, pages 285 - 291, edited by A.R. Katritzky and A.J. Boulton, Academic Press; and G.W.H. Cheeseman and E.S.g. Werstiuk in Advances in Heterocyclic Chemistry, Volume 22, pages 390 - 392, edited by A.R. Katritzky and A.J. Boulton, Academic Press.

[0046] In an environment and under physiological conditions, since the salts of chemical compounds are in equilibrium with their corresponding non-salt forms, those skilled in the art recognize that the salts share the biological utility of the non-salt forms. Thus, various salts of the compound of formula 1 are useful for controlling plant diseases caused by fungal plant pathogens (i.e., are agriculturally suitable). Salts of the compound of formula 1 include acid addition salts with inorganic or organic acids such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid or valeric acid. When the compound of formula 1 contains an acidic moiety such as a carboxylic acid, the salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium. Accordingly, the present invention includes a compound selected from formula 1, its N-oxide and agriculturally suitable salts.

[0047] Compounds selected from Formula 1, their stereoisomers, N-oxides, and salts typically exist in more than one form, and thus Formula 1 includes all crystalline and amorphous forms of the compounds represented by Formula 1. Amorphous forms include embodiments that are solids such as waxes and rubbers, and further embodiments that are liquids such as solutions and melts. Crystalline forms include embodiments that represent essentially a single crystal form and embodiments that represent a mixture of polymorphs (i.e., different crystal forms). The term "polymorph" refers to specific crystal forms of a chemical compound that can crystallize in different crystal forms, and these forms have different arrangements and / or conformations of molecules in the crystal lattice. Polymorphs can have the same chemical composition, but they can also have different compositions depending on the presence or absence of co-crystallized water or other molecules, and these can be weakly or strongly bound in the lattice. Polymorphs may differ in chemical, physical, and biological properties such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspension, dissolution rate, and bioavailability. It will be apparent to those skilled in the art that a polymorph of a compound represented by Formula I may exhibit beneficial effects (e.g., suitability for the manufacture of useful formulations, improved biological performance) compared to another polymorph or a mixture of polymorphs of the same compound represented by Formula I. The production and isolation of specific polymorphs of the compounds represented by Formula I can be achieved by methods known to those skilled in the art, including, for example, crystallization using a selected solvent and temperature.

[0048] The embodiments of the present invention described in the gist of the invention include those described below. In the following embodiments, Formula 1 includes its stereoisomers, N-oxides and salts, and references to " compounds of Formula 1" include the definitions of the substituents specified in the gist of the invention, unless further defined in the embodiments.

[0049] Embodiment 1. A compound of Formula 1, wherein A is A-1, A-3 or A-4.

[0050] Embodiment 1a. A compound according to Embodiment 1, wherein A is A-1 or A-3.

[0051] Embodiment 2. The compound of Embodiment 1, wherein A is A-1.

[0052] Embodiment 3. The compound of Embodiment 1, wherein A is A-3.

[0053] Embodiment 4. The compound of Embodiment 1, wherein A is A-4.

[0054] Embodiment 5. The compound of Formula 1, wherein A is A-2.

[0055] Embodiment 6. Q is CR 6 in the compound of Formula 1 or any one of Embodiments 1 to 5.

[0056] Embodiment 7. Q is N in the compound of Formula 1 or any one of Embodiments 1 to 5.

[0057] Embodiment 8. Y is CR 7a R 7b or O in the compound of Formula 1 or any one of Embodiments 1 to 7.

[0058] Embodiment 9. Y is CR 7a R 7b or NR 8 in the compound of Formula 1 or any one of Embodiments 1 to 7.

[0059] Embodiment 10. Y is CR 7a R 7b in the compound of Embodiment 8 or 9.

[0060] Embodiment 11. Y is O in the compound of Embodiment 8.

[0061] Embodiment 12. Y is NR 8 in the compound of Embodiment 9.

[0062] Embodiment 13. W is O in the compound of Formula 1 or any one of Embodiments 1 to 12.

[0063] Embodiment 14. A compound of Formula 1 or any one of Embodiments 1 to 12, wherein W is S.

[0064] Embodiment 15. A compound of Formula 1 or any one of Embodiments 1 to 14, wherein R 1 and R 2 are each independently halogen, cyano, hydroxy, 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.

[0065] Embodiment 16. A compound according to Embodiment 15, 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.

[0066] Embodiment 17. A compound according to Embodiment 16, wherein R 1 and R2 is 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, the compound of embodiment 16.

[0067] Embodiment 18. R 1 and R 2 is independently, halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy or C1-C3 alkylthio, the compound of embodiment 17.

[0068] Embodiment 19. R 1 and R 2 is independently, halogen, cyano, methyl, halomethyl, methoxy or halomethoxy, the compound of embodiment 18.

[0069] Embodiment 20. R 1 and R 2 is independently, Br, Cl, F, methyl, trifluoromethyl, methoxy or trifluoromethoxy, the compound of embodiment 19.

[0070] Embodiment 21. R 1 and R 2 is independently, Cl, F or methyl, the compound of embodiment 20.

[0071] Embodiment 22. R 1 and R 2 is independently Cl or F, the compound of embodiment 21.

[0072] Embodiment 23. R 1 and R 2 is F respectively, the compound of embodiment 22.

[0073] Embodiment 24. R 3A compound of formula 1 or any one of embodiments 1 to 23, wherein it is H, C1-C3 alkyl, C2-C4 alkylcarbonyl or C2-C4 alkoxycarbonyl.

[0074] Embodiment 25. R 3 is a compound of Embodiment 24, which is H, methyl, methylcarbonyl or methoxycarbonyl.

[0075] Embodiment 26. R 3 is a compound of Embodiment 25, which is H or methyl.

[0076] Embodiment 27. R 3 is a compound of Embodiment 26, which is H.

[0077] Embodiment 28. R 4 is a compound of formula 1 or any one of embodiments 1 to 27, which is methyl, methoxy, ethoxy, methylamino or dimethylamino.

[0078] Embodiment 29. R 4 is a compound of Embodiment 28, which is methyl, methoxy or ethoxy.

[0079] Embodiment 30. R 4 is a compound of Embodiment 29, which is methoxy.

[0080] Embodiment 31. Each R 5 is a compound of formula 1 or any one of embodiments 1 to 30, which is independently halogen, cyano, methyl or methoxy.

[0081] Embodiment 32. Each R 5 is a compound of Embodiment 31, which is independently halogen or methyl.

[0082] Embodiment 33. Each R 5 is a compound of Embodiment 32, which is methyl.

[0083] Embodiment 34. n is 0 or 1, a compound of formula 1 or any one of embodiments 1 to 33.

[0084] Embodiment 35. The compound of Embodiment 34, wherein n is 0.

[0085] Embodiment 36. R 6 is H, halogen, nitro, amino, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, -ZC(=O)V, CR 10a =NOR 10b 、ON=CR 11a R 11b 、CR 12a =NNR 12b R 12c or -L-J, a compound of Formula 1 or any one of Embodiments 1 to 35.

[0086] Embodiment 37. R 6 is H, halogen, nitro, amino, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, -ZC(=O)V, CR 10a =NOR 10b 、CR 12a =NNR 12b R 12c or -L-J, the compound of Embodiment 36.

[0087] Embodiment 38. R 6 is H, halogen, nitro, amino, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, CR 10a =NOR 10b or -L-J, the compound of Embodiment 37.

[0088] Embodiment 39. R 6 is H, halogen, amino, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C4 alkenyloxy, C2-C4 haloalkenyloxy, CR 10a =NOR 10b or -L-J, the compound of Embodiment 38.

[0089] Embodiment 40. R 6 is H, halogen, amino, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CR 10a =NOR 10b or -L-J, the compound of Embodiment 39.

[0090] Embodiment 40a. R 6 is H, Br, Cl, I, amino, methyl, i-propyl, trifluoromethyl, CH2F, CHF2, methoxy, ethoxy, i-propyloxy, trifluoromethoxy, CH2FO, CHF2O, CH=NOCH3, CH=NOCH2CH3, the compound of Embodiment 40.

[0091] Embodiment 41. R 6is a compound of Embodiment 40a, which is H, Br, Cl, I, amino, methyl, i-propyl, trifluoromethyl, CHF2, methoxy, ethoxy, i-propyloxy, trifluoromethoxy, CHF2O, CH=NOCH3, CH=NOCH2CH3, C(CH3)=NOCH3 or -L-J.

[0092] Embodiment 41a. R 6 is a compound of Embodiment 41, which is H, Br, Cl, I, amino, methoxy, ethoxy, i-propyloxy, trifluoromethoxy, CHF2O, C(CH3)=NOCH3 or -L-J.

[0093] Embodiment 42. R 6 is a compound of Embodiment 41, which is H, Br, Cl, I, amino, methoxy, ethoxy, i-propyloxy, trifluoromethoxy, C(CH3)=NOCH3 or -L-J.

[0094] Embodiment 43. R 6 is a compound of Embodiment 42, which is H, Br, Cl, amino, methoxy, ethoxy or i-propyloxy.

[0095] Embodiment 44. R 6 is a compound of Embodiment 43, which is H, Br, Cl, amino or methoxy.

[0096] Embodiment 45. R 7a is a compound of Formula 1 or any one of Embodiments 1 to 44, which is H, hydroxy, halogen, cyano, methyl, halomethyl, methoxy or halomethoxy.

[0097] Embodiment 46. R 7a is a compound of Embodiment 45, which is H, halogen, methyl or methoxy.

[0098] Embodiment 47. R 7a is a compound of Embodiment 46, which is H or methyl.

[0099] Embodiment 48. R 7aThe compound of Embodiment 47, which is H.

[0100] Embodiment 49. R 7b is H, methyl, halomethyl, methoxy or halomethoxy, and is a compound of Formula 1 or any one of Embodiments 1 to 48.

[0101] Embodiment 50. R 7b is H, methyl or methoxy, and is a compound of Embodiment 49.

[0102] Embodiment 51. R 7b is H or methyl, and is a compound of Embodiment 50.

[0103] Embodiment 52. R 7b is H, and is a compound of Embodiment 51.

[0104] Embodiment 53. R 8 is H, methyl, halomethyl or methylcarbonyl, and is a compound of Formula 1 or any one of Embodiments 1 to 44.

[0105] Embodiment 54. R 8 is H or methyl, and is a compound of Embodiment 53.

[0106] Embodiment 55. R 8 is H, and is a compound of Embodiment 54.

[0107] Embodiment 56. Z is a direct bond, O, NH, CH2 or CH(OCH3), and is a compound of Formula 1 or any one of Embodiments 1 to 55.

[0108] Embodiment 57. Z is a direct bond, O or CH2, and is a compound of Embodiment 56.

[0109] Embodiment 58. Z is a direct bond, and is a compound of Embodiment 57.

[0110] Embodiment 59. Z is O, and is a compound of Embodiment 57.

[0111] Compound of Embodiment 57 where Z is CH2.

[0112] Embodiment 60. 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, a compound of Formula 1 or any one of Embodiments 1 to 59a.

[0113] Embodiment 61. 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, a compound of Embodiment 60.

[0114] Embodiment 62. R 9 , R 10b , R 11a and R 12c are each H, methyl, ethyl or C2-C4 alkenyl, a compound of Embodiment 61.

[0115] Embodiment 63. R 9 , R 10b , R 11a and R 12c are each H or methyl, a compound of Embodiment 62.

[0116] Embodiment 64. R 9 , R 10b , R 11a and R 12c are each H, a compound of Embodiment 63.

[0117] Embodiment 65. R 9 , R 10b , R 11a and R 12c are each methyl, a compound of Embodiment 63.

[0118] Embodiment 66. R 10a 、R 11b 、R 12a and R 12b are each independently H, methyl or halomethyl, a compound of Formula 1 or any one of Embodiments 1 to 65.

[0119] Embodiment 67. R 10a 、R 11b 、R 12a and R 12b are each independently H or methyl, the compound of Embodiment 66.

[0120] Embodiment 68. R 10a 、R 11b 、R 12a and R 12b are each H, the compound of Embodiment 67.

[0121] Embodiment 69. R 10a 、R 11b 、R 12a and R 12b are each methyl, the compound of Embodiment 68.

[0122] Embodiment 70. L is a direct bond, CH2, O, S, NR 13 、OCH2, CH2O or C(=O), a compound of Formula 1 or any one of Embodiments 1 to 69.

[0123] Embodiment 71. L is a direct bond, CH2, O, OCH2, CH2O or C(=O), the compound of Embodiment 70.

[0124] Embodiment 72. L is a direct bond, CH2, O, OCH2 or CH2O, the compound of Embodiment 71.

[0125] Embodiment 73. L is a direct bond, O or OCH2, the compound of Embodiment 72.

[0126] Embodiment 74. L is a direct bond, the compound of Embodiment 72.

[0127] Compound of Embodiment 72, where L is CH2.

[0128] Compound of Embodiment 72, where L is O.

[0129] Compound of Embodiment 72, where L is OCH2 or CH2O.

[0130] Compound of Formula 1 or any one of Embodiments 1 - 797, where J is selected from J-1 to J-71 shown in Separate Table A.

[0131] Appendix A [Chemical Formula] [Chemical Formula] [Chemical Formula] [Chemical Formula] Here, the floating bond is connected to L via any available carbon or nitrogen atom of the indicated ring; and x is 0, 1, 2, or 3.

[0132] Compound of Embodiment 78, where 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-56, J-57, J-58, J-59, J-60, J-61, J-63, J-64, J-65, J-66, J-67, J-69, or J-70.

[0133] Compound of Embodiment 79, where J is J-4, J-5, J-6, J-22, J-23, J-24, J-35, J-36, J-37, J-38, J-57, J-58, J-63, J-64, J-65, J-66, J-67, J-69, or J-70.

[0134] Embodiment 81. The compound of Embodiment 80, wherein J is J-6, J-22, J-35, J-37, J-58, J-64, J-65, J-66, J-67, J-69 or J-70.

[0135] Embodiment 82. The compound of Embodiment 81, wherein J is J-35.

[0136] Embodiment 83. The compound of Embodiment 81, wherein J is J-58.

[0137] Embodiment 84. The compound of Embodiment 81, wherein J is J-66.

[0138] Embodiment 85. The compound of Embodiment 81, wherein J is J-67.

[0139] Embodiment 86. The compound of Embodiment 81, wherein J is J-69.

[0140] Embodiment 87. The compound of Embodiment 81, wherein J is J-70.

[0141] Embodiment 88. The compound of Embodiment 81, wherein J is J-65, J-66 or J-67.

[0142] Embodiment 88a. The compound of Embodiment 88, wherein J is J-66 or J-67.

[0143] Embodiment 89. The compound of any one of Embodiments 78 to 88a, wherein x is 0, 1 or 2.

[0144] Embodiment 89a. The compound of Embodiment 89, wherein x is 0 or 1.

[0145] Embodiment 90. The compound of any one of Embodiments 89 or 89a, wherein x is 0.

[0146] Embodiment 91. Each R 14is independently halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy or C(=O)OR 15 A compound of formula 1 or any one of embodiments 1 to 89.

[0147] Embodiment 92. Each R 14 is independently halogen, cyano, methyl, halomethyl, methoxy, halomethoxy or C(=O)OR 15 A compound of embodiment 91.

[0148] Embodiment 93. Each R 14 is independently halogen, methyl, methoxy or C(=O)OR 15 A compound of embodiment 92.

[0149] Embodiment 94. Each R 14 is independently halogen, methyl or C(=O)OR 15 A compound of embodiment 93.

[0150] Embodiment 95. Each R 14 is independently halogen or methyl, a compound of embodiment 94.

[0151] Embodiment 95a. Each R 14 is independently Br, Cl, F or methyl, a compound of embodiment 95.

[0152] Embodiment 96. Each R 15 is independently C1-C3 alkyl, C1-C3 haloalkyl or cyclopropyl, a compound of formula 1 or any one of embodiments 1 to 94.

[0153] Embodiment 97. Each R 15 is independently C1-C3 alkyl or C1-C3 haloalkyl, a compound of embodiment 96.

[0154] Embodiment 98. Each R 15 is independently methyl or ethyl, a compound of embodiment 97.

[0155] Embodiment 99. Each R 15 is methyl, the compound of Embodiment 98.

[0156] Embodiments of the invention that include any other embodiments described herein in addition to the above-described Embodiments 1 to 99 can be combined in any manner, and the descriptions of the variables in the embodiments are relevant not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula 1. Further, embodiments of the invention that include any other embodiments described herein in addition to the above-described Embodiments 1 to 99, and any combinations thereof, are relevant to the compositions and methods of the invention.

[0157] Combinations of Embodiments 1 to 99 are illustrated as follows: Embodiment A. In the formula, A is A-1, A-3 or A-4; Q is CR 6 ; Y is CR 7a CR 7b ; W is O; R 1 and R 2 are each independently halogen, 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; R 3 is H, methyl, methylcarbonyl or methoxycarbonyl; R 4 is methyl, methoxy, ethoxy, methylamino or dimethylamino; Each R 5 is independently halogen or methyl; R 6is H, halogen, nitro, amino, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, -ZC(=O)V, CR 10a =NOR 10b 、CR 12a =NNR 12b R 12c or -L-J; R 7a is H, halogen, methyl or methoxy; R 7b is H or methyl; Z is a direct bond, O, NH, CH2 or CH(OCH3); R 9 、R 10b and R 12c are each H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl or C2-C4 haloalkenyl; R 10a 、R 12a and R 12b are each independently H, methyl or halomethyl; L is a direct bond, CH2, O, OCH2 or CH2O;

[0158] J is selected from J-1 to J-71

Chemical formula

Chemical formula

Chemical formula

[0159] Embodiment B. In the formula, A is A-1; R 1 and R 2 are each independently Br, Cl, F, methyl, trifluoromethyl, methoxy, or trifluoromethoxy; R 3 is H or methyl; R 4 is methyl, methoxy, or ethoxy; each R 5 is methyl; R 6 is H, halogen, amino, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C4 alkenyloxy, C2-C4 haloalkenyloxy, CR 10a =NOR 10b or -L-J; R 7a is H or methyl; R 7b is H or methyl; R 10b is H, methyl, C2-C4 alkenyl, or C2-C4 haloalkenyl; R 10a is H or methyl; L is a direct bond, O, or OCH2; J is J-6, J-22, J-35, J-37, J-58, J-64, J-65, J-66, J-67, J-69, or J-70; and each R 14 is independently halogen or methyl, Compound of Embodiment A

[0160] Embodiment C. In the formula, R 1 and R 2 are each independently Cl, F, or methyl; R 3 is H; R 4 is methoxy; n is 0; R 6 is H, Br, Cl, I, amino, methyl, i-propyl, trifluoromethyl, CH2F, CHF2, methoxy, ethoxy, i-propyloxy, trifluoromethoxy, CH2FO, CHF2O, CH=NOCH3, CH=NOCH2CH3, C(CH3)=NOCH3, or -L-J; R 7a is H; R 7b is H; and J is J-65, J-66, or J-67, Compound of Embodiment B

[0161] Embodiment D. In the formula, R 1 and R 2 are each independently Cl or F; R 6 is H, Br, Cl, I, amino, methoxy, ethoxy, i-propyloxy, trifluoromethoxy, CHF2O, C(CH3)=NOCH3, or -L-J; J is J-66 or J-67; x is 0, 1, or 2; and R 14 is Br, Cl, F, or methyl, Compound of Embodiment C

[0162] Embodiment E. In the formula, R 1 and R 2 are each F; and R 6is H, Br, Cl, amino, methoxy, ethoxy or i-propyloxy, the compound of Embodiment D.

[0163] Specific embodiments include: Methyl N-[[5-[1-(2,6-difluoro-4-nitrophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 1); Methyl N-[[5-[1-(2,6-difluoro-4-methoxyphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 3); Methyl N-[[5-[1-(2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 4); Methyl N-[[5-[1-(4-amino-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 5); Methyl N-[[5-[1-(4-chloro-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 6); Methyl N-[[5-[1-(4-bromo-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 7); Methyl N-[[5-[1-(2,6-difluoro-4-iodophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 8); Methyl N-[[5-[1-(2,6-difluoro-4-hydroxyphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 10); Methyl N-[[5-[1-(4-ethoxy-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 11); Methyl N-[[5-[1-[4-(cyclobutyloxy)-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 13); Methyl N-[[5-[1-[2,6-difluoro-4-(1-methylethoxy)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 14); Methyl N-[[5-[1-[4-(difluoromethoxy)-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 15); Methyl N-[[5-[1-[2,6-difluoro-4-(2-propyn-1-yloxy)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 30); Methyl N-[[5-[1-(2,6-difluoro-4-methoxyphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 33); Methyl N-[[5-[1-(4-cyclopropyl-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 41); Methyl N-[[5-[1-[4-[(1,1-dimethylethyl)thio]-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 42); Methyl N-[[5-[1-[4-[(difluoromethyl)thio]-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 43); Methyl N-[[5-[1-(4-ethynyl-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 53); Methyl N-[[5-[1-[2,6-difluoro-4-(1-methylethyl)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 63); Methyl N-[[5-[1-[2,6-difluoro-4-(trifluoromethyl)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 64); Methyl N-[[5-[1-(2,6-dichloro-4-cyclopropylphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 65); Methyl N-[[5-[1-[4-(cyclopropyloxy)-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 66); Methyl N-[[5-[1-(2,6-difluoro-4-formylphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 67); Methyl N-[[5-[1-(4-acetyl-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 68); Methyl 3,5-difluoro-4-[3-[3-[[(methoxycarbonyl)amino]methyl]-4-methylphenyl]-1H-pyrazol-1-yl]benzoate (Compound 70); Methyl N-[[5-[1-[2,6-difluoro-4-(hydroxymethyl)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 71); Methyl N-[[5-[1-[2,6-difluoro-4-(trifluoromethoxy)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 78); Methyl N-[[5-[1-[2,6-difluoro-4-[1-(methoxyimino)ethyl]phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 83); Methyl N-[[5-[1-[4-(difluoromethyl)-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 87); Methyl N-[[5-[2-[2,6-difluoro-4-(1-methylethyl)phenyl]-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 108); Methyl N-[[5-[2-(4-amino-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 115); Methyl N-[[5-[2-(4-chloro-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 117); Methyl N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 118); Methyl N-[[5-[1-(4-chloro-2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 121); Methyl N-[[5-[1-(4-amino-2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 131); and Methyl N-[[5-[1-(2,6-difluoro-4-nitrophenyl)-1H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 132) Compounds of formula 1 selected from the group consisting of.

[0164] The present invention provides a bactericidal composition comprising a compound of formula 1 (including all its stereoisomers, N-oxides, and salts), and at least one other bactericide. Embodiments of this composition Of note are compositions comprising a compound corresponding to any of the above compound embodiments.

[0165] The present invention provides a bactericidal composition comprising a compound of formula 1 (including all its stereoisomers, N-oxides, and salts) (i.e., in a bactericidally effective amount), and at least one further component selected from the group consisting of surfactants, solid diluents, and liquid diluents. Of note as an embodiment of this composition is a composition comprising a compound corresponding to any of the above compound embodiments.

[0166] The present invention provides a method for controlling plant diseases caused by fungal plant pathogens, which comprises applying to a plant or a part thereof, or to a plant seed, a bactericidally effective amount of a compound of formula 1 (including all its stereoisomers, N-oxides, and salts). Of note as an embodiment of this method is a method which comprises applying a bactericidally effective amount of a compound corresponding to any of the above compound embodiments. Of particular note is an embodiment in which the compound is applied as a composition of the present invention.

[0167] The compound of formula 1 can be prepared using one or more of the following methods and variations described in Schemes 1 - 12. The definitions of A, Q, R 1 , R 2 , R 3 , R 4 , R 5 , W, Y and n are, unless otherwise indicated, as defined above in the summary of the invention. The compounds of formulae 1a - 1e are a subset of formula 1, and all substituents for formulae 1a - 1e are, unless otherwise indicated, as defined above for formula 1.

[0168] As shown in Scheme 1, the compound of formula 1 can be prepared by reacting the compound of formula 2 with the compound 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 related 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 International Publication WO2014 / 066120. Also, Example 1 herein illustrates the method of Scheme 1. These reactions typically require the presence of a base, such as a metal carbonate like potassium carbonate, as well as a suitable catalyst and ligand, such as copper(I) iodide and a ligand like trans-1,2-diamino-N,N'-dimethylcyclohexane. This reaction is generally carried out in an aprotic solvent such as dioxane or toluene at a temperature between ambient temperature and the boiling point of the solvent. When the compound of formula 3 contains an electron-withdrawing substituent (e.g., R 1 R 2 and / or R 6 is nitro, cyano or ester) and X is halogen, direct nucleophilic substitution of X by the compound of formula 2 can be achieved. These reactions are carried out in a solvent such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, dioxane, tetrahydrofuran or acetonitrile at a temperature between approximately ambient temperature and 130 °C in the presence of a base such as an alkali metal carbonate, hydride, alkoxide or trialkylamine. For reaction conditions, see Bioorganic&Medicinal Chemistry Letters 2014, 24(24), 5805-5813; Bioorganic&Medicinal See Chemistry Letters 2010, 20(15), 4521 - 4525; Journal of Materials Chemistry A: Materials for Energy and Sustainability 2014, 2(21), 7917 - 7926; and PCT International Publication WO2016 / 187667. Also, Examples 2, 7, 11, and 17 (Step A) herein illustrate the production of the compound of Formula 1 by direct nucleophilic substitution. For the compound of Formula 3 where X is boronic acid, the 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 such as dichloromethane or chloroform, at a temperature between approximately ambient temperature and the boiling point of the solvent, and in the presence of oxygen. For the main references, see, for example, Tetrahedron 2018, 74(5), 606 - 617; and Tetrahedron Lett. 1998, 39(19), 2933 - 2936.

[0169] Scheme 1 [Chemical formula]

[0170] Compounds of Formula 3 are widely available from commercial sources and can be readily prepared using commercially available precursors and known methods (see, for example, US2013 / 0158004 and WO2018 / 011094).

[0171] In some cases, the method of Scheme 1 gives rise to two positional isomers. For example, as shown in Scheme 2, the reaction of a compound of formula 2a (i.e., formula 2 where A is A-3) with a compound of formula 3 typically gives a mixture of isomers of a compound of formula 1a (i.e., formula 1 where A is A-3) and a compound of formula 1b (i.e., formula 1 where A is A-4). Purification of the positional isomers can be achieved using standard techniques such as column chromatography. For related references, see, for example, PCT International Publication WO2009 / 013211. Also, the method of Scheme 2 is illustrated in Example 18, Step F.

[0172] Scheme 2

Chemical formula

[0173] As shown in Scheme 3, the compound of formula 2a can be prepared by reacting the 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, trimethylsilyl azide 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 combined with a mild reducing agent and, for example, copper(II) sulfate can be used together with sodium ascorbate. The reaction is typically carried out in a solvent such as N,N-dimethylformamide, tetrahydrofuran, methanol, tert-butanol, dimethyl sulfoxide (optionally containing water) at a temperature of about 25 - 100 °C. The use of a low-boiling solvent may, in some cases, require increasing the pressure to facilitate carrying out the reaction at a temperature above the normal boiling point of the solvent. For the main 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; as well as PCT International Publication WO2004 / 072243. The method of Scheme 3 is also illustrated in Example 18, Step E of this example.

[0174] Scheme 3

Chemical formula

[0175] As shown in Scheme 4 and Method A below, the compound of Formula 4 can be prepared from the compound of Formula 5 and the alkyne of Formula 6 using Sonogashira reaction coupling conditions. Sonogashira coupling is well-known in the literature. For example, see 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. in Tetrahedron Organic Series, Volume 20; Pergamon Press: New York, 2000.

[0176] As shown in Scheme 4, Method B, the compound of Formula 5 can be reacted with ethynyltrimethylsilane (Formula 7) in the presence of a suitable palladium catalyst (e.g., tetrakis(triphenylphosphine)palladium or dichlorobis(triphenylphosphine)palladium(II)) and a suitable copper catalyst (copper(I) iodide as described above) to produce the compound of Formula 4. This 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; in some cases, the reaction may 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 the compound of Formula 4 can be carried out using well-known conditions such as treatment in methanol or ethanol with an alkali metal hydroxide or alkali metal carbonate, such as potassium hydroxide, sodium hydroxide or potassium carbonate. The reaction is preferably carried out in a suitable organic solvent. Typically, this method is most satisfactorily carried out at a temperature in the range 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; and also refer to Example 18, Steps A and B herein.

[0177] Scheme 4

Chemical formula

[0178] As shown in Scheme 5, the compound of formula 2 can be prepared by Suzuki coupling of the boron intermediate of formula 8 of the compound of formula 5 [wherein A (i.e., A-1, A-2, A-3 or A-4) is bonded to boron via a carbon atom ring member and is unsubstituted on the N atom ring member (i.e., A is a 5-membered heteroaromatic ring containing ring members of -(NH)- and -(C-B(OH)2)-)]. This 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)2 or PdCl2 are used in combination with ligands such as triphenylphosphine or 1,1'-bis(diphenylphosphino)ferrocene (dppf). The conditions for Suzuki coupling are well documented in the literature; see, for example, Angewandte Chemie International Edition 2006, 45(21), 3484-3488 and Tetrahedron Letters 2002, 43(16), 2885-2888. The boron intermediate of formula 8 is commercially available and can be prepared from the corresponding halide or trifluoromethanesulfonate by methods known in the literature; see, for example, PCT International Publication WO2007 / 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.

[0179] Other coupling procedures provide numerous alternatives for the introduction of the heterocyclic A ring on formula 5, including the coupling methods disclosed by Heck, Stille and Kumada. Also see, for example, Zificsak et al., Tetrahedron 2004, 60, 8991-9016.

[0180] Scheme 5 [Chemical formula]

[0181] As shown in Scheme 6, the compound of formula 5 can be prepared by reacting the amine of formula 9 with the acid chloride of formula 10 in the presence of a base such as potassium carbonate, triethylamine or pyridine. This reaction can be carried out without using a solvent other than those of formulas 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 to 50 °C. For reaction conditions, see, for example, PCT International Publication WO2004 / 037770 and European Patent No. EP1586552. Also, the method of Scheme 6 is illustrated in Example 18, Step D of this example.

[0182] For the synthesis of the compound of formula 10, see Advanced Organic Synthesis, Fourth Edition, Wiley & Sons 1992, 437, and the references cited therein. The compound of formula 9 is commercially available and can be easily synthesized by general methods known to those skilled in the art.

[0183] Scheme 6 [Chemical formula]

[0184] As shown in Scheme 7, the compound of formula 1 can be prepared from the compound of formula 11 by reaction with the acid chloride of formula 10 in a manner similar to the method of Scheme 6. The method of Scheme 7 is illustrated in Example 17, Step F of this specification.

[0185] Scheme 7 [Chemical formula]

[0186] As shown in Scheme 8, the compound of Formula 11 can be prepared from the nitrile of Formula 12 by using a suitable reducing agent such as lithium aluminum hydride or borane / tetrahydrofuran complex or tris(pentafluorophenyl)borane at a temperature between ambient temperature and the boiling point of the solvent in an aprotic solvent such as tetrahydrofuran. For related examples, refer to the procedures and references included in PCT International Publication WO2011 / 079102 and WO2011 / 073444. Also, the method of Scheme 8 is illustrated in Example 17, Step E of this specification.

[0187] The nitrile of Formula 12 can also be converted to the amine of Formula 11 by catalytic hydrogenation. These reactions are traditionally carried out in a lower alcohol solvent such as methanol or ethanol in the presence of a transition metal such as palladium(0) on carbon, Raney nickel, or platinum oxide at a temperature between ambient temperature and 100 °C under a hydrogen gas atmosphere at a pressure between 1 and 7500 kPa. For related examples, refer to the procedures and references included in PCT Patent Application Publication WO2009 / 152868 and WO2010 / 023161.

[0188] Scheme 8 [Chemical formula]

[0189] As shown in Scheme 9, the compound of Formula 13 [wherein A (i.e., A-1, A-2, A-3, or A-4) is unsubstituted on the N-atom ring member (i.e., A is a 5-membered heteroaromatic ring containing a ring member -(NH)-)] can be coupled with the compound of Formula 3 using a method similar to that of Scheme 1 to produce the compound of Formula 12. Example 17, Step A of this specification illustrates the method of Scheme 9.

[0190] Scheme 9 [Chemical formula]

[0191] As shown in Scheme 10, the compound of Formula 13 can be prepared from the compound of Formula 14. In a typical procedure, the compound of Formula 14 is 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 and 150 °C. For related procedures, see PCT Patent Application Publication WO2012 / 032528 and WO2011 / 133882 and the references contained therein.

[0192] Scheme 10

Chemical formula

[0193] As shown in Scheme 11, the compound of Formula 14 can be prepared by first reacting the 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 and 100 °C to obtain 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 obtain the compound of Formula 14.

[0194] Scheme 11

Chemical formula

[0195] The compounds of formula 1 and their intermediates described herein can be subjected to various electrophilic, nucleophilic, organometallic, oxidation and reduction reactions to add substituents or modify existing substituents, thereby obtaining other functionalized compounds of formula 1. For example, as shown in Scheme 13, a compound of formula 1c (i.e., a compound of formula 1 wherein Q is CR 6 and R 6 is NH2) can be used with Fe, Zn or SnCl2 in an acidic aqueous solution at a temperature ranging from ambient temperature to reflux temperature to reduce the corresponding nitro compound of formula 1e (i.e., a compound of formula 1 wherein Q is CR 6 and R 6 is NO2). Alcohol cosolvents such as methanol, ethanol and i-propanol may be used. In subsequent reactions, the amino compound of formula 1c can be converted to a halogen in the presence of a halogen source under diazotization conditions to obtain formula 1d (i.e., a compound of formula 1 wherein Q is CR 6 and R 6 is a halogen). Various halogen sources can be used in the method of Scheme 12. The presence of a Lewis acid such as titanium(IV) isopropoxide may also be advantageous. For example, tert-butyl nitrile is added to a solution of the amino compound of formula 1c in a solvent such as acetonitrile in the presence of CuBr2 to obtain the corresponding brominated compound of formula 1d. Similarly, the amino compound of formula 1c is converted to a diazonium salt according to general procedures well known to those skilled in the art and then typically in a solvent such as water, acetic acid or trifluoroacetic acid with a mineral acid containing the same halide atom (e.g., R 6It can be converted to the corresponding compound of formula 1d by treating with sodium nitrite in the presence of HI aqueous solution) and then treating with the corresponding copper(I) or copper(II) salt. Many known reduction, diazotization and halogenation methods can be easily adapted to produce the compounds of formulas 1c and 1d. For example, see the procedures and references included in US Patent Applications US2017 / 0121300, US2017 / 069105, and US2017 / 038909, and PCT Patent Application Publication WO2017 / 036357. Also, the method of Scheme 12 is illustrated in Examples 3 and 4 herein.

[0196] Scheme 12

Chemical formula

[0197] It is recognized that some of the reagents and reaction conditions described above for producing the compounds of formula 1 may not be compatible with certain functional groups present in the intermediates. In these cases, incorporating a protecting / deprotecting sequence or functional group interconversion into the synthesis will help obtain the desired product. The use and selection of protecting groups will be apparent to those skilled in chemical synthesis (see, for example, T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). It will be understood by those skilled in the art that in some cases, after introducing the specified reagents shown in the individual schemes, additional conventional synthetic steps not described in detail may be necessary to complete the synthesis of the compounds of formula 1. It will also be understood by those skilled in the art that it may be necessary to carry out combinations of the steps described in the above schemes in an order other than the order shown by the specific order presented for producing the compounds of formula 1.

[0198] One of ordinary skill in the art will also understand that the compounds and intermediates of Formula 1 described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.

[0199] Even without further elaboration, it is believed that one of ordinary skill in the art can, using the preceding description, utilize the present invention to its fullest extent. Accordingly, the following examples are merely illustrative and should not be construed in any way as limiting the present disclosure. The steps in the following examples illustrate the procedures for each step in the overall synthetic transformation, and the starting materials for each step may not necessarily be produced by the specific manufacturing runs described for other examples or steps. Percentages are by mass unless chromatography solvent mixtures or other instructions indicate otherwise. Parts and percentages for chromatography solvent mixtures are by volume unless otherwise indicated. 1 1H NMR spectra are reported in ppm as downfield shifts from tetramethylsilane; "s" means singlet, "d" means doublet, "t" means triplet, "m" means multiplet, "br s" means broad singlet, and "dd" means double doublet. Mass spectra are reported as the molecular weight of the parent ion (M+1) of the highest isotope abundance formed by the addition of H + (molecular weight 1) to the molecule, and these are observed by liquid chromatography mass spectrometry (LCMS) connected to a mass spectrometer using either atmospheric pressure chemical ionization (AP + ) or electrospray ionization (ESI + ).

[0200] Example 1 Production of Methyl N-[[5-[1-(2,6-difluoro-4-methoxyphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 3) Methyl N-[[2-methyl-5-(1H-pyrazol-3-yl)phenyl]methyl]carbamate (1.12 g, 4.57 mmol) (for the production method, refer to PCT International Publication WO2008124092), copper(I) iodide (0.17 g, 0.914 mmol) and 2-bromo-1,3-difluoro-5-methoxy-benzene (1.32 g, 5.94 mmol) were added with potassium carbonate (11.4 mmol), followed by N,N-dimethylformamide (8 mL). The reaction mixture was bubbled with nitrogen gas for 30 minutes, then trans-N,N'-dimethylcyclohexane-1,2-diamine (0.26 g, 1.83 mmol) was added. 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 obtained substance was purified by silica gel column chromatography (eluting with a gradient of 20 - 80% ethyl acetate in hexane) to obtain the title compound, which is a compound of the present invention, as a colorless oil (0.43 g). 1 1H NMR (CDCl3): δ 7.74 (d, 1H), 7.67 (dd, 1H), 7.59 (d, 1H), 7.22 (d, 1H), 6.74 (d, 1H), 6.61 (d, 2H), 4.87 (br s, 1H), 4.41 (d, 2H), 3.84 (s, 3H), 3.69 (s, 3H), 2.36 (s, 3H). LCMS: m / z: 388 [M+H] +

[0201] Example 2 N-[[5-[1-(2,6-difluoro-4-nitrophenyl)-1H-pyrazol- 3-yl]-2-methylphenyl]methyl]carbamate (Compound 1) Methyl N-[[2-methyl-5-(1H-pyrazol-3-yl)phenyl]methyl]carbamate (0.45 g, 1.84 mmol) (for the production method, refer to PCT International Publication WO2008124092) was added to a stirred solution in dimethyl sulfoxide (5 mL) with 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 substance was purified by column chromatography (eluting with a gradient of 10 - 50% ethyl acetate in hexane) to obtain the title compound, which is a compound of the present invention, as a yellow solid (0.44 g). 1 1H NMR (CDCl3): 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).

[0202] Example 3 Production of Methyl N-[[5-[1-(4-amino-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 5) Methyl [[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) were added iron powder (555 mg, 9.95 mmol) portionwise. The reaction mixture was heated to reflux for 1.5 h, then cooled to room temperature, and filtered through a pad of Celite® (diatomaceous earth filter aid), rinsed 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 - 100% ethyl acetate in hexane) to give the title compound, a yellow solid (0.3 g), which is a compound of the present invention. 1 1H NMR (CDCl3): 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).

[0203] Example 4 Production of Methyl N-[[5-[1-(4-bromo-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 7) Methyl [[5-[1-(4-amino-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (i.e., the product of Example 3) (90 mg, 0.242 mmol) in a mixture of acetonitrile (2 mL) was added copper(II) bromide (65 mg, 0.290 mmol). The reaction mixture was cooled to about 0 °C and then 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 silica gel column chromatography (eluting with a gradient of 10 - 40% ethyl acetate in hexane). The resulting material was further purified by column chromatography (eluting with a gradient of 0 - 10% ethyl acetate in dichloromethane) to obtain the title compound, which is a compound of the present invention, as a yellow oil. 1 H NMR (CDCl3): 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). LCMS: m / z: 436 [M+H] +

[0204] Example 5 Production of Methyl N-[[5-[1-(2,6-difluoro-4-hydroxyphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 10) Methyl N-[[5-[1-(2,6-difluoro-4-methoxyphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (i.e., the product of Example 1) (1.20 g, 3.10 mmol) in dichloromethane (30 mL) was added dropwise with boron tribromide (1 M solution in dichloromethane, 9.40 mL, 9.30 mmol) at 0 °C. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was quenched slowly with water (35 mL), followed by dropwise addition of methanol (35 mL), and then stirred at room temperature for 1 hour. 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 eluted by silica gel column chromatography (eluting with a gradient of 20 - 70% ethyl acetate in hexane) to obtain the title compound, which is a compound of the present invention, as a white solid (0.87 g). 1 1H NMR (CDCl3): δ 7.74 (br s, 1H), 7.63 (dd, 1H), 7.60 (d, 1H), 7.24 (d, 1H), 6.75 (d, 1H), 6.46 (d, 2H), 4.95 (br s, 1H), 4.42 (d, 2H), 3.69 (s, 3H), 2.37 (s, 3H).

[0205] Example 6 Production of Methyl N-[[5-[1-[2,6-difluoro-4-(1-methylethoxy)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 14) To a mixture of methyl N-[[5-[1-(2,6-difluoro-4-hydroxyphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (i.e., the product of Example 5) (87 mg) in tetrahydrofuran (3 mL) were 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 hours and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with a gradient of 10 - 50% ethyl acetate in hexane) to obtain the title compound, which is a compound of the present invention, as a white solid (85 mg). 1 1H NMR (CDCl3): δ 7.75 (d, 1H), 7.67 (dd, 1H), 7.59 (d, 1H), 7.22 (d, 1H), 6.74 (d, 1H), 6.58 (d, 2H), 4.54 (m, 1H), 4.83 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 2.36 (s, 3H), 1.37 (d, 6H). LCMS: m / z: 416 [M+H] +

[0206] Example 7 Production of Methyl 3,5-difluoro-4-[3-[3-[[(methoxycarbonyl)amino]methyl]-4-methylphenyl]-1H-pyrazol-1-yl]benzoate (Compound 70) Methyl N-[[2-methyl-5-(1H-pyrazol-3-yl)phenyl]methyl]carbamate (2.58 g, 10.5 mmol) (for the production method, refer to PCT International Publication WO2008124092) and methyl 3,4,5-trifluorobenzoate (2.41 g, 12.6 mmol) in dimethyl sulfoxide (10 mL) were added potassium carbonate (4.35 g, 31.5 mmol). The reaction mixture was stirred at room temperature for 48 hours 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 substance was purified by column chromatography (eluting with a gradient of 10 - 50% ethyl acetate in hexane) to obtain the title compound, which is a light red solid (3.55 g). 1 1H NMR (CDCl3): δ 7.76 (d, 2H), 7.74 (m, 2H), 7.68 (d, 1H), 7.24 (d, 1H), 6.80 (d, 1H), 4.87 (br s, 1H), 4.42 (d, 2H), 3.97 (s, 3H), 3.70 (s, 3H), 2.37 (s, 3H).

[0207] Example 8 Production of Methyl N-[[5-[1-[2,6-difluoro-4-(hydroxymethyl)phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 71) Methyl (3,5-difluoro-4-[3-[3-[[(methoxycarbonyl)amino]methyl]-4-methylphenyl]-1H-pyrazol-1-yl]benzoate) (i.e., the product of Example 7) (3.55 g, 8.55 mmol) in methanol (45 mL) was added portionwise with sodium borohydride (1.94 g, 51.3 mmol). The reaction mixture was stirred overnight at room temperature, 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 - 100% ethyl acetate in hexane) to give the title compound, a compound of the invention, as a white solid (2.52 g). 1 1H 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).

[0208] Example 9 Production of Methyl N-[[5-[1-(2,6-difluoro-4-formylphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 67) Methyl N-[[5-[1-[2,6-difluoro-4-(hydroxymethyl)phenyl]-1H-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 portionwise with Dess-Martin periodinane (2.52 g, 5.94 mmol). The reaction mixture was stirred overnight at room temperature, then quenched with aqueous sodium carbonate and extracted with ethyl acetate (2x). The combined extracts were filtered and rinsed with ethyl acetate. The filtrate was washed with saturated aqueous sodium bicarbonate (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 - 60% ethyl acetate in hexane) to give the title compound, a compound of the invention, as a white solid (1.78 g). 1 1H NMR (CDCl3): δ 9.98 (t, 1H), 7.76 (m, 2H), 7.69 (dd, 1H), 7.62 (d, 2H), 7.24 (d, 1H), 6.83 (d, 1H), 4.86 (br s, 1H), 4.43 (d, 2H), 3.71 (s, 3H), 2.38 (s, 3H).

[0209] Example 10 Production of Methyl N-[[5-[1-[4-(difluoromethyl)-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 87) To a mixture of methyl N-[[5-[1-(2,6-difluoro-4-formylphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (i.e., the product of Example 9) (0.25 g, 0.65 mmol) in dichloromethane (10 mL) was added dropwise Deoxo-Fluor® (0.36 mL, 1.95 mmol) at about 0 °C, followed by the addition of one drop of ethanol. The reaction mixture was stirred at room temperature overnight and then slowly poured into saturated aqueous sodium carbonate (200 mL). After 30 minutes, the layers were separated and the aqueous layer was extracted with dichloromethane (1x). 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 10 - 50% ethyl acetate in hexane) to give the title compound, a colorless oil, which is a compound of the present invention (0.23 g). 1 1H NMR (CDCl3): δ 7.75 (d, 1H), 7.71 - 7.68 (m, 2H), 7.27 (d, 2H), 7.23 (d, 1H), 6.80 (d, 1H), 6.78 - 6.55 (t, 1H), 4.85 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 2.37 (s, 3H). LCMS: m / z: 408 [M + H] +

[0210] Example 11 Production of Methyl N-[[5-[1-(4-acetyl-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 68) Methyl N-[[2-methyl-5-(1H-pyrazol-3-yl)phenyl]methyl]carbamate (2.0 g, 8.16 mmol) (for the production method, refer to PCT International Publication WO2008124092) and 1-(3,4,5-trifluorophenyl)ethanone (2.0 g, 11.4 mmol) in dimethyl sulfoxide (9 mL) were added potassium carbonate (3.38 g, 24.5 mmol). The reaction mixture was stirred overnight at room temperature 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 obtained substance was purified by silica gel column chromatography (eluted with a gradient of 10 - 70% ethyl acetate in hexane) to obtain the title compound, which is a compound of the present invention, as a pale orange solid (2.10 g). 1 1H NMR (CDCl3): 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).

[0211] Example 12 Production of Methyl N-[[5-[1-[2,6-difluoro-4-[1-(methoxyimino)ethyl]phenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 83) A mixture of methyl N-[[5-[1-(4-acetyl-2,6-difluorophenyl)-1H-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 to 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 obtain the title compound, which is a compound of the present invention, as an amber solid (239 mg). 1 1H NMR (CDCl3): 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] +

[0212] Example 13 Production of Methyl N-[[5-[1-(2,6-difluoro-4-iodophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 8) To a mixture of methyl N-[[5-[1-(4-amino-2,6-difluorophenyl)-1H-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 tert-butyl nitrite (0.84 mL, 7.04 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 5 hours and then an additional diiodomethane (12 mL, 150 mmol) was added. After stirring overnight, the reaction mixture was diluted with ethyl acetate and washed with saturated sodium metabisulfite (3x), saturated sodium chloride solution (2x), and hydrochloric acid (1N 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 0-10% ethyl acetate in hexane) to give the title compound, a grayish-white solid, which is the compound of the present invention (1.0 g). 1 H NMR (CDCl3): 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).

[0213] Example 14 Preparation of methyl N-[[5-[1-(4-ethynyl-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 53) Step A: Production of Methyl N-[[5-[1-(2,6-difluorophenyl-4-(2-(trimethylsilyl)ethynyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate Methyl N-[[5-[1-(2,6-difluoro-4-iodophenyl)-1H-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) were combined, and triethylamine (0.063 mL, 0.455 mmol) was added. 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 silica gel column chromatography (eluting with a gradient of 5 - 40% ethyl acetate in hexane) to give the title compound as a pale brown oil (0.17 g). 1 H NMR (CDCl3): δ 7.74 (d, 1H), 7.67 (m, 2H), 7.23 (d, 1H), 7.16 (d, 2H), 6.77 (d, 1H), 4.84 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 2.37 (s, 3H), 0.27 (s, 9H).

[0214] Step B: Production of Methyl N-[[5-[1-(4-ethynyl-2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 53) Methyl [[5-[1-(2,6-difluorophenyl)-4-(2-(trimethylsilyl)ethynyl)-1H-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 left overnight at room temperature. 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 - 50% ethyl acetate in hexane) to give the title compound, a compound of the invention, as an amber oil (0.109 g). 1 1H NMR (CDCl3): δ 7.75 (d, 1H), 7.68 - 7.66 (m, 2H), 7.23 (d, 1H), 7.20 (d, 2H), 6.78 (d, 1H), 4.84 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 3.24 (s, 1H), 2.37 (s, 3H). LCMS m / z: 382 [M+H] +

[0215] Example 15 Production of Methyl N-[[5-[1-[4-[(1,1-dimethylethyl)thio]-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 42) A mixture of methyl N-[[5-[1-(2,6-difluoro-4-iodophenyl)-1H-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 nitrogen stream for 10 - 15 minutes, 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 hour, 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 silica gel column chromatography (eluting with a gradient of 10 - 50% ethyl acetate in hexane) to give the title compound, a compound of the invention, as an orange oil (0.189 g). 1 1H NMR (CDCl3): δ 7.75 (d, 1H), 7.69 - 7.67 (m, 2H), 7.27 (d, 2H), 7.23 (d, 1H), 6.79 (d, 1H), 4.84 (br s, 1H), 4.42 (d, 2H), 3.70 (s, 3H), 2.37 (s, 3H), 1.37 (s, 9H).

[0216] Example 16 Preparation of methyl N-[[5-[1-[4-[(difluoromethyl)thio]-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 43) Step A: Production of Methyl N-[[5-[1-(2,6-difluoro-4-mercaptophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate Methyl [[5-[1-[4-[(1,1-dimethylethyl)thio]-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (i.e., the product of Example 15) (0.16 g, 0.360 mmol) in dichloromethane (5 mL) was added dropwise with boron tribromide (1 M solution in dichloromethane, 1.10 mL, 1.08 mmol) at about 0 °C. The reaction mixture was stirred overnight at room temperature and quenched with water (6 mL) and methanol (6 mL). After stirring for 2 hours, 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 - 100% ethyl acetate in hexane to afford the title compound as a solid (77 mg). 1 1H NMR (CDCl3): 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).

[0217] Step B: Production of Methyl N-[[5-[1-[4-[(difluoromethyl)thio]-2,6-difluorophenyl]-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate Methyl N-[[5-[1-(2,6-difluoro-4-mercaptophenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (i.e., the product of Step A) (77 mg, 0.198 mmol) in a mixture of acetonitrile and water (1:1, 2 mL) was treated with 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 - 50% ethyl acetate in hexane) to give the title compound, a grayish white solid, which is a compound of the invention (64 mg). 1 1H NMR (CDCl3): 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] +

[0218] Example 17 Preparation of Methyl N-[[5-[1-(2,6-dichlorocyclopropylphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate (Compound 65) Step A: Production of 5-[1-(2,6-dichloro-4-nitrophenyl)-1H-pyrazol-3-yl]-2-methylbenzonitrile 2-Methyl-5-(1H-pyrazol-3-yl)benzonitrile (3.0 g, 16.4 mmol) (for the production method, refer to PCT International Publication WO2014066120), a mixture of 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 hours, and then stirred overnight at room temperature. The reaction mixture was diluted with water, and the resulting precipitate was collected by filtration and washed with water. The solid precipitate was triturated with a mixture of hexane / 1-chlorobutane, filtered, and air-dried to obtain the title compound (3.59 g). 1 1H NMR (CDCl3): 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).

[0219] Step B: Production of 5-[1-(4-amino-2,6-dichlorophenyl)-1H-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 (34.5 mL), 5-[1-(2,6-dichloro-4-nitrophenyl)-1H-pyrazol-3-yl]-2-methylbenzonitrile (i.e., the product of step A) (6.07 g, 16.26 mmol) was added little by little while maintaining the reaction temperature at about 25 °C. The reaction mixture was stirred overnight and then 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 obtain the title product (6.8 g). 1H NMR (CDCl3): 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). 1 1H NMR (CDCl3): 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).

[0220] Step C: Production of 5-[1-(4-bromo-2,6-dichlorophenyl)-1H-pyrazol-3-yl]-2-methylbenzonitrile A mixture of 5-[1-(4-amino-2,6-dichlorophenyl)-1H-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 under reflux overnight, then cooled to room temperature and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 20% ethyl acetate in hexane) to give the title compound (4.3 g). 1 1H NMR (CDCl3): δ 8.22 (s, 1H), 7.96 (d, 1H), 7.66 (s, 2H), 7.58 (s, 1H), 7.36 (d, 1H), 6.80 (s, 1H), 2.57 (s, 3H).

[0221] Step D: Production of 5-[1-(2,6-dichloro-4-cyclopropylphenyl)-1H-pyrazol-3-yl]-2-methylbenzonitrile A mixture of 5-[1-(4-bromo-2,6-dichlorophenyl)-1H-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 (0 - 10% ethyl acetate in hexane) to give the title compound (0.90 g). 1 1H NMR (CDCl3): 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).

[0222] Step E: Production of 5-[1-(2,6-dichloro-4-cyclopropylphenyl)-1H-pyrazol-3-yl]-2-methylbenzenemethanamine hydrochloride 5-[1-(2,6-Dichloro-4-cyclopropylphenyl)-1H-pyrazol-3-yl]-2-methylbenzonitrile (i.e., to a mixture of 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 overnight at room temperature, cooled to about 0 - 5 °C, and then hydrochloric acid (4 N solution in dioxane, 2.02 mL) was added dropwise. The resulting precipitate was collected by filtration and air-dried to give the title compound as a solid (0.82 g). 1 H NMR(CDCl3):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(

[0223] Process F: Preparation of Methyl [[5-[1-(2,6-Dichloro-4-cyclopropylphenyl)-1H-pyrazol-3-yl]-2-methylphenyl]methyl]carbamate 5-[1-(2,6-Dichloro-4-cyclopropylphenyl)-1H-pyrazol-3-yl]-2-methylbenzenemethanamine 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) were added methyl chloroformate (0.21 g, 2.21 mmol) at about 0 - 5 °C. The reaction mixture was stirred overnight at room temperature and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 0% - 100% ethyl acetate in hexane) to give the title compound, a compound of the present invention, as a solid (0.87 g). 11H NMR (CDCl3): 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). LCMS: m / z 430 [M+H] +

[0224] Example 18 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)-1H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 132) Process A: Preparation of 2-Methyl-5-[2-(trimethylsilyl)ethynyl]benzonitrile To a mixture of 2-amino-5-bromobenzonitrile (50 g, 255 mmol) and ethynyltrimethylsilane (181 mL, 1275 mmol) in tetrahydrofuran (600 mL) were added bis(triphenylphosphine)palladium(II) dichloride (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 hours and then concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (eluting with 5% ethyl acetate in petroleum ether) to give the title compound as a solid (45 g). 1 1H NMR (CDCl3): δ 7.68 (d, J = 1.6 Hz, 1H), 7.63 (dd, J = 8.0, 1.6 Hz, 1H), 7.24 (s, 1H), 2.53 (s, 3H), 0.24 (s, 9H).

[0225] Process B: Preparation of 5-Ethynyl-2-methylbenzonitrile 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 with potassium hydroxide (67 mL, 1% in methanol). The reaction mixture was stirred at room temperature for 16 h and then distilled to remove 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 substance was purified by silica gel column chromatography (eluting with 12% ethyl acetate in petroleum ether) to obtain the title compound as a solid (15 g). 1 H NMR (CDCl3): δ 7.70 (d, J = 1.2 Hz, 1H), 7.57 ( dd, J = 8.4, 2.0 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 3.12 (s, 1H), 2.55 (s, 3H).

[0226] Process C: Preparation of 5-Ethynyl-2-methylbenzenemethanamine Hydrochloride To a mixture of diphenylsilane (81 mL, 443 mmol) in chloroform (250 mL) were added tris(2,3,4,5,6-pentafluorophenyl)borane (2.7 g, 5.3 mmol), followed by 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 then concentrated under reduced pressure. Hydrochloric acid (2N solution in diethyl ether) was added to the resulting substance and the mixture was stirred for 1 h. The resulting solid precipitate was collected by filtration and dried to obtain the title compound as a solid (30 g). 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).

[0227] Process D: Preparation of Methyl [(5-ethynyl-2-methylphenyl)methyl]carbamate A mixture of 5-ethynyl-2-methylbenzenemethanamine 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) was added dropwise with methyl chloroformate (23.3 g, 248.6 mmol) at 0 °C over 20 minutes. The reaction mixture was stirred at room temperature for 16 hours, 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 give the title compound as a solid (25 g). 1 H NMR (CDCl3): δ 7.38 (br s, 1H), 7.33 - 7.31 (m, 1H), 7.13 - 7.11 (m, 1H), 4.83 (brs, 1H) 4.34 (d, J = 5.6 Hz, 2H), 3.71 (s, 3H), 3.04 (s, 1H), 2.32 (s, 3H).

[0228] Process E: Preparation of Methyl N-[[5-(1H-1,2,3-triazol-4-yl)-2-methylphenyl]methyl]carbamate To a mixture of [(5-ethynyl-2-methylphenyl)methyl]carbamic acid methyl (i.e., the product of Step D) (30 g, 165.7 mmol) in N,N-dimethylformamide (117 mL) were added methanol (12 mL), trimethylsilyl azide (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 hours, 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 give the title compound as a solid (4 g). 11H NMR (CDCl3): δ 11.8 (br s, 1H), 7.94 (s, 1H), 7.71 (s, 1H), 7.64 - 7.61 (m, 1H), 7.24 (s, 1H), 4.93 (br s, 1H), 4.43 (d, J = 6.0 Hz, 2H), 3.71 (s, 3H), 2.37 (s, 3H).

[0229] Process 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)-1H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]ca rbamate (Compound 132) To a mixture of methyl N-[[5-(1H-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, 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 give methyl N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 118), the compound of the present invention, as a solid (2 g). 1 1H NMR (DMSO-d6): δ 8.77 (s, 1H), 8.45 (dd, J = 9.2, 2 Hz, 2H), 7.80 (s, 1H), 7.76 - 7.74 (m, 1H), 7.69 - 7.66 (m, 1H), 7.32 (d, J = 8.0 Hz, 1H), 4.24 (d, J = 5.6 Hz, 2H), 3.55 (s, 3H), 2.33 (s, 3H). LCMS: m / z: 404 [M+H] + 。

[0230] A solid containing 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)-1H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 132) was also obtained. This solid was further purified by silica gel chromatography to obtain methyl N-[[5-[1-(2,6-difluoro-4-nitrophenyl)-1H-1,2,300-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 132), which is a compound of the present invention, as a solid (800 mg). 1 1H NMR (DMSO-d6): δ 9.08 (s, 1H), 8.50 (d, J = 7.6 Hz, 2H), 7.83 - 7.82 (m, 2H), 7.71 - 7.67 (m, 2H), 7.29 (d, 8.4 Hz, 1H), 4.24 (d, J = 6.4 Hz, 2H), 3.57 (s, 3H), 2.32 (s, 3H). LCMS: m / z: 404 [M+H] + 。

[0231] Example 19 Preparation of Methyl N-[[5-[2-(4-Amino-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 115) Methyl N-[[5-[2-(2,6-difluoro-4-nitrophenyl)-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (i.e., the product of step F of Example 18, Compound 118) (2 g, 4.9 mmol) in a mixture of 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 to reflux for 1.5 hours, stirred at room temperature for 16 hours, then filtered through a pad of Celite® (diatomaceous earth filter aid) and rinsed with ethyl acetate (30 mL). The filtrate was diluted with water and extracted with ethyl acetate. The combined organic layers 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 give the title compound, a solid (1.6 g), which is a compound of the present invention. 1 1H NMR (CDCl3): δ 8.08 (s, 1H), 7.74 - 7.73 (m, 1H), 7.67 - 7.65 (m, 1H), 7.24 (s, 1H), 6.33 - 6.30( m, 2H), 4.89 (br s, 1H), 4.42 (d, J = 5.2 Hz, 2H), 4.13 (s, 2H), 3.70 (s, 3H), 2.37 (s, 3H LCMS: m / z: 374 [M + H] + 。

[0232] The following compounds were prepared in the same manner as in the method of Example 19: Methyl N-[[5-[1-(4-amino-2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 131). 1 1H NMR (CDCl3): δ 7.91 (s, 1H), 7.81 (s, 1H), 7.70 (d, 1H), 7.25 (s, 1H), 6.35 (d, 2H), 4.93 (br s, 1H), 4.45 (s, 2H), 4.19 (br s, 2H), 3.71 (s, 3H), 2.39 (s, 3H).

[0233] Example 20 Preparation of Methyl N-[[5-[2-(4-Chloro-2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 117) 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) was added to a mixture in carbon tetrachloride (125 mL), and n-butyl nitrite (3.3 g, 32.17 mmol) was added. The reaction mixture was heated to reflux for 16 hours, then filtered through a pad of Celite® (diatomaceous earth filter aid) and rinsed 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 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 give the title compound, a compound of the invention, as a solid (0.12 g). 1 H NMR (CDCl3): δ 8.13 (s, 1H), 7.74 - 7.73 (m, 1H), 7.66 (dd, J = 8.0, 1.6 Hz, 1H), 7.28 (s, 1H), 7.19 - 7.15 (m, 2H), 4.90 (brs, 1H), 4.43 (d, J = 5.6 Hz, 2H), 4.71 (s, 3H), 2.38 (s, 3H). LCMS: m / z: 393 [M + H] + 。

[0234] The following compounds were prepared in the same manner as in the method of Example 20: Methyl N-[[5-[1-(4-chloro-2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl]-2-methylphenyl]methyl]carbamate (Compound 121). 1 H NMR (CDCl3): δ 7.98 (s, 1H), 7.79 (brs, 1H), 7.70 (d, J = 6.4 Hz, 1H), 7.27 - 7.20 (m, 3H), 4.91 (br s, 1H), 4.44 - 4.43 (m, 2H), 3.71 (s, 3H), 2.38 (s, 3H). LCMS: m / z: 393 [M+H] + 。

[0235] By the procedures described herein, together with methods known in the art, the following compounds of Tables 1A - 33D can be produced. The following abbreviations are used in the table below: 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.

[0236]

Table 1

[0237] The present disclosure also includes Tables 2A - 33A, which are each of the same configuration as Table 1A above, except that the column headings of Table 1A (i.e., "R 1 and R 2 are F") are replaced by the respective column headings shown below. For example, in Table 2A, the column heading is "R 1 and R 2 are Cl", and R 6 is as defined in Table 1A above.

[0238]

Table 2

[0239] Table 1B Table 1B is the same as Table 1A except that the chemical structure in Table 1A is replaced by the following structure:

Chem.

[0240] Table 2B - 33B Tables 2B to 33B are constructed in the same way as Tables 2A to 33A.

[0241] Table 1C Table 1C is the same as Table 1A except that the chemical structure in Table 1A is replaced by the following structure: [Chemical formula]

[0242] Table 2C - 33C Tables 2C to 33C are constructed in the same way as Tables 2A to 33A.

[0243] Table 1D Table 1D is the same as Table 1A except that the chemical structure in Table 1A is replaced by the following structure: [Chemical formula]

[0244] Table 2D - 33D Tables 2D to 33D are constructed in the same way as Tables 2A to 33A.

[0245] Formulation / Practicality The compounds of formula 1 of the present invention (including their N-oxides, hydrates, and salts) are generally used as a bactericidal active ingredient in a composition, i.e., a formulation, together with at least one additional component that functions as a carrier, selected from the group consisting of surfactants, solid diluents, and liquid diluents. The components of the formulation or composition are selected to be compatible with the physical properties of the active ingredient, the mode of application, and environmental factors such as the type of soil, humidity, and temperature.

[0246] Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (emulsions Examples include liquids (including aqueous liquids), suspending agents, emulsifying agents (including microemulsions and / or suspoemulsions), etc., which may in some cases be thickened to form gels. General types of aqueous liquid compositions are solutions, SC agents (suspension concentrates), CS agents (capsule suspensions), thick emulsions, microemulsions, and suspoemulsions. General types of non-aqueous liquid compositions are emulsions, microemulsifiable concentrates, DC agents (dispersible concentrates), and OD agents (oil dispersions).

[0247] General types of solid compositions are powders, dusts, granules, pellets, pills, aromatic tablets, tablets, filled films (including seed coatings), etc., which may be water-dispersible (“hydratable”) or water-soluble. Films and coatings formed from film-forming solutions or fluid suspensions are particularly useful for seed treatment. The active ingredient can be (micro)encapsulated and further formed into a suspension or solid dosage form; 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 emulsion formulations and dry granule formulations. High-strength compositions are mainly used as intermediates for further formulation.

[0248] Sprayable formulations are typically spread in a suitable medium prior to spraying. Such liquid and solid formulations are formulated to be readily diluted in a medium which is typically water, but may also be another suitable medium such as an aromatic or paraffinic hydrocarbon or a vegetable oil. The application rate can range from about 1 liter to several thousand liters per hectare, but more typically can range from about 10 liters to several hundred liters per hectare. Sprayable formulations can be tank-mixed with water or another suitable medium for foliar treatment by aerial or ground spraying, or for application to the plant growth medium. Liquid and dry formulations can be measured directly into a drip irrigation system or measured into the furrow between rows during seeding. Liquid and solid formulations may be applied to seeds of crops and desirable vegetation as a seed treatment prior to seeding to protect against emerging roots and other underground plant parts and / or leaves by systemic uptake.

[0249] Formulations typically contain an effective amount of active ingredient, diluent, and surfactant within the following suitable ranges which total 100% by weight.

[0250] [Table 3]

[0251] Examples of solid diluents include clays such as bentonite, montmorillonite, attapulgite, and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, saccharides (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate, sodium bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins etal., Handbook of Insecticide Dust Diluents and Carriers, 2nd Edition, Dorland Books, Caldwell, New Jersey.

[0252] Examples of the liquid diluent include water, N,N-dimethylalkanamide (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidone (e.g., N-methylpyrrolidone), alkyl phosphate (e.g., triethyl phosphate), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oil, linear paraffin, isoparaffin), alkylbenzene, alkylnaphthalene, glycerin, glycerol triacetate, sorbitol, aromatic hydrocarbon, dearomatized aliphatic, alkylbenzene, alkylnaphthalene, ketone, such as cyclohexanone, 2-heptanone, isophorone, and 4-hydroxy-4-methyl-2-pentanone, acetate, such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate, and isobornyl acetate, other esters, such as alkylated lactate ester, dibasic ester, alkyl benzoate, and aryl benzoate, and γ-butyrolactone, and an alcohol which may be linear, branched, saturated, or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol, cresol, and benzyl alcohol. The liquid diluent also includes glycerol esters of saturated and unsaturated fatty acids (typically C6-C 22 ), such as vegetable seed and fruit oils (e.g., olive, sesame, linseed, sesame, corn (maize), peanut, sunflower, grape seed, safflower, cottonseed, soybean, rapeseed, coconut, and palm kernel oils), animal It also includes fat of animal origin (e.g., beef tallow, lard, lard, cod liver oil, fish oil), and mixtures thereof. The liquid diluent also includes alkylated fatty acids (e.g., methylated, ethylated, butylated), where the fatty acids can be obtained by hydrolysis of glycerol esters of plant and animal origin and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents guide, Second Edition, Interscience, New York, 1950.

[0253] The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, the surfactant (also known as a "surface active agent") generally modifies, and most frequently decreases, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, the surfactant can be useful as a wetting agent, dispersing agent, emulsifying agent, or defoaming agent.

[0254] Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful in the compositions of the present invention include, but are not limited to: alkoxylated alcohols, such as those based on natural and synthetic alcohols (branched or straight-chain), and produced from alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; ethoxylated amines, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides, such as ethoxylated soybean oil, castor oil and rapeseed oil; alkylphenol alkoxylates, such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecylphenol ethoxylate (produced from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers produced from ethylene oxide or propylene oxide and reverse block polymers with terminal blocks produced from propylene oxide; ethoxylated fatty acids; ethoxylated fatty acid esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those produced 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, alkyl 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 and alkyl polysaccharides.

[0255] Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohols or alkylphenol ethoxylates; diphenylsulfonate derivatives; lignin and lignin derivatives, such as lignosulfonates; maleic acid or succinic acid or their anhydrides; olefin sulfonates; phosphate esters, such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates, and phosphate esters of styrylphenol ethoxylates; protein-based surfactants; sarcosine derivatives; styrylphenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides, such as N,N-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkylnaphthalenes; sulfonates of fractionated petroleum; sulfosuccinamic acid salts; and sulfosuccinates and their derivatives, such as dialkyl sulfosuccinates. Examples include dialkyl sulfosuccinates.

[0256] Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkylpropanediamine, tripropylene triamine, and dipropylene tetramine, and ethoxylated amines, ethoxylated diamines, and propoxylated amines (produced from amines and ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts, and bis-quaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

[0257] Mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants are also useful in the compositions of the present invention. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in various published references, including McCutcheon’s Division, McCutcheon’s Emulsifiers and Detergents, published annually in international and North American editions by The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, 7th Edition, John Wiley and Sons, New York, 1987.

[0258] The compositions of the present disclosure may also contain formulation aids and additives known to those skilled in the art as formulation adjuvants. Such formulation aids and additives include: pH (buffers), foaming during processing (antifoaming agents such as polyorganosiloxanes (e.g., Rhodorsil® 416)), sedimentation of the active ingredient (suspending agents), viscosity (thixotropic thickeners), microbial growth in the container (antimicrobial agents), product freezing (antifreeze agents), color (pigment / dye dispersions (e.g., Pro-lzed® Colorant Red)), wash-off (film-forming agents or stickers), evaporation (evaporation retardants), and other formulation attributes can be controlled. Examples of film-forming agents include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes. Examples of formulation aids and examples of additives include those listed in McCutcheon’s Volume 2: Functional Materials, published annually in the international and North American editions by McCutcheon’s Division, The Manufacturing Confectioner Publishing Co.; and PCT International Publication No. WO03 / 024222.

[0259] The compounds of formula I and any other active ingredients are typically incorporated into the compositions of the invention by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsions, can be prepared simply by mixing the ingredients. When the solvent of a liquid composition intended for use as an emulsion is immiscible with water, an emulsifier is typically added to emulsify the active ingredient-containing solvent when diluted with water. An active ingredient slurry having a particle size up to 2,000 μm can be wet milled using a media mill to obtain particles having an average diameter of less than 3 μm. The aqueous slurry can be made into a finished SC formulation (see, e.g., U.S. 3,060,084) or further processed by spray drying to form wettable granules. Dry formulations generally require a dry grinding process, which results in an average particle size in the range of 2 to 10 μm. Powders and dusts can be prepared by mixing and usually grinding (e.g., using a hammer mill or a fluid energy mill). Granules and pellets can be prepared by spraying the active substance onto a preformed granular carrier or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pages 147 - 48, Perry’s Chemical Engineer’s Handbook, 4th Edition, McGraw - Hill, New York, 1963, page 8 - 57 and the following, and WO91 / 13546. Pellets can be prepared as described in U.S. 4,172,714. Wettable and water - soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE3,246,493. 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 gB2,095,558 and U.S. 3,299,566.

[0260] One embodiment of the present invention relates to a method for controlling a fungal pathogen, which includes diluting a bactericidal composition of the present invention (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 bactericide) with water, and optionally adding an adjuvant to form a diluted composition, and contacting a fungal pathogen or its environment with an effective amount of the above diluted composition.

[0261] A spray composition formed by diluting a bactericidal composition of the present invention at a sufficient concentration with water may provide sufficient effectiveness for controlling a fungal pathogen, but separately formulated adjuvant products may also be added to the spray tank mixture. These additional adjuvants are generally known as "spray adjuvants" or "tank mix adjuvants", and these include any substances that are mixed in a spray tank to improve the performance of an insecticide or to change the physical properties of a spray mixture. Adjuvants can be anionic or nonionic surfactants, emulsifiers, petroleum-based crop oils, seed oils derived from crops, acidifying agents, buffering agents, thickening agents or defoaming agents. Adjuvants are used to enhance effectiveness (e.g., bioavailability, adhesion, penetration, uniformity of coverage and persistence of protection), or to minimize or eliminate problems with spray application related to incompatibility, foaming, drift, evaporation, volatilization and decomposition. To obtain optimal performance, adjuvants are selected with respect to the properties of the active ingredient, formulation and target (e.g., crops, harmful insects).

[0262] The amount of adjuvant added to the spray mixture is generally in the range of about 2.5% to 0.1% by volume. The application rate of the adjuvant added to the spray mixture is typically about 1 to 5 L per hectare. Representative examples of spray adjuvants include: Adigor® (Syngenta), 47% methylated rapeseed oil in liquid hydrocarbon; Silwet® (Helena Chemical Company), polyalkylene oxide-modified heptamethyltrisiloxane; and Assist® (BASF), a 17% surfactant blend in 83% paraffinic mineral oil.

[0263] One method of seed treatment is to spray or dust the seeds with the compound of the present invention (i.e., as a formulated composition) before sowing the seeds. The composition formulated for seed treatment generally contains a film-forming agent or an adhesive. Thus, typically the seed coating composition of the present invention contains a biologically effective amount of the compound of formula 1 and a film-forming agent or an adhesive. The seeds can be coated by spraying a flowable formulation directly onto a rotating bed of seeds and then drying the seeds. Alternatively, other dosage forms such as wettable powders, solutions, suspoemulsions, emulsions, and emulsions in water may be sprayed onto the seeds. This process is particularly useful for forming a film coating on the seeds. A variety of coating machines and coating processes are available to those skilled in the art. Suitable processes include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects, 19 94 BCPC Mongraph No.57, and those listed in the references cited therein.

[0264] For further information on formulation technology, see Pesticide Chemistry and Bioscience, The Food-Environment Challenge, edited by T. Brooks and T. R. Roberts, Proceedings of the 9th International Congress See T.S. Woods, "The Formulator’s Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pages 120 - 133. U.S. 3,235,361, column 6, lines 16 - column 7, line 19 and Examples 10 - 41; U.S. 3,309,192, column 5, line 43 - column 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, column 3, line 66 - column 5, line 17 and Examples 1 - 4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pages 81 - 96; Hance etal., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.

[0265] In the following examples, all percentages are by weight and all formulations are made by conventional methods. Compound numbers refer to the compounds in Index Tables A - G. Even without further elaboration, it is considered that those skilled in the art can utilize the present invention to its full extent using the previous descriptions. Therefore, the following examples are for illustrative purposes only and should not be construed as limiting the present disclosure in any way.

[0266] Example A High-Strength Concentrate Compound 1 98.5% Silica aerosol 0.5% Synthetic amorphous fine silica 1.0%

[0267] Example B Wettable Powder Compound 3 65.0% Dodecylphenol polyethylene glycol ether 2.0% Sodium lignosulfonate 4.0% Sodium aluminosilicate 6.0% Montmorillonite (calcined) 23.0%

[0268] Example C Granules Compound 4 10.0% Attapulgite granules (low volatile matter, 0.71 / 0.30 mm; U.S.S. No.25 - 50 sieve) 90.0%

[0269] Example D Extruded Pellets Compound 5 25.0% Sodium sulfate anhydrous 10.0% Crude calcium lignosulfonate 5.0% Sodium alkyl naphthalene sulfonate 1.0% Calcium / magnesium bentonite 59.0%

[0270] Example E Emulsion Compound 6 10.0% Polyoxyethylene sorbitol hexaoleate 20.0% C6 - C 10 Fatty acid methyl ester 70.0%

[0271] Example F Microemulsion Compound 7 5.0% Polyvinylpyrrolidone - vinyl acetate copolymer 30.0% Alkyl polyglycoside 30.0% Glyceryl monooleate 15.0% Water 20.0%

[0272] Example G Seed Treatment Compound 8 20.00% Polyvinylpyrrolidone-vinyl acetate copolymer 5.00% Montan wax 5.00% Calcium lignosulfonate 1.00% Polyoxyethylene / polyoxypropylene block copolymer 1.00% Stearyl alcohol (POE20) 2.00% Polyorganosilane 0.20% Red pigment dye 0.05% Water 65.75%

[0273] Example H Fertilizer Stick Compound 10 2.50% Pyrrolidone-styrene copolymer 4.80% Tristyrylphenyl 16-ethoxylate 2.30% Talc 0.80% Corn starch 5.00% Sustained release fertilizer 36.00% Kaolin 38.00% Water 10.60%

[0274] Example I SC Agent Compound 33 35% Butyl polyoxyethylene / polypropylene block copolymer 4.0% Stearic acid / polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Silicone defoamer 0.1% 1,2 - Benzisothiazolin - 3 - one 0.1% Water 53.7%

[0275] Example J EW Agent (Emulsion in Water) Compound 41 10.0% Butyl polyoxyethylene / polypropylene block copolymer 4.0% Stearic acid / polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Silicone defoamer 0.1% 1,2 - Benzisothiazolin - 3 - one 0.1% Aromatic petroleum - based hydrocarbon 20.0 Water 58.7%

[0276] Example K OD Agent (Oil Dispersion) Compound 68 25% Hexaoleic acid polyoxyethylene sorbitol 15% Organically modified bentonite clay 2.5% Fatty acid methyl ester 57.5%

[0277] Example L Suspension Emulsion Compound 115 10.0% Imidacloprid 5.0% Butyl polyoxyethylene / polypropylene block copolymer 4.0% Stearic acid / polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Silicone defoamer 0.1% 1,2 - Benzisothiazolin - 3 - one 0.1% Aromatic petroleum - based hydrocarbon 20.0% Water 53.7%

[0278] Water - soluble and water - miscible formulations are typically diluted with water prior to application to form an aqueous composition. An aqueous composition (e.g., a spray tank composition) for direct application to a plant or a part thereof typically contains at least about 1 ppm or more (e.g., 1 ppm to 100 ppm) of the compound of the present invention.

[0279] Seeds are usually treated in an amount of about 0.001 g (more typically about 0.1 g) to about 10 g per kilogram of seeds (i.e., about 0.0001 to 1 mass% of the seeds before treatment). A flowable formulation formulated for seed treatment typically contains about 0.5 to about 70% of the active ingredient, about 0.5 to about 30% of a film - forming adhesive, about 0.5 to about 20% of a dispersant, 0 to about 5% of a thickener, 0 to about 5% of a pigment and / or dye, 0 to about 2% of an antifoaming agent, about 1% of a preservative, and 0 to about 75% of a diluent.

[0280] The compounds of the present invention are useful as plant disease control agents. Accordingly, the present invention further includes a method for controlling plant diseases caused by fungal plant pathogens, which comprises applying an effective amount of the compound of the present invention or a fungicidal composition containing the compound to a plant to be protected or a part thereof, or to seeds of a plant to be protected. The compounds and / or compositions of the present invention provide control of diseases caused by a wide range of fungal plant pathogens in the Ascomycota, Basidiomycota, Zygomycota, and oomycete-like fungi. They are effective in controlling a wide range of plant diseases, particularly leaf diseases, of ornamental plants, turfgrass, vegetables, cereals, grains, and fruit crops. These pathogens include, but are not limited to, those listed in Table 1-1. For ascomycetes and basidiomycetes, both names for the sexual / sexual generation / perfect stage, as well as the asexual / asexual generation / imperfect stage (in parentheses), are listed when both are known. Synonyms of pathogens are indicated by an equal sign. For example, following the name of the sexual / sexual generation / perfect stage Phaeosphaeria nodorum, the corresponding asexual / asexual generation / imperfect stage name Stagnospora nodorum and the synonymous old name Septoria nodorum are listed.

[0281]

Table 4

[0282]

Table 5

[0283] In addition to their fungicidal activity, the compositions or combinations are effective against Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and amylovora), Xanthomonas campestris, Pseudomonas syringae, and It also has activity against bacteria such as other related species. By controlling harmful microorganisms, the compounds of the present invention are useful for improving (i.e., increasing) the ratio of beneficial microorganisms to harmful microorganisms that are in contact with crop plants or their propagules (e.g., seeds, bulbs, corms, tubers, cuttings) or are in the agronomic environment of crop plants or their propagules.

[0284] The compounds of the present invention are useful in the treatment of all plants, plant parts and seeds. Varieties and cultivars of plants and seeds can be obtained by conventional propagation and breeding methods or by genetic engineering methods. Genetically modified plants or seeds (transgenic plants or seeds) are those in which a foreign gene (transgene) has been stably integrated into the genome of the plant or seed. The transgene, defined by its specific location in the plant genome, is called a transformation event or transgenic event.

[0285] Genetically modified plant varieties that can be treated according to the present invention include those that are resistant to one or more biotic stresses (pests such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (such as drought, low temperature, soil salinity, etc.), or those that include other desirable characteristics. Plants can be genetically modified, for example, to exhibit traits such as herbicide tolerance, insect resistance, improved oil profile or drought tolerance.

[0286] Treatment of genetically modified plants and seeds with the compounds of the present invention can result in supra-additive or enhanced effects. For example, a decrease in application rate, an expansion of the activity spectrum, increased tolerance to biotic and abiotic stresses or enhanced storage stability can be higher than expected from the mere additive effect of the application of the compounds of the present invention to genetically modified plants and seeds.

[0287] The compounds of the present invention are useful in seed treatment for protecting seeds from plant diseases. In the context of the present disclosure and the claims, treating the seeds means contacting the seeds with a biologically effective amount of the compounds of the present invention, which are typically formulated as compositions of the present invention. This seed treatment protects the seeds from pathogens of soil-borne diseases and generally can also protect the roots and other plant parts in contact with the soil of the seedlings emerging from the germinating seeds. The seed treatment can also provide foliar protection by translocation of the compounds of the present invention or a second active ingredient in the growing plant. The seed treatment can be applied to all types of seeds, including those from plants genetically transformed to express specialized traits. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxins, or herbicide resistance, such as glyphosate acetyltransferase conferring resistance to glyphosate. The seed treatment with the compounds of the present invention can also increase the vitality of the plants growing from the seeds.

[0288] The compounds of the present invention and their compositions, both alone and in combination with other fungicides, nematicides and insecticides, are particularly useful in seed treatment for agricultural crops, including but not limited to maize or corn, soybeans, cottonseed, cereals (e.g., wheat, oats, barley, rye and rice), potatoes, vegetables and oilseeds.

[0289] Furthermore, the compounds of the present invention are useful in treating post-harvest diseases of fruits and vegetables caused by fungi and bacteria. These infections can occur before, during and after harvest. For example, the infection can occur before harvest and then remain dormant until a certain point during ripening (e.g., the host starts tissue changes in a way that the infection can progress); also, the infection can occur from surface wounds caused by mechanical or insect damage. In this regard, the compounds of the present invention can reduce losses due to post-harvest diseases that can occur at any time from harvest to consumption. Damage (i.e., damage resulting from quantity and quality) can be reduced. The treatment of post-harvest diseases using the compounds of the present invention increases the period during which perishable edible plant parts (e.g., fruits, seeds, leaves, stems, bulbs, tubers) can be stored refrigerated or non-refrigerated after harvest and can be kept in an edible state without significant or harmful decomposition or contamination by fungi or other microorganisms. Treatment of edible plant parts before or after harvest using the compounds of the present invention can also reduce the formation of toxic metabolites of fungi or other microorganisms, such as mycotoxins like aflatoxin.

[0290] Plant disease control is typically achieved by applying an effective amount of the compounds of the present invention, either before or after infection, to the parts of the plant to be protected (e.g., roots, stems, leaves, fruits, seeds, tubers or bulbs) or to the medium (soil or sand) in which the plant to be protected is growing. The compounds can also be applied to protect seeds and seedlings emerging from the seeds. The compounds can also be applied via irrigation water for treating plants. Pre-harvest control of post-harvest pathogens infecting agricultural products is typically achieved by field application of the compounds of the present invention, and if the infection occurs post-harvest, the compounds can be applied to the harvested agricultural products as dips, sprays, fumigants, linings for treated packaging materials and boxes.

[0291] The application rates (i.e., fungicidally effective amounts) for these compounds may be affected by factors such as the plant disease to be controlled, the plant species to be protected, ambient humidity and temperature, and should be determined under the actual use conditions. A person skilled in the art can readily determine the fungicidally effective amount required for the desired level of plant disease control by simple experiments. Leaves can typically be protected when treated with an amount of the active ingredient ranging from less than about 1 g / ha to about 5,000 g / ha. Seeds and seedlings can typically be protected when the seeds are treated with an amount ranging from about 0.001 g (more typically about 0.1 g) to about 10 g per kilogram of seeds.

[0292] The compounds of the present disclosure can also be mixed with one or more other biologically active compounds or agents to form multi-component pesticides that provide an even broader range of agricultural protection. These compounds or agents include fungicides, insecticides, nematicides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and root stimulants, chemical sterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, phytohormones, other biologically active compounds or entomopathogenic bacteria, viruses or fungi. Accordingly, the present disclosure also relates to compositions comprising a compound of formula I (in a fungicidally effective amount) and at least one further biologically active compound or agent (in a biologically effective amount), and which may further comprise at least one surfactant, solid diluent or liquid diluent. The other biologically active compounds or agents can be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent. In the mixtures of the present disclosure, one or more other biologically active compounds or agents can be formulated together with the compound of formula I to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of formula I, and these formulations are mixed (e.g., in a spray tank) before application or are applied sequentially.

[0293] As described in the gist of the present invention, one aspect of the present invention is a fungicidal composition comprising a compound of formula 1, its N-oxide, or a salt (i.e., component a), and at least one other fungicide (i.e., component b) (i.e., a mixture or combination). Of note are combinations such that the other fungicidal active ingredient has a different site of action from the compound of formula 1. In certain instances, combinations with at least one other fungicidal active ingredient having a similar control spectrum but a different site of action are particularly advantageous for resistance management. Accordingly, the compositions of the present invention may further comprise at least one further fungicidal active ingredient in a fungicidally effective amount having a similar control spectrum but a different site of action.

[0294] It should be noted that in addition to the compound of Formula 1 of component (a), as component (b), it contains at least one bactericidal compound selected from the group consisting of the mechanism of action (MOA) classes (A) nucleic acid synthesis, (B) mitosis and cell division, (C) respiration, (D) amino acid and protein synthesis, (E) signal transduction, (F) lipid synthesis and cell membrane integrity, (G) sterol biosynthesis of the cell membrane, (H) cell wall biosynthesis in the membrane, (I) melanin synthesis in the cell wall, (P) host plant defense induction, multi-site contact activity, and unknown mechanisms of action defined by FRAC.

[0295] The target sites of action recognized or proposed by FRAC, together with those FRAC target site codes belonging to the MOA classes above, are: (A1) RNA polymerase I, (A2) adenosine deaminase, (A3) DNA / RN biosynthesis (proposed), (A4) DNA topoisomerase, (B1 - B3) β - tubulin polymerization in mitosis, (B4) cell division (proposed), (B5) delocalization of spectrin - like proteins, (C1) complex I NADH oxidoreductase, (C2) complex II: succinate dehydrogenase, (C3) complex III: cytochrome bc1 (ubiquinol oxidase) Qo site, (C4) complex III: cytochrome bc1 (ubiquinone reductase) Qi site, (C5) uncoupling of oxidative phosphorylation, (C6) inhibitors of oxidative phosphorylation, ATP synthase, (C7) ATP production (proposed), (C8) complex III: cytochrome bc1 (ubiquinone reductase) Qx (unknown) site, (D1) methionine biosynthesis (proposed), (D2 - D5) protein biosynthesis, (E1) signal transduction (mechanism of action unknown), (E2 - E3) histidine kinases in MAP / osmotic signal transduction, (F2) phospholipid biosynthesis, methyltransferase, (F3) lipid peroxidation (proposed), (F4) cell membrane permeability, fatty acids (proposed), (F6) microbial perturbation of the pathogen cell membrane, (F7) cell membrane perturbation (proposed), (G1) C14 - demethylase of sterol biosynthesis, (G2) Δ14 - reductase and Δ8→Δ7 - isomerase in sterol biosynthesis, (G3) 3 - keto reductase, C4 - demethylation, (G4) squalene epoxidase of sterol biosynthesis, (H3) trehalase and inositol biosynthesis, (H4) chitin synthase, (H5) cellulose synthase, (I1) reductase of melanin biosynthesis, and (I2) dehydratase of melanin biosynthesis.

[0296] Particularly noteworthy is that in addition to the compound of formula 1 of component (a), as component (b), class (b1) methyl benzimidazolecarbamate (MBC) fungicide; (b2) dicarboximide fungicide; (b3) demethylation inhibitor (DMI) fungicide; (b4) phenylamide fungicide; (b5) amine / morpholine fungicide; (b6) phospholipid biosynthesis inhibitor fungicide; (b7) succinate dehydrogenase inhibitor fungicide; (b8) hydroxy(2-amino-)pyrimidine fungicide; (b9) anilinopyrimidine fungicide; (b10) N-phenylcarbamate fungicide; (b11) quinone outside inhibitor (QoI) fungicide; (b12) phenylpyrrole fungicide; (b13) azanaphthalene fungicide; (b14) lipid peroxidation inhibitor fungicide; (b15) melanin biosynthesis inhibitor - reductase (MBI-R) fungicide; (b16) melanin biosynthesis inhibitor - dehydratase (MBI-D) fungicide; (b17) sterol biosynthesis inhibitor (SBI): class III fungicide; (b18) squalene-epoxidase inhibitor fungicide; (b19) polyoxin fungicide; (b20) phenylurea fungicide; (b21) quinone inside inhibitor (QiI) fungicide; (b22) benzamide and thiazole carboxamide fungicide; (b23) enopyranuronic acid antibiotic fungicide; (b24) hexopyranosyl antibiotic fungicide; (b25) glucopyranosyl antibiotic: protein synthesis fungicide; (b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicide; (b27) cyanoacetamide oxime fungicide; (b28) carbamate fungicide; (b29) oxidative phosphorylation uncoupler fungicide; (b30) organotin fungicide; (b31) carboxylic acid fungicide; (b32) heteroaromatic fungicide; (b33) phosphonate fungicide; (b34) phthalic amide fungicide; (b35) benzotriazine fungicide; (b36) benzene-sulfonamide fungicide; (b37) pyridazinone fungicide; (b38) thiophene-car ruboxamide fungicide; (b39) complex I NADH oxidoreductase inhibitor fungicide; (b40) carboxylic acid amide (CAA) fungicide; (b41) tetracycline antibiotic fungicide; (b42) thiocarbamate fungicide; (b43) benzamide fungicide; (b44) microbial fungicide; (b45) Q xI. Fungicides; (b46) Plant extract fungicides; (b47) Host plant defense induction fungicides; (b48) Multi-site contact active fungicides; (b49) Fungicides other than the fungicides of classes (b1) to (b48); and at least one fungicidal compound selected from the group consisting of salts of compounds of classes (b1) to (b48).

[0297] Further explanations of these classes of fungicidal compounds are provided below.

[0298] (b1) "Methyl benzimidazole carbamate (MBC) fungicides" (FRAC code 1) inhibit mitosis by binding to β-tubulin during microtubule polymerization. Inhibition of microtubule polymerization can disrupt cell division, intracellular transport, and cell structure. Examples of methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides. Examples of benzimidazoles include benomyl, carbendazim, fuberidazole, and thiabendazole. Examples of thiophanates include thiophanate and thiophanate-methyl.

[0299] (b2) "Dicarboximide fungicides" (FRAC code 2) inhibit MAP / histidine kinase in osmotic signal transduction. Examples include chlozolinate, iprodione, procymidone, and vinclozolin.

[0300] (b3) "Demethylation inhibitor (DMI) fungicides" (FRAC code 3) (sterol biosynthesis inhibitors (SBI): class I) inhibit the C14-demethylase enzyme that plays a role in sterol production. Sterols such as ergosterol are necessary for membrane structure and function and are essential for the development of a functional cell wall. Therefore, exposure to these fungicides can cause abnormal growth and even the death of sensitive fungi. DMI fungicides are divided into several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines, pyridines, and triazolylthiones. Triazoles include azaconazole, bitertanol, bromoconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxyconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, mefentrifluconazole, metconazole, myclobutanil, penconazole, propiconazole, quinconazole,simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, uniconazole, uniconazole-P, α-(1-chlorocyclopropyl)-α-[2-(2,2-dichlorocyclopropyl)ethyl]-1H-1,2,4-triazole-1-ethanol, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1H-1,2,4-triazole, rel-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, and rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole.Examples of imidazoles include econazole, imazalil, oxpoconazole, prochloraz, pefurazoate, and triflumizole. Examples of pyrimidines include fenarimol, nuarimol, and triarimol. Examples of piperazines include triho. Examples of pyridines include buthiobate, pyrifenox, pyrisoxazole (3-[(3R)-5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine, a mixture of 3R,5R- and 3R,5S-isomers), and (αS)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]-3-pyridinemethanol. Examples of triazolinethiones include prothioconazole and 2-[2-(1-chlorocyclopropyl)-4-(2,2-dichlorocyclopropyl)-2-hydroxybutyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione. 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, pp. 205-258.

[0301] (b4) "Phenylamide fungicides" (FRAC code 4) are specific inhibitors of RNA polymerase in oomycete fungi. Susceptible fungi exposed to these fungicides show a reduced ability to incorporate uridine into rRNA. Growth and development in susceptible fungi are prevented by exposure to this class of fungicides. Examples of phenylamide fungicides include acylalanines, oxazolidinones, and butyrolactone fungicides. Examples of acylalanines include benalaxyl, benalaxyl-M (also known as kiralaxyl), furalaxyl, metalaxyl, and metalaxyl-M (also known as mefenoxam). An example of an oxazolidinone is oxadixyl. An example of a butyrolactone is ofurace.

[0302] (b5) "Amine / morpholine fungicides" (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 necessary for membrane structure and function and are essential for the development of a functional cell wall. Therefore, exposure to these fungicides can result in abnormal growth and even the death of susceptible fungi. Examples of amine / morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholines, piperidines, and spiroketal-amine fungicides. Examples of morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph, and trimorphamide. Examples of piperidines include fenpropidin and piperalin. An example of a spiroketal-amine is spiroxamine.

[0303] (b6) "Phospholipid biosynthesis inhibitor fungicides" (FRAC code 6) inhibit fungal growth by affecting phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phosphorothiolate and dithiolane fungicides. Examples of phosphorothiolates include edifenphos, iprobenphos, and pyrazophos. An example of a dithiolane is isoprothiolane.

[0304] (b7) "Succinate dehydrogenase inhibitor (SDHI) fungicides" (FRAC code 7) inhibit complex II fungal respiration by disrupting a key enzyme in the Krebs cycle (TCA cycle) called succinate dehydrogenase. Inhibition of respiration prevents the fungus from producing ATP and thus inhibits growth and reproduction. SDHI fungicides include phenylbenzamides, furancarboxamides, oxathiin carboxamides, thiazole carboxamides, pyrazole-4-carboxamides, pyridine carboxamides, phenyloxoethyl Examples include thiophenamides and pyridinylethylbenzamides. Examples of benzamides include benodanil, flutolanil, and mepronil. An example of a furancarboxamide is fenfuram. Examples of oxathiinecarboxamides include carboxin and oxycarboxin. An example of a thiazolecarboxamide is tifluzamide.Examples of pyrazole-4-carboxamides include benzovindiflupyr (N-[9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide), bixafen, fluindapyr, fluxapyroxad (3-(difluoromethyl)-1-methyl-N-(3’,4’,5’-trifluoro[1,1’-biphenyl]-2-yl)-1H-pyrazole-4-carboxamide), flutolanil, isoflucypram, isopyrazam (3-(difluoromethyl)-1-methyl-N-[1,2,3,4-tetrahydro-9-(1-methylethyl)-1,4-methanonaphthalen-5-yl]-1H-pyrazole-4-carboxamide), penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide), penthiopyrad, pidiflumetofen, sedaxane (N-[2-[1,1’-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide), N-[2-(1S,2R)-[1,1’-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, 3-(difluoromethyl)-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-1-methyl-1H-pyrazole-4-carboxamide, N-[2-(2,4-dichlorophenyl)2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide and N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-N-[[2-(1-methylethyl)phenyl]methyl]-1H-pyrazole-4-carboxamide. An example of pyridinecarboxamides is boscalid. An example of phenyloxoethylthiopheneamides is isophenamid (N-[1,1-dimethyl-2-[2-methyl-4-(1-methylethoxy)phenyl]-2-oxoethyl]-3-methyl-2-thiophenecarboxamide).Examples of pyridinylethylbenzamides include fluopyram.

[0305] (b8) "Hydroxy-(2-amino-)pyrimidine fungicides" (FRAC code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol, and ethirimol.

[0306] (b9) "Anilide pyrimidine fungicides" (FRAC code 9) are proposed to inhibit the biosynthesis of the amino acid methionine and disrupt the secretion of hydrolases that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim, and pyrimethanil.

[0307] (b10) "N-phenylcarbamic acid fungicides" (FRAC code 10) bind to β-tubulin and inhibit mitosis by disrupting microtubule polymerization. Inhibition of microtubule polymerization can disrupt cell division, intracellular transport, and cell structure. An example is diethofencarb.

[0308] (b11) "Quinone outside inhibitor (QoI) fungicides" (FRAC code 11) inhibit complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the "quinone outside" (Q o ) site of the cytochrome bc1 complex located in the inner mitochondrial membrane of fungi. Inhibition of mitochondrial respiration interferes with normal fungal growth and development. Examples of quinone outside inhibitor fungicides include Methoxyacrylates, methoxycarbamates, oxyiminoacetates, oxyiminoacetamides, and dihydrodioxazine fungicides (collectively also known as strobilurin fungicides), and oxazolidinediones, imidazolinones, and benzylcarbamate fungicides. Examples of methoxyacrylates include azoxystrobin, coumoxystrobin ((αE)-2-[[(3-butyl-4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]methyl]-α-(methoxymethylene)benzeneacetic acid methyl ester), enoxastrobin ((αE)-2-[[[(E)-[(2E)-3-(4-chlorophenyl)-1-methyl-2-propen-1-ylidene]amino]oxy]methyl]-α-(methoxymethylene)benzeneacetic acid methyl ester) (also known as enestroburin), flufenoxystrobin ((αE)-2-[[2-chloro-4-(trifluoromethyl)phenoxy]methyl]-α-(methoxymethylene)benzeneacetic acid methyl ester), picoxystrobin, and pyraoxystrobin ((αE)-2-[[[3-(4-chlorophenyl)-1-methyl-1H-pyrazol-5-yl]oxy]methyl]-α-(methoxymethylene)benzeneacetic acid methyl ester). Examples of methoxycarbamates include pyraclostrobin, pyrametostrobin (N-[2-[[(1,4-dimethyl-3-phenyl-1H-pyrazol-5-yl)oxy]methyl]phenyl]-N-methoxycarbamic acid methyl ester), and triclopyricarb (N-methoxy-N-[2-[[(3,5,6-trichloro-2-pyridinyl)oxy]methyl]phenyl]carbamic acid methyl ester). Examples of oxyiminoacetates include kresoxim-methyl and trifloxystrobin.Examples of the oxyiminoacetamides include dimoxystrobin, fenaminstrobin ((αE)-2-[[[(E)-[(2E)-3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-ylidene]amino]oxy]methyl]-α-(methoxyimino)-N-methylbenzeneacetamide), metominostrobin, orysastrobin, and α-[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]ethoxy]imino]methyl]benzeneacetamide. Examples of the dihydrodioxazines include fluoxastrobin. Examples of the oxazolidinediones include famoxadone. Examples of the imidazolinones include fenamidone. Examples of the benzylcarbamates include pyribencarb. Class (b11) also includes mandestrobin (2-[(2,5-dimethylphenoxy)methyl]-α-methoxy-N-benzeneacetamide).

[0309] (b12) "Phenylpyrrole fungicides" (FRAC code 12) inhibit MAP / histidine kinases related to osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.

[0310] (b13) "Azanaphthalene fungicides" (FRAC code 13) are proposed to inhibit signal transduction by an as yet unknown mechanism. They have been shown to interfere with germination and / or appressorium formation in fungi causing powdery mildew. Examples of azanaphthalene fungicides include aryloxyquinolines and quinazolinones. Examples of aryloxyquinolines include quinoxyfen. Examples of quinazolinones include proquinazid.

[0311] (b14) "Lipid peroxidation inhibitor fungicides" (FRAC code 14) are proposed to inhibit lipid peroxidation that affects membrane synthesis in fungi. Members of this class, such as etridiazole, can also affect other biological processes such as respiration and melanin biosynthesis. Lipid peroxidation fungicides include aromatic hydrocarbons and 1,2,4-thiadiazole fungicides. Aromatic hydrocarbon fungicides include biphenyl, chloroneb, dichloran, quintozene, tecnazene, and tolclofos-methyl. Etridiazole is an example of 1,2,4-thiadiazoles.

[0312] (b15) "Melanin biosynthesis inhibitor - reductase (MBI-R) fungicides" (FRAC code 16.1) inhibit the naphthal reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor - reductase fungicides include isobenzofuranone, pyrroloquinolinone, and triazolobenzothiazole fungicides. Fusaride is an example of isobenzofuranones. Pyroquilon is an example of pyrroloquinolinones. Tricyclazole is an example of triazolobenzothiazoles.

[0313] (b16) "Melanin biosynthesis inhibitor - dehydratase (MBI-D) fungicides" (FRAC code 16.2) inhibit citral dehydrogenase in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitor - dehydratase fungicides include cyclopropanecarboxamide, carboxamide, and propionamide fungicides. Carpropamid is an example of cyclopropanecarboxamides. Diclocymet is an example of carboxamides. Phenoxanil is an example of propionamides.

[0314] (b17) “Sterol biosynthesis inhibitor (SBI): Class III fungicides (FRAC code 17) inhibit 3-ketoreductase during C4-demethylation in sterol production. SBI: Class III inhibitors include hydroxyanilide fungicides and amino-pyrazolinone fungicides. Hydroxyanilides include fenhexamid. Amino-pyrazolinones include fenpyrazamine (S-2-propen-1-yl 5-amino-2,3-dihydro-2-(1-methylethyl)-4-(2-methylphenyl)-3-oxo-1H-pyrazole-1-carbothioate).

[0315] (b18) “Squalene-epoxidase inhibitor fungicides” (FRAC code 18) (SBI: Class IV) inhibit squalene-epoxidase in the sterol biosynthesis pathway. Sterols such as ergosterol are necessary for membrane structure and function and are essential for the development of a functional cell wall. Therefore, exposure to these fungicides can cause abnormal growth and even death of susceptible fungi. Squalene-epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides. Thiocarbamates include pyributicarb. Allylamines include naftifine and terbinafine.

[0316] (b19) “Polyoxin fungicides” (FRAC code 19) inhibit chitin synthase. An example is polyoxin.

[0317] (b20) “Phenylurea fungicides” (FRAC code 20) are proposed to affect cell division. An example is pencycuron.

[0318] (b21) “Quinone inside inhibitor (QiI) fungicides” (FRAC code 21) inhibit complex III mitochondrial respiration in fungi by affecting ubiquinone reductase. The reduction of ubiquinone is the “quinone inside” (Q of the cytochrome bc1 complex i) It is blocked at the site, which is located in the inner mitochondrial membrane of the fungus. By inhibiting mitochondrial respiration, normal fungal growth and development are hindered. Examples of quinone internal inhibitor fungicides include cyanoimidazole and sulfamoyl triazole fungicides. Examples of cyanoimidazoles include cyazofamid. Examples of sulfamoyl triazoles and include amisulbrom.

[0319] (b22) "Benzamide and thiazole carboxamide fungicides" (FRAC code 22) bind to β-tubulin and inhibit mitosis by disturbing microtubule polymerization. Inhibition of microtubule polymerization can disrupt cell division, intracellular transport, and cell structure. Examples of benzamides include zoxamide. Examples of thiazole carboxamides include ethaboxam.

[0320] (b23) "Enopyranuronate antibiotic fungicides" (FRAC code 23) inhibit fungal growth by affecting protein biosynthesis. An example is blasticidin-S.

[0321] (b24) "Hexopyranosyl antibiotic fungicides" (FRAC code 24) inhibit fungal growth by affecting protein biosynthesis. An example is kasugamycin.

[0322] (b25) "Glucopyranosyl antibiotics: protein synthesis fungicides" (FRAC code 25) inhibit fungal growth by affecting protein biosynthesis. An example is streptomycin.

[0323] (b26) "Glucopyranosyl antibiotics: trehalase and inositol biosynthesis fungicides" (FRAC code 26) inhibit trehalase and inositol biosynthesis. An example is validamycin.

[0324] (b27) Examples of "cyanoacetamide oxime fungicides (FRAC code 27)" include cymoxanil.

[0325] (b28) "Carbamic acid fungicides" (FRAC code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with fatty acid synthesis in the cell membrane and then disrupt nuclear permeability. Propamacarb, iodocarb, and prothiocarb are examples of this class of fungicides.

[0326] (b29) "Oxidative phosphorylation uncoupling fungicides" (FRAC code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. By inhibiting respiration, normal fungal growth and development are disrupted. This class includes 2,6-dinitroanilines such as fluazinam, and crotonic acid dinitrophenyls such as dinocap, meptyldinocap, and binapacryl.

[0327] (b30) "Organotin fungicides" (FRAC code 30) inhibit adenosine triphosphate (ATP) synthase in the oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride, and fentin hydroxide.

[0328] (b31) "Carboxylic acid fungicides" (FRAC code 31) inhibit fungal growth by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). An example is oxolinic acid.

[0329] (b32) "Heteroaromatic fungicides" (Fungicide Resistance Action Committee (FRAC) code 32 ) is proposed to affect DNA / ribonucleic acid (RNA) synthesis. Examples of heteroaromatic bactericides include isoxazoles and isothiazolones. An example of isoxazoles is hymexazole, and an example of isothiazolones is octhilinone.

[0330] (b33) Examples of "phosphonate bactericides" (FRAC code 33) include phosphorous acid and its various salts, and an example of these is fosetyl-aluminum.

[0331] (b34) An example of "phthalic amide bactericides" (FRAC code 34) is teclofthalam.

[0332] (b35) An example of "benzotriazine bactericides" (FRAC code 35) is triazoxide.

[0333] (b36) An example of "benzene-sulfonamide bactericides" (FRAC code 36) is flusulfamide.

[0334] (b37) An example of "pyridazinone bactericides" (FRAC code 37) is dichlomezine.

[0335] (b38) "Thiophene-carboxamide bactericides" (FRAC code 38) are proposed to affect ATP production. An example is silthiofam.

[0336] (b39) "Complex I NADH oxidoreductase inhibitor bactericides" (FRAC code 39) inhibit electron transfer in mitochondria, and examples of these include pyrimidine amines such as diflumetorim, and pyrazole-5-carboxamides such as tolfenpyrad.

[0337] (b40) The "carboxylic acid amide (CAA) fungicide" (FRAC code 40) inhibits cellulose synthase, which interferes with the growth of the target fungus and leads to death. Examples of carboxylic acid amide fungicides include oxycarboxin amide, valinamide, and other carbamates, and mandelic acid amide fungicides. Examples of oxycarboxin amides include dimethomorph, flumorph, and pyrimorph (3-(2-chloro-4-pyridinyl)-3-[4-(1,1-dimethylethyl)phenyl]-1-(4-morpholinyl)-2-propen-1-one). Examples of valinamide and other carbamates include benzovulcarb, benzovulcarb-isopropyl, iprovalicarb, tolprocarb (2,2,2-trifluoroethyl N-[(1S)-2-methyl-1-[[(4-methylbenzoyl)amino]methyl]propyl]carbamate), and valifenalate (methyl N-[(1-methylethoxy)carbonyl]-L-valyl-3-(4-chlorophenyl)-β-alaninate) (also known as valiphenal). Examples of 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.

[0338] (b41) The "tetracycline antibiotic fungicide" (FRAC code 41) inhibits the growth of fungi by affecting protein synthesis. An example is oxytetracycline. It can be mentioned.

[0339] (b42) An example of the "thiocarbamic acid fungicide" (FRAC code 42) is methasulphocarb.

[0340] (b43) The "benzamide fungicide" (FRAC code 43) inhibits fungal growth by the delocalization of spectrin-like proteins. Examples include pyridinylmethylbenzamide fungicides such as fluopicolide (now FRAC code 7, pyridinylethylbenzamides).

[0341] (b44) The "microbial fungicide" (FRAC code '44) disrupts the fungal pathogen cell membrane. Microbial fungicides include Bacillus species such as Bacillus amyloliquefaciens strains QST 713, FZB24, MB1600, D747 and the bactericidal lipopeptides they produce.

[0342] (b45) "Q x I fungicide" (FRAC code 45) inhibits complex III mitochondrial respiration in fungi by affecting ubiquinone reductase at an unknown (Q x ) site of the cytochrome bc1 complex. Inhibition of mitochondrial respiration interferes with normal fungal growth and development. Q x I fungicides include triazolopyrimidylamines such as ametoctradin (5-ethyl-6-octyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine).

[0343] (b46) "Plant extract fungicides" are proposed to act by cell membrane disruption. Plant extract fungicides include terpene hydrocarbons and terpene alcohols such as extracts from Melaleuca alternifolia (tea tree).

[0344] (b47) The "host plant defense-inducing fungicide" (FRAC code P) induces the defense mechanism of the host plant. Examples of host plant defense-inducing fungicides include benzothiadiazoles, benzisothiazole, and thiadiazole-carboxamide fungicides. An example of benzothiadiazoles is acibenzolar-S-methyl. An example of benzisothiazoles is probenazole. Examples of thiadiazole-carboxamides include thiadinyl and isothianyl.

[0345] (b48) The "multi-site contact-active fungicide" inhibits fungal growth through multiple sites of action and has a contact / preventive action. Fungicides in this class include: (b48.1) "copper fungicides" (FRAC code M1), (b48.2) "sulfur fungicides" (FRAC code M2), (b48.3) "dithiocarbamate fungicides" (FRAC code M3), (b48.4) "phthalimide fungicides" (FRAC code M4), (b48.5) "chloronitrile fungicides" (FRAC code M5), (b48.6) "sulfamide fungicides" (FRAC code M6), (b48.7) multi-site contact "guanidine fungicides" (FRAC code M7), (b48.8) "triazine fungicides" (FRAC code M8), (b48.9) "quinone fungicides" (FRAC code M9), (b48.10) "quinoxaline fungicides" (FRAC code M10), and (b48.11) "maleimide fungicides" (FRAC code M11). "Copper fungicides" are typically inorganic compounds containing copper in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate, and copper hydroxide, and compositions such as Bordeaux mixture (tribasic copper sulfate) are included. "Sulfur fungicides" are inorganic chemical substances containing rings or chains of sulfur atoms; an example is elemental sulfur. "Dithiocarbamate fungicides" contain a dithiocarbamate molecular moiety; examples include mancozeb, methylam, propineb, ferbam, maneb, thiram, zineb, and dithiram. "Phthal "Imide fungicides" contain a phthalimide molecular moiety; examples include folpet, captan, and captafol. "Chloronitrile fungicides" contain an aromatic ring substituted with chloro and cyano; an example is chlorothalonil. Examples of "sulfamide fungicides" include dichlofluanid and tolyfluanid. Examples of multi-site contact "guanidine fungicides" include guazatine, iminoctadine albesilate, and iminoctadine triacetate. An example of a "triazine fungicide" is anilazine. An example of a "quinone fungicide" is dithianon. An example of a "quinoxaline fungicide" is quinomethionate (also known as chinomethionate). An example of a "maleimide fungicide" is fluoroimide.

[0346] (b49) "Fungicides other than those of classes (b1) to (b48)" include specific fungicides whose mode of action is unknown. These include: (b49.1), "phenyl-acetamide fungicides" (FRAC code U6), (b49.2) "aryl-phenyl-ketone fungicides" (FRAC code U8), (b49.3) "guanidine fungicides" (FRAC code U12), (b49.4) "thiazolidine fungicides" (FRAC code U13), (b49.5) "pyrimidine-hydrazone fungicides" (FRAC code U14), and (b49.6) compounds that bind to oxysterol-binding proteins described in PCT International Publication WO2013 / 009971. Examples of phenyl-acetamides include difenoconazole and N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]-methylene]benzeneacetamide. Examples of aryl-phenyl ketones include benzophenones such as metrafenone, and benzoylpyridines such as pyriofenone ((5-chloro-2-methoxy-4-methyl-3-pyridinyl)(2,3,4-trimethoxy-6-methylphenyl)methanone). Examples of guanidines include dodine. Examples of thiazolidines include flutianil ((2Z)-2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile). Examples of pyrimidinone hydrazones include ferimzone. Class (b49.6) includes oxathiapiprolin (1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone) and its R-enantiomer, 1-[4-[4-[5R-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone (registration number 1003319-79-6).(b49) The class includes bethoxazin, flometoquine carbonate (2-ethyl-3,7-dimethyl-6-[4-(trifluoromethoxy)phenoxy]-4-quinolinyl methyl), fluoroimide, neo-asozin (iron methanearsonate), picarbutrazox (N-[6-[[[[((Z)1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamic acid 1,1-dimethylethyl), pyrrolnitrin, quinomethionate, tebufloquin (6-(1,1-dimethylethyl)-8-fluoro-2,3-dimethyl-4-quinolinyl acetate), tolnifanide (N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide), 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one, 3-butyn-1-yl, N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate, (N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide), N’-[4-[4-chloro-3-(trifluoromethyl). )Phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidoamide, N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, 2,6-dimethyl-1H,5H-[1,4]dithieno[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone, 5-fluoro-2-[(4-methylphenyl)methoxy]-4-pyrimidinamine, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine, and N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamic acid 4-fluorophenyl, N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamic acid pentyl, N-[4-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-thiazolyl]carbamic acid pentyl, and N-[6-[[[[(Z)-(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamic acid pentyl are also included. Class (b46) further includes mitotic inhibitors and cell division inhibitor fungicides in addition to the above specific classes (e.g., (b1), (b10), and (b22)).

[0347] For further "fungicides other than fungicides of classes (1) to (46)" whose mechanism of action is unknown or which have not yet been classified, bactericidal compounds selected from the following components (b49.7) to (b49.12) are mentioned.

[0348] Component (b49.7) relates to a compound of formula 49.7 [Chemical formula] [wherein R b1 is [Chemical formula] as shown]

[0349] Examples of the compound of formula b49.7 include (b49.7a) 2-[1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylic acid (2-chloro-6-fluorophenyl)methyl (Registration Number 1299409-40-7) and (b49.7b) 2-[1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylic acid (1R)-1,2,3,4-tetrahydro-1-naphthalenyl (Registration Number 1299409-42-9). The method for producing the compound of formula b46.2 is described in PCT International Publication WO2009 / 132785 and WO2011 / 0 51243.

[0350] Component (b49.8) relates to a compound of formula b49.8

Chemical formula

[0351] Examples of the compound of formula b49.8 include (b49.8a) 1-[4-[4-[5-[(2,6-difluorophenoxy)methyl]-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone. The method for producing the compound of formula b49.8 is described in PCT International Patent Application No. PCT / US11 / 64324.

[0352] Component (b4799) is of formula b49.9

Chemical formula

[0353] Examples of the compound of formula b49.9 include (b49.9a) 2-methylpropanoic acid [[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 (registration number 517875-34-2), (b49.9b) 2-methylpropanoic acid (3S,6S,7R,8R)-3-[[[3-(acetyloxy)-4-methoxy-2-pyridinyl]car (Bonil]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl (registration number 234112-93-7), (b49.9c) (3S,6S,7R,8R)-3-[[[3-[(acetyloxy)methoxy]-4-methoxy-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate (registration number 517875-31-9), (b49.9d) (3S,6S,7R,8R)-3-[[[4-methoxy-3-[[(2-methylpropoxy)carbonyl]oxy]-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate (registration number 328256-72-0), and (b49.9e) N-[[3-(1,3-benzodioxol-5-ylmethoxy)-4-methoxy-2-pyridinyl]carbonyl]-O-[2,5-dideoxy-3-O-(2-methyl-1-oxopropyl)-2-(phenylmethyl)-L-arabinonoyl]-L-serine, (1→4’)-lactone (registration number 1285706-70-8). The method for producing the compound of formula b49.9 is described in PCT International Publication WO99 / 40081, WO2001 / 014339, WO2003 / 035617 and WO2011044213.

[0354] Component (b49.10) is a compound of formula 49.10 [In the formula, R is H or F, and R b6 is -CF2CHFCF3 or -CF2CF2H]. Examples of the compound of formula b49.10 are (b49.10a) b7 is -CF2CHFCF3 or -CF2CF2H], and (b49.10a) 3-(Difluoromethyl)-N-[4-fluoro-2-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-1-methyl-1H-pyrazole-4-carboxamide (Registration No. 1172611-40-3) and (b49.10b) 3-(difluoromethyl)-1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-1H-pyrazole-4-carboxamide (Registration No. 923953-98-4). The compounds of formula 49.10 can be prepared by the methods described in PCT International Publication WO2007 / 017450.

[0355] Component b49.11 is a compound of formula b49.11 [Chemical formula] [wherein, R b8 is halogen, C1-C4 alkoxy or C2-C4 alkynyl; R b9 is H, halogen or C1-C4 alkyl; R b10 is C1-C 12 alkyl, C1-C 12 haloalkyl, C1-C 12 alko xy, C2-C 12 alkoxyalkyl, C2-C 12 alkenyl, C2-C 12 alkynyl, C4-C 12 alkoxyalkenyl, C4-C 12 alkoxyalkynyl, C1-C 12 alkylthio or C2-C 12 alkylthioalkyl; R b11 is methyl or -Y b13 -R b12 ; R b12 is C1-C2 alkyl; and Y b13 is CH2, O or S] relates to the compounds of.

[0356] Examples of compounds of formula b49.11 include (b49.11a) 2-[(3-bromo-6-quinolinyl)oxy]-N-(1,1-dimethyl-2-butyn-1-yl)-2-(methylthio)acetamide, (b49.11b) 2[(3-ethynyl-6-quinolinyl)oxy]-N-[1-(hydroxymethyl)-1-methyl-2-propyn-1-yl]-2-(methylthio)acetamide, (b49.11c) N-(1,1-dimethyl-2-butyn-1-yl)-2-[(3-ethynyl-6-quinolinyl)oxy]-2-(methylthio)acetamide, (b49.11d) 2-[(3-bromo-8-methyl-6-quinolinyl)oxy]-N-(1,1-dimethyl-2-propyn-1-yl)-2-(methylthio)acetamide and (b49.11e) 2-[(3-bromo-6-quinolinyl)oxy]-N-(1,1-dimethylethyl)butanamide. Compounds of formula b49.11, their use as fungicides and methods of manufacture are generally known; see, for example, PCT International Publication Nos. WO2004 / 047538, WO2004 / 108663, WO2006 / 058699, WO2006 / 058700, WO2008 / 110355, WO2009 / 030469, WO2009 / 049716 and WO2009 / 087098.

[0357] Component 49.12 relates to N’-[4-[[3-[(4-chlorophenyl)methyl]-1,2,4-thiadiazol-5-yl]oxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, which is thought to inhibit C24-methyltransferase involved in the biosynthesis of sterols.

[0358] Accordingly, of note is a mixture (i.e., composition) comprising a compound of formula 1 and at least one bactericidal compound selected from the group consisting of classes (1) to (49) described above. Also of note is a composition comprising the above mixture (in a bactericidally effective amount) and further comprising at least one additional component selected from the group consisting of a surfactant, a solid diluent, and a liquid diluent. Of particular note is a mixture (i.e., composition) comprising a compound of formula 1 and at least one bactericidal compound selected from the group of specific compounds listed above in connection with classes (1) to (49). Also of particular note is a composition comprising the above mixture (in a bactericidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of a surfactant, a solid diluent, and a liquid diluent.

[0359] Examples of component (b) fungicides include acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl (including benalaxyl-M), benodanil, benomyl, benthiavalicarb (including benthiavalicarb-isopropyl), benzovindiflupyr, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromoconazole, buthiopyram, buthiobate, captan, captan, carbendazim, carboxin, carpropamid, chloroneb, chlorothalonil, chlorozolinate, clotrimazole, copper hydroxide, copper oxychloride, copper sulfate, coumoxystrobin, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, dichlomezine, diclomezine, dichloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin ン, diniconazole (including diniconazole-M), dinocap, dichlofluanid, dithianons, dodemorph, dodine, econazole, edifenphos, enoxastrobin (also known as enestroburin), epoxyconazole, etaconazole, ethaboxam, etirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenaminstrobin, fenbuconazole, fenfluram, fenhexamid, phenoxanil, fenpiclonil, fenpropimorph, fenpropidin, fenpyrazamine, fenbutatin acetate, fenbutatin chloride, fenbutatin hydroxide, ferbam, ferimzone, fluoxastrobin, florylpicoxamid, fluazinam, fluazinil, fluopicoxystrobin, fluindapyr, flumorph, fluopicolide, fluopyram, flouroimide, fluoxastrobin, flutriafol, flupyradifurone, fluthianil, flutolanil, flutriafol, fluxapyroxad, folpet, fthalide, fuberidazole, fluralaxyl, flupropacil, guazatine, hexaconazole, hymexazol, imazalil, imibenconazole, iminoctadine albesilate, iminoctadine triacetate, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoconazole, isofetamid, isoprothiolane, isoflucypram, isopyrazam, isothianil, kasugamycin, kresoxim-methyl, mancozeb, mandepropamid, mandestrobin, maneb, mepanipyrim, mepronil, meptyldinocap, metalaxyl (including metalaxyl-M / mefenoxam), mefenoxam, metconazole, methiocarb, methiram, metominostrobin, metrafenone, miconazole, microbutanil, naftifine, neoazoxystrobin, nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxathiapiprolin, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, pefurazoate, penconazole, pencycuron, penflufen, penthiopyrad, phosphorous acid (its salts, e.g.,hosethyl-aluminum), picarbutrazox, picoxystrobin, piperine, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, proquinazid, prothiocarb, prothioconazole, pyraclostrobin, pyra-metostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyrifluophenone, pyrisooxazole, pyroquilon, pyrrolnitrin, kinkonazole, quinomethionate, quinoxyfen, quintozene, sedaxane, silthiopham, simconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, tecnazene, techlofthalam, terbinafine, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, thiazinyl, tolclofos-methyl, tolfenpyrad, tolprocarb, triflumizole, triazimefon, triadimenol, triarimol, triticonazole, triazoxide, tribasic copper sulfate, tricyclazole, triclopyricarb, tridemorph, trifloxystrobin, triflumizole, triforine, trimorphamide, uniconazole, uniconazole-P, validamycin, valifenalate (also known as valifenal), vinclozolin, dinneb, ziram, zoxamide, (3S,6S,7R,8R)-3-[[[3-[(acetyloxy)methoxy]-4-methoxy-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate, (3S,6S,7R,8R)-3-[[[3-(acetyloxy)-4-methoxy-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate, N-[[3-(1,3-benzodioxol-5-ylmethoxy)-4-methoxy-2-pyridinyl]carbonyl]-O-[2,5-dideoxy-3-O-(2-methyl-1-oxopropyl)-2-(phenylmethyl)-L-arabinonoil]-L-serine, (1→4’)-lactone,N-[2-(1S,2R)-[1,1'-Bicyclopropyl]-2-ylphenyl]-3-、 (Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, 2-[(3-bromo-6-quinolinyl)oxy]-N-(1,1-dimethyl-2-butyn-1-yl)-2-(methylthio)acetamide, 2-[(3-bromo-6-quinolinyl)oxy]-N-(1,1-dimethylethyl)butanamide, 2-[(3-bromo-8-methyl-6-quinolinyl)oxy]-N-(1,1-dimethyl-2-propyn-1-yl)-2-(methylthio)acetamide, 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one, N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamic acid 3-butyn-1-yl, α-(1-chlorocyclopropyl)-α-[2-(2,2-dichlorocyclopropyl)ethyl]-1H-1,2,4-triazole-1-ethanol, 2-[2-(1-chlorocyclopropyl)-4-(2,2-dichlorocyclopropyl)-2-hydroxybutyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, (αS)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]-3-pyridinemethanol, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1H-1,2,4-triazole, rel-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine, 2-[1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylic acid (2-chloro-6-fluorophenyl)methyl, N’-[4-[[3-[(4-chlorophenyl)methyl]-1,2,[[4-Thiazol-5-yl]oxy]-2,5-dimethylphenyl]-N-ethyl-N-methyl-methanimidamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide, N’-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-N-[[2-(1-methylethyl)phenyl]methyl]-1H-pyrazole-4-carboxamide, N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, N-[2-(2,4-dichlorophenyl)-2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, N-(3’,4’-difluoro[1,1’-biphenyl]-2-yl)-3-(trifluoromethyl)-2-pyrazinecarboxamide, 3-(difluoromethyl)-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-1-methyl-1H-pyrazole-4-carboxamide, 3-(difluoromethyl)-N-[4-fluoro-2-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-1-methyl-1H-pyrazole-4-carboxamide, 5,8-difluoro-N-[2-[3-methoxy-4-[[4-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]ethyl]-4-quinazolinamine, 3-(difluoromethyl)-1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-1H-pyrazole-4-carboxamide, 1-[4-[4-[5R-[(2,6-difluorophenoxy)methyl]-4,5-Dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, N-(1,1-dimethyl-2-butyn-1-yl)- yl)-2-[(3-ethynyl-6-quinolinyl)oxy]-2-(methylthio)acetamide, 2,6-dimethyl-1H,5H-[1,4]dithieno[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone, 2-[(3-ethynyl-6-quinolinyl)oxy]-N-[1-(hydroxymethyl)-1-methyl-2-propyn-1-yl]-2-(methylthio)acetamide, N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamic acid 4-fluorophenyl, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine, 5-fluoro-2-[(4-methylphenyl)methoxy]-4-pyrimidinamine, (3S,6S,7R,8R)-3-[[[4-Methoxy-3-[[(2-methylpropoxy)carbonyl]oxy]-2-pyridinyl]carbonyl]amino]-6-methyl-4,9-dioxo-8-(phenylmethyl)-1,5-dioxonan-7-yl 2-methylpropanoate, α-(methoxyimino)-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]ethoxy]imino]methyl]benzeneacetamide, 2-methylpropanoic acid [[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, N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamic acid pentyl, N-[4-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-thiazolyl]carbamic acid pentyl, and N-[6-[[[[(Z)-(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamic acid pentyl and 2-[1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylic acid (1R)-1,2,3,4-tetrahydro-1-naphthalenyl are mentioned. Therefore, of note is a bactericidal composition comprising, as component (a), a compound of formula 1 (or its N-oxide or salt) and, as component (b), at least one bactericide selected from the previous list.

[0360] Particularly noteworthy are the compound of formula 1 (or its N-oxide or salt) (i.e., component (a) in the composition), and azoxystrobin, benzovindiflupyr, bixafen, captan, carpropamid, chlorothalonil, copper hydroxide, copper oxychloride, copper sulfate, cymoxanil, cyproconazole, cyprodinil, diethofencarb, difenoconazole, dimethomorph, epoxyconazole, ethaboxam, fenarimol, fenhexamid, fluazinam, fluoxastrobin, fluopyram, fludioxonil, fluindapyr, fluopicolide, flutianil, lutiarazole, fluxapyroxad, folpet, iprodione, isofetamid, isoflucypram, isopyrazam, kresoxim-methyl, mancozeb, mandestrobin, meptyldinocap, metalaxyl (including metalaxyl-M / mefenoxam), mefentrifluconazole, metconazole, metrafenone, microbutanil, oxathiapiprolin, penflufen, penthiopyrad, phosphorous acid (including its salts, e.g., fosetyl-aluminum), picoxystrobin, propiconazole, proquinazid, prothioconazole, pyraclostrobin, pyrimethanil, sedaxane spiroxamine, sulfur, tebuconazole, thiophanate-methyl, trifloxystrobin, zoxamide, α-(1-chlorocyclopropyl)-α-[2-(2,2-dichlorocyclopropyl)ethyl]-1H-1,2,4-triazole-1-ethanol, 2-[2-(1-chlorocyclopropyl)-4-(2,2-dichlorocyclopropyl)-2-hydroxybutyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, N-[2-(2,4-dichlorophenyl)-2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, 3-(difluoromethyl)-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-1-methyl-1H-pyrazole-4-carboxamide, 1-[4-[4- [5R-(2,6-Difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamic acid 1,1-dimethylethyl, 2,6-dimethyl-1H,5H-[1,4]dithieno[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine, 5-fluoro-2-[(4-methylphenyl)methoxy]-4-pyrimidinamine, (αS)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-4-isoxazolyl]-3-pyridinemethanol, rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1H-1,2,4-triazole, rel-2-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione, and rel-1-[[(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole (i.e., as component (b) in the composition).

[0361] Examples of other biologically active compounds or agents that can be formulated with the compounds of the present invention are: Pesticide compounds or agents against harmful invertebrates, such as abamectin, acephate, acetamiprid, acrinathrin, afidopyropen (cyclopropanecarboxylic acid [(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-[(cyclopropylcarbonyl)oxy]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-6,12-dihydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridinyl)-2H,11H-naphtho[2,1-b]pyrano[3,4-e]pyran-4-yl]methyl]), amidoflumet (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyantraniliprole (3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide), cyclaniliprole (3-bromo-N-[2-bromo-4-chloro-6-[[(1-cyclopropylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide), cycloxaprid ((5S,8R)-1-[(6-chloro-3-pyridinyl)methyl]-2,3,5,6,7,8-hexahydro-9-nitro-5,8-epoxy-1H-imidazo[1,2-a] Azepine), Siflumetofen, Sifluthrin, Beta-Sifluthrin, Cyhalothrin, Lambda-Cyhalothrin, Cypermethrin, Cyromazine, Deltamethrin, Diafenthiuron, Diazinon, Dieldrin, Diflubenzuron, Dimefluthrin, Dimethoate, Dinotefuran, Dioxabenzofos, Emamectin, Endosulfan, Esfenvalerate, Ethiprole, Phenothiocarb, Fenoxycarb, Fenpropathrin, Fenvalerate, Fipronil, Flonicamid, Flubendiamide, Flucitranate, Fluopicolide ((αE)-2-[[2-Chloro-4-(trifluoromethyl)phenoxy]methyl]-α-(methoxymethylene)benzeneacetic acid methyl), Fluensulfone (5-Chloro-2-[(3,4,4-trifluoro-3-buten-1-yl)sulfonyl]thiazole), Flupiprole (1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-[(2-methyl-2-propene, -1-Imino]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile), flupyradifurone (4-[[(6-chloro-3-pyridinyl)methyl](2,2-difluoroethyl)amino]-2(5H)-furanone), tau-fluvalinate, flufenoxuron (UR-50701), flufenoxon, fonophos, halofenozide, heptafluthrin (2,2-dimethyl-3-[(1Z)-3,3,3-trifluoro-1-propen-1-yl]cyclopropanecarboxylic acid [2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl), hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, meperfluthrin ((1R,3S)-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid [2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl), metaflumizone, metaaldehyde, methamidophos, methidathion, mesomil, methoprene, methoxychlor, methoxyphenozide, metofluthrin, milbemycin oxime, momfluorothrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl-3-(2-cyano-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylate), monocrotophos, nicotine, nitenpyram, nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, piflubumide (1,3,5-trimethyl-N-(2-methyl-1-oxopropyl)-N-[3-(2-methylpropyl)-4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]-1H-pyrazole-4-carboxamide), parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, pymetrozine, pyrafluprole, pyrethrin, pyridalyl, pyrifluquinazon, pyriminostrobin ((αE)-2-[[[2-[(2,4-dichlorophenyl)amino]-6-(trifluoromethyl)-4-pyrimidinyl]oxy]methyl]-α-(methoxymethylene)benzeneacetic acid methyl), pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spirotetramat, sulfoxaflor, sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon and triflumuron; and biological agents including entomopathogenic bacteria, for example, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, and encapsulated delta-endotoxins of Bacillus thuringiensis (for example, Cellcap, MPV, MPVII); entomopathogenic fungi, for example, green muscardine fungus; and entomopathogenic viruses including nucleopolyhedroviruses (NPV) such as HzNPV, AfNPV; and granulosis viruses (GV) such as CpGV.,

[0362] The compounds and compositions of the present invention can be applied to plants genetically transformed to express a protein toxic to harmful invertebrates (e.g., Bacillus thuringiensis delta-endotoxin). The effect of the externally applied fungicidal compounds of the present invention can provide an enhanced effect together with the expressed toxin protein.

[0363] General references for these various agricultural protectants (i.e., insecticides, fungicides, nematicides, acaricides, herbicides, and biological agents) include The Pesticide Manual, 13th Edition, C.D.S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. g. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2001.

[0364] For embodiments in which one or more of these various mixing partners are used, the mass ratio of these various mixing partners (in total) to the compound of formula 1 is typically between about 1:3000 and about 3000:1. Of note is a mass ratio between about 1:300 and about 300:1 (e.g., between about 1:30 and about 30:1). One skilled in the art can readily determine the biologically effective amount of the active ingredient necessary for the desired range of biological activity by simple experimentation. It will be apparent that including these additional components can broaden the range of diseases controlled beyond that controlled by the compound of formula 1 alone.

[0365] In certain instances, combinations of the compounds of the invention with other biologically active (especially fungicidal) compounds or agents (i.e., active ingredients) can produce a greater-than-additive (i.e., enhanced) effect. It is always desirable to reduce the amount of active ingredient released into the environment while ensuring effective pest control. Such combinations can be advantageous for reducing crop production costs and the environmental burden if an enhanced effect of the fungicidal active ingredient occurs at an application rate that produces an agriculturally satisfactory level of fungal control.

[0366] Also, in certain instances, combinations of the compounds of the invention with other biologically active compounds or agents can produce a less-than-additive (i.e., phytotoxicity-reducing) effect on organisms beneficial to the agricultural environment. For example, the compounds of the invention can reduce the phytotoxicity of herbicides to crop plants or protect beneficial insect species (e.g., insect predators, pollinators such as bees) from insecticides.

[0367] Fungicides of note for formulation with the compounds of formula 1 to provide useful mixtures in seed treatment include, but are not limited to, amisulbrom, azoxystrobin, boscalid, carbendazim, carboxin, cymoxanil, cyproconazole, difenoconazole, dimethomorph, florylpicoxamid, fluazinam, fluoxastrobin, fluphenoxystrobin, fluquinconazole, fluopicolide, fluxapyroxad, ipconazole, iprodione, metalaxyl, mefenoxam, mefentrifluconazole, metconazole, microbutanil, paclobutrazole, penflufen, picoxystrobin, prothioconazole, pyraclostrobin, sedaxane, silthiopham, tebuconazole, thiabendazole, thiophanate-methyl, thiram, trifloxystrobin and triticonazole.

[0368] Invertebrate pest control compounds or agents that can be formulated with the compounds of Formula 1 to provide useful mixtures in seed treatments include, but are not limited to, abamectin, acetamiprid, acrinathrin, afidopiropen, amitraz, avermectin, azadirachtin, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyclaniliprole, cyflutri beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, flubendiamide, fluensulfone, flufenoxuron, flufiprole, flupyradifuron, fluvalinate, formetanate, fosthiazate, heptafluthrin, hexaflumuron, hydramethylnon, ibuprofen, Midacloprid, indoxacarb, lufenuron, meperfluthrin, metaflumizone, methiocarb, methomyl, methoprene, methoxyfenozide, momfluorothrin, nitenpyram, nithiazine, novaluron, oxamyl, piflubumid, pymetrozine, pyrethrins, pyridaben, pyriminostrobin, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxin, Bacillus thuringiensis virus strains, and Nucleopolyhydrosis virus strains.

[0369] Compositions containing the compounds of formula 1 useful for seed treatment may further contain bacteria and fungi having the ability to provide protection from the deleterious effects of phytopathogenic fungi or bacteria and / or soil-borne animals such as nematodes. Bacteria exhibiting nematicidal properties include, but are not limited to, Bacillus firmus, Bacillus cereus, Bacillius subtiliis, and Pasteuria penetrans. A suitable Bacillus firmus strain is the CNCM I-1582 strain (GB-126), which is marketed as BioNem TM and is commercially available. A suitable Bacillus cereus strain is the NCMM I-1592 strain. Both Bacillus strains are disclosed in US 6,406,690. Other suitable bacteria exhibiting nematicidal activity are Bacillus amyloliquefaciens IN937a and Bacillus subtilis strain gB03. Bacteria exhibiting fungicidal properties include, but are not limited to, Bacillus pumilus strain gB34. Fungal species exhibiting nematicidal properties include, but are not limited to, Myrothecium verrucaria, Paecilomyces lilacinus, and Purpureocillium lilacinum.

[0370] Seed treatment may also include one or more nematicides of natural origin such as harpins, elicitor proteins isolated from certain bacterial plant pathogens such as Erwinia amylovora. One example is the Harpin-N-Tek seed treatment technology available as N-Hibit TM Gold CST.

[0371] Seed treatment can also include one or more species of legume rhizobia, such as the microsymbiotic nitrogen-fixing bacterium Bradyrhizobium japonicum. These inocculants can optionally include one or more lipo-chitooligosaccharides (LCOs), which are nodulation (Nod) factors produced by rhizobia during the initiation of nodule formation on the roots of leguminous plants. For example, the seed treatment technology under the trade name Optimize® incorporates LCO Promoter in combination with the inoculant. Technology TM into it.

[0372] Seed treatment can also include one or more isoflavones that can increase the level of mycorrhizal colonization by mycorrhizal fungi. Mycorrhizal fungi improve plant growth by enhancing the uptake of nutrients such as water, sulfates, nitrates, phosphates, and metals. Examples of isoflavones include, but are not limited to, genistein, biochanin A, formononetin, daidzein, glycitein, hesperetin, naringenin, and pratensein. Formononetin is available as an active ingredient in mycorrhizal inoculant products such as PHC Colonize® AG.

[0373] Seed treatment can also include one or more plant activators that induce systemic acquired resistance in plants after contact with pathogens. An example of a plant activator that induces such a protective mechanism is acibenzolar-S-methyl.

[0374] The following tests demonstrate the control efficacy of the compounds of the present invention against specific pathogens. However, the pathogen control protection provided by the compounds is not limited to these species. Refer to Index Tables A - E below for the description of the compounds. The following abbreviations are used in Index Tables A - E: Me means methyl, 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." represents "compound", and the abbreviation "Ex." represents "Example", followed by the number of the compound produced in that example. The abbreviation "m.p." represents the melting point. "AP + (M+1) The value reported in the column is the molecular weight of the observed molecular ion formed by the addition of H + (molecular weight 1) to the molecule having the highest isotope abundance (i.e., M). The presence of one or more molecular ions containing isotopes of higher atomic weight with lower abundance (e.g., 37 Cl, 81 Br) is not reported. The reported MS peaks were observed by mass spectrometry using electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI).

[0375]

Table 6

[0376]

Table 7

[0377]

Table 8

[0378]

Table 9

[0379]

Table 10

[0380]

Table 11

[0381]

Table 12

[0382]

Table 13

[0383]

Table 14

[0384] Biological Examples of the Present Invention Overall protocol for manufacturing test suspensions for Tests A - F: The test compound was first dissolved in acetone in an amount equal to 3% of the final volume, and then suspended at the desired concentration (ppm) in a 50 / 50 (by volume) mixture of acetone containing 250 ppm of the surfactant PEG400 (polyhydric alcohol ester) and purified water. The resulting suspension was then used in Tests A - F.

[0385] Test A The test solution was sprayed onto the run - off point on wheat seedlings. The next day, the seedlings were inoculated with a spore suspension of Zymoseptoria tritici (the pathogen of wheat leaf blotch), and incubated at 24 °C for 48 hours under a saturated atmosphere, then transferred to a growth chamber at 20 °C for 17 days, after which disease scoring was carried out.

[0386] Test B The test liquid agent was sprayed on the exudation points on wheat seedlings. The next day, the seedlings were inoculated with a spore suspension of Puccinia recondita f.sp. tritici (the pathogen of wheat leaf rust), and incubated at 20 °C for 24 hours in a saturated atmosphere, then transferred to a growth chamber at 20 °C for 7 days, and disease scoring was performed after that period. f.sp. tritici (the pathogen of wheat leaf rust), and incubated at 20 °C for 24 hours in a saturated atmosphere, then transferred to a growth chamber at 20 °C for 7 days, and disease scoring was performed after that period.

[0387] Test C The test suspension agent was sprayed on the exudation points on wheat seedlings. The next day, the seedlings were inoculated with spore powder of Blumeria graminis f.sp. tritici (the pathogen of wheat powdery mildew, also known as Erysiphe graminis f.sp. tritici), and incubated in a growth chamber at 20 °C for 8 days, and visual disease scoring was performed after that period.

[0388] Test D The test liquid agent was sprayed on the exudation points on soybean seedlings. The next day, the seedlings were inoculated with a spore suspension of Phakopsora pachyrhizi (the pathogen of Asian soybean rust), and incubated at 22 °C for 24 hours in a saturated atmosphere, then transferred to a growth chamber at 22 °C for 8 days, and visual disease scoring was performed after that period.

[0389] Test E The test suspension agent was sprayed on the exudation points on tomato seedlings. The next day, the seedlings were inoculated with a spore suspension of Botrytis cinerea (the pathogen of tomato gray mold), and incubated at 20 °C for 48 hours in a saturated atmosphere, then transferred to a growth chamber at 24 °C for 3 days, and visual disease scoring was performed after that period.

[0390] Test F The test suspension was sprayed at the outflow point on the tomato seedlings. The next day, the seedlings were seeded with a spore suspension of Alternaria solani (the pathogen of tomato early blight), and incubated at 27 °C for 48 hours under a saturated atmosphere, then transferred to a growth chamber at 20 °C for 3 days, and visual disease scoring was performed after that period.

[0391] The results for Tests A - F are shown in Table A below. A score of 100 indicates 100% disease control, and a score of 0 indicates no disease control (compared to the control). A dash (-) indicates that the compound was not tested.

[0392] [Table 15]

[0393] [Table 16]

[0394] [Table 17]

[0395] [Table 18]

[0396] [Table 19]

Claims

【Claim 1】 Formula 11 【Chemical 1】 [wherein, A is 【Chemical 2】 and In the formula, the bond extending to the right is bonded to the ring containing Q, and the bond extending to the left is bonded to the phenyl ring having a Y-N(R 3 )H substituent; Q is CR 6 and; Y is CR 7a R 7b and; R 1 and R 2 are each F; R 3 is H; n is 0; R 6 is Br, Cl, I, amino, methyl, i-propyl, trifluoromethyl, CHF 2 , methoxy, ethoxy, i-propyloxy or trifluoromethoxy; R 7a is H; R 7b is a compound selected from H] and salts thereof.

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