Microbiocidal pyrazole derivatives

Abstract

A compound of formula (I) wherein the substituents are as defined in claim 1 and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, which can be used as fungicides. # imgabs0 #

Description

[0001] The present invention relates to microbicidal pyrazole derivatives, for example as active ingredients, which have microbicidal activity, in particular fungicidal activity. The invention also relates to the preparation of these pyrazole derivatives, to intermediates useful in the preparation of these pyrazole derivatives, to the preparation of these intermediates, to agrochemical compositions comprising at least one of these pyrazole derivatives, to the preparation of these compositions, and to the use of these pyrazole derivatives or compositions in agriculture or horticulture for controlling or preventing infection of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, in particular fungi.

[0002] According to a first aspect of the present invention, there is provided a compound having formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof:

[0003]

[0004] in

[0005] R 1 is selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, or C3-C6-cycloalkyl;

[0006] R 2 is selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C2-alkyl-C1-C4-alkoxy, C1-C2-alkyl-C1-C4-alkoxy-C1-C2-alkoxy, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimido, N-hydroxy-C1-C4-alkyl-carbonimido, or C1-C4-alkoxycarbonyl;

[0007] R 3 is selected from hydrogen, halogen, or C1-C4-alkyl;

[0008] R 4 is selected from hydrogen, halogen, C1-C4-alkyl, cyano, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-alkylaminocarbonyl, or di(C1-C4-alkylamino)carbonyl;

[0009] R 5 and R 6 independently selected from hydrogen, or C1-C4-alkyl;

[0010] A 1 、A 2 and A 3 Independently selected from CR7 、N、NR 8 , O or S, provided that A 1 、A 2 and A 3 At least one of is selected from N, O or S, and A 1 、A 2 and A 3 No more than one of them is O or S;

[0011] R 7 and R 8 independently selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, or C2-C4-alkynyl;

[0012] B 1 It's CR 9 or N, B 2 It's CR 10 or N, B 3 It's CR 11 or N, B 4 It's CR 12 or N, provided that B 1 、B 2 、B 3 and B 4 Only one of them is N;

[0013] R 10 、R 11 、R 12 and R 13 independently selected from hydrogen, halogen, amino, hydroxy, carboxylic acid, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C2-C4-alkenyloxy, C2-C4-alkynyloxy, C1-C4-alkylsulfanyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di(C 1-C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimido, N-hydroxy-C1-C4-alkyl-carbonimido, C1-C4-alkylaminocarbonyl, di(C1-C4-alkyl)aminocarbonyl, C1-C4-alkylcarbonylamino, C1-C4-alkylsulfonylamino, trifluoromethylsulfonyloxy, phenyl, 5-membered or 6-membered heteroaryl, or C wherein the 5-membered or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, with the proviso that not more than one is O or S; and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and

[0014] Z 1 is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any of the pyridyl-, pyrazin-, pyridazine-, and pyrimidin- moieties is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkynyl, C1-C4-haloalkoxy, C1-C4-alkoxy, C1-C4-alkylsulfanyl, C1-C4-alkylsulfinyl, or C1-C4-alkylsulfonyl.

[0015] Surprisingly, it has been found that, for practical purposes, the compounds of formula (I) possess very advantageous levels of biological activity for protecting plants from diseases caused by fungi.

[0016] According to a second aspect of the present invention, there is provided an agrochemical composition comprising a fungicidal effective amount of a compound of formula (I) according to the present invention. Such an agricultural composition may further comprise at least one additional active ingredient and / or an agrochemically acceptable diluent or carrier.

[0017] According to a third aspect of the present invention, there is provided a method for controlling or preventing infection of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I) according to the present invention, or a composition comprising the compound of formula (I), is applied to the plant, its part or its locus.

[0018] According to a fourth aspect of the present invention, there is provided the use of a compound of formula (I) according to the present invention as a fungicide. According to this particular aspect of the present invention, the use may exclude methods of treating the human or animal body by surgery or therapy and diagnostic methods performed on the human or animal body.

[0019] Compounds of formula (I) with at least one basic center can form acid addition salts, for example, with strong inorganic acids (such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrohalic acids), strong organic carboxylic acids (such as unsubstituted or, for example, halogen-substituted C1-C4-alkanecarboxylic acids, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid), or organic sulfonic acids (such as unsubstituted or, for example, halogen-substituted C1-C4-alkanesulfonic acids or arylsulfonic acids, for example methanesulfonic acid or p-toluenesulfonic acid). The compounds of formula (I) having at least one acidic group can form salts, for example, with bases, for example mineral salts, such as alkali metal or alkaline earth metal salts, for example sodium salts, potassium salts or magnesium salts; or with ammonia or organic amines (such as morpholine, piperidine, pyrrolidine, mono-, di- or tri-lower alkylamines, for example ethylamine, diethylamine, triethylamine or dimethylpropylamine, or mono-, di- or trihydroxy lower alkylamines, for example monoethanolamine, diethanolamine or triethanolamine).

[0020] In each case, the compounds of formula (I) according to the invention are in free form, in oxidized form (such as N-oxides), or in salt form (eg agronomically usable salt forms).

[0021] N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen-containing heteroaromatic compounds. They are described, for example, in the book "Heterocyclic N-oxides" by A. Albini and S. Pietra, CRC Press, Boca Raton, 1991.

[0022] The compounds of formula (I) according to the invention also include hydrates which may be formed during salt formation.

[0023] When substituents are indicated as "optionally substituted", this means that they may or may not carry one or more identical or different substituents, for example, one, two or three R xSubstituents. For example, C1-C6 alkyl substituted with 1, 2 or 3 halogens may include, but is not limited to, -CH2Cl, -CHCl2, -CCl3, -CH2F, -CHF2, -CF3, -CH2CF3 or -CF2CH3 groups. As another example, C1-C6 alkoxy substituted with 1, 2 or 3 halogens may include, but is not limited to, CH2ClO-, CHCl2O-, CCl3O-, CH2FO-, CHF2O-, CF3O-, CF3CH2O- or CH3CF2O- groups. In addition, as used herein, the term "alternatively substituted" may be used interchangeably with the term "unsubstituted or substituted".

[0024] As used herein, the term "halogen" or "halo" refers to fluorine (fluorine / fluoro), chlorine (chlorine / chloro), bromine (bromine / bromo) or iodine (iodine / iodo), preferably fluorine, chlorine or bromine. This also applies accordingly to halogen in combination with other meanings, such as haloalkyl, haloalkenyl, haloalkynyl, haloalkoxy and halocycloalkyl.

[0025] As used herein, amino refers to a -NH2 group.

[0026] As used herein, cyano refers to a -CN group.

[0027] As used herein, the term "hydroxyl" or "hydroxy" refers to an -OH group.

[0028] As used herein, the term "carboxylic acid" refers to a -COOH group.

[0029] As used herein, the term "C1-C n "-alkyl" refers to a saturated straight or branched hydrocarbon radical having 1 to n carbon atoms, attached via any carbon atom, such as any of the following: methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl.

[0030] As used herein, the term "C2-C n"-Alkenyl" refers to a straight or branched alkenyl chain moiety having two to n carbon atoms and one or two double bonds, for example, vinyl, prop-1-enyl, but-2-enyl.

[0031] As used herein, the term "C2-C n -alkynyl" refers to a straight or branched alkynyl chain moiety having two to n carbon atoms and one triple bond, for example ethynyl, prop-2-ynyl, but-3-ynyl,

[0032] As used herein, the term "C3-C n "-cycloalkyl" refers to a three (3) to n-membered cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0033] As used herein, the term "C1-C n "-alkoxy" refers to a straight or branched saturated alkyl group having one (1) to n carbon atoms (as mentioned above) attached via an oxygen atom, i.e., for example, any of the following groups: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy and 1,1-dimethylethoxy. As used herein, the term "C2-C n "-Alkenyloxy" refers to a straight or branched alkenyl chain (as mentioned above) having two (2) to n carbon atoms attached via an oxygen atom.

[0034] As used herein, the term "C 2- C n "Alkynyloxy" refers to a group having the formula -OR a A group in which R a is C as generally defined above 2- C n Alkynyl.

[0035] As used herein, the term "C1-C n -alkoxy-C1-C n -alkyl" refers to a C1-C n - Alkoxy-substituted alkyl (as mentioned above). Examples are methoxymethyl, methoxyethyl, ethoxymethyl and propoxymethyl.

[0036] As used herein, the term "C1-C n -alkyl-C1-C n -alkoxy" refers to a group having the formula -CR a -OR b A group in which R a is C1-C as defined above n -alkyl, and R b Refers to C1-C as defined above n -alkyl.

[0037] As used herein, the term "C1-C n -alkyl-C1-C n -alkoxy-C1-C n -alkoxy" refers to a group having the formula -CR a -OR b -OR c A group in which R a is C1-C as defined above n -alkyl, and R b and R c Refers to C1-C as defined above n -alkyl.

[0038] As used herein, the term "C3-C n -cycloalkyl-C1-C n -alkyl" refers to a C3-C n - cycloalkyl substituted alkyl (as mentioned above). Examples are cyclopropylmethyl, cyclopropylethyl. Similarly, the term "C3-C n -halogenated cycloalkyl-C1-C n "-alkyl" refers to an alkyl group substituted by a cycloalkyl group, wherein the cycloalkyl group is substituted by one or more identical or different halogen atoms. Examples are 3,3-difluorobutylmethyl and 1-chlorocyclopropylmethyl.

[0039] As used herein, the term "C1-C n"-haloalkyl" refers to straight-chain or branched saturated alkyl groups (as mentioned above) having 1 to n carbon atoms, attached via any carbon atom, wherein some or all of the hydrogen atoms in these groups may be replaced by fluorine, chlorine, bromine and / or iodine, i.e., for example, any of the following: chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl or nonafluorobutyl. Accordingly, the term "C1-C2 fluoroalkyl" will refer to a C1-C2 alkyl group with 1, 2, 3, 4, or 5 fluorine atoms, such as any of the following: difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl or pentafluoroethyl. Similarly, as used herein, the term "C2-C n -haloalkenyl" or "C2-C n -haloalkynyl" refers to a C2-C n -alkenyl or C2-C n -alkynyl. Similarly, as used herein, the term "C3-C n -halogenated cycloalkyl" or "C1-C n -haloalkoxy" refers to a C3-C4 substituted by one or more halogen atoms which may be the same or different. n -cycloalkyl or C1-C n -alkoxy.

[0040] As used herein, the term "C1-C n -alkylthio" or "C1-C n -alkylsulfanyl" refers to a C1-C n -alkyl.

[0041] As used herein, the term "C1-C n -haloalkylthio" or "C1-C n -haloalkylsulfanyl" refers to a C1-Cn Halogenated alkyl.

[0042] As used herein, the term "C1-C n -alkylsulfinyl" refers to a C1-C1-C1-alkylsulfinyl group attached through the sulfur atom of a sulfinyl (or S(=O)-) group. n alkyl.

[0043] As used herein, the term "C1-C n -alkylsulfonyl" refers to a C1-C2-alkylsulfonyl group attached through the sulfur atom of a sulfonyl (or S(=O)2-) group. n alkyl.

[0044] As used herein, the term "C1-C n -alkylsulfonyl-C1-C n -alkyl" refers to a C1-C n Alkylsulfonyl-substituted C1-C n alkyl.

[0045] As used herein, the term "C1-C n -alkylcarbonyl" refers to a C1-C ... n -alkyl.

[0046] As used herein, the term "C1-C n -alkoxycarbonyl" refers to a C1-C ... n -alkoxy moiety.

[0047] As used herein, the term "C1-C n -alkoxycarbonyl-C1-C n -alkyl" refers to a "C1-C n -alkoxycarbonyl substituted C1-C n -alkyl.

[0048] As used herein, the term "benzoyl" refers to a phenyl group attached through the carbon atom of a carbonyl (C=O) group.

[0049] As used herein, the term "C1-C n -haloalkoxycarbonyl" refers to a C1-C ... n -haloalkoxy.

[0050] As used herein, the term "C2-C n -alkenyloxycarbonyl" refers to a C2-C n -alkenyloxycarbonyl.

[0051] As used herein, the term "C1-C n -alkylaminocarbonyl" refers to a C1-C ... n -alkylamino (or R a NHC(=O)-, where R a It is C1-C n -alkyl).

[0052] As used herein, the term "aminocarbonyl-C1-C n -alkyl" refers to a C1-C1-C1-alkyl substituted by an aminocarbonyl (or NH2C(=O)-) group n -alkyl.

[0053] As used herein, the term "C1-C n -alkylaminocarbonyl-C1-C n -alkyl" refers to a C1-C n -alkylaminocarbonyl (or R a C1-C n -alkyl, where R a It is C1-C n -alkyl. C1-C n -Alkyl groups may be substituted.

[0054] As used herein, the term "N-Cl-C n- "Alkylamino" refers to a group having the formula -NH-R a A group in which R a is C1-C as defined above n -alkyl.

[0055] As used herein, the term "N,N-di(C1-C n "alkyl)amino" refers to a group having the formula -N(R a )R a A group in which each R a are C1-n alkyl groups as defined above which may be the same or different.

[0056] As used herein, the term "C1-C n -alkylcarbonyloxy-C1-C n -alkyl" refers to a C1-C n -alkylcarbonyloxy (or R a C1-C substituted with C(=O)O-) group n -alkyl, where R a It is C1-C n -haloalkyl.

[0057] As used herein, the term "C1-Cn -alkoxycarbonyloxy-C1-C n -alkyl" refers to a C1-C n -alkoxycarbonyloxy (or R c C1-C substituted with C(=O)O-) group n -alkyl, where R c It is C1-C n -alkoxy. C1-C n -Alkoxy groups may be substituted.

[0058] As used herein, the term "N-C1-C4 alkoxy-C-C1-C4 alkyl-carbonimido" refers to a group having the formula -C(R a )=NO(R b ) group, wherein R a is C as generally defined above 1- C4 alkyl, and R b is C as generally defined above 1- C4 alkyl.

[0059] As used herein, the term "N-hydroxy-C-C1-C4 alkyl-carbonimido" refers to a group having the formula -C(R a )=NOH group, wherein R a is C1-C4 alkyl as generally defined above.

[0060] As used herein, the term "heteroaryl" refers to a 5- or 6-membered aromatic monocyclic group containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S. Examples of heteroaryl groups include, but are not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidinyl, or pyridyl. The term "heteroaryl-C1-C n -alkyl" or "heteroaryl-C3-C n -cycloalkyl" refers to a C1-C ... n -alkyl or C3-C n -cycloalkyl. Heteroaryl-C1-C n -alkyl or heteroaryl-C3-C n -Cycloalkyl may optionally be substituted on the heteroaryl, alkyl and / or cycloalkyl groups.

[0061] As used herein, the term "control" refers to reducing the number of pests, eliminating pests, and / or preventing further pest damage, such that damage to plants or to plant-derived products is reduced.

[0062] As used herein, the term "pest" refers to insects and molluscs present in agriculture, horticulture, forestry, storage of products of plant origin (such as fruit, grain and wood); and those pests associated with damage to man-made structures. The term pest covers all stages of the pest life cycle.

[0063] As used herein, the term "effective amount" refers to an amount of a compound or a salt thereof that provides the desired effect upon single or multiple administrations.

[0064] The effective amount is readily determined by one skilled in the art using known techniques and by observing the results obtained under similar circumstances. In determining the effective amount, many factors are taken into account, including, but not limited to, the type of plant or derived product being applied; the pest to be controlled and its life cycle; the specific compound being applied; the type of application; and other relevant circumstances.

[0065] As used herein, the term "room temperature" or "RT" or "rt" or "ambient temperature" refers to a temperature of about 15° C. to about 35° C. For example, rt may refer to a temperature of about 20° C. to about 30° C.

[0066] The following list provides substituents R for compounds of formula (I) of the present invention. 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 11 、R 12 、R 13 、B 1 、B 2 、B 3 、B 4 、A 1 、A 2 、A 3 and Z 1 For any of these substituents, any definition given below may be combined with any definition of any other substituent given below or elsewhere in this document.

[0067] In one embodiment of the present invention, R 1 Selected from hydrogen, C1-C 4- Alkyl, C2-C 4- In another embodiment of the present invention, R 1 is a C1-C4 alkyl group. Preferably, R1 is a C1-C3 alkyl group. More preferably, R 1 is methyl, ethyl, or isopropyl. Still more preferably, R 1 It's methyl.

[0068] In one embodiment of the present invention, R 2 is selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C2-alkyl-C1-C4-alkoxy, C1-C2-alkyl-C1-C4-alkoxy-C1-C2-alkoxy, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimido, N-hydroxy-C1-C4-alkyl-carbonimido, or C1-C4-alkoxycarbonyl. Preferably, R 2 is hydrogen, halogen, C1-C3 alkyl, C1-C3-alkoxy, C3-C6-cycloalkyl, C1-C2-alkyl-C1-C2-alkoxy, C1-C2-alkyl-C1-C4-alkoxy-C1-C2-alkoxy, C1-C2-alkylcarbonyl, N-C1-C 2- Alkoxy-C-C1-C 2- More preferably, R 2 is hydrogen, halogen, C1-C3 alkyl, C1-C3-alkoxy, C3-C6-cycloalkyl, or C1-C2-alkyl-C1-C2-alkoxy. Still even more preferably, R 2 is hydrogen, halogen, C1-C3 alkyl, C1-C3-alkoxy, or C1-C2-alkyl-C1-C2-alkoxy.

[0069] In one embodiment of the present invention, R 2 Selected from hydrogen, halogen, C1-C 4- Alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6 cycloalkyl, C1-C 4- Alkylcarbonyl, N-C1-C4 alkoxy-C-C1-C4 alkyl-carbonimide, N-hydroxy-C-C1-C4 alkyl-carbonimide, or C1-C 4- In another embodiment of the present invention, R 2 It is hydrogen, halogen, C1-C 4- Alkyl, C3-C 6- Cycloalkyl, C1-C 4- Alkylcarbonyl, N-C1-C 4- Alkoxy-C1-C 4-Alkyl-carbonimide, or N-hydroxy-C1-C 4- Preferably, R 2 It is hydrogen, halogen, C1-C3 alkyl, cyclopropyl, C1-C 2- Alkylcarbonyl, N-C1-C 2- Alkoxy-C-C1-C 2- More preferably, R 2 It is hydrogen, halogen, C1-C 3- alkyl, cyclopropyl, acetyl, -C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, or -C(CH3)=NOH. Still more preferably, R 2 is selected from hydrogen, halogen, or C1-C4 alkyl. In a preferred embodiment of the present invention, R 2 is selected from hydrogen, halogen, or C1-C3 alkyl. Most preferably, R 2 is hydrogen, chlorine, or methyl. In a preferred embodiment, R 2 In another preferred embodiment, R 2 In another preferred embodiment, R 2 In another preferred embodiment, R 2 It is cyclopropyl.

[0070] In another embodiment of the present invention, R 2 is selected from hydrogen, halogen, C1-C4-alkyl, or C3-C6-cycloalkyl. 2 is hydrogen, halogen, C1-C3-alkyl, or C3-C6-cycloalkyl. More preferably, R 2 is hydrogen, chlorine, methyl, or cyclopropyl.

[0071] In another embodiment of the present invention, R 2 is selected from C1-C4-alkoxy, C1-C2-alkyl-C1-C4-alkoxy, or C1-C2-alkyl-C1-C4-alkoxy-C1-C2-alkoxy. 2 is C1-C3-alkoxy, C1-C2-alkyl-C1-C3-alkoxy, or C1-C2-alkyl-C1-C3-alkoxy-C1-C2-alkoxy. More preferably, R 2 It is methoxy, ethoxy, methoxymethyl, or ethoxymethyl.

[0072] In an embodiment of the present invention, R 3 is selected from hydrogen, halogen, or C1-C4 alkyl. 3 is hydrogen, fluorine, chlorine, or methyl. More preferably, R 3is hydrogen or methyl. Even more preferably, R 3 It's hydrogen.

[0073] In one embodiment of the present invention, R 4 is selected from hydrogen, halogen, C1-C4 alkyl, cyano, C1-C4 alkylcarbonyl, C1-C4 alkoxycarbonyl, C1-C4 alkylaminocarbonyl, or di(C1-C4 alkyl)aminocarbonyl. In another embodiment of the present invention, R 4 is hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4-alkylcarbonyl, or C1-C4-alkoxycarbonyl. 4 is hydrogen, chlorine, fluorine, C1-C3-alkyl, cyano, or CO2Me. More preferably, R 4 is hydrogen, methyl, ethyl, isopropyl, or cyano. Even more preferably, R 4 is hydrogen or methyl. In one embodiment, R 4 In another embodiment, R 4 It's methyl.

[0074] In one embodiment of the present invention, R 5 and R 6 are independently selected from hydrogen or C1-C4 alkyl. 5 and R 6 are independently selected from hydrogen or C1-C2-alkyl. More preferably, R 5 and R 6 are independently selected from hydrogen or methyl. Even more preferably, R 5 and R 6 It's hydrogen.

[0075] In one embodiment of the present invention, A 1 、A 2 and A 3 Independently selected from CR 7 、N、NR 8 , O or S, provided that A 1 、A 2 and A 3 At least one of is selected from N, O or S, and A 1 、A 2 and A 3 No more than one of them is O or S.

[0076] In another embodiment of the present invention, A 1 、A 2 and A 3 Independently selected from CR 7 , N, O or S, provided that A 1 、A 2 and A 3At least one of is selected from N, O or S, and A 1 、A 2 and A 3 No more than one of them is O or S.

[0077] In one embodiment of the present invention, R 7 and R 8 are independently selected from hydrogen, C1-C4 alkyl, C2-C4 alkenyl, or C2-C4 alkynyl. 7 and R 8 are independently selected from hydrogen or C1-C4 alkyl. More preferably, R 7 and R 8 are independently selected from hydrogen or methyl. More preferably, R 7 and R 8 It's hydrogen.

[0078] In one embodiment of the present invention, B 1 It's CR 9 or N, B 2 It's CR 10 or N, B 3 It's CR 11 or N, B 4 It's CR 12 or N, provided that B 1 、B 2 、B 3 and B 4 Only one of them is N.

[0079] In another embodiment of the present invention, B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 , and B 4 It's CR 12 , or B 1 It's N, B 2 It's CR 10 , B 3 It's CR 11 , and B 4 It's CR 12 , or B 1 It's CR 9 , B 2 It's N, B 3 It's CR 11 , and B 4 It's CR 12 , or B 1 It's CR 9 , B 2 It's CR 10 , B3 is N, and B 4 It's CR 12 , or B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 , and B 4 is N. Preferably, B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 , and B 4 It's CR 12 , or B 1 It's N, B 2 It's CR 10 , B 3 It's CR 11 , and B 4 It's CR 12 , or B 1 It's CR 9 , B 2 It's N, B 3 It's CR 11 , and B 4 It's CR 12 More preferably, B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 , and B 4 It's CR 12 .

[0080] In one embodiment of the present invention, R 9 、R 10 、R 11 and R 12 independently selected from hydrogen, halogen, amino, hydroxy, carboxylic acid, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkoxy-C1-C4 alkyl, NC 1- C4 alkylamino, N,N-di(C 1-C4 alkyl)amino, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyl, N-C1-C4 alkoxy-C1-C4 alkyl-carbonimido, N-hydroxy-C1-C4 alkyl-carbonimido, C1-C4 alkylaminocarbonyl, di(C1-C4 alkylamino)carbonyl), C1-C4 alkylcarbonylamino, C1-C4 alkylsulfonylamino, trifluoromethylsulfonyloxy, phenyl, 5-membered or 6-membered heteroaryl, or C3 -C6 cycloalkyl; wherein the 5-membered or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, with the proviso that not more than one is O or S; and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6 cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy.

[0081] In another embodiment of the present invention, R 9 and R 10 independently selected from hydrogen, halogen, hydroxy, cyano, amino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkoxy-C1-C4 alkyl, N-C1-C4 alkylamino, N,N-di(C1-C4 alkyl)amino, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyl, N-C1-C4 alkoxy-C1-C4 alkyl C1-C4 alkyl-carbonimido, N-hydroxy-C1-C4 alkyl-carbonimido, trifluoromethylsulfonyloxy, carboxyl, phenyl, 5-membered or 6-membered heteroaryl, or C3-C6 cycloalkyl, wherein the 5-membered or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S; and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy.

[0082] In another embodiment of the present invention, R 9 and R 10independently selected from hydrogen, halogen, cyano, amino, C1-C3 alkyl, C1-C2 haloalkyl, C1-C3 haloalkoxy, C1-C4 alkoxy, C2-C3 alkenyloxy, C2-C3 alkynyloxy, C1-C2 alkylsulfanyl, C1-C2 alkylsulfinyl, C1-C2 alkylsulfonyl, C1-C2 alkoxy-C1-C2 alkyl, C1-C3 alkoxycarbonyl, C1-C2 alkylcarbonyl, N-C1-C2 alkoxy-C1-C2 alkyl-carbonimide, N-hydroxy-C1 -C2 alkyl-carbonimido, hydroxy, C1-C2 alkylaminocarbonyl, di(C1-C2 alkyl)aminocarbonyl, trifluoromethyl-sulfonyloxy, carboxyl, phenyl, 5-membered or 6-membered heteroaryl, or C3-C6 cycloalkyl; wherein the 5-membered or 6-membered heteroaryl contains 1 or 2 heteroatoms independently selected from N and O; and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano or methyl.

[0083] In a preferred embodiment, R 9 and R 10 independently selected from hydrogen, halogen, cyano, amino, C1-C3 alkyl, C1-C2 haloalkyl, C1-C3 haloalkoxy, C1-C4 alkoxy, C2-C3 alkenyloxy, C2-C3 alkynyloxy, C1-C2 alkylsulfanyl, C1-C2 alkylsulfinyl, C1-C2 alkylsulfonyl, C1-C2 alkoxy-C1-C2 alkyl, C1-C3 alkoxycarbonyl, C1-C2 alkylcarbonyl, N-C1-C2 alkoxy-C-C1-C2 alkyl-carbonimido, N-hydroxy-C1-C2 alkyl-carbonimido, hydroxy, C1-C2 alkylaminocarbonyl, di(C1-C2 alkylamino)carbonyl, trifluoromethylsulfonyloxy, carboxyl, phenyl, 2-cyanophenyl phenyl, 3-cyanophenyl, 4-cyanophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], (3-cyanopyrazol-1-yl), (4-cyanopyrazol-1-yl), (5-chloropyrazol-1-yl), (4-chloropyrazol-1-yl), (3-chloropyrazol-1-yl), (5-fluoropyrazol-1-yl), (4-fluoropyrazol-1-yl), (3-fluoropyrazol-1-yl), (3,5-dimethylpyrazol-1-yl), (5-methylpyrazol-1-yl), (4-methylpyrazol-1-yl), (3-methylpyrazol-1-yl), pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl.

[0084] More preferably, R 9 and R 10independently selected from hydrogen, chlorine, fluorine, bromine, methyl, ethyl, trifluoromethyl, difluoromethyl, difluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, methoxy, ethoxy, propoxy, allyloxy, prop-2-ynyloxy, methylsulfanyl, methylsulfinyl, methyl-sulfonyl, methoxymethyl, ethoxymethyl, 2-methoxy-ethoxymethyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, acetyl, propionyl, -C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, -C(CH3)=NOH, methyl-aminocarbonyl, di(methylamino)carbonyl, trifluoromethylsulfonyloxy, cyano, carboxyl, phenyl, 2-cyanophenyl, 3- 1-cyanophenyl, 4-cyanophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], (3-cyanopyrazol-1-yl), (4-cyanopyrazol-1-yl), (5-chloropyrazol-1-yl), (4-chloropyrazol-1-yl), (3-chloropyrazol-1-yl), (5-fluoropyrazol-1-yl), (4-fluoropyrazol-1-yl), (3-fluoropyrazol-1-yl), (3,5-dimethylpyrazol-1-yl), (5-methylpyrazol-1-yl), (4-methylpyrazol-1-yl), (3-methylpyrazol-1-yl), pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl.

[0085] Even more preferably, R 9 and R 10 independently selected from hydrogen, chlorine, fluorine, bromine, methyl, trifluoromethyl, difluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, methoxy, propoxy, allyloxy, prop-2-ynyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, methoxymethyl, 2-, methoxy, ethoxymethyl, methoxycarbonyl, acetyl, propionyl, -C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, -C(CH3)=NOH, methylaminocarbonyl, di(methylamino)carbonyl, trifluoromethylsulfonyloxy, cyano, carboxyl, phenyl, 2-cyanophenyl, 3-cyanophenyl , 4-cyanophenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], (3-cyanopyrazol-1-yl), (4-cyanopyrazol-1-yl), (5-chloropyrazol-1-yl), (4-chloropyrazol-1-yl), (3-chloropyrazol-1-yl), (5-fluoropyrazol-1-yl), (4-fluoropyrazol-1-yl), (3-fluoropyrazol-1-yl), (3,5-dimethylpyrazol-1-yl), (5-methylpyrazol-1-yl), (4-methylpyrazol-1-yl), (3-methylpyrazol-1-yl), pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl.

[0086] Still even more preferably, R 9 and R 10 Independently selected from hydrogen, chlorine, fluorine, bromine, methoxy, cyano, amino, carboxyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, (3-cyanopyrazol-1-yl), (4-cyanopyrazol-1-yl), (5-chloropyrazol-1-yl), (4-chloropyrazol-1-yl), (3-chloropyrazol-1-yl), (5-fluoropyrazol-1-yl), (4-fluoropyrazol-1-yl), (3-fluoropyrazol-1-yl), (3,5-dimethylpyrazol-1-yl), (5-methylpyrazol-1-yl), (4-methylpyrazol-1-yl), (3-methylpyrazol-1-yl), pyrazol-1-yl, cyclopropyl, and 1-cyanocyclopropyl.

[0087] In yet another embodiment of the present invention, R 9 and R 10 independently selected from hydrogen, halogen, cyano, amino, C1-C4 alkoxy, phenyl, 5-membered or 6-membered heteroaryl, or C3-C6 cycloalkyl; wherein the 5-membered or 6-membered heteroaryl contains 1 heteroatom selected from N; and wherein any one of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, cyano or methyl.

[0088] More preferably, R 9 and R 10 R is independently selected from hydrogen, chlorine, bromine, methoxy, cyano, amino, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, (3-cyanopyrazol-1-yl), (4-cyanopyrazol-1-yl), (3,5-dimethylpyrazol-1-yl), (5-methylpyrazol-1-yl), (4-methylpyrazol-1-yl), (3-methylpyrazol-1-yl), pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. Even more preferably, R 10 and R 11 are independently selected from hydrogen, chlorine, bromine, cyano, or amino.

[0089] In another embodiment of the present invention, R 9 and R 10 are independently selected from hydrogen, halogen, or cyano. More preferably, R 10 and R 11 are independently selected from hydrogen, chlorine, bromine, or cyano.

[0090] In another embodiment of the present invention, R 11 and R 12 are independently selected from hydrogen, halogen, cyano, C1-C4 alkyl, or C1-C4 alkoxy. 11 and R 12are independently selected from hydrogen, chlorine, bromine, fluorine, or methyl. More preferably, R 11 and R 12 It's hydrogen.

[0091] In one embodiment, Z 1 is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any of the pyridyl-, pyrazin-, pyridazine-, or pyrimidin- moieties is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from halogen, C1-C4 haloalkyl, cyano, C1-C4 alkyl, C3-C6-cycloalkyl, C2-C4 alkynyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, or C1-C4 alkylsulfonyl. Preferably, Z 1 is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any of the pyridinyl-, pyrazin-, pyridazine- or pyrimidin- moieties is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl. More preferably, Z 1 is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any of the pyridinyl-, pyrazin-, pyridazine- or pyrimidin- moieties is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from fluoro, trifluoromethyl, difluoromethyl, or methyl. More preferably, Z 1 is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any of the pyridyl-, pyrazin-, pyridazine- or pyrimidine- moieties is unsubstituted or substituted with 1 to 2 substituents selected from fluorine.

[0092] In another more preferred embodiment of the present invention, Z 1Selected from 5-fluoropyrimidin-4-yl, 3,6-difluoro-2-pyridinyl, 4,6-difluoro-2-pyridinyl, 4,5-difluoro-2-pyridinyl, 5,6-difluoro-2-pyridinyl, 3-fluoro-4-pyridinyl, 2-fluoro-4-pyridinyl, 2,3-difluoro-4-pyridinyl, 2,5-difluoro-4-pyridinyl, 2,6-difluoro-4-pyridinyl, 3,5-difluoro-4-pyridinyl, 2,5-difluoro-4-pyridinyl, 2-fluoro-3-pyridinyl Pyridyl, 6-fluoro-3-pyridyl, 5-fluoro-3-pyridyl, 4-fluoro-3-pyridyl, 2,6-difluoro-3-pyridyl, 2,5-difluoro-3-pyridyl, 2,4-difluoro-3-pyridyl, 4,6-difluoro-3-pyridyl, 5,6-difluoro-3-pyridyl, 6-fluoropyrimidin-4-yl, 2-fluoropyrimidin-4-yl, 2,5-difluoropyrimidin-4-yl, 2,6-difluoropyrimidin-4-yl, 5,6-difluoropyrimidin-4-yl -yl, 4-fluoropyrimidin-5-yl, 2-fluoropyrimidin-5-yl, 2,4-difluoropyrimidin-5-yl, 4-fluoropyrimidin-2-yl, 5-fluoropyrimidin-2-yl, 4,5-difluoropyrimidin-2-yl, 4,6-difluoropyrimidin-2-yl, 4-fluoropyridazin-3-yl, 5-fluoropyridazin-3-yl, 6-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, 4,6-difluoropyridazin-3-yl, 5,6-difluoropyridazin-3-yl, 3-fluoropyridazin- Preferably, Z is 4-fluoropyridin-5-yl, 6-fluoropyridin-4-yl, 5-fluoropyridin-4-yl, 3,6-difluoropyridin-4-yl, 5,6-difluoropyridin-4-yl, 3,5-difluoropyridin-4-yl, 3,5-difluoro-2-pyridinyl, 3,4-difluoro-2-pyridinyl, 6-fluoro-2-pyridinyl, 4-fluoro-2-pyridinyl, 5-fluoro-2-pyridinyl, 3-fluoro-2-pyridinyl, 4,5-difluoro-3-pyridinyl, or 4-fluoropyrimidin-5-yl. 1 is selected from 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 6-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, 2-fluoro-4-pyridyl, 5-fluoropyrimidin-4-yl, 5-fluoropyrimidin-2-yl, 4-fluoropyridazin-3-yl, 5-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, or 5-fluoropyridazin-4-yl. More preferably, Z 1 is selected from 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, 2,6-difluoro-3-pyridyl, 4-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl or 5-fluoropyridazin-4-yl. Even more preferably, Z 1 is selected from 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 2,6-difluoro-3-pyridyl, or 3,5-difluoro-2-pyridyl. 1Selected from 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 2,6-difluoro-3-pyridyl, or 3,5-difluoro-2-pyridyl.

[0093] In another preferred embodiment, Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C3-C6-cycloalkyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, or C1-C4 alkylsulfonyl. Preferably, Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any one of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl. More preferably, Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any one of the pyridyl-parts is unsubstituted or substituted with 1 to 2 substituents selected from fluorine. Still more preferably, Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, or 2,6-difluoro-3-pyridyl. Even more preferably, Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 2,6-difluoro-3-pyridyl, or 3,5-difluoro-2-pyridyl. Most preferably, Z 1 is 2,6-difluoro-3-pyridyl, or 3,5-difluoro-2-pyridyl. In one embodiment, Z 1 In another embodiment, Z 1 It is 3,5-difluoro-2-pyridyl.

[0094] In another embodiment of the present invention, Z 1 is selected from 6-membered heteroaryl; wherein the heteroaryl contains 1 or 2 heteroatoms selected from N; and wherein the 6-membered heteroaryl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, or C1-C4 alkylsulfonyl. In one embodiment of the present invention, Z 1is selected from 6-membered heteroaryl; wherein the heteroaryl contains 1 or 2 heteroatoms selected from N; and wherein the 6-membered heteroaryl is unsubstituted or substituted with 1 to 2 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, or C1-C4 alkoxy. Preferably, Z 1 is selected from 6-membered heteroaryl; wherein the heteroaryl contains 1 or 2 heteroatoms selected from N; and wherein the 6-membered heteroaryl is unsubstituted or substituted by 1 to 2 substituents independently selected from halogen or C1-C4 haloalkyl. More preferably, Z 1 wherein the heteroaryl group comprises 1 or 2 heteroatoms selected from N; and wherein the 6-membered heteroaryl group is unsubstituted or substituted with 1 to 2 substituents selected from fluorine.

[0095] In yet another embodiment of the present invention, Z 1 is selected from 6-membered heteroaryl; wherein the heteroaryl contains 1 heteroatom selected from N; and wherein the 6-membered heteroaryl is unsubstituted or substituted with 1 to 2 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, or C1-C4 alkoxy. Preferably, Z 1 is selected from 6-membered heteroaryl; wherein the heteroaryl contains 1 heteroatom selected from N; and wherein the 6-membered heteroaryl is unsubstituted or substituted by 1 to 2 substituents independently selected from halogen or C1-C4 haloalkyl. More preferably, Z 1 is selected from 6-membered heteroaryl; wherein the heteroaryl contains 1 heteroatom selected from N; and wherein the 6-membered heteroaryl is unsubstituted or substituted with 1 to 2 substituents selected from fluorine.

[0096] Accordingly, the present invention makes available compounds of formula (I) having R as defined above in all combinations / permutations. 1 、R 2 、R 3 、R 4 、R 5 、R 6 、A 1 、A 2 、A 3 、R 7 、R 8 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1 .

[0097] Examples according to the present invention are provided as listed below.

[0098] In one embodiment of the present invention, there is provided a compound having formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof:

[0099]

[0100] in

[0101] R 1 is selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, or C3-C6-cycloalkyl;

[0102] R 2 is selected from hydrogen, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimido, N-hydroxy-C1-C4-alkyl-carbonimido, or C1-C4-alkoxycarbonyl;

[0103] R 3 is selected from hydrogen, halogen, or C1-C4-alkyl;

[0104] R 4 is selected from hydrogen, halogen, C1-C4-alkyl, cyano, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-alkylaminocarbonyl, or di(C1-C4-alkylamino)carbonyl;

[0105] R 5 and R 6 independently selected from hydrogen, or C1-C4-alkyl;

[0106] A 1 、A 2 and A 3 Independently selected from CR 7 、N、NR 8 , O or S, provided that A 1 、A 2 and A 3 At least one of is selected from N, O or S, and A 1 、A 2 and A 3 No more than one of them is O or S;

[0107] R 7 and R 8independently selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, or C2-C4-alkynyl;

[0108] B 1 It's CR 9 or N, B 2 It's CR 10 or N, B 3 It's CR 11 or N, B 4 It's CR 12 or N, provided that B 1 、B 2 、B 3 and B 4 Only one of them is N;

[0109] R 10 、R 11 、R 12 and R 13 independently selected from hydrogen, halogen, amino, hydroxy, carboxylic acid, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C2-C4-alkenyloxy, C2-C4-alkynyloxy, C1-C4-alkylsulfanyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di(C 1- C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimido, N-hydroxy-C1-C4-alkyl-carbonimido, C1-C4-alkylaminocarbonyl, di(C1-C4-alkyl)aminocarbonyl, C1-C4-alkylcarbonylamino, C1-C4-alkylsulfonylamino, trifluoromethylsulfonyloxy, phenyl, 5-membered or 6-membered heteroaryl, or C wherein the 5-membered or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, with the proviso that not more than one is O or S; and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and

[0110] Z 1is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any of the pyridyl-, pyrazin-, pyridazine-, and pyrimidin- moieties is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkynyl, C1-C4-haloalkoxy, C1-C4-alkoxy, C1-C4-alkylsulfanyl, C1-C4-alkylsulfinyl, or C1-C4-alkylsulfonyl.

[0111] In another embodiment of the present invention, there is provided a compound having formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof:

[0112]

[0113] in

[0114] R 1 is selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, or C3-C6-cycloalkyl;

[0115] R 2 is selected from C1-C4-alkoxy, C1-C2-alkyl-C1-C4-alkoxy, or C1-C2-alkyl-C1-C4-alkoxy-C1-C2-alkoxy;

[0116] R 3 is selected from hydrogen, halogen, or C1-C4-alkyl;

[0117] R 4 is selected from hydrogen, halogen, C1-C4-alkyl, cyano, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-alkylaminocarbonyl, or di(C1-C4-alkylamino)carbonyl;

[0118] R 5 and R 6 independently selected from hydrogen, or C1-C4-alkyl;

[0119] A 1 、A 2 and A 3 Independently selected from CR 7 、N、NR 8 , O or S, provided that A 1 、A 2 and A 3 At least one of is selected from N, O or S, and A 1 、A2 and A 3 No more than one of them is O or S;

[0120] R 7 and R 8 independently selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, or C2-C4-alkynyl;

[0121] B 1 It's CR 9 or N, B 2 It's CR 10 or N, B 3 It's CR 11 or N, B 4 It's CR 12 or N, provided that B 1 、B 2 、B 3 and B 4 Only one of them is N;

[0122] R 10 、R 11 、R 12 and R 13 independently selected from hydrogen, halogen, amino, hydroxy, carboxylic acid, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C2-C4-alkenyloxy, C2-C4-alkynyloxy, C1-C4-alkylsulfanyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di(C 1- C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimido, N-hydroxy-C1-C4-alkyl-carbonimido, C1-C4-alkylaminocarbonyl, di(C1-C4-alkyl)aminocarbonyl, C1-C4-alkylcarbonylamino, C1-C4-alkylsulfonylamino, trifluoromethylsulfonyloxy, phenyl, 5-membered or 6-membered heteroaryl, or C wherein the 5-membered or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, with the proviso that not more than one is O or S; and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and

[0123] Z 1is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any of the pyridyl-, pyrazin-, pyridazine-, and pyrimidin- moieties is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkynyl, C1-C4-haloalkoxy, C1-C4-alkoxy, C1-C4-alkylsulfanyl, C1-C4-alkylsulfinyl, or C1-C4-alkylsulfonyl.

[0124] In an embodiment of the present invention, the compound having formula (I) may be a compound having formula (IA):

[0125]

[0126] in

[0127] R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the present invention, and A is selected from A1 to A36:

[0128]

[0129] in indicates the position of attachment to the C(=O) group and the arrow indicates the position of attachment to Z 1 The position of the group, and where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1is as defined for the compounds of formula (I) according to the invention, and wherein R 8 is selected from hydrogen or C1-C4 alkyl.

[0130] Preferably, the compound of formula (I) may be a compound of formula (IA) wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compound of formula (I) according to the present invention, and A is selected from one of A1 to A36, and wherein R 8 Selected from methyl.

[0131] In an embodiment of the present invention, in the compound having formula (IA), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the present invention, and A is selected from A1, A4, A6, A7, A9, A10, A13 or A15:

[0132]

[0133] in indicates the position of attachment to the C(=O) group and the arrow indicates the position of attachment to Z 1 The position of the group, and where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B4 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0134] In another embodiment of the present invention, in the compound having formula (IA), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention, and A is selected from A4, A6, A7, A9 or A10,

[0135]

[0136] in indicates the position of attachment to the C(=O) group and the arrow indicates the position of attachment to Z 1 The position of the group.

[0137] In another embodiment of the present invention, in the compound having formula (IA), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention, and A is selected from A4, A7, A9 or A10,

[0138]

[0139] in indicates the position of attachment to the C(=O) group and the arrow indicates the position of attachment to the Z1 The position of the group.

[0140] In another preferred embodiment of the present invention, in the compound having formula (IA), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention, and A is selected from A4 or A9,

[0141]

[0142] in indicates the position of attachment to the C(=O) group and the arrow indicates the position of attachment to Z 1 The position of the group.

[0143] In yet another embodiment of the present invention, in the compound having formula (IA), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention, and A is selected from A4.

[0144] In yet another embodiment of the present invention, in the compound having formula (IA), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention, and A is selected from A9.

[0145] In an embodiment of the present invention, the compound having formula (I) may be a compound having formula (I-A1), wherein B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 And B 4 It's CR 12 , and A is as defined for the compound having formula (IA):

[0146]

[0147] where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0148] Preferably, in the compound having formula (I-A1), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0149] Preferably, in the compound having formula (I-A1), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0150] Preferably, in the compound having formula (I-A1), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0151] Preferably, in the compound having formula (I-A1), R 1 is methyl; R 2 is hydrogen, chlorine, methyl, or cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0152] Preferably, in the compound having formula (I-A1), R 1 is a C1-C3 alkyl group; R2 is hydrogen, halogen, or C1-C3 alkyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-moieties is unsubstituted or substituted with 1 to 2 substituents selected from fluorine.

[0153] Preferably, in the compound having formula (I-A1), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4 or A9; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-moieties is unsubstituted or substituted with 1 to 2 substituents selected from fluorine.

[0154] In another preferred embodiment, in the compound of formula (I-A1), R 1 is a C1-C3 alkyl group; R 2 is C1-C3-alkoxy, C1-C2-alkyl-C1-C3-alkoxy, or C1-C2-alkyl-C1-C3-alkoxy-C1-C2-alkoxy; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 9 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0155] Preferably, in the compound having formula (I-A1), R 1is a C1-C3 alkyl group; R 2 is C1-C3-alkoxy, C1-C2-alkyl-C1-C3-alkoxy, or C1-C2-alkyl-C1-C3-alkoxy-C1-C2-alkoxy; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0156] Preferably, in the compound of formula (I-A1), R 1 is a C1-C3 alkyl group; R 2 is C1-C3-alkoxy, C1-C2-alkyl-C1-C3-alkoxy, or C1-C2-alkyl-C1-C3-alkoxy-C1-C2-alkoxy; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A7, A9, or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0157] Preferably, in the compound having formula (I-A1), R 1 is methyl; R 2 is C1-C3-alkoxy, or C1-C2-alkyl-C1-C3-alkoxy; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A7, A9, or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0158] Preferably, in the compound having formula (I-A1), R 1 is a C1-C3 alkyl group; R 2 is C1-C3-alkoxy, or C1-C2-alkyl-C1-C3-alkoxy; R 3 is hydrogen; R 4 is hydrogen or methyl;

[0159] R 5 and R 6 is hydrogen; A is A4, A7, A9, or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-moieties is unsubstituted or substituted with 1 to 2 substituents selected from fluorine.

[0160] In an embodiment of the present invention, the compound having formula (I) may be a compound having formula (I-A2), wherein B 1 It's N, B 2 It's CR 10 , B 3 It's CR 11 And B 4 It's CR 12 , and A is as defined for the compound having formula (IA):

[0161]

[0162] where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0163] Preferably, in the compound of formula (I-A2), R 1 is a C1-C3 alkyl group; R3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 2 、R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0164] Preferably, in the compound of formula (I-A2), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 10 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0165] Preferably, in the compound of formula (I-A2), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 10 is hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0166] Preferably, in the compound of formula (I-A2), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 10 is hydrogen, halogen, or cyano; R 11 、R12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0167] In an embodiment of the present invention, the compound having formula (I) may be a compound having formula (I-A3), wherein B 1 It's CR 9 , B 2 It's N, B 3 It's CR 11 And B 4 It's CR 12 , and A is as defined for the compound having formula (IA):

[0168]

[0169] where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0170] Preferably, in the compound having formula (I-A3), R 1 is a C1-C3 alkyl group; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 2 、R 9 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0171] Preferably, in the compound having formula (I-A3), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 9 、R 11 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0172] Preferably, in the compound having formula (I-A3), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 is hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0173] Preferably, in the compound having formula (I-A3), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 is hydrogen, halogen, or cyano; R 11 、R 12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0174] In an embodiment of the present invention, the compound having formula (I) may be a compound having formula (I-A4), wherein B 1 It's CR 9 , B 2 It's CR 10 , B 3 is N and B 4 It's CR 12 , and A is as defined for the compound having formula (IA):

[0175]

[0176] where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0177] Preferably, in the compound having formula (I-A4), R 1 is a C1-C3 alkyl group; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 2 、R 9 、R 10 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0178] Preferably, in the compound having formula (I-A4), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 9 、R 10 、R 12 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0179] Preferably, in the compound having formula (I-A4), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 12 is hydrogen; and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0180] Preferably, in the compound having formula (I-A4), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 12 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0181] In an embodiment of the present invention, the compound having formula (I) may be a compound having formula (I-A5), wherein B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 And B 4 is N, and A is as defined for the compound having formula (IA):

[0182]

[0183] where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 11 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0184] Preferably, in the compound having formula (I-A5), R 1 is a C1-C3 alkyl group; R3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 2 、R 9 、R 10 、R 11 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0185] Preferably, in the compound having formula (I-A5), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is as defined for compounds of formula (IA), and R 9 、R 10 、R 11 and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0186] Preferably, in the compound having formula (I-A5), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 is hydrogen; and Z 1 is as defined for the compounds of formula (I) according to the invention.

[0187] Preferably, in the compound having formula (I-A5), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 is hydrogen; A is A4, A6, A7, A9 or A10; R 9 、R 10are independently selected from hydrogen, halogen, or cyano; R 11 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0188] The presence of one or more possible asymmetric carbon atoms in any of the compounds according to the invention selected from the compounds of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4) or (I-A5) or the compounds listed in Tables A-1 to A-23 or the compounds listed in Table P (below) means that these compounds may exist in the form of chiral isomers, i.e., enantiomers or diastereomers.

[0189] In one embodiment, the compound of formula (I) according to the present invention is selected from the compounds listed in any one of Tables A-1 to A-23.

[0190] In another embodiment, the compound of formula (I) according to the present invention is selected from the compounds listed in Table P (below).

[0191] In another preferred embodiment, the compound of formula (I) according to the present invention is selected from N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazole-2-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazole-2-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazole-2-carboxamide, -2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3-pyridyl)-1,3,4-thiadiazole-2-carboxamide, N-[2-(6-chloro-2-pyridyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3-pyridyl)-1,3,4-thiadiazole-2-carboxamide, N-[2-(6-chloro-2-pyridyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3-fluoro-2-pyridyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(5-fluoro-2-pyridyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(4,6-difluoro-3-pyridinyl)-1,3,4-thiadiazole-2-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(4,6-difluoro-3-pyridinyl)-1,3,4-thiadiazole-2-carboxamide 4-thiadiazole-2-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(6-fluoro-3-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(5-cyclopropyl-1-methyl-pyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide5-difluoro-2-pyridyl)isoxazole-5-carboxamide, N-[2-(6-chloro-2-pyridyl)-2-(5-cyclopropyl-1-methyl-pyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3-fluoro-4-pyridyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridyl)-2-(1-methylpyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridyl)-1,2,4-oxadiazole-5-carboxamide, N-[2-(6-cyano-2-pyridyl)-2-(1,3,5-trimethylpyridyl) -4-yl)propyl]-3-(3,5-difluoro-2-pyridyl)isoxazole-5-carboxamide, N-[2-(6-cyano-2-pyridyl)-2-(1,3,5-trimethylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxamide, N-[2-(6-cyano-2-pyridyl)-2-(1,3,5-trimethylpyrazol-4-yl)ethyl]-3-(3,5-difluoro-2-pyridyl)isoxazole-5-carboxamide, N-[2-(6-cyano-2-pyridyl)-2-(1,3,5-trimethylpyrazol-4-yl)ethyl]-5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxamide, N-[2-(6-cyano-2-pyridyl)-2-(1,3,5-trimethylpyrazol-4-yl)ethyl]-5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxamide, 2-pyridinyl)-2-(1,5-dimethylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1,5-dimethylpyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)-1,2,4-oxadiazole-5-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1,3,5-trimethylpyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1,3,5-trimethylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide )isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1,3,5-trimethylpyrazol-4-yl)ethyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1,3,5-trimethylpyrazol-4-yl)ethyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-2-(3,5-difluoro-2-pyridinyl)oxazole-4-carboxamide, or N-[2-(6-chloro-2-pyridinyl)-2-(1,5-dimethylpyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide.5-difluoro-2-pyridyl)isoxazole-5-carboxamide.

[0192] In another preferred embodiment, the compound of formula (I) according to the present invention is selected from N-[2-(6-chloro-2-pyridinyl)-2-[5-(methoxymethyl)-1-methyl-pyrazol-4-yl]propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(5-methoxy-1-methyl-pyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)ethyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)ethyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-cyano-2-pyridinyl)-2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol- 4-yl]ethyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol-4-yl]propyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide , N-[2-(6-chloro-2-pyridinyl)-2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol-4-yl]propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)ethyl]-3-(3,5-difluoro-2-pyridinyl)isoxazole-5-carboxamide, N-[2-(6-chloro-2-pyridinyl)-2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol-4-yl]propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide,3-dimethyl-pyrazol-4-yl]ethyl]-3-(3,5-difluoro-2-pyridyl)isoxazole-5-carboxamide, or N-[2-(6-chloro-2-pyridyl)-2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol-4-yl]ethyl]-5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxamide.

[0193] According to a fifth aspect of the present invention, there is provided an intermediate compound having formula (III) or a salt thereof:

[0194]

[0195] where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 and R 12 corresponds to the same definitions as for the compounds of formula (I) according to the invention.

[0196] The intermediates of formula (III) have the same R as for the compounds of formula (I) according to the present invention and their corresponding preferred embodiments. 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、R 9 、R 10 、R 11 and R 12 The same definition.

[0197] Preferably, in the intermediate of formula (III), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 It is hydrogen; B 1 It's CR 9 , B 2 It's CR10 , B 3 It's CR 11 , B 4 It's CR 12 ; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 is hydrogen; and Z 1 are as defined for the compounds of formula (I) according to the present invention and their corresponding preferences.

[0198] More preferably, in the intermediate having formula (III), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 It is hydrogen; B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 , B 4 It's CR 12 ; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R 11 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

[0199] Even more preferably, in the intermediate of formula (III), R 1 is a C1-C3 alkyl group; R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cyclopropyl; R 3 is hydrogen; R 4 is hydrogen or methyl; R 5 and R 6 It is hydrogen; B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 , B 4 It's CR 12 ; R 9 、R 10 are independently selected from hydrogen, halogen, or cyano; R11 is hydrogen; and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-moieties is unsubstituted or substituted with 1 to 2 substituents selected from fluorine.

[0200] The presence of one or more possible asymmetric carbon atoms in the compounds of formula (III) according to the invention means that these compounds may exist in the form of chiral isomers, ie in the form of enantiomers or diastereomers.

[0201] According to the sixth aspect of the present invention, there is provided an intermediate having formula (II)

[0202]

[0203] Among them A 1 、A 2 、A 3 and Z 1 corresponds to the same definitions as for the compounds of formula (I) according to the invention.

[0204] The intermediate compounds of formula (II) have the same A as for the compounds of formula (I) according to the present invention and their corresponding preferred embodiments. 1 、A 2 、A 3 and Z 1 The same definition.

[0205] In one embodiment of the present invention, the intermediate having formula (II) may be a compound having formula (II-1):

[0206]

[0207] where Z 1 is as defined for the compounds of formula (I) according to the present invention, and A is selected from A1 to A36 as defined above for the compounds of formula (IA).

[0208] Preferably, in the intermediate having formula (II-1), Z 1 is as defined for the compounds of formula (I) according to the present invention, and A is selected from A4, A7, A9, or A10,

[0209]

[0210] in indicates the position of attachment to the C(=O) group and the arrow indicates the position of attachment to the Z 1 The position of the group.

[0211] Even more preferably, in the intermediate having formula (II-1), A is selected from A4, A7, A9 or A10, and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any one of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl. Even more preferably, in the intermediate of formula (II-1), A is selected from A4, A7, A9 or A10, and Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-moieties is unsubstituted or substituted with 1 to 2 substituents selected from fluorine.

[0212] Compounds of formula (I) according to the present invention can be prepared as shown in the following schemes, wherein, unless otherwise stated, the definition of each variable is as defined above for compounds of formula (I).

[0213] In any of the following schemes, the presence of one or more possible asymmetric carbon atoms in the compounds of formula (I) according to the invention means that these compounds may exist in the form of chiral isomers, ie in the form of enantiomers or diastereomers.

[0214] Compounds of formula (I) can be prepared by reacting compounds of formula (III) with compounds of formula (II) using dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), or N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDAC HCl) together with additives such as 1-hydroxybenzotriazole (HOBt), hydroxy-3,4-dihydro-4-oxo-1,2,3-benzotriazine (HODhbt), N-hydroxysuccinimide (HOSu), 1-hydroxy-7-aza-1H-benzotriazole (HOAt), or 4-(N,N-dimethylamino)pyridine (DMAP). This reaction is shown in Scheme 1.

[0215]

[0216] Solution 1

[0217] Alternatively, the compound of formula (I) can be prepared by reacting a compound of formula (IIa) with a compound of formula (III) in an inert solvent (such as tetrahydrofuran (THF), ethyl acetate (EtOAc), dichloromethane (DCM), toluene, etc.), optionally in the presence of an inorganic base (such as sodium hydroxide or aqueous potassium carbonate), or in the presence of an organic base (such as trimethylamine (TEA) or diisopropylamine). The latter reaction with an organic base can be optionally carried out in the presence of a catalyst such as 4-dimethylaminopyridine (DMAP). The compound of formula (IIa) (wherein X 0 is halogen, preferably chlorine) can be prepared from a compound of formula (II) by treating it with a halogenating agent such as thionyl chloride (SOCl2) or oxalyl chloride (COCl2) in an inert solvent as described above, optionally in the presence of a catalytic amount of N,N-dimethylformamide (DMF) (Scheme 2).

[0218]

[0219] Option 2

[0220] The acylation reaction of carboxylic acids (such as compounds of formula (II)) with amines (such as compounds of formula (III)) is well known to those skilled in the art and is described, for example, in Eur. J. Org. Chem. [European Organic Chemistry] 2020, 4641-4651 and references cited therein, and is carried out by the methods described below.

[0221] Compounds of formula (II) are commercially available or can be prepared according to or in analogy to procedures described in the literature, for example, WO 2018 / 019929, Org. Proc. Res. Dev. 2020, 24(2), 228-234, WO 2018 / 019929, Lett. Org. Chem. 2010, 7(7), 502-507 and J. Het Chem. 2015, 52(6), 1823-1833.

[0222] A compound of formula (III) or a salt thereof (wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 and B 4 is as defined above for compounds of formula (I)) can be prepared by one skilled in the art by the reaction of a nitrile of formula (IV) wherein R1 、R 2 、R 3 、R 4 、B 1 、B 2 、B 3 and B 4 is prepared by reaction between a compound as defined above for the compound of formula (I) and a suitable nucleophile such as (dimethyl sulfide) borohydride (BMS) in a suitable aprotic solvent such as THF, for example as described in J. Org. Chem. 1981, 47, 3153. Alternatively, the Grignard reagent R 5 MgBr or R 6 MgBr (where R 5 and R 6 are as defined above for compounds of formula (I)) can be added sequentially or simultaneously as nucleophiles to compounds of formula (IV) to allow the preparation of more highly substituted amines of formula (III). i Such Grignard addition to nitrile is carried out in the presence of Pr)4) in an inert solvent such as diethyl ether, tert-butyl methyl ether and cyclopentyl methyl ether (see Synlett [Synthesis Letters] 2007, (4), 652-654). The reaction is shown in Scheme 3.

[0223]

[0224] Option 3

[0225] The compound of formula (IV) (wherein R 1 、R 2 、R 3 、R 4 、B 1 、B 2 、B 3 and B 4 is as defined above for compounds of formula (I)) can be prepared by those skilled in the art according to known methods. More specifically, compounds of formula (IV) and intermediates thereof can be prepared from compounds of formula (V) (Scheme 4).

[0226]

[0227] Option 4

[0228] For example, a compound having formula (IV) (R 1 、R 2 、R 3 、R 4 、B 1 、B 2、B 3 and B 4 is as defined above for compounds of formula (I), and R 4 Other than hydrogen) can be prepared by one skilled in the art by using a strong base (such as n-butyl lithium or sodium hydride) in an inert solvent (such as THF) at low temperature, followed by the addition of a suitable alkylating agent R 4 -X 0 (where X 0 is halogen) (eg iodomethane) and a compound of formula (IVa) (wherein R 4 is hydrogen, and R 1 、R 2 、R 3 、B 1 、B 2 、B 3 and B 4 is prepared by deprotonation of a compound of formula (IVa) wherein R 4 is hydrogen, and R 1 、R 2 、R 3 、B 1 、B 2 、B 3 and B 4 (as defined above for compounds of formula (I)) can be prepared from an alcohol of formula (V) by treatment with cyanotrimethylsilane (TMSCN) in the presence of a base (such as lithium carbonate) in a non-polar solvent (such as DCM) at a temperature between 0° C. and the boiling point of the reaction mixture. Such transformations are well known in the literature under various conditions, for example as described in Org. Lett. [Organic Chemistry Communications] 2008, 10, 4570 and references therein. The reaction is shown in Scheme 4.

[0229] Compounds of formula (V) can be prepared from compounds of formula (VI), prepared from any one of compounds of formula (VIa), (VIb), (VIc), (VId) or (VIe), respectively, as shown in Scheme 5.

[0230]

[0231] Option 5

[0232] As shown in Scheme 5, a compound of formula (VII) (wherein R 1 、R 2 and R 3 is as defined above for the compound of formula (I), and X 01is bromine or iodine) is metallated with a suitable reagent such as turbo Grignard reagent (isopropylmagnesium chloride-lithium chloride complex) or alkyllithium (such as n-butyllithium) to obtain an intermediate Grignard reagent or alkyllithium reagent (M is MgX 01 or lithium). Such metals are inserted into CX 01 The reaction of the metallated substance (VIIa) with the metallated substance (VIIa) is well known to those skilled in the art and is usually carried out at a temperature between -78°C and room temperature in an inert solvent such as an ether (e.g., tert-butyl methyl ether or THF). The solution of the metallated substance (VIIa) is then treated with (VIa), (VIb), (VIc), (VId), or (VIe) with a compound of formula (VI) to give a compound of formula (V). Similar reactions of this type have been described, for example, in WO 2012 / 102297 and Bio.Med.Chem.Lett. [Bioorganic and Medicinal Chemistry Express], 2017, 27(17), 4044-4050(X 01 is Br, n-butyllithium) and Ang.Chem., Int.Ed. [Applied Chemistry International Edition], 2016, 55(17), 5332-5336, US2014 / 0349990, WO 2002 / 004424, WO 2021 / 009068 (X 01 It is I, Turbo Grignard reagent).

[0233] Compounds of formula (VI) and (VII) are commercially available or readily prepared by methods known to those skilled in the art.

[0234] The further synthesis of the compound of formula (I) comprises treating the compound of formula (VIII) with a base such as sodium hydride or n-butyl lithium in an inert solvent such as THF and subsequently reacting with a compound of formula (IX) wherein R 4 is as described in formula (I), and X 02 is alkylated with a leaving group such as a halogen, mesylate or tosylate to produce a compound of formula (X).

[0235]

[0236] Option 6

[0237] The compound of formula (X) wherein R is then treated with a strong base such as sodium hydride or an alkyl lithium base such as n-butyl lithium in an inert solvent such as THF or tert-butyl methyl ether at a temperature between -78°C and room temperature. 1 、R 2 、R 3 and R 4is as defined above for the compound of formula (I), followed by the addition of a compound of formula (XI), any one of the compounds of formula (XIa), (XIb), (XIc), (XId) or (XIe), respectively (wherein R 9 、R 10 、R 11 and R 12 is as defined above for the compound of formula (I), and X 03 is a leaving group such as halogen, preferably F, Cl or Br) to give compounds of formula (IV) (Scheme 7).

[0238]

[0239] Option 7

[0240] As previously described in Schemes 1, 2 and 3, a compound of formula (IV) is converted to a compound of formula (I). One skilled in the art will recognize that the conversion of compound (VIII) to a compound of formula (IV) can be performed sequentially or in the same reaction vessel, enabling streamlined conversion of a compound of formula (VIII) to a compound of formula (IV). This is described in more detail in the Preparation Examples.

[0241] The compound of formula (Ia) (wherein R 1 、R 2 、R 3 、R 5 , Q, A 1 、A 2 、A 3 and Z 1 is as described above for the compound of formula (I), and R 4 and R 6 is hydrogen) can also be prepared by reacting a compound of formula (XII) (wherein R 5 (as described above for compounds with formula (I)) are treated with a compound with formula (VI), which is any one of the compounds of formula (VIa), (VIb), (VIc), (VId) or (VIe), to obtain a compound with formula (XIII). These compounds can be separated and converted into compounds with formula (XIV) by treating with anhydrides (such as trifluoroacetic anhydride) in an inert solvent (such as DCM) in the presence of a base (such as triethylamine). The reaction is shown in Scheme 8.

[0242]

[0243] Option 8

[0244] Those skilled in the art will appreciate that compounds of formula (VI) can be converted to compounds of formula (XIV) without the need to isolate the intermediate of formula (XIII). Such reactions (known as Henry reactions) are well described in the literature, as demonstrated in Tetrahedron. 2001, 57(6), 915-945 and references cited therein. Compounds of formula (XIV) can be converted to compounds of formula (XV) (Scheme 9) by treatment with a compound of formula (VIIa) in an inert solvent such as THF (see Scheme 5).

[0245]

[0246] Option 9

[0247] Similar Michael additions of organometallic compounds to nitroolefins have been reported, for example, in Org. Lett. [Organic Chemistry Communications] 2007, 9, 85-87. The nitro group in the compound of formula (XV) is reduced to an amine to give a compound of formula (IIIa) (wherein R 1 、R 2 、R 3 、R 5 、B 1 、B 2 、B 3 and B 4 is as defined above for compounds of formula (I), and R 4 and R 6 is hydrogen) can be achieved by various methods generally known to those skilled in the art, such as Bechamp reduction, or reduction with hydrogen in the presence of a metal catalyst (Scheme 10).

[0248]

[0249] Plan 10

[0250] Compounds of formula (IIIa) are converted to compounds of formula (Ia) by the methods described in Schemes 1 and 2.

[0251] Additional compounds according to the present invention may be prepared by derivatization using key central intermediates at subsequent stages of the synthesis. For example, a compound of formula (I) wherein B 1 It's CX 04 , B 2 It's CR 10 , B 3 It's CR 11 , B 4 It's CR 12 , R 1 、R2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for the compound of formula (I), and X 04 is halogen, preferably bromine or chlorine, i.e. a compound of formula (Ia):

[0252]

[0253] This allows for further chemical reactions such as palladium-catalyzed carbonylation, Suzuki reaction, Stiller coupling, copper-catalyzed introduction of sulfonyl, haloalkyl, and cyano moieties, and SnAr reactions with various nucleophiles. Examples of such reactions are shown in Scheme 11.

[0254]

[0255] Plan 11

[0256] As shown in Scheme 11, a compound having formula (Ia) (wherein B 1 It's CX 04 , B 2 It's CR 10 , B 3 It's CR 11 , B 4 It's CR 12 , and R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for compounds of formula (I), and R 9is a cyano group, i.e. a compound of formula (Ib) can be obtained from a compound of formula (Ia) by treatment with an inorganic cyanide source (e.g. CuCN) in an inert solvent (e.g. dimethylformamide (DMF) or N-methyl-2-pyrrolidone) at a temperature between 0°C and 150°C. Such reactions are well known in the literature, for example, in J. Het. Chem. [Journal of Heterocyclic Chemistry] 1987, 24(2), 373-6, Liebigs Ann. Chem. [Liebig Chemical Yearbook] 1994, (10), 1049-53, and Org. Prep. Proc. Int. [International Organic Preparation and Procedure] 1985, 17(6), 391-9. Other methods for introducing a cyano group by replacing a halogen atom are known in the art. See, for example, Science of Synthesis [Synthesis Science] 2004, 19, 173-195.

[0257] A compound of formula (I) (wherein B 1 It's CR 9a , B 2 It's CR 10 , B 3 It's CR 11 , B 4 It's CR 12 , and R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for compounds of formula (I), and R 9a is a C1-C4 haloalkyl group, i.e. a compound of formula (Ic)) can be prepared by reacting a compound of formula (XVI) (wherein R 9a is C1-C4 haloalkyl) to treat a compound of formula (Ia) (wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A2 、A 3 and Z 1 is as defined above for the compound of formula (I), and X 04 is halogen, preferably bromine). This type of reaction is known in the literature (Org. Lett. [Organic Chemistry Communications] 2014, 16 (6), 1744-1747). A compound of formula (I) (wherein B 1 It's CR 9b , B 2 It's CR 10 , B 3 It's CR 11 , B 4 It's CR 12 , and R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for compounds of formula (I), and R 9b wherein X is phenyl, 5-membered or 6-membered heteroaryl or C3-C6 cycloalkyl, wherein the 5-membered or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6 cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy, i.e., a compound of formula (Id)) can be prepared by a Suzuki reaction (as shown in Scheme 11), which comprises, for example, reacting a compound of formula (Ia) (wherein X is phenyl, 5-membered or 6-membered heteroaryl or C3-C6 cycloalkyl, wherein the 5-membered or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6 cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy 04 is a leaving group such as, for example, chloro, bromo or iodo) and a compound of formula (XVIIa) wherein Y b1 It may be a boron-derived functional group such as, for example, B(OH)2 or B(OR b1 )2, where R b1 Can be C1-C4 alkyl or two groups OR b1The reaction is carried out over a palladium-based catalyst (e.g., tetrakis(triphenylphosphine)-palladium or (1,1'-bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1:1 complex)) in the presence of a base (e.g., sodium carbonate or cesium fluoride) in a solvent or solvent mixture (e.g., a mixture of 1,2-dimethoxyethane and water, or dioxane and water, or methylTHF and water), preferably under an inert atmosphere. The reaction temperature may preferably range from room temperature to the boiling point of the reaction mixture. Such Suzuki reactions are well known to those skilled in the art and have been reviewed in, for example, J. Organomet. Chem. 1999, 576, 147-168.

[0258] Alternatively, the compound of formula (Ic) can be prepared by reacting the compound of formula (XVIIb) (wherein Y b2 The present invention can be prepared by the Stirler reaction of a trialkyltin derivative, preferably tri-n-butyltin, with a compound having formula (Ia). Such a Stirler reaction is carried out in the presence of a palladium catalyst (e.g., tetrakis(triphenylphosphine)palladium(0) or (1,1'-bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1:1 complex)), in an inert solvent (e.g., DMF, acetonitrile, or dioxane), optionally in the presence of an additive (e.g., cesium fluoride or lithium chloride), and optionally in the presence of another catalyst (e.g., copper(I) iodide). Such Stieler couplings are also well known to those skilled in the art and have been described, for example, in J. Org. Chem. 2005, 70, 8601-8604, J. Org. Chem. 2009, 74, 5599-5602, and Angew. Chem. Int. Ed. 2004, 43, 1132-1136. A large number of compounds of formula (XVIIa) and (XVIIb) are commercially available or can be prepared by those skilled in the art. Additional compounds obtainable from compounds of formula (Ia) are shown in Scheme 12.

[0259]

[0260] Plan 12

[0261] As shown in Scheme 12, a compound having formula (I) (wherein B 1 It's CX 04 , B 2 It's CR 10 , B 3 It's CR 11 , B 4 It's CR 12 , and R1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for the compound of formula (I), and X 04 is a leaving group such as, for example, chlorine, bromine or iodine, i.e. a compound of formula (Ia)) can be treated with a compound of formula (XVIII) under Stiller reaction conditions to give a compound of formula (Ie). The compound of formula (Ie) can be isolated or directly hydrolyzed under aqueous acidic conditions to give a compound of formula (If). Such reactions are known in the literature and have been described, for example, in Synthesis 2001, (10), 1551-1555 and Tetrahedron 2001, 57(13), 2507-2514. The reaction is carried out by reacting a compound of formula (XIX) (or a salt thereof) (wherein R 13 is hydrogen or C1-C4 alkyl) to treat a compound having formula (If) to convert the compound having formula (If) into a compound having formula (Ig) (wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for compounds of formula (I), and R 13 is hydrogen or C1-C4 alkyl). Many examples for the preparation of such oximes are known in the literature (see, for example, Molecules 2019, 24, 2470 and references cited therein) and are familiar to those skilled in the art.

[0262] The compound of formula (I) (wherein R 1 、R 2 、R 3 、R4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for the compound of formula (I), and X 04 Further compounds prepared by using a leaving group like for example chloro, bromo or iodo, ie compounds having formula (Ia), are shown in Scheme 13.

[0263]

[0264] Plan 13

[0265] As shown in Scheme 13, compounds of formula (Ia) can be carbonylated to give compounds of formula (I) (wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for compounds of formula (I), and R 14 is a C1-C4 alkyl group, i.e. a compound of formula (Ih). In such alkoxycarbonylation, an alcohol R is reacted with a phosphine ligand such as triphenylphosphine or 1,1'-bis(diphenylphosphino)ferrocene under pressure in the presence of a metal catalyst such as a palladium catalyst (e.g. palladium(II) acetate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)Pd(dppf)Cl2; bis(triphenylphosphino)dichloropalladium(II)PdCl2(PPh3)2 or bis(diphenylphosphino)propane]dichloropalladium(II)PdCl2(dippp)). 14 OH solvent (usually in methanol or ethanol) (where R 14is C1-C4 alkyl), optionally in the presence of a cosolvent (e.g. toluene, dioxane or N,N-dimethylformamide) and preferably in the presence of a base (e.g. trimethylamine) at a temperature between 20° C. and 200° C., preferably between 50° C. and 180° C. The compound of formula (Ia) is reacted with carbon monoxide. Such carbonylation reactions are well known to those skilled in the art and also in the literature (see J. Org. Chem. 2008, 73, 7102-7107 and references cited therein). Such compounds of formula (Ih) can be readily saponified to compounds of formula (Ii) under conditions known to those skilled in the art (e.g., aqueous sodium hydroxide, potassium hydroxide or lithium hydroxide in methanol, ethanol, THF or dioxane at room temperature or up to reflux). Alternatively, treatment of ester compounds of formula (Ih) with a halide anion (preferably chloride ion, for example derived from lithium chloride (or alternatively sodium chloride or potassium chloride)) in a solvent such as DMF, N,N-dimethylacetamide or N-methyl-2-pyrrolidone can also produce carboxylic acid compounds of formula (Ii). The reaction temperature for such O-demethylation preferably ranges from 20°C to the boiling point of the reaction mixture, or the reaction can be carried out under microwave irradiation. Compounds of formula (Ii) can be converted to amides of formula (Ij) wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for compounds of formula (I), and R 15 and R 16 are independently hydrogen or C1-C4 alkyl, ie compounds of formula (Ij). Such reactions typically involve activation of the carboxyl group followed by reaction with compound R 15 R 16 NH treatment or using a coupling agent with formula R 15 R 16 Direct conversion of the acid to the amide is then carried out by treatment of the NH compound. These methods have been discussed above in Schemes 1 and 2.

[0266] Compounds of formula (Ii) can be converted into compounds of formula (I) (wherein R 1 、R 2 、R 3 、R4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for compounds of formula (I), and R 9 is an amino group, i.e., a compound of formula (Ik)). In the Curtius rearrangement, a compound of formula (Ij) is treated with an organic azide in the presence of a suitable base, and optionally in the presence or absence of a Lewis acid, in an inert solvent at a temperature between 50°C and 200°C. Examples of organic azides include TMSN3, sodium azide, diphenylphosphoryl azide or tosyl azide, and a suitable solvent may be toluene, xylene, THF or acetonitrile. Examples of suitable Lewis acids may include, in particular, Zn(OTf)2. The isocyanate formed in the rearrangement reacts with water to form a carbamate, which decarboxylates under the reaction conditions to the corresponding amine of formula (lk). Alternatively, these reactions can be carried out in an alcohol (e.g., tert-butyl alcohol), thereby allowing the isolation of tert-butyl carbamate. These, in turn, can be cleaved in a separate step by methods known to those skilled in the art with an acid (e.g., trifluoroacetic acid) to produce a compound of formula (Ik). Examples of such Curtius reactions have been reported, for example, in Org. Lett. [Organic Chemistry Communications] 2005, 7, 4107-4110, J. Med. Chem. [Medicinal Chemistry Journal] 2006, 49 (12), 3614-3627 and Tetrahedron [Tetrahedron] 1974, 30, 2151-2157. The compound of formula (Ik) thus obtained can be amidated to a compound of formula (Im) (wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 10 、R 11 、R 12 、A 1 、A 2 、A 3 and Z 1 is as defined above for compounds of formula (I), and R 18 is C1-C4 alkyl). Those skilled in the art will recognize that this chemical reaction can be applied to any compound of formula (I) where R9 、R 10 、R 11 or R 12 position, when the following group is a leaving group such as a halogen atom.

[0267] Compounds of Formula (VI), (VII), (VIII), (IX), (XI), (XII), (XVI), (XVIIa), (XVIIb), (XIX) and (XX) are readily prepared by one skilled in the art or are commercially available.

[0268] A compound of formula (II) (wherein A 1 It's N, A 2 YesO,A 3 is CH, and Z 1 As described in formula (I), compounds having formula (IIc) can be prepared as shown in Scheme 14.

[0269]

[0270] Plan 14

[0271] As shown in Scheme 14, a compound of formula (IIc) wherein Z 1 is as above and X 05 is C1-C4 alkyl) can be prepared by hydrolyzing a compound of formula (IIb) with, for example, an alkaline earth metal hydroxide in water or with a water-miscible organic solvent (such as THF, methanol, ethanol, etc.). Such ester hydrolysis is well known to those skilled in the art. A compound of formula (IIb) can be prepared by treating a compound of formula (XXIII) (where Z is C1-C4 alkyl) with hydroxylamine hydrochloride in a polar solvent (such as ethanol) and optionally in the presence of a base (such as TEA, K2CO3, etc.). 1 is as defined above for the compound of formula (I), and X 05 is C1-C4 alkyl).

[0272] The compound of formula (XXIII) is prepared by making a compound of formula (XXI) (wherein Z 1 is as defined above for the compound of formula (I)) and a compound of formula (XXII) or a compound of formula (XXIIa) (wherein X 05(C1-C4 alkyl) is reacted in the presence of a base (such as potassium tert-butoxide, sodium cyanide or bis(trimethylsilyl)lithium amide) in a solvent (such as THF or toluene) to prepare. Reaction sequences similar to those for preparing compounds of formula (IIb) and (IIc) described in Scheme 14 are described in, for example, CN 111072582 and WO 2019 / 195810 and WO 2018 / 019929. Additional reaction conditions for preparing compounds of formula (XXIII) are described in, for example, Bioorg. & Med. Chem. 2016, 109, 350-359.

[0273] A compound of formula (II) (wherein A 1 YesO,A 2 and A 3 is N, and Z 1 As previously described, compounds of formula (IIe) can be prepared as shown in Scheme 15.

[0274]

[0275] Plan 15

[0276] As shown in Scheme 15, compounds of formula (IIe) are obtained by ester hydrolysis of compounds of formula (IId) as previously described in Scheme 14. Compounds of formula (IId) (wherein Z 1 is as defined in formula (I) and X 05 is C1-C4 alkyl) is prepared by reacting a compound of formula (XXIIa) with a compound of formula (XXIV) in a solvent (such as acetonitrile, chloroform or THF) optionally in the presence of a base (such as pyridine or triethylamine). Such reactions have been reported, for example, in Bioorg. & Med. Chem. [Bioorganic and Medicinal Chemistry] 2016, 24 (22), 5693-5701 and CN114933573. A compound of formula (XXIV) (wherein Z 1 (as defined above for compounds of formula (I)) can be obtained by treating a compound of formula (XXV) with hydroxylamine hydrochloride in the presence of a base (such as K2CO3 or Na2CO3) in a polar solvent (such as ethanol). The reaction can also be carried out using a solution of hydroxylamine in the absence of a base. Such reactions have been described, for example, in Bioorg. & Med. Chem. Lett. [Biological Organic and Medicinal Chemistry Express] 2020, 30 (21), 127508 and Bioorg. Med. Chem. Lett. [Biological Organic and Medicinal Chemistry Express] 2016, 26 (23), 5679-5684.

[0277] The compound of formula (XXIV) (wherein Z 1 is as defined above for the compound of formula (I)) can also be treated with potassium ferrocyanide trihydrate and hydroxylamine hydrochloride to treat a compound of formula (XXVI) wherein Z 1 is prepared by a Pd-catalyzed cyanation and amidoximation "one-pot" synthesis as defined above for compounds of formula (I), as described in, for example, Org. Biomol. Chem. 2015, 13(9), 2541-2545.

[0278] A compound of formula (II) (wherein A 1 and A 2 is N, and A 3 It is O and Z 1 is as previously described (ie, a compound of formula (IIg)), and A 1 and A 2 is N, and A 3 It is S and Z 1 is as previously described (ie compounds of formula (IIi)) can be prepared as shown in Scheme 16.

[0279]

[0280] Plan 16

[0281] As shown in Scheme 16, compounds of formula (IIg) and (IIi) are obtained by ester hydrolysis of (IIf) and (IIg), respectively. In the latter compound, X 05 and Z 1 Is as previously described. The compound with formula (IIf) is obtained from the compound with formula (IIf) by dehydration of the compound with formula (XXVII). The compound with formula (XXVII) is obtained by acylation of the hydrazide with the compound with formula (XXVIII) with the compound with formula (XXIIa). The sequence of such reactions producing oxadiazoles is well known to those skilled in the art. Similar reactions are described in Bioorg.Med.Chem.Lett. [Biological Organic and Medicinal Chemistry Express] 2005, 15, 1423-1428 and WO 2006 / 044617. The compound with formula (XXVII) can also be obtained by reacting an activated carboxylic acid with formula (XXIXa) (wherein Z 1 and X 05are as described previously and in Scheme 1, respectively) with a compound of formula (XXX). Compounds of formula (XXIXa) can be prepared from the corresponding acid of formula (XXIX) as described in Scheme 1. Such reactions are described, for example, in J. Prakt. Chem. 1985, 327, 109-116. Compounds of formula (IIh) can also be prepared from a common intermediate of formula (XXVII) (where Z 1 and X 05

[0065] The 2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-2-1 ...

[0282] A compound of formula (II) (wherein A 1 YesO,A 2 It's N, A 3 is a methine group, and Z 1 As previously described, compounds of formula (IIk) can be prepared, for example, as shown in Scheme 17.

[0283]

[0284] Plan 17

[0285] As shown in Scheme 17, compounds of formula (IIk) are readily obtained by hydrolysis of esters of formula (IIj) by methods known to those skilled in the art and as described above. Compounds of formula (IIj) can be obtained by reacting a compound of formula (XXXI) with a compound of formula (XXXII) in the presence of an oxidizing agent (e.g., (diacetoxyiodo)benzene or N-chlorosuccinimide) in an inert solvent (e.g., methanol or DMF). Such reaction sequences have been described, for example, in J. Het. Chem. [Journal of Heterocyclic Chemistry] 2013, 50(4), 774-780 and J. Chin. Chem. Soc. [Journal of the Chinese Chemical Society] 2007, 54(3), 643-652. Compounds of formula (XXXI) are readily prepared from compounds of formula (XXXIII) (wherein Z1 is as described in formula (I)) by treatment with hydroxylamine under conditions well known to those skilled in the art.

[0286] The compound of formula (I) as defined in any embodiment of the present invention can be converted into another compound as defined in any embodiment of the present invention in a manner known per se by replacing one or more substituents of the starting compound with another or other substituents according to the present invention in a conventional manner. It will also be understood by those skilled in the art that the compound of formula (I) can be further converted into another derivative of formula (I) by, for example, alkylation, nucleophilic substitution, elimination, C-C bond formation reaction in the presence of a metal catalyst, heteroatom-carbon bond formation in the presence of a metal catalyst, oxidation and reduction.

[0287] Depending on the reaction conditions and starting materials chosen as appropriate in the respective case, it is possible, for example, to replace only one substituent with another substituent according to the invention in one reaction step or to replace several substituents with other substituents according to the invention in one and the same reaction step.

[0288] The salts of the compounds of formula (I) can be prepared in a manner known per se. Thus, for example, acid addition salts of compounds of formula (I) are obtained by treatment with a suitable acid or a suitable ion exchange reagent, and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchange reagent.

[0289] Salts of compounds of formula (I) can be converted in a customary manner into the free compounds (I), acid addition salts (for example by treatment with suitable basic compounds or with suitable ion exchange reagents) and salts with bases (for example by treatment with suitable acids or with suitable ion exchange reagents).

[0290] Salts of compounds of formula (I) can be converted in a manner known per se into other salts, acid addition salts of compounds of formula (I), for example into other acid addition salts, for example by treating salts of inorganic acids (such as hydrochlorides) with suitable metal salts of the acid (such as sodium, barium or silver salts, for example with silver acetate) in a suitable solvent in which the inorganic salt formed (such as silver chloride) is insoluble and therefore precipitates from the reaction mixture.

[0291] Depending on the procedure or reaction conditions, compounds of formula (I) having salt-forming properties can be obtained in free form or in the form of salts.

[0292] The compounds of formula (I) and, where appropriate, their tautomers, in each case in free form or in salt form, may be present in the form of one of the possible isomers or as a mixture of these isomers, for example in the form of pure isomers (such as enantiomers and / or diastereomers) or as isomer mixtures (such as enantiomeric mixtures, for example racemates, or diastereomeric mixtures), depending on the number of asymmetric carbon atoms present in the molecule, the absolute and relative configuration and / or on the configuration of non-aromatic double bonds present in the molecule, the invention relating to the pure isomers and also to all possible isomer mixtures and is to be understood in this sense in every case above and below, even in every case without specific mention of stereochemical details.

[0293] Diastereomeric mixtures or racemic mixtures of compounds of formula (I) in free form or in salt form, the acquisition of which may depend on the starting materials and procedures chosen, can be separated in a known manner into the pure diastereomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and / or chromatography.

[0294] Enantiomeric mixtures obtainable in an analogous manner (e.g., racemates) can be resolved into the optical enantiomers by known methods, for example, by recrystallization from optically active solvents; by chromatography on chiral adsorbents, for example, high performance liquid chromatography (HPLC) on acetylcellulose; by cleavage with specific immobilized enzymes with the aid of suitable microorganisms; via the formation of containing compounds, for example, using chiral crown ethers, in which only one enantiomer is complexed; or by conversion into diastereomeric salts, for example, by reacting the basic end product racemate with an optically active acid (e.g., a carboxylic acid, for example, camphoric acid, tartaric acid or malic acid, or a sulfonic acid, for example, camphorsulfonic acid) and separating the diastereomeric mixtures obtainable in this way, for example, by fractional crystallization based on their different solubilities, thereby obtaining the diastereomers from which the desired enantiomer can be freed by the action of suitable reagents, for example, basic reagents.

[0295] Pure diastereomers or enantiomers can be obtained according to the invention not only by separation of the appropriate isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the method according to the invention with starting materials having the appropriate stereochemistry.

[0296] If the individual components have different biological activities, it is advantageous to isolate or synthesize the biologically more effective isomers, such as enantiomers or diastereomers or isomer mixtures, such as enantiomeric mixtures or diastereomeric mixtures, in each case.

[0297] As an example, compounds with more than one asymmetric carbon atom may exist as diastereoisomers, which may be separated optionally using, for example, supercritical fluid chromatography (SFC) chromatography with a chiral column. Such diastereoisomers may show different fungicidal activity profiles, but all isomers and diastereomers form part of the present invention.

[0298] The compound of formula (I) has at least two chiral carbon atoms (two stereocenters, wherein an asterisk (*) indicates a chiral carbon atom), so that there are at least four available stereoisomers. These at least four stereoisomers consist of two groups of enantiomers.

[0299]

[0300] For compounds of formula (I), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、A 1 、A 2 、A 3 、A 4 and Z 1 is as defined for compounds of formula (I), and wherein R 4 , and R 5 and R 6 At least one of the is not hydrogen, and the relationship between enantiomers and diastereomers is shown in Scheme 18.

[0301]

[0302] Plan 18

[0303] Those skilled in the art are well aware of the diastereomers and enantiomers of formula (I) as shown in Scheme 18 (wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、B 1 、B 2 、B 3 、B 4 、A 1 、A 2 、A 3 、A 4 and Z1 is as defined for formula (I), and wherein R 4 , and R 5 and R 6 at least one of which is not hydrogen) is within the scope of the present invention.

[0304] The compounds of formula (I) and, where appropriate, their tautomers (in each case in free form or in salt form) can, if appropriate, also be obtained in the form of hydrates and / or include other solvents, such as those which can be used for crystallization of compounds present in solid form.

[0305] As already indicated, surprisingly, it has now been found that the compounds of formula (I) according to the invention have, for practical purposes, a very advantageous level of biological activity for protecting plants from diseases caused by fungi.

[0306] Compounds with formula (I) according to the present invention can be used as active ingredients such as for controlling plant pests in the agricultural sector and related fields of use, or on non-living materials, for controlling spoilage microorganisms or organisms potentially harmful to people. The feature of these novel compounds is to have excellent activity, good plant tolerance and environmental safety under low application rates. They have very useful therapeutic, preventative and systemic characteristics and can be used to protect a lot of cultivated plants. Compounds with formula (I) can be used to suppress or destroy the harmful organism that occurs on the plant or plant part (fruit, flower, leaf, stem, tuber, root) of different useful plant crops, while also protecting those plant parts that grow later from the infringement of for example phytopathogenic microorganisms.

[0307] The present invention further relates to a method for controlling or preventing infestation of plants or plant propagation material and / or harvested food crops susceptible to attack by microorganisms by treating the plants or plant propagation material and / or harvested food crops, wherein an effective amount of a compound of formula (I) according to the invention is applied to the plants, parts thereof or the locus thereof.

[0308] It is also possible to use the compounds of formula (I) according to the present invention as fungicides. As used herein, the term "fungicide" means a compound that controls, modifies, or prevents the growth of fungi. The term "fungicidally effective amount" when used means an amount of such a compound or combination of such compounds that is capable of having an effect on the growth of fungi. The effects of control or modification include all deviations from natural development, such as killing, retardation, etc., and prevention includes the formation of a barrier or other defense in or on a plant to prevent fungal infection.

[0309] It is also possible to use the compound with formula (I) according to the present invention as a seed dressing for processing plant propagation materials (for example, seeds, such as fruits, tubers or grains) or plant cuttings, for protecting against fungal infections and against the phytopathogenic fungi present in the soil. Propagation materials can be processed with a composition comprising a compound with formula (I) before planting: for example, seed dressing can be used before sowing. The active compound with formula (I) can also be applied to grain (coating) by dipping seeds in a liquid formulation or by coating them with a solid formulation. When planting propagation materials, compositions can also be applied to the planting site, for example, to the furrow of seed during sowing. The invention further relates to such methods for processing plant propagation materials, and relates to the plant propagation materials so processed.

[0310] Furthermore, the compounds of formula (I) according to the invention can be used for controlling fungi in related fields, for example in the protection of industrial materials (including wood and wood-related technical products), in food storage, in hygiene management.

[0311] Additionally, the present invention can be used to protect non-living materials such as wood, wallboard, and paint from fungal attack.

[0312] The compounds of formula (I) according to the invention are effective, for example, against fungi and fungal vectors of diseases and phytopathogenic bacteria and viruses. These fungi and fungal vectors of diseases and phytopathogenic bacteria and viruses are, for example: Agaricus spp., Alternaria species, Aphanomyces species, Aspergillus species, Aspergillus species (including A. flavus, A. fumigatus, A. nidulans, A. niger, A. terreus), A. pullulans species (including A. pullulans), Blastomyces dermatitidis, B. graminis, B. oleraceus, B. lettuce, and B. oleraceus. lactucae), Botrytis species (including B. dothidea and B. obtusa), Botrytis species (including B. cinerea), Candida species (including C. albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, and C. tropicalis), Cephaloascus fragrans, Cephaloascus species, Cercospora species (including C. arachidicola), Cercosporidium personatum, Cladosporium species, Cergot, Coccidioides immitis, Coccidioidomyces species, Colletotrichum species (including C. musae), Corynespora species (including Corynespora cassiicola), Cryptococcus neoformans, Diaporthe species (including Diaporthe miriciae (also known as Diaporthe ueckeri or Diaporthe ueckerae)), Subsporus species, Entomophthora species, Entomophthora species, Epidermophyton species, Erwinia amylovora, Powdery Mildew species (including E. cichoracearum), Eutypa lata, Fusarium species (including Fusarium culmorum, Fusarium graminearum, F.langsethiae, Fusarium moniliforme, Fusarium gloeosporium, Fusarium solani, Fusarium oxysporum, Fusarium laminarum), wheat take-all pathogen (Gaeumannomyces graminis), Gibberella fujikuroi, Gloeodes pomigena, Gloeosporium musarum, Glomerella cingulate, Guignardia bidwellii, Gymnosporangium juniperi-virginianae, Helminthosporium species, H. capsulatum species, Histoplasma species (including H. capsulatum), red thread pathogen, Leptographium lindbergi, Leveillula taurica, Lophodermium seditiosum, Microdochium nivale), Microsporum species, Streptozoa species, Mucor species, Mycosphaeria species (including Mycosphaeria graminicola and M. pomi), Blight fungus, Spruce fungus, Paracoccidioides species, Penicillium species (including Penicillium digitatum and Penicillium italicum), True mold species, Downy mildew species (including Downy mildew of maize, Downy mildew of philippines, and Downy mildew of sorghum), Downy mildew species, Septoria glumene, Puccinia pachyrhizi, Phellinus igniarus, Phellaria species, Phoma species, Phomopsis viticola (Phomopsis graminicola), Phomopsis spp. viticola), Phytophthora species (including Phytophthora infestans), Plasmopara species (including Plasmopara hallii and P. viticola), Gastrosporium species, Pseudocercosporella species (including P. leucotricha), Polymyxa graminis, Polymyxabetae, Pseudocercosporella herpotrichoides, Pseudomonas species, Pseudoperonospora species (including Pseudoperonospora spp. and Pseudoperonospora spp.), Pseudopezi. za tracheiphila, Downy Mildew species (including barley rust (P.hordei), wheat leaf rust (P.recondita), stripe rust (P.Striiformis), wheat brown rust (P.triticina)), Sclerotinia species, Pythium species, Pythium species (including Pythium ultimum), Pythium species, Rhizoctonia species, Rhizoctonia microsporus (Rhizoctonia ulminata) zo muc o r pusillus), Rhizopus arrhizus, Rhizopus spp., Hyphomyces spp. (including Scedosporium apiosporum and Scedosporium prolificum), Schizontosis (Schi zo thyrium pomi), Sclerotinia species, Sclerotinia species, Septoria species (including S. nodorum, S. tritici), Sphaerotheca macularis, Sphaerotheca fusca (Sphaerotheca fuliginea), Sporothorix species, Stagonospora nodorum, Stemphylium species, Stereum hirsutum, Thanatephorus cucumeris, Thielaviopsis basicola, Tilletia species, Trichoderma species spp.) (including T. harzianum, T. pseudokoningii, T. viride), Trichophyton spp., Typhula spp., Uncinula necator, Urocystis spp., Ustilago spp., Venturia spp. (including V. inaequalis), Verticillium spp., and Xanthomonas spp.

[0313] The compounds of formula (I) according to the present invention can be used, for example, for lawns, ornamental plants such as flowers, shrubs, broad-leaved trees or evergreen plants such as pines, as well as for tree injection, pest management and the like.

[0314] Within the scope of the present invention, target crops and / or useful plants to be protected typically include perennial and annual crops, such as berry plants, for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals, for example barley, maize (corn), millet, oats, rice, rye, sorghum, triticale and wheat; fiber plants, for example cotton, flax, hemp, jute and sisal; field crops, for example sugar beets and fodder beets, coffee beans, hops, mustard, rapeseed (canola), poppies, sugar cane, sunflower, tea and tobacco; fruit trees, for example apples, apricots, avocados, bananas, cherries, citrus, nectarines, peaches, pears and plums; grasses, for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, black mulberry, citrus fruit ... Wheatgrass, St. Augustine grass, and zoysia grass; herbs such as basil, borage, chives, cilantro, lavender, lovage, mint, oregano, parsley, rosemary, sage, and thyme; legumes such as beans, lentils, peas, and soybeans; tree nuts such as almonds, cashews, groundnuts, hazelnuts, peanuts, pecans, pistachios, and walnuts; palms such as oil palms; ornamental plants such as flowers, shrubs, and trees; other trees such as cocoa, coconut, olive, and rubber trees; vegetables such as asparagus, eggplant, broccoli, cabbage, carrots, cucumbers, garlic, lettuce, zucchini, melon, okra, onions, peppers, potatoes, pumpkin, rhubarb, spinach, and tomatoes; and vines such as grapes.

[0315] The term "useful plants" is to be understood as also including useful plants which have been rendered tolerant to herbicides such as bromoxynil or classes of herbicides such as, for example, HPPD inhibitors, ALS inhibitors such as primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-acetone-shikimate-3-phosphate-synthetase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen oxidase) inhibitors as a result of conventional methods of breeding or genetic engineering. Examples of crops which have been rendered tolerant to imidazolinones such as imazamox by conventional methods of breeding (mutagenesis) are Summer rapeseed (canola). Examples of crops that have been rendered tolerant to herbicides or herbicides by genetic engineering methods include glyphosate-resistant and glufosinate-resistant maize varieties, which are based on Herculex and Commercially available under the trade name GLUTAMIDE.

[0316] The term "useful plants" is to be understood as also including useful plants which have been transformed by the use of recombinant DNA techniques in such a way that they are able to synthesize one or more selectively acting toxins, as are known, for example, from toxigenic bacteria, in particular those of the genus Bacillus.

[0317] Examples of such plants are: (corn variety expressing CryIA(b) toxin); YieldGard (corn variety expressing CryIIIB(b1) toxin); YieldGard (maize varieties expressing CryIA(b) and CryIIIB(b1) toxins); (corn variety expressing Cry9(c) toxin); Herculex (a corn variety expressing the CryIF(a2) toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) that confers tolerance to the herbicide glufosinate-ammonium); NuCOTN (cotton variety expressing CryIA(c) toxin); Bollgard (cotton variety expressing CryIA(c) toxin); Bollgard (cotton varieties expressing CryIA(c) and CryIIA(b) toxins); (cotton varieties expressing VIP toxin); (potato variety expressing CryIIIA toxin); GT Advantage (GA21 glyphosate tolerance trait), CBAdvantage (Bt11 corn borer (CB) trait), RW (corn rootworm trait) and

[0318] The term "crops" is to be understood as also including crop plants which have been transformed by the use of recombinant DNA techniques so as to enable them to synthesize one or more selectively acting toxins, such as are known, for example, from toxigenic bacteria, in particular those of the genus Bacillus.

[0319] Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus japonicus; or insecticidal proteins from Bacillus thuringiensis, such as delta-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C, or vegetative insecticidal proteins (Vips), for example Vip1, Vip2, Vip3, or Vip3A; or insecticidal proteins of nematode-parasitic bacteria, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophila, or Xenorhabdus spp. nematophilus); toxins produced by animals, such as scorpion toxins, spider toxins, bee toxins and other insect-specific neurotoxins; toxins produced by fungi, such as streptomycin, plant lectins, such as pea lectin, barley lectin or snowdrop lectin; agglutinin; protease inhibitors, such as trypsin inhibitors, serine protease inhibitors, potato glycoproteins, cysteine ​​protease inhibitors, papain inhibitors; ribosome inactivating proteins (RIPs), such as ricin, maize-RIP, abrin, luffain, saporin or bryophyllin; steroid metabolizing enzymes, such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysteroid inhibitors, HMG-COA-reductase, ion channel blockers, such as sodium channel or calcium channel blockers, juvenile hormone esterase, diuretic hormone receptor, stilbene synthase, bibenzyl synthase, chitinase and glucanase.

[0320] Further, in the context of the present invention, δ-endotoxins (e.g., Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C) or vegetative insecticidal proteins (Vips) (e.g., Vip1, Vip2, Vip3, or Vip3A) are understood to include, but are not limited to, mixed toxins, truncated toxins, and modified toxins. Mixed toxins are recombinantly produced by combining different domains of those proteins (see, e.g., WO 02 / 15701). Truncated toxins, such as truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of a naturally occurring toxin are replaced. In such amino acid substitutions, it is preferred that a non-naturally occurring protease recognition sequence be inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G recognition sequence is inserted into the Cry3A toxin (see WO 2003 / 018810).

[0321] Examples of such toxins or transgenic plants capable of synthesizing such toxins are disclosed in, for example, EP-0374753, WO 93 / 07278, WO 95 / 34656, EP 0427529, EP 0451878 and WO 03 / 052073.

[0322] Methods for producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95 / 34656, EP 0 367 474, EP 0 401 979 and WO 90 / 13651.

[0323] The toxins included in the transgenic plants render the plants tolerant to harmful insects. Such insects can be found in any insect taxonomic group but are particularly common among beetles (Coleoptera), two-winged insects (Diptera), and moths (Lepidoptera).

[0324] Transgenic plants comprising one or more genes encoding insecticide resistance and expressing one or more toxins are known and some of them are commercially available. Examples of such plants are: (corn variety expressing Cry1Ab toxin); YieldGard (corn variety expressing Cry3Bb1 toxin); YieldGard (corn varieties expressing Cry1Ab and Cry3Bb1 toxins); (corn variety expressing Cry9C toxin); Herculex (a corn variety expressing the Cry1Fa2 toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) that confers tolerance to the herbicide glufosinate-ammonium); NuCOTN (cotton variety expressing Cry1Ac toxin); Bollgard (cotton variety expressing Cry1Ac toxin); Bollgard (cotton varieties expressing Cry1Ac and Cry2Ab toxins); (cotton variety expressing Vip3A and Cry1Ab toxins); (potato variety expressing Cry3A toxin); GT Advantage (GA21 glyphosate tolerance trait), CB Advantage (Bt11 corn borer (CB) trait) and

[0325] Further examples of such genetically modified crops are:

[0326] 1. Bt11 maize, from Syngenta Seeds SAS, 27 Chemin de l'Hobit, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. This genetically modified maize is resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia inermis) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenicly expresses the PAT enzyme to confer tolerance to the herbicide glufosinate ammonium.

[0327] 2. Bt176 maize, from Syngenta Seeds, 27 Rue de Hobbitt, F-31 790 Saint-Sauveur, France, registration number C / FR / 96 / 05 / 10. This genetically modified maize is resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia inermis) by transgenic expression of the toxin Cry1Ab. Bt176 maize also transgenicly expresses the enzyme PAT to confer tolerance to the herbicide glufosinate ammonium.

[0328] 3. MIR604 maize, from Syngenta Seeds, 27 Rue de Hobbit, F-31790 Saint-Sauveur, France, registration number C / FR / 96 / 05 / 10. This maize plant is rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055, modified by insertion of a cathepsin G protease recognition sequence. The preparation of these transgenic maize plants is described in WO 2003 / 018810.

[0329] 4. MON 863 maize, from Monsanto Europe SA, 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C / DE / 02 / 9. MON 863 expresses the Cry3Bb1 toxin and confers resistance to certain coleopteran insects.

[0330] 5. IPC 531 cotton, from Monsanto Europe AB, 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C / ES / 96 / 02.

[0331] 6.1507 Zea mays, from Pioneer Overseas Corporation, Avenue Tedesco, 7B-1160 Brussels, Belgium, registration number C / NL / 00 / 10. Genetically modified maize expressing the protein Cry1F for resistance to certain lepidopteran insects and the protein PAT for tolerance to the herbicide glufosinate-ammonium.

[0332] 7. NK603×MON 810 maize, from Monsanto Europe, 270-272 Boulevard Tervuren, B 1150 Brussels, Belgium, registration number C / GB / 02 / M3 / 03. This is a conventionally bred hybrid maize variety, constructed by crossing the genetically modified varieties NK603 and MON 810. NK603×MON 810 maize is transgenic for the expression of the protein CP4 EPSPS obtained from the Agrobacterium strain CP4, rendering it herbicide tolerant. (contains glyphosate), and also Cry1Ab toxin from Bacillus thuringiensis subsp. kurstakia, which confers resistance to certain lepidopteran insects, including the European corn borer.

[0333] The compounds of formula (I) according to the invention can be used to control or prevent phytopathogenic diseases, in particular phytopathogenic fungi, such as Alternaria on fruits, vegetables and potatoes; Botrytis cinerea on strawberries, tomatoes, sunflowers, legumes, vegetables and grapes; Rhizoctonia solani on potatoes and vegetables; Uncinaria viticola on grapes; Cladosporium, bryozoans, powdery mildew and cucurbitaceae on cucurbits; Cercospora spp. on cucurbits and solanaceous crops; Fusarium spp. on cereals; Leptosphaeria spp. on cereals; and Saccharomyces spp. on cereals.

[0334] As used herein, the term "locus" means a place in or on which plants grow, or where seeds of cultivated plants are sown, or where seeds are to be placed in the soil. It includes soil, seeds, and seedlings, as well as established vegetation.

[0335] The term "plant" refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, leaves and fruit.

[0336] The term "plant propagation material" should be construed as meaning the reproductive parts of a plant, such as seeds, which can be used for the propagation of a plant, and vegetative materials, such as cuttings or tubers (e.g., potatoes). Examples of the term "plant propagation material" include seed (strictly speaking), root, fruit, tuber, corm, rhizome, and plant parts. Examples of the term "plant propagation material" include germinated plants and young plants that will be transplanted after germination or after emergence. These young plants can be protected before transplanting by being processed completely or in part by dipping. Preferably, "plant propagation material" should be construed as meaning a seed.

[0337] The compound with formula (I) according to the present invention can be used in unmodified form, or preferably, used together with the adjuvant conventionally adopted in the preparation field.For this purpose, they can be conveniently formulated as emulsifiable concentrates, pastes that can be coated, directly sprayable or dilutable solutions or suspensions, dilution emulsions, wettable powders, soluble powders, dusts, particles and also capsules, for example, in polymeric substances in a known manner.For the type of composition, according to the intended purpose and the environment at that time, application method is selected, such as spraying, atomizing, dusting, broadcasting, smearing or watering.Composition can also contain other adjuvants, such as stabilizers, defoamers, viscosity modifiers, adhesives or tackifiers, together with fertilizers, micronutrient donors or other preparations for obtaining special effects.

[0338] Suitable carriers and adjuvants, for example for agricultural use, can be solid or liquid and are substances useful in formulation technology, such as natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, adhesives or fertilizers. Such carriers are for example described in WO 1997 / 33890.

[0339] Suspension concentrates are aqueous formulations in which finely divided solid particles of the active compound are suspended. Such formulations contain anti-settling agents and dispersants and may further include wetting agents to enhance activity, as well as defoamers and crystal growth inhibitors. For use, these concentrates are diluted in water and typically applied as a spray to the area to be treated. The amount of active ingredient can range from 0.5% to 95% of the concentrate.

[0340] Wettable powders are in the form of finely divided particles that disperse readily in water or other liquid carriers. These particles contain the active ingredient enclosed in a solid matrix. Typical solid matrices include Fuller's earth, kaolin, silica, and other readily wettable organic or inorganic solids. Wettable powders typically contain from 5% to 95% active ingredient plus a small amount of a wetting agent, dispersant, or emulsifier.

[0341] Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquids and may consist entirely of the active compound and a liquid or solid emulsifier, or may also contain a liquid carrier such as xylene, heavy aromatic naphtha, isophorone, and other nonvolatile organic solvents. In use, these concentrates are dispersed in water or other liquids and typically applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.

[0342] Granular formulations include both extrudates and coarser granules and are typically applied undiluted to the area to be treated. Typical carriers for granular formulations include sand, Fuller's earth, attapulgite clay, bentonite, montmorillonite, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, crushed corn cobs, crushed peanut shells, sugar, sodium chloride, sodium sulfate, sodium silicate, sodium borate, magnesium oxide, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulfate, and other organic or inorganic materials that absorb or can be coated with the active compound. Granular formulations typically contain 5% to 25% active ingredient, which may include surfactants such as heavy aromatic naphtha, kerosene and other petroleum fractions, or vegetable oils; and / or adhesives such as dextrins, glues, or synthetic resins.

[0343] Dusts are free-flowing mixtures of the active ingredient with finely divided solids such as talc, clay, flour and other organic and inorganic solids which act as dispersants and carriers.

[0344] Microcapsules are typically droplets or particles of the active ingredient encapsulated within an inert porous shell that allows the encapsulated material to escape into the environment at a controlled rate. The encapsulated droplets typically have a diameter of 1 to 50 microns. The encapsulated liquid typically comprises 50% to 95% of the capsule's weight and may contain a solvent in addition to the active compound. The encapsulated particles are typically porous particles, with a porous membrane sealing the particle pores, retaining the active species in liquid form within the pores. The particle diameter typically ranges from 1 mm to 1 cm and preferably 1 mm to 2 mm. The particles are formed by extrusion, coagulation, or spheronization, or are naturally occurring. Examples of such materials include vermiculite, sintered clay, kaolin, attapulgite clay, sawdust, and carbon granules. Shell or membrane materials include natural and synthetic rubbers, fiber materials, styrene-butadiene copolymers, polyacrylonitrile, polyacrylates, polyesters, polyamides, polyureas, polyurethanes, and starch xanthate.

[0345] Other useful formulations for agrochemical applications include simple solutions of the active ingredient in a solvent (such as acetone, alkylated naphthalenes, xylene and other organic solvents) in which the active ingredient is completely soluble at the desired concentration. Pressurized sprays can also be used, in which the active ingredient is dispersed in finely divided form due to evaporation of a low-boiling dispersant solvent carrier.

[0346] Suitable agricultural adjuvants and carriers useful for formulating the compositions of the present invention in the above-mentioned formulation types are well known to those skilled in the art.

[0347] Liquid carriers that can be used include, for example, water, toluene, xylene, naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol rosin acid ester, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl Formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, dipropylene glycol (diproxitol), alkyl pyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, α-pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glycerol diacetate, glycerol monoethyl Acid esters, triacetin, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, dichloromethane, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyol Ethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols (such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc.), ethylene glycol, propylene glycol, glycerol, and N-methyl-2-pyrrolidone. Water is generally the carrier of choice for dilution of concentrates.

[0348] Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaxeous earth, lime, calcium carbonate, bentonite, Fuller's earth, cottonseed hulls, wheat flour, soy flour, pumice, wood flour, walnut shell flour, and lignin.

[0349] A wide range of surfactants are advantageously employed in the liquid and solid compositions, especially those designed to be diluted with a carrier prior to application. These agents, when used, typically comprise 0.1% to 15% by weight of the formulation. They may be anionic, cationic, nonionic, or polymeric in nature and may serve as emulsifiers, wetting agents, suspending agents, or for other purposes. Typical surfactants include alkyl sulfates, such as diethanolammonium lauryl sulfate; alkylaryl sulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C.sub.18 ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol-C.sub.16 ethoxylate; soaps, such as sodium stearate; alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; salts of dialkyl sulfosuccinates, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and dialkyl phosphates.

[0350] Other adjuvants commonly used in agricultural compositions include crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet regulators, pigments, antioxidants, foaming agents, defoamers, opacifiers, compatibilizing agents, antifoaming agents, masking agents, neutralizing and buffering agents, corrosion inhibitors, dyes, flavor enhancers, spreading agents, penetration aids, micronutrients, emollients, lubricants, and fixatives.

[0351] In addition, further, other biocidal active ingredients or compositions can be combined with the composition of the present invention and used in the method of the present invention and applied simultaneously or sequentially with the composition of the present invention. When applied simultaneously, these other active ingredients can be formulated or mixed in, for example, a spray tank together with the composition of the present invention. These other biocidal active ingredients can be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and / or plant growth regulators.

[0352] The pesticides mentioned herein using their common names are known, for example, from “The Pesticide Manual”, 15th edition, British Crop Protection Council 2009.

[0353] In addition, the compositions of the present invention may also be administered with one or more inducers of systemic acquired resistance ("SAR" inducers). SAR inducers are known and described, for example, in U.S. Pat. No. 6,919,298 and include, for example, salicylates and the commercial SAR inducer acibenzolar-S-methyl.

[0354] The compounds of formula (I) according to the present invention are usually used in the form of agrochemical compositions and can be applied to crop areas or crops to be treated simultaneously or sequentially with other compounds. For example, these other compounds can be fertilizers or micronutrient donors or other preparations that affect plant growth. They can also be selective herbicides or non-selective herbicides, together with insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with other carriers, surfactants or adjuvants commonly used in the formulation field to promote application.

[0355] The compounds of formula (I) according to the invention can be used in the form of (fungicide) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredients at least one compound of formula (I) or at least one preferred individual compound as defined herein (in free form or in the form of an agrochemically usable salt) and at least one of the above-mentioned adjuvants.

[0356] Therefore, the present invention provides a composition, preferably a fungicidal composition, comprising at least one compound of formula (I) according to the present invention, an agriculturally acceptable carrier and optionally an adjuvant. An agriculturally acceptable carrier is, for example, a carrier suitable for agricultural use. Agricultural carriers are well known in the art. Preferably, in addition to comprising a compound of formula (I), the composition may comprise at least one or more pesticidal active compounds, such as additional fungicidal active ingredients.

[0357] The compound with formula (I) according to the present invention can be the sole active ingredient of composition, or it can be mixed with one or more other active ingredients (such as pesticides, fungicides, synergists, herbicides or plant growth regulators) when appropriate.In some cases, other active ingredients can produce unexpected synergistic activity.

[0358] Examples of suitable additional active ingredients include the following: acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, aniline fungicides, antibiotic fungicides, aromatic fungicides, arsenic-containing fungicides, arylphenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged biphenyl fungicides, carbamate fungicides, phenylcarbamate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphorus fungicides, Organotin fungicides, oxathiin fungicides, oxazole fungicides, phenylsulfamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobilurin fungicides, sulfonanilide fungicides, thiadiazole fungicides, thiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides, triazolopyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.

[0359] Examples of suitable additional active ingredients include the following: petroleum, 1,1-bis(4-chlorophenyl)-2-ethoxyethanol, 2,4-dichlorophenylbenzenesulfonate, 2-fluoro-N-methyl-N-1-naphthylacetamide, 4-chlorophenylphenyl sulfone, acetofenapyr, aldicarb, sirox, fosfoline, amitriptyline, amitriptyline hydrogen oxalate, amitraz, arsenic trioxide, azobenzene, azophos, benomyl, benoxafos, benzyl benzoate, Bixafen, bromethrin, bromophenoxate, bromophos, bromopyralid, buprofezin, butacarb, butacarb, butylpyridaben, calcium polysulfide, octachlorocamphene, chlormethoxam, trithion, cypermethrin, chlorpyrifos, chlordimeform, chlordimeform hydrochloride, chlorfenapyr, chlorfenapyr, chlorfenapyr, ethyl chlorfenapyr, chlorfenapyr (chloromebuform), chlorfenapyr, propyl chlorfenapyr, chlorfenapyr, chlorfenapyr I, chlorfenapyr II, chlorfenapyr, closantel, coumaphos , crotamiton, baclofos, thiophanate, fruit insect phosphorus, DCPM, DDT, dinapron, dinapron-O, dinapron-S, demex-methyl, demex-O, demex-O-methyl, demex-S, demex-S-methyl, demex-S-methyl sulfone, bacteriostatic, dichlorvos, dicliphos, dichlorvos, dimethoate, methylphos, dinex, dinex-diclexine, diclofenac-4, Diclofenac-6, diclofenac, nitropentyl, nitrooctyl, nitrobutyl, dimethoate, sulfodiphenyl, disulfiram, DNOC, dofenapyn, doramectin, fenoxaphos, eprinomectin, thiophos, ethiophos, cypermethrin, fenbutatin, fenthiocarb, fenpyrad, fenpyrad-8, fenpyrad-9, fentrifanil, fluazifop-butyl, flufenoxuron, fluazifop-1, flufenoxuron, fluazifop-1, flufenoxuron, FMC 1137, fenvalerate, fenvalerate hydrochloride, formparanate, γ-HCH, chlorpyrifos, benzyl methoxyfen, hexadecyl cyclopropanecarboxylate, isocarbophos, jasmonate I, jasmonate II, iodine, lindane, propanil, cypermethrin, dithiophos, methylthiophene, fenvalerate, methyl bromide, mefenvalerate, chlorpyrifos, milbemid oxime, propylamine, monocrotophos, maltodextrin, moxidectin, naled, 4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3 -pyridyl) methoxy] pyridazin-3-one, fluazifop, nikkomycin, pentocyanamide, pentocyanamide 1:1 zinc chloride complex, omethoate, isothiocarb, sulfone, pp'-DDT, parathion, permethrin, fenthion, phosalone, thiophanate, phosphamidon, polychloroterpenes, polynactins, prochlorperazine, cypermethrin, propoxur, ethidium thiophanate, pyrethrin I, pyrethrin II, pyrethrin, pyridazithion, pyrimithiophos,Quinalphos, quintiofos, R-1492, glyphosate, rotenone, octamidine, clomartin, selamectin, threon, SSI-121, sulfluramid, sulfotep, sulfur, fluazifop, t-fluvalinate, TEPP, terbucarb, tetrachlorvinphos, thiafenox, pyrimidine, chlorpyrifos, methyl sulfophos, chlorpyrifos, thiafenox, thiafenox, thiafenox, thiafenox, thiafenox-methyl, chlorpyrifos, thiafenox, triazophos, triazuron, triclopyrox, triamcinol, aphidoxine, vaniliprole, bethoxazin, copper dioctanoate, copper sulfate, cybutryne, dichloronaphthoquinone, dichlorophen , mycophenolic acid, triphenyltin, slaked lime, sodium mancozeb, quinone, quinone, simazine, triphenyltin acetate, triphenyltin hydroxide, phosphine, piperazine, thiophanate, chloralose, fenthion, pyridin-4-amine, strychnine, 1-hydroxy-1H-pyridine-2-thione, 4-(quinoxalin-2-ylamino)benzenesulfonamide, 8-hydroxyquinoline sulfate, bronopol, copper hydroxide, cresol, dispyrithione, dodixan, sodium sulfone, formaldehyde, mercury phenanthene, kasugamycin, kasugamycin hydrochloride hydrate, nickel bis(dimethyldithiocarbamate), trichloromethylpyridine, octhiothione, oxolinic acid, oxytetracycline, hydroxyquinoline potassium sulfate, thiabendazole, streptomycin, streptomycin sesquisulfate, chlorothiazide, thimerosal, cotton brown-banded tormentor GV, Agrobacterium radiobacterium, Amblyseius species (Amblyseius spp.), celery armyworm (NPV), Anagrus atomus, Aphelinus abdominalis, Aphidius colemani, Aphidoletes aphidimyza, Spodoptera falciparum (NPV), Bacillus sphaericus Neide, Beauveria brongniartii, Chrysoperla carnea, Cryptolaemus montrouzieri, codling moth (GV), Dacnusa sibirica, Diglyphus isaea, Encarsia formosa, Eretmocerus eremicus, Heterorhabditis bacteriophora) and Heterorhabditis megidis, Hippodamia convergens,Leptomastix dactylopii, Macrolophus caliginosus, cabbage looper (NPV), Metaphycus helvolus, Metarhizium anisopliae var. acridum, Metarhizium anisopliae var. anisopliae, Neodiprion sertifer (NPV) and Neodiprion lecontei (NPV), species of the genus Pseudomonas, Paecilomyces fumosoroseus, Phytoseiulus persimilis, Steinernema bibionis, Steinernema carpocapsae ... glaseri), Steinernema riobrave, Steinernema riobravis, Steinernema scapterisci, Steinernema spp., Trichogramma species, Typhlodromus occidentalis, Verticillium lecanii, apholate, bisazir, busulfan, dimatif, hemel, hemp, metepa, methiotepa, methylapholate, morzid, penfluron, tepa, thiohemp a), thiotiba, trothamide, urethaneimine, (E)-dec-5-en-1-yl acetate and (E)-dec-5-en-1-ol, (E)-tridec-4-en-1-yl acetate, (E)-6-methylhept-2-en-4-ol, (E,Z)-tetradec-4,10-dien-1-yl acetate, (Z)-dodec-7-en-1-yl acetate, (Z)-hexadec-11-enal, (Z)-hexadec-11-en-1-yl acetate, (Z)-hexadec-13-en-11-yn-1-yl acetate, (Z)-eicos-13-en-10-one, (Z)-tetradec-7-en-1-al,(Z)-tetradec-9-en-1-ol, (Z)-tetradec-9-en-1-yl acetate, (7E,9Z)-dodec-7,9-dien-1-yl acetate, (9Z,11E)-tetradec-9,11-dien-1-yl acetate, (9Z,12E)-tetradec-9,12-dien-1-yl acetate, 14-methyloctadec-1-ene, 4-methylnon-5-ol and 4-methylnon-5-one, α-polystyrene, western pine beetle aggregation pheromone, dodecadienol, kodamine, pyrrolidone, epoxynonadecane, dodec-8-en-1-yl acetate, dodec-9-en-1-yl acetate, dodec-8,10-dien-1-yl acetate, dominic Luer (domin icalure), ethyl 4-methyloctanoate, eugenol, southern pine beetle aggregation pheromone, trap-ene mixture, trap-ene mixture I, trap-ene mixture II, trap-ene mixture III, trap-ene mixture IV, hexane attractant, tooth beetle dienol, small beetle alcohol, scarab sex attractant, trimethyldioxytricyclononane, moth attractant (litlure), cabbage looper sex attractant, trap-ene ester, montomocic acid (megatomoic acid), trap-ene ether, trap-ene, octadec-2,13-dien-1-yl acetate, octadec-3,13-dien-1-yl acetate, Hekangbi, coconut rhinoceros beetle aggregation pheromone, non-lecon, trap-ene ring, sordidin, fungi-eating acetone, tetradec-11-ene -1-Aminoacetate, Mediterranean fruit fly attractant, Mediterranean fruit fly attractant A, Mediterranean fruit fly attractant B1, Mediterranean fruit fly attractant B2, Mediterranean fruit fly attractant C, trunc-call, 2-(octylthio)ethanol, butopyronoxyl, butoxy(polypropylene glycol), dibutyl adipate, dibutyl phthalate, dibutyl succinate, DEET, dimethylcarbate, dimethyl phthalate, ethyl hexanediol, hexamide, methoquin-butyl, methylneodecanamide, oxamates ate), picaridin, 1-dichloro-1-nitroethane, 1,1-dichloro-2,2-di(4-ethylphenyl)ethane, 1,2-dichloropropane and 1,3-dichloropropylene, 1-bromo-2-chloroethane, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate, 2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate, 2-(2-butoxyethoxy)ethyl thiocyanate, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate, 2-(4-chloro-3,5-xylyloxy)ethanol, 2-chlorovinyl diethyl phosphate,2-Imidazolidinone, 2-isovalerylindan-1,3-dione, 2-methyl(prop-2-ynyl)aminophenylmethylcarbamate, 2-thiocyanatoethyl laurate, 3-bromo-1-chloroprop-1-ene, 3-methyl-1-phenylpyrazol-5-yldimethylcarbamate, 4-methyl(prop-2-ynyl)amino-3,5-dimethyltoluenemethylcarbamate, 5,5-dimethyl-3-oxocyclohex-1-enyldimethylcarbamate, acethion, acrylonitrile, aldrin, alloamicin, cypermethrin, α-cyfluthrin, aluminum phosphide, cypermethrin, neonicotinoids, ethylmethidathion, methylpyrifos, Bacillus thuringiensis delta-endotoxin, barium hexafluorosilicate, barium polysulfide, cypermethrin, Bayer 22 / 190, Bayer 22408, β-cyfluthrin Ester, beta-cypermethrin, bioethanomethrin, biopermethrin, bis(2-chloroethyl) ether, borax, bromophenazone, bromo-DDT, cypermethrin, chlordane, butathiofos, butathiofos, calcium arsenate, calcium cyanide, carbon disulfide, carbon tetrachloride, cypermethrin hydrochloride, cevadine, borneol, chlordane, chlordecone, chloroform, chloropicrin, chloranilphos, chlorprazophos, cis-resmethrin, cismethrin, clocythrin, copper acetylarensite, copper arsenate, copper oleate, coumithoate, cryolite, CS 708, benzonitrile, cypermethrin, cypermethrin, d-methrin, DAEP, dazomethon, decarbofuran, diamidafos, isochlor, dimethoate, dicresyl, cypermethrin, dieldrin, diethyl 5-methylpyrazol-3-yl phosphate, dilor, tetrafluthrin, demicarb, pyrethrin, methyl chlorpyrifos, difenocarb, propanol, pentotropol, dinoseb, fenpyroxen, vesiculophos, thiopyrafos, DSP, ecdysterone, EI 1642, EMPC, EPBP, Oxfordshire etaphos, ethiofencarb, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, EXD, fenthion, ethiofencarb, fenitrothion, fenoxacrim, cypermethrin, fenthion, ethyl fenthion, flucofuron, butylfenthion, phosphamidon, butylfenthion, furathiocarb, pyrethroid, guanidine salt, guanidine acetate, sodium tetrathiocarbonate, halfenprox, HCH, HEOD, heptachlor, cypermethrin, quinolinic acid, IPSP, chlorfenapyr, carbofuran, isodrin, isofenphos, transplanting agent, rice blast, oxathion, juvenile hormone I, juvenile hormone II, juvenile hormone III,Chlorpentyl, methoprene, lead arsenate, bromophenophos, pyralid, thiathiophos, m-cumyl methylcarbamate, magnesium phosphide, phosphorus azide, methyl thiamethoxam, thiamethoxam, mercurous chloride, methyl sulfoxide, metamifene, metamifene potassium salt, metamifene sodium salt, methylsulfonyl fluoride, butenamidophos, methoprene, methoxychlor, methyl isothiocyanate, methyl chloroform, dichloromethane, chlorpyrifos, mirex, naphthiophos, naphthalene, NC-170, nicotine, sulfuric acid Nicotine, nithiazine, pronicotine, O-5-dichloro-4-iodophenyl O-ethylethylphosphonothioate, O,O-diethyl O-4-methyl-2-oxo-2H-benzopyran-7-ylphosphonothioate, O,O-diethyl O-6-methyl-2-propylpyrimidin-4-ylphosphonothioate, O,O,O',O'-tetrapropyl dithiopyrophosphate, oleic acid, p-dichlorobenzene, methyl parathion, pentachlorophenol, pentachlorophenyl laurate, PH 60-38, fenthion, parachlorothion, phosphine, methyl phoxim, methamidophos, polychlorinated dicyclopentadiene isomers, potassium arsenite, potassium thiocyanate, precocious phosphazene I, precocious phosphazene II, precocious phosphazene III, amidothrin, fluthrin, fenthiocarb, prothiophos, pyraclostrobin, anti-pyrethroids, quassia extract, quinalphos-methyl, fenthiocarb, iodosamide, resmethrin, rotenone, thiamethoxam, ryanodine, sabadilla, octamidine, chlorpyrifos Dan, SI-0009, thiopropionitrile, sodium arsenite, sodium cyanide, sodium fluoride, sodium hexafluorosilicate, sodium pentachlorophenol, sodium selenate, sodium thiocyanate, sulcofuron, sulcofuron-sodium, sulfuryl fluoride, thioprolin, tar, thiabendazim, TDE, butylpyrimidinphos, temephos, cypermethrin, tetrachloroethane, thiochlorvos, cypermethrin, cypermethrin oxalate, cypermethrin, cypermethrin sodium, tralomethrin, trans-permethrin, aphid Wei, trichlormetaphos-3, chlorpyrifos, chlorpyrifos, trifluoromethoxycarb (tolprocarb), chlorpyrifos-butyl, methoprene, veratridine, veratridine, XMC, zetamethrin, zinc phosphide, tolfenphos, chlorfluanid, tetrafluanid, bis(tributyltin) oxide, bromoacetamide, iron phosphate, niclosamide-ethanolamine, tributyltin oxide, pyrimorph, snail killer, 1,2-dibromo-3-chloropropane, 1,3-dichloropropylene, 3,4-dichlorotetrahydrothiophene 1,1-dioxide, 3-(4-chlorophenyl)-5-methylrhodanine, 5-methyl-6-thioxo-1,3,5-thiadiazin-3-yl acetic acid, 6-isopentenylaminopurine, anisiflupurin, benclothiaz, cytokinin, DCIP, furfural, isamidophos, kinetin, verrucous myroculitis composition, tetrachlorothiophene, xylenol, zeatin,Potassium ethyl xanthate, acibenzolar, acibenzolar-S-methyl, Reynoutria sachalinensis extract, α-chlorohydrin, antoconazole, barium carbonate, dimethoate, brodifacoum, bromethalin, bromethalin, chlorfenapyr, cholecalciferol, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, calciferol, fludioxaline, fluoroacetamide, fludioxaline, fludioxaline hydrochloride, fludioxaline, fludioxaline, phosphorus, fludioxaline, fludioxaline, scilla glycosides, sodium fluoroacetate, thallium sulfate, warfarin, 2-(2-butoxyethoxy)ethyl piperate, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone, farnesol with nerolidol, synergistic alkynyl ether, MGK 264, piperonyl butoxide, piperonyl aldehyde, propylisomer, S421, synergistic powder, sesasmolin, sulfoxide, anthraquinone, copper naphthenate, copper oxychloride, dicyclopentadiene, salamine, zinc naphthenate, zinc ziram, imanin, ribavirin, clorindole hydrazide, mercuric oxide, thiophanate-methyl, azaconazole, bifenthionol, fuconazole, cyproconazole, difenoconazole, diniconazole, flufenoxam, fenbuconazole, fluquinconazole, flusilazole, flutriafol, furapyramide, hexaconazole, imazalil, imipenem, picronil, metconazole , myclobutanil, paclobutrazol, pyrifenox, penconazole, prothioconazole, pyrifenox, prochloraz, propiconazole, pyraclostrobin, simeconazole, tebuconazole, fluconazole, triadimefon, triadimenol, triflumizole, trimethirimol, pyrimidine, chlorfenapyr, flufenapyr, bupirimate, dimethirimol, ethirimol, dodecacyclic morpholine, fenpropidin, fenpropimorph , spiroxafil, tridemorph, cyprodinil, pyraclostrobin, pyrimethanil; fenpiclonil, fludioxonil, benalaxyl, furaxyl, metalaxyl, R metalaxyl; furamide, oxadixyl, carbendazim, debacarb, thiabendazole, chlozolinate, dichlozoline, myclozoline, procymidone (procymidone), vinclozoline, boscalid, carboxin, methylfuran, flutolanil, oxamyl, carboxin, penthiopyrad, thiofuran, dodine, biguanide, azoxystrobin, enestroburin, enestroburin, flutoxanil, fluoxastrobin, kresoxim-methyl, oxazolidinone, trifloxystrobin, trifloxystrobin, pyraclostrobin,Pyraclostrobin, pyraclostrobin, ferbam, mancozeb, maneb, maneb, methanone, propineb, maneb, captol, captan, pyraclostrobin, folpet, tolylfluanid, Bordeaux mixture, copper oxide, mancozeb, quinoline copper, phthalostrobin, kefansan, chlorfenapyr, chlorfenapyr, tolclofos-methyl, difop-butyl, benzthiopyrad, blasticidin-S, chloroneb, chlorothalonil, cyfluanid, cymoxanil, cyclobutrifluram, diclocymet, diclomezine, dicloran, diethofencarb , dimethomorph, flumorph, dithianon, ethaboxam, etridiazole, famoxadone, fenamidone, fenoxanil, ferimzone, fluazinam, flumetylsulforim, fluopicolide, fluoxytioconazole, flusulfamide, flupyroxamide, fenamoxadone, fosetylaluminium, oxamoxadone hymexazol, propineb, cyazofamid, methasulfocarb, methaquinone, pencycuron, phthalides, polyoxins, propamocarb, pyrimidine, proquinazid, pyroquilon, pyriofenone, quinoxyfen, pentachloronitrobenzene, thiazide, triazoxide, tricyclazole, triazine, validamycin, valerian, zoxamide, mandipropamid , flubeneteram, isopyrazam, sedaxane, benzovinflumizone, fluoxazoline hydroxylamine, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro-biphenyl-2-yl)-amide, isoflurane, isothiocyanate, dipymetitrone, 6-ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithiino[1,2-c]isothiazole-3-carbonitrile, 2-(difluoromethyl)-N-[3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide,4-(2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazine-3-carbonitrile, (R)-3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide, 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine, 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, fluindapyr, jiaxiangjunzhi, lvbenmixianan, dichlobenzole entiazox), mandestrobin, 3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone, 2-[2-fluoro-6-[(8-fluoro-2-methyl-3-quinolinyl)oxy]phenyl]propan-2-ol, oxathiapiprolin, tert-butyl N-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridinyl]carbamate, pyraziflumid, inpyrfluxam, trolprocarb, clofoconazole, isotrifluanid ipfentrifluconazole, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide, N'-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine, N'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine, [2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chloro-phenyl] methanesulfonate, N-[6-[[( Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridinyl]carbamic acid but-3-ynyl ester, N-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamic acid methyl ester, 3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine, flubendiamide (pyridachlometyl), 3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide, 1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methyl-phenyl]-4-methyl-tetrazol-5-one,1-Methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]tetrazol-5-one, aminopyrifen, pyraclostrobin, indazolesulfamide, fluopicolide, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide, florylpicoxamid, benzylpyrimidine Fenpicoxamid, metarylpicoxamid, tebufloquin, ipflufenoquin, quinofumelin, isofetamidoamine, 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolane-2-yl]methoxy]phenyl]methyl]pyrazole-3-carboxylic acid ethyl ester (can be made from WO 2020 / 056090), ethyl 1-[[4-[(Z)-2-ethoxy-3,3,3-trifluoro-prop-1-enyloxy]phenyl]methyl]pyrazole-3-carboxylate (can be prepared by the method described in WO 2020 / 056090), methyl N-[[4-[1-(4-cyclopropyl-2,6-difluoro-phenyl)pyrazol-4-yl]-2-methyl-phenyl]methyl]carbamate (can be prepared by the method described in WO 2020 / 097012), methyl N-[[4-[1-(2,6-difluoro-4-isopropyl-phenyl)pyrazol-4-yl]-2-methyl-phenyl]methyl]carbamate (can be prepared by the method described in WO 2020 / 097012), 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)-N-[2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (which can be prepared by the method described in WO 2020 / 109391), 6-chloro-N-[2-(2-chloro-4-methyl-phenyl)-2,2-difluoro-ethyl]-3-(3-cyclopropyl-2-fluoro-phenoxy)-5-methyl-pyridazine-4-carboxamide (which can be prepared by the method described in WO 2020 / 109391), 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)-N-[2-(3,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (which can be prepared by the method described in WO 2020 / 109391). 2020 / 109391), N-[2-[2,4-dichloro-phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide, N-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide, thiocyanatomycin, cyanocyanatomycin,5-Amino-1,3,4-thiadiazole-2-thiol zinc salt (2:1), fluopyram, flufenoxadiazam, fluthiazolin, fluopyram, pyrapropoyne, picarbutrazox, 2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indan-4-yl)pyridine-3-carboxamide, 2-(difluoromethyl) -N-((3R)-1,1,3-trimethylindan-4-yl)pyridine-3-carboxamide, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile, metyltetraprole, α-(1,1-dimethylethyl)-α-[4'-(trifluoromethoxy)[1, 1'-diphenyl]-4-yl]-5-pyrimidinemethanol, fluoxapiprolin, enoxastrobin, (Z)-3-methoxy-2-[2-methyl-5-[4-(trifluoromethyl)triazol-2-yl]phenoxy]prop-2-enoic acid methyl ester, (Z)-3-methoxy-2-[2-methyl-5-(4-propyltriazol-2-yl)phenoxy]prop-2-enoic acid methyl ester , (Z)-2-[5-(3-isopropylpyrazol-1-yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoic acid methyl ester, (Z)-3-methoxy-2-[2-methyl-5-(3-propylpyrazol-1-yl)phenoxy]prop-2-enoic acid methyl ester, (Z)-3-methoxy-2-[2-methyl-5-[3-(trifluoromethyl)pyrazol-1-yl]phenoxy]prop-2-enoic acid methyl ester (these compounds can be prepared by the method described in WO 2020 / 079111), (Z)-2-(5-cyclohexyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoic acid methyl ester, (Z)-2-(5-cyclopentyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoic acid methyl ester (these compounds can be prepared by the method described in WO 2020 / 193387), 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-sulfanyl-1,2,4 -triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile, trinexapac-ethyl, syringostaryl, Zhongshengmycin, thiophanate-copper, thiazole zinc, amitolin, iprodione, cinclostrobin,N'-[5-Bromo-2-methyl-6-[(1S)-1-methyl-2-propoxy-ethoxy]-3-pyridinyl]-N-ethyl-N-methyl-formamidine, N'-[5-Bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridinyl]-N-ethyl-N-methyl-formamidine, N'-[5-Bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridinyl]-N-ethyl-N-methyl-formamidine, -ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine, N'-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-isopropyl-N-methyl-formamidine (these compounds can be prepared by WO 2015 / 155075); N'-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine (this compound can be prepared by the method described in IPCOM000249876D); N-isopropyl-N'-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine, N'-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidine (these compounds can be prepared by the method described in WO 2018 / 228896); N-ethyl-N'-[5-methoxy-2-methyl-4-[(2-trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl-formamidine, N-ethyl-N'-[5-methoxy-2-methyl-4-[(2-trifluoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine (these compounds can be prepared by the method described in WO2019 / 110427); N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl] -8-Fluoro-quinoline-3-carboxamide, N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide, 8-Fluoro-N-[(1R)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide,8-Fluoro-N-[(1S)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide, N-((1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide, N-((1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide (these compounds can be prepared by WO 2017 / 153380); 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline, 4,4-difluoro-3,3-dimethyl-1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline, 4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline, 1-(6-chloro-7-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline (these compounds can be prepared by WO 2017 / 153380); 2017 / 025510); 1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline, 6-chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline, 4,4-difluoro-1-(5-fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline, 3-(4,4-difluoro-3,3-dimethyl-1-isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole (these compounds can be prepared by WO 2016 / 156085); N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propionamide, N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propionamide, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, 1,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea,3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propionamide, 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, 5,5-dimethyl-2-[[ 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylic acid ethyl ester, N,N-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-1,2,4-triazol-3-amine (these compounds can be prepared by WO 2017 / 055473, WO 2017 / 055469, WO 2017 / 093348 and WO2017 / 118689); 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (this compound can be prepared by WO 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (this compound can be prepared by the method described in WO 2017 / 029179); 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile (this compound can be prepared by the method described in WO 2016 / 156290); 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile (this compound can be prepared by the method described in WO 2-amino-6-methyl-pyridine-3-carboxylic acid (4-phenoxyphenyl) methyl ester (this compound can be prepared by the method described in WO 2014 / 006945); 2,6-dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetraone (this compound can be prepared by the method described in WO 2011 / 138281);N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide; N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide; (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamine (this compound can be prepared by the method described in WO 2018 / 153707); N'-(2-chloro-5-methyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine; N'-[2-chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]-N-ethyl-N-methyl-formamidine (this compound can be prepared by the method described in WO 2-(Difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide (this compound can be prepared by the method described in WO 2014 / 095675); (5-methyl-2-pyridyl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone, (3-methylisoxazol-5-yl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone (these compounds can be prepared by the method described in WO 2017 / 220485); 2-Oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide (this compound can be prepared by the method described in WO 2014 / 095675); 2018 / 065414); 1-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4-carboxylic acid ethyl ester (this compound can be prepared by WO 2018 / 158365); 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide, N-[(E)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, N-[(Z)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, N-[N-methoxy-methyl-carbonimido]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (these compounds can be prepared by the method described in WO 2018 / 202428).

[0360] The compounds of the present invention can also be used in combination with anthelmintics. Such anthelmintics include compounds selected from the macrolide class, such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemaketin, and milbemycin derivatives, as described in EP 0357460, EP 0444964, and EP 0594291. Additional anthelmintics include semisynthetic and biosynthetic avermectin / milbemycin derivatives, such as those described in US 5,015,630, WO 9415944, and WO 9522552. Additional anthelmintics include benzimidazoles, such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxbendazole, parbendazole, and other members of this class. Additional anthelmintics include imidazothiazoles and tetrahydropyrimidines, such as tetramisole, levamisole, pyrantel pamoate, octadalafil, or morantel. Additional anthelmintics include flukeicides (such as triclabendazole and clorsulon) and tapeworms (such as praziquantel and ethacital).

[0361] The compounds of the present invention may be used in combination with derivatives and analogs of the paraherquamide / marcfortine class of anthelmintics and antiparasitic oxazolines such as those disclosed in US 5478855, US 4639771 and DE-19520936.

[0362] The compounds of the present invention can be used in combination with derivatives and analogs of the general class of dioxomorpholine antiparasitic agents as described in WO 9615121 and also with anthelmintic active cyclic depsipeptides such as those described in WO 9611945, WO 9319053, WO9325543, EP 0626375, EP 0382173, WO 9419334, EP 0382173, and EP 0503538.

[0363] The compounds of the present invention can be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as chlorfenuron; ecdysone agonists such as tebufenozide; neonicotinoids such as imidacloprid, etc.

[0364] The compounds of the present invention may be used in combination with terpene alkaloids, such as those described in WO 95 / 19363 or WO 04 / 72086, in particular the compounds disclosed therein.

[0365] Other examples of such biologically active compounds that can be used in combination with the compounds of the present invention include, but are not limited to, the following:

[0366] Organophosphates: acephate, methyl pyraclofos, ethyl azinphos-methyl, bromophos, ethyl bromophos, cadusin, chlorethoxyphos, chlorpyrifos, chlorfenapyr, chlormethylphos, demeton, demeton-S-methyl, demeton-S-methyl sulfone, chlormet, diazinon, dichlorvos, dicrotophos, dimethoate, ethion, ethion, ethoprophos, oxamethon, fenamiphos, fenitrothion, fensulfuron, fenthion, fenthion, pyrifos, fenfophos, anthiophos, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl, anthiophanate-methyl Phosphorus, acaricide, methamidophos, methidathion, methyl parathion, mevinphos, monocrotophos, dibromophos, omethoate, methyl oxo-demeton, paraoxon, parathion, methyl parathion, fenthion, phosalone, thiocyanate, phosphamidon, phosphamidon, phosphamidon, phosphamidon, phosphamidon, phosphamidon, phosphamidon, phosphamidon, phosphamidon, phosphamidon, phosphamidon-methyl, profenofos, propanphos, proetamphos, prothiophos, pyraclofos, pyridazinphos, quinalphos, thiocarb, temeton, terbufos, butylpyrimidinphos, stirofos, thimeton, triazophos, trichlorfon, and chlorpyrifos.

[0367] Carbamates: aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, chlorpyrifos, carbofuran, butylsulfuron, difenocarb, ethiofencarb, fenoxycarb, fensulfuron, furathiocarb, HCN-801, isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m-isopropylphenylbutynyl (methyl) carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, long-lasting carb, triazolam, UC-51717.

[0368] Pyrethroids: flumethrin, allethrin, alphametrin, 5-benzyl-3-furylmethyl (E)-(1R)-cis-2,2-dimethyl-3-(2-oxathiolan-3-ylidenemethyl) cyclopropanecarboxylate, bifenthrin, β-cypermethrin, flucypermethrin, alpha-cypermethrin, β-cypermethrin, bio-allethrin, bio-allethrin ((S)-cyclopentyl isomer), bio-resmethrin, bifenthrin, NCI-85193, Pyrethrins, cyhalothrin, cypermethrin (cythithrin), cypermethrin, deltamethrin, dextromethorphan, esfenvalerate, etofenprox, pentothrin, fenpropathrin, cypermethrin, flucythrin, flucythrin, fluvalinate (D isomer), imiprothrin, lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrin (natural product), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluan, t-fluvalinate, tefluthrin, tralomethrin, zeta-cypermethrin.

[0369] Arthropod growth regulators: a) Chitin synthesis inhibitors: benzoylureas: chlorfluanidone, diflubenzuron, fluazifop, flufenoxuron, flubendiamide, hexaflumuron, chlorfenuron, noflubenzuron, diflubenzuron, thiophanate-methyl, buprofen, benzylpezil, hexathiacyclon, etoxazole, chlorfentazine; b) Ecdysone antagonists: chlorfenapyr, methoxyfenopyr, tebufenozide; c) Juvenile hormone analogs: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) Lipid biosynthesis inhibitor: spirodiclofen.

[0370] Other antiparasitic drugs: acequinoxaline, amitraz, AKD-1022, ANS-118, azadirachtin, Bacillus thuringiensis, sulfamethoxazole, bifenazate, binapacryl, bromocriptine, BTG-504, BTG-505, toxaphene, cartap, dimethoate, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, clothianidin, cypermethrin, diacloden, cypermethrin, DBI-3204, diclofenac, dihydroxybenzoic acid Methyldihydroxypyrrolidine, diclofenac, diclofenac, endosulfan, ethiprole, fenvalerate, fenflufen, flumite, MTI-800, fenpyroximate, fenflufen, flumethrin, bromothrin, flumite, trifluroxyfen, fluproxyfen, halofenprox, hydrazone, IKI-220, natronite, NC-196, neem guard), nidinorterfuran, nitenpyram, SD-35651, WL-108477, pyridalyl, propargite, protrifenbute, pymetrozine, pyridabenz, pyrimidifen, NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, flutosan, silomadine, spinosad, tebufenpyrad, triclopyraclostrobin, tetracycline, thiacloprid, thiamethoxam, tolfenpyrad, triazolam, triacylsuccinate, synergistic ether, vertalec, and YI-5301.

[0371] Biological agents: Bacillus thuringiensis ssp. aizawai, Bacillus thuringiensis ssp. kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, viruses and fungi.

[0372] Bactericides: chlortetracycline, oxytetracycline, streptomycin.

[0373] Other biologic agents: enrofloxacin, febantel, penxacillin, meloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovicidin, tolamectin, ceftiofur, carprofen, mefluazione, praziquantel, triclabendazole.

[0374] The following mixtures of compounds of formula (I) with active ingredients are preferred. The abbreviation "TX" means a compound selected from the compounds of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4) or (I-A5), or a compound selected from the compounds listed in Tables A-1 to A-23 or the compounds listed in Table P (below), and a compound selected from the group consisting of petroleum + TX, 1,1-bis(4-chlorophenyl)-2-ethoxyethanol + TX, 2,4-dichlorophenylbenzenesulfonate + TX, 2-fluoro-N-methyl-N-1-naphthylacetamide + TX, 4-chlorophenylphenyl sulfone + TX, acetofenapyr + TX, aldicarb + TX, sirox + TX, cypermethrin + TX, chlorpyrifos + TX, oxalic acid hydrogen Amidophos + TX, amitraz + TX, cypermethrin + TX, cypermethrin + TX, arsenic trioxide + TX, azobenzene + TX, azophos + TX, benomyl + TX, benoxafos + TX, benzyl benzoate + TX, bixafen + TX, bromethrin + TX, bromophos + TX, bromopyralid + TX, buprofezin + TX, butacarb + TX, butacarb + TX, butylpyridaben + TX, calcium polysulfide + TX, octachlorocamphene + TX, chlormethoxam + TX, trithion + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin + TX, ethyl cypermethrin +TX, chloromebuform +TX, chlormebufen +TX, chlorfenapyr +TX, chlorfenapyr +TX, chlorfenapyr I +TX, chlorfenapyr II +TX, chlorfenapyr +TX, closantel +TX, coumaphos +TX, crotamiton +TX, baclofos +TX, thiophanate +TX, demeton +TX, DCPM +TX, DDT +TX, demeton +TX, demeton-O +TX, demeton-S +TX, methyl demeton +TX, demeton-O +TX, demeton-O-methyl +TX, demeton-S +TX, demeton-S-methyl +TX, demeton-S-methyl sulfoxide (demeton-S-methylsulfon) +TX, dichlorvos +TX, dichlorvos +TX, dicliphos +TX, dienochlor +TX, diflubenzuron +TX, dinex +TX, dinex-diclexine +TX, dinocton-4 +TX, dinocton-6 +TX, dinocton +TX, dinopenton +TX, dinosulfon +TX, nitrobenzene +TX, dimethoate +TX, dimethoate +TX, diphenyl sulfone +TX, disulfiram +TX, DNOC +TX, dofenapyn +TX, doramectin +TX, endoxifen +TX,Eprinomectin + TX, phosphine + TX, ethimphos + TX, antifungal + TX, fenbutatin + TX, fenthiocarb + TX, fenpyrad + TX, fenpyrad + TX, fenpyrad + TX, fenamipyraclostrobin + TX, fentrifanil + TX, fluazifop + TX, flufenoxuron + TX, fluazifop + TX, fluazifop + TX, FMC 1137+TX, fenvalerate+TX, fenvalerate hydrochloride+TX, formparanate+TX, γ-HCH+TX, chlorpyrifos+TX, benzyl methoxyfen+TX, hexadecyl cyclopropane carboxylate+TX, isocarbophos+TX, jasmonate I+TX, jasmonate II+TX, iodonium chloride+TX, lindane+TX, propanil+TX, cypermethrin+TX, dithiophos+TX, methylthiophene+TX, cypermethrin+TX, methyl bromide+TX, methylthiophene+TX, cypermethrin+TX, methyl bromide+TX, cypermethrin+TX, chlorpyrifos+TX, milbemycin+TX, propylamine+TX, monocrotophos+TX, malathion+TX, moxidectin+TX, Naled + TX, 4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one + TX, fluazifop + TX, nikkomycin + TX, pentocyanamide + TX, pentocyanamide 1:1 zinc chloride complex + TX, omethoate + TX, isothiocarb + TX, sulfamethoxam + TX, pp'-DDT + TX, parathion + TX, permethrin + TX, fenthion + TX, phosalone + TX, thiophanate + TX, phosphamidon + TX, chlorinated turpentine (polychloroterpenes) + TX, acaricide (polynact ins)+TX, Proclonol+TX, Fenoxacar+TX, Propoxur+TX, Ethiophanate+TX, Pyrethrin I+TX, Pyrethrin II+TX, Pyrethrin+TX, Pyrithiophos+TX, Pyrithiophos+TX, Quinalphos+TX, Quintiofos+TX, R-1492+TX, Glyphosate+TX, Rotenone+TX, Octamphos+TX, Clamine+TX, Selamectin+TX, Threonathion+TX, SSI-121+TX, Sufilam+TX, Sulfluramid+TX, Sultep+TX, Sulfur+TX, Fluoride Acefenazine + TX, τ-fluvalinate + TX, TEPP + TX, terbucarb + TX, tetrachlorvinphos + TX, acarbamide + TX, thiafenox + TX, pyrifos + TX, long-lasting carbamide + TX, methyl bethiocarb + TX, chlorpyrifos + TX, thiazolin + TX, thiamethoxam + TX, thiazolin + TX, triazophos + TX, triazuron + TX, triclopyralid + TX, triamcin + TX, aphidoxazole + TX, vaniliprole + TX, bethoxazin + TX, copper dioctanoate + TX,Copper sulfate + TX, cybutryne + TX, dichloronaphthoquinone + TX, dichlorophen + TX, endoxan + TX, triphenyltin + TX, slaked lime + TX, sodium mancozeb + TX, quinone + TX, quinone + TX, simazine + TX, triphenyltin acetate + TX, triphenyltin hydroxide + TX, fusulin + TX, piperazine + TX, thiophanate + TX, chloralose + TX, fenthion + TX, pyridin-4-amine + TX, strychnine + TX, 1-hydroxy-1H-pyridine-2-thione + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide + TX, 8-hydroxyquinoline sulfate + TX, bromide Nitroalcohol + TX, copper hydroxide + TX, cresol + TX, dipyrithione + TX, dodixan + TX, sodium disulfide + TX, formaldehyde + TX, mercurophen + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, nickel bis(dimethyldithiocarbamate) + TX, trichloromethylpyridine + TX, octhiazide + TX, oxolinic acid + TX, oxytetracycline + TX, potassium hydroxyquinoline sulfate + TX, thiabendazole + TX, streptomycin + TX, streptomycin sesquisulfate + TX, chloranthracene + TX, thimerosal + TX, cotton brown-banded tormenter GV + TX, Agrobacterium radiobacterium + TX, Amblyseius species spp.)+TX, celery armyworm NPV+TX, Anagrus atomus+TX, Aphelinus abdominalis+TX, Aphidius colemani+TX, Aphidoletes aphidimyza+TX, Spodoptera falcatus NPV+TX, Bacillus sphaericus Neide+TX, Beauveria brongniartii+TX, Chrysoperla carnea+TX, Cryptolaemus montrouzieri+TX, codling moth GV+TX, Dacnusa sibirica+TX, Diglyphus isaea+TX, Encarsia spp. formosa)+TX, Eretmocerus eremicus+TX, Heterorhabditis bacteriophora and H. megidis+TX, Hippodamia convergens+TX, Leptomastix dactylopii+TX,Macrolophus caliginosus+TX, cabbage armyworm NPV+TX, Metaphycus helvolus+TX, Metarhizium anisopliaevar.acridum+TX, Metarhizium anisopliaevar.anisopliae+TX, Neodiprion sertifer NPV and N.lecontei NPV+TX, species of the genus Microsporum+TX, Paecilomyces fumosoroseus+TX, Phytoseiulus persimilis+TX, Steinernema bibionis+TX, Steinernema serrata+TX, and Steinernema serrata. carpocapsae)+TX, Steinernema nematode+TX, Steinernema glaseri+TX, Steinernema riobrave+TX, Steinernema riobravis+TX, Steinernema scapterisci+TX, Steinernema spp.+TX, Trichogramma species+TX, Typhlodromus occidentalis)+TX, Verticillium lecanii+TX, apholonate+TX, bis(aziridine) methylaminophosphine sulfide (bisazir)+TX, busulfan+TX, dimatif+TX, hemelamine+TX, hempa+TX, metepa+TX, methiotepa+TX, methyl apholonate Apholate) + TX, Morzid + TX, Penfluron + TX, Tepa + TX, Thiohempa + TX, Thiohempa + TX, Tetramethylenetetramine + TX, Urethaneimine + TX, (E)-Deca-5-en-1-yl acetate and (E)-Deca-5-en-1-ol + TX, (E)-Tridec-4-en-1-yl acetate + TX, (E)-6-Methylhept-2-en-4-ol + TX, (E,Z)-Tetradec-4,10-dien-1-yl acetate + TX, (Z)-Dodec-7-en-1-yl acetate + TX,(Z)-hexadec-11-enal + TX, (Z)-hexadec-11-en-1-yl acetate + TX, (Z)-hexadec-13-en-11-yn-1-yl acetate + TX, (Z)-eicos-13-en-10-one + TX, (Z)-tetradec-7-en-1-al + TX, (Z)-tetradec-9-en-1-ol + TX, (Z)-tetradec-9-en-1-yl acetate + TX, ( 7E,9Z)-dodeca-7,9-dien-1-yl acetate + TX, (9Z,11E)-tetradec-9,11-dien-1-yl acetate + TX, (9Z,12E)-tetradec-9,12-dien-1-yl acetate + TX, 14-methyloctadec-1-ene + TX, 4-methylnonan-5-ol and 4-methylnonan-5-one + TX, α-polystyrene + TX, western pine beetle aggregation pheromone + TX , dodecadienol + TX, decyl ketone + TX, epoxy nonadecane + TX, dodec-8-en-1-yl acetate + TX, dodec-9-en-1-yl acetate + TX, dodec-8,10-dien-1-yl acetate + TX, dominicalure + TX, 4-methyloctanoic acid ethyl ester + TX, eugenol + TX, southern pine beetle gathering pheromone + TX, attractant Killing agent mixture + TX, killing agent mixture I + TX, killing agent mixture II + TX, killing agent mixture III + TX, killing agent mixture IV + TX, hexane attractant + TX, tooth beetle dienol + TX, small beetle dienol + TX, scarab sex attractant + TX, trimethyldioxytricyclononane + TX, moth attractant (litlure) + TX, cabbage looper sex attractant + TX, killing ester + TX, megatomoic acid acid)+TX, entophore+TX, entophore+TX, octadec-2,13-dien-1-yl acetate+TX, octadec-3,13-dien-1-yl acetate+TX, Hekangbi+TX, Coconut Rhinoceros Beetle Aggregation Pheromone+TX, Feilekang+TX, Insect Ring+TX, Sodiding+TX, Fungi-eating Methanol+TX, Tetradec-11-en-1-yl Acetate+TX, Mediterranean Fruit Fly Attractant+TX, Mediterranean Fruit Fly Attractant A+TX, Mediterranean Fruit Fly Attractant B1+TX, Mediterranean Fruit Fly Attractant B2+TX, Mediterranean Fruit Fly Attractant Agent C+TX, trunc-call+TX, 2-(octylthio)ethanol+TX, butopyronoxyl+TX, butoxy(polypropylene glycol)+TX, dibutyl adipate+TX, dibutyl phthalate+TX, dibutyl succinate+TX, DEET+TX, dimethylcarbate+TX, dimethyl phthalate+TX, ethyl hexanediol+TX, hexamide+TX, methoquin-butyl+TX,Methylneodecanamide + TX, oxamate + TX, picaridin + TX, 1-dichloro-1-nitroethane + TX, 1,1-dichloro-2,2-di(4-ethylphenyl)ethane + TX, 1,2-dichloropropane and 1,3-dichloropropylene + TX, 1-bromo-2-chloroethane + TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate + TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate + TX, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate + TX, 2-(2-butoxyethoxy)ethyl thiocyanate + TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenylmethylcarbamate + TX, 2-(4-chloro-3,5-xylyloxy)ethanol + TX, 2-chlorovinyldiethyl phosphate + TX, 2-imidazolidinone + TX, 2-isovalerylindan-1,3-dione + TX, 2-methyl(prop-2-ynyl)aminophenylmethylcarbamate + TX, 2-thiocyanatoethyl laurate + TX, 3-bromo-1-chloroprop-1-ene + TX, 3-methyl-1-phenylpyrazol-5-yldimethylcarbamate + TX, 4-methyl(prop-2-ynyl)amino-3,5-xylylmethylcarbamate + TX, 5,5-dimethyl-3-oxocyclohex-1-enyldimethyl Carbamate + TX, acethion + TX, acrylonitrile + TX, aldrin + TX, aloamicin + TX, chlorpyrifos + TX, α-deceprin + TX, aluminum phosphide + TX, chlorpyrifos + TX, neonicotinoid + TX, ethylthiocarb + TX, methylpyrifos + TX, Bacillus thuringiensis δ-endotoxin + TX, barium hexafluorosilicate + TX, barium polysulfide + TX, cypermethrin + TX, Bayer 22 / 190 + TX, Bayer 22408 + TX, β-cyfluthrin + TX, β-cypermethrin + TX, bioethanomethrin + TX, biopermethrin + TX, bis(2-chloroethyl) ether + TX, borax + TX, bromine Benzophenone + TX, bromo-DDT + TX, chlordane + TX, chlordecanone + TX, chlorpromazine + TX, butathiofos + TX, butyl phosphate + TX, calcium arsenate + TX, calcium cyanide + TX, carbon disulfide + TX, carbon tetrachloride + TX, cypermethrin hydrochloride + TX, cevadine + TX, borneol + TX, chlordane + TX, chlordecone + TX, chloroform + TX, chloropicrin + TX, chloraniloxime + TX, chlorprazophos + TX, cis-resmethrin + TX, cismethrin + TX, clocythrin (alias) + TX,Copper acetyl arsenite + TX, copper arsenate + TX, copper oleate + TX, coumithoate + TX, cryolite + TX, CS 708+TX, benzonitrile+TX, cypermethrin+TX, cypermethrin+TX, cypermethrin+TX, d-methrin+TX, DAEP+TX, dazomethon+TX, decarbofuran+TX, diamidafos+TX, isochlorvinphos+TX, dimethophos+TX, dicresyl+TX, cypermethrin+TX, dieldrin+TX, diethyl 5-methylpyrazol-3-yl phosphate+TX, dilor+TX, tetrafluthrin+TX, demaquinetosulfuron+TX, pyrethrin+TX, methylchlorfenapyr+TX, difenocarb+TX, propanol+TX, pentotropol+TX, dinoseb+TX, fenpyroxene+TX, vesiculophos+TX, thiopyrafos+TX, DSP+TX, ecdysterone+TX, EI 1642+TX, EMPC+TX, EPBP+TX, Oxfordshire etaphos+TX, ethiofencarb+TX, ethyl formate+TX, dibromoethane+TX, dichloroethane+TX, ethylene oxide+TX, EXD+TX, pyrifos+TX, ethiofencarb+TX, fenitrothion+TX, fenoxacrim+TX, cypermethrin+TX, fenthion+TX, ethylfenthion+TX, fluchlorbiprofen+TX cofuron)+TX, butylfenthion+TX, phosphonium arsenate+TX, butylcyclothion+TX, furathiocarb+TX, pyrethroid+TX, biguanide salt+TX, biguanide acetate+TX, sodium tetrathiocarbonate+TX, halfenprox+TX, HCH+TX, HEOD+TX, heptachlor+TX, cypermethrin+TX, HHDN+TX, hydrogen cyanide+TX, quinoline carbendazim+TX, IPSP+TX, chlorfenapyr+TX, carbochlorin+TX TX, isoaldrin + TX, isofenphos + TX, transplanting spirit + TX, rice blast + TX, oxathiapiprolin + TX, juvenile hormone I + TX, juvenile hormone II + TX, juvenile hormone III + TX, chlorpentyl + TX, methoprene + TX, lead arsenate + TX, bromofenphos + TX, pyralid + TX, thiathion + TX, m-isopropyl methylcarbamate + TX, magnesium phosphide + TX, phosphorus azide + TX, methyl azofenphos + TX, thiamethoxam + TX, mercurous chloride + TX , methyl sulfoxide + TX, metamex + TX, metamex potassium + TX, metamex sodium + TX, methylsulfonyl fluoride + TX, butenamidophos + TX, methoprene + TX, methoxythrin + TX, methoxychlor + TX, methyl isothiocyanate + TX, methyl chloroform + TX, dichloromethane + TX, anthracene + TX, anthelmintic + TX, naphthiophos + TX, naphthalene + TX, NC-170 + TX, nicotine + TX, nicotine sulfate + TX, nithiazine + TX, pronicotine + TX,O-5-dichloro-4-iodophenyl O-ethylethylphosphonothioate + TX, O,O-diethyl O-4-methyl-2-oxo-2H-chromen-7-ylphosphonothioate + TX, O,O-diethyl O-6-methyl-2-propylpyrimidin-4-ylphosphonothioate + TX, O,O,O',O'-tetrapropyl dithiopyrophosphate + TX, oleic acid + TX, p-dichlorobenzene + TX, methyl parathion + TX, pentachlorophenol + TX, pentachlorophenyl laurate + TX, PH 60-38+TX, fenthion+TX, parachlorothion+TX, phosphine+TX, methyl phoxim+TX, methamidophos+TX, polychlorinated dicyclopentadiene isomers+TX, potassium arsenite+TX, potassium thiocyanate+TX, precocious plant I+TX, precocious plant II+TX, precocious plant III+TX, amidothrin+TX, fluthrin+TX, fenvalerate+TX, prothiophos+TX, pyraclostrobin+TX, anti-pyrethroid+TX, quassia extract+TX, quinalphos-methyl+TX, fenvalerate+TX, iodophos-amide+TX, resmethrin+TX, dervine Ketone + TX, thiamethoxam + TX, ryanodine + TX, ryanodine + TX, sabadilla + TX, octamethoxazole + TX, clostridium + TX, SI-0009 + TX, thiamethoxam + TX, sodium arsenite + TX, sodium cyanide + TX, sodium fluoride + TX, sodium hexafluorosilicate + TX, sodium pentachlorophenol + TX, sodium selenate + TX, sodium thiocyanate + TX, sulcofuron + TX, sulcofuron-sodium + TX, sulfuryl fluoride + TX, thioprolin + TX, tar + TX, thiophene Afenacet + TX, TDE + TX, butylpyrimidophos + TX, dimethophos + TX, cyclopentyl thiocarb + TX, tetrachloroethane + TX, thiochlorvos + TX, cyclohexane + TX, cyclohexane oxalate + TX, cypermethrin + TX, cypermethrin sodium + TX, tralomethrin + TX, permethrin + TX, triazolam + TX, trichlormetaphos-3 + TX, chlorpyrifos + TX, cyclohexane + TX, tolprocarb + TX, chlorpyrifos + TX, thiophanate + TX, veratridine + TX , Veratridine + TX, XMC + TX, zetamethrin + TX, zinc phosphide + TX, tolfenphos + TX, chlorfluanidine + TX, tetrafluanidine + TX, bis(tributyltin) oxide + TX, bromoacetamide + TX, iron phosphate + TX, niclosamide-ethanolamine + TX, tributyltin oxide + TX, pyrimorph + TX, snail killer + TX, 1,2-dibromo-3-chloropropane + TX, 1,3-dichloropropylene + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide + TX, 3-(4-chlorophenyl)-5-methylrhodanine + TX,5-Methyl-6-thioxo-1,3,5-thiadiazin-3-yl acetic acid + TX, 6-isopentenylaminopurine + TX, 2-fluoro-N-(3-methoxyphenyl)-9H-purin-6-amine + TX, benclothiaz + TX, cytokinin + TX, DCIP + TX, furfural + TX, isamidophos + TX, kinetin + TX, verrucous myroculitis combination + TX, tetrachlorothiophene + TX, xylenol + TX, zeatin + TX, potassium ethylxanthate + TX, acibenzolar + TX, acibenzolar-S-methyl + TX, Reynoutria sachalinensis) extract + TX, α-chlorohydrin + TX, Antu + TX, barium carbonate + TX, bismuth urea + TX, brodifacoum + TX, brodifacoum + TX, brodifacoum + TX, chlorofacitin + TX, cholecalciferol + TX, chlorfenapyr + TX, chlorfenapyr + TX, chlorfenapyr + TX, chlorfenapyr + TX, chlorfenapyr + TX, chlorfenapyr + TX, chlorfenapyr + TX, chlorfenapyr + TX, thiazolin + TX, diphacin + TX, calciferol + TX, fludioxaline + TX, fluoroacetamide + TX, fludioxaline Pyridine + TX, flurbiprofen hydrochloride + TX, warfarin + TX, fosfomycin + TX, phosphorus + TX, warfarin + TX, warfarin + TX, scilla glycoside + TX, sodium fluoroacetate + TX, thallium sulfate + TX, warfarin + TX, 2-(2-butoxyethoxy)ethyl piperate + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone + TX, farnesol with nerolidol + TX, synergistic acetyl ether + TX, MGK 264 + TX, synergistic butoxide + TX, synergistic aldehyde + TX, synergistic ester (propyl isomer)+TX, S421+TX, Zengxiaosan+TX, sesasmolin+TX, sulfoxide+TX, anthraquinone+TX, copper cyclohexane+TX, copper oxychloride+TX, dicyclopentadiene+TX, salam+TX, zinc cyclohexane+TX, ziram+TX, imanin+TX, ribavirin+TX, mercuric oxide+TX, thiophanate-methyl+TX, azaconazole+TX, bifenthiazolin+TX, fuconazole+TX, cyproconazole+TX, difenoconazole+TX, diniconazole+TX, fluoxepiconazole+TX, fenbuconazole+TX, fluquinconazole+TX, flusilazole+TX, powder azole Alcohol + TX, furazolidone + TX, hexaconazole + TX, imazalil + TX, imidazole + TX, imipenem + TX, piclonil + TX, metconazole + TX, myclobutrazol + TX, paclobutrazol + TX, blastifen + TX, penconazole + TX, prothioconazole + TX, pyrifenox + TX, prochloraz + TX, propiconazole + TX, pyraconazole + TX, simeconazole + TX, tebuconazole + TX, fluconazole + TX, triadimefon + TX, triadimenol + TX, triflumizole + TX, triclosan + TX, pyrimidine alcohol + TX, chlorfenapyr + TX, flufenapyr + TX,Bupirimate + TX, dimethirimol + TX, ethirimol + TX, dodecacyclic morpholine + TX, fenpropidin + TX, fenpropimorph + TX, spiroxafil + TX, tridemorph + TX, cyprodinil + TX, pyraclostrobin + TX, pyrimethanil + TX; fenpiclonil + TX, fludioxonil + TX, benalaxyl + TX, furalaxyl + TX, metalaxyl + TX, R-metalaxyl + TX; furamide + TX; oxadixyl + TX, carbendazim + TX, imidacloprid Debacarb + TX, Maisuining + TX, Thiabendazole + TX, Chlozolinate + TX, Dichlozoline + TX, Myclozoline + TX, Procymidone + TX, Vinclozoline + TX, Boscalid + TX, Carboxin + TX, Furam + TX, Flutolanil + TX, Metformin + TX, Oxycarboxin + TX, Penthiopyrad + TX, Thiaflutamide + TX, Dodine + TX, Biguanide + TX, Azoxystrobin +TX, enestroburin +TX, enestroburin +TX, enestroburin +TX, flutoxanil +TX, fluoxastrobin +TX, enestroburin +TX, fluoxastrobin +TX, enestroburin +TX, fenoxystrobin +TX, fenoxystrobin +TX, fenoxystrobin +TX, pyraclostrobin +TX, pyraclostrobin +TX, ferbam +TX, mancozeb +TX, maneb +TX, maneb +TX, mesab +TX, maneb +TX, captol +TX, captan +TX, pyraclostrobin +TX, folpet +TX, tolylfluanid +TX, Bordeaux mixture +TX, copper oxide +TX, mancozeb +TX, quinoline copper +TX, phthalostrobin +TX, kewensan +TX, isoprena +TX, chlorpyrifos+TX, tolclofos-methyl+TX, dithiazolin+TX, benzathiapiprolin+TX, blasticidin+TX, chloroneb+TX, chlorothalonil+TX, flutolanil+TX, cymoxanil+TX, flutolanil+TX, diclocymet+TX, diclomezine+TX, dicloran+TX, diethofencarb+TX, dimethomorph+TX, flumorph+TX, dithianon+TX, ethaboxam+TX, etridiazole+TX, famoxadone+TX,Fenamidone + TX, fenoxanil + TX, ferimzone + TX, fluazinam + TX, fluopicolide + TX, flusulfamide + TX, fluopyram + TX, fenhexamid + TX, fosetyl-aluminium + TX, hymexazol + TX, propineb + ​​TX, cyazofamid + TX, methasulfocarb + TX, mefenoxam + TX, pencycuron on)+TX, phthalide+TX, polyoxins+TX, propamocarb+TX, pyraclostrobin+TX, proquinazid+TX, pyroquilon+TX, pyriofenone+TX, quinoxyfen+TX, pentachloronitrobenzene+TX, thiazolamide+TX, triazoxide+TX, tricyclazole+TX, triamcinol+TX, validamycin+TX, valosin+TX, zoxamide+TX, mandipropamid+TX, fluphenazine+TX, pyraclostrobin( isopyrazam) + TX, sedaxane + TX, benzovinflumizone + TX, fluopyram + TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro-biphenyl-2-yl)-amide + TX, isoflucycline + TX, isothiocyanate + TX, dipymetitrone + TX, 6-ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithiino[1,2-c]isothiazole-3-carbonitrile + TX, 2-(difluoromethyl)-N-[3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, 4-(2,6-difluorophenyl)- 6-Methyl-5-phenyl-pyridazine-3-carbonitrile + TX, (R)-3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine + TX, 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine + TX, flufenoxam + TX, jiaxiangjunzhi + TX, lvbenmixianan + TX, dichlobentiazox + TX,Mandestrobin + TX, 3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone + TX, 2-[2-fluoro-6-[(8-fluoro-2-methyl-3-quinolinyl)oxy]phenyl]propan-2-ol + TX, oxathiapiprolin + TX, tert-butyl N-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridinyl]carbamate + TX, pyraziflumid + TX, inpyrfluxam + TX, trolprocarb + TX , chlorfluanidazole + TX, ipfentrifluconazole + TX, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, N'-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine + TX, N'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine + TX, [2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl] -3-chloro-phenyl] methanesulfonate + TX, N-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridinyl]carbamic acid but-3-ynyl ester + TX, N-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamic acid methyl ester + TX, 3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine + TX, flubendiamide (pyridachlometyl) + TX, 3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 1-[2-[[1-(4-chlorophenyl) 1-Methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]tetrazol-5-one+TX, aminopyrifen+TX, pyrazoconazole+TX, indazolesulfamide+TX, fluopicolide+TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamine+TX, pyrithione+TX, fenpicoxamid+TX, isobutylethoxyquinoline+TX,Ipflufenoquin + TX, quinofumelin + TX, isopyram + TX, N-[2-[2,4-dichloro-phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, N-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, benzathiostrobin + TX, cyproconazole + TX, 5-amino-1,3,4-thiadiazole-2-thiol zinc salt (2:1) + TX, fluopyram + TX, fluthiazolinone + TX, fluopyram + TX, pyrapropoyne + TX, Piperidazole (picarbutrazox) + TX, 2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indan-4-yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylindan-4-yl)pyridine-3-carboxamide + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, metyltetraprole + TX, α-(1,1-dimethylethyl)-α-[4'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl] -5-pyrimidinemethanol + TX, fluoxapiprolin + TX, enoxastrobin + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-sulfanyl-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-sulfanyl-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, -triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, trinexapac-ethyl + TX, syringostibrate + TX, zhongshengmycin + TX, thiophanate-methyl + TX, thiabendazole zinc + TX, amitolin (amectotractin) + TX, iprodione + TX, N-octyl-N'-[2-(octylamino)ethyl]ethane-1,2-diamine + TX; N'-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX,N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds can be prepared by WO 2015 / 155075); N'-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX (this compound can be prepared by the method described in IPCOM000249876D); N-isopropyl-N'-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine + TX, N'-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds can be prepared by the method described in WO 2018 / 228896); N-ethyl-N'-[5-methoxy-2-methyl-4-[2-trifluoromethyl)oxetane-2-yl]phenyl]-N-methyl-formamidine + TX, N-ethyl-N'-[5-methoxy-2-methyl-4-[2-trifluoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine + TX (these compounds can be prepared by WO 2019 / 110427); N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide+TX, N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide+TX, Benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide + TX, 8-fluoro-N-[(1R)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide + TX, 8-fluoro-N-[(1S)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide + TX, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX,N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide+TX, N-((1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide+TX, N-((1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide+TX (these compounds can be prepared by WO 2017 / 153380); 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline+TX, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline+TX, 4,4-difluoro-3,3-dimethyl -1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline+TX, 4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline+TX, 1-(6-chloro-7-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline+TX (these compounds can be prepared by WO 2017 / 025510); 1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline+TX, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline+TX, 6-chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline+TX, 4,4-difluoro-1-(5-fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline+TX, 3-(4,4-difluoro-3,3-dimethyl-1-isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole+TX (these compounds can be prepared by WO 2016 / 156085); N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide+TX, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propionamide+TX, N-ethyl-2-methyl-N-[[4 -[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propionamide+TX, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX, 1,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX,3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX, N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propionamide+TX, 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one+TX, 5,5-dimethyl -2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one+TX, 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylic acid ethyl ester+TX, N,N-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-1,2,4-triazol-3-amine+TX. The compounds in this paragraph can be prepared by WO 2017 / 055473, WO 2017 / 055469,Prepared by the method described in WO 2017 / 093348 and WO 2017 / 118689; 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol+TX (this compound can be prepared by the method described in WO 2017 / 029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol+TX (this compound can be prepared by the method described in WO 2017 / 029179); 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile+TX (this compound can be prepared by the method described in WO 2016 / 156290); 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound can be prepared by the method described in WO 2016 / 156290); 2-amino-6-methyl-pyridine-3-carboxylic acid (4-phenoxyphenyl) methyl ester + TX (this compound can be prepared by the method described in WO2014 / 006945); 2,6-dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c']bipyrrole-1,3,5,7(2H,6H)-tetraone + TX (this compound can be prepared by the method described in WO 2011 / 138281); N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX; N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX; (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamine+TX (this compound can be prepared by the method described in WO 2018 / 153707); N'-(2-chloro-5-methyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine+TX; N'-[2-chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]-N-ethyl-N-methyl-formamidine+TX (this compound can be prepared by the method described in WO 2016 / 202742); 2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX (this compound can be prepared by the method described in WO 2014 / 095675); (5-methyl-2-pyridyl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone + TX,(3-methylisoxazol-5-yl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone + TX (these compounds can be prepared by the method described in WO 2017 / 220485); 2-oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide + TX (this compound can be prepared by the method described in WO 2018 / 065414); 1-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4-carboxylic acid ethyl ester + TX (this compound can be prepared by the method described in WO 2018 / 158365); 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide+TX, N-[(E)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX, N-[(Z)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide Amide + TX, N-[N-methoxy-C-methyl-carbonimido]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX (these compounds can be prepared by the method described in WO2018 / 202428), chloroindole hydrazide + TX, flusulfuron + TX, fluconazole + TX, flufenoxadiazam + TX, and metaylpicoxamid + TX.

[0375] References in brackets after the active ingredient, e.g. [3878-19-1], refer to Chemical Abstracts Registration Numbers. The mixed partners described above are known. In the case where the active ingredients are included in "The Pesticide Manual" [The Pesticide Manual - A World Compendium; 13th edition; Editor: CDSTomLin; The British Crop Protection Council], they are described therein by the entry number given above in parentheses for the specific compound; e.g. the compound "avermectin" is described by entry number (1). In the case where "[CCN]" is added above to a specific compound, the compound in question is included in the "Compendium of Pesticide Common Names", which can be found on the Internet [A.Wood; Compendium of Pesticide Common Names , 1995-2004]; for example, the compound "acetoprole" is described on the Internet at http: / / www.alanwood.net / pesticides / acetoprole.html.

[0376] Most of the active ingredients described above are referred to by what are referred to as "common names" above, with the corresponding "ISO common name" or another "common name" being used in different cases. If a name is not a "common name," the kind of name used is replaced by the name given in parentheses for the specific compound; in this case, the IUPAC name, IUPAC / Chemical Abstracts name, "Chemical Name," "Conventional Name," "Compound Name," or "Development Code" is used, or if neither one of those names nor the "common name" is used, the "synonym" is used. "CAS Registry Number" means the Chemical Abstracts Registry Number.

[0377] Active ingredient mixtures of compounds selected from compounds of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4) or (I-A5), or selected from the compounds listed in Tables A-1 to A-23 or the compounds listed in Table P (below) are preferably in a mixing ratio of 100:1 to 1:100, especially 50:1 to 1:50, more especially 20:1 to 1:20, even more especially 10:1 to 1:10 and still more especially 5:1 to 1:5. Those mixing ratios are by weight.

[0378] The mixtures as described above may be used in a method for controlling pests which comprises applying a composition comprising a mixture as described above to the pests or their environment, excluding methods for treating the human or animal body by surgery or therapy and diagnostic methods performed on the human or animal body.

[0379] Mixtures comprising a compound selected from a compound of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4) or (I-A5), or a compound selected from the compounds listed in Tables A-1 to A-23 or Table P (below) and one or more active ingredients as described above can be applied, for example, in a single "ready-to-use" form, as a combined spray mixture consisting of separate formulations of the individual active ingredient components, such as a "tank mix," and in combination with a single active ingredient when applied sequentially, i.e., one after the other within a reasonably short period of time (e.g., a few hours or days). The order in which the compound selected from a compound of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4) or (I-A5), or a compound selected from the compounds listed in Tables A-1 to A-23 or Table P (below) and one or more active ingredients as described above is applied is not critical for the practice of the present invention.

[0380] The compositions according to the invention may also contain further solid or liquid adjuvants, such as stabilizers, for example non-epoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soybean oil), defoamers (for example silicone oils), preservatives, viscosity regulators, adhesives and / or tackifiers, fertilizers or other active ingredients for achieving specific effects, such as bactericides, fungicides, nematicides, plant activators, molluscicides or herbicides.

[0381] The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries, for example by grinding, screening and / or compressing the solid active ingredient; and in the presence of at least one auxiliary, for example by intimately mixing the active ingredient with one or more auxiliary agents and / or grinding the active ingredient with one or more auxiliary agents. These methods for preparing the compositions and the use of compound (I) for preparing these compositions are also subject matter of the present invention.

[0382] Another aspect of the present invention relates to the use of a compound of formula (I) or preferably of the compounds as defined herein according to the invention, a composition comprising at least one compound of formula (I) or at least one preferred compound as defined herein, or a fungicidal or insecticidal mixture comprising at least one compound of formula (I) or at least one preferred compound as defined herein in admixture with other fungicides or insecticides as described above, for controlling or preventing infestation of plants, for example useful plants (such as crop plants), their propagation material (such as seeds), harvested crops (such as harvested food crops), or non-living materials by insects or phytopathogenic microorganisms, preferably fungal organisms.

[0383] Another aspect of the present invention relates to a method for controlling or preventing infestation of plants, for example useful plants (such as crop plants), their propagation material (such as seeds), harvested crops (such as harvested food crops), or non-living materials by phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans (especially fungal organisms), which method comprises applying a compound of formula (I) according to the invention or preferably the various compounds as defined herein as active ingredient to these plants, parts of these plants or the locus thereof, their propagation material, or any part of these non-living materials.

[0384] Control or prevention means the reduction of infestation by insects or phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans, especially fungal organisms, to such a level that an improvement is demonstrated.

[0385] The preferred method of controlling or preventing crop plants from being infected by plant pathogenic microorganisms (especially fungal organisms) or insects is foliar application, which includes applying the compound with formula (I) according to the present invention or containing at least one agrochemical composition with the compound with formula (I). Frequency of application and application ratio will depend on the risk of infection by the corresponding pathogen or insect. However, the compound with formula (I) according to the present invention can also be applied to the soil (soil application) by the root (systemic effect) penetration plant through the soil by soaking the place of plant with liquid formulation or by applying the compound in solid form, for example, in granular form to the soil. In rice crops, such granules can be applied to the paddy field of irrigation. Compound with formula (I) can also be applied to seeds (coating) by impregnating seeds or tubers with the liquid formulation of fungicide or dressing it with solid formulation.

[0386] Formulations, e.g. compositions containing a compound of formula (I) according to the invention and, if desired, solid or liquid adjuvants or monomers for encapsulating the compound of formula (I), can be prepared in a known manner, typically by intimately mixing and / or grinding the compound with extenders, e.g. solvents, solid carriers and, optionally, surface-active compounds (surfactants).

[0387] Advantageous application rates are generally 5g to 2kg of active ingredient (ai) per hectare (ha), preferably 10g to 1 kg ai / ha, most preferably 20g to 600g ai / ha. When used as a seed drench, a suitable dosage is 10mg to 1g active substance / kg seed.

[0388] As used herein, the term "g ai / ha" refers to an application rate given in grams [g] of active ingredient [ai] per unit surface [ha]. The unit hectare (symbol ha) is equal to an area with a side length of 100 m (1 hm2). 2 ) or a square of 10,000 square meters. The hectare is a commonly used unit of area in the metric system.

[0389] When the combinations according to the invention are used to treat seed, application rates of 0.001 to 50 g of compound of formula (I) per kg of seed, preferably 0.01 to 10 g per kg of seed, are generally sufficient.

[0390] Suitably, the composition according to the invention comprising a compound of formula (I) is administered prophylactically (meaning before development of the disease) or therapeutically (meaning after development of the disease).

[0391] The composition of the present invention can be used in any conventional form, for example in the form of a twin pack, a dry seed treatment powder (DS), a seed treatment emulsion (ES), a seed treatment flowable concentrate (FS), a seed treatment solution (LS), a seed treatment water-dispersible powder (WS), a seed treatment capsule suspension (CF), a seed treatment gel (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspoemulsion (SE), a capsule suspension (CS), a water-dispersible granule (WG), an emulsifiable granule (EG), an oil-in-oil emulsion (EO), an oil-in-water emulsion (EW), a microemulsion (ME), an oil dispersible suspension (OD), an oil suspension concentrate (OF), an oil-soluble liquid (OL), a soluble concentrate (SL), an ultra low volume suspension concentrate (SU), an ultra low volume liquid (UL), a concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0392] Such compositions can be produced in a conventional manner, for example by mixing active ingredients with suitable formulation inerts (diluents, solvents, fillers and optionally other formulation ingredients, such as surfactants, biocides, antifreeze agents, adhesives, thickeners and compounds providing auxiliary effects). Conventional slow-release formulations intended to last for a long time can also be used. In particular, formulations to be applied in a spray form (such as water-dispersible concentrates (such as EC, SC, DC, OD, SE, EW, EO, etc.), wettable powders and granules) can contain surfactants (such as wetting agents and dispersants) and other compounds providing auxiliary effects, such as condensation products of formaldehyde with naphthalene sulfonates, alkyl aryl sulfonates, lignin sulfonates, fatty alkyl sulfates and ethoxylated alkylphenols and ethoxylated fatty alcohols.

[0393] The combination of the present invention and the diluent are used in the form of a suitable seed dressing formulation, for example an aqueous suspension or dry powder having good adhesion to the seed, in a manner known per se. Such seed dressing formulations are known in the art. The seed dressing formulations may contain a single active ingredient or a combination of active ingredients in encapsulated form, for example as sustained-release capsules or microcapsules.

[0394] In some embodiments, the present invention provides the preparation of the present invention.Usually, these preparations comprise by weight 0.01% to 90% activating agent, 0% to 20% agriculturally acceptable surfactant and 10% to 99.99% solid or liquid preparation inert agent and one or more adjuvants, and this activating agent is by at least according to the compound with formula (I) of the present invention alternatively together with other activating agents (particularly microbicide or preservative etc.) form.The concentrated form of composition contains by weight between about 2% and 80%, preferably between about 5% and 70% activating agent.The application form of preparation can for example contain by weight 0.01% to 20%, preferably by weight 0.01% to 5% activating agent.Yet commercial product will preferably be formulated as concentrate, and end-user will usually use the preparation of dilution.

[0395] While it is preferred to formulate commercial products as concentrates, the end user will generally use dilute formulations.

[0396] The application rate varies within wide limits and depends on the nature of the soil, the application method, the crop plants, the harmful organisms to be controlled, the prevailing climatic conditions, and other factors dictated by the application method, the time of application, and the target crop. In general, the compound can be applied at an application rate of 1 l / ha to 2000 l / ha, in particular 10 l / ha to 1000 l / ha.

[0397] A preferred formulation may have the following composition (wt %):

[0398] Emulsifiable concentrates :

[0399] Active ingredient: 1% to 95%, preferably 60% to 90%

[0400] Surfactant: 1% to 30%, preferably 5% to 20%

[0401] Liquid carrier: 1% to 80%, preferably 1% to 35%

[0402] Dust agent :

[0403] Active ingredient: 0.1% to 10%, preferably 0.1% to 5%

[0404] Solid carrier: 99.9% to 90%, preferably 99.9% to 99%

[0405] Suspension concentrate:

[0406] Active ingredient: 5% to 75%, preferably 10% to 50%

[0407] Water: 94% to 24%, preferably 88% to 30%

[0408] Surfactant: 1% to 40%, preferably 2% to 30%

[0409] wettable powder :

[0410] Active ingredient: 0.5% to 90%, preferably 1% to 80%

[0411] Surfactant: 0.5% to 20%, preferably 1% to 15%

[0412] Solid carrier: 5% to 95%, preferably 15% to 90%

[0413] Granules:

[0414] Active ingredient: 0.1% to 30%, preferably 0.1% to 15%

[0415] Solid carrier: 99.5% to 70%, preferably 97% to 85%

[0416] The disclosure of this application enables every combination of the embodiments disclosed herein.

[0417] The compounds according to the following Tables A-1 to A-23 can be prepared according to the above-mentioned method. These examples are subsequently intended to illustrate the present invention and to show preferred compounds with formula (I). In any one of the following Tables A-1 to A-23, the presence of one or more possible asymmetric carbon atoms in the compounds with formula (I) according to the present invention means that these compounds can exist in chiral isomer form, that is, in the form of enantiomers or diastereomers.

[0418] Table A : This table discloses 75 compounds of formula (Iaa) according to the present invention, wherein:

[0419] where G has the formula defined as

[0420]

[0421]

[0422]

[0423]

[0424] The following compounds represent specific compounds of formula (Iaa) as described in Tables A-1 to A-23, wherein G is as defined in Table A. For example, compound A-1.G1 represents a compound of formula (Iaa) wherein R 2 、R 4 、R 5 、R 6 、R 10 、R 11 and B 1 is as defined in Table A-1 and G is G1 as defined in Table A.

[0425] Table A-1: This table provides 75 compounds A-1.G1 to A-1.G75 of formula (Iaa), wherein R 2 、R 4 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CH, and G is as defined in Table A. For example, compound A-1.G1 has the following structure:

[0426]

[0427] Table A-2: This table provides 75 compounds A-2.G1 to A-2.G75 of formula (Iaa), wherein R 2 、R 4 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCl, and G is as defined in Table A.

[0428] Table A-3: This table provides 75 compounds A-3.G1 to A-3.G75 of formula (Iaa), wherein R 2 It is CH3, R 4 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CH, and G is as defined in Table A.

[0429] Table A-3: This table provides 75 compounds A-3.G1 to A-3.G75 of formula (Iaa), wherein R2 It is CH3, R 4 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CH, and G is as defined in Table A.

[0430] Table A-4: This table provides 75 compounds A-4.G1 to A-4.G75 of formula (Iaa), wherein R 2 It is CH3, R 4 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCl, and G is as defined in Table A.

[0431] Table A-5: This table provides 75 compounds A-5.G1 to A-5.G75 of formula (Iaa), wherein R 4 It is CH3, R 2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CH, and G is as defined in Table A.

[0432] Table A-6: This table provides 75 compounds A-6.G1 to A-6.G75 of formula (Iaa), wherein R 4 It is CH3, R 2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCl, and G is as defined in Table A. For example, compound A-6.G3 has the following structure:

[0433]

[0434] Table A-7: This table provides 75 compounds A-7.G1 to A-7.G75 of formula (Iaa), wherein R 4 It is CH3, R 2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CBr, and G is as defined in Table A.

[0435] Table A-8: This table provides 75 compounds A-8.G1 to A-8.G75 of formula (Iaa), wherein R 4 It is CH3, R 2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCN, and G is as defined in Table A.

[0436] Table A-9: This table provides 75 compounds A-9.G1 to A-9.G75 of formula (Iaa), wherein R 4 It is CH3, R 2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCOCH3, and G is as defined in Table A.

[0437] Table A-10: This table provides 75 compounds A-10.G1 to A-10.G75 of formula (Iaa), wherein R 4 It is CH3, R 2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCOCH3, and G is as defined in Table A.

[0438] Table A-11: This table provides 75 compounds A-11.G1 to A-11.G75 of formula (Iaa), wherein R 4 It is CH3, R 2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CC=N(OCH3)CH3, and G is as defined in Table A. For example, compound A11-G72 has the following structure.

[0439]

[0440] Table A-12: This table provides 75 compounds A-12.G1 to A-12.G75 of formula (Iaa), wherein R 4 It is CH3, R2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is CNH2, and G is as defined in Table A.

[0441] Table A-13: This table provides 75 compounds A-13.G1 to A-13.G75 of formula (Iaa), wherein R 2 and R 4 It is CH3, R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCl, and G is as defined in Table A.

[0442] Table A-14: This table provides 75 compounds A-14.G1 to A-14.G75 of formula (Iaa), wherein R 2 and R 4 It is CH3, R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCN, and G is as defined in Table A.

[0443] Table A-15: This table provides 75 compounds A-15.G1 to A-15.G75 of formula (Iaa), wherein R 2 It is Cl, R 4 It is CH3, R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCl, and G is as defined in Table A.

[0444] Table A-16: This table provides 75 compounds A-16.G1 to A-16.G75 of formula (Iaa), wherein R 2 It is Cl, R 4 It is CH3, R 5 、R 6 、R 10 and R 11 It's H, B 1 is CCN, and G is as defined in Table A. For example, compound A-16.G64 has the following structure.

[0445]

[0446] Table A-17: This table provides 75 compounds A-17.G1 to A-17.G75 of formula (Iaa), wherein R 4 It is CH3, R 10 It is Cl, R 2 、R 5 、R 6 and R 11 It's H, B 1 is CH, and G is as defined in Table A.

[0447] Table A-18: This table provides 75 compounds A-18.G1 to A-18.G75 of formula (Iaa), wherein R 4 It is CH3, R 10 It is CN, R 2 、R 5 、R 6 and R 11 It's H, B 1 is CH, and G is as defined in Table A.

[0448] Table A-19: This table provides 75 compounds A-19.G1 to A-19.G75 of formula (Iaa), wherein R 4 It is CH3, R 11 It is Cl, R 2 、R 5 、R 6 and R 10 It's H, B 1 is CH, and G is as defined in Table A.

[0449] Table A-20: This table provides 75 compounds A-20.G1 to A-20.G75 of formula (Iaa), wherein R 4 It is CH3, R 11 It is CN, R 2 、R 5 、R 6 and R 10 It's H, B 1 is CH, and G is as defined in Table A.

[0450] Table A-21: This table provides 75 compounds A-21.G1 to A-21.G75 of formula (Iaa), wherein R 4 It is CH3, R 11 is OCH3, R 2 、R 5 、R 6 and R10 It's H, B 1 is CCl, and G is as defined in Table A.

[0451] Table A-22: This table provides 75 compounds A-22.G1 to A-22.G75 of formula (Iaa), wherein R 4 It is CH3, R 2 、R 5 、R 6 、R 10 and R 11 It's H, B 1 is N, and G is as defined in Table A. For example, compound A-22.G18 has the following structure:

[0452]

[0453] Table A-23: This table provides 75 compounds A-23.G1 to A-23.G75 of formula (Iaa), wherein R 4 is CH3, R10 is Cl, R 2 、R 5 、R 6 and R 11 It's H, B 1 is N, and G is as defined in Table A.

[0454] Examples

[0455] The following examples serve to illustrate the invention and are not meant to limit the invention in any way.

[0456] The compounds of the invention can be distinguished from known compounds by a greater efficacy at low application rates, which can be demonstrated by a person skilled in the art using the experimental procedures outlined in the examples, using lower application rates (if necessary), for example, 60 ppm, 20 ppm or 2 ppm.

[0457] Compounds of formula (I) may have a number of benefits, including, among others, favorable levels of biological activity for protecting plants from diseases caused by fungi or superior properties for use as agrochemical active ingredients (e.g., higher biological activity, favorable activity spectrum, increased safety (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).

[0458] Throughout this specification, temperatures are given in degrees Celsius and "mp" means melting point. LC / MS means liquid chromatography mass spectrometry, and a description of the apparatus and methods follows.

[0459] Recorded on a Bruker 400 MHz spectrometer1 H NMR and 19 F NMR measurements, chemical shifts relative to TMS ( 1 H) and CFCl3( 19 F) Standards are given in ppm. Spectra were measured in deuterated solvents as specified. The compounds were characterized using any of the following LCMS methods. Characteristic LCMS values ​​obtained for each compound are the retention time ("Rt", reported in minutes) and the measured molecular ion (M+H) + or (MH) - .

[0460] The following LC-MS method was used to analyze these compounds:

[0461] Method A (LC-MS): Spectra were recorded on a mass spectrometer from Waters (SQD2 or QDA single quadrupole mass spectrometer) equipped with an electrospray source (polarity: positive and negative switching, capillary: 0.8-3.00 kV, cone range: 25 ° C, source temperature: 120 ° C -150 ° C, desolvation temperature: 500 ° C -600 ° C, cone gas flow: 50 L / h, desolvation gas flow: 1000 L / h, mass range: 110 to 850 Da) and Acquity UPLC from Waters: quaternary solvent manager, heated column compartment, diode array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30x2.1 mm, temperature: 40°C, DAD wavelength range (nm): 200 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH: gradient: 0 min 10% B; 0-0.2 min 10%-50% B; 0.2-0.6 min 50-100% B; 0.6-1.3 min 100% B; 1.3-1.4 min 100-10% B; 1.4-1.6 min 10% B; flow rate (mL / min) 0.6.

[0462] Method B (LC-MS):Spectra were recorded on a mass spectrometer from Waters (Acquity QDa mass spectrometer) equipped with an electrospray source (polarity: positive and negative switching, capillary: 0.8 kV, cone range: 25 V, extractor: V (QDa detector without extractor voltage), source temperature: 120°C, desolvation temperature: 600°C, cone gas flow: 50 L / h, desolvation gas flow: 1000 L / h, mass range: 110 to 850 Da) and an Acquity UPLC from Waters: quaternary solvent manager, heated column compartment, diode array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30x2.1 mm, temperature: 40°C, DAD wavelength range (nm): 200 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH: Gradient: 0 min 10% B; 0-0.2 min 10%-50% B; 0.2-0.6 min 50-100% B; 0.6-1.3 min 100% B; 1.3-1.4 min 100-10% B; 1.4-1.6 min 10% B; flow rate (mL / min) 0.6.

[0463] Method C (LC-MS): Spectra were recorded on a mass spectrometer from Agilent Technologies (6410 triple quadrupole mass spectrometer) equipped with an electrospray source (polarity: positive or negative ion, MS2 scan, capillary voltage: 4.00 kV, fragmentor voltage: 100 V, desolvation temperature: 350°C, gas flow: 11 L / min, nebulizer gas: 45 psi, mass range: 110 to 1000 Da) and a 1200 series HPLC from Agilent: quaternary pump, heated column compartment and VWD detector. Column: KINETEX EVO C18, 2.6 μm, 50 x 4.6 mm, temperature: 40°C, detector VWD wavelength: 254 nm, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.1% HCOOH: gradient: 0 min 10% B, 90% A; 0.9-1.8 min 100% B; 1.8-2.2 min 100-10% B; 2.2-2.5 min 10% B; flow rate (mL / min) 1.8.

[0464] Method D (LC-MS):Spectra were recorded on a mass spectrometer from Agilent Technologies (MSD-IQ mass spectrometer) equipped with an electrospray source (polarity: positive or negative ion, MS2 scan, capillary voltage: 3.5 kV, fragmentor voltage: 110 V, desolvation temperature: 325°C, gas flow: 13 L / min, nebulizer gas: 55 psi, mass range: 110 to 850 Da) and a 1290 series HPLC from Agilent: quaternary pump, heated column compartment and diode array detector. Column: AGILENTPOROSHELL 120EC-C18, 1.9 μm, 50 x 2.1 mm, temperature: 40°C, DAD wavelength range (nm): 190 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.1% HCOOH: gradient: 0-0.5 min 10% B, 90% A; 1.2-1.5 min 95% B, 5% A; 1.8-2.5 min 10% B, 90% A; flow rate (mL / min) 0.8

[0465] Preparation Examples

[0466]

[0467]

[0468] The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable grinder to obtain a wettable powder which can be diluted with water to give a suspension of the desired concentration.

[0469]

[0470] The combination is thoroughly mixed with adjuvants and the mixture is thoroughly ground in a suitable grinder to obtain a dust that can be used directly for seed treatment.

[0471] Emulsifiable concentrates

[0472]

[0473] Emulsions of any desired dilution which can be used in plant protection can be obtained from these concentrates by dilution with water.

[0474]

[0475] Ready-to-use dusts are obtained by mixing the combination with a carrier and grinding the mixture in a suitable grinder. Such dusts can also be used for dry seed dressing of seeds.

[0476] Extruder pellets

[0477]

[0478] The combination is mixed with the adjuvants and ground, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

[0479] Coated granules

[0480] Active ingredient 8%

[0481] Polyethylene glycol (molecular weight 200) 3%

[0482] Kaolin 89%

[0483] This finely ground combination is applied uniformly in a mixer to the kaolin moistened with polyethylene glycol. In this way, dust-free coated granules are obtained.

[0484] Suspension concentrates

[0485]

[0486] The finely ground combination is intimately mixed with adjuvants to give a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation materials can be treated and protected against microbial infestation by spraying, pouring or immersion.

[0487] Flowable concentrate for seed treatment

[0488]

[0489]

[0490] The finely ground combination is intimately mixed with adjuvants to give a flowable concentrate from which solutions of any desired dilution can be obtained by dilution with water and which can be used directly for seed treatment. Using such dilutions, living plants as well as plant propagation materials can be treated and protected against microbial infestation by spraying, pouring or immersion.

[0491] Extended-release capsule suspension

[0492] 28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate / polymethylene-polyphenyl isocyanate mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 parts of a defoamer, and 51.6 parts of water until the desired particle size is reached. To this emulsion, 2.8 parts of a mixture of 1,6-hexanediamine in 5.3 parts of water are added. The mixture is stirred until the polymerization reaction is complete. The resulting capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersant. The capsule suspension formulation contains 28% active ingredient. The diameter of the medium capsules is 8-15 microns. The resulting formulation is applied to the seeds as an aqueous suspension in a device suitable for this purpose.

[0493] Formulation types include emulsion concentrates (EC), suspension concentrates (SC), suspoemulsions (SE), capsule suspensions (CS), water-dispersible granules (WG), emulsifiable granules (EG), emulsions, water-in-oil emulsions (EO), oil-in-water emulsions (EW), microemulsions (ME), oil dispersions (OD), oil suspensions (OF), oil-soluble concentrates (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume concentrates (UL), finished products (TK), dispersible concentrates (DC), wettable powders (WP), soluble granules (SG), or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0494] abbreviation

[0495] CDCl3 deuterated chloroform

[0496] DABCO 1,4-diazabicyclo[2.2.2]octane, also known as triethylenediamine or TEDA

[0497] DCC Dicyclohexylcarbodiimide

[0498] DCM dichloromethane (methylene chloride or methylene dichloride)

[0499] DMF dimethylformamide

[0500] DMSO dimethyl sulfoxide

[0501] DMSO-d6 deuterated dimethyl sulfoxide

[0502] EtOAc

[0503] HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate

[0504] HCl

[0505] h / hrs hours

[0506] LC-MS Liquid chromatography mass spectrometry (LC-MS or LCMS)

[0507] rh relative humidity

[0508] rt Room temperature (rt or RT)

[0509] Rt retention time

[0510] ssp. subspecies

[0511] T3P Propanephosphonic anhydride, also known as 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphanin-2,4,6-trioxide

[0512] TBME tert-butyl methyl ether

[0513] TEA triethylamine (Et3N)

[0514] THF Tetrahydrofuran

[0515] Preparation Example

[0516] The compounds of formula (I) according to the present invention can be prepared using the synthetic techniques described above and below.

[0517] "Mp" refers to melting point in °C. Free radicals represent methyl groups. Recorded on a Bruker 400 MHz spectrometer (or 600 MHz as indicated). 1 H NMR and 19 F NMR measurements, chemical shifts relative to TMS ( 1 H) and CFCl3( 19 F) Standards are given in ppm. Spectra were measured in deuterated solvents as specified. The compounds were characterized using any of the following LC-MS methods. Characteristic LCMS values ​​obtained for each compound are the retention time ("Rt", reported in minutes) and the measured molecular ion (M+H) + or (MH) - .

[0518] Example P1: N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)- Preparation of 1,3,4-thiadiazole-2-carboxamide (Compound P-3, Table P)

[0519] Table P

[0520] Step 1: Preparation of 2-(1-methylpyrazol-4-yl)propionitrile

[0521]

[0522] Under argon at -78 ℃ to 2-(1-methyl isophthalic acid H-pyrazole-4-yl) acetonitrile (1.5g, 11.8mmol) in THF (35mL) solution, add N-butyl lithium (5.9mL, 11.8mmol, 2.5M in hexane), and the gained light yellow suspension is stirred at this temperature for 25min and then add iodomethane (0.73mL, 11.8mmol). The gained yellow reaction mixture is stirred at -78 ℃ for 5min, is warmed to room temperature and stirs for 30min again. The reaction mixture is diluted with water and extracted with EtOAc (x3). The organic layer merged is washed with salt water, dried over sodium sulfate and concentrated in vacuo, to obtain 2-(1-methylpyrazole-4-yl) propionitrile. The crude reaction product is used in the next step as it is.

[0523] Step 2: Preparation of 2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propionitrile

[0524]

[0525] To a solution of 2- (1- methylpyrazole -4- bases) propionitrile (1.59g, 11.8mmol) in THF (35mL) was added N-butyl lithium (5.9mL, 11.8mmol, 2.5M in hexane) at -78°C under argon. The obtained light green suspension was stirred at this temperature for 10min and then 2,6- dichloropyridine (1.77g, 11.8mmol) was slowly added. The obtained green suspension was stirred at -78°C for 5min, warmed to room temperature and stirred for another 10min under argon. The reaction mixture was diluted with water and extracted with EtOAc (x3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained crude residue was purified by flash chromatography eluted with EtOAc / cyclohexane to obtain 2- (6- chloro-2-pyridyl) -2- (1- methylpyrazole -4- bases) propionitrile as a light yellow oil.

[0526] LCMS (Method A): retention time 1.04 min, m / z 247 (M+H)

[0527] Step 3: Preparation of 2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propan-1-amine

[0528]

[0529] At room temperature under argon, 2-(6-chloro-2-pyridyl)-2-(1-methylpyrazole-4-yl) propionitrile sample (1.00g, 4.05mmol) dissolved in THF (12mL) is dropwise processed with borane dimethyl sulfide complex (1.15mL, 12.2mmol). Gained yellow solution is stirred at 65 DEG C for 3 hours and then cooled to 0 DEG C.Then orange solution (intense gas release!) is carefully dropwise processed with concentrated HCl (2.72mL, 16.3mmol).Then the reaction mixture is stirred at 50 DEG C for 1h, and then cooled to room temperature again and alkalized to pH 12 with NaOH 6N.Gained mixture is extracted with EtOAc (x3).The organic layer merged is washed once with salt water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain 2-(6-chloro-2-pyridyl)-2-(1-methylpyrazole-4-yl) third-1-amine as light brown oil.

[0530] LCMS (Method B): retention time 0.26 min, m / z 251 (M+H)

[0531] Step 4: Preparation of tert-butyl N-[(3,5-difluoropyridine-2-carbonyl)amino]carbamate

[0532]

[0533] At room temperature under argon, a solution of tert-butyl N-aminocarbamate (0.82 g, 6.26 mmol) in EtOAc (12 mL) was dropwise treated with a solution of 3,5-difluoropyridine-2-carbonyl chloride (1.17 g, 6.26 mmol) in EtOAc (12 mL). The reaction mixture was stirred at room temperature for 1 hour, after which LCMS showed that the reaction was complete. The reaction mixture was diluted with water, extracted with EtOAc (x3), and the combined organic layer was dried over sodium sulfate and concentrated in vacuo to obtain the title compound as a light yellow solid.

[0534] LCMS (Method B): retention time 0.57 min, m / z 174 (M-99)

[0535] Step 5: Preparation of 3,5-difluoropyridine-2-carbohydrazide

[0536]

[0537] The sample of N-[(3,5-difluoropyridine-2-carbonyl) amino] tert-butyl carbamate (1.7g, 6.2mmol) was dissolved in HCl / dioxanes (16mL, 4mol / L) and stirred at room temperature for 12 hours. After the reaction was completed (monitored by LCMS and TLC), the reaction mixture was quenched with sodium bicarbonate and extracted with EtOAc (x3). The organic layer merged was dried over sodium sulfate and concentrated in vacuo to obtain 3,5-difluoropyridine-2-carbohydrazide as a light yellow solid.

[0538] LCMS (Method B): retention time 0.16 min, m / z 174 (M+1)

[0539] Step 6: Preparation of methyl 2-[2-(3,5-difluoropyridine-2-carbonyl)hydrazine]-2-oxo-acetate

[0540]

[0541] 3,5-difluoropyridine-2-carbonyl (0.7g, 4mmol) and triethylamine (1mL, 10mmol) are dissolved in the solution in acetonitrile (7mL) and are cooled to 0 DEG C and dropwise processed with methyl oxalyl chloride (0.4mL, 4mmol).Gained reaction mixture is at room temperature stirred 1 hour.Then reaction mixture is diluted with EtOAc (20mL) and extracted (x3).By the organic layer merged through dried over sodium sulfate and vacuum concentration, to obtain 2-[2-(3,5-difluoropyridine-2-carbonyl) hydrazine-2-oxo-methyl acetate.

[0542] LCMS (Method B): retention time 0.19 min, m / z 260 (M+1)

[0543] Step 7: Preparation of methyl 5-(3,5-difluoro-2-pyridyl)-1,3,4-thiadiazole-2-carboxylate

[0544]

[0545] By 2-[2-(3,5-difluoropyridine-2-carbonyl) hydrazine radical]-2-oxo-methyl acetate (0.5g, 2mmol) and phosphorus pentasulfide (0.1mL, 1mmol) solution in toluene (5mL) reflux 3 hours.By LCMS monitoring reaction process, and after completing, by reaction mixture water cancellation and EtOAc extraction (x3).By the organic layer merged dried over sodium sulfate and vacuum concentration, to obtain crude product, by this crude product by silica gel column chromatography (being used in the 0-25%EtOAc wash-out in hexamethylene) obtain 5-(3,5-difluoro-2-pyridyl)-1,3,4-thiadiazole-2-methyl-formiate.

[0546] LCMS (Method B): retention time 1.02 min, m / z 258 (M+1)

[0547] Step 8: N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)- Preparation of 1,3,4-thiadiazole-2-carboxamide (Compound P-3, Table P)

[0548] To a solution of 5-(3,5-difluoro-2-pyridyl)-1,3,4-thiadiazole-2-methylformate (0.05g, 0.19mmol) in toluene (1mL) was added 2-(6-chloro-2-pyridyl)-2-(1-methylpyrazole-4-yl)propan-1-amine (0.058g, 0.23mmol) at 0°C. A solution of trimethylaluminum solution (2.0mol / L) in toluene (0.29mL, 0.58mmol) was added thereto, and the mixture was then heated to 70°C. After the reaction was completed (LCMS analysis), the reaction mixture was slowly quenched in an ice-cold saline solution, and the saline solution was then extracted with EtOAc (x3). The combined organic layer was dried over sodium sulfate and concentrated in vacuo. The crude product was adsorbed on silica and purified by normal phase column chromatography using (0-60% EtOAc in cyclohexane) to obtain pure compound N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazole-2-carboxamide as a white solid.

[0549] LCMS (Method B): retention time 1.15 min, m / z 476 (M+H)

[0550] 1 H NMR (400MHz, CDCl3) δppm 8.46 (d, J = 2.25Hz, 1H), 8.30 (br t,J=6.32Hz,1H),7.59(t,J=7.82Hz,1H),7.45(ddd,J=9.72,7.72,2.31Hz,1H),7.33(s ,1H),7.29-7.21(m,2H),7.14-7.10(m,1H),4.18-4.03(m,2H),3.87(s,3H),1.74(s,3H)

[0551] Example P2: N-[2-(6-cyano-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2- Preparation of pyridyl)-1,3,4-thiadiazole-2-carboxamide (Compound P-2, Table P)

[0552] Table P

[0553] By N-[2-(6-chloro-2-pyridyl)-2-(1-methylpyrazole-4-yl) propyl group]-5-(3,5-difluoro-2-pyridyl)-1,3,4-thiadiazole-2-carboxamide (0.1g, 0.21mmol, prepared as described in Example P1 above) and zinc cyanide (0.05g, 0.42mmol) in DMF (1.05mL) degassed 10min under nitrogen. In this solution, tetrakis(triphenylphosphine)palladium (0) (24.5mg, 0.021mmol) is added, and the gained light brown suspension is stirred at 120 DEG C in microwave for 3 hours. Reaction process is monitored by LCMS, and after completing, reaction mixture is cooled and diluted with ice-cold water (20mL).Mixture is extracted with EtOAc (x3) and then the organic layer washed with salt water, dried over sodium sulfate, and concentrated in vacuo. The crude product was absorbed onto silica gel and purified by combiflash chromatography eluting with 0-80% EtOAc in cyclohexane to afford the product as a yellow gummy solid. The product was further purified by reverse phase column chromatography using 0-70% acetonitrile in water to afford N-[2-(6-cyano-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazole-2-carboxamide as a yellow gummy mass.

[0554] LCMS (Method B): retention time 1.04 min, m / z 467 (M+H)

[0555] 1 H NMR (400MHz, CDCl3) δppm 8.46 (d, J = 2.25Hz, 1H), 8.00 (br t,J=6.44Hz,1H),7.77(t,J=7.85Hz,1H),7.63(d,J=7.67Hz,1H),7.45-7.42(m,2H),7 .30-7.31(m,1H),7.26(d,J=0.75Hz,1H),4.25-4.05(m,2H),3.88(s,3H),1.76(s,3H)

[0556] Example P3: N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)- Preparation of (4-(2-(2-pyridyl)isoxazole-3-carboxamide) (Compound P-1, Table P)

[0557] Table P

[0558] Step 1: Preparation of 3,5-difluoro-N-methoxy-N-methyl-pyridine-2-carboxamide

[0559]

[0560] To a suspension of 3,5-difluoropyridine-2-carboxylic acid (10 g, 62.8 mmol) and N, O-dimethylhydroxylamine hydrochloride (6.56 g, 66.0 mmol) in EtOAc (250 mL) at room temperature, 1-propanephosphonic anhydride (74.8 mL, 125 mmol) was added, followed by N, N-diisopropylethylamine (33.0 mL, 188 mmol). The resulting reaction mixture was stirred at room temperature for 18 hours, whereupon TLC analysis showed that the reaction was complete. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (x3). The combined organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by combined flash chromatography to obtain 3,5-difluoro-N-methoxy-N-methyl-pyridine-2-carboxamide as a brown liquid.

[0561] LCMS (Method B): retention time 0.60 min, m / z 203 (M+H)

[0562] Step 2: Preparation of 1-(3,5-difluoro-2-pyridyl) ketene

[0563]

[0564] At -15 DEG C under nitrogen, methylmagnesium bromide (2M in THF, 33mL, 98.9mmol) solution is added dropwise to 3,5-difluoro-N-methoxy-N-methyl-pyridine-2-carboxamide (10g, 49.4mmol) in anhydrous THF (150mL). The gained light brown suspension is warmed to room temperature and stirred for 1 hour, wherein LCMS and TLC analysis show that the reaction is complete. At 0 DEG C, the reaction mixture is slowly quenched with concentrated hydrochloric acid (10.7mL, 118mmol). The mixture is extracted with EtOAc (x3), and the organic layer is merged, washed with water and brine successively, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to obtain 1- (3,5-difluoro-2-pyridyl) ketene as a brown liquid, which is used without further purification.

[0565] LCMS (Method A): retention time 0.94 min, m / z 158.0 (M+H)

[0566] Step 3: Preparation of ethyl 5-(3,5-difluoro-2-pyridyl)-5-hydroxy-4H-isoxazole-3-carboxylate

[0567]

[0568] To a solution of 1-(3,5-difluoro-2-pyridyl) ethyl ketone (2.00g, 12.09mmol) and diethyl oxalate (9.22mL, 66.5mmol) in toluene (40mL) at -78°C, potassium tert-butoxide (1.39g, 12.1mmol) was added. Cooling bath was removed, and the resulting suspension was warmed to room temperature and stirred for 20min. The reaction mixture was then cooled to -5°C-0°C and hydroxylamine hydrochloride (1.71g, 24.2mmol) and acetic acid (2.16mL, 36.2mmol) were added, and the resulting reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was poured into water (50mL) and extracted with EtOAc (x3). The organic layer merged was washed with salt water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The resulting crude residue containing ethyl 5-(3,5-difluoro-2-pyridinyl)-5-hydroxy-4H-isoxazole-3-carboxylate was used as such in the next step.

[0569] LCMS (Method B): retention time 1.63 min, m / z 272 (M+)

[0570] Step 4: Preparation of ethyl 5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxylate

[0571]

[0572] To a solution of 5- (3,5-difluoro-2-pyridyl) -5-hydroxy -4H-isoxazole -3- ethyl formate (12.8g, 47.0mmol) in toluene (256mL) at room temperature, p-toluenesulfonic acid (8.52g, 47.0mmol) was added, the reaction mixture was heated to 90 DEG C and stirred for 16 hours. After the reaction was completed, the mixture was cooled to 0 DEG C and slowly quenched with saturated sodium bicarbonate aqueous solution. The mixture was extracted with EtOAc (3x 25mL) and the combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by reverse phase column and purified again by normal phase to obtain 5- (3,5-difluoro-2-pyridyl) isoxazole -3- ethyl formate as a white solid.

[0573] LCMS (Method B): retention time 1.88 min, m / z 255.0 (M+H)

[0574] Step 5: Preparation of 5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxylic acid

[0575]

[0576] To a solution of 5- (3,5- bis-fluoro- 2- pyridyl) isoxazole -3- ethyl formate (4.95g, 18.5mmol) in THF (20mL) and water (5mL) is added lithium hydroxide hydrate (0.88g, 37.0mmol) at room temperature, and the resulting reaction mixture is stirred at room temperature for 2 hours. After the completion of the reaction, the reaction mixture is diluted with water and extracted with TBME. The water layer is then acidified with 2N HCl. This makes solid precipitation, the solid is filtered through a Buchner funnel and dried under reduced pressure, to obtain 5- (3,5- bis-fluoro- 2- pyridyl) isoxazole -3- formic acid as a pale solid.

[0577] LCMS (Method B): retention time 0.31 min, m / z 227 (M+H)

[0578] Step 6: N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)- Preparation of (4-(2-(2-pyridyl)isoxazole-3-carboxamide) (Compound P-1, Table P)

[0579] At room temperature to 2-(6-chloro-2-pyridyl)-2-(1-methylpyrazole-4-yl) third-1-amine (13.7g, 53.6mmol, as described in Example P1 below preparation) and 5-(3,5-difluoro-2-pyridyl) isoxazole-3-formic acid (13.5g, 53.6mmol) in EtOAc (214mL) solution of add N, N-diisopropylethylamine (28.1mL, 161mmol) and 1-propanephosphonic anhydride (63.9mL, 107mmol).Reactant mixture is stirred at room temperature, is monitored by TLC and LCMS.After the reaction is completed, mixture is diluted with cold water and extracted with EtOAc (x3).By the organic layer washed with salt water (40mL) merged, dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by reverse phase combined flash chromatography using 0-70% acetonitrile in water to give the product N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(3,5-difluoro-2-pyridinyl)isoxazole-3-carboxamide as an off-white solid.

[0580] LCMS (Method B): retention time 1.12 min, m / z 459 (M+H)

[0581] 1 H NMR (400MHz, CDCl3) δppm 8.52(d,1H),8.01(t,1H),7.61-7.57(t,1H),7.43-7.39(m,1H),7.33(s,1H),7. 28-7.22(m,3H),7.12-7.10(d,1H),4.12-4.01(m,2H),3.88(s,3H),1.73(s,3H)

[0582] 19 F NMR (400 MHz, chloroform-d) δ ppm -114.22 (s, 1F) -118.96 (s, 1F)

[0583] Example P4: N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3-pyridinyl)- Preparation of 1,3,4-thiadiazole-2-carboxamide (Compound P-7, Table P)

[0584] Table P

[0585] Step 1: Preparation of 2,6-difluoropyridine-3-carbonyl chloride

[0586]

[0587] A sample of 2,6-difluoropyridine-3-carboxylic acid (10.0 g, 59.7 mmol) was dissolved in EtOAc (200 mL) and dropwise treated with oxalyl chloride (7.89 mL, 89.6 mmol). Catalytic dimethylformamide (0.46 mL, 5.9 mmol) was added dropwise and the resulting reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was concentrated in vacuo to obtain the crude title product, which was used as is without any further purification.

[0588] Step 2: Preparation of tert-butyl N-[(2,6-difluoropyridine-3-carbonyl)amino]carbamate

[0589]

[0590] At room temperature under agitation by 2,6- difluoropyridine -3- carbonyl chloride (11g, 58.8mmol) solution in EtOAc (110mL) is added dropwise to the solution of N- aminocarbamic acid tert-butyl ester (7.78g, 58.8mmol) in EtOAc (80mL).Gained reaction mixture is stirred at room temperature and then diluted with water and extracted with EtOAc (x3).By the organic layer washed with salt water merged, dried over sodium sulfate, and concentrated in vacuo, to obtain the thick title compound in white solid, it is used in the next step as it is without any further purification.

[0591] LCMS (Method B): retention time 0.99 min, m / z 174 (M-100)

[0592] Step 3: Preparation of 2,6-difluoropyridine-3-carbohydrazide

[0593]

[0594] Under stirring, a sample of N-[(2,6-difluoropyridine-3-carbonyl) amino] tert-butyl carbamate (8.9 g, 31 mmol) was dissolved in 4M hydrochloric acid in dioxane (77 mL, 310 mmol) and the resulting reaction mixture was stirred at room temperature for 12 hours. After the completion of the reaction, the reaction mixture was diluted with water and extracted with EtOAc (x3). The organic layer merged was washed with salt water, dried over sodium sulfate and concentrated in vacuo to obtain the title compound in a light yellow solid, which was used in the next step as is without any further purification.

[0595] LCMS (Method B): retention time 0.19 min, m / z 174 (M+H)

[0596] Step 4: Preparation of methyl 2-[2-(2,6-difluoropyridine-3-carbonyl)hydrazine]-2-oxo-acetate

[0597]

[0598] By 2,6- difluoropyridine -3- carbohydrazide (3.45g, 18.9mmol) and triethylamine (5.3mL, 37.9mmol) in DCM (35mL) solution is cooled to 0 DEG C and is processed dropwise with methyl oxalyl chloride (1.82mL, 18.9mmol).Reaction process is monitored by LCMS, and after completion, reaction mixture is quenched with 150mL saturated sodium bicarbonate solution and extracted with EtOAc (2x100mL).The organic layer merged is washed with water and salt water successively, dried over sodium sulfate, and concentrated in vacuo to obtain the title compound in light yellow solid, which is used in the next step as it is without further purification.

[0599] LCMS (Method C): retention time 0.30 min, m / z 260 (M+H)

[0600] Step 5: Preparation of methyl 5-(2,6-difluoro-3-pyridyl)-1,3,4-thiadiazole-2-carboxylate

[0601]

[0602] To 2- [2- (2,6- difluoropyridine -3- carbonyl) hydrazine] -2- oxo- -acetic acid methyl esters (0.75g, 2.31mmol) in THF (15mL) solution, Lawesson reagent (1.15g, 2.78mmol) was added, and the reaction mixture was refluxed for 3 hours. The progress of the reaction was monitored by LCMS and after completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with salt water, dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by silica gel chromatography (eluting with 0-30% EtOAc in cyclohexane) to provide 5- (2,6- difluoro -3- pyridyl) -1,3,4- thiadiazole -2- methyl formate as a light yellow solid.

[0603] LCMS (Method A): Retention time 1.07 min, 258 (M+H)

[0604] Step 6: N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3-pyridinyl)- Preparation of 1,3,4-thiadiazole-2-carboxamide (Compound P-7, Table P)

[0605] To a solution of 5-(2,6-difluoro-3-pyridyl)-1,3,4-thiadiazole-2-carboxylic acid methyl ester (0.15 g, 0.55 mmol) and 2-(6-chloro-2-pyridyl)-2-(1-methylpyrazol-4-yl)propan-1-amine (0.17 g, 0.66 mmol, prepared as described in Example P1 above) in toluene (3 mL) was added dropwise trimethylaluminum (2.0 mol / L) in toluene (0.83 mL, 1.66 mmol) at 0 ° C. The resulting reaction mixture was stirred at 70 ° C for 2 hours. After completion of the reaction, the reaction mixture was slowly quenched with ice-cold brine solution and extracted with EtOAc (3 x 20 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The crude product was adsorbed onto silica and purified by normal phase column chromatography eluting with 0-50% EtOAc in cyclohexane to give N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3-pyridinyl)-1,3,4-thiadiazole-2-carboxamide as a light brown solid.

[0606] LCMS (Method B): retention time 1.17 min, m / z 476 (M+H)

[0607] 1 H NMR (400MHz, CDCl3) δppm 8.92-9.00 (m, 1H), 8.41 (br t,J=6.30Hz,1H),7.60(t,J=7.65Hz,1H),7.32(s,1H),7.23-7.30(m,2H),7.12(d,J=7 .70Hz,1H),7.08(dd,J=8.38,2.63Hz,1H),4.04-4.18(m,2H),3.88(s,3H),1.74(s,3H)

[0608] Example P5: N-[2-(6-cyano-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3- Preparation of pyridyl)-1,3,4-thiadiazole-2-carboxamide (Compound P-6, Table P)

[0609] Table P

[0610] To a solution of N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3-pyridinyl)-1,3,4-thiadiazole-2-carboxamide (70 mg, 0.14 mmol) in 1,4-dioxane (0.35 mL) and water (0.35 mL) in a microwave (MV) vial were added potassium acetate (13.8 mg, 0.14 mmol) and potassium ferrocyanide (27 mg, 0.07 mmol), and the resulting reaction mixture was degassed with nitrogen for 5 min. To the reaction mixture was added (2-dicyclohexylphosphine-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]methanesulfonate palladium(II) (12.1 mg, 0.014 mmol), the MW vial was sealed and heated in a microwave at 110 ° C for 2 hours. The solution was cooled to room temperature, quenched with water, and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by combined flash chromatography (silica gel) eluted with 10%-20% EtOAc in cyclohexane to give N-[2-(6-cyano-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-5-(2,6-difluoro-3-pyridinyl)-1,3,4-thiadiazole-2-carboxamide as a light yellow solid.

[0611] LCMS (Method B): retention time 1.10 min, m / z 467 (M+H)

[0612] 1 H NMR(400MHz,CDCl3)δppm 8.92-8.99(m,1H),8.12(br t,J=6.44Hz,1H),7.79(t,J=7.88Hz,1H),7.64(dd,J=7.57,0.81Hz,1H),7.45(dd,J=8.19,0.81Hz, 1H),7.25-7.30(m,2H),7.08(dd,J=8.38,2.75Hz,1H),4.08-4.23(m,2H),3.89(s,3H),1.76(s,3H)

[0613] Example P6: N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)- Preparation of 1,2,4-oxadiazole-5-carboxamide (Compound P-18, Table P)

[0614] Table P

[0615] Step 1: Preparation of 3,5-difluoro-N'-hydroxy-pyridine-2-carboximidamide

[0616]

[0617] To the suspension of 3,5-difluoropyridine-2-carbonitrile (10g, 70.0mmol) in methanol (10mL / g, 100mL), potassium carbonate (14.5g, 105.0mmol) and hydroxylamine hydrochloride (12.7g, 175.0mmol) are added. The reaction mixture is stirred at room temperature for 2h. After the completion of the reaction (monitored by LCMS and TLC), the reaction mixture is diluted with water (60mL) and extracted with EtOAc (2x50mL). The combined organic layer is washed with salt water, through Na2SO4 and is dried and concentrated in vacuo to obtain a crude product. It is purified by the combined flash chromatography of 40%-60% EtOAc in cyclohexane to obtain 3,5-difluoro-N'-hydroxy-pyridine-2-formamidine in a solid.

[0618] LCMS (Method D): retention time 0.29 min, m / z 174 (M+H)

[0619] Step 2: Preparation of methyl 3-(3,5-difluoro-2-pyridyl)-1,2,4-oxadiazole-5-carboxylate

[0620]

[0621] At 0 DEG C under argon to 3,5-difluoro-N '-hydroxy-pyridine-2-carbonitrile (0.1g, 0.58mmol) in acetonitrile (3.5mL / mmol, 2.0mL) and pyridine (0.14mL, 1.73mmol) in a solution of 2-chloro-2-oxo-acetic acid methyl esters (0.11g, 0.08mL, 0.87mmol).Reaction mixture is warmed to room temperature, stirred for 30min, and then stirred for 2h at 80 DEG C.After the reaction is completed (monitored by LCMS and TLC), reaction mixture is diluted with water (50mL) and saturated ammonium chloride, and extracted with DCM (3x 80mL).By the organic layer merged through Na2SO4Dry and be concentrated in vacuo to obtain crude product. This was purified by combined flash chromatography using 30%-40% EtOAc in cyclohexane to give methyl 3-(3,5-difluoro-2-pyridinyl)-1,2,4-oxadiazole-5-carboxylate as a white solid.

[0622] LCMS (Method A): retention time 1.01 min, m / z 242 (M+H)

[0623] 1 H NMR (400MHz, CDCl3) δppm 8.61 (d, J = 2.00Hz, 1H) 7.49 (t, J = 8.44Hz, 1H) 4.13 (s, 3H)

[0624] Step 3: Preparation of lithium 3-(3,5-difluoro-2-pyridyl)-1,2,4-oxadiazole-5-carboxylate

[0625]

[0626] To a solution of 3-(3,5-difluoro-2-pyridyl)-1,2,4-oxadiazole-5-methyl formate (0.5 g, 2.1 mmol) in THF and water (2: 1, 7.5 mL) was added lithium hydroxide monohydrate (89 mg, 2.1 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 h. After the reaction was completed (monitored by LCMS), the reaction mixture was concentrated in vacuo to obtain 3-(3,5-difluoro-2-pyridyl)-1,2,4-oxadiazole-5-lithium formate.

[0627] LCMS (Method A): retention time 0.23 min, m / z 228 (M+H)

[0628] 1 H NMR(400MHz,DMSO-d6)δppm 8.72-8.78(m,1H)8.19-8.28(m,1H)

[0629] Step 4: N-[2-(6-chloro-2-pyridinyl)-2-(1-methylpyrazol-4-yl)propyl]-3-(3,5-difluoro-2-pyridinyl)- Preparation of 1,2,4-oxadiazole-5-carboxamide (Compound P-18, Table P)

[0630] To a suspension of 2-(6-chloro-2-pyridyl)-2-(1-methylpyrazole-4-yl)propan-1-amine (100mg, 0.4mmol) and 3-(3,5-difluoro-2-pyridyl)-1,2,4-oxadiazole-5-lithium formate (0.44mmol) in EtOAc (5mL / mmol) was added N-ethyl-N-isopropyl-propan-2-amine (1.6mmol) and T3P (50% by mass) in EtOAc (1.2mmol, 50% by mass) at 0°C. The reaction mixture was warmed to room temperature and stirred for 24h, where LCMS and TLC analysis showed that the reaction was complete. The reaction mixture was diluted with water (20ml) and extracted with EtOAc (2x 25ml). The combined organic layer was dried over Na2SO4 and concentrated in vacuo to obtain a crude product. This was absorbed onto celite and purified by reverse phase combined flash chromatography using CH3CN and water as eluents to afford the title product.

[0631] LCMS (Method A): rt=1.06, m / z=460 (M+H)

[0632] 1H NMR (400MHz, CDCl3) δppm 8.58 (d, J = 2.38Hz, 1H) 8.46 (br s,1H)7.60(t,J=7.88Hz,1H)7.46(ddd,J=9.60,7.66,2.38Hz,1H)7.24-7. 31(dd,2H)7.12(d,J=7.38Hz,1H)4.03-4.15(m,2H)3.88(s,3H)1.73(s,3H)

[0633] Preparation of intermediates

[0634] Using the methods described in the above examples, the intermediates described below can be used to prepare additional examples of compounds of formula (I)

[0635] Example I-1: Preparation of 2-(6-chloro-2-pyridyl)-2-(5-cyclopropyl-1-methyl-pyrazol-4-yl)propan-1-amine

[0636]

[0637] Step 1: Preparation of 5-cyclopropyl-1-methyl-pyrazole

[0638]

[0639] 5- bromo- 1- methyl- pyrazole (1.0g, 6.1mmol) is dissolved in toluene (20mL) and DMF (4.0mL). To the solution, cyclopropylboronic acid (1.7g, 19mmol) and cesium carbonate (7.9g, 24mmol) are added, and the reaction mixture is purged with nitrogen for 10min. To the solution, Pd (dppf) Cl is added CH Cl (0.25g, 0.30mmol), and the resulting reaction mixture is stirred at 100°C for 6 hours. After the reaction is completed (monitored by LCMS and TLC), the reaction mixture is quenched with water (20mL) and filtered through diatomaceous earth. The filtrate is extracted with EtOAc (2X 30mL) and the combined organic layer is dried over sodium sulfate and concentrated in vacuo to obtain 5- cyclopropyl -1- methyl- pyrazole, which is used as it is in the next step.

[0640] LCMS: (Method A): Retention time 0.87 min, m / z 123 (M+H)

[0641] Step 2: Preparation of 4-bromo-5-cyclopropyl-1-methyl-pyrazole

[0642]

[0643] To the stirred solution of 5-cyclopropyl-1-methyl-pyrazole (2g, 14.7mmol) in acetonitrile (80mL), add N-bromosuccinimide (2.94g, 16.2mmol), and reactant mixture was at room temperature stirred 18 hours. After the reaction was completed (monitored by LCMS and TLC), the reactant mixture was quenched with water, and water layer was extracted with EtOAc (X3). The organic layer merged was washed with sodium thiosulfate, salt water successively, and then dried over sodium sulfate and concentrated in vacuo to obtain crude product. Crude compound is purified by the combined flash chromatography of the 0-10%EtOAc in hexamethylene to obtain title compound.

[0644] LCMS: (Method A): Retention time 1.13 min, m / z 201 (M+H)

[0645] Step 3: Preparation of (6-chloro-2-pyridyl)-(5-cyclopropyl-1-methyl-pyrazol-4-yl)methanol

[0646] Under argon, 4-bromo-5-cyclopropyl-1-methyl-pyrazole (1.0g, 4.7mmol) is dissolved in THF (10mL) and is cooled to-78 ℃.In this solution, the N-butyl lithium (2.5mol / L) in hexane (2.4mL, 1.6g, 4.7mmol) is dropwise added. The gained reaction mixture is stirred to 30min at this temperature, and the 6-chloropyridine-2-carboxaldehyde (0.74g, 5.2mmol) in THF (10mL) is dropwise added at-78 ℃. After stirring for 1 hour at this temperature, the reaction mixture is warmed to room temperature and stirred for another 1 hour. Then the reaction mixture is cooled to 0 ℃, and then acidified with 2N hydrochloric acid. Water layer is extracted with EtOAc (3x100mL) and the organic layer merged is dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by combined flash chromatography using 30%-40% EtOAc in cyclohexane to give (6-chloro-2-pyridinyl)-(5-cyclopropyl-1-methyl-pyrazol-4-yl)methanol as a white solid.

[0647] LCMS: (Method A): Retention time 1.10 min, m / z 264 (M+H)

[0648] Step 4: Preparation of 2-(6-chloro-2-pyridyl)-2-(5-cyclopropyl-1-methyl-pyrazol-4-yl)acetonitrile

[0649]

[0650] To a solution of (6- chloro-2-pyridyl)-(5-cyclopropyl-1-methyl-pyrazole-4-yl) methanol (0.6g, 2.28mmol) in acetonitrile (22.8mL) was added lithium carbonate (0.034g, 0.45mmol), trimethylsilyl cyanide (1.41mL, 1.05g, 10.2mmol) and iodine (1.04g, 4.10mmol) at room temperature. The reaction mixture was heated to 60°C and stirred for 6 hours. After the reaction was completed (monitored by LCMS and TLC), the reaction mixture was cooled to room temperature and quenched with saturated sodium thiosulfate solution and extracted with EtOAc (3x 100mL). The combined organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to obtain a crude product in a light brown residue. The crude compound was purified by combined flash chromatography using 5%-40% EtOAc in cyclohexane to obtain the title compound in a light yellow gummy mass.

[0651] LCMS: (Method A): Retention time 1.24 min, m / z 273 (M+H)

[0652] Step 5: Preparation of 2-(6-chloro-2-pyridyl)-2-(5-cyclopropyl-1-methyl-pyrazol-4-yl)propionitrile

[0653]

[0654] At -78 DEG C through 15min time period, under argon to 2- (6- chloro-2-pyridyl) -2- (5- cyclopropyl -1- methyl -pyrazol -4- bases) acetonitrile (0.10g, 0.367mmol) in THF (1.10mL) solution of N- butyllithium (2.5mol / L) in hexane (0.22mL) is added dropwise. The gained light yellow suspension is stirred at this temperature for 25min, and iodomethane (0.034mL, 0.55mmol) is added. The gained yellow solution is stirred at -78 DEG C for 15min and then warmed to room temperature. After stirring at room temperature for 2 hours, it is shown that the reaction is complete (monitored by LCMS and TLC). The reaction mixture is then quenched with saturated aqueous ammonium chloride solution (20mL), extracted with EtOAc (2 × 20mL), dried over sodium sulfate, filtered, and concentrated in vacuo to obtain the crude product in the form of a brown oil. This was purified by combined flash chromatography eluting with 30%-40% EtOAc in cyclohexane to give the title compound as a pale yellow gum.

[0655] LCMS (Method A): retention time 1.25 min, m / z 287.1 (M+H)

[0656] Step 6: Preparation of 2-(6-chloro-2-pyridyl)-2-(5-cyclopropyl-1-methyl-pyrazol-4-yl)ethanamine

[0657] To a solution of 2-(6-chloro-2-pyridyl)-2-(5-cyclopropyl-1-methyl-pyrazole-4-yl)propionitrile (0.040 g, 0.14 mmol) in THF (0.41 mL) is added borane dimethyl sulfide complex (0.70 mL, 1.40 mmol) at room temperature under a nitrogen atmosphere. The resulting reaction mixture is stirred at 60 ° C for 6 h, and then cooled to 0 ° C. Concentrated HCl (0.093 mL, 0.56 mmol) (violent gas evolution!) is added dropwise to the reaction mixture, and the resulting reaction mixture is stirred at 60 ° C for 1 hour. The reaction mixture is cooled to room temperature and basified to pH 12 with NaOH 6N. The resulting mixture is extracted with EtOAc (x3) and the combined organic layer is washed once with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to obtain the title compound as a light brown oil, which can be used for the preparation of a compound with formula (I) without further purification.

[0658] LCMS (Method A): retention time 0.92 min, m / z 291.1 (M+H)

[0659] Example I-4: Preparation of 2-(3,5-difluoro-2-pyridyl)oxazole-4-carboxylic acid

[0660]

[0661] Step 1: Preparation of ethyl 2-(3,5-difluoro-2-pyridyl)oxazole-4-carboxylate

[0662]

[0663] By oxazole-4-carboxylic acid ethyl ester (CAS [23012-14-8], 0.34g, 2.44mmol) and 2- bromo-3,5-difluoro-pyridine (CAS [660425-16-1], 0.5g, 2.44mmol) solution in 1,4-dioxane (3.5mL) is stirred at room temperature.To this solution, pivalic acid (0.0852mL, 0.73mmol), potassium carbonate (0.70g, 4.89mmol), tri-tert-butylphosphonium tetrafluoroborate (CAS [131274-22-1], 0.14g, 0.48mmol) and palladium (II) acetate (0.056g, 0.24mmol) are added, and the reaction mixture is warmed to 90 DEG C and stirred at this temperature for 16 hours (monitored by LCMS and TLC).The reaction mixture is quenched with water (20mL) and extracted with EtOAc (3X 20mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude compound.This was purified by combined flash chromatography using 0-50% EtOAc in cyclohexane as eluent to afford the title compound as a brown gummy mass.

[0664] LCMS: (Method A): Retention time 1.00 min, m / z 255 (M+H)

[0665] Step 2: Preparation of 2-(3,5-difluoro-2-pyridyl)oxazole-4-carboxylic acid

[0666] To the solution of 2- (3,5-difluoro-2-pyridyl) oxazole-4-ethyl formate (0.2g, 0.78mmol) in THF (0.8mL) and water (0.2mL), lithium hydroxide (0.075g, 3.14mmol) is added, and gained reaction mixture is stirred at room temperature. After the completion of the reaction (monitored by LCMS and TLC), reaction mixture is quenched with ice-cold water (20mL) and extracted with TBME (2x 20ml). Organic layer is discarded, and water layer is acidified with 2N HCl and extracted with EtOAc (3x 20ml). The combined extract is dried over sodium sulfate, filtered, and concentrated in vacuo to obtain the title compound in off-white solid.

[0667] LCMS: (Method A): Retention time 0.41 min, m / z 227 (M+H)

[0668] Example I-3: 2-(6-chloro-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propan-1-amine preparation

[0669]

[0670] Step 1: Preparation of 5-chloro-1,3-dimethyl-pyrazole-4-carbaldehyde

[0671]

[0672] A solution of 2,5-dimethylpyrazole-3-ol (10g, 44.6mmol) and phosphorus oxychloride (V) (21.2mL) was stirred at 90°C for 1h. After the reaction was completed (monitored by LCMS and TLC), the reaction mixture was concentrated in vacuo and the residue was treated with a saturated aqueous sodium bicarbonate solution (until pH was alkaline), the aqueous layer was extracted with EtOAc (× 3), and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo to obtain a crude product. The crude product was purified by combined flash chromatography using 20%-30% EtOAc in cyclohexane to obtain 5-chloro-1,3-dimethyl-pyrazole-4-carboxaldehyde as a white solid.

[0673] LCMS (Method D): retention time 1.0 min, m / z 159 (M+H)

[0674] Step 2: Preparation of 5-methoxy-1,3-dimethyl-pyrazole-4-carbaldehyde

[0675]

[0676] To a solution of 5-chloro-1,3-dimethyl-pyrazole-4-carboxaldehyde (8.3g, 52mmol) in methanol (83mL) was added sodium methoxide (23mL, 100mmol) at room temperature under argon. The resulting reaction mixture was stirred at 60°C for 6h, after which LCMS and TLC showed that the reaction was complete. The reaction mixture was diluted with water (50mL) and saturated aqueous ammonium chloride solution and extracted with EtOAc (150mL x 3). The combined organic layer was dried over Na2SO4 and concentrated in vacuo to obtain a crude product. The product was purified by combined flash chromatography using 30%-40% EtOAc in cyclohexane to obtain the title compound as a white solid.

[0677] LCMS (Method A): retention time 0.34 min, m / z 155 (M+H)

[0678] Step 3: Preparation of 2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)acetonitrile

[0679]

[0680] To a solution of potassium tert-butoxide (11 g, 95 mmol) in 1,2-dimethoxyethane (130 mL) was added p-methylsulfonylmethyl isocyanide (11 g, 54 mmol) in DME (5 mL) at -65 ° C under argon. The reaction mixture was stirred at -65 ° C to -60 ° C for about 1 to 2 hours. 5-methoxy-1,3-dimethyl-pyrazole-4-carboxaldehyde (6.3 g, 39 mmol) was added to the reaction mixture at -65 ° C to -60 ° C over 1 hour and stirred at this temperature for 2 h (note: a thick substance was observed). Methanol (4.1 mL) was added at -65 ° C to obtain a clear solution. The reaction mixture was then heated to 80 ° C for 2 h. After the reaction was complete (monitored by LCMS and TLC), it was cooled to 0 ° C and quenched with 5% acetic acid in water (until the pH became slightly acidic), stirred for 5 min, and then diluted with EtOAc (10 mL). The aqueous and organic layers were separated and the aqueous layer was extracted with EtOAc (60 mL), the combined organic layers were washed with brine solution (10 mL), dried over Na2SO4, and concentrated in vacuo. The crude compound was purified by combined flash chromatography using 50%-70% EtOAc in cyclohexane to give the title compound as a brown liquid.

[0681] LCMS (Method D): retention time 0.74 min, m / z 166 (M+H)

[0682] Step 4: Preparation of 2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propionitrile

[0683]

[0684] To a solution of potassium tert-butoxide (83 mg, 0.72 mmol) and 2- (5- methoxy -1,3- dimethyl - pyrazole -4- bases) acetonitrile (100 mg, 0.60 mmol) in DMSO (10 mL) was added iodomethane (0.042 mL, 0.66 mmol) at room temperature, and the reaction mixture was stirred at room temperature under nitrogen for 30 min. The reaction mixture was diluted with cold water (20 mL) and saturated aqueous ammonium chloride solution and extracted with EtOAc (40 mL × 3). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude compound was purified by combined flash chromatography using 50% -60% EtOAc in cyclohexane to obtain the title compound as a colorless liquid.

[0685] LCMS (Method D): retention time 1.31 min, m / z 180 (M+H)

[0686] Step 5: Preparation of 2-(6-chloro-2-pyridyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propionitrile

[0687]

[0688] By 2- (5- methoxy -1,3- dimethyl - pyrazole -4- bases) propionitrile (1.5g, 6.7mmol) solution in DMSO (15mL) and potassium tert-butoxide (1.2g, 11mmol) are stirred at room temperature for 10min, and then dropwise add 2,6- dichloropyridine (1.1g, 7.4mmol) solution in DMSO (5mL).Reactant mixture is stirred at room temperature for 30min under nitrogen.After the completion of the reaction (monitored by LCMS and TLC), reactant mixture is diluted with cold water (20mL) and saturated ammonium chloride and extracted with EtOAc (40mL × 3).The organic layer merged is washed with salt water, through Na2SO4 is dried and concentrated in vacuo.The crude product is purified by the combined flash chromatography of 50% -70% EtOAc in cyclohexane to obtain the title compound in yellow oil.

[0689] LCMS (Method A): retention time 1.06 min, m / z 291 (M+H)

[0690] Step 6: Preparation of 2-(6-chloro-2-pyridyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propan-1-amine Preparation

[0691]

[0692] To a solution of 2-(6-chloro-2-pyridyl)-2-(5-methoxy-1,3-dimethyl-pyrazole-4-yl)propionitrile (1.53 g, 4.21 mmol) in THF (12.6 mL) is added borane dimethyl sulfide complex (21 mL, 42.1 mmol) at room temperature under nitrogen. The resulting reaction mixture is stirred at 70 ° C for 1 h. After completion, 6N HCl (0.95 mL, 5.75 mmol, strong gas evolution!) is added dropwise to the reaction mixture and stirred at 60 ° C for 1 h. After it is cooled to room temperature, it is basified to pH 12 with 6N NaOH and extracted with EtOAc (50 mL × 3). The combined organic layer is washed with brine, dried over Na2SO4, and concentrated in vacuo to give the title compound as a yellow oil, which is used in the next step without further purification.

[0693] LCMS (Method A): retention time 0.13 min, m / z 295 (M+H).

[0694] One skilled in the art will recognize that omitting step 4 allows for the preparation of the following compounds, namely:

[0695]

[0696] Example I-4: [2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl] chloride Preparation of ammonium chloride

[0697]

[0698] Step 1: N-[2-(6-chloro-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]amino Preparation of tert-butyl formate

[0699]

[0700] To a solution of 2-(6-chloro-2-pyridyl)-2-(5-methoxy-1,3-dimethyl-pyrazole-4-yl)propan-1-amine (1.5g, 4.3mmol) in THF (23mL) in water (15mL) was added sodium bicarbonate (1.7g, 19mmol) and di-tert-butyl dicarbonate (1.1mL, 4.3mmol) at 0°C. The resulting reaction mixture was stirred at room temperature for 2h, quenched with water and extracted with EtOAc (X3). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo to obtain a crude product. It was purified by combined flash chromatography using 60%-80% EtOAc in cyclohexane to obtain the title compound as a yellow oil.

[0701] LCMS (Method A): retention time 1.11 min, m / z 395 (M+H)

[0702] Step 2: N-[2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]amino Preparation of tert-butyl formate

[0703]

[0704] To a solution of tert-butyl N-[2-(6-chloro-2-pyridyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]carbamate (1.4 g, 3.2 mmol) in toluene (7.0 mL) and water (7.0 mL) at room temperature were added potassium acetate (0.89 g, 8.9 mmol) and potassium ferrocyanide (4.9 g, 13 mmol). The reaction mixture was degassed under nitrogen for 10 min. To this reaction mixture was added palladium(II) (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]methanesulfonate (1.4 g, 1.6 mmol), and the reaction mixture was stirred at 90° C. for 4 h. The reaction mixture was quenched with water, extracted with EtOAc (×3), and the combined organic layers were washed with brine, dried over Na 2 SO 4 , and concentrated in vacuo to afford the crude product, which was purified by combined flash chromatography using 80% EtOAc in cyclohexane to afford the title compound as a brown oil.

[0705] LCMS (Method D): retention time 1.76 min, m / z 386 (M+H)

[0706] Step 3: [2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]chloride Preparation of ammonium

[0707] To a solution of tert-butyl N-[2-(6-cyano-2-pyridyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propyl]carbamate (320 mg, 0.74 mmol) in diethyl ether (3.2 mL) was added 2M HCl in diethyl ether (1.5 mL, 3 mmol) at 0 ° C. The reaction mixture was warmed to room temperature and stirred at room temperature for 6 h. Upon completion, the reaction mixture was concentrated in vacuo at 30 ° C to give the title compound as a yellow solid.

[0708] LCMS (Method A): retention time 0.39 min, m / z 286 (M+H)

[0709] Example I-5: [2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)ethyl] chloride Preparation of ammonium chloride (similar to the preparation of 2-(6-cyano-2-pyridinyl)-2-(5-methoxy-1,3-dimethyl-pyrazol-4-yl)propane [Ammonium Chloride Procedure]

[0710]

[0711] LCMS (Method A): retention time 0.20 min, m / z 272 (M+H)

[0712] Example I-6: 2-(6-chloro-2-pyridinyl)-2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol-4-yl]ethanamine Preparation

[0713]

[0714] Step 1: Preparation of (2,5-dimethylpyrazol-3-yl)methanol

[0715]

[0716] At room temperature, sodium borohydride (0.2g, 57mmol) is added to a solution of 2,5-dimethylpyrazole-3-ethyl formate (0.2g, 1mmol) in ethanol (2mL). Reactant mixture is stirred to 3h at 60 DEG C. After the reaction is completed (monitored by LCMS and TLC), reactant mixture is quenched with saturated ammonium chloride solution and extracted with EtOAc (x3). The organic layer merged is washed with water and salt water successively, through NaSODry, and is concentrated in vacuo to obtain title compound.

[0717] LCMS (Method A): retention time 0.37 min, m / z 127 (M+H)

[0718] Step 2: Preparation of 5-(methoxymethyl)-1,3-dimethyl-pyrazole

[0719]

[0720] To a solution of (2,5-dimethylpyrazole-3-yl)methanol (0.6 g, 4.75 mmol) in THF (6 mL) was added sodium hydride (0.20 g, 5.23 mmol) and stirred for 30 min at 0 ° C., and then iodomethane (0.32 mL, 5.23 mmol) was added, and the resulting reaction mixture was warmed to room temperature and stirred for 3 h. The reaction mixture was diluted with 2N HCl (20 mL) and extracted with EtOAc (2 x 30 ml). The combined organic layers were washed with cold water, brine, dried over Na SO dried, and concentrated in vacuo to obtain the title compound.

[0721] LCMS (Method A): retention time 0.94 min, m / z 141 (M+H)

[0722] Step 3: Preparation of 5-(methoxymethyl)-1,3-dimethyl-pyrazole-4-carbaldehyde

[0723]

[0724] To a solution of 5-(methoxymethyl)-1,3-dimethyl-pyrazole (0.7g, 5mmol) in DMF (3mL, 40mmol) was added phosphoryl chloride (2mL, 20mmol) at 0°C. The reaction mixture was stirred at 80°C for 6h (monitored by LCMS). After the reaction was complete, the reaction mixture was slowly poured into crushed ice and 6N NaOH solution was added until the pH was 12. The resulting reaction mixture was extracted with EtOAc (3x 30mL) and the combined organic layers were washed with water and brine in sequence, dried over anhydrous Na2SO4 and concentrated in vacuo. The title product was obtained as a brown solid.

[0725] 1 H NMR (400MHz, CDCl3) δppm 9.96 (s, 1H) 4.75 (s, 2H) 3.85 (s, 3H) 3.38 (s, 3H) 2.45 (s, 3H)

[0726] Step 4: Preparation of 2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol-4-yl]acetonitrile

[0727]

[0728] Similar to Example I-3, step 3 is carried out.

[0729] LCMS (Method A): retention time 0.20 min, m / z 180 (M+H)

[0730] 1H NMR (400MHz, CDCl3) δppm 4.47 (s, 2H) 3.82 (s, 3H) 3.52 (s, 2H) 3.39 (s, 3H) 2.27 (s, 3H)

[0731] Step 5: Preparation of 2-(6-chloro-2-pyridinyl)-2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol-4-yl]acetonitrile preparation

[0732]

[0733] Similar to Example I-3, step 5 is carried out.

[0734] LCMS (Method A): retention time 1.01 min, m / z 291 (M+H)

[0735] 1 H NMR(400MHz, CDCl3)δppm 7.66(t,1H)7.24-7.32(m,2H)5.27(s,1H)4.49-4.61(m,2H)3.83(s,3H)3.36(s,3H)2.23(s,3H)

[0736] Step 6: Preparation of 2-(6-chloro-2-pyridinyl)-2-[5-(methoxymethyl)-1,3-dimethyl-pyrazol-4-yl]ethanamine preparation

[0737]

[0738] Similar to Example 1-3, step 6 is performed

[0739] LCMS (Method A): Retention time: 0.39 min, m / z 295 (M+H)

[0740] Examples of synthesized compounds of formula (I) are shown in Table P.

[0741] Table P: Synthesized compounds and spectroscopic and physicochemical data

[0742]

[0743]

[0744]

[0745]

[0746]

[0747]

[0748]

[0749]

[0750]

[0751]

[0752] Biological Examples

[0753] Example B-1: Alternaria solani / tomato / leaf disc (early blight)

[0754] Tomato leaf disc cultivar Baby is placed on the agar in multiwell plate (24-hole specification), and is sprayed with the test compound of the preparation diluted in water.After using 2 days, leaf disc is inoculated with the spore suspension of fungus.In climate chamber under the light scheme of 12 / 12h (illumination / darkness), at 23 ℃ / 21 ℃ (day / night) and 80%rh, the leaf disc of incubation inoculation, and the activity of compound is assessed as, when the disease damage of appropriate level occurs on untreated check leaf disc (after using 5-7 days), with the disease control percentage ratio compared with untreated.

[0755] The following compounds gave at least 80% control of Alternaria solani at 200 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-5, P-9, P-10, P-12, P-13, P-14, P-15, P-16, P-17, P-18, P-20, P-22, P-23, P-24, P-25, P-26, P-27, P-28, P-39, P-42, P-43, and P-45

[0756] Example B-2: Botryotinia fuckeliana (Botrytis cinerea) cinerea)) / Liquid culture (Botrytis cinerea)

[0757] Fungal conidia from frozen storage were directly mixed into nutrient broth (Vogels broth). After placing a (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3 to 4 days after application.

[0758] The following compounds gave at least 80% control of Botrytis cinerea at 20 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-7, P-8, P-9, P-10, P-12, P-13, P-14, P-15, P-16, P-17, P-18, P-23, P-24, P-25, P-26, P-38, and P-39

[0759] Example B-3: Colletotrichum cucurbitae (Cucurbit anthracnose) / Liquid Culture (Anthracnose)

[0760] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB-potato dextrose broth). After placing a (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plate was incubated at 24°C and growth inhibition was measured photometrically 3 to 4 days after application.

[0761] The following compounds gave at least 80% control of melon bushworm at 20 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-7, P-8, P-9, P-10, P-11, P-12, P-13, P-14, P-15, P-16, P-17, P-18, P-23, P-24, P-38, and P-39

[0762] Example B-4: Blumeria graminis f. sp. tritici (Wheat Powdery Mildew (Erysiphegraminis f.sp.tritici) / wheat / leaf discs preventive (powdery mildew on wheat)

[0763] Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. One day after application, leaf discs were inoculated by shaking powdery mildew-infected plants on these test plates. The inoculated leaf discs were incubated at 20° C. and 60% rh in a climate chamber under a light regime of 24 h dark followed by 12 h light / 12 h dark, and the activity of the compound was assessed as the percentage of disease control compared to the untreated test segments when appropriate levels of disease damage appeared (6-8 days after application).

[0764] The following compounds gave at least 80% control of wheat powdery mildew at 200 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-1, P-2, P-3, P-9, P-10, P-11, P-12, P-13, P-14, P-15, P-16, P-17, P-18, P-22, P-23, P-24, P-25, P-26, P-27, P-28, P-29, P-35, P-38, P-39, P-40, P-41, and P-43.

[0765] Example B-5: Fusarium spp. / Liquid Culture (Head Blight)

[0766] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB-potato dextrose broth). After placing a (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and growth inhibition was determined photometrically 3 to 4 days after application.

[0767] The following compounds gave at least 80% control of Fusarium oxysporum at 20 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-1, P-3, P-4, P-5, P-8, P-9, P-10, P-12, P-13, P-16, P-17, P-18, P-23, and P-26

[0768] Example B-6: Fusarium spp. / Wheat / Spikelet Preventive (Head Blight)

[0769] Wheat spikelets of the cultivar Monsun were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. One day after application, the spikelets were inoculated with a spore suspension of the fungus. The inoculated spikelets were incubated at 20°C and 60% rh in a climate chamber under a light regime of 72 h semi-darkness followed by 12 h light / 12 h dark. The activity of the compound was assessed as the percentage of disease control compared to the untreated spikelets when the appropriate level of disease damage appeared (6-8 days after application).

[0770] The following compounds gave at least 80% control of Fusarium oxysporum at 200 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-3, P-9, P-13, P-18 and P-23

[0771] Example B-7: Corn Gibberellic acid (Fusarium spp.) / Wheat / Spikelet Preventive (Fusarium spp.)

[0772] Wheat spikelet cultivar Monsun was placed on agar in a multiwell plate (24-well format) and sprayed with the prepared test compound diluted in water. One day after application, the spikelets were inoculated with a spore suspension of the fungus. In a climate chamber, the inoculated test leaf discs were incubated at 20°C and 60% rh under a light regime of 72h semi-darkness followed by 12h light / 12h darkness. The activity of the compound was assessed as the percentage of disease control when the appropriate level of disease damage appeared on the untreated control spikelets (6-8 days after application) compared to the untreated control.

[0773] The following compounds gave at least 80% control of Gibberella zeae at 200 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-1, P-9, P-13, P-18 and P-23

[0774] Example B-8: Phaeosphaerianodorum (Septorianodorum) / wheat / leaf disc Preventive (glume blight)

[0775] Wheat leaf segments cultivar Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. 2 days after application, the leaf discs were inoculated with a spore suspension of the fungus. The inoculated test leaf discs were incubated at 20°C and 75% rh in a climate chamber under a 12 h light / 12 h dark light regime, and the activity of the compound was assessed as the percentage of disease control compared to the untreated test leaf discs when the appropriate level of disease damage appeared (5-7 days after application).

[0776] The following compounds gave at least 80% control of Septoria nodosum at 200 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-3, P-4, P-5, P-8, P-9, P-10, P-13, P-14, P-15, P-16, P-17, P-18, P-20, P-23, P-24, P-25, P-26, P-27, P-28, P-35, P-38, P-39, and P-45

[0777] Example B-9: Monographella nivalis (Snow mold) / Liquid culture (cereal root Rot)

[0778] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB-potato dextrose broth). After placing a (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and growth inhibition was determined photometrically 4 to 5 days after application.

[0779] The following compounds gave at least 80% control of Thielavia nivalis at 20 ppm when compared to untreated controls which showed extensive disease development under the same conditions: P-1, P-3, P-4, P-5, P-7, P-8, P-9, P-10, P-12, P-13, P-14, P-16, P-17, P-18, P-20, P-23, P-24, P-25, P-26, and P-39

[0780] Example B-10: Mycosphaerella arachis (Cercospora arachis) / Liquid Culture (Early Leaf Spot)

[0781] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB-potato dextrose broth). Af...

Claims

1. A compound of formula (I), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof in R 1 is selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, or C3-C6-cycloalkyl; R 2 is selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C2-alkyl-C1-C4-alkoxy, C1-C2-alkyl-C1-C4-alkoxy-C1-C2-alkoxy, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimido, N-hydroxy-C1-C4-alkyl-carbonimido, or C1-C4-alkoxycarbonyl; R 3 is selected from hydrogen, halogen, or C1-C4-alkyl; R 4 is selected from hydrogen, halogen, C1-C4-alkyl, cyano, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-alkylaminocarbonyl, or di(C1-C4-alkylamino)carbonyl; R 5 and R 6 independently selected from hydrogen, or C1-C4-alkyl; A 1 、A 2 and A 3 Independently selected from CR 7 、N、NR 8 , O or S, provided that A 1 、A 2 and A 3 At least one of is selected from N, O or S, and A 1 、A 2 and A 3 No more than one of them is O or S; R 7 and R 8 independently selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, or C2-C4-alkynyl; B 1 It's CR 9 or N, B 2 It's CR 10 or N, B 3 It's CR 11 or N, B 4 It's CR 12 or N, provided that B 1 、B 2 、B 3 and B 4 Only one of them is N; R 10 、R 11 、R 12 and R 13 independently selected from hydrogen, halogen, amino, hydroxy, carboxylic acid, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C2-C4-alkenyloxy, C2-C4-alkynyloxy, C1-C4-alkylsulfanyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di(C 1- C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimido, N-hydroxy-C1-C4-alkyl-carbonimido, C1-C4-alkylaminocarbonyl, di(C1-C4-alkyl)aminocarbonyl, C1-C4-alkylcarbonylamino, C1-C4-alkylsulfonylamino, trifluoromethylsulfonyloxy, phenyl, 5-membered or 6-membered heteroaryl, or C wherein the 5-membered or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, with the proviso that not more than one is O or S; and wherein any of the phenyl, 5-membered or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and Z 1 is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any of the pyridyl-, pyrazin-, pyridazine-, and pyrimidin- moieties is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkynyl, C1-C4-haloalkoxy, C1-C4-alkoxy, C1-C4-alkylsulfanyl, C1-C4-alkylsulfinyl, or C1-C4-alkylsulfonyl.

2. The compound of formula (I) according to claim 1, wherein R 1 It is a C1-C3 alkyl group.

3. A compound of formula (I) according to claim 1 or claim 2, wherein R 2 is hydrogen, halogen, C1-C3 alkyl, or C3-C6-cycloalkyl; and R 3 It's hydrogen.

4. A compound of formula (I) according to any one of claims 1 to 3, wherein R 4 is hydrogen or methyl.

5. A compound of formula (I) according to any one of claims 1 to 4, wherein R 5 and R 6 It's hydrogen.

6. A compound of formula (I) according to any one of claims 1 to 5, wherein Z 1 is 2-pyridyl, 3-pyridyl, or 4-pyridyl; wherein any of the pyridyl-parts is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl.

7. The compound of formula (I) according to claim 6, wherein Z 1 It is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 2,6-difluoro-3-pyridyl, or 3,5-difluoro-2-pyridyl.

8. A compound of formula (I) according to any one of claims 1 to 7, wherein The compound of formula (I) is a compound of formula (IA) where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 9 、R 10 、R 11 、R 12 、B 1 、B 2 、B 3 、B 4 and Z 1 corresponds to the same definition as for the compound of formula (I) according to any one of claims 1 to 7, and A is in indicates the position of attachment to the C(=O) group and the arrow indicates the position of attachment to the Z 1 The position of the group.

9. The compound of formula (IA) according to claim 8, wherein A is selected from A4, A7, A9, or A10, in indicates the position of attachment to the C(=O) group and the arrow indicates the position of attachment to the Z 1 The position of the group.

10. The compound according to any one of claims 1 to 9, wherein B 1 It's CR 9 , B 2 It's CR 10 , B 3 It's CR 11 , and B 4 It's CR 12 , and among them R 9 and R 10 are independently selected from hydrogen, halogen, or cyano; and R 11 and R 12 Independently selected from hydrogen, halogen, cyano, C1-C4 alkyl, or C1-C4 alkoxy.

11. The compound according to claim 10, wherein R 9 and R 10 are independently selected from hydrogen, chlorine, bromine, or cyano; and R 11 and R 12 It's hydrogen.

12. An agrochemical composition comprising a fungicidally effective amount of the compound according to any one of claims 1 to 11.

13. The agrochemical composition according to claim 12, further comprising at least one additional active ingredient and / or an agrochemically acceptable diluent or carrier.

14. A method for controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound according to any one of claims 1 to 11 or a composition comprising said compound is applied to the plants, parts thereof or the locus thereof.

15. Use of a compound according to any one of claims 1 to 11 as a fungicide.

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