Pesticidal heterocyclic derivatives having sulfur-containing substituents

Abstract

Compounds of formula (I), wherein Q is as defined in claim 1. Furthermore, the present application relates to agrochemical compositions comprising compounds of formula (I), to the preparation of these compositions, and to the use of said compounds or compositions for combating, preventing or controlling animal pests, including arthropods, in particular insects, molluscs, nematodes, or representatives of the order Acarina, in agriculture or horticulture.

Description

[0001] This invention relates to heterocyclic derivatives containing sulfur substituents that have pest-killing activity (particularly insecticidal activity), methods for their preparation, compositions containing such compounds, and their use in controlling animal pests (including arthropods and particularly insects, or representatives of the order Acari).

[0002] Dihydropyrrolidone and phthalimide derivatives with sulfur-containing substituents and heterocyclic benzo[a]cyclization have been described in the literature, for example in J. Org. Chem. [Organic Chemistry Journal] 2003, 62, 8240 and Bull. ChemSoc. Chim. Belg. [Bulletin of the Belgian Chemical Society] 1997, 106, 151. However, none of these references describe any biocidal activity. Structurally different biocidal heterocyclic derivatives with sulfur-containing substituents have been described, for example, in WO 2012 / 012086848, WO 2013 / 018928, WO 2019 / 131575 and WO 2020 / 013147.

[0003] It has now been unexpectedly discovered that certain novel bioactive derivatives with sulfur-containing substituents possess advantageous properties as biocides.

[0004] Therefore, the present invention provides compounds having formula I,

[0005]

[0006] in

[0007] Q is a group selected from the group consisting of: formulas Qa, Qb, and Qc.

[0008]

[0009] The arrow indicates the attachment point to the nitrogen atom in the tricyclic ring;

[0010] And A represents CH or N;

[0011] X is S, SO, or SO2;

[0012] R1 is a C1-C4 alkyl or a C3-C6 cycloalkyl-C1-C4 alkyl;

[0013] Q1 is hydrogen, halogen, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, C1-C6 cyanoalkyl, C1-C6 cyanoalkoxy, C1-C6 haloalkoxy, -N(R3)2, -N(R3)C(=O)R4, -N(R3)CON(R3)2, (oxazolidin-2-one)-3-yl, or 2-pyridinyloxy; or

[0014] Q1 is a five- to six-membered aromatic or heteroaromatic ring system, with a ring carbon atom connected to a ring containing a substituent A. The ring system is unsubstituted or mono- or polysubstituted with substituents selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthioalkyl, C1-C4 alkylsulfinyl, and C1-C4 alkylsulfonyl; and the ring system may contain one, two, or three cyclic heteroatoms selected from the group consisting of: nitrogen, oxygen, and sulfur, wherein the ring system may not contain more than one epoxy atom and may not contain more than one cyclic sulfur atom; or

[0015] Q1 is a five-membered heteroaromatic ring system with a ring containing a substituent A connected via a cyclic nitrogen atom, wherein the ring system is unsubstituted or monosubstituted or polysubstituted with substituents selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthioalkyl, C1-C4 alkylsulfinyl, and C1-C4 alkylsulfonyl; and the ring system contains 1, 2, or 3 cyclic heteroatoms selected from the group consisting of: nitrogen, oxygen, and sulfur, wherein the ring system contains at least one cyclic nitrogen atom and may not contain more than one cyclic oxygen atom and may not contain more than one cyclic sulfur atom;

[0016] R2 is hydrogen or a C1-C4 alkyl group;

[0017] Each R3 is independently hydrogen, C1-C4 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl;

[0018] R5 is a C1-C4 alkyl group;

[0019] R6 is hydrogen, halogen, C1-C4 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, C1-C6 cyanoalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CO(NR3R4), -NR3COR4, (C3-C8)cycloalkyl-(C1-C6)alkyl-, (C3-C8)cycloalkyl monosubstituted with cyano-(C1-C6)alkyl-; or

[0020] R6 is a five- to six-membered saturated, partially saturated, or heteroaromatic ring system connected to an imidazole ring via a ring nitrogen atom. This imidazole ring is connected to a substituent R5. The ring system is unsubstituted or mono- or polysubstituted with substituents selected from the group consisting of: halogens, cyano groups, C1-C4 alkyl groups, C1-C4 haloalkyl groups, C1-C4 alkoxy groups, C1-C4 haloalkoxy groups, C1-C4 alkylthioalkyl groups, C1-C4 alkylsulfinyl groups, and C1-C4 alkylsulfonyl groups; C3-C The ring system comprises 6 cycloalkyl groups, C3-C6 cycloalkyl groups monosubstituted with cyano, C1-C6 cyanoalkyl groups, (C3-C8)cycloalkyl-(C1-C6)alkyl-, and (C3-C8) cycloalkyl groups monosubstituted with cyano-(C1-C6)alkyl-, and the ring system contains 1, 2, or 3 cyclic heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein the ring system contains at least one cyclic nitrogen atom and may not contain more than one epoxide atom and may not contain more than one cyclic sulfur atom; or

[0021] R6 is a five- to six-membered saturated, partially saturated, aromatic, or heteroaromatic ring system in which a ring carbon atom is attached to an imidazole ring linked to a substituent R5. The ring system is unsubstituted or mono- or polysubstituted with substituents selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthioalkyl, C1-C4 alkylsulfinyl, and C1-C4 alkylsulfonyl. ; C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, C1-C6 cyanoalkyl, (C3-C8)cycloalkyl-(C1-C6)alkyl-, (C3-C8)cycloalkyl monosubstituted with cyano-(C1-C6)alkyl-, and the ring system may contain 1, 2 or 3 cyclic heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, wherein the ring system may not contain more than one epoxy atom and may not contain more than one cyclic sulfur atom; and

[0022] R4 is a C3-C6 cycloalkyl-C1-C4 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, or C3-C6 cycloalkyl.

[0023] The present invention also provides agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of compounds having Formula I.

[0024] Compounds of formula I having at least one basic center can form acid addition salts, for example, with: strong inorganic acids (such as mineral acids, such as perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid, or hydrohalic acid), strong organic carboxylic acids (such as unsubstituted or, for example, halogenated C1-C4 alkylcarboxylic acids, such as acetic acid, such as saturated or unsaturated dicarboxylic acids, such as oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid, or phthalic acid, such as hydroxycarboxylic acids, such as 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, halogenated C1-C4 alkylsulfonic acids or arylsulfonic acids, such as methanesulfonic acid or p-toluenesulfonic acid). Compounds of Formula I having at least one acidic group can, for example, form salts with bases, such as mineral salts, like alkali metal or alkaline earth metal salts, such as sodium, potassium, or magnesium salts; or form salts with ammonia or organic amines (such as morpholine, piperidine, pyrrolidine, mono-, di-, or tri-alkylamines, such as ethylamine, diethylamine, triethylamine, or dimethylpropylamine, or mono-, di-, or tri-hydroxyalkylamines, such as monoethanolamine, diethanolamine, or triethanolamine).

[0025] In each case, the compound having formula (I) according to the invention is in a free form, in an oxidized form (such as an N-oxide) or in a salt form (e.g., in the form of an agronomically available salt).

[0026] N-oxides are the oxidized forms of tertiary amines or nitrogen-containing heteroaromatic compounds. For example, they are described by A. Albini and S. Pietra in their 1991 book, "Heterocyclic N-oxides," published by CRC Press in Boca Raton.

[0027] The compounds of formula I according to the invention also include hydrates that may form during salt formation.

[0028] When a substituent is indicated to be further substituted, this means that it contains one or more of the same or different substituents, for example, one to four substituents. Typically, no more than three such optional substituents are present simultaneously. Preferably, no more than two such substituents are present simultaneously (i.e., the group is substituted by one or both of the indicated substituents). When the additional substituent is a larger group such as a cycloalkyl or phenyl group, it is most preferred that only one such optional substituent is present. When a group is indicated to be substituted with, for example, an alkyl group, this includes those groups that are part of other groups, such as alkyl groups in alkylthio groups.

[0029] As used in this article, the term "C1-C" n"Alkyl" refers to a saturated straight-chain or branched hydrocarbon group having 1 to n carbon atoms attached via any one of the carbon atoms, such as any one of the following groups: 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 in this article, the term "C1-C" n "Haloalkyl" refers to a straight-chain or branched saturated alkyl group (as mentioned above) having 1 to n carbon atoms attached via any one 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., any one 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 The alkyl group includes 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 carrying 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.

[0031] As used in this article, the term "C1-C" n"Alkoxy" refers to a straight-chain or branched saturated alkyl group (as mentioned above) with 1 to n carbon atoms attached via an oxygen atom, i.e., any one of the following: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, or 1,1-dimethylethoxy.

[0032] As used in this article, the term "C1-C" n "Haloalkoxy" refers to the C1-C alkoxy group mentioned above. n An alkoxy group, partially or wholly replaced by fluorine, chlorine, bromine and / or iodine, i.e., any one of the following: chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy Pentafluoroethoxy, 2-fluoropropoxy, 3-fluoropropoxy, 2,2-difluoropropoxy, 2,3-difluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 2-bromopropoxy, 3-bromopropoxy, 3,3,3-trifluoropropoxy, 3,3,3-trichloropropoxy, 2,2,3,3,3-pentafluoropropoxy, heptafluoropropoxy, 1-(fluoromethyl)-2-fluoroethoxy, 1-(chloromethyl)-2-chloroethoxy, 1-(bromomethyl)-2-bromoethoxy, 4-fluorobutoxy, 4-chlorobutoxy, or 4-bromobutoxy.

[0033] As used in this article, the term "C1-C" n "alkylthioalkyl" refers to a straight-chain or branched saturated alkyl group (as mentioned above) with 1 to n carbon atoms attached via a sulfur atom, such as any of the following: methylthio, ethylthio, n-propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2-methylpropylthio, or 1,1-dimethylethylthio.

[0034] As used in this article, the term "C1-C" n"alkyl sulfinyl" refers to a straight-chain or branched saturated alkyl group (as mentioned above) having 1 to n carbon atoms attached via a sulfur atom of the sulfinyl group, i.e., any one of the following: methyl sulfinyl, ethyl sulfinyl, n-propyl sulfinyl, 1-methyl ethyl sulfinyl, n-butyl sulfinyl, 1-methyl propyl sulfinyl, 2-methyl propyl sulfinyl, 1,1-dimethyl ethyl sulfinyl, n-pentyl sulfinyl, 1-methyl butyl sulfinyl, 2-methyl butyl sulfinyl, 3-methyl butyl sulfinyl, 1,1-dimethyl propyl sulfinyl, 1,2-dimethyl propyl sulfinyl, 2,2-dimethyl propyl sulfinyl, or 1-ethyl propyl sulfinyl.

[0035] As used in this article, the term "C1-C" n "alkylsulfonyl" refers to a straight-chain or branched saturated alkyl group (as mentioned above) having 1 to n carbon atoms attached via the sulfur atom of the sulfonyl group, i.e., any one of the following: methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, 1-methylpropylsulfonyl, 2-methylpropylsulfonyl or tert-butylsulfonyl.

[0036] As used in this article, the term "C1-C" n "Cyanoalkyl" refers to a straight-chain or branched saturated alkyl group having 1 to n carbon atoms that is replaced by a cyano group (as mentioned above), such as cyanomethylene, cyanoethylene, 1,1-dimethylcyanomethyl, cyanomethyl, cyanoethyl, and 1-dimethylcyanomethyl.

[0037] The term "C3-C" used in this article n "Cycloalkyl" refers to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic hydrocarbon having 3 to n carbon atoms, preferably 3 to 8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclic [2.2.1]heptyl and bicyclic [2.2.2]octyl.

[0038] The term "C3-C" used in this article is replaced by "cyanomono" n "Cycloalkyl" refers to saturated or partially unsaturated monocyclic, bicyclic, or tricyclic hydrocarbons having 3 to n carbon atoms that are substituted with a cyano group (as mentioned above).

[0039] As used in this article, in terms such as "C3-C" n The suffix "-C1-C" after "cycloalkyl" n Alkyl group (where n is an integer from 1 to 6) refers to a compound formed by C3-C4 atoms. n Cycloalkyl-substituted straight-chain or branched saturated alkyl groups. C3-C n cycloalkyl-C1-C n An example of an alkyl group is, for example, cyclopropylmethyl.

[0040] Halogens are typically fluorine, chlorine, bromine, or iodine. This also applies accordingly to halogens combined with other meanings, such as alkyl halogens.

[0041] In the context of this invention, the term "monosubstituted or polysubstituted" in the definition of Q1 or R6 substituents typically means, depending on the chemical structure of the substituent, monosubstituted to quintuplet substituted, more preferably monosubstituted, disubstituted or trisubstituted.

[0042] In the context of this invention, the phrases “Q1 is a five- to six-membered aromatic ring system connected by a ring carbon atom to a ring containing a substituent A…” and “Q1 is a five-membered aromatic ring system connected by a ring nitrogen atom to a ring containing a substituent A…”, as applicable, refer to the specific embodiment of substituent Q1 and the connection of group Q represented by formula Qa or formula Qb, as applicable.

[0043] In the context of this invention, the phrases “R6 is a five- to six-membered saturated, partially saturated, or heteroaromatic ring system connected by a ring carbon atom to an imidazole ring, which is connected to a substituent R5…” and “R6 is a five- to six-membered saturated, partially saturated, heteroaromatic ring system connected by a ring nitrogen atom to an imidazole ring connected to a substituent R5…”, as applicable, refer to the specific embodiment of substituent R6 and the connection manner of group Q represented by any formula Qc in Formula I, as applicable.

[0044] In the context of this invention, examples of "Q1 is a five- to six-membered aromatic ring system, which is connected to a ring containing a substituent A by a ring carbon atom, ...; and the ring system may contain 1, 2 or 3 cyclic heteroatoms..." are, but are not limited to, phenyl, pyrazolyl, triazolyl, pyridyl and pyrimidinyl; preferably phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidin-2-yl, pyrimidin-4-yl and pyrimidin-5-yl.

[0045] In the context of this invention, examples of "Q1 is a five-membered aromatic ring system connected by a cyclic nitrogen atom to a ring containing a substituent A, ...; and the ring system comprises 1, 2 or 3 cyclic heteroatoms..." are, but are not limited to, pyrazolyl, pyrroloyl, imidazoyl and triazolyl; preferably, pyrrolo-1-yl, pyrazol-1-yl, triazol-2-yl, 1,2,4-triazol-1-yl, triazol-1-yl and imidazo-1-yl.

[0046] In the context of this invention, examples of “R6 is a five- to six-membered saturated, partially saturated, aromatic or heteroaromatic ring system connected to an imidazole ring via a ring carbon atom, the imidazole ring being connected to a substituent R5, ..."; and the ring system may contain one, two or three cyclic heteroatoms..." are, but are not limited to, phenyl, pyrazolyl, imidazole, triazolyl, pyridinyl, isoxazolyl, dihydroisooxazolyl, oxazolyl and pyrimidinyl.

[0047] In the context of this invention, examples of “R6 being a five- to six-membered saturated, partially saturated, heteroaromatic ring system with a cyclic nitrogen atom connected to an imidazole ring linked to a substituent R5, ..." and the ring system comprising one, two, or three cyclic heteroatoms, ..." are, but are not limited to, pyrazolyl, pyrroleyl, imidazoleyl, and triazoleyl.

[0048] The following provides certain embodiments according to the present invention.

[0049] Example 1 provides a compound having Formula I as defined above, or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer, or N-oxide thereof.

[0050] Example 2 provides the compound according to Example 1 or its agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide, wherein Q is Qa and the preferred definitions of R1, R2, X, A, Q1, R3 and R4 are listed below.

[0051] Example 3 provides the compound according to Example 1 or its agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide, wherein Q is Qb and the preferred definitions of R1, R2, X, A, Q1, R3 and R4 are listed below.

[0052] Example 4 provides the compound according to Example 1 or its agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide, wherein Q is Qc and the preferred definitions of R1, R5, R6, X, R3 and R4 are listed below.

[0053] Regarding Examples 1-4, the preferred definitions of R1, R2, X, A, Q1, R5, R6, R3, and R4 are as follows: any combination thereof.

[0054] Preferably, A is N or CH.

[0055] Ideally, A is N.

[0056] Preferably, X is S or SO2.

[0057] Ideally, X is SO2.

[0058] Preferably, R1 is a C1-C4 alkyl or a C3-C6 cycloalkyl-C1-C4 alkyl.

[0059] More preferably, R1 is a C1-C4 alkyl group.

[0060] Even more preferably, R1 is ethyl or cyclopropylmethyl.

[0061] Most preferably, R1 is an ethyl group.

[0062] When Q is Qa, preferably, Q1 is hydrogen, halogen, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, C1-C6 cyanoalkyl, C1-C6 haloalkoxy, -N(R3)2, -N(R3)COR4, -N(R3)CON(R3)2, (oxazolidin-2-one)-3-yl or 2-pyridinyloxy;

[0063] It is also preferred that when Q1 is a five- to six-membered aromatic ring system connected to a ring containing substituent A via a ring carbon atom, the ring system is unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and the ring system may contain one or two cyclic nitrogen atoms;

[0064] It is also preferred that when Q1 is a five-membered aromatic ring system connected to a ring containing substituent A via a cyclic nitrogen atom, the ring system is unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and the ring system contains 2 or 3 cyclic nitrogen atoms.

[0065] More preferably, Q1 is hydrogen, halogen, trifluoromethyl, cyclopropyl, cyanocyclopropyl, cyanoisopropyl, trifluoroethoxy, (oxazolidinyl-2-one)-3-yl, 2-pyridyloxy, an N-linked pyrazolyl group that may be monosubstituted with chlorine or trifluoromethyl, an N-linked triazolyl group, a C-linked pyrimidinyl group, -N(R3)2, -N(R3)COR4, or -N(R3)CON(R3)2, wherein in each of these, R3 is independently hydrogen or methyl and R4 is methyl, ethyl, or cyclopropyl.

[0066] Most preferably, Q1 is hydrogen, bromine, trifluoromethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 2,2,2-trifluoroethoxy, -NH(CH3), -N(CH3)COCH3, -N(CH3)COCH2CH3, -N(CH3)CO(cyclopropyl), -N(H)CONH(CH3), -N(CH3)CONH(CH3), (oxazolidinyl-2-one)-3-yl, 2-pyridyloxy, pyrazol-1-yl, 3-chloro-pyrazol-1-yl, 3-trifluoromethyl-pyrazol-1-yl, 1,2,4-triazol-1-yl, or pyrimidin-2-yl.

[0067] It is also preferred that Q1 is selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl, preferably trifluoromethyl or difluoroethyl; C1-C6 haloalkoxy, preferably trifluoroethoxy or difluoropropoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl that may be monosubstituted by cyanocyclopropyl; N-linked pyrazolyl that may be monosubstituted by chlorine; C-linked pyrazolyl that may be N-substituted by cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole that may be monosubstituted by cyclopropyl; and C-linked isoxazole that may be monosubstituted by cyclopropyl.

[0068] Further preferred is when Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-(1 -Cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 4-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0069] Preferably, each R3 is independently hydrogen or a C1-C4 alkyl group.

[0070] Most preferably, each R3 is independently hydrogen or methyl.

[0071] Preferably, R4 is a C1-C6 alkyl or a C3-C6 cycloalkyl.

[0072] More preferably, R4 is methyl, ethyl, or cyclopropyl.

[0073] Most preferably, R4 is a methyl group.

[0074] Preferably, R2 is hydrogen or a C1-C4 alkyl group.

[0075] More preferably, R2 is hydrogen or methyl.

[0076] Most preferably, R2 is hydrogen.

[0077] When Q is Qb, preferably, Q1 is hydrogen, halogen, C3-C6 cycloalkyl, -N(R3)2, -N(R3)COR4, -N(R3)CON(R3)2 or (oxazolidin-2-one)-3-yl;

[0078] It is also preferred that when Q1 is a five- to six-membered aromatic ring system connected to a ring containing substituent A via a ring carbon atom, the ring system is unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and the ring system may contain one or two cyclic nitrogen atoms;

[0079] It is also preferred that when Q1 is a five-membered aromatic ring system connected to a ring containing substituent A via a cyclic nitrogen atom, the ring system is unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and the ring system contains 2 or 3 cyclic nitrogen atoms.

[0080] More preferably, Q1 is hydrogen, halogen, cyclopropyl, (oxazolidin-2-one)-3-yl, N-linked pyrazolyl group that may be monosubstituted with chlorine or trifluoromethyl, N-linked triazolyl group, C-linked pyrimidinyl group, -N(R3)2, -N(R3)COR4, or -N(R3)CON(R3)2, wherein in each of these, R3 is independently hydrogen or methyl and R4 is methyl, ethyl, or cyclopropyl.

[0081] Most preferably, Q1 is hydrogen, bromine, cyclopropyl, -NH(CH3), -N(CH3)COCH3, -N(CH3)COCH2CH3, -N(CH3)CO(cyclopropyl), -N(H)CONH(CH3), -N(CH3)CONH(CH3), (oxazolidin-2-one)-3-yl, pyrazol-1-yl, 3-chloro-pyrazol-1-yl, 3-trifluoromethyl-pyrazol-1-yl, 1,2,4-triazol-1-yl, or pyrimidin-2-yl.

[0082] It is also preferred that Q1 is selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl, preferably trifluoromethyl or difluoroethyl; C1-C6 haloalkoxy, preferably trifluoroethoxy or difluoropropoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl that may be monosubstituted by cyanocyclopropyl; N-linked pyrazolyl that may be monosubstituted by chlorine; C-linked pyrazolyl that may be N-substituted by cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole that may be monosubstituted by cyclopropyl; and C-linked isoxazole that may be monosubstituted by cyclopropyl.

[0083] Further preferred is when Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-(1 -Cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 4-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0084] When Q is Qc, preferably, R5 is a C1-C4 alkyl group.

[0085] More preferably, R5 is methyl or ethyl.

[0086] Most preferably, R5 is a methyl group.

[0087] Preferably, R6 is hydrogen, halogen, C3-C6 cycloalkyl, C1-C6 haloalkoxy, -CO(NR3R4), or -NR3COR4;

[0088] Preferably, R6 is a five-membered heteroaromatic ring system linked to an imidazole ring via a cyclic nitrogen atom. This imidazole ring is connected to a substituent R5. The ring system is unsubstituted or monosubstituted by substituents selected from the group consisting of halogens, C3-C6 cycloalkyl groups, or C1-C4 haloalkyl groups, wherein the ring system contains two cyclic nitrogen atoms; or

[0089] Preferably, R6 is a five- to six-membered partially saturated, aromatic or heteroaromatic ring system linked to an imidazole ring via a ring carbon atom, the imidazole ring being linked to a substituent R5, the ring system being unsubstituted or monosubstituted by substituents selected from the group consisting of: C1-C4 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, (C3-C8)cycloalkyl-(C1-C6)alkyl-, or (C3-C8)cycloalkyl monosubstituted with cyano-(C1-C6)alkyl-, and the ring system may contain two cycloheteratomes selected from the group consisting of nitrogen and oxygen, wherein the ring system may not contain more than one epoxy atom.

[0090] More preferably, R6 is hydrogen, halogen, cyclopropyl, trifluoroethoxy, -CO(NR3R4) or -NR3COR4, wherein in each of these, R3 is methyl and R4 is trifluoroethoxy, an N-linked pyrazolyl group monosubstituted by chlorine, cyclopropyl or trifluoromethyl, a C-linked pyrimidinyl group monosubstituted by cyclopropyl, difluoromethyl, difluoroethyl, cyanocyclopropylmethyl or cyclopropylmethyl, a C-linked dihydroisoxazole monosubstituted by chlorine, trifluoromethyl or cyclopropyl, or a phenyl group monosubstituted by chlorine, fluorine, cyclopropyl or cyano.

[0091] Most preferably, R6 is hydrogen, cyclopropyl, 2,2,2-trifluoroethoxy, -CONCH3(CH2CF3), -N(CH3)COCH2CF3, or a substituent selected from J1 to J12.

[0092]

[0093] Preferably, R6 is selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl, preferably trifluoromethyl or difluoroethyl; C1-C6 haloalkoxy, preferably trifluoroethoxy or difluoropropoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl monosubstituted with cyanocyclopropyl; N-linked pyrazolyl monosubstituted with chlorine; C-linked pyrazolyl group N-substituted with cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole monosubstituted with cyclopropyl; and C-linked isoxazole monosubstituted with cyclopropyl.

[0094] Further preferred is that R6 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-(1- Cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 4-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0095] Preferably, each R3 is independently a C1-C4 alkyl group.

[0096] Most preferably, each R3 is independently a methyl group.

[0097] Preferably, R4 is independently a C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 haloalkoxy.

[0098] Most preferably, R4 is independently methyl or -CH2CF3.

[0099] The following describes another embodiment of the invention.

[0100] A preferred group of compounds having formula I is represented by the following: compounds having formula I-A1

[0101]

[0102] Where A, R1, R2, X, Q1, R3, and R4 are as defined above under Equation I.

[0103] In a preferred set of compounds having the formula I-A1, A is CH or N; R1 is C1-C4 alkyl or C3-C6 cycloalkyl-C1-C4 alkyl; R2 is hydrogen or C1-C4 alkyl; X is S or SO2; Q1 is hydrogen, halogen, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, C1-C6 cyanoalkyl, C1-C6 haloalkoxy, -N(R3)2, -N(R3)COR4, -N(R3)CON(R3)2, (oxazolidinyl-2-one)-3-yl or 2-pyridyloxy; wherein each R3 is independently hydrogen or C1-C4 alkyl; and R4 is C1-C6 alkyl or C3-C6 cycloalkyl.

[0104] In another preferred group of compounds having formula I-A1, A is CH or N; R1 is ethyl or cyclopropylmethyl; R2 is hydrogen or methyl; X is S or SO2; and Q1 is hydrogen, bromine, trifluoromethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 2,2,2-trifluoroethoxy, -NH(CH3), -N(CH3)COCH3, -N(CH3)COCH2CH3, -N(CH3)CO(cyclopropyl), -N(H)CONH(CH3), -N(CH3)CONH(CH3), (oxazolidin-2-one)-3-yl, or 2-pyridyloxy.

[0105] In another preferred group of compounds having the formula I-A1, A is N; R1 is ethyl; R2 is hydrogen; X is SO2; and Q1 is hydrogen, bromine, trifluoromethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 2,2,2-trifluoroethoxy, -NH(CH3), -N(CH3)COCH3, -N(CH3)COCH2CH3, -N(CH3)CO(cyclopropyl), -N(H)CONH(CH3), -N(CH3)CONH(CH3), (oxazolidin-2-one)-3-yl, or 2-pyridyloxy.

[0106] In another group of further preferred compounds having formula I-A1, Q1 is a five- to six-membered aromatic ring system connected via a ring carbon atom to a ring containing a substituent A, said ring system being unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and said ring system may contain one or two cyclic nitrogen atoms. More preferably, in this embodiment, Q1 is a C-linked pyrimidinyl group.

[0107] Also preferred are compounds of formula I-A1, wherein Q1 is a five-membered aromatic ring system connected via a cyclic nitrogen atom to a ring containing a substituent A, said ring system being unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and said ring system containing 2 or 3 cyclic nitrogen atoms. More preferably in this embodiment, Q1 is an N-linked pyrazolyl group that may be monosubstituted with chlorine or trifluoromethyl; or Q1 is an N-linked triazolyl group.

[0108] In all preferred embodiments of the compounds having formula I-A1 mentioned above and the compounds having formula I-A1, unless otherwise stated, A, R1, R2, R3, X, Q1, and R4 are as defined above under formula I; preferably, A is CH or N, more preferably, A is N; preferably, R1 is ethyl or cyclopropylmethyl, most preferably, R1 is ethyl; preferably, X is S or SO2, most preferably, X is SO2; preferably, R2 is hydrogen; preferably, Q1 is hydrogen, halogen, trifluoromethyl, cyclopropyl, cyanocyclopropyl, cyanoisopropyl, trifluoroethoxy, (oxazolidinyl-2-one)-3-yl, 2-pyridyloxy, N-linked pyrazolyl group that can be monosubstituted with chlorine or trifluoromethyl, N-linked triazolyl group, C-linked pyrimidinyl group, -N(R3)2, -N( R3)COR4 or -N(R3)CON(R3)2, wherein in each of these, R3 is independently hydrogen or methyl and R4 is methyl, ethyl or cyclopropyl; more preferably, Q1 is hydrogen, bromine, trifluoromethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, 2,2,2-trifluoroethoxy, -NH(CH3), -N(CH3)COCH3, -N(CH3)COCH2CH3, -N(CH3)CO(cyclopropyl), -N(H)CONH(CH3), -N(CH3)CONH(CH3), (oxazolidinyl-2-one)-3-yl, 2-pyridyloxy, pyrazol-1-yl, 3-chloro-pyrazol-1-yl, 3-trifluoromethyl-pyrazol-1-yl, 1,2,4-triazol-1-yl or pyrimidin-2-yl.

[0109] Another preferred set of compounds according to this embodiment is a compound having the formula (I-A1-1), which is a compound having the formula (I-A1), wherein A is N; R1 is ethyl; X is SO2; R2 is hydrogen; and preferably, Q1 is hydrogen, halogen, trifluoromethyl, cyclopropyl, cyanocyclopropyl, cyanoisopropyl, 2-pyridyloxy, an N-linked pyrazolyl group that can be monosubstituted by chlorine or trifluoromethyl, or -N(R3)COR4, wherein R3 is methyl and R4 is methyl or ethyl; more preferably, Q1 is hydrogen, bromine, trifluoromethyl, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-methyl-ethyl, -N(CH3)COCH3, 2-pyridyloxy, 3-chloro-pyrazol-1-yl, or 3-trifluoromethyl-pyrazol-1-yl.

[0110] Another preferred group of compounds according to this embodiment is a compound having the formula (I-A1-2), wherein Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; pyrimidine-5 -yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl;

[0111] Preferably, in formula (I-A1-2), Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl ; pyrimidin-5-yl; and pyrimidin-2-yl; more preferably, Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; and pyrimidin-2-yl.

[0112] Another preferred group of compounds having formula I is represented by compounds having formulas I-A2.

[0113]

[0114] Where A, R1, R2, X, Q1, R3, and R4 are as defined above under Equation I.

[0115] In a preferred set of compounds having formulas I-A2, A is CH or N; R1 is C1-C4 alkyl or C3-C6 cycloalkyl-C1-C4 alkyl; R2 is hydrogen or C1-C4 alkyl; X is S or SO2; Q1 is hydrogen, halogen, C3-C6 cycloalkyl, -N(R3)2, -N(R3)COR4, -N(R3)CON(R3)2 or (oxazolidin-2-one)-3-yl; wherein each R3 is independently hydrogen or C1-C4 alkyl; and R4 is C1-C6 alkyl or C3-C6 cycloalkyl.

[0116] In another preferred group of compounds having formula I-A2, A is CH or N; R1 is ethyl or cyclopropylmethyl; R2 is hydrogen or methyl; X is S or SO2; and Q1 is hydrogen, bromine, cyclopropyl, -NH(CH3), -N(CH3)COCH3, -N(CH3)COCH2CH3, -N(CH3)CO(cyclopropyl), -N(H)CONH(CH3), -N(CH3)CONH(CH3) or (oxazolidin-2-one)-3-yl.

[0117] In another preferred group of compounds having formula I-A2, A is N; R1 is ethyl; R2 is hydrogen; X is SO2; and Q1 is hydrogen, bromine, cyclopropyl, -NH(CH3), -N(CH3)COCH3, -N(CH3)COCH2CH3, -N(CH3)CO(cyclopropyl), -N(H)CONH(CH3), -N(CH3)CONH(CH3) or (oxazolidin-2-one)-3-yl.

[0118] In another group of further preferred compounds having formula I-A2, Q1 is a five- to six-membered aromatic ring system connected via a ring carbon atom to a ring containing a substituent A, said ring system being unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and said ring system may contain one or two cyclic nitrogen atoms. More preferably, in this embodiment, Q1 is a C-linked pyrimidinyl group.

[0119] Also preferred are compounds having formula I-A2, wherein Q1 is a five-membered aromatic ring system connected via a cyclic nitrogen atom to a ring containing substituent A, said ring system being unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and said ring system containing 2 or 3 cyclic nitrogen atoms. More preferably in this embodiment, Q1 is an N-linked pyrazolyl group that may be monosubstituted with chlorine or trifluoromethyl; or Q1 is an N-linked triazolyl group.

[0120] In all preferred embodiments of the compounds having formulas I-A2 mentioned above, unless otherwise stated, A, R1, R2, R3, X, Q1, and R4 are as defined above under formula I; preferably, A is CH or N, more preferably, A is N; preferably, R1 is ethyl or cyclopropylmethyl, most preferably, R1 is ethyl; preferably, X is S or SO2, most preferably, X is SO2; preferably, R2 is hydrogen; preferably, Q1 is hydrogen, halogen, cyclopropyl, (oxazolidinyl-2-one)-3-yl, N-linked pyrazolyl group monosubstituted with chloro or trifluoromethyl, N-linked triazolyl group, C-linked pyrimidinyl group, -N(R 3)2, -N(R3)COR4, or -N(R3)CON(R3)2, wherein in each of these, R3 is independently hydrogen or methyl and R4 is methyl, ethyl, or cyclopropyl; more preferably, Q1 is hydrogen, bromine, cyclopropyl, -NH(CH3), -N(CH3)COCH3, -N(CH3)COCH2CH3, -N(CH3)CO(cyclopropyl), -N(H)CONH(CH3), -N(CH3)CONH(CH3), (oxazolidin-2-one)-3-yl, pyrazol-1-yl, 3-chloro-pyrazol-1-yl, 3-trifluoromethyl-pyrazol-1-yl, 1,2,4-triazol-1-yl, or pyrimidin-2-yl.

[0121] Another preferred set of compounds according to this embodiment is a compound having the formula (I-A2-1), which is a compound having the formula (I-A2), wherein A is N; R1 is ethyl; X is SO2; R2 is hydrogen; and preferably, Q1 is hydrogen, halogen, cyclopropyl, N-linked pyrazolyl group that may be monosubstituted with chlorine or trifluoromethyl, N-linked triazolyl group, C-linked pyrimidinyl group or -N(R3)COR4, wherein R3 is methyl and R4 is methyl or ethyl; more preferably, Q1 is hydrogen, bromine, cyclopropyl, -N(CH3)COCH3, 3-chloro-pyrazol-1-yl, 3-trifluoromethyl-pyrazol-1-yl, 1,2,4-triazol-1-yl or pyrimidin-2-yl.

[0122] Another preferred group of compounds according to this embodiment is a compound having the formula (I-A2-2), which is a compound having the formula (I-A2), wherein Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; pyrimidine-5 -yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl;

[0123] Preferably, in formula (I-A2-2), Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl ; pyrimidin-5-yl; and pyrimidin-2-yl; more preferably, Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; and pyrimidin-2-yl.

[0124] Another preferred group of compounds having formula I is represented by the following: compounds having formula I-B1

[0125]

[0126] Where X, R1, R3, R4, R5 and R6 are as defined above under Equation I.

[0127] In a preferred set of compounds having formula I-B1, X is S or SO2; R1 is C1-C4 alkyl or C3-C6 cycloalkyl-C1-C4 alkyl; R5 is C1-C4 alkyl; R6 is hydrogen, halogen, C3-C6 cycloalkyl, C1-C6 haloalkoxy, -CO(NR3R4), or -NR3COR4; wherein each R3 is independently C1-C4 alkyl; and each R4 is independently C1-C6 alkyl or C3-C6 cycloalkyl.

[0128] In another preferred group of compounds having formula I-B1, X is S or SO2; R1 is ethyl or cyclopropylmethyl; R5 is methyl or ethyl; and R6 is hydrogen, cyclopropyl, 2,2,2-trifluoroethoxy, -CONCH3(CH2CF3) or -N(CH3)COCH2CF3.

[0129] In another preferred group of compounds having formula I-B1, X is SO2; R1 is ethyl; R5 is methyl; and R6 is hydrogen, cyclopropyl, 2,2,2-trifluoroethoxy, -CONCH3(CH2CF3) or -N(CH3)COCH2CF3.

[0130] In another, more preferred group of compounds having formula I-B1, R6 is a five-membered heteroaromatic ring system linked to an imidazole ring via a cyclic nitrogen atom. This imidazole ring is linked to a substituent R5, and the ring system is unsubstituted or monosubstituted by a substituent selected from the group consisting of halogens, C3-C6 cycloalkyl groups, or C1-C4 haloalkyl groups, wherein the ring system contains two cyclic nitrogen atoms. More preferably, R6 is an N-linked pyrazolyl group that may be monosubstituted by chlorine, cyclopropyl, or trifluoromethyl.

[0131] In another preferred group of compounds having formula I-B1, R6 is a five- to six-membered partially saturated, aromatic or heteroaromatic ring system linked by a ring carbon atom to an imidazole ring, the imidazole ring being linked to a substituent R5, the ring system being unsubstituted or monosubstituted by a substituent selected from the group consisting of: C1-C4 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, (C3-C8)cycloalkyl-(C1-C6)alkyl-, or (C3-C8)cycloalkyl monosubstituted with cyano-(C1-C6)alkyl-, and the ring system may contain two cycloheteratomes selected from the group consisting of nitrogen and oxygen, wherein the ring system may not contain more than one epoxy atom. In this embodiment, more preferably, R6 is a C-linked pyrimidinyl group, a C-linked pyrazolyl group that can be monosubstituted by cyclopropyl, difluoromethyl, difluoroethyl, cyanocyclopropylmethyl or cyclopropylmethyl, a C-linked dihydroisoxazole that can be monosubstituted by chloro, trifluoromethyl or cyclopropyl, or a phenyl group that can be monosubstituted by chloro, fluorine, cyclopropyl or cyclopropyl substituted by cyano.

[0132] In all preferred embodiments of the compounds having formula I-B1 mentioned above, unless otherwise stated, X, R1, R3, R4, R5, and R6 are as defined above under formula I; preferably, X is S or SO2, most preferably, X is SO2; preferably, R1 is ethyl or cyclopropylmethyl, most preferably, R1 is ethyl; preferably, R6 is hydrogen, cyclopropyl, 2,2,2-trifluoroethoxy, -CONCH3(CH2CF3), -N(CH3)COCH2CF3, which can be chlorinated, cyclopropyl Or a trifluoromethyl monosubstituted N-linked pyrazolyl group, a C-linked pyrimidinyl group, a C-linked pyrazolyl group that may be monosubstituted by cyclopropyl, difluoromethyl, difluoroethyl, cyanocyclopropylmethyl or cyclopropylmethyl, a C-linked dihydroisoxazole that may be monosubstituted by chloro, trifluoromethyl or cyclopropyl, or a phenyl group that may be monosubstituted by chloro, fluorine, cyclopropyl or cyano; more preferably, R6 is hydrogen, cyclopropyl, 2,2,2-trifluoroethoxy, -CONCH3(CH2CF3), -N(CH3)COCH2CF3 or a substituent selected from J1 to J12.

[0133]

[0134] Another preferred group of compounds according to this embodiment is a compound having the formula (I-B1-1), wherein R6 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; pyrimidine-5 -yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0135] Preferably, in formula (I-B1-1), R6 is selected from the group consisting of: cyclopropyl; 2,2,2-trifluoroethoxy; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-(1-cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 4-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole- 5-yl; and 3-cyclopropyl-isoxazole-5-yl; more preferably, R6 is selected from the group consisting of: cyclopropyl; 2,2,2-trifluoroethoxy; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0136] A distinguished group of compounds according to the invention are those having the formula IC.

[0137]

[0138] in

[0139] Q is a group selected from the following groups: formulas Qa-1, Qb-1, and Qc-1.

[0140]

[0141] The arrow indicates the attachment point to the nitrogen atom in the tricyclic ring;

[0142] And among them

[0143] R5 is a C1-C6 alkyl group; preferably, R5 is methyl or ethyl; even more preferably, R5 is methyl; and

[0144] Q1 and R6 are each independently selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl, preferably trifluoromethyl or difluoroethyl; C1-C6 haloalkoxy, preferably trifluoroethoxy or difluoropropoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl monosubstituted with cyanocyclopropyl; N-linked pyrazolyl monosubstituted with chlorine; C-linked pyrazolyl monosubstituted with cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole monosubstituted with cyclopropyl; and C-linked isoxazole monosubstituted with cyclopropyl.

[0145] A preferred set of compounds according to this embodiment are compounds having formula (IC-1), which is a compound having formula (IC), or any preferred embodiment of a compound having formula (IC), wherein

[0146] Q1 and R6 are each independently selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-(1 -Cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 4-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0147] Another preferred group of compounds according to this embodiment is a compound having formula (IC-2), which is a compound having formula (IC), or any preferred embodiment of a compound having formula (IC), wherein...

[0148] Q1 and R6 are each independently selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)benzene 3-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0149] Another group of outstanding compounds according to the invention are those having formulas I-C1, which are compounds having formula (IC), wherein

[0150] R5 is a C1-C6 alkyl group; preferably, R5 is methyl or ethyl; even more preferably, R5 is methyl.

[0151] Q is a group selected from the following groups: formulas Qa-1, Qb-1, and Qc-1.

[0152] The arrow indicates the attachment point to the nitrogen atom in the tricyclic ring;

[0153] And among them

[0154] Q1 is independently selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl, preferably trifluoromethyl or difluoroethyl; C1-C6 haloalkoxy, preferably trifluoroethoxy or difluoropropoxy; -N(CH3)COCH3; N-linked triazolyl; and C-linked pyrimidinyl; and

[0155] R6 is selected from the group consisting of: cyclopropyl; C1-C6 haloalkoxy, preferably trifluoroethoxy; C-linked pyrimidinyl; phenyl monosubstituted with cyanocyclopropyl; N-linked pyrazolyl monosubstituted with chlorine; C-linked pyrazolyl monosubstituted with cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole monosubstituted with cyclopropyl; and C-linked isoxazole monosubstituted with cyclopropyl.

[0156] A preferred set of compounds according to this embodiment are compounds having the formula (I-C1-1), which is a compound having the formula (I-C1), or any preferred embodiment of a compound having the formula (I-C1), wherein

[0157] Q1 is independently selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl; pyrimidin-5-yl; and pyrimidin-2-yl; and

[0158] R6 is selected from the group consisting of: cyclopropyl; 2,2,2-trifluoroethoxy; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-(1-cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 4-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0159] A preferred set of compounds according to this embodiment are compounds having the formula (I-C1-2), which is a compound having the formula (I-C1), or any preferred embodiment of a compound having the formula (I-C1), wherein

[0160] Q1 is independently selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; and pyrimidin-2-yl; and

[0161] R6 is selected from the group consisting of: cyclopropyl; 2,2,2-trifluoroethoxy; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

[0162] Compounds according to the invention can have any number of benefits, particularly including favorable levels of bioactivity for protecting plants against insects or superior properties for use as active ingredients in agrochemicals (e.g., higher bioactivity, favorable activity spectrum, increased safety, improved physicochemical properties, or increased biodegradability or environmental characterization). In particular, it has been unexpectedly found that certain compounds having formula (I) can exhibit favorable safety relative to non-target arthropods, especially pollinators (such as honeybees, solitary bees, and bumblebees). Most particularly, relative to the Italian bee (Apis mellifera).

[0163] In another aspect, the present invention provides a composition comprising an effective amount of an insecticidal, acaricidal, nematicidal, or molluscicidal compound as defined in any of the embodiments having formula (I), (I-A1), (I-A2), (I-B1), and (IC), or an agriculturally chemically acceptable salt, stereoisomer, enantiomer, tautomer, or N-oxide thereof, and optionally, an adjuvant or diluent.

[0164] In another aspect, the present invention provides a method for combating and controlling insects, mites, nematodes, or mollusks, the method comprising applying to the pest, the pest's site, or plants susceptible to the pest an effective amount of an insecticidal, acaricidal, nematodeicidal, or molluskic compound as defined in any of the examples (above) of the compounds having formula (I), (I-A1), (I-A2), (I-B1), and (IC), or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer, or N-oxide thereof, or a composition as defined above.

[0165] In another aspect, the present invention provides a method for protecting plant propagation material from attacks by insects, mites, nematodes or mollusks, the method comprising treating the propagation material or the site in which the propagation material is grown with a composition as defined above.

[0166] The method for preparing compounds having formula I according to the present invention is, in principle, carried out by methods known to those skilled in the art. More specifically, the subgroup of compounds having formula I (where X is SO (sulfoxide) and / or SO2 (sulfone)),

[0167] Option 1a:

[0168]

[0169] Option 1b:

[0170]

[0171] It can be obtained by oxidation of the corresponding sulfide compound having formula I (where X is S), which involves reagents such as m-chloroperoxybenzoic acid (mCPBA), hydrogen peroxide, potassium persulfate preparations (oxone), sodium periodate, sodium hypochlorite, or tert-butyl hypochlorite, and other oxidants (schemes 1a, 1b, and 2). The oxidation reaction is typically carried out in the presence of a solvent. Examples of solvents used in the reaction include aliphatic halogenated hydrocarbons such as dichloromethane and chloroform; alcohols such as methanol and ethanol; acetic acid; water; and mixtures thereof. The amount of oxidant used in this reaction is typically 1 to 3 moles, preferably 1 to 1.2 moles, relative to 1 mole of sulfide compound I generating sulfoxide compound I, and preferably 2 to 2.2 moles of oxidant relative to 1 mole of sulfide compound I generating sulfone compound I. Such oxidation reactions are disclosed, for example, in WO2013 / 018928.

[0172] Option 2:

[0173]

[0174] Compounds having formula I (where Q is as defined above under formula I) can be prepared by the following method (Scheme 3).

[0175] Option 3:

[0176]

[0177] The compound having formula VII is reacted with a compound having formula VIII (where Q is as defined in formula I above, and LG3 is a halogen (or pseudohalogen leaving group, such as trifluoromethanesulfonate)) in the presence of a base (such as sodium carbonate, potassium carbonate, or cesium carbonate, or sodium hydride), in a suitable solvent (such as tetrahydrofuran, dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile), at a temperature between 0°C and 150°C, optionally under microwave irradiation.

[0178] Alternatively, compounds having formula I (where Q is as defined above under formula I) can be prepared in the presence of a base (such as sodium carbonate, potassium carbonate, or cesium carbonate, or potassium tert-butoxide), in the presence of a metal catalyst, or a copper catalyst (such as copper iodide (I)), optionally in the presence of a ligand (such as a diamine ligand (e.g., N,N′-dimethylethylenediamine or trans-cyclohexyldiamine) or dibenzylacetone (dba), or 1,10-phenanthroline), at a temperature between 30°C and 180°C, optionally under microwave irradiation, or in the presence of a palladium catalyst (e.g., palladium(II) acetate, bis(dibenzylacetone)palladium(O) (Pd(dba)2) or tris(dibenzylacetone)dipalladium(O) (Pd2(dba)3 (optionally in the form of a chloroform adduct)); or a palladium precatalyst (e.g., tert-BuBrettPhos Pd G3[(2-di-tert-butylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate or BrettPhos Pd The compound having formula VII is prepared by reacting a compound having formula VIII (where Q is as defined in formula I above, and where LG3 is a halogen (or pseudohalogen leaving group, such as trifluoromethanesulfonate), preferably bromine or iodine) with G3[(2-di-cyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium methanesulfonate (II)) at a temperature between 60°C and 120°C, optionally under microwave irradiation, in the presence of a ligand (e.g., SPhos, t-BuBrettPhos or Xantphos).

[0179] The above reactions can be carried out in the presence of solvents such as toluene, dimethylformamide (DMF), N-methylpyrrolidine (NMP), dimethyl sulfoxide (DMSO), dioxane, and tetrahydrofuran (THF) and are described in literature, such as WO 2012031004, WO2009042907 and Synthetic Communications 41:67–72, 2011.

[0180] Alternatively, a compound having formula I (where Q is as defined above under formula I) can be prepared by reacting a compound having formula VI (where LG2 is a leaving group (e.g., Br, Cl, or I (preferably bromine)) and a compound having formula IX (where Q is as defined above under formula I) with a compound having formula IX (where Q is as defined above under formula I) in the presence of a base (e.g., sodium carbonate, potassium carbonate, or cesium carbonate, or sodium hydride, N,N-diisopropylethylamine, or KOtBu) and a solvent (e.g., ethanol, methanol, dioxane, toluene, acetonitrile, DMF, DMA, DMSO, THF) at a temperature between 0°C and 150°C, optionally under microwave irradiation) with a compound having formula IX (where Q is as defined above under formula I) in the presence of a base (e.g., sodium carbonate, potassium carbonate, or cesium carbonate, or sodium hydride, N,N-diisopropylethylamine, or KOtBu) and a solvent (e.g., ethanol, methanol, dioxane, toluene, acetonitrile, DMF, DMA, DMSO, THF) in the presence of ... toluene, acetonitrile, DMF, DMA, or THF) in the presence of a leaving group (e.g., Br, Cl, or I (preferably bromine)) under microwave irradiation) in the presence of a leaving group (e.g., Br, Cl, or I (preferably bromine)) and a compound having formula IX (e.g., C1-C6 alkyl, benzyl, or phenyl) in the presence of a leaving group (e.g

[0181] Alternatively, a compound having formula I (wherein Q is as defined above in formula I) can be prepared, for example, by cyclizing a compound having formula X (wherein Q is as defined in formula I) in the presence of phosphoryl chloride (other amide coupling agents, such as thionyl chloride SOCl2, HATU or EDCI, may also be used), optionally in the presence of a base (such as triethylamine, pyridine or humin' base), optionally in the presence of a solvent or diluent (such as toluene or xylene), at a temperature between 0°C and 180°C, preferably between 20°C and 120°C (Scheme 3).

[0182] Compounds having formula I (where Q is as defined above under formula I) can also be prepared by the following method

[0183] Option 4:

[0184]

[0185] A compound having formula Xa (where Q is as defined above in Formula I and X0 is a halogen, preferably chlorine, or X0 is X) is cyclized in the presence of a base (such as triethylamine, N,N-diisopropylethylamine, or pyridine), optionally in the presence of a catalyst (such as 4-dimethylaminopyridine DMAP), in an inert solvent (such as dichloromethane, tetrahydrofuran, dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, ethyl acetate, or toluene) at a temperature between 0°C and 50°C. 01 or X 02 (Scheme 4). Certain bases (such as pyridine and triethylamine) can be successfully used as both bases and solvents.

[0186] Compounds having formula Xa (where Q is as defined above under formula I, and where X0 is a halogen, preferably chlorine, or X0 is X 01 or X 02The compound X can be prepared by activating a compound having formula X (where Q is as defined above under formula I) using methods known to those skilled in the art and described, for example, in Tetrahedron, 2005, 61(46), 10827-10852. Preferably, the activated substance Xa is formed (where Q is as defined above under formula I, and where X0 is a halogen, preferably chlorine). For example, in an inert solvent (e.g., dichloromethane CH2Cl2 or tetrahydrofuran THF), at a temperature between 20°C and 100°C (preferably 25°C), in the presence of a catalytic amount of N,N-dimethylformamide DMF, by treating X with, for example, oxalyl chloride (COCl)2 or thionyl chloride SOCl2. Alternatively, compounds having formula X can be treated in an inert solvent (e.g., pyridine or tetrahydrofuran THF) optionally in the presence of a base (e.g., triethylamine) at a temperature of 50°C–180°C with, for example, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide EDC or dicyclohexylcarbodiimide DCC, to generate an activated substance Xa (where X0 is X...). 01 or X 02 ).

[0187] Compounds having formula VII can be prepared by reacting a compound having formula VI (wherein LG2 is a leaving group (e.g., Br, Cl, or I (preferably bromine)) with ammonia or an ammonia substitute (e.g., NH4OH) in the presence of a solvent (e.g., ethanol, methanol, dioxane, toluene, DMF, DMA, DMSO, THF) at a temperature between 0°C and 150°C, optionally under microwave irradiation) with ammonia or an ammonia substitute (e.g., NH4OH).

[0188] A compound having formula X (wherein Q is as defined above under formula I) can be prepared by the following (Scheme 3): a nucleophilic substitution reaction of a compound having formula VI (wherein LG2 is a leaving group such as Br, Cl or I (preferably bromine) and R is a C1-C6 alkyl, benzyl or phenyl group) with an amino compound having formula IX (wherein Q is as defined above under formula I), followed by in-situ hydrolysis of the resulting intermediate ester having formula XVII (see also Scheme 8) (wherein Q is as defined above under formula I and R is a C1-C6 alkyl, benzyl or phenyl group).

[0189]

[0190] Unhydrolyzed ester compounds of formula XVII, generated in situ, can be isolated and converted via saponification in the presence of a suitable base (e.g., sodium hydroxide NaOH, lithium hydroxide LiOH, or barium hydroxide Ba(OH)2) and a solvent (e.g., ethanol, methanol, dioxane, tetrahydrofuran, or water (or mixtures thereof)) to form carboxylic acids of formula X. Alternatively, clapico-type conditions (e.g., heating substrate XVII in the presence of sodium chloride or lithium chloride in N-methylpyrrolidone or aqueous dimethyl sulfoxide DMSO, optionally under microwave irradiation) can be used to convert compounds of formula XVII to compounds of formula X. Direct conversion of compounds of formula VI to compounds of formula X can be carried out in the presence of a base (especially sodium hydride, KOtBu, butyllithium, or diisopropylaminolithium) and a solvent (e.g., dioxane, DMF, DMA, DMSO, or THF) at temperatures between -30°C and 150°C.

[0191] The above reaction for preparing a compound having formula X can also be carried out by reacting a compound having formula VI with a compound having formula IXa (where Q is as defined above in formula I, and PG is an amino protecting group, such as tert-butoxycarbonyl (BOC)) under similar conditions as described above (for preparing a compound having formula X by reacting a compound having formula VI with a compound having formula IX), and then deprotecting the amino protecting group PG.

[0192]

[0193] Deprotection of the amino protecting group is well known to those skilled in the art. For example, the BOC protecting group can be removed, for example, in the presence of an acid (such as hydrochloric acid or trifluoroacetic acid), optionally in the presence of an inert solvent (such as dichloromethane, tetrahydrofuran, dioxane, or trifluorotoluene), at a temperature between 0°C and 70°C. This method of forming compounds of formulas X (and I) from compounds having formulas VI and IXa is detailed in Scheme 3a and reflects the specific case where the group PG of IXa is a tert-butoxycarbonyl (BOC), defining compounds of formula XIX, wherein Q is as defined above in formula I.

[0194] Option 3a (The previously mentioned definition of substituents remains valid):

[0195]

[0196] Compounds having formula VI and compounds having formula XIX react in the presence of a base (such as sodium carbonate, potassium carbonate or cesium carbonate, or sodium hydride, or N,N-diisopropylethylamine or potassium tert-butoxide KOtBu) and in the presence of a solvent (such as ethanol, methanol, dioxane, toluene, acetonitrile, DMF, N,N-dimethylacetamide DMA, DMSO, or THF) at a temperature between 0°C and 150°C, optionally under microwave irradiation, to form compounds having formula XVIIa.

[0197] At temperatures between 0°C and 70°C, optionally in the presence of an inert solvent (such as dichloromethane, tetrahydrofuran, dioxane, or trifluorotoluene), the removal of the tert-butoxycarbonyl (BOC) group from a compound having formula XVIIa via acid (such as hydrochloric acid or trifluoroacetic acid) yields a compound having formula XVII. In the presence of a solvent (such as ethanol, methanol, dioxane, tetrahydrofuran, or water (or mixtures thereof)), a compound having formula XVII is saponified in the presence of a suitable base (e.g., sodium hydroxide NaOH, lithium hydroxide LiOH, or barium hydroxide Ba(OH)₂) to form a carboxylic acid having formula X (alternatively, Krapcho-type conditions as described above can be used). For example, the cyclization of a compound having formula X to a compound having formula I can be achieved in the presence of phosphoryl chloride (other amide coupling agents, such as thionyl chloride SOCl2, HATU, or EDCI, may also be used), optionally in the presence of a base (such as triethylamine, pyridine, or humrind), optionally in the presence of a solvent or diluent (such as toluene or xylene), at a temperature between 0°C and 180°C, preferably between 20°C and 120°C. Alternatively, the direct cyclization of a compound having formula XVII to a compound having formula I can be achieved under the conditions mentioned in Scheme 8 below.

[0198] Compounds having formula VI (where LG2 is a leaving group (e.g., Br, Cl or I (preferably bromine)) and R is C1-C6 alkyl, benzyl or phenyl) are known or can be prepared by methods known to those skilled in the art.

[0199] For example, a compound having formula VI (where LG2 is a leaving group (e.g., Br, Cl, or I (preferably bromine)) and R is a C1-C6 alkyl, benzyl, or phenyl) can be prepared by benzyl halogenation initiated by a radical of a compound having formula V (where R is a C1-C6 alkyl, benzyl, or phenyl). This reaction is well known to those skilled in the art and can be carried out in the presence of an electrophilic halogenating agent (such as Br2, NBS, Cl2, or NIS), in the presence of a radical initiator (e.g., AIBN (azobisisobutyronitrile) or benzoyl peroxide), or under photochemical conditions, at temperatures ranging from 20°C to the boiling point of the mixture, and in the presence of a solvent (such as toluene, xylene, acetonitrile, hexane, dichloroethane, or carbon tetrachloride). Such reactions are known by the name Wohl–Ziegler bromination and have been reported in the literature, for example in Synthesis, 2015, 47, 1280–1290 and J. Am. Chem. Soc., 1963, 85(3), pp. 354–355.

[0200] Compounds having formula V (where R is a C1-C6 alkyl, benzyl, or phenyl) can be prepared by a Suzuki reaction (Scheme 3), which involves, for example, reacting a compound having formula IVa (where LG1 is a halogen Br, Cl, I (preferably Cl), and R is a C1-C6 alkyl, benzyl, or phenyl) with trimethylcycloboroxane or potassium methyltrifluoroborate and other methylboronic acid equivalents. The reaction can be catalyzed by a palladium-based catalyst (e.g., tetrakis(triphenylphosphine)palladium(0), (1,1'-bis(diphenylphosphine)ferrocene)dichloro-palladium-dichloromethane (1:1 complex) or chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (XPhos cyclic palladium complex)) in the presence of a base (such as sodium carbonate, tripotassium phosphate, or cesium fluoride) in a solvent or solvent mixture (such as, for example, a mixture of dioxane, acetonitrile, N,N-dimethylformamide, 1,2-dimethoxyethane, and water, or a dioxane / water mixture, or a toluene / water mixture), preferably under an inert atmosphere. The reaction temperature can preferably be in the range from room temperature to the boiling point of the reaction mixture, or the reaction can be carried out under microwave irradiation. Such Suzuki reactions are well known to those skilled in the art and have been reviewed, for example, in J. Organomet. Chem. 576, 1999, 147-168.

[0201] Alternatively, compounds having formula V (where R is C1-C6 alkyl, benzyl, or phenyl) can be prepared according to scheme 3b.

[0202] Option 3b:

[0203]

[0204] In scheme 3b, a compound having formula V (where R is C1-C6 alkyl, benzyl, or phenyl) can be prepared from a compound having formula Va by an esterification reaction (which involves reacting a compound having formula Va with an alcohol R-OH (where R is C1-C6 alkyl, benzyl, or phenyl) in the presence of an acid catalyst (e.g., sulfuric acid, or a Lewis acid, such as Sc(OTf)3 or FeCl3). Such reactions are well known to those skilled in the art and are known under the name Fischer esterification, and have been reported in the literature, for example in J. Org. Chem., 2006, 71, 3332-3334, Chem. Commun., 1997, 351-352, and Synthesis, 2008, 3407-3410. This esterification reaction can also be carried out by reacting a compound having formula Va with TMSCHN2 to form a compound having formula V, where R is a methyl group, and is reported in Angew. Chem. Int. Ed. 2007, 46, 7075. Compounds having formula Va can be prepared by oxidation of compounds having formula Vb. Such reactions are well known to those skilled in the art. Examples of reagents that promote this conversion include potassium persulfate preparations (Oxone), KMnO4, NaClO2 (known under the name of Pinnick's oxidation), AgNO3 in the presence of metal hydroxides, or Ag2O (known under the name of Tollen's reagent). Such reactions are known in the literature and described, for example, in Acta Chem. Scand. 1973, 27: 888–890; Tetrahedron 1981, 37(11): 2091–2096; Ber. Deut. Chem. Gessel. 15(1882), pp. 1635–1639; Org. Synth. 1953, 33, 94. Compounds having the formula Vb can be produced by compounds having the formula Vc (where LG... 11 It is a halogen, such as Br, Cl, or I (preferably Cl)) prepared via a similar procedure as described in Scheme 3, converting a compound having formula IVa into a compound having formula V. A compound having formula Vc (wherein LG) 11Halogens, such as Br, Cl, or I (preferably Cl), can be prepared from compounds having the formula Vd via halogenation and in-situ oxidation (using halogenating agents such as iodine, bromine, chlorine, N-chlorosuccinimide, or N-bromosuccinimide). Alternatively, halogenation can be performed and an oxidizing agent can be used in a subsequent step to form a compound having the formula Vc from the compound having the formula Vd in two steps. Compounds having the formula Vd are known in the literature, CAS Registry No. 72768-97-9.

[0205] A compound having formula IVa (where LG1 is a halogen Br, Cl, or I (preferably Cl), and R is a C1-C6 alkyl, benzyl, or phenyl) can be prepared by reacting the compound having formula IV (where R is a C1-C6 alkyl, benzyl, or phenyl) with a nitrite ester (such as tert-butyl nitrite t-BuONO, isoamyl nitrite, or sodium nitrite) in the presence of a hydrohalic acid H-LG1 and a copper salt Cu-LG1 (where LG1 is a halogen, such as Br, Cl, or I (preferably Cl)) under Sandmeyer-type reaction conditions. This conversion is preferably carried out in an inert solvent (such as acetonitrile, or a halogenated solvent such as 1,2-dichloroethane, or water) at a temperature between 0°C and 150°C, preferably in the range from room temperature to the boiling point of the reaction mixture. Compounds having formula IV (where R is C1-C6 alkyl, benzyl, or phenyl) can be prepared from compounds having formula III (where LG1 is a halogen, preferably Br, Cl, or I) by methods found, for example, in WO 2016 / 020286, which involve carbonylation reactions in which a compound having formula III is reacted with carbon monoxide (usually under pressure) in the presence of a metal catalyst such as a palladium catalyst (e.g., palladium(II) acetate) in an alcohol ROH solvent (optionally in the presence of a co-solvent) (where R is C1-C6 alkyl, benzyl, or phenyl), and optionally in the presence of a phosphine ligand, and optionally in the presence of a base, at a temperature between 0°C and 180°C. Compounds having formula III (where LG1 is a halogen, preferably Br, Cl, or I) can be prepared by a halogenation reaction, which involves, for example, reacting a compound having formula II with a halogenating agent (e.g., N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), or N-iodosuccinimide (NIS), or alternatively, deschloride, bromine, or iodine). Such halogenation reactions are carried out in an inert solvent (e.g., chloroform, carbon tetrachloride, 1,2-dichloroethane, acetic acid, ether, acetonitrile, or N,N-dimethylformamide) at a temperature between 20°C and 200°C, preferably between room temperature and 100°C.

[0206] Compounds having formula VI

[0207]

[0208] in

[0209] LG2 being a leaving group (e.g., Br, Cl, or I) and R being a C1-C6 alkyl, benzyl, or phenyl group is novel and has been specifically developed for the preparation of compounds having formula I according to the invention, and thus represents another object of the invention. Preferred options and preferred embodiments of the substituents in compounds having formula I are also effective for compounds having formula VI. Preferably, LG2 is bromine or chlorine; even more preferably, LG2 is bromine. Preferably, R is a C1-C6 alkyl group; even more preferably, R is methyl or ethyl.

[0210] Alternatively, a compound having formula I (where Q is as defined above under formula I) can be prepared by following scheme 5 by performing an amidation reaction of a compound having formula X (where Q is as defined above under formula I).

[0211] Option 5:

[0212]

[0213] The reaction details (amidation reaction) for converting a compound having formula X into a compound having formula I are described in Scheme 6, and follow the methods and conditions already described in Schemes 3 and 4 above (the path from a compound having formula X to a compound having formula Xa to a compound having formula I).

[0214] Option 6:

[0215]

[0216] A compound having formula X (where Q is as defined above under formula I) can be prepared by reacting a compound having formula XII with a compound having formula IX (where Q is as defined above under formula I) under reducing amination conditions (Scheme 6). The reaction can be carried out in the presence of a reducing agent (especially, for example, sodium cyanoborohydride or sodium triacetoxyborohydride), optionally in the presence of an acid (e.g., trifluoroacetic acid, formic acid, or acetic acid), and at a temperature ranging from 0 °C to the boiling point of the mixture. The reaction can be carried out in the presence of an inert solvent (e.g., ethanol, methanol, dioxane, or tetrahydrofuran). Such reactions involving multi-step transformations from a compound having formula XII to a compound having formula I have been described in the literature, for example in Bioorganic & Medicinal Chemistry Letters 26(2016) 5947–5950.

[0217] Compounds having formula XII can be prepared from compounds having formula XI (where LG2 is chlorine, bromine, or iodine (preferably bromine), and R is C1-C6 alkyl, benzyl, or phenyl) by hydrolysis and subsequent intramolecular cyclization (Scheme 5). This reaction can be carried out under alkaline conditions using metal hydroxides, for example, in the presence of a solvent (such as dioxane, tetrahydrofuran, or water) using an aqueous solution of sodium hydroxide at temperatures ranging from 20 to 150 °C, as reported in Synlett [Synthetic Express] 1992, (6), 531-533, or under acidic aqueous conditions, for example, in the presence of a solvent (such as water, dioxane, or a halogenated solvent (such as dichloroethane)) using acetic acid, hydrochloric acid, or sulfuric acid, as reported in Tetrahedron [Tetrahedron] 62 (2006) 9589-9602.

[0218] Compounds having formula XI (wherein LG2 is chlorine, bromine, or iodine (preferably bromine), and R is C1-C6 alkyl, benzyl, or phenyl) can be prepared from compounds having formula V (wherein R is C1-C6 alkyl, benzyl, or phenyl) by methods similar to those described in Scheme 3 for converting compounds having formula V into compounds having formula VI. An excess of the electrophilic halogenating agent is preferred, more preferably at least about two equivalents.

[0219] Alternatively, a compound having formula I (where Q is as defined above under formula I) can be prepared from a compound having formula XV (where Q is as defined above under formula I) by selective reduction of the carbonyl functional group (Scheme 7).

[0220] Option 7:

[0221]

[0222] This reaction can be carried out in the presence of a reducing agent (e.g., NaBH4, LiAlH4, palladium on carbon) in the presence of hydrogen, or in the presence of a combination of two reducing agents (e.g., NaBH4, followed by triethylsilane). Such reactions have been described, for example, in US 20100160303 A1.

[0223] Compounds having formula XV (where Q is as defined above under formula I) can be prepared from compounds having formula XIV (where Q is as defined above under formula I, and R is C1-C6 alkyl, benzyl, or phenyl) by hydrolysis and subsequent cyclization, as described in Scheme 4 for converting compounds having formula X into compounds having formula I.

[0224] A compound having formula XIV (where Q is as defined above under formula I, and R is C1-C6 alkyl, benzyl, or phenyl) can be prepared by reacting a compound having formula XIII (where R is C1-C6 alkyl, benzyl, or phenyl) with a compound having formula IX (where Q is as defined above under formula I) via an amidation reaction already described in scheme 4.

[0225] Compounds having formula XIII (where R is C1-C6 alkyl, benzyl, or phenyl) can be prepared by benzyl oxidation of compounds having formula V (where R is C1-C6 alkyl, benzyl, or phenyl). This reaction can be carried out in the presence of oxygen in the presence of an oxidizing agent (such as KMNO4, nBu4MnO4, K2S2O8), or under photochemical conditions in the presence of oxygen, and at temperatures ranging from 20°C to the boiling point of the solvent. The reaction is carried out in the presence of an inert solvent (such as acetonitrile, ethyl acetate, DMSO, dichloroethane). Such reactions are known in the literature, for example in Synthesis 2017, 49, 4007-4016, Synthesis 2006, 1757-1759, and IOSR Journal of Applied Chemistry 2014, 7, 16-27.

[0226] Alternatively, a compound having formula I (where Q is as defined above in formula I) can be prepared by cyclization of a compound having formula XVII (where Q is as defined above in formula I and R is C1-C6 alkyl, benzyl, or phenyl) (Scheme 8):

[0227] Option 8:

[0228]

[0229] This reaction can be carried out in the presence of a base (especially potassium tert-butoxide, lithium diisopropylamide, sodium hydride), at a temperature ranging from -20°C to the boiling point of the reaction mixture, and in the presence of an inert solvent (such as tetrahydrofuran, dioxane, DMA, DMSO, or DMF). Such reactions have been reported, for example, in Synlett [Synthetic Letters] 2006(4):591-594.

[0230] Compounds having formula XVII (where Q is as defined above in formula I, and R is C1-C6 alkyl, benzyl, or phenyl) can be prepared by reacting a compound having formula XVI (where R is C1-C6 alkyl, benzyl, or phenyl) with a compound having formula IX (where Q is as defined above in formula I) under photoelectrophoretic conditions. Such reactions are well known to those skilled in the art and can be carried out in the presence of phosphine reagents (such as triphenylphosphine, tributylphosphine, or polymer-supported triphenylphosphine), in the presence of azodicarbonate reagents (such as diethyl azodicarbonate, diisopropyl azodicarbonate), at temperatures ranging from 0°C to 100°C, and in the presence of inert solvents (such as acetonitrile, dichloromethane, tetrahydrofuran, or toluene). Such reactions have been reported, for example, in Synthesis, 1981(1), 1-28.

[0231] Compounds having formula XVI (where R is C1-C6 alkyl, benzyl, or phenyl) can be prepared by reacting compounds having formula XIII (where R is C1-C6 alkyl, benzyl, or phenyl) with reducing agents, such as metal hydrides like lithium aluminum hydride, DIBAL-H, or boranes (especially diborane, borane tetrahydrofuran complexes), in the presence of an inert solvent (such as tetrahydrofuran). Such reactions have been reported in Tetrahedron Letters, 1982, 23, 2475-2478.

[0232] Alternatively, compounds of formula I (where Q is as defined above in formula I)

[0233] Option 8a:

[0234]

[0235] Compounds having formula XVIIa (where Q is as defined above in formula I, and R is C1-C6 alkyl, benzyl, or phenyl) can be prepared by thermally mediated BOC deprotection followed by Lewis acid-mediated intramolecular cyclization (Scheme 8a). Such reactions can be carried out in the presence of Lewis acids such as bis(trimethylaluminum)-1,4-diazabicyclo[2.2.2]octane adducts (also known as DABAL-Me3) or lanthanum trifluoromethanesulfonate, etc. Such reactions can be carried out in the presence of solvents (e.g., toluene, xylene, or N-methyl-2-pyrrolidone, etc.) at temperatures between 25°C and 250°C, optionally under microwave conditions. The formation of amide bonds using such procedures has been reported, for example, in Tetrahedron Letters (2006), 47(32), 5767-5769.

[0236] Compounds having formula XVII-a

[0237]

[0238] in

[0239] Q is as defined above under Equation I, and R a The substituents (hydrogen, C1-C6 alkyl, benzyl, or phenyl) are novel and have been specifically developed for the preparation of compounds having formula I according to the invention, and thus represent another object of the invention. Preferred options and preferred embodiments of the substituents in compounds having formula I are also effective for compounds having formula XVII-a. Preferably, Ra is hydrogen or C1-C6 alkyl; even more preferably, Ra is hydrogen, methyl, or ethyl; most preferably, Ra is hydrogen.

[0240] Compounds having formula IX (where Q is as defined above in formula I) can be prepared by deprotection reaction (removal of BOC group) of compounds having formula XIX (where Q is as defined above in formula I) (Scheme 9).

[0241] Option 9:

[0242]

[0243] The reaction can be carried out in the presence of an acid (especially trifluoroacetic acid, hydrochloric acid, or sulfuric acid) under the conditions described above.

[0244] Compounds having formula XIX (wherein Q is as defined above in formula I) can be prepared by reacting a compound having formula XVIII (wherein Q is as defined above in formula I) with an organoazide in the presence of a suitable base and tert-butanol t-BuOH, and optionally a Lewis acid, in the presence of a coupling agent, and in the presence of an inert solvent, at a temperature between 50°C and the boiling point of the reaction mixture. The reaction can be carried out in the presence of a coupling agent (such as T3P), or by activating the carboxylic acid with SOCl2 or oxaloyl chloride, or other coupling agents as described in Scheme 4 for converting compounds having formula X to compounds having formula Xa. Examples of organoazides include TMSN3, sodium azide, or toluenesulfonyl azide, and suitable solvents can be toluene, xylene, THF, or acetonitrile. Examples of suitable Lewis acids can include, in particular, Zn(OTf)2, Sc(OTf)2, or Cu(OTf)2.

[0245] Compounds having formula XIX can also be prepared by reacting compounds having formula XVIII with diphenylphosphohydrazides in the presence of an organic base (especially triethylamine or diisopropylethylamine), in tert-butanol t-BuOH and an inert solvent (e.g., a halogenated solvent (such as dichloromethane or dichloroethane) or a cyclic ether (especially tetrahydrofuran)), and at a temperature ranging from 50°C to the boiling point of the reaction mixture. Such reactions, which convert carboxylic acids into BOC-protected amines, are known by the art as the Curtius reaction and have been reported in, for example, Org. Lett., 2005, 7, 4107-4110; Journal of Medicinal Chemistry, 49(12), 3614-3627; and J. Am. Chem. Soc., 1972, 94(17), pp. 6203-6205.

[0246] Compounds having formula XIX (where Q is as defined above in formula I) can also be prepared by a Hofmann-rearrangement reaction from compounds having formula XX (where Q is as defined above in formula I). ​​The reaction can be carried out in the presence of a base (e.g., an aqueous solution of a metal hydroxide, such as sodium hydroxide or potassium hydroxide, or an organic base, such as DBU (1,8-diazabicyclo(5.4.0)undec-7-ene)), in the presence of an electrophilic halogenating agent (such as chlorine, bromine, or N-bromosuccinimide), and at a temperature ranging from 20 °C to the boiling point of the reaction mixture. Such reactions are known by the name Hofmann-rearrangement and have been reported in the literature, for example, in Chem. Ber. [Acta Chimica Sinica] 1881, 14, 2725.

[0247] A compound having formula XX (where Q is as defined above in formula I) can be prepared by reacting a compound having formula XVIII (where Q is as defined above in formula I) with ammonia NH3 or other ammonia substitutes (e.g., NH4OH) in the presence of a carboxylic acid activator, as described in Scheme 4.

[0248] Compounds having formula XVIII (where Q is a group selected from the group consisting of formulas Qa and Qb, and A, Q1, R2, X, and R1 are as defined above in formula I) are known, commercially available, or can be prepared by those skilled in the art. In particular, the following subgroups of compounds having formula XVIII are known in the literature and described below:

[0249] 5-(1-Cyano-1-methyl-ethoxy)-3-ethylsulfonyl-pyridine-2-carboxylic acid (CAS2417036-66-7, described in WO 2020141136); 5-(1-Cyano-1-methyl-ethyl)-3-ethylsulfonyl-pyridine-2-carboxylic acid (CAS2225113-81-3, described in WO 2018077565); 5-(1-Cyano-1-methyl-ethyl)-3-ethylsulfonyl-pyridine-2-carboxylic acid (CAS 2243224-65-7, described in WO 2018153778); 5-(1-Cyanocyclopropyl)-3-ethylthioalkyl-pyridine-2-carboxylic acid (CAS 2225113-77-7, described in WO 2018153778). 2019234158); 5-(1-cyanocyclopropyl)-3-ethylsulfonyl-pyridine-2-carboxylic acid (CAS 1879106-82-7, described in WO 2016087265); 3-ethylthioalkyl-5-(trifluoromethyl)pyridine-2-carboxylic acid (CAS1421952-02-4, described in WO 2016107831); 3-ethylsulfonyl-5-(trifluoromethyl)pyridine-2-carboxylic acid (CAS 1421953-19-6, described in CN110606828); 3-ethylsulfonyl-6-(1,2,4-triazol-1-yl)pyridine-2-carboxylic acid (CAS 2016034-28-7, described in WO 2019008115); 5-[acetyl(methyl)amino]-3-ethylsulfonyl-pyridine-2-carboxylic acid (CAS 2632239-16-6, described in WO 2021053110); 6-cyclopropyl-3-ethylthioalkyl-pyridine-2-carboxylic acid (CAS 1970134-21-4, described in WO 2016116338); 3-ethylsulfonyl-6-pyrimidin-2-yl-pyridine-2-carboxylic acid (CAS 1970134-19-0, described in WO 2016116338).

[0250] A compound having formula XVIII (where Q is a group having formula Qc, and X, R5, R6 and R1 are as defined above in formula I) can be defined as a compound having formula XVIII-c.

[0251]

[0252] Some compounds having the formula XVII-c (where X is S (sulfide)) are known in the literature (CAS 2234901-66-5, CAS 2236074-76-1) and described in WO 2018130443 and WO 2018130437.

[0253] A subgroup of compounds having formula IX (where Q is defined as Qa, X is SO2, A is N, and R1, R2, and Q1 are as defined in formula I) can be defined as compounds having formula IX-1 (scheme 9a).

[0254] Option 9a :

[0255]

[0256] Compounds having formula IX-1 can be prepared by an amination reaction involving, for example, reacting a compound having formula IX-1a (where R1, R2, and Q1 are as defined in formula I, and LG4 is a halogen, preferably F, Br, or Cl) with ammonia or a salt thereof (such as a hydrohalide salt, preferably a hydrochloride or hydrobromide, or any other equivalent salt). The source of nitrogen can be ammonia (NH3) itself or an ammonia equivalent, such as ammonium hydroxide NH4OH, ammonium chloride NH4Cl, ammonium acetate NH4OAc, ammonium carbonate (NH4)2CO3, and other NH3 substitutes. This conversion is optionally carried out under microwave irradiation at a temperature between 0°C and 150°C (preferably in the range from room temperature to the boiling point of the reaction mixture), optionally in the presence of a base, preferably in a suitable solvent (or diluent) (such as alcohols, amides, esters, ethers, nitriles, and water, particularly preferably methanol, ethanol, 2,2,2-trifluoroethanol, propanol, isopropanol, N,N-dimethylformamide, N,N-dimethylacetamide, dioxane, tetrahydrofuran, dimethoxyethane, acetonitrile, ethyl acetate, water, or mixtures thereof).

[0257] A compound having formula IX-1a (where R1, R2 and Q1 are as defined in formula I and LG4 is a halogen, preferably F, Br or Cl) can be prepared by oxidizing a compound having formula IX-1b (where R1, R2 and Q1 are as defined in formula I and LG4 is a halogen, preferably F, Br or Cl) under the conditions described above.

[0258] Compounds having formula IX-1b (wherein R1, R2, and Q1 are as defined in formula I and LG4 is a halogen, preferably F, Br, or Cl) can be prepared by reacting a compound having formula IX-1c (wherein R2 and Q1 are as defined in formula I and LG4 is a halogen, preferably F, Br, or Cl) with a nitrite ester (such as tert-butyl nitrite t-BuONO, isoamyl nitrite, or sodium nitrite) in the presence of a hydrohalic acid and a disulfide R1S-SR1 or alternatively a thiol R1SH (wherein R1 is as defined above in formula I) under Sandmeier-type reaction conditions. This conversion is preferably carried out in an inert solvent (such as acetonitrile, or a halogenated solvent such as 1,2-dichloroethane) at a temperature between 0°C and 150°C, preferably in the range from room temperature to the boiling point of the reaction mixture, optionally in the presence of a copper salt.

[0259] Compounds having formula IX-a

[0260]

[0261] in

[0262] R1 and X are as defined above in Equation I, and Q 1a It is trifluoromethyl, 1,1-difluoroethyl or

[0263] -N(CH3)COCH3 is novel and was specifically developed for the preparation of compounds having formula I according to the invention, and thus represents another object of the invention. Preferred options and preferred embodiments of the substituents in compounds having formula I are also effective for compounds having formula IX-a.

[0264] A subgroup of compounds having formula I (where Q is defined as Qb, and A, Q1, R2, X and R1 are as defined in formula I) can be defined as compounds having formula I-Qb (Scheme 10).

[0265] Option 10

[0266]

[0267] In the specific case of Scheme 10, when Q1 is an optionally substituted triazole connected via a cyclic nitrogen atom to a ring containing a group A, then a compound having formula I-Qb (where X is SO or SO2) can be produced from a compound having formula XXIb (where A, R1, and R2 are as defined above in Formula I, and where X is SO or SO2, and where X... bIt is prepared by reacting a leaving group, such as, for example, chloride, bromide, or iodide (preferably chloride or bromide), or aryl sulfonate or alkyl sulfonate (such as trifluoromethanesulfonate) with an optionally substituted triazole Q1-H (containing suitable NH functionality) (XXIIaa) (where Q1 is an N-linked triazole group), in a solvent (such as an alcohol (e.g., methanol, ethanol, isopropanol, or a high-boiling straight or branched alcohol), pyridine, or acetic acid), optionally in the presence of an additional base (such as potassium carbonate K2CO3 or cesium carbonate Cs2CO3), optionally in the presence of a copper catalyst (e.g., copper iodide (I)), at a temperature between 30°C and 180°C, optionally under microwave irradiation (CN bond formation).

[0268] In the specific case of Scheme 10, when Q1 is -N(R3)C(=O)R4 or -N(R3)CON(R3)2 (where R3 and R4 are as defined in Formula I), a compound having Formula I-Qb (where X is SO or SO2) can be prepared by reacting a compound having Formula XXIb (where A, R1, and R2 are as defined in Formula I and where X is SO or SO2, and where Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or an aryl sulfonate or alkyl sulfonate (e.g., trifluoromethanesulfonate)) with a reagent Q1-H(XXIIaa) equivalent to HN(R3)COR4 or HN(R3)CON(R3)2 (where R3 and R4 are as defined in Formula I) (CN bond formation). This reaction is carried out in the presence of a base (such as potassium carbonate, cesium carbonate, sodium hydroxide), in an inert solvent (such as toluene, dimethylformamide DMF, N-methylpyrrolidone NMP, dimethyl sulfoxide DMSO, dioxane, tetrahydrofuran THF, etc.), optionally in the presence of a catalyst (such as palladium(II) acetate, bis(dibenzylacetone)palladium(O) (Pd(dba)2) or tris(dibenzylacetone)dipalladium(O) (Pd2(dba)3), optionally in the form of a chloroform adduct) or a palladium precatalyst (such as tert-BuBrettPhos PdG3[(2-di-tert-butylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate or BrettPhos Pd The procedure was performed in the presence of G3[(2-di-cyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium methanesulfonate(II)], and optionally in the presence of a ligand (e.g., SPhos, t-BuBrettPhos, or Xantphos), at a temperature between 60°C and 120°C, and optionally under microwave irradiation.

[0269] In a specific case of Scheme 10, when Q1 is -N(R3)2 (where R3 is as defined in Formula I), a compound having Formula I-Qb (where X is SO or SO2) can be prepared by reacting a compound having Formula XXIb (where A, R1, and R2 are as defined in Formula I and where X is SO or SO2, and where Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or an aryl sulfonate or alkyl sulfonate (such as trifluoromethanesulfonate)) with a reagent Q1-H(XXIIaa) (equivalent to HN(R3)2, where R3 is as defined in Formula I), or a salt thereof (such as a hydrohalide salt, preferably a hydrochloride or hydrobromide, or a trifluoroacetate, or any other equivalent salt) (CN bond formation). This reaction is typically carried out in an inert solvent (such as alcohols, amides, esters, ethers, nitriles, and water, particularly preferably methanol, ethanol, 2,2,2-trifluoroethanol, propanol, isopropanol, N,N-dimethylformamide, N,N-dimethylacetamide, dioxane, tetrahydrofuran, dimethoxyethane, acetonitrile, ethyl acetate, toluene, water, or mixtures thereof), at a temperature between 0°C and 150°C, optionally under microwave radiation or pressure using an autoclave, optionally in the presence of a copper catalyst (such as copper powder, copper iodide (I), or copper sulfate (optionally in hydrate form) or mixtures thereof), optionally in the presence of a ligand (e.g., a diamine ligand (e.g., N,N′-dimethylethylenediamine or trans-cyclohexyldiamine) or dibenzylacetone (dba) or 1,10-phenanthroline), and optionally in the presence of a base (e.g., potassium phosphate).

[0270] The reagents HN(R3)2, HN(R3)COR4, or HN(R3)CON(R3)2 (where R3 and R4 are as defined in Formula I) are known, commercially available, or can be prepared by methods known to those skilled in the art.

[0271] Alternatively, compounds having formula I-Qb (where X is SO or SO2) can be prepared by the Suzuki reaction, which involves, for example, making a compound having formula XXIb (where A, R1, and R2 are as defined in formula I, and where X is SO or SO2, and where Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or an aryl sulfonate or alkyl sulfonate (such as trifluoromethanesulfonate)) with a compound having formula (XXII) (where Q1 is as defined in formula I, and where Y... b1 It can be a boron-derived functional group, such as B(OH)2 or B(OR). b1 )2, where R b1 It can be a C1-C4 alkyl group, or two groups OR b1It can form a five-membered ring with boron atoms, such as in the reaction of pinacol boronic acid ester. The reaction can be catalyzed by palladium-based catalysts (e.g., tetrakis(triphenylphosphine)palladium(O), (1,1'-bis(diphenylphosphine)ferrocene)dichloro-palladium-dichloromethane (1:1 complex), or chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (XPhos cyclic palladium complex)) in the presence of a base (such as sodium carbonate, tripotassium phosphate, or cesium fluoride) in a solvent or solvent mixture (such as, for example, a mixture of dioxane, acetonitrile, N,N-dimethylformamide, 1,2-dimethoxyethane, and water, or a dioxane / water mixture, or a toluene / water mixture), preferably under an inert atmosphere. The reaction temperature can preferably be in the range from room temperature to the boiling point of the reaction mixture, or the reaction can be carried out under microwave irradiation. Such Suzuki reactions are well known to those skilled in the art and have been reviewed, for example, in J. Organomet. Chem. 576, 1999, 147-168.

[0272] Alternatively, compounds having formula I-Qb (where X is SO or SO2) can be produced by compounds having formula (XXIIa) (where Q1 is as defined above, and where Y...). b2 It is prepared by a Stieler reaction between a trialkyltin derivative, preferably tri-n-butyltin or trimethyltin, and a compound having the formula XXIb (where A, R1, and R2 are as defined in Formula I, and X is SO or SO2, and Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or an aryl sulfonate or alkyl sulfonate (such as trifluoromethanesulfonate)). Such Stieler reactions are typically carried out in the presence of a palladium catalyst (e.g., tetrakis(triphenylphosphine)palladium(O) or bis(triphenylphosphine)palladium(II) chloride), in an inert solvent (e.g., N,N-dimethylformamide, acetonitrile, toluene, 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 iodide(I)). Such Stieler couplings are 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.

[0273] When Q1 is a five-membered aromatic ring system with a ring containing a group A connected via a cyclic nitrogen atom, then a compound having formula I-Qb (where X is SO or SO2) can be formed by reacting a compound having formula XXIb (where A, R1, and R2 are as defined in formula I, and where X is SO or SO2, and where Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or an aryl sulfonate or alkyl sulfonate (such as trifluoromethanesulfonate)) with a heterocyclic Q1-H (which contains a suitable NH functionality) (XXIIaa) (where X is a cyclic nitrogen atom connected to a ring containing a group A). Q1 (as defined above) is prepared by reacting in the presence of a base (such as potassium carbonate K2CO3 or cesium carbonate Cs2CO3), optionally in the presence of a copper catalyst (such as copper iodide (I)), with or without additives (such as L-proline, N,N'-dimethylcyclohexane-1,2-diamine or N,N'-dimethyl-ethylenediamine), in an inert solvent (such as N-methylpyrrolidone NMP or N,N'-dimethylformamide DMF), at a temperature between 30°C and 150°C, optionally under microwave irradiation.

[0274] The oxidation of a compound having the formula XXIb (where A, R1, and R2 are as defined in Formula I, and where X is S, and where Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or an aryl sulfonate or an alkyl sulfonate (such as trifluoromethanesulfonate)) with a suitable oxidant to a compound having the formula XXIb (where X is SO or SO2) can be achieved under the conditions described above.

[0275] Numerous compounds having the formulas (XXII), (XXIIa), and (XXIIaa) are commercially available or can be prepared by those skilled in the art.

[0276] Alternatively, a compound having the formula I-Qb (where X is SO or SO2) can be prepared from a compound having the formula XXIb (where X is S (sulfide)) by means of the same chemical process as described above, but by changing the order of the steps (i.e., by running XXIb (X is S) to I-Qb (X is S) via Suzuki, Stieler or CN bonds, followed by an oxidation step to form I-Qb (X is SO or SO2)).

[0277] A subgroup of compounds having formula I (where Q is defined as Qa, and A, Q1, R2, X, and R1 are as defined in formula I) can be defined as compounds having formula I-Qa (Scheme 11). The chemical process described previously in Scheme 10 for obtaining compounds having formula I-Qb from compounds having formula XXIb can be similarly applied to prepare compounds having formula I-Qa from compounds having formula XXIa (Scheme 11), wherein all previously mentioned definitions of substituents remain valid.

[0278] Option 11:

[0279]

[0280] A subgroup of compounds having formula I (where Q is defined as Qc, and A, Q1, R1, R5, X, and R6 are as defined in formula I) can be defined as compounds having formula I-Qc (Scheme 12). The chemical process described previously in Scheme 10 for obtaining compounds having formula I-Qb from compounds having formula XXIb can be similarly applied to prepare compounds having formula I-Qc from compounds having formula XXIc (Scheme 12), wherein all previously mentioned definitions of substituents remain valid.

[0281] Option 12 :

[0282]

[0283] A large number of compounds having the formulas (XXII-1), (XXIIa-1), and (XXIIaa-1) (where each R6 is as defined in Formula I, Y) b1 and Y b2 (As defined in Scheme 10 above) can be commercially available or prepared by those skilled in the art.

[0284] Alternatively, compounds having formula XVIII-c (where X is SO2, and where R5, R6, and R1 are as defined above in formula I)

[0285] Option 13:

[0286]

[0287] The preparation (Scheme 13) can be achieved by the saponification reaction of a compound of formula XXIII (where R5, R6 and R1 are as defined above in Formula I, and Rx is C1-C6 alkyl, benzyl or phenyl) in the presence of a suitable base (e.g., sodium hydroxide NaOH, lithium hydroxide LiOH or barium hydroxide Ba(OH)2) and a solvent (e.g., ethanol, methanol, dioxane, tetrahydrofuran or water (or mixtures thereof)) under the conditions already described above (see the discussion in Scheme 3 regarding the conversion of (VI) to (X) and in Scheme 3a regarding the conversion of (XVII) to (X); alternatively, Krapcho-type conditions as described above may also be used).

[0288] A compound having formula XXIII, wherein R5, R6, and R1 are as defined above in formula I, and Rx is a C1-C6 alkyl, benzyl, or phenyl group, can be formed from a compound having formula XXIV (where R5 and R1 are as defined above in formula I, and Rx is a C1-C6 alkyl, benzyl, or phenyl group, and Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or an aryl sulfonate or (halogenated) alkyl sulfonate, such as trifluoromethanesulfonate) via a Suzuki, Stil, or CN bond (involving a reagent having formula XXII-1, XXIIa-1, or XXIIaa-1, wherein R6 is as defined above in formula I, and Y... b1 and Y b2 Prepared under the conditions described above (see the discussion of converting (XXIb) to (I-Qb) in Scheme 10, as defined in Scheme 10).

[0289] Compounds having formula XXIV (where R5 and R1 are as defined above in formula I, and Rx is a C1-C6 alkyl, benzyl, or phenyl group, and Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or aryl sulfonate or (halo)alkyl sulfonate such as trifluoromethanesulfonate) can be prepared by oxidation (involving a suitable oxidizing agent and under the conditions described above) of compounds having formula XXV (where R5 and R1 are as defined above in formula I, and Rx is a C1-C6 alkyl, benzyl, or phenyl group, and Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or aryl sulfonate or (halo)alkyl sulfonate such as trifluoromethanesulfonate).

[0290] Compounds having the formula XXV (where R5 and R1 are as defined above in Formula I, and Rx is a C1-C6 alkyl, benzyl, or phenyl group, and Xb is a leaving group, such as chlorine, bromine, or iodine (preferably chlorine or bromine), or an aryl sulfonate or (halogenated) alkyl sulfonate such as trifluoromethanesulfonate) are known or can be prepared according to procedures described in the literature. For example, compounds having the formula XXV (where R1 is ethyl, R5 is methyl, Xb is bromine, and Rx is ethyl (CAS2407490-49-5)) are described in WO 2018130443, WO2018130437, and WO 2020002082.

[0291] The reactants can react in the presence of a base. Examples of suitable bases are alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamines, alkylene diamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides, and carbocyclic amines. Examples that may be mentioned are sodium hydroxide, sodium hydride, sodium amino, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamino, potassium bis(trimethylsilyl)amino, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinine ring, N-methylmorpholine, benzyltrimethylammonium hydroxide, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

[0292] These reactants can react with each other as is, i.e., without the addition of solvents or diluents. However, in most cases, it is advantageous to add an inert solvent or diluent, or a mixture thereof. If the reaction is carried out in the presence of a base, then these excess bases (such as triethylamine, pyridine, N-methylmorpholine, or N,N-diethylaniline) can also act as solvents or diluents.

[0293] These reactions are advantageously carried out in a temperature range from about -80°C to about +140°C, preferably from about -30°C to about +100°C, and in many cases in the range between ambient temperature and about +80°C.

[0294] A compound having Formula I can be converted into another compound having Formula I in a manner known per se by replacing one or more substituents of a starting compound having Formula I with another substituent according to the invention in a conventional manner, and by post-modifying the compound with reactions known to those skilled in the art (such as oxidation, alkylation, reduction, acylation and other methods).

[0295] Depending on the chosen reaction conditions and starting materials appropriate to the specific circumstances, it may be possible, for example, to replace only one substituent with another substituent according to the invention in a single reaction step, or to replace multiple substituents with other substituents according to the invention in the same reaction step.

[0296] Salts of compounds having formula I can be prepared in ways known per se. Thus, for example, acid addition salts of compounds having formula I are obtained by treatment with a suitable acid or a suitable ion exchanger, and salts with a base are obtained by treatment with a suitable base or a suitable ion exchanger.

[0297] Salts of compounds having formula I can be converted in a conventional manner into free compound I, acid addition salts (e.g., by treatment with a suitable basic compound or a suitable ion exchanger reagent), and salts with bases (e.g., by treatment with a suitable acid or a suitable ion exchanger reagent).

[0298] Salts of compounds having formula I can be converted in a manner known per se into other salts of compounds having formula I, acid addition salts, for example, into other acid addition salts, such as by treating salts of inorganic acids (e.g., hydrochlorides) in a suitable solvent with a suitable metal salt of the acid (e.g., a salt of sodium, barium, or silver, e.g., silver acetate), in which the inorganic salt (e.g., silver chloride) formed is insoluble and thus precipitates out of the reaction mixture.

[0299] Depending on the procedure or reaction conditions, these compounds of formula I with salt-forming properties can be obtained in free form or as salts.

[0300] Depending on the number of asymmetric carbon atoms present in the molecule, the absolute and relative configurations, and / or depending on the configuration of the non-aromatic double bonds present in the molecule, compounds having Formula I and, where appropriate, their tautomers (in each case, in free or salt form) may exist as one of the possible isomers or as mixtures of these, for example, as pure isomers, such as enantiomers and / or diastereomers, or as mixtures of isomers, such as mixtures of enantiomers, such as racemic mixtures, diastereomer mixtures, or mixtures of racemic mixtures; the present invention relates to pure isomers as well as all possible mixtures of isomers, and should be understood so in each case above and below, even if stereochemical details are not explicitly mentioned in each case.

[0301] A mixture of diastereomers or racemic mixtures of compounds of Formula I, in free or salt form (their acquisition may depend on the selected starting materials and procedures), can be isolated into pure diastereomers or racemic mixtures in a known manner, based on the physicochemical differences of these components, for example by stepwise crystallization, distillation and / or chromatography.

[0302] An enantiomer mixture (e.g., a racemic mixture) that can be obtained in a similar manner can be resolved into optical enantiomers by known methods, such as by recrystallization from an optically active solvent; by chromatography on a chiral adsorbent, such as high-performance liquid chromatography (HPLC) on acetylcellulose; by cleavage with a specific immobilized enzyme using suitable microorganisms; by forming a containing compound, such as using a chiral crown ether, in which only one enantiomer is complexed; or by conversion into salts of diastereomers, such as by reacting the basic final product racemic mixture with an optically active acid (e.g., a carboxylic acid, such as camphoric acid, tartaric acid, or malic acid, or a sulfonic acid, such as camphorsulfonic acid), and the diastereomer mixture that can be obtained in this manner can be separated, for example by stepwise crystallization based on its different solubilities, from which the desired enantiomer can be freed by the action of a suitable reagent (e.g., a basic reagent).

[0303] Pure diastereomers or enantiomers can be obtained according to the invention, not only by separating a suitable mixture of isomers, but also by methods of commonly known diastereoselective or enantiomeric synthesis, for example by using starting materials with suitable stereochemistry according to the invention.

[0304] N-oxides can be prepared by reacting a compound having formula I with a suitable oxidant (e.g., H₂O₂ / urea adduct) in the presence of an acid anhydride (e.g., trifluoroacetic anhydride). Such oxidations are known from the literature, for example from J. Med. Chem., 32(12), 2561-73, 1989 or WO 2000 / 15615.

[0305] If individual components have different biological activities, it is advantageous to isolate or synthesize biologically more effective isomers in each case, such as enantiomers or diastereomers, or mixtures of isomers, such as mixtures of enantiomers or diastereomers.

[0306] If appropriate, compounds having Formula I and, where appropriate, their tautomers (in free or salt form in each case) can also be obtained as hydrates and / or include other solvents, such as those that can be used to crystallize compounds that exist in solid form.

[0307] Compounds having Formula I according to Tables A-1 to A-12, D-1 to D-12, E-1 to E-12, and G1 to G-12 can be prepared according to the method described above. The following examples are intended to illustrate the present invention and to show preferred compounds having Formula I in the form of compounds having Formulas I-1 to I-4.

[0308] The following tables illustrate the specific compounds of this invention.

[0309] In these tables, CH2cPr refers to CH2-cyclopropyl.

[0310] The following tables illustrate the specific compounds of this invention.

[0311]

[0312] Table A-1 provides 20 compounds having formula I-1 from A-1.001 to A-1.020, where X is S, R1 is CH2CH3, R5 is methyl and R6 is as defined in Table B.

[0313] Table B: R6 substituent definition

[0314]

[0315]

[0316]

[0317]

[0318] Table A-2 provides 20 compounds having formula I-1, from A-2.001 to A-2.020, where X is S, R1 is CH2CH3, R5 is ethyl and R6 is as defined in Table B.

[0319] Table A-3 provides 20 compounds having formula I-1, from A-3.001 to A-3.020, where X is S, R1 is CH2cPr, R5 is methyl and R6 is as defined in Table B.

[0320] Table A-4 provides 20 compounds having formula I-1, A-4.001 to A-4.020, where X is S, R1 is CH2cPr, R5 is ethyl and R6 is as defined in Table B.

[0321] Table A-5 provides 20 compounds having formula I-1, A-5.001 to A-5.020, where X is SO, R1 is CH2CH3, R5 is methyl and R6 is as defined in Table B.

[0322] Table A-6 provides 20 compounds having formula I-1, A-6.001 to A-6.020, where X is SO, R1 is CH2CH3, R5 is ethyl and R6 is as defined in Table B.

[0323] Table A-7 provides 20 compounds having formula I-1, A-7.001 to A-7.020, where X is SO, R1 is CH2cPr, R5 is methyl and R6 is as defined in Table B.

[0324] Table A-8 provides 20 compounds having formula I-1, A-8.001 to A-8.020, where X is SO, R1 is CH2cPr, R5 is ethyl and R6 is as defined in Table B.

[0325] Table A-9 provides 20 compounds having formula I-1, A-9.001 to A-9.020, where X is SO2, R1 is CH2CH3, R5 is methyl and R6 is as defined in Table B.

[0326] Table A-10 provides 20 compounds having formula I-1 from A-10.001 to A-10.020, where X is SO2, R1 is CH2CH3, R5 is ethyl and R6 is as defined in Table B.

[0327] Table A-11 provides 20 compounds having formula I-1 from A-11.001 to A-11.020, wherein X is SO2, R1 is CH2cPr, R5 is methyl and R6 is as defined in Table B.

[0328] Table A-12 provides 20 compounds having formula I-1 from A-12.001 to A-12.020, wherein X is SO2, R1 is CH2cPr, R5 is ethyl and R6 is as defined in Table B.

[0329] The following tables illustrate other specific compounds of the present invention.

[0330]

[0331] Table D-1 provides 19 compounds having formula I-2, from D-1.001 to D-1.019, where X is S, R1 is CH2CH3, A is N, and Q1 is as defined in Table C.

[0332] Table C: Q1 Substituent Definition

[0333]

[0334]

[0335]

[0336] Table D-2 provides 19 compounds having formula I-2, from D-2.001 to D-2.019, where X is S, R1 is CH2CH3, A is CH and Q1 is as defined in Table C.

[0337] Table D-3 provides 19 compounds having formula I-2, from D-3.001 to D-3.019, where X is S, R1 is CH2cPr, A is N, and Q1 is as defined in Table C.

[0338] Table D-4 provides 19 compounds having formula I-2, from D-4.001 to D-4.019, where X is S, R1 is CH2cPr, A is CH, and Q1 is as defined in Table C.

[0339] Table D-5 provides 19 compounds having formula I-2, D-5.001 to D-5.019, where X is SO, R1 is CH2CH3, A is N, and Q1 is as defined in Table C.

[0340] Table D-6 provides 19 compounds having formula I-2, from D-6.001 to D-6.019, where X is SO, R1 is CH2CH3, A is CH and Q1 is as defined in Table C.

[0341] Table D-7 provides 19 compounds having formula I-2, D-7.001 to D-7.019, where X is SO, R1 is CH2cPr, A is N, and Q1 is as defined in Table C.

[0342] Table D-8 provides 19 compounds having formula I-2, D-8.001 to D-8.019, where X is SO, R1 is CH2cPr, A is CH and Q1 is as defined in Table C.

[0343] Table D-9 provides 19 compounds having formula I-2, from D-9.001 to D-9.019, where X is SO2, R1 is CH2CH3, A is N, and Q1 is as defined in Table C.

[0344] Table D-10 provides 19 compounds having formula I-2, from D-10.001 to D-10.019, where X is SO2, R1 is CH2CH3, A is CH and Q1 is as defined in Table C.

[0345] Table D-11 provides 19 compounds having formula I-2, from D-11.001 to D-11.019, where X is SO2, R1 is CH2cPr, A is N, and Q1 is as defined in Table C.

[0346] Table D-12 provides 19 compounds having formula I-2, from D-12.001 to D-12.019, where X is SO2, R1 is CH2cPr, A is CH and Q1 is as defined in Table C.

[0347] The following tables illustrate other specific compounds of the present invention.

[0348]

[0349] Table E-1 provides 19 compounds having formula I-3, from E-1.001 to E-1.019, where X is S, R1 is CH2CH3, A is N, and Q1 is as defined in Table C.

[0350] Table E-2 provides 19 compounds having formula I-3, E-2.001 to E-2.019, where X is S, R1 is CH2CH3, A is CH and Q1 is as defined in Table C.

[0351] Table E-3 provides 19 compounds having formula I-3, E-3.001 to E-3.019, where X is S, R1 is CH2cPr, A is N, and Q1 is as defined in Table C.

[0352] Table E-4 provides 19 compounds having formula I-3, E-4.001 to E-4.019, where X is S, R1 is CH2cPr, A is CH and Q1 is as defined in Table C.

[0353] Table E-5 provides 19 compounds having formula I-3, E-5.001 to E-5.019, where X is SO, R1 is CH2CH3, A is N, and Q1 is as defined in Table C.

[0354] Table E-6 provides 19 compounds having formula I-3, E-6.001 to E-6.019, where X is SO, R1 is CH2CH3, A is CH and Q1 is as defined in Table C.

[0355] Table E-7 provides 19 compounds having formula I-3, E-7.001 to E-7.019, where X is SO, R1 is CH2cPr, A is N, and Q1 is as defined in Table C.

[0356] Table E-8 provides 19 compounds having formula I-3, E-8.001 to E-8.019, where X is SO, R1 is CH2cPr, A is CH and Q1 is as defined in Table C.

[0357] Table E-9 provides 19 compounds having formula I-3, E-9.001 to E-9.019, where X is SO2, R1 is CH2CH3, A is N, and Q1 is as defined in Table C.

[0358] Table E-10 provides 19 compounds having formula I-3, from E-10.001 to E-10.019, where X is SO2, R1 is CH2CH3, A is CH and Q1 is as defined in Table C.

[0359] Table E-11 provides 19 compounds having formula I-3, from E-11.001 to E-11.019, where X is SO2, R1 is CH2cPr, A is N, and Q1 is as defined in Table C.

[0360] Table E-12 provides 19 compounds having formula I-3, E-12.001 to E-12.019, where X is SO2, R1 is CH2cPr, A is CH and Q1 is as defined in Table C.

[0361] The following tables illustrate other specific compounds of the present invention.

[0362]

[0363] Table G-1 provides 10 compounds having formula I-4, from G-1.001 to G-1.010, where X is S, R1 is CH2CH3, A is N, and Q1 is as defined in Table F.

[0364] Table F: Q1 Substituent Definition

[0365]

[0366]

[0367] Table G-2 provides 10 compounds having formula I-4, from G-2.001 to G-2.010, where X is S, R1 is CH2CH3, A is CH and Q1 is as defined in Table F.

[0368] Table G-3 provides 10 compounds having formula I-4, from G-3.001 to G-3.010, where X is S, R1 is CH2cPr, A is N, and Q1 is as defined in Table F.

[0369] Table G-4 provides 10 compounds having formula I-4, from G-4.001 to G-4.010, where X is S, R1 is CH2cPr, A is CH, and Q1 is as defined in Table F.

[0370] Table G-5 provides 10 compounds having formula I-4, from G-5.001 to G-5.010, where X is SO, R1 is CH2CH3, A is N, and Q1 is as defined in Table F.

[0371] Table G-6 provides 10 compounds G-6.001 to G-6.010 having formula I-4, where X is SO, R1 is CH2CH3, A is CH and Q1 is as defined in Table F.

[0372] Table G-7 provides 10 compounds G-7.001 to G-7.010 having formula I-4, where X is SO, R1 is CH2cPr, A is N, and Q1 is as defined in Table F.

[0373] Table G-8 provides 10 compounds having formula I-4, from G-8.001 to G-8.010, where X is SO, R1 is CH2cPr, A is CH and Q1 is as defined in Table F.

[0374] Table G-9 provides 10 compounds G-9.001 to G-9.010 having formula I-4, where X is SO2, R1 is CH2CH3, A is N, and Q1 is as defined in Table F.

[0375] Table G-10 provides 10 compounds having formula I-4, from G-10.001 to G-10.010, where X is SO2, R1 is CH2CH3, A is CH and Q1 is as defined in Table F.

[0376] Table G-11 provides 10 compounds having formula I-4, from G-11.001 to G-11.010, where X is SO2, R1 is CH2cPr, A is N, and Q1 is as defined in Table F.

[0377] Table G-12 provides 10 compounds having formula I-4, from G-12.001 to G-12.010, where X is SO2, R1 is CH2cPr, A is CH and Q1 is as defined in Table F.

[0378] The compounds of Formula I according to the invention are active ingredients with preventative and / or therapeutic value in the field of pest control. Even at low application rates, they exhibit a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish, and plants. These active ingredients according to the invention act on all or individual developmental stages of normally susceptible and resistant animal pests (such as insects or representatives of mites). The insecticidal or acaricidal activity of the active ingredients according to the invention can be directly manifested, i.e., immediate or only after some time (e.g., during molting), resulting in pest destruction; or indirectly manifested, for example, by reducing oviposition and / or hatching rates, corresponding to a good destruction rate (mortality rate) of at least 50% to 60%.

[0379] Examples of animal pests mentioned above are:

[0380] From the order Acari, for example,

[0381] Species of the genera *Acalitus*, *Aculus*, *Acaricalus*, *Aceria*, *Acarus siro*, *Amblyomma*, *Argas*, *Boophilus*, *Brevipalpus*, *Bryobia*, *Calipitrimerus*, *Chorioptes*, *Dermanyssusgallinae*, *Dermatophagoides*, *Eotetranychus*, and *Eriophyes*. Species of the genera *Hemitarsonemus*, *Hyalomma*, *Ixodes*, *Olygonychus*, *Ornithodoros*, *Polyphagotarsone latus*, *Panonychus*, *Phyllocoptruta oleivora*, *Phytonemus*, *Polyphagotarsonemus*, *Psoroptes*, *Rhipicephalus*, *Rhizoglyphus*, and *Sarcoptes*. spp.), species of the genera *Steneotarsonemus*, *Tarsonemus*, and *Tetranychus*;

[0382] From lice, for example,

[0383] Species of the genera *Haematopinus* spp., *Linognathus* spp., *Pediculus* spp., *Pemphigus* spp., and *Phylloxera* spp.;

[0384] From Coleoptera, for example,

[0385] Species of the genera *Agriotes* spp., *Amphimallon majale*, *Anomala orientalis*, *Anthonomus* spp., *Aphodius* spp., *Astylus atromaculatus*, *Ataenius* spp., *Atomaria linearis*, *Chaetocnema tibialis*, *Cerotomas* spp., *Conoderus* spp., *Cosmopolites* spp., *Cotinis nitida*, *Curculio* spp., *Cyclocephalas* spp., *Dermestes* spp., and *Diabrotica*. spp.), Argentine rhinoceros beetle (Diloboderus abderus), phytophagous ladybug species (Epilachna spp.), Eremnus species, black cane beetle (Heteronychus arator), coffee berry beetle (Hypothenemus hampei), Lagria vilosa, potato beetle (Leptinotarsa ​​decemlineata), rice weevil species (Lissorhoptrus spp.), Liogenys species, Maecolaspis species, chestnut velvet beetle (Maladera castanea), American leaf beetle species (Megascelis spp.), rapeseed flower beetle (Melighetes aeneus), dwarf beetle species (Melolontha spp.), Myochrousarmatus, sawmill beetle species (Orycaephilus spp.), ear-beaked weevil species (Otiorhynchus spp.), dwarf horned beetle species (Phyllophaga spp.), species of the genus *Phlyctinus*, species of the genus *Popillia*, species of the genus *Psylliodes*, species of the genus *Rhyssomatus aubtilis*, species of the genus *Rhizopertha*, family Scarabidae, species of the genus *Sitophilus*, and species of the genus *Sitotroga*.), species of the genera *Somaticus*, *Sternechus subsignatus*, *Tenebrio*, *Tribolium*, and *Trogoderma*.

[0386] From the order Diptera, for example,

[0387] Species of the genera *Aedes*, *Anopheles*, *Antherigonasoccata*, *Bactrocea oleae*, *Bibio hortulanus*, *Bradysia*, *Calliphora erythrocephala*, *Ceratitis*, *Chrysomyia*, *Culex*, *Cuterebra*, *Dacus*, *Delia*, *Drosophila melanogaster*, *Fannia*, *Gastrophilus*, *Geomyza tripunctata*, and *Glossina*. Species of the genera *Hypodermas*, *Hyppobosca*, *Liriomyza*, *Lucilia*, *Melanagromyza*, *Musca*, *Oestrus*, *Orseolia*, *Oscinella frit*, *Pegomyia hyoscyami*, *Phorbia*, *Rhagoletis*, *Rivelia quadrifasciata*, *Scatella*, *Sciara*, and *Stomoxys*. spp.), species of the genus Tabanus spp., species of the genus Tannia spp., and species of the genus Tipula spp.;

[0388] From Hemiptera, for example,

[0389] *Acanthocoris scabrator*, *Acanthocoris*, *Amblypeltanitida*, *Bathycoelia thalassina*, *Clavigralla*, *Clavigralla tomentosicollis*, *Creontiades*, *Dichelops furcatus*, *Edessa*, *Euschistus*, *Eurydema pulchrum*, *Horcias nobilellus*, *Acanthocoris*, *Nesidiocoris*, *Neomegalotomus*, *Nesidiocoris* (tenguis), Green Bug, Nysiussimulans, Oebalus insularis, Skin Bug, Wall Bug, Red Hunter Bug, Cocoa Mischief Bug, Scaptocoriscastanea, Black Bug (Scotinophara spp.), Thyanta, Trident Bug, Vatigailludens;

[0390] Pea webless long-tubed aphid (Acyrthosium pisum), species of the genus *Adalges*, *Agalliana ensigera*, *Talguiron vein psyllid*, species of the genus *Aleurodicus*, species of the genus *Aleurocanthus*, sugarcane hole whitefly, soft-haired whitefly (*Aleurothrixus floccosus*), cabbage whitefly (*Aleyrodes brassicae*), cotton leafhopper (*Amarasca biguttula*), lemon long-spotted leafhopper, species of the genus *Nephrodisiac*, aphids, species of the genus *Aspidiotus*, *Aphididae*, *Aphid*, species of the genus *Aspidiotus*, *Aphidia gracilis*, potato / tomato psyllid (*Bactericera cockerelli*), species of the genus *Aphidia*, species of the genus *Brachycaudus*, cabbage aphid, species of the genus *Cavariella*, etc. *Aegopodii Scop.*, *C.* species, *C.* species, *C.* species, *C.* species, *C.* species, *C.* species, *C.* species, *C.* species, *C.* species, *C.* soft scale, *C.* yellow-winged corn leafhopper, *C.* species, *C.* citrus psyllid, *C.* species, *C.* species, *C.* small green leafhopper, *C.* woolly apple aphid, *C.* species ... erysimi), Lyogenys maidis, species of the genus *Lyogenys*, species of the genus *Lyogenys*, species of the genus *Metcalfa pruinosa*, *Metcalfa pruinosa*, *Metcalfa pruinosa*, *Metcalfa pruinosa*, *Metcalfa pruinosa*, species of the genus *Metcalfa pruinosa*, species of the genus *Neotoxoptera*, species of the genus *Neotoxoptera*, species of the genus *Nilaparvata*, and species of the genus *Nilaparvata*.), Pear Green Aphid, Odonaspis ruthae, Sugarcane Cotton Aphid, Myrica Marginata Whitefly, Coxsackia, Species of the genus *Pseudatomoscelis*, Species of the genus *Gallus*, Corn Lanternfly, Species of the genus *Phylloxera*, Species of the genus *Phylloxera*, Species of the genus *Pseudatomoscelis*, Species of the genus *Pulvinaria*, Species of the genus *Pulvinaria*, Species of the genus *Pulvinaria*, Species of the genus *Quesada gigas*, Species of the genus *Recilia dorsalis*, Species of the genus *Pseudocybe ... (Festinus), striped planthopper (Tarophagus Proserpina), species of the genus *Heterophora*, species of the genus *Aphis*, species of the genus *Tridiscus sporoboli*, species of the genus *Trionymus*, African psyllid, arrowhead scale, flame leafhopper, and *Zyginidia scutellaris*.

[0391] From Hymenoptera, for example,

[0392] Species from the genera *Acromyrmex*, *Arge* spp., *Attaspp.*, *Cephus* spp., *Diprion* spp., *Diprionidae*, *Gilpinia polytoma*, *Hoplocampa* spp., *Lasius* spp., *Monomorium pharaonis*, *Neodiprions* pp., *Pogonomyrmex* spp., *Solenopsis* spp., and *Vespa* spp.;

[0393] From the order Isoptera, for example,

[0394] Species of the genera *Coptotermes* spp., *Corniternes cumulans*, *Incisitermes* spp., *Macrotermes* spp., *Mastotermes* spp., *Microtermes* spp., and *Reticulitermes* spp.; tropical fire ant (*Solenopsis geminate*).

[0395] From the order Lepidoptera, for example,

[0396] Species of the genera *Longwinged Roller*, *Brown-banded Roller*, *Clearwing Moth*, *Noctuid Moth*, cotton leafhopper, *Amylois*, *Lysimachia*, *Yellow Roller*, *Argyresthia spp.*, *Betweenleaf Roller*, *Striped Roller*, cotton leafminer, corn leafminer, powdery leafminer, peach fruit borer, *Grass moth*, *Colored Roller*, *Chrysoteuchia topiaria*, grape fruit borer, *Leaf Roller*, *Cloud Roller*, *Striped Roller*, *Sheath Moth*, *Colias lesbia*, *Cosmophila* (flava), species of the genera *Pterocarya*, *Catharanthus*, *Ophiopogon*, *Epinotus*, *Estigmene*, *Etiella*, *Etiella*, *Epinotus ... *Bifidalis*, species of *Bombyx moth*, species of *Minter*, species of *Malacosomaspp.*, *Cabbage noctuid moth*, *Tobacco hawk moth*, species of *Mythimna spp.*, species of *Noctuid moth*, species of *Geometrid moth*, *Orniodes indica*, European corn borer, species of *Small leafroller*, species of *Brown leafroller*, *Small-eyed noctuid moth*, *Stem borer*, *Red bollworm*, *Coffee leafminer*, *Armorworm*, *Potato leafminer*, cabbage white butterfly, species of *Butterfly*, diamondback moth, species of *Small white nest moth*, species of *Geometrid moth*, *Rachiplusia nu*, *Richia albicosta*, species of *Scirpophaga* spp.), species of the genera *Steel borer*, *Long-haired leafroller*, *Grey-winged leafroller*, *Cotton leafroller*, *Clearwinged moth*, *Heterodactylus*, *Roller moth*, *Powdered leafroller*, *Tomato leafminer*, and *Ophiopogon*.

[0397] From the order Mallophaga, for example,

[0398] Species of the genera *Damalinea* and *Trichodectes*;

[0399] From the order Orthoptera, for example,

[0400] Species of the genera *Blatta*, *Blattella*, *Gryllotalpa*, *Leucophaea maderae*, *Locusta*, *Neocurtilla hexadactyla*, *Periplaneta*, *Scapteriscus*, and *Schistocerca*;

[0401] From the order Psocoptera, for example,

[0402] Species of the genus *Liposcelis*;

[0403] From the order Siphonaptera, for example,

[0404] Species of the genera *Ceratophyllus* spp., *Ctenocephalides* spp., and *Xenopsylla cheopis*;

[0405] From the order Thysanoptera, for example,

[0406] Calliothrips phaseoli, Frankliniella spp., Heliothrips spp., Hercinothrips spp., Parthenothrips spp., Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., and Thripsspp.

[0407] From the order Thysanura, for example, silverfish (Lepisma saccharina).

[0408] The active ingredients according to the invention can be used to control (i.e., suppress or destroy) pests of the types described above, which are particularly found on plants, especially useful and ornamental plants in agriculture, horticulture and forestry, or on the organs of these plants, such as fruits, flowers, leaves, stems, tubers or roots, and in some cases, even plant organs formed at a later point in time remain protected against these pests.

[0409] In particular, suitable target crops are: cereals such as wheat, barley, rye, oats, rice, corn, or sorghum; sugar beets such as sugar beets or forage beets; fruits such as pome, stone fruits, or seedless small fruits such as apples, pears, plums, peaches, apricots, cherries, or berries such as strawberries, raspberries, or blackberries; legumes such as beans, lentils, peas, or soybeans; and oilseed crops such as rapeseed, mustard, poppies, olives, sunflowers, coconuts, castor beans, and cocoa beans. Or peanuts; cucurbit crops, such as pumpkins, cucumbers, or melons; fiber plants, such as cotton, flax, hemp, or jute; citrus fruits, such as oranges, lemons, grapefruits, or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, or bell peppers; Lauraceae, such as avocados, cinnamon, or camphor; and also tobacco, nuts, coffee, eggplant, sugarcane, tea, pepper, grapevines, hops, plantains, and latex plants.

[0410] The compositions and / or methods of the present invention can also be used on any ornamental plants and / or vegetable crops (including flowers, shrubs, broad-leaved trees and evergreens).

[0411] For example, this invention can be used for any of the following ornamental plant species: Ageratum species, Alonsoa spp. species, Anemone species, Anisodontea capsenisis, Chrysanthemum species, Snapdragon species, Aster species, Begonia species (e.g., Rieger begonia, Begonia semperflorens, B. tubéreux), Bougainvillea species, Brachycome spp. species, Brassica species (ornamental plants), Calceolaria species, Chili pepper, Vinca minor, Canna species, Cornflower species, Chrysanthemum species, Cineraria species (C. maritime), Coreopsis species, Crassula coccinea, Cupeaignea, Dahlia species, Delphinium species, Bleeding heart, Dorotheantus species spp.), lisianthus, forsythia species, fuchsia species, geranium gnaphalium, semperflorens species, globe amaranth, heliotrope species, sunflower species, hibiscus species, hydrangea species, hydrangea species, crape myrtle species, impatiens species (African impatiens), Iresines spp., kalanchoe species, lantana, Marchflower, lion's ear flower species, lily species, pine needle chrysanthemum species, ground cherry species, peppermint species, dragon's face chrysanthemum species, marigold species, carnation species, canna species, oxalis species, daisy species, geranium species (shield geranium, horseshoe geranium), violet species (pansy), petunia species, oleander species, peperomia species spp.), species of the genera *Poinsettia*, *Parthenocissus* (including five-leaved *Parthenocissus* and *Parthenocissus tricuspidata*), species of the genera *Primula*, *Rhododendron*, species of the genera *Rosa*, species of the genera *Datura*, species of the genera *Viola*, species of the genera *Salvia*, *Scaevola aemola*, *Schizanthus wisetonensis*, species of the genera *Sedum*, species of the genera *Solanum*, species of the genera *Surfinia*, species of the genera *Marigold*, species of the genera *Nicotiana*, species of the genera *Verbena*, species of the genera *Zinnia*, and other flower bed plants.

[0412] For example, this invention can be used for any of the following vegetable species: Allium (garlic, onion, shallot (A. oschaninii), leek, scallion, green onion), parsley, celery, asparagus, beet, Brassica (cabbage, Chinese cabbage, turnip), chili, chickpea, endive, chicory (chicory, endive), watermelon, cucumber (cucumber, melon), squash (zucchini, squash), artichoke (artichoke, spiny artichoke), carrot, fennel, St. John's wort, lettuce, tomato (tomato, cherry tomato), mint, basil, parsley, common bean (bean, green bean), pea, radish, edible rhubarb, rosemary, sage, black ginseng, eggplant, spinach, neovalerian (lettuce valerian, V. eriocarpa), and broad bean.

[0413] Preferred ornamental plant species include African violet, Begonia, Dahlia, Sedum, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Cornflower, Coreopsis, Delphinium, Mentha, Oleander, Yellow Daisy, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Sage, Hydrangea, Rosemary, Sage, St. John's wort, Mint, Sweet pepper, Tomato, and Cucumber.

[0414] The active ingredients according to the invention are particularly suitable for controlling bean aphids, cucumber leaf beetles, tobacco shoot moths, peach aphids, diamondback moths, and sea takin moths on cotton, vegetables, corn, rice, and soybean crops. These active ingredients according to the invention are also particularly suitable for controlling cabbage leafminer (preferably on vegetables), codling moths (preferably on apples), small green leafhoppers (preferably in vegetables and vineyards), potato leaf beetles (preferably on potatoes), and rice stem borers (preferably on rice).

[0415] The active ingredients according to the invention are particularly suitable for controlling bean aphids, cucumber leaf beetles, tobacco shoot moths, peach aphids, diamondback moths, and sea takin moths on cotton, vegetables, corn, rice, and soybean crops. These active ingredients according to the invention are also particularly suitable for controlling cabbage leafminer (preferably on vegetables), codling moths (preferably on apples), small green leafhoppers (preferably in vegetables and vineyards), potato leaf beetles (preferably on potatoes), and rice stem borers (preferably on rice).

[0416] In another aspect, the present invention may also relate to a method for controlling damage to plants and their parts caused by plant parasitic nematodes (endoparasitic, semi-endoparasitic, and ectoparasitic nematodes), particularly the following plant parasitic nematodes: root knot nematodes, northern root knot nematode (Meloidogyne hapla), southern root knot nematode (Meloidogyne incognita), Javan root knot nematode (Meloidogyne javanica), peanut root knot nematode (Meloidogyne arenaria), and other root knot nematode species; cyst-forming nematodes, potato golden nematode (Globodera rostochiensis), and other Globodera species; cereal cyst nematode (Heterodera avenae), soybean cyst nematode (Heteroderaglycines), and beet cyst nematode (Heterodera... *Heterodera trifolii* and other species of the genus *Heterodera*; *Seed gall nematodes* and *Anguina* species; *Stem and foliar nematodes* and *Aphelenchoides* species; *Sting nematodes*, *Belonolaimus longicaudatus* and other species of the genus *Belonolaimus*; *Pine nematodes*, *Bursaphelenchus xylophilus* and other species of the genus *Bursaphelenchus*; *Ring nematodes*. Species of the genera *Criconema*, *Criconemella*, *Criconemoides*, and *Mesocriconema*; *Stemand bulb nematodes*, *Ditylenchus destructor*, *Ditylenchus dipsaci*, and other *Ditylenchus* species; *Awl nematodes* and *Dolichodorus* species;Spiral nematodes, Heliocotylenchus multicinctus and other species of the genus *Helicotylenchus*; Sheath and sheathoid nematodes, species of the genus *Hemicycliophora* and *Hemicriconemoides*; species of the genus *Hirshmanniella*; species of the genus *Lancenematodes* and *Hoploaimus*; species of the genus *false rootknot nematodes* and *Nacobbus*; Needle nematodes, Longidoruselongatus and other species of the genus *Longidorus*; Pin nematodes and species of the genus *Pratylenchus*; Lesion nematodes. * *Pratylenchus neglectus*, *Pratylenchus penetrans*, *Pratylenchus curvitatus*, *Pratylenchus goodeyi*, and other species of the genus *Pratylenchus*; *Burrowing nematodes*, *Radipholus similis*, and other species of the genus *Radipholus*; *Reniform nematodes*, *Rotylenchus robustus*, *Rotylenchus reniformis*, and other species of the genus *Rotylenchus*; species of the genus *Scutellonema*; *Stubby root nematodes*, *Trichodorus*, and other species of the genus *Trichodorus*. primitivus) and other species of the genus *Trichodorus*, species of the genus *Paratrichodorus*; Stunt nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other species of the genus *Tylenchorhynchus*;Citrus nematode species (Citrus nematodes, Tylenchulus); Dagger nematodes and Xiphinema species; and other plant-parasitic nematode species, such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp., and Quinisulcius spp.

[0417] The compounds of this invention may also possess activity against mollusks. Examples include, for instance, the family Pomacea canaliculata; the family Arionidae (including the black slug *A. ater*, the ringed slug *A. circumscriptus*, the brown slug *A. hortensis*, and the red slug *A. rufus*); and the family Bradybaenidae (including the shrubby slug *Bradybaena*). fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euophalia; Galba (G. trunculata); Heliclia (H. itala, H. obvia); Helicigona (Helicidae) arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); The genera *Lymnaea*; the family Milax (including *M. gates*, *M. marginatus*, and *M. sowerbyi*); the genus *Opeas*; the genus *Pomacea* (including *P. canaticulata*); and the genera *Vallonia* and *Zanitoides*.

[0418] The term "crop" should be understood to also include crop plants that have been transformed using recombinant DNA technology to enable them to synthesize one or more selectively acting toxins, such as those known to come from toxin-producing bacteria, particularly those of the genus Bacillus.

[0419] Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, such as those from Bacillus cereus or Bacillus thuringiensis; or insecticidal proteins from Bacillus thuringiensis, such as δ-endotoxins, such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C, or vegetative insecticidal proteins (Vip), such as Vip1, Vip2, Vip3, or Vip3A; or insecticidal proteins from bacterial colonizing nematodes, such as species of the genus *Photorhabdus* or species of the genus *Xenorhabdus*, such as *Photorhabdus luminescens* and *Xenorhabdus*. nematophilus; animal-derived toxins such as scorpion venom, spider venom, bee venom, and other insect-specific neurotoxins; fungal toxins such as streptotoxins; lectins such as pea lectin, barley lectin, or snowdrop lectin; agglutinin; protease inhibitors such as trypsin inhibitors, serine inhibitors, potato glycoproteins, cystatin, and papain inhibitors; ribosome-inactivating proteins (RIPs) such as ricin, maize-RIP, absinthecin, loofah seed toxin, saponin toxin, or cassia root toxin; steroid metabolic enzymes such as 3-hydroxysteroid oxidase, decidual steroid-UDP-glycosyltransferase, cholesterol oxidase, decidualin inhibitors, HMG-COA-reductase, ion channel blockers such as sodium or calcium channel blockers, juvenile hormone esterase, diuretic hormone receptor, stilbene synthase, bibenzyl synthase, chitinase, and glucanase.

[0420] In the context of this invention, δ-endotoxins (e.g., Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C) or vegetative insecticidal proteins (Vip) (e.g., Vip1, Vip2, Vip3, or Vip3A) should be understood to obviously also include mixed toxins, truncated toxins, and modified toxins. Mixed toxins are generated through novel recombination of different combinations of the different domains of those proteins (see, for example, WO 02 / 15701). Truncated toxins, such as truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are substituted. In such amino acid substitutions, it is preferable to insert a non-naturally occurring protease recognition sequence into the toxin, for example, as in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into the Cry3A toxin (see WO 03 / 018810).

[0421] Examples of such toxins or genetically modified plants capable of synthesizing such toxins are disclosed, for example, in EP-A-0 374 753, WO 93 / 07278, WO 95 / 34656, EP-A-0 427 529, EP-A-451 878 and WO 03 / 052073.

[0422] Methods for preparing such transgenic plants are generally known to those skilled in the art and are described in, for example, the disclosures mentioned above. CryI type deoxyribonucleic acid and its preparation are known, for example, from WO 95 / 34656, EP-A-0 367474, EP-A-0 401 979 and WO 90 / 13651.

[0423] The toxins contained in genetically modified plants make them resistant to harmful insects. Such insects can exist in any insect taxonomy, but are particularly common in beetles (Coleoptera), dipterans (Diptera), and moths (Lepidoptera).

[0424] Transgenic plants containing one or more genes encoding resistance to insecticides and expressing one or more toxins are known, and some of these are commercially available. Examples of such plants are: (Corn variety expressing Cry1Ab toxin); YieldGard (A maize variety expressing the Cry3Bb1 toxin); YieldGard (A maize variety that expresses Cry1Ab and Cry3Bb1 toxins); (A maize variety that expresses the Cry9C toxin); Herculex (A maize variety that expresses the Cry1Fa2 toxin and the enzyme that induces tolerance to the herbicide glufosinate-ammonium, phosphatidylcholine N-acetyltransferase (PAT)); NuCOTN (Cotton variety expressing Cry1Ac toxin); Bollgard (Cotton variety expressing Cry1Ac toxin); Bollgard (Cotton variety expressing Cry1Ac and Cry2Ab toxins); (Cotton variety expressing Vip3A and Cry1Ab toxins); (Potato variety that expresses Cry3A toxin); GT Advantage (GA21 glyphosate resistance) CB Advantage (Bt11 corn borer (CB) traits) and

[0425] Other examples of such genetically modified crops are:

[0426] 1. Bt11 maize, from Syngenta Seeds SAS, Chemin del 'Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. A genetically modified maize variety that expresses a truncated Cry1Ab toxin to resist the European corn borer (corn borer and mealybug). Bt11 maize is also genetically modified to express the PAT enzyme to gain tolerance to the herbicide glufosinate.

[0427] 2. Bt176 maize, from Syngenta Seed Company, 27 Hobbit Road, F-31 790 Saint-Soville, France, Registry No. C / FR / 96 / 05 / 10. A genetically modified maize variety that expresses the Cry1Ab toxin transgenic to resist the European corn borer (corn borer and mealybug). Bt176 maize is also transgenic to express the enzyme PAT for tolerance to the herbicide glufosinate.

[0428] 3. MIR604 maize, from Syngenta Seed Company, 27 Hobbit Road, F-31 790 Saint-Soville, France, Registry No. C / FR / 96 / 05 / 10. This is a transgenic maize plant resistant to insects by expressing a modified Cry3A toxin. This toxin is modified by inserting a cathepsin-G-protease recognition sequence, Cry3A055. The preparation of this type of transgenic maize plant is described in WO 03 / 018810.

[0429] 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 Cry3Bb1 toxin and is resistant to certain Coleoptera insects.

[0430] 5. IPC 531 cotton, from Monsanto Europe, 270-272 Teflon Boulevard, B-1150 Brussels, Belgium, registration number C / ES / 96 / 02.

[0431] 6. 1507 maize, from Pioneer Overseas Corporation, Avenue Tedesco, 7B-1160 Brussels, Belgium, Registry No. C / NL / 00 / 10. Genetically modified maize expressing the protein Cry1F to acquire resistance to certain lepidopteran insects and expressing the PAT protein to acquire tolerance to the herbicide glufosinate.

[0432] 7. NK603 × MON 810 maize, from Monsanto Europe, 270-272 Teflon Boulevard, B-1150 Brussels, Belgium, registration number C / GB / 02 / M3 / 03. It was created by crossing the genetically modified variety NK603 with MON 810, resulting in a conventionally bred hybrid maize variety. NK603 × MON 810 maize transgenically expresses the protein CP4 EPSPS obtained from the Agrobacterium strain CP4, thus enabling herbicide tolerance. (Contains glyphosate), and also expresses the Cry1Ab toxin obtained from Bacillus thuringiensis Kurstak subspecies, making it resistant to certain lepidopteran insects, including the European corn borer.

[0433] Transgenic crops of insect-resistant plants were also described in BATS (Zentrum für Biosicherheit und Nachhaltigkeit, BATS Center, Clarastrasse 13, Basel 4058, Switzerland) report 2003. http: / / bats.ch )middle.

[0434] The term "crop" should be understood to also include crop plants that have been transformed using recombinant DNA technology to enable them to synthesize selectively active resistance substances, such as so-called "pathogenesis-associated proteins" (PRPs, see, for example, EP-A-0 392 225). Examples of such resistance substances and transgenic plants capable of synthesizing such resistance substances are known, for example, from EP-A-0 392 225, WO 95 / 33818, and EP-A-0 353 191. Methods for producing such transgenic plants are generally known to those skilled in the art and are described, for example, in the disclosures mentioned above.

[0435] Crops can also be modified to increase their resistance to pathogens such as fungi (e.g., Fusarium, Anthracnose, or Phytophthora), bacteria (e.g., Pseudomonas), or viruses (e.g., Potato Leaf Roll Virus, Tomato Spotted Wilt Virus, Cucumber Mosaic Virus).

[0436] Crops also include those that have increased resistance to nematodes such as soybean heterodera.

[0437] Crops that are tolerant to abiotic stresses include those that have increased tolerance to drought, high salinity, high temperature, cold, frost or light radiation, for example, through the expression of NF-YB or other proteins known in the art.

[0438] Antipathogenic substances that can be expressed by such transgenic plants include, for example, ion channel blockers, such as sodium and calcium channel blockers, such as viral KP1, KP4, or KP6 toxins; stilbene synthase; bibenzyl synthase; chitinase; glucanase; so-called "pathogenesis-associated proteins" (PRPs; see, for example, EP-A-0 392 225); antipathogenic substances produced by microorganisms, such as peptide antibiotics or heterocyclic antibiotics (see, for example, WO 95 / 33818); or proteins or polypeptide factors involved in plant pathogen defense (so-called "plant disease resistance genes," as described in WO 03 / 000906).

[0439] Other applications of the compositions according to the invention include the protection of stored articles and storage rooms, as well as the protection of raw materials such as timber, textiles, flooring, or buildings, and also in the field of hygiene, particularly the protection of humans, livestock, and productive animals from the types of pests mentioned.

[0440] The present invention also provides methods for controlling pests (such as mosquitoes and other disease vectors; see also http: / / www.who.int / malaria / vector_control / irs / en / ). In one embodiment, the method for controlling pests includes applying the composition of the invention to the target pests, their site, surface, or substrate by brushing, rolling, spraying, coating, or impregnation. By way of example, the method of the invention is contemplated for IRS (Indoor Residual Spray) application to surfaces (such as wall, ceiling, or floor surfaces). In another embodiment, the application of such compositions to substrates, such as nonwoven or woven materials, in the form of mesh fabrics, quilts, blankets, curtains, and tents (or which can be used in the manufacture of these articles) is contemplated.

[0441] In one embodiment, a method for controlling such pests includes applying a biocidally effective amount of the composition of the invention to the target pests, their site, or a surface or substrate to provide effective residual biocidal activity on the surface or substrate. Such application can be carried out by brushing, rolling, spraying, coating, or impregnating the biocidal composition of the invention. By way of example, the method of the invention is considered for IRS application to surfaces (such as wall, ceiling, or floor surfaces) to provide effective residual biocidal activity on the surface. In another embodiment, the application of such a composition for residual control of pests on a substrate, such as a fabric material in the form of (or that may be used in the manufacture of) netting, coverings, bedding, curtains, and tents, is considered.

[0442] The substrate to be treated (including nonwovens, fabrics, or meshes) can be made of natural fibers (such as cotton, raffia leaf fibers, jute, flax, sisal, burlap, or wool) or synthetic fibers (such as polyamide, polyester, polypropylene, polyacrylonitrile, etc.). Polyester is particularly suitable. Methods for treating textiles are known, for example, WO 2008 / 151984, WO 2003 / 034823, US 5631072, WO 2005 / 64072, WO 2006 / 128870, EP 1724392, WO 2005113886, or WO2007 / 090739.

[0443] Another application of the compositions according to the invention is in the field of tree injection / trunk treatment for all ornamental trees, as well as all kinds of fruit and nut trees.

[0444] In the field of tree injection / trunk treatment, the compounds according to the invention are particularly suitable for combating wood-boring insects from the Lepidoptera and Coleoptera mentioned above, especially those listed in Tables A and B below:

[0445] Table A. Examples of economically important invasive wood-boring insects.

[0446]

[0447] Table B. Examples of local wood-boring insects of economic importance.

[0448]

[0449]

[0450]

[0451]

[0452] This invention can also be used to control any insect pests that may be present in lawn grasses, including, for example, beetles, caterpillars, fire ants, ground pearls, millipedes, sowbugs, mites, mole crickets, scale insects, mealybugs, ticks, froghoppers, southern wheat bugs, and grubs. This invention can be used to control insect pests at all stages of their life cycle, including eggs, larvae, nymphs, and adults.

[0453] Specifically, this invention can be used to control insect pests fed on the roots of lawn grasses, including grubs (such as Cyclocephala spp.) (e.g., the marked scarab beetle, C. lurida), Rhizotrogus (e.g., the European scarab beetle, R. majalis), Cotinus (e.g., the green June beetle, C. nitida), Popillia spp. (e.g., the Japanese beetle, the ladybug (P. japonica)), Phyllophaga spp. (e.g., the May / June beetle), Ataenius (e.g., the black turfgrass beetle, A. spretulus), and Malladera spp. (e.g., the Asiatic garden beetle). (beetle), M. castanea and Tomarus), ground pearl (Margarodes spp.)), mole cricket (brownish-yellow, southern and short-winged; Scapteriscus spp., Gryllotalpa africana) and leafjackets (European crane fly, Tipula spp.)).

[0454] This invention can also be used to control insect pests in lawn grasses of thatched houses, including armyworms (such as the fall armyworm Spodoptera frugiperda and the common armyworm Pseudaletia unipuncta), root cutters, weevils (species of the genus Sphenophorus, such as S. venatus verstitus and S. parvulus), and grass moths (such as species of the genus Crambus and the tropical grass moth Herpetogramma phaeopteralis).

[0455] This invention can also be used to control insect pests in turfgrass that live on the ground and feed on the leaves of turfgrass. These insect pests include wheat bugs (such as southern wheat bugs and southern stem bugs (Blissus insularis)), bermudagrass mite (Eriophyes cynodoniensis), grass mealybug (Antonina graminis)), two-lined grasshopper (Propsapia bicincta), leafhoppers, root-cutting moths (Noctuidae), and wheat aphids.

[0456] This invention can also be used to control other harmful organisms in lawn grasses, such as introduced red imported fire ants (Solenopsis invicta) that create nests in lawns.

[0457] In the field of hygiene, the compositions according to the invention are effective against antiparasitic parasites such as hard ticks, soft ticks, scabies mites, fall mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice, and fleas.

[0458] Examples of this type of parasite are:

[0459] Lice: Species of the genera *Linognathus*, *Phtirus*, *Phtirus*, and *Phtirus*.

[0460] Trichophagia: Species of the genera *Hymenopteris*, *Hymenopteris*, *Hymenopteris*, *Hymenopteris*, *Hymenopteris*, *Hymenopteris*, *Hymenopteris*, *Hymenopteris*, *Hymenopteris*, *Hymenopteris*, and *Hymenopteris*.

[0461] Diptera and the suborders Nematocerina and Brachycerina, such as species of the genera *Aedes*, *Anopheles*, *Culex*, *Simulium*, *Eusimulium*, *Phlebotomus*, *Lutzomyia*, *Culicoides*, *Chrysops*, *Hybomitra*, *Atylotus*, *Tabanus*, *Haematopota*, and *Philipomyia*. spp.), species of the genera *Braulaspp.*, *Musca spp.*, *Hydrotaea spp.*, *Hippobosca spp.*, *Haematobia spp.*, *Morellia spp.*, *Fannia spp.*, *Glossina spp.*, *Calliphora spp.*, *Lucilia spp.*, *Chrysomyia spp.*, *Wohlfahrtia spp.*, *Sarcophagas spp.*, *Oestrus spp.*, *Hypoderma spp.*, *Gasterophilus spp.*, *Hippobosca spp.*, and *Lipoptena*. spp.) and species of the genus Melophagos (Melophagus spp.).

[0462] Siphonapterida, including species of the genera *Pulex*, *Xenopsylla*, and *Xenopsylla*.

[0463] Heteropterida, including species of the genera *Pycnodon*, *Triatomine*, *Aspergillus*, and *Panstrongylus* spp.

[0464] Blattodea, including species such as the Oriental cockroach (Blatta orientalis), the American cockroach (Periplaneta americana), the German cockroach (Blattelagermanica), and species of the genus Supella (Supella spp.).

[0465] Acaria (subclass Acaria, family Acarida), and Metastigmata and Mesostigmata, including species of the genera *Argas*, *Ornithodorus*, *Otobius*, *Ixodes*, *Amblyommas*, *Boophilus*, *Dermacentor*, *Haemophysalis*, *Hyalomma*, *Rhipicephalus*, *Dermanyssus*, *Raillietia*, and *Pneumonyssus*. spp.), species of the genus *Sternostoma* spp., and species of the genus *Varroaspp.*.

[0466] Actinedida (prostigmata) and Acaridida (Astigmata), including species of the genera *Acarapis*, *Cheyletiella*, *Ornithocheyletia*, *Myobia*, *Psorergates*, *Demodex*, *Trombicula*, *Listrophorus*, *Acarus*, *Tyrophagus*, *Caloglyphus*, *Hypodectes*, and *Pterolichus*. Species of the genera *Psoroptes*, *Chorioptes*, *Otodectes*, *Sarcoptes*, *Notoedress*, *Knemidocoptes*, *Cytodites*, and *Laminosioptes*.

[0467] The compositions according to the invention are also suitable for protecting materials such as wood, textiles, plastics, adhesives, glues, paints, paper and cards, leather, flooring and buildings from insect infestation.

[0468] The compositions according to the invention can be used, for example, to combat the following pests: beetles such as the North American house longhorn beetle (Hylotrupes bajulus), the long-haired longhorn beetle (Chlorophorus pilosis), the furniture thief (Anobium punctatum), the red-haired thief (Xestobium rufovillosum), the comb-horned thief (Ptilinuspecticornis), the dendrobium pertinex, the pine bud thief (Ernobius mollis), the primed carpini, the brown powder beetle (Lyctus brunneus), the African powder beetle (Lyctus africanus), the southern powder beetle (Lyctus planicollis), the oak powder beetle (Lyctus linearis), the pubescens powder beetle (Lyctus pubescens), and the breast powder beetle (Trogoxylon). The species include *Aequale*, *Minthesrugicollis*, species of *Xyleborus* spec., species of *Tryptodendron* spec., *Apate monachus*, *Bostrychus capucins*, *Heterobostrychus brunneus*, species of *Sinoxylon* spec., and *Dinoderus minutus*, as well as hymenopterans such as *Sirex juvencus*, *Urocerus gigas*, *Urocerus gigas taignus*, and *Urocerus augu*, and termites such as *Kalotermes flavicollis*, *Cryptotermes brevis*, and *Heterotermes*. The termites include *Indicola*, *Reticulitermes flavipes*, *Reticulitermes santonensis*, *Reticulitermes lucifugus*, *Mastotermes darwiniensis*, *Zootermopsis nevadensis*, and *Coptotermes formosanus*, as well as wood-boring insects such as silverfish (*Lepisma saccharina*).

[0469] The compounds according to the invention can be used as pest control agents in their unmodified form, but they are generally formulated into compositions in a variety of ways using formulation aids (such as carriers, solvents, and surfactants). These formulations can be in various physical forms, for example, as powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent compressed tablets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, flowable oils, aqueous dispersions, oily dispersions, suspensions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as a carrier), impregnated polymer films, or in other known forms, such as those described in the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, 1st Edition, Second Revision (2010). Such formulations can be used directly or diluted before use. It can be diluted with, for example, water, liquid fertilizer, micronutrients, biological organisms, oil or solvents.

[0470] These formulations can be prepared, for example, by mixing the active ingredients with formulation aids to obtain compositions in the form of finely dispersed solids, particles, solutions, dispersions, or emulsions. These active ingredients can also be formulated with other aids, such as finely dispersed solids, mineral oils, oils of plant or animal origin, modified oils of plant or animal origin, organic solvents, water, surfactants, or combinations thereof.

[0471] These active ingredients can also be contained in very fine microcapsules. Microcapsules contain the active ingredient within a porous carrier. This allows the active ingredient to be released into the environment in a controlled amount (e.g., slow release). Microcapsules typically have a diameter from 0.1 to 500 micrometers. The amount of active ingredient they contain is approximately 25% to 95% by weight of the capsule. These active ingredients can be in the form of a monolithic solid, fine particles in a solid or liquid dispersion, or in a solution-suitable form. The encapsulating membrane can contain, for example, natural or synthetic rubber, cellulose, styrene / butadiene copolymers, polyacrylonitrile, polyacrylates, polyesters, polyamides, polyureas, polyurethanes, or chemically modified polymers, as well as starch xanthates, or other polymers known to those skilled in the art. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely dispersed particles within a solid matrix of a base substance, but these microcapsules themselves are not encapsulated.

[0472] Suitable formulation aids for preparing compositions according to the invention are known in themselves. As liquid carriers, the following can be used: water, toluene, xylene, petroleum ether, vegetable oil, acetone, methyl ethyl ketone, cyclohexanone, acid anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, butenyl carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol, 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, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, α-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glyceryl acetate, glyceryl diacetate, glyceryl triacetate, deca-acetate, etc. Hexadecane, hexanediol, isopentyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, isopropyl acetone, methoxypropanol, methyl isopentyl ketone, methyl isobutyl ketone, methyl lauryl ketone, methyl octanoate, methyl oleate, dichloromethane, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleyleneamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate Propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols with higher molecular weights, such as pentanol, tetrahydrofuranol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone, etc.

[0473] Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin, and similar substances.

[0474] Many surfactants can be advantageously used in both solid and liquid formulations, especially those that can be diluted with a carrier before use. Surfactants can be anionic, cationic, nonionic, or polymeric, and they can be used as emulsifiers, wetting agents, suspending agents, or for other purposes. Typical surfactants include, for example, salts of alkyl sulfates, such as diethanolammonium dodecyl sulfate; salts of alkyl aryl sulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol / olefin oxide addition products, such as ethoxylated nonylphenol; alcohol / olefin oxide addition products, such as ethoxylated tridecyl alcohol; soaps, such as sodium stearate; salts of alkyl naphthalene sulfonates, such as sodium dibutylnaphthalene sulfonate; salts of dialkyl sulfosuccinates, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary ammonium compounds, such as dodecyltrimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of monoalkyl and dialkyl phosphate esters; and other substances, such as those described in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing. Corp.), Ridgewood, New Jersey (1981).

[0475] Other adjuvants that can be used in formulations for killing pests include crystallization inhibitors, viscosity modifiers, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, defoamers, complexing agents, substances that neutralize or change pH and buffer solutions, corrosion inhibitors, fragrances, wetting agents, absorption enhancers, micronutrients, plasticizers, flow aids, lubricants, dispersants, thickeners, antifreeze agents, microbial agents, and liquid and solid fertilizers.

[0476] The compositions according to the invention may include additives comprising oils of plant or animal origin, mineral oils, alkyl esters of such oils, or mixtures of such oils with oil derivatives. The amount of oil additive in the compositions according to the invention is typically from 0.01% to 10% of the mixture to be applied. For example, the oil additive may be added to the spray can at the desired concentration after the spray mixture has been prepared. Preferred oil additives include mineral oils or plant-derived oils, such as rapeseed oil, olive oil, or sunflower oil; emulsified vegetable oils; alkyl esters of plant-derived oils, such as methyl derivatives; or animal-derived oils, such as fish oil or tallow. Preferred oil additives include C8-C... 22 Alkyl esters of fatty acids, especially C 12 -C 18Methyl derivatives of fatty acids, such as lauric acid, palmitic acid, and methyl esters of oleic acid (methyl laurate, methyl palmitate, and methyl oleate, respectively). Many oil derivatives are known in the Compendium of Herbicide Adjuvants, 10th edition, Southern Illinois University, 2010.

[0477] These compositions of the invention generally comprise from 0.1% to 99%, particularly from 0.1% to 95% by weight, of the compounds of the invention and from 1% to 99.9% by weight, of formulation aids, which preferably comprise from 0% to 25% by weight of surfactants. Commercial products may preferably be formulated as concentrates, while end users will typically use diluted formulations.

[0478] Application rates vary over a wide range and depend on soil properties, application method, crop species, pests to be controlled, primary climatic conditions, and other factors governed by application method, application time, and target crop. Generally, compounds can be applied at rates ranging from 1 l / ha to 2000 l / ha, particularly from 10 l / ha to 1000 l / ha.

[0479] Preferred formulations may have the following composition (wt%):

[0480] Emulsifiable concentrate :

[0481] Active ingredient: 1% to 95%, preferably 60% to 90%

[0482] Surfactant: 1% to 30%, preferably 5% to 20%

[0483] Liquid carrier: 1% to 80%, preferably 1% to 35%

[0484] dust :

[0485] Active ingredient: 0.1% to 10%, preferably 0.1% to 5%

[0486] Solid carrier: 99.9% to 90%, preferably 99.9% to 99%.

[0487] Suspension concentrate:

[0488] Active ingredient: 5% to 75%, preferably 10% to 50%

[0489] Water: 94% to 24%, preferably 88% to 30%

[0490] Surfactant: 1% to 40%, preferably 2% to 30%

[0491] wettable powder :

[0492] Active ingredient: 0.5% to 90%, preferably 1% to 80%

[0493] Surfactant: 0.5% to 20%, preferably 1% to 15%

[0494] Solid carrier: 5% to 95%, preferably 15% to 90%

[0495] Granules:

[0496] Active ingredient: 0.1% to 30%, preferably 0.1% to 15%.

[0497] Solid carrier: 99.5% to 70%, preferably 97% to 85%

[0498] The following examples further illustrate (but do not limit) the invention.

[0499]

[0500] The combination is thoroughly mixed with these adjuvants and the mixture is thoroughly ground in a suitable grinder to obtain a wettable powder that can be diluted with water to give a suspension of the desired concentration.

[0501] <![CDATA[ Powder for dry seed treatment ]]> a) b) c) Active ingredients 25％ 50％ 75％ Light mineral oil 5％ 5％ 5％ Highly dispersed silica 5％ 5％ - Kaolin 65％ 40％ - talc - 20％

[0502] The combination is thoroughly mixed with the adjuvant and the mixture is thoroughly ground in a suitable grinder to obtain a powder that can be used directly for seed treatment.

[0503] <![CDATA[ Emulsifiable concentrate ]]> Active ingredients 10％ Octylphenol polyethylene glycol ether (4-5 mol of ethylene oxide) 3％ Calcium dodecylbenzenesulfonate 3％ Castor oil polyethylene glycol ether (35 mol ethylene oxide) 4％ Cyclohexanone 30％ xylene mixture 50％

[0504] Emulsions with any required dilution that can be used in plant protection can be obtained by diluting such concentrates with water.

[0505] <![CDATA[ dust ]]> a) b) c) Active ingredients 5％ 6％ 4％ talc 95％ - - Kaolin - 94％ - Mineral packing - - 96％

[0506] A ready-to-use powder is obtained by mixing the mixture with a carrier and grinding the mixture in a suitable grinder. This type of powder can also be used for dry seed dressing.

[0507] <![CDATA[ Extruder granules ]]> Active ingredients 15％ Sodium lignosulfonate 2％ Carboxymethyl cellulose 1％ Kaolin 82％

[0508] Mix the combination with these additives and grind them, then wet the mixture with water.

[0509] The mixture is extruded and then dried in an air stream.

[0510] <![CDATA[ Coated granules ]]> Active ingredients 8％ Polyethylene glycol (molecular weight 200) 3％ Kaolin 89％

[0511] This finely ground mixture is applied evenly to kaolin moistened with polyethylene glycol in a mixer. This process yields dust-free coated granules.

[0512] suspension concentrate

[0513] Active ingredients 40％ Propylene glycol 10％ Nonylphenol polyethylene glycol ether (15 mol ethylene oxide) 6％ Sodium lignosulfonate 10％ Carboxymethyl cellulose 1％ Silicone oil (in the form of a 75% emulsion in water) 1％ water 32％

[0514] The finely ground mixture is tightly blended with adjuvants to obtain a suspension concentrate, from which a suspension concentrate can be diluted with water to obtain a suspension with any desired dilution. Using such dilutions, living plants along with their propagation material can be treated and protected against microbial infection by spraying, pouring, or immersion.

[0515] Flowable concentrate for seed treatment

[0516]

[0517] The finely ground mixture is tightly blended with adjuvants to obtain a suspension concentrate, from which a suspension concentrate can be diluted with water to obtain a suspension with any desired dilution. Using such dilutions, living plants along with their propagation material can be treated and protected against microbial infection by spraying, pouring, or immersion.

[0518] Sustained-release capsule suspension

[0519] 28 parts of the mixture were combined with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate / polymethylene-polyphenyl isocyanate mixture (8:1). This mixture was emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 parts of an antifoaming agent, and 51.6 parts of water until the desired particle size was achieved. 2.8 parts of a 1,6-hexanediamine mixture in 5.3 parts of water were added to this emulsion. The mixture was stirred until polymerization was complete. The resulting capsule suspension was stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersant. This capsule suspension formulation contained 28% of the active ingredient. The diameter of the medium capsule was 8-15 micrometers. The resulting formulation was applied to seeds as an aqueous suspension in a suitable apparatus for this purpose.

[0520] Formulation types include emulsion concentrates (EC), suspension concentrates (SC), suspension emulsions (SE), capsule suspensions (CS), water-dispersible granules (WG), emulsifiable granules (EG), water-in-oil emulsions (EO), oil-in-water emulsions (EW), microemulsions (ME), oil dispersions (OD), oil suspensions (OF), oil-soluble liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), technical grade (TK), dispersible concentrates (DC), wettable powders (WP), soluble granules (SG), or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0521] Preparation example:

[0522] “Mp” refers to the melting point in °C. The free radical represents the methyl group. Recorded on a Brucker 400MHz spectrometer. 1 HNMR measurements, with chemical shifts relative to TMS standards, are given in ppm. Spectra were measured in deuterated solvents as indicated. These compounds were characterized using any of the following LCMS methods. Characteristic LCMS values ​​obtained for each compound are retention time (“Rt”, recorded in minutes) and the measured molecular ion (M+H). + Or (MH) - .

[0523] LCMS method:

[0524] Method 1:

[0525] Spectra were recorded on a Waters mass spectrometer (SQD single quadrupole mass spectrometer) equipped with an electro-jet source (polarity: positive or negative ion, full scan, capillary voltage: 3.00 kV, cone range: 41 V, source temperature: 150 °C, desolvation temperature: 500 °C, cone gas flow rate: 50 L / Hr, desolvation gas flow rate: 1000 L / Hr, mass range: 110 to 800 Da) and a Waters Class H UPLC: quaternary pump, heated column chamber, and diode array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30 × 2.1 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; 0.2-0.2 min 10%-50% B; 0.2-0.7 min 50%-100% B; 0.7-1.3 min 100% B; 1.3-1.4 min 100%-10% B; 1.4-1.6 min 10% B; Flow rate (mL / min): 0.6.

[0526] Method 2:

[0527] Spectra were recorded on a mass spectrometer (6410 triple quadrupole mass spectrometer) from Agilent Technologies, equipped with an electro-ejector source (polarity: positive or negative ion, MS2 scan, capillary voltage: 4.00 kV, fragmentation voltage: 100 V, desolvation temperature: 350 °C, gas flow rate: 11 L / min, nebulizer gas: 45 psi, mass range: 110 to 1000 Da) and an Agilent 1200 Series HPLC: quaternary pump, heated column chamber, and diode array detector. Column: KINETEX EVO C18, 2.6 μm, 50 × 4.6 mm, temperature: 40 °C, DAD wavelength range (nm): 210 to 400, 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.

[0528] Method 3:

[0529] Spectra were recorded on a Waters mass spectrometer (SQD single quadrupole mass spectrometer) equipped with an electro-jet source (polarity: positive or negative ion, full scan, capillary voltage: 3.00 kV, cone range: 41 V, source temperature: 150 °C, desolvation temperature: 500 °C, cone gas flow rate: 50 L / Hr, desolvation gas flow rate: 1000 L / Hr, mass range: 110 to 800 Da) and a Waters Class H UPLC: quaternary pump, heated column chamber, and diode array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30 × 2.1 mm, temperature: 40 °C, DAD wavelength range (nm): 210 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH; gradient: 0 min 10% B; 0.2-0.2 min 50% B; 0.2-0.7 min 100% B; 0.7-1.3 min 100% B; 1.3-1.4 min 10% B; 1.4-1.6 min 10% B; flow rate (mL / min) 0.8.

[0530] Example P1: 1-[6-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-6- Preparation of [5-ethylsulfonyl-3-pyridyl]cyclopropanecarboxynitrile (compound P1)

[0531]

[0532] Step A1: Preparation of (2,2-difluoro-1,3-benzodioxane-5-yl)methanol (intermediate I-1)

[0533]

[0534] Sodium borohydride (4.57 g, 114.84 mmol) was slowly added to a 0°C cooled solution of 15 g (76.56 mmol) of 2,2-difluoro-1,3-benzodioxane-5-carboxaldehyde (CAS 656-42-8) in methanol (75 mL). The reaction mixture was stirred overnight at room temperature. After completion, the reaction mixture was concentrated under vacuum, quenched with an aqueous solution of ammonium chloride, and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under vacuum to give a colorless liquid (2,2-difluoro-1,3-benzodioxane-5-yl)methanol. 1 H NMR (400MHz, CDCl3) δppm: 1.91 (br s, 1H), 4.69 (br s, 2H), 7.03-7.09 (m, 2H), 7.14 (s, 1H).

[0535] Step A2: Preparation of 6-chloro-2,2-difluoro-1,3-benzodioxane-5-carboxaldehyde (intermediate I-2)

[0536]

[0537] N-chlorosuccinimide (17.20 g, 126.24 mmol) was added to a solution of (2,2-difluoro-1,3-benzodioxane-5-yl)methanol (intermediate I-1 prepared as described above) (10 g, 50.49 mmol) in acetonitrile (60 mL). The reaction mixture was stirred overnight at room temperature. After completion, the reaction mixture was concentrated under vacuum, milled with cyclohexane, filtered through a Buchner funnel, and the filtrate was concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 0-30% ethyl acetate in cyclohexane) to give pure 6-chloro-2,2-difluoro-1,3-benzodioxane-5-carboxaldehyde as a colorless liquid. 1 H NMR (400MHz, CDCl3) δppm: 7.22 (s, 1H), 7.66 (s, 1H), 10.41 (s, 1H).

[0538] Step A3: Preparation of 2,2-difluoro-6-methyl-1,3-benzodioxane-5-carboxaldehyde (intermediate I-3)

[0539]

[0540] Methylboric acid (1.14 g, 17.22 mmol) was added to a solution of 6-chloro-2,2-difluoro-1,3-benzodioxane-5-carboxaldehyde (intermediate I-2 prepared as described above) (1 g, 4.30 mmol) in toluene (10 mL), followed by the addition of potassium carbonate (1.78 g, 12.92 mmol) in water (3 mL) while purging with nitrogen for 10 min. A 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (0.18 g, 0.21 mmol) was added, and the reaction mixture was heated at 90 °C for 15 h. The reaction mixture was cooled to room temperature and concentrated under vacuum. The reactants were diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 0 to 30% ethyl acetate in cyclohexane) to give 2,2-difluoro-6-methyl-1,3-benzodioxane-5-carboxaldehyde, which is a brown oil. 1 H NMR (400MHz, CDCl3) δppm: 2.72 (s, 3H), 6.99 (s, 1H), 7.56 (s, 1H), 10.27 (s, 1H).

[0541] Step A4: Preparation of 2,2-difluoro-6-methyl-1,3-benzodioxane-5-carboxylic acid (intermediate I-4)

[0542]

[0543] A solution of sodium hydroxide (0.33 g, 8.06 mmol) in water (6.8 mL) was added dropwise to a solution of silver nitrate (0.57 g, 3.22 mmol) in water (6.8 mL) at room temperature. 2,2-Difluoro-6-methyl-1,3-benzo[a]dioxane-5-carboxaldehyde (intermediate I-3 prepared as described above) (0.34 g, 1.61 mmol) was added in portions to the reaction mixture over 20 minutes. The reaction mixture was stirred at room temperature for 2 hours. After stirring, the reaction mixture was filtered through diatomaceous earth and the filtrate was acidified with 2N hydrochloric acid. The resulting solid was filtered, washed with cold water, and dried under vacuum to give 2,2-difluoro-6-methyl-1,3-benzo[a]dioxane-5-carboxylic acid as a white solid. LCMS (Method 2): Rt = 1.42 min, m / z = 215 (MH). - . 1 H NMR (400MHz, DMSO-d6) δppm: 2.54 (s, 3H), 7.41 (s, 1H), 7.77 (s, 1H).

[0544] Step A5: Ethyl 2,2-difluoro-6-methyl-1,3-benzodioxane-5-carboxylate (Intermediate I-5) Preparation

[0545]

[0546] A solution of 2,2-difluoro-6-methyl-1,3-benzodioxane-5-carboxylic acid (intermediate I-4 prepared as described above) (0.23 g, 1.01 mmol) in ethanol (10 mL) was stirred at room temperature for 15 minutes. Sulfuric acid (0.02 mL, 0.40 mmol) was added dropwise to the reaction mixture (exothermic reaction was observed). The reaction mixture was heated at 60 °C for 12 hours. After completion, the reaction mixture was concentrated under vacuum, neutralized with an aqueous sodium bicarbonate solution, and the product was extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum to give ethyl 2,2-difluoro-6-methyl-1,3-benzodioxane-5-carboxylic acid ester. The crude product was used as is in the next step. 1 H NMR (400MHz, CDCl3) δppm: 1.41 (t, 3H), 2.64 (s, 3H), 4.37 (q, 2H), 6.97 (s, 1H), 7.67 (s, 1H).

[0547] Step A6: Ethyl 6-(bromomethyl)-2,2-difluoro-1,3-benzodioxane-5-carboxylate (intermediate) Preparation of I-6)

[0548]

[0549] At room temperature, N-bromosuccinimide (0.196 g, 1.06 mmol) and azobisisobutyronitrile (0.016 g, 0.097 mmol) were added to a solution of ethyl 2,2-difluoro-6-methyl-1,3-benzodioxane-5-carboxylate (intermediate I-5 prepared as described above) (0.25 g, 0.97 mmol) in trifluorotoluene (3 mL). The reaction mixture was heated at 90 °C for 3 hours. The reaction mixture was cooled to room temperature and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 0 to 30% ethyl acetate in cyclohexane) to give ethyl 6-(bromomethyl)-2,2-difluoro-1,3-benzodioxane-5-carboxylate as a colorless, viscous substance. 1 H NMR (400MHz, CDCl3) δppm: 1.39 -1.47 (m, 3H), 4.38-4.45 (m, 2H), 4.97 (s, 2H), 7.20 (s, 1H), 7.71 (s, 1H).

[0550] Step B1: tert-butyl N-[5-(1-cyanocyclopropyl)-3-ethylthioalkyl-2-pyridyl]carbamate (middle) Preparation of intermediate I-7) and 1-(6-amino-5-ethylthio-3-pyridyl)cyclopropaneformitrile (intermediate I-8)

[0551]

[0552] Triethylamine (0.519 mL, 3.68 mmol) and diphenylphosphoazide (0.81 mL, 3.68 mmol) were added to a solution of 5-(1-cyanocyclopropyl)-3-ethylthioalkyl-pyridine-2-carboxylic acid (CAS 2225113-77-7, prepared as described in WO2018108726) in toluene (10 mL). After stirring at room temperature for 30 minutes, tert-butanol (0.69 mL, 7.37 mmol) was added, and the reaction mixture was heated at 90 °C for 3 hours. The reaction mixture was diluted with water (100 mL), and the product was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with saturated sodium bicarbonate solution (20 mL) and brine (30 mL), dried over sodium sulfate, and concentrated under vacuum to obtain a mixture of tert-butyl N-[5-(1-cyanocyclopropyl)-3-ethylthioalkyl-2-pyridyl]carbamate (intermediate I-7) and 1-(6-amino-5-ethylthioalkyl-3-pyridyl)cyclopropanecarbamate (intermediate I-8), which was used as is in the next step. LCMS of tert-butyl N-[5-(1-cyanocyclopropyl)-3-ethylthioalkyl-2-pyridyl]carbamate (intermediate I-7) (Method 3): Rt = 0.96 min, m / z = 264 [(M+H)] + -56].

[0553] Step B2: Preparation of 1-(6-amino-5-ethylthio-3-pyridyl)cyclopropaneformonitrile (Intermediate I-8)

[0554]

[0555] Under cooling conditions, 2,2,2-trifluoroacetic acid (2.9 mL, 38 mmol) was added to a mixture of 1-(6-amino-5-ethylthioalkyl-3-pyridyl)cyclopropanecarboxylon and tert-butyl N-[5-(1-cyanocyclopropyl)-3-ethylthioalkyl-2-pyridyl]carbamate (a mixture of intermediates I-7 and I-8 prepared as described above) in dichloromethane (10 mL), and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with water (50 mL), neutralized with a saturated aqueous sodium bicarbonate solution, and the product was extracted with dichloromethane (3 x 25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 30% ethyl acetate in cyclohexane) to give 1-(6-amino-5-ethylthioalkyl-3-pyridyl)cyclopropanecarboxylon. LCMS (Method 3): Rt = 0.25 min, m / z = 220(M+H) + .

[0556] Step B3: Preparation of 1-(6-amino-5-ethylsulfonyl-3-pyridyl)cyclopropanecarboxylonitrile (Intermediate I-9)

[0557]

[0558] 3-chloroperoxybenzyl acid (12 g, 48 mmol, 70 wt%) was added to a solution of 1-(6-amino-5-ethylthio-3-pyridyl)cyclopropanecarboxynitrile (intermediate I-8 prepared as described above) (5.0 g, 23 mmol) in dichloromethane (75 mL) cooled to 0 °C. After stirring at 0 °C for 30 min, the reaction mixture was quenched with 2 M sodium hydroxide aqueous solution, and the product was extracted with dichloromethane (2 x 20 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 70% ethyl acetate in cyclohexane) to give 1-(6-amino-5-ethylsulfonyl-3-pyridyl)cyclopropanecarboxynitrile. LCMS (Method 1): Rt = 0.76 min, m / z = 252 (M+H) + . 1 H NMR (400MHz, DMSO-d6) δppm:1.05-1.19(m,3H),1.39-1.51(m,2H),1.61-1.73(m,2H),3.27-3.34(m,2H))6.90(br s,2H),7.79(d,1H),8.28(d,1H).

[0559] Step B4: tert-butyl N-[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]carbamate (middle) Preparation of intermediate I-10

[0560]

[0561] Sodium hydride (1.8 g, 44 mmol, 60% by mass) was added to a 0°C cooled solution of 1-(6-amino-5-ethylsulfonyl-3-pyridyl)cyclopropanecarboxynitrile (intermediate I-9 prepared as described above) (4.8 g, 19 mmol) in N,N-dimethylformamide (50 mL). After stirring at 0°C for 60 minutes, a solution of tert-butoxycarbonyl tert-butyl carbonate (5 g, 23 mmol) in N,N-dimethylformamide (15 mL) was added to the mixture. An additional 10 mL of N,N-dimethylformamide was added to the reactants and stirring was continued overnight at room temperature. The reactants were quenched with ice water, and the product was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, and concentrated under vacuum to obtain a yellow solid, tert-butyl N-[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]carbamate. The crude product was used as is in the next step. LCMS (Method 1): Rt = 0.97 min, m / z = 296 [(M+H)] + -56].

[0562] Step C1: Ethyl 6-[[tert-butoxycarbonyl-[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl] Preparation of [amino]methyl]-2,2-difluoro-1,3-benzodioxane-5-carboxylate (intermediate I-11)

[0563]

[0564] An intermediate of tert-butyl N-[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]carbamate (intermediate I-10 prepared as described above) (0.17 g, 0.47 mmol) in acetonitrile (10 mL) was mixed with ethyl 6-(bromomethyl)-2,2-difluoro-1,3-benzodioxane-5-carbamate (intermediate I-6 prepared as described above) (0.16 g, 0.47 mmol) and cesium carbonate (0.23 g, 0.70 mmol). The reaction mixture was heated at 50 °C for 12 hours. The reactants were diluted with water, and the product was extracted with ethyl acetate. The organic layer was washed twice with water, then washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 10% to 50% ethyl acetate in cyclohexane) to give a gel-like ethyl 6-[[tert-butoxycarbonyl-[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]amino]methyl]-2,2-difluoro-1,3-benzodioxane-5-carboxylate. LCMS (Method 2): Rt = 1.69 min, m / z = 594 (M+H) + .

[0565] Step C2: Ethyl 6-[[[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]amino]methyl]-2, Preparation of 2-difluoro-1,3-benzodioxane-5-carboxylate (intermediate I-12)

[0566]

[0567] A solution of ethyl 6-[[tert-butoxycarbonyl-[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylate (intermediate I-11 prepared as described above) (0.215 g, 0.34 mmol) in trifluoroacetic acid (3 mL) was stirred for 3 hours. Afterward, the reaction mixture was neutralized with an aqueous sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate (2x), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum to obtain ethyl 6-[[[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylate. The crude product was used as is in the next step. LCMS (Method 2): Rt = 1.65 min, m / z = 494 (M+H) + .

[0568] Step C3: 6-[[[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]amino]methyl]-2,2-di Fluoro-1,3-benzodioxane-5-carboxylic acid (intermediate I-13)

[0569]

[0570] A solution of lithium hydroxide monohydrate (0.054 g, 1.30 mmol) in water (2 mL) was added to a solution of ethyl 6-[[[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylate (intermediate I-12 prepared as described above) (0.17 g, 0.32 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature for 12 hours. Additional lithium hydroxide monohydrate (0.054 g, 1.30 mmol) was added, and the reaction mixture was heated at 50 °C for 3 hours. After completion, the reaction mixture was concentrated under vacuum, the residue was acidified with 1 N hydrochloric acid aqueous solution, and the product was extracted with ethyl acetate. The organic layer was washed twice with water and brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was used as is in the next step. LCMS (Method 2): Rt = 1.49 min, m / z = 466(M+H) + .

[0571] Step C4: 1-[6-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-6- Preparation of [5-ethylsulfonyl-3-pyridyl]cyclopropanecarboxynitrile (compound P1)

[0572]

[0573] Phosphoryl chloride (0.09 mL, 0.97 mmol) was added to a solution of 6-[[[5-(1-cyanocyclopropyl)-3-ethylsulfonyl-2-pyridyl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylic acid (intermediate I-13 prepared as described above) (0.16 g, 0.32 mmol) in pyridine (1 mL) cooled to 0 °C. The reaction mixture was brought to room temperature and stirred under a nitrogen atmosphere for 2 hours. The reaction mixture was acidified with 2N hydrochloric acid aqueous solution (15 mL), and the product was extracted with ethyl acetate (2 x 30 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 50% ethyl acetate in cyclohexane) to give 1-[6-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopentenono[4,5-f]isoindol-6-yl)-5-ethylsulfonyl-3-pyridyl]cyclopropanecarboxylonitrile (compound P1) as a white solid. LCMS (Method 1): Rt = 1.08 min, m / z = 448 (M+H) + . 1H NMR(400MHz, CDCl3)δppm:1.38(t,3H),1.55-1.63(m,2H),1.93-2.01(m,2H), 3.54(q,2H),4.98(s,2H),7.23(s,1H),7.57(s,1H),8.19(d,1H),8.84(d,1H).

[0574] Example P2: 1-[4-[4-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopentene[4,5-f]isoindene] Preparation of (indo-6-yl)-5-ethylsulfonyl-1-methyl-imidazol-2-yl]phenyl]cyclopropanecarboxynitrile (compound P2)

[0575]

[0576] Step 1: Preparation of ethyl 1-methylimidazolium-4-carboxylate (intermediate I-14)

[0577]

[0578] N,N-dimethylformamide (1.23 mL, 15.9 mmol) was added in a single injection to a solution of 1-methylimidazolium-4-carboxylic acid (20.0 g, 159 mmol) in ethanol (200 mL). The mixture was cooled to 0–5 °C, and then thionyl chloride (34.7 mL, 476 mmol) was added dropwise over 15 minutes at 0–5 °C. The cooling was then removed, and the mixture was stirred from 0–5 °C to 24 °C for one hour, followed by stirring at 80 °C for 6 hours under a nitrogen atmosphere. After completion, the reactants were concentrated under vacuum, quenched with a saturated aqueous solution of sodium bicarbonate (100 mL), and the product was extracted with ethyl acetate (3 x 200 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum to give ethyl 1-methylimidazolium-4-carboxylate. This material was used as is in the next step. LCMS (Method 2): Rt = 0.31 min, m / z = 155 (M+H) + .

[0579] Step 2: Preparation of ethyl 2-bromo-1-methyl-imidazolium-4-carboxylate (intermediate I-15)

[0580]

[0581] To a solution of ethyl 1-methylimidazolium-4-carboxylate (intermediate I-14 prepared as described above) (20.0 g, 130 mmol) in tetrahydrofuran (200 mL), N-bromosuccinimide (23.6 g, 130 mmol) and potassium tribasic phosphate (29.0 g, 130 mmol) were added, and the mixture was stirred at room temperature for 16 hours under a nitrogen atmosphere. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (3 x 100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 35% ethyl acetate in cyclohexane) to give ethyl 2-bromo-1-methylimidazolium-4-carboxylate as a white solid. LCMS (Method 2): Rt = 0.85 min, m / z = 233 / 235 (M+H) + . 1 H NMR (400MHz, CDCl3) δppm: 1.37 (t, 3H), 3.68 (s, 3H), 4.36 (q, 2H), 7.64 (s, 1H).

[0582] Step 3: Preparation of ethyl 2-bromo-5-ethylthio-1-methyl-imidazolium-4-carboxylate (Intermediate I-16)

[0583]

[0584] To a solution of N-isopropylpropyl-2-amine (2.4 mL, 17 mmol) in tetrahydrofuran (20 mL), n-butyllithium (2.0 mol / L, 10 mL, 20 mmol in cyclohexane) was added at -78 °C under a nitrogen atmosphere. The resulting solution was stirred at -78 °C for 30 minutes. The solution was then warmed to 0 °C and stirred at 0 °C for 30 minutes. This newly prepared diisopropylaminolithium solution was then added dropwise at -78 °C to a solution of ethyl 2-bromo-1-methyl-imidazolium-4-carboxylate (intermediate I-15 prepared as described above) (2.5 g, 11 mmol) and (ethyl dithioalkyl)ethane (2.6 g, 21 mmol) in tetrahydrofuran (25 mL). The resulting solution was stirred at -78 °C for 30 minutes. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution, and the product was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 20% ethyl acetate in cyclohexane) to give pure ethyl 2-bromo-5-ethylthioalkyl-1-methyl-imidazolium-4-carboxylate as a brown, viscous oil. LCMS (Method 2): Rt = 1.36 min, m / z = 293 / 295 (M+H) + . 1H NMR (400MHz, CDCl3) δppm: 1.21 (t, 3H), 1.40 (t, 3H), 2.92 (q, 2H), 3.71 (s, 3H), 4.40 (q, 2H).

[0585] Step 4: Preparation of ethyl 2-bromo-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate (Intermediate I-17)

[0586]

[0587] 3-chloroperoxybenzyl acid (8.32 g, 33.8 mmol, 70% by mass) was added to a 0°C cooled solution of ethyl 2-bromo-5-ethylthioalkyl-1-methyl-imidazolium-4-carboxylate (intermediate I-16 prepared as described above) (4.50 g, 15.3 mmol) in acetonitrile (45 mL). The reaction mixture was stirred at room temperature for 4 hours. After completion, the reaction mixture was quenched with 2N sodium hydroxide aqueous solution (50 mL) and water (50 mL), and the product was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 30% ethyl acetate in cyclohexane) to give ethyl 2-bromo-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate as a viscous oil. LCMS (Method 2): Rt = 1.31 min, m / z = 325 / 327(M+H) + . 1 H NMR (400MHz, CDCl3) δppm: 1.35-1.44 (m, 6H), 3.67 (q, 2H), 3.97 (s, 3H), 4.43 (q, 2H).

[0588] Step 5: Ethyl 2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate Preparation of (Intermediate I-18)

[0589]

[0590] In a microwave-safe vial, cesium carbonate (1.50 g, 4.61 mmol) and 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)phenyl]cyclopropanecarboxylonitrile (CAS 1206641-31-7) (1.24 g, 4.61 mmol) were added to a stirred solution of ethyl 2-bromo-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate (intermediate I-17 prepared as described above) (0.50 g, 1.53 mmol) in 3 mL of 1,4-dioxane (3 mL) at room temperature. The reaction mixture was degassed with nitrogen for 15 min, and then tetrakis(triphenylphosphine)palladium(0) (0.18 g, 0.15 mmol) was added under a nitrogen atmosphere. The vial was sealed and heated at 110 °C for 60 min under microwave irradiation. The reaction mixture was quenched with water (50 mL), and the product was extracted with ethyl acetate (2 x 50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 25% ethyl acetate in cyclohexane) to give a gel-like ethyl 2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate. LCMS (Method 2): Rt = 1.41 min, m / z = 388 (M+H) + .

[0591] Step 6: 2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylic acid (intermediate) Preparation of I-19)

[0592]

[0593] A solution of lithium hydroxide monohydrate (0.162 g, 3.87 mmol) in water (4 mL) was added to a solution of ethyl 2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate (intermediate I-18 prepared as described above) (1.00 g, 2.58 mmol) in tetrahydrofuran (15 mL), and the mixture was stirred for 10 hours. Additional lithium hydroxide monohydrate (0.162 g, 3.87 mmol) was added, and stirring was continued at 45 °C for 1 hour. After completion, the reaction mixture was quenched with water (50 mL), acidified with 2N hydrochloric acid aqueous solution (20 mL), and the product was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude product was washed with n-pentane (2 x 10 mL) to give pure 2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylic acid as a white solid. LCMS (Method 1): Rt = 0.94 min, m / z = 360 (M+H) + .

[0594] Step 7: tert-butylN-[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4- Preparation of [α]carbamate (intermediate I-20)

[0595]

[0596] Triethylamine (0.36 g, 3.56 mmol) was added to a solution of 2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylic acid (intermediate I-19 prepared as described above) (0.80 g, 2.22 mmol) in tert-butanol (16 mL) at room temperature. The mixture was heated to 90 °C and stirred for 10 min. Diphenylphosphohydrazine (1.00 g, 3.56 mmol) was added dropwise over 15 min, and the resulting reaction mixture was stirred at 90 °C for 40 min. The reaction mixture was cooled to room temperature, quenched with ice-cold water (30 mL), diluted with brine (20 mL), and extracted with ethyl acetate (3 x 70 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 60% ethyl acetate in cyclohexane) to give tert-butyl N-[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]carbamate as a white solid. LCMS (Method 1): Rt = 1.08 min, m / z = 429 (MH) - . 1 HNMR (400MHz, CDCl3) δppm: 1.37-1.44 (m, 3H), 1.44-1.56 (m, 11H), 1.73-1. 91(m,2H),3.25(q,2H),3.81(s,3H),7.39(d,2H),7.63(d,2H),7.83(s,1H).

[0597] Step-8: Ethyl 6-[[tert-butoxycarbonyl-[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1- [Methyl-imidazol-4-yl]amino]methyl]-2,2-difluoro-1,3-benzodioxane-5-carboxylate (intermediate I-) 21) Preparation

[0598]

[0599] Ethyl 6-(bromomethyl)-2,2-difluoro-1,3-benzodioxane-1-methyl-imidazol-4-yl)carbamate (intermediate I-20 prepared as described above) (0.21 g, 0.46 mmol) and cesium carbonate (0.22 g, 0.69 mmol) were added to a solution of tert-butyl N-[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazolium-4-yl]carbamate (intermediate I-6 prepared as described above) (0.17 g, 0.50 mmol) and acetonitrile (0.22 g, 0.69 mmol) in acetonitrile (10 mL). The reaction mixture was heated at 50 °C for 12 h, then diluted with water and extracted with ethyl acetate. The organic layer was washed with water, then with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 10% to 50% ethyl acetate in cyclohexane) to give a gel-like ethyl 6-[[tert-butoxycarbonyl-[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylate]. LCMS (Method 1): Rt = 1.29 min, m / z = 617 [(M+H)] + -56].

[0600] Step-9: Ethyl 6-[[[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazolium-4- Preparation of [amino]methyl]-2,2-difluoro-1,3-benzo[m]dioxane-5-carboxylate (intermediate I-22)

[0601]

[0602] A solution of ethyl 6-[[tert-butoxycarbonyl-[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylate (intermediate I-21 prepared as described above) (0.23 g, 0.32 mmol) in trifluoroacetic acid (2 mL) was stirred at room temperature for 2 hours. Afterward, the reactants were neutralized with an aqueous sodium bicarbonate solution, and the product was extracted with ethyl acetate (2x). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum to give ethyl 6-[[[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylate]. The crude product was used as is in the next step. 1H NMR (400MHz, CDCl3) δppm:1.35-1.48(m,6H),1.51-1.57(m,2H),1.86-1.90(m,2H),3.22(q,2H),3.81(s,3H),4.43(q,2H),4.86(s,2H),5.26(br s,1H),7.48-7.52(m,3H),7.58(d,2H),7.77(s,1H).

[0603] Step-10: 6-[[[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl] Preparation of [amino]methyl]-2,2-difluoro-1,3-benzo[m]dioxacyclopenten-5-carboxylic acid (intermediate I-23)

[0604]

[0605] A solution of lithium hydroxide monohydrate (0.055 g, 1.26 mmol) in water (2 mL) was added to a solution of ethyl 6-[[[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylate] (intermediate I-22 prepared as described above) (0.19 g, 0.31 mmol) in tetrahydrofuran (6 mL). The reaction mixture was stirred at room temperature for 1 hour. Additional lithium hydroxide monohydrate (0.054 g, 1.30 mmol) was added and stirring continued at 50 °C for 3 hours. After completion, the reaction mixture was concentrated under vacuum, the residue was acidified with 1 N hydrochloric acid aqueous solution, and the product was extracted with ethyl acetate. The organic layer was washed with water (2x) followed by brine, dried over sodium sulfate, filtered, and concentrated under vacuum to obtain 6-[[[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylic acid]. The crude product was used as is in the next step. LCMS (Method 1): Rt = 1.09 min, m / z = 545 (M+H) + .

[0606] Example P2: 1-[4-[4-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopentene[4,5-f]isoindene] Preparation of (indo-6-yl)-5-ethylsulfonyl-1-methyl-imidazol-2-yl]phenyl]cyclopropanecarboxynitrile (compound P2)

[0607]

[0608] Phosphoryl chloride (0.05 mL, 0.62 mmol) was added to a solution of 6-[[[2-[4-(1-cyanocyclopropyl)phenyl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]amino]methyl]-2,2-difluoro-1,3-benzo[m-dioxane-5-carboxylic acid (intermediate I-23 prepared as described above) (0.18 g, 0.31 mmol) in pyridine (1 mL) cooled to 0 °C. The reaction mixture was brought to room temperature and stirred under a nitrogen atmosphere for 2 h. The reaction mixture was acidified with 2N hydrochloric acid aqueous solution (15 mL), and the product was extracted with ethyl acetate (2 x 30 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 50% ethyl acetate in cyclohexane) to give 1-[4-[4-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopentenono[4,5-f]isoindol-6-yl)-5-ethylsulfonyl-1-methyl-imidazol-2-yl]phenyl]cyclopropane-formonitrile (compound P2) as a white solid. LCMS (Method 1): Rt = 1.10 min, m / z = 527 (M+H) + . 1 HNMR(400MHz, CDCl3)δppm:1.46-1.56(m,5H),1.83-1.89(m,2H),3.63-3.72(m,2 H),3.95(s,3H),4.92(s,2H),7.21(s,1H),7.47(m,2H),7.59(s,1H),7.65(m,2H).

[0609] Example P8: 6-[3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)-2-pyridyl]-2,2-difluoro-5H-[1, Preparation of [3] m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P8)

[0610]

[0611] Compound P8 was prepared using intermediates I-6 (as described above) and I-65 (as described below) as starting materials, similar to the preparation of compound P1 described above. LCMS (Method 1): Rt = 1.16 min, m / z = 481 (M+H) + .

[0612] Example P3: 6-[2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-] Preparation of [4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindole-7-one (compound P3)

[0613]

[0614] Compound P3 was prepared using intermediates I-6 (as described above) and I-27 (as described below) as starting materials, similar to the preparation of compound P2 described above. LCMS (Method 1): Rt = 1.10 min, m / z = 495 (M+H) +.

[0615] Example P10: 6-(6-cyclopropyl-3-ethylsulfonyl-2-pyridyl)-2,2-difluoro-5H-[1,3]-m-dioxane Preparation of cyclopenteno[4,5-f]isoindole-7-one (compound P10)

[0616]

[0617] Compound P10 was prepared using intermediates I-6 (as described above) and I-59 (as described below) as starting materials, similar to the preparation of compound P1 described above. LCMS (Method 1): Rt = 1.14 min, m / z = 423 (M+H) + .

[0618] Example P6: 6-[5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazol-4-yl]-2,2-di Preparation of fluoro-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindole-7-one (compound P6)

[0619]

[0620] Compound P6 was prepared using intermediates I-6 (as described above) and I-33 (as described below) as starting materials, similar to the preparation of compound P2 described above. LCMS (Method 1): Rt = 1.12 min, m / z = 484 (M+H) + .

[0621] Example P12: 6-[5-(2,2-difluoropropoxy)-3-ethylsulfonyl-2-pyridyl]-2,2-difluoro-5H-[1, Preparation of [3] m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P12)

[0622]

[0623] Compound P12 was prepared using intermediates I-6 (as described above) and I-67 (as described below) as starting materials, similar to the preparation of compound P1 described above. LCMS (Method 1): Rt = 1.12 min, m / z = 477 (M+H) + .

[0624] Example P21: 6-[2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro- Preparation of 5H-[1,3]-m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P21)

[0625]

[0626] Compound P21 was prepared using intermediates I-6 (as described above) and I-45 (as described below) as starting materials, similar to the preparation of compound P2 described above. LCMS (Method 1): Rt = 1.08 min, m / z = 486 / 488 (M+H) + .

[0627] Example P23: 6-[5-(1,1-difluoroethyl)-3-ethylsulfonyl-2-pyridyl]-2,2-difluoro-5H-[1,3] Preparation of m-dioxacyclopenteno[4,5-f]isoindole-7-one (compound P23)

[0628]

[0629] Compound P23 was prepared using intermediates I-6 (as described above) and I-63 (as described below) as starting materials, similar to the preparation of compound P1 above. LCMS (Method 1): Rt = 1.12 min, m / z = 447 (M+H) + .

[0630] Example P26: 6-[2-(3-cyclopropylisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2, Preparation of 2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P26)

[0631]

[0632] A suspension of 6-[2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindol-7-one (compound P3 prepared as described above) (330 mg, 0.634 mmol) and manganese oxide (IV) (334 mg, 3.804 mmol) in toluene (5 mL) was heated at 110 °C for 5 hours. The reaction mixture was diluted with ethyl acetate and water, the layers were separated, the organic phase was washed with water (2x), then with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by combiflash (silica gel, 50-100% ethyl acetate in cyclohexane) to give pure 6-[2-(3-cyclopropylisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopentenon[4,5-f]isoindole-7-one (compound P26) as a solid.

[0633] LCMS (Method 1): Rt = 1.14 min, m / z = 493(M+H) + .

[0634] Example P25: 2-[[6-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopentene[4,5-f]isoindole- Preparation of 6-yl)-5-ethylsulfonyl-3-pyridyl]oxy]-2-methylpropionitrile (compound P25)

[0635]

[0636] Compound P25 was prepared using intermediates I-6 (as described above) and I-53 (as described below) as starting materials, similar to the preparation of compound P1 above. LCMS (Method 1): Rt = 1.14 min, m / z = 466 (M+H) + .

[0637] Table P: Examples of compounds having formula (I)

[0638]

[0639]

[0640]

[0641]

[0642]

[0643]

[0644]

[0645] Preparation of representative intermediates:

[0646] Example I-27: tert-butylN-[2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl] Preparation of [Imidazole-4-yl]carbamate (intermediate I-27)

[0647]

[0648] Step 1: Preparation of ethyl 5-ethylsulfonyl-1-methyl-2-vinyl-imidazolium-4-carboxylate

[0649]

[0650] Tributyltin (1.08 mL, 3.50 mmol) was added to a solution of ethyl 2-bromo-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate (intermediate I-17 prepared as described in step 4 of Example P2) (1.00 g, 2.92 mmol) in toluene (8 mL), and the solution was degassed with nitrogen for 10 min. Then, [1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium(II) complex (0.0147 g, 0.175 mmol) was added, and the reaction mixture was heated in a microwave at 130 °C for 1 h. The reaction mixture was concentrated under vacuum. The residue was dissolved in ethyl acetate, washed twice with water, and then once with brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 50% ethyl acetate in cyclohexane) to give ethyl 5-ethylsulfonyl-1-methyl-2-vinyl-imidazolium-4-carboxylate as a brown oil. LCMS (Method 2): Rt = 0.87 min, m / z = 273(M+H) + . 1 H NMR (400MHz, CDCl3) δppm: 6.61-6.69(m,1H)6.52-6.48(m,1H)5.79(dd,J=11.01,1.25Hz,1H)4.46(q,2H)3.96(s,3H)3.66(q,2H)1.36-1.47(m,6H).

[0651] Step 2: Ethyl 2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol- Preparation of 4-carbamate

[0652]

[0653] Under nitrogen atmosphere, a drop of trifluoroacetic acid was added to a solution of ethyl 5-ethylsulfonyl-1-methyl-2-vinyl-imidazolium-4-carboxylate (prepared as described above) (0.28 g, 0.925 mmol) in methanol (4.2 mL), followed by diacetoxyiodobenzene (0.36 g, 1.11 mmol), cyclopropaneformaldehyde oxime (0.105 g, 1.11 mmol), and another drop of trifluoroacetic acid. The reaction mixture was stirred at room temperature for 12 hours and then concentrated under vacuum. The crude product was purified by combiflash (silica gel, ethyl acetate in cyclohexane) to give ethyl 2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate. LCMS (Method 1): Rt = 0.99 min, m / z = 356 (M+H) + . 1 H NMR (400MHz, CDCl3) δppm: 5.61 (dd, J=10.67, 7.65Hz, 1H) 4.43 (qd, J=7.15, 1.63Hz, 2H) 4.03 (s, 3 H)3.88-3.97(m,1H)3.54-3.69(m,2H)3.16(dd,J=16.81,10.79Hz,1H)1.82-1.89(m,1H)1.42(br t,J=7.15Hz,3H)1.39(br t,J=7.40Hz,3H)0.84-1.02(m,4H).

[0654] Step 3: 2-(3-Cyclopropyl-4,5-Dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-methyl Preparation of acid (intermediate I-26)

[0655]

[0656] A solution of lithium hydroxide monohydrate (0.71 g, 16 mmol) in water (2 mL) was added to a solution of ethyl 2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylic acid (prepared as described above) (2.4 g, 6.4 mmol) in tetrahydrofuran (10 mL) at 0 °C. The reaction mixture was stirred at room temperature for 12 hours. After completion, the reaction mixture was concentrated under vacuum, and the residue was acidified with 1 N hydrochloric acid aqueous solution and poured into ethyl acetate. The organic layer was separated, washed twice with water, then once with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give 2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylic acid. This material was used as is in the next step. LCMS (Method 1): Rt = 0.15 min, m / z = 328 (M+H) + .

[0657] Step 4: tert-butylN-[2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl- Preparation of imidazole-4-yl]carbamate (intermediate I-27)

[0658]

[0659] Triethylamine (1.0 g, 10 mmol) was added to a solution of 2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylic acid (intermediate I-26 prepared as described above) (2.20 g, 6.4 mmol) in tert-butanol (33 mL) at room temperature. The mixture was heated to 90 °C and stirred for 10 min. Diphenylphosphohydrazine (1.19 mL, 5.43 mmol) was added dropwise over 10 min, and the resulting reaction mixture was stirred at 90 °C for 60 min. The reaction mixture was cooled to room temperature, quenched with ice-cold water (100 mL), and the product was extracted with ethyl acetate. The combined organic layers were washed twice with water and once with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 20-70% ethyl acetate in cyclohexane) to give tert-butyl N-[2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]carbamate. LCMS (Method 1): Rt = 1.09 min, m / z = 343 [M+H-56] + . 1HNMR(400MHz, CDCl3)δppm:0.84-1.01(m,4H)1.26-1.40(m,3H)1.52(s,9H)1.80-1.87(m,1H)3.13-3.24 (m,3H)3.81-3.87(m,1H)3.88(s,2H)4.14(d,J=7.09Hz,1H)5.58(dd,J=10.76,8.31Hz,1H)7.77(s,1H).

[0660] Example I-33: tert-butylN-[5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazol-4-yl] Preparation of carbamate (intermediate I-33)

[0661]

[0662] Step 1: Preparation of ethyl 5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazolium-4-carboxylate

[0663]

[0664] Potassium carbonate (6.4 g, 46 mmol) and cuprous iodide (0.44 g, 2.3 mmol) were added to a solution of 2,2,2-trifluoroethanol (7.8 g, 77 mmol) and ethyl 2-bromo-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate (intermediate I-17 prepared as described in step 4 of Example P2) (5.0 g, 15 mmol) in pyridine (50 mL) at 0 °C. The reaction mixture was stirred at 16 °C for 16 h. The reaction mixture was then poured into ice-cold water and stirred for 5 min. The aqueous layer was extracted with ethyl acetate (2 x 100 mL), the combined organic layers were washed with water, then with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was ground with n-pentane, filtered, and dried under vacuum to give ethyl 5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazolium-4-carboxylate. The crude material was used as is in the next step. LCMS (Method 1): Rt = 1.33 min, m / z = 345(M+H) + .

[0665] Step 2: 5-Ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazol-4-carboxylic acid (intermediate I-32) Preparation

[0666]

[0667] A solution of lithium hydroxide monohydrate (0.73 g, 17 mmol) in water (2 mL) was added to a solution of ethyl 5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazolium-4-carboxylic acid (prepared as described above) (2.0 g, 5.8 mmol) in tetrahydrofuran (20 mL) at 0 °C. The reaction mixture was stirred at room temperature for 3 hours. After completion, the reaction mixture was acidified with 2N hydrochloric acid aqueous solution and diluted with water. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum to give 5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazolium-4-carboxylic acid. This material was used as is in the next step. LCMS (Method 1): Rt = 0.95 min, m / z = 317 (M+H) + .

[0668] Step 3: tert-butylN-[5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazol-4-yl]amino Preparation of formate ester (intermediate I-33)

[0669]

[0670] Triethylamine (0.2 g, 2 mmol) was added to a solution of 5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazolium-4-carboxylic acid (intermediate I-32 prepared as described above) (0.40 g, 1 mmol) in tert-butanol (8 mL) at room temperature. The mixture was heated to 90 °C and stirred for 10 min. Diphenylphosphohydrazine (0.4 mL, 2 mmol) was added dropwise over 15 min, and the resulting reaction mixture was stirred at 90 °C for 40 min. The reaction mixture was cooled to room temperature, quenched with ice-cold water (100 mL) and brine (40 mL), and the product was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 40% ethyl acetate in cyclohexane) to give tert-butyl N-[5-ethylsulfonyl-1-methyl-2-(2,2,2-trifluoroethoxy)imidazol-4-yl]carbamate. LCMS (Method 1): Rt = 1.10 min, m / z = 288 [M+H-100] + . 1 H NMR (400MHz, CDCl3) δppm 1.26-1.44 (m, 3H) 1.61 (s, 9H) 3.17 (q, J = 7.46Hz, 2H) 3.59 (s, 3H) 4.89 (q, J = 8.07Hz, 2H) 7.85 (s, 1H).

[0671] Example I-45: tert-butylN-[2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]amino Preparation of carbamate (intermediate I-45)

[0672]

[0673] Step 1: Preparation of ethyl 2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylate

[0674]

[0675] At room temperature, N,N'-dimethylethane-1,2-diamine (0.542 g, 6.15 mmol), potassium carbonate (1.70 g, 12.3 mmol), and 3-chloro-1H-pyrazole (3.47 g, 33.8 mmol) were added to a solution of ethyl 2-bromo-5-ethylsulfonyl-1-methyl-imidazolium-4-carboxylate (intermediate I-17 prepared as described in step 4 of Example P2) in N,N-dimethylformamide (100 mL), followed by the addition of cuprous iodide (0.586 g, 3.08 mmol). The reaction mixture was stirred at 120 °C for 16 hours. Water was then added and the aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with water, dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 0-25% ethyl acetate in cyclohexane) to give ethyl 2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylate, a pale yellow semi-solid. LCMS (Method 1): Rt = 1.09 min, m / z = 347 (M+H) + . 1 H NMR (400MHz, CDCl3) δppm 1.43(td,J=7.31,2.02Hz,6H)3.67(q,J=7.46Hz,2H)4.11-4.17(m,3H)4.46(q,J=7.13Hz,2H)6.47(d,J=2.69Hz,1H)8.12(d,J=2.69Hz,1H).

[0676] Step 2: 2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylic acid (intermediate I-46) preparation

[0677]

[0678] A solution of lithium hydroxide monohydrate (0.889 g, 21 mmol) in water (19.6 mL) was added to a solution of ethyl 2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylic acid (prepared as described above) (4.90 g, 14.1 mmol) in tetrahydrofuran (73.5 mL) at room temperature. The reaction mixture was stirred at room temperature for 16 hours. After completion, the reaction mixture was quenched with water (100 mL), acidified with 2N hydrochloric acid aqueous solution (20 mL), and the product was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude material was washed twice with n-pentane and dried to give 2-(3-cyclopropyl-4,5-dihydroisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylic acid as a white solid. This material was used as is in the next step. LCMS (Method 1): Rt = 0.92 min, m / z = 319(M+H) + . 1 H NMR(400MHz,DMSO-d6)δppm 1.28 (t, J = 7.40Hz, 3H) 3.67 (q, J = 7.34Hz, 2H) 3.83 (s, 3H) 6.80 (d, J = 2.69Hz, 1H) 8.41 (d, J = 2.57Hz, 1H) 13.27-14.12 (m, 1H).

[0679] Step 3: tert-butylN-[2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]aminomethyl Preparation of ester (intermediate I-45)

[0680]

[0681] Triethylamine (2.10 g, 20.6 mmol) was added to a solution of 2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-carboxylic acid (intermediate I-46 prepared as described above) (4.10 g, 12.9 mmol) in tert-butanol (82 mL) at room temperature. The mixture was heated to 90 °C and stirred for 10 min. Diphenylphosphohydrazine (4.53 mL, 20.6 mmol) was added dropwise over 15 min, and the resulting reaction mixture was stirred at 90 °C for 40 min. The reaction mixture was cooled to room temperature, quenched with ice-cold water (100 mL) and brine (40 mL), and the product was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 40% ethyl acetate in cyclohexane) to give tert-butyl N-[2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]carbamate. LCMS (Method 2): Rt = 1.37 min, m / z = 388 (MH) -. 1 H NMR (400MHz, CDCl3) δppm 1.37 (t, J = 7.40Hz, 3H) 1.56 (s, 9H) 3.22 (d, J = 7.46Hz, 2H) 4.04 (s, 3H) 6.41 (d, J = 2.81Hz, 1H) 8.23 ​​(d, J = 2.69Hz, 1H).

[0682] Example I-65: tert-butylN-[3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)-2-pyridyl]carbamic acid Preparation of ester (intermediate I-65)

[0683]

[0684] Step 1: Preparation of ethyl 5-bromo-3-ethylthioalkyl-pyridine-2-carboxylate

[0685]

[0686] Sulfuric acid (1.9 mL, 34.31 mmol) was added dropwise to a solution of 5-bromo-3-ethylthioalkyl-pyridine-2-carboxylic acid (CAS 1857366-13-2) (10.0 g, 34.31 mmol, 89.94% by mass) in ethanol (85 mL), and the mixture was refluxed at 80 °C for 3 h. The reaction mixture was cooled to 24 °C and alkalized with a saturated aqueous sodium bicarbonate solution (50 mL), then diluted with brine. The aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude material was ground with cold methyl tert-butyl ether (20 mL) and stirred at 24 °C for 15 min. The resulting precipitate was filtered through a Buchner funnel and dried under vacuum to give ethyl 5-bromo-3-ethylthioalkyl-pyridine-2-carboxylic acid ester as a light brown solid. The crude product was used as is in the next step. LCMS (Method 1): Rt = 1.05 min, m / z = 290 / 292(M+H) + .

[0687] Step 2: Preparation of ethyl-3-ethylthioalkyl-5-hydroxypyridine-2-carboxylate

[0688]

[0689] Cesium carbonate (34.4 g, 105.6 mmol) was added to a solution of ethyl 5-bromo-3-ethylthioalkyl-pyridine-2-carboxylate (prepared as described above) (15.0 g, 47.99 mmol) in N,N-dimethylformamide (95.98 mL), followed by (E)-benzaldehyde oxime (6.81 mL, 62.39 mmol), and the reaction mixture was stirred at 80 °C for 15 h. The reaction mixture was quenched with ice-cold water, acidified with 2N hydrochloric acid aqueous solution, and extracted in ethyl acetate (3 x 100 mL). The combined organic layers were washed with water (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The resulting residue was ground with tert-butyl methyl ether, the solid was separated by filtration and dried under vacuum to give ethyl 3-ethylthioalkyl-5-hydroxy-pyridine-2-carboxylate as a brown solid. The crude product was used as is in the next step. LCMS (Method 1): Rt = 0.98 min, m / z = 228(M+H) + .

[0690] Step 3: Preparation of ethyl-3-ethylthioalkyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate

[0691]

[0692] Potassium carbonate (4.99 g, 36.15 mmol) and 2,2,2-trifluoroethyl 4-methylbenzenesulfonate (5.97 g, 23.50 mmol) were added to a solution of ethyl 3-ethylthioalkyl-5-hydroxy-pyridine-2-carboxylate (prepared as described above) (4.108 g, 18.07 mmol) in N,N-dimethylformamide (20 mL) under nitrogen atmosphere, and the reaction mixture was stirred at 75 °C for 15 hours. The reaction mixture was diluted with ice-cold water (200 mL), and the product was extracted with ethyl acetate (3 x 60 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 0-40% ethyl acetate in cyclohexane) to give ethyl 3-ethylthioalkyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate as a grayish-white solid. LCMS (Method 1): Rt = 1.15 min, m / z = 310(M+H) + .

[0693] Step 4: Preparation of ethyl 3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate

[0694]

[0695] 3-chloroperoxybenzyl acid (4.25 g, 17.24 mmol, 70 wt%) was added to a solution of ethyl 3-ethylthioalkyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate (prepared as described above) (2.424 g, 7.837 mmol) in acetonitrile (20 mL) cooled to 0 °C. The reaction mixture was stirred at room temperature for 1.5 h. The reaction mixture was carefully concentrated under vacuum and the residue was quenched with 2N sodium hydroxide aqueous solution (20 mL). Water (60 mL) and ethyl acetate (40 mL) were added and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (2 × 50 mL). The combined organic layers were washed with brine (60 mL), dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 0-40% ethyl acetate in cyclohexane) to give ethyl 3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate as a grayish-white solid. LCMS (Method 2): Rt = 1.09 min, m / z = 342(M+H) + .

[0696] Step 5: Preparation of 3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylic acid (intermediate I-50)

[0697]

[0698] A solution of lithium hydroxide monohydrate (1.077 g, 24.38 mmol) in water (7 mL) was added to a solution of ethyl 3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylic acid (prepared as described above) (2.080 g, 6.094 mmol) in tetrahydrofuran (20 mL), and the reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated under vacuum, acidified with 1 N hydrochloric acid aqueous solution, and the product was extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with water (50 mL) and brine, dried over sodium sulfate, filtered, and concentrated under vacuum to give 3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylic acid (I-50) as a grayish-white solid. The crude product was used as is in the next step. LCMS (Method 2): Rt = 0.91 min, m / z = 314 (M+H) + .

[0699] Step 6: tert-butyl N-[3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)-2-pyridyl]carbamate Preparation of (Intermediate I-65)

[0700]

[0701] Triethylamine (1.0441 g, 10.215 mmol) was added to a solution of 3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylic acid (intermediate I-50 prepared as described above) (2 g, 6.3847 mmol) in tert-butanol (40 mL), and the reaction mixture was heated at 90 °C for 10 min. Diphenylphosphoazide (2.24 mL, 10.21 mmol) was added dropwise over 15 min, and the resulting reaction mixture was stirred at 90 °C for 45 min. The reaction mixture was quenched with ice-cold water (50 mL), and the product was extracted with ethyl acetate (3 x 70 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 0-50% ethyl acetate in cyclohexane) to give tert-butyl N-[3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)-2-pyridyl]carbamate (I-65). LCMS (Method 1): Rt = 1.14 min, m / z = 383 [(MH)] - .

[0702] Example I-59: Preparation of tert-butyl N-(6-cyclopropyl-3-ethylsulfonyl-2-pyridyl)carbamate (Part 2) Interstitial I-59)

[0703]

[0704] Step 1: Preparation of ethyl 6-chloro-3-ethylsulfonyl-pyridine-2-carboxylate

[0705]

[0706] Potassium carbonate (11.07 g, 80.106 mmol) was added dropwise to a solution of 6-chloro-3-ethylsulfonyl-pyridine-2-carboxylic acid (CAS 1848219-28-2) (10 g, 40.05 mmol) in methylsulfinylmethane (100 mL) cooled to 0 °C, followed by iodoethane (6.44 mL, 80.106 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was poured into ice-cold water, and the product was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 20% ethyl acetate in cyclohexane) to give ethyl 6-chloro-3-ethylsulfonyl-pyridine-2-carboxylic acid ester. LCMS (Method 1): Rt = 1.05 min, m / z = 278 (M+H) + .

[0707] Step 2: Preparation of ethyl 6-cyclopropyl-3-ethylsulfonyl-pyridine-2-carboxylate

[0708]

[0709] Potassium carbonate (14.0 g, 100 mmol) and cyclopropylboronic acid (7.6 g, 84 mmol) were added to a solution of ethyl 6-chloro-3-ethylsulfonyl-pyridine-2-carboxylate (prepared as described above) (9.3 g, 33 mmol) in toluene (93 mL) and water (28 mL), and the reaction mixture was degassed with nitrogen for 10 min. A 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (1.4 g, 1.70 mmol) was added, and the reaction mixture was degassed with nitrogen for another 5 min and stirred at 110 °C under a nitrogen atmosphere for 5 h. The reaction mixture was cooled to room temperature, diluted with water, extracted with ethyl acetate (3x), and washed with brine. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 20% ethyl acetate in cyclohexane) to give ethyl 6-cyclopropyl-3-ethylsulfonyl-pyridine-2-carboxylate as a solid. LCMS (Method 1): Rt = 1.08 min, m / z = 284(M+H) + .

[0710] Step 3: Preparation of 6-cyclopropyl-3-ethylsulfonyl-pyridine-2-carboxylic acid (intermediate I-48)

[0711]

[0712] Lithium hydroxide monohydrate (0.89 g, 21 mmol) was added to a solution of ethyl 6-cyclopropyl-3-ethylsulfonyl-pyridine-2-carboxylic acid ester (prepared as described above) (2.0 g, 7.1 mmol) in tetrahydrofuran (16 mL) and water (4 mL) at 0–5 °C. The reaction mixture was stirred at room temperature for 24 hours. After completion, the reaction mixture was concentrated under vacuum and the residue was acidified with 2N hydrochloric acid aqueous solution. The white precipitate formed was filtered through a Buchner funnel, and the solid residue was washed with cold water, then with cyclohexane, and then dried under vacuum to give 6-cyclopropyl-3-ethylsulfonyl-pyridine-2-carboxylic acid (I-48) as a solid. The crude product was used as is in the next step. LCMS (Method 1): Rt = 0.66 min, m / z = 256 (M+H) + .

[0713] Step 4: Preparation of tert-butyl N-(6-cyclopropyl-3-ethylsulfonyl-2-pyridyl)carbamate (intermediate) Body I-59)

[0714]

[0715] Triethylamine (1.4 mL, 10 mmol) was added to a solution of 6-cyclopropyl-3-ethylsulfonyl-pyridinyl-2-carboxylic acid (intermediate I-48 prepared as described above) (1.7 g, 6.3 mmol) in tert-butanol (26 mL), and the reaction mixture was heated at 90 °C for 10 min. Diphenylphosphohydride (2.2 mL, 10 mmol) was added dropwise over 10 min, and the resulting reaction mixture was stirred at 90 °C for 60 min. The reaction mixture was quenched with ice-cold water (100 mL), and the product was extracted with ethyl acetate (2x). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 20%–70% ethyl acetate in cyclohexane) to give tert-butyl N-(6-cyclopropyl-3-ethylsulfonyl-2-pyridinyl)carbamate (I-59). LCMS (Method 1): Rt = 1.14 min, m / z = 327(M+H) + .

[0716] LCMS (Method 2): Rt = 1.42 min, m / z = 327(M+H) + .

[0717] Example I-67: tert-butyl N-[5-(2,2-difluoropropoxy)-3-ethylsulfonyl-2-pyridyl]carbamate Preparation of (Intermediate I-67)

[0718]

[0719] Step 1: Preparation of methyl 5-acetone oxy-3-ethylthioalkyl-pyridine-2-carboxylate

[0720]

[0721] A solution of methyl 3-ethylthioalkyl-5-hydroxypyridine-2-carboxylate (CAS 2417036-63-4) (8.0 g, 38.0 mmol) in N,N-dimethylformamide (80 mL) was added with potassium carbonate (16.0 g, 110.0 mmol), followed by 1-chloropropane-2-one (10.0 g, 110.0 mmol). The reaction mixture was stirred overnight at room temperature. After completion, the reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (3 x 150 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 30% ethyl acetate in cyclohexane) to give methyl 5-acetoneoxy-3-ethylthioalkyl-pyridine-2-carboxylate. LCMS (Method 1): Rt = 0.84 min, m / z = 270 (M+H) + .

[0722] Step 2: Preparation of methyl 5-(2,2-difluoropropoxy)-3-ethylthioalkyl-pyridine-2-carboxylate

[0723]

[0724] N-ethyl-N-(trifluoro-λ) was added to a 0°C cooled solution of methyl 5-acetone oxy-3-ethylthioalkyl-pyridine-2-carboxylate (prepared as described above) (8.3 g, 31 mmol) in dichloromethane (170 mL). 4 5-(2,2-difluoropropoxy)-3-ethylthioalkyl-pyridine-2-carboxylate (16 mL, 120 mmol). The reaction mixture was brought to room temperature and stirred for 16 hours. The reaction mixture was quenched with solid sodium bicarbonate, diluted with water (100 mL), and extracted with dichloromethane (3 x 80 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 30% ethyl acetate in cyclohexane) to give methyl 5-(2,2-difluoropropoxy)-3-ethylthioalkyl-pyridine-2-carboxylate. LCMS (Method 1): Rt = 1.43 min, m / z = 292 (M+H) + .

[0725] Step 3: Preparation of 5-(2,2-difluoropropoxy)-3-ethylthioalkyl-pyridine-2-carboxylic acid

[0726]

[0727] A solution of lithium hydroxide monohydrate (1.8 g, 43 mmol) in water (34 mL) was added to a solution of methyl 5-(2,2-difluoropropoxy)-3-ethylthioalkyl-pyridine-2-carboxylic acid ester (prepared as described above) (8.4 g, 29 mmol) in tetrahydrofuran (130 mL). The reaction mixture was stirred at room temperature for 2 hours. The reactants were acidified with 2N HCl aqueous solution, diluted with water (100 mL), and the product was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum to give 5-(2,2-difluoropropoxy)-3-ethylthioalkyl-pyridine-2-carboxylic acid. The crude product was used as is in the next step. LCMS (Method 1): Rt = 0.91 min, m / z = 276 (MH) - .

[0728] Step 4: Tert-butyl N-[5-(2,2-difluoropropoxy)-3-ethylthioalkyl-2-pyridyl]carbamate preparation

[0729]

[0730] Triethylamine (3.5 mL, 25 mmol) was added to a solution of 5-(2,2-difluoropropoxy)-3-ethylthioalkyl-pyridin-2-carboxylic acid (prepared as described above) (4.5 g, 15 mmol) in tert-butanol (68 mL), and the reaction mixture was heated at 90 °C for 10 min. Then, diphenylphosphohydrazine (5.4 mL, 25 mmol) was added dropwise over 10 min, and the resulting mixture was stirred at 90 °C for 60 min. The reaction mixture was quenched with ice-cold water (100 mL), and the product was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 20%–70% ethyl acetate in cyclohexane) to give tert-butyl N-[5-(2,2-difluoropropoxy)-3-ethylthioalkyl-2-pyridinyl]carbamate. LCMS (Method 1): Rt = 1.16 min, m / z = 293[(M+H)-56] + .

[0731] Step 5: tert-butyl N-[5-(2,2-difluoropropoxy)-3-ethylsulfonyl-2-pyridyl]carbamate Preparation of (Intermediate I-67)

[0732]

[0733] 3-Chlorobenzoic acid (2 g, 12.135 mmol) was added to a solution of tert-butyl N-[5-(2,2-difluoropropoxy)-3-ethylthioalkyl-2-pyridyl]carbamate (prepared as described above) (4.5 g, 12 mmol) in ethanol (45 mL) at 15–20 °C. The reaction mixture was stirred at room temperature for 12 hours. The reaction was quenched with saturated sodium sulfite (5 mL), and the resulting mixture was then added to an ice-cold solution of sodium carbonate (1.5 g, 14 mmol) in water (200 mL) and stirred for 30 minutes. The resulting white precipitate was filtered through a Buchner funnel, and the solid residue was washed with cold water, then with cyclohexane, and dried under vacuum to give tert-butyl N-[5-(1-cyano-1-methyl-ethoxy)-3-ethylsulfonyl-2-pyridyl]carbamate (I-67) as a white solid. LCMS (Method 1): Rt = 1.13 min, m / z = 325[(M+H)-56] + and 281[(M+H)-100] + .

[0734] Example I-63: tert-butyl N-[5-(1,1-difluoroethyl)-3-ethylsulfonyl-2-pyridyl]carbamate Preparation of (Intermediate I-63)

[0735]

[0736] Step 1: Preparation of ethyl 5-bromo-3-ethylthioalkyl-pyridine-2-carboxylate

[0737]

[0738] Sulfuric acid (1.9 mL, 34.31 mmol) was added dropwise to a solution of 5-bromo-3-ethylthioalkyl-pyridine-2-carboxylic acid (CAS 1857366-13-2) (10.0 g, 34.31 mmol, 89.94% by mass) in ethanol (85 mL), and the mixture was refluxed at 80 °C for 3 h. The reaction mixture was cooled to 24 °C and alkalized with a saturated aqueous sodium bicarbonate solution (50 mL), then diluted with brine. The aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude material was ground with cold methyl tert-butyl ether (20 mL) and stirred at 24 °C for 15 min. The resulting precipitate was filtered through a Buchner funnel and dried under vacuum to give ethyl 5-bromo-3-ethylthioalkyl-pyridine-2-carboxylic acid ester as a light brown solid. The crude product was used as is in the next step. LCMS (Method 1): Rt = 1.05 min, m / z = 290 / 292(M+H) + .

[0739] Step 2: Preparation of ethyl 5-bromo-3-ethylsulfonyl-pyridine-2-carboxylate

[0740]

[0741] 3-chloroperoxybenzyl acid (61.63 g, 196.43 mmol) was added to a solution of ethyl 5-bromo-3-ethylthioalkyl-pyridine-2-carboxylate (prepared as described above) (20.0 g, 65.47 mmol) in ethanol (200 mL) at 0 °C. The reaction mixture was stirred at room temperature for 12 hours. After completion, the reaction mixture was quenched with a saturated aqueous solution of sodium sulfite (5 mL), and the resulting mixture was added to an ice-cold solution of sodium carbonate (7.1 g, 67 mmol) in water (200 mL) and stirred for 30 minutes. The resulting white precipitate was filtered through a Buchner funnel, and the solid residue was washed with cold water, then washed with cyclohexane, and dried under vacuum to give ethyl 5-bromo-3-ethylsulfonyl-pyridine-2-carboxylate as a white solid. LCMS (Method 1): Rt = 1.06 min, m / z = 322 / 324 [(M+H)] + .

[0742] Step 3: Preparation of ethyl 5-acetyl-3-ethylsulfonyl-pyridine-2-carboxylate

[0743]

[0744] Tributyl(1-ethoxyvinyl)tin (6.727 g, 17.692 mmol) was added to a solution of ethyl 5-bromo-3-ethylsulfonyl-pyridine-2-carboxylate (prepared as described above) (5 g, 14.743 mmol) in N,N-dimethylformamide (58.97 mL), and the reaction mixture was degassed with nitrogen for 15 min. Bis(triphenylphosphine)palladium(II) dichloride (0.522 g, 0.737 mmol) was added to the reaction mixture, and the mixture was heated at 80 °C for 3 h. The reaction mixture was cooled and 2N HCl aqueous solution (20 mL) was added. After stirring at room temperature for 30 min, the reaction mixture was quenched with KF aqueous solution and diluted with water (100 mL) and ethyl acetate (100 mL). The solution was filtered through diatomaceous earth, and the residue was washed with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 30%-40% ethyl acetate in cyclohexane) to give ethyl 5-acetyl-3-ethylsulfonyl-pyridine-2-carboxylate. LCMS (Method 2): Rt = 1.16 min, m / z = 286 [(M+H)] + .

[0745] Step 4: Preparation of ethyl 5-(1,1-difluoroethyl)-3-ethylsulfonyl-pyridine-2-carboxylate

[0746]

[0747] Under a nitrogen atmosphere, bis(2-methoxyethyl)aminosulfonyl-pyridine-2-carboxylate (prepared as described above) (3.5 g, 12 mmol) was added dropwise to a solution of ethyl 5-acetyl-3-ethylsulfonyl-pyridine-2-carboxylate in toluene (35 mL). The reaction mixture was stirred at 80 °C for 12 h, then quenched with saturated sodium bicarbonate solution and diluted with ice-cold water (100 mL). The aqueous phase was extracted with ethyl acetate (3 x 75 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude compound was purified by combiflash (silica gel, 30%–40% ethyl acetate in cyclohexane) to give ethyl 5-(1,1-difluoroethyl)-3-ethylsulfonyl-pyridine-2-carboxylate. LCMS (Method 1): Rt = 1.02 min, m / z = 308 (M+H) + .

[0748] Step 5: Preparation of 5-(1,1-difluoroethyl)-3-ethylsulfonyl-pyridine-2-carboxylic acid (intermediate I-49)

[0749]

[0750] A solution of lithium hydroxide monohydrate (0.6799 g, 27.82 mmol) in water (6 mL) was added to a solution of ethyl 5-(1,1-difluoroethyl)-3-ethylsulfonyl-pyridine-2-carboxylic acid (prepared as described above) (3.0 g, 9.27 mmol) in tetrahydrofuran (24 mL) at 5 °C. The reaction mixture was stirred at room temperature for 12 hours. After completion, the reaction mixture was concentrated under vacuum and acidified with 2N hydrochloric acid aqueous solution. The resulting white precipitate was filtered through a Buchner funnel, washed with cold water, then washed with cyclohexane, and dried under vacuum to give 5-(1,1-difluoroethyl)-3-ethylsulfonyl-pyridine-2-carboxylic acid (I-49) as a white solid. LCMS (Method 2): Rt = 0.77 min, m / z = 280 (M+H) + .

[0751] Step-6: Tert-butyl N-[5-(1,1-difluoroethyl)-3-ethylsulfonyl-2-pyridyl]carbamate (middle) Preparation of intermediate I-63

[0752]

[0753] Triethylamine (1.8 mL, 13 mmol) was added to a solution of 5-(1,1-difluoroethyl)-3-ethylsulfonyl-pyridin-2-carboxylic acid (intermediate I-49 prepared as described above) (2.4 g, 8.2 mmol) in tert-butanol (36 mL), and the reaction mixture was heated at 90 °C for 10 min. Diphenylphosphoazide (2.9 mL, 13 mmol) was added dropwise over 10 min, and the resulting reaction mixture was stirred at 90 °C for 40 min. The reaction mixture was quenched with ice-cold water (30 mL), and the product was extracted with ethyl acetate (2x). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 60% ethyl acetate in cyclohexane) to give tert-butyl N-[5-(1,1-difluoroethyl)-3-ethylsulfonyl-2-pyridinyl]carbamate (I-63). LCMS (Method 2): Rt = 1.37 min, m / z = 295[(M+H)-56] + .

[0754] LCMS (Method 1): Rt = 1.08 min, m / z = 349 (MH) - .

[0755] Example I-53: tert-butylN-[5-(1-cyano-1-methyl-ethoxy)-3-ethylsulfonyl-2-pyridyl]amino Preparation of formate ester (intermediate I-53)

[0756]

[0757] Step-1: tert-butylN-[5-(1-cyano-1-methyl-ethoxy)-3-ethylthioalkyl-2-pyridyl]aminomethyl Preparation of esters

[0758]

[0759] Triethylamine (3.21 mL, 22.83 mmol) was added to a solution of 5-(1-cyano-1-methyl-ethoxy)-3-ethylthioalkyl-pyridine-2-carboxylic acid (CAS 2417036-66-7, as described in WO 2020141136) (4 g, 14.27 mmol) in tert-butanol (40 mL), and the reaction mixture was heated to 90 °C. After 10 min, diphenylphosphoazide (5.021 mL, 22.83 mmol) was added dropwise over 15 min, and the resulting reaction mixture was stirred at 90 °C for 40 min. The reaction mixture was quenched with water (30 mL) and brine (20 mL), and the product was extracted with ethyl acetate (2 x 50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by combiflash (silica gel, 40%-60% ethyl acetate in cyclohexane) to give tert-butyl N-[5-(1-cyano-1-methyl-ethoxy)-3-ethylthioalkyl-2-pyridyl]carbamate. LCMS (Method 1): Rt = 1.17 min, m / z = 282 [(M+H)-56] + .

[0760] Step-2: tert-butylN-[5-(1-cyano-1-methyl-ethoxy)-3-ethylsulfonyl-2-pyridyl]aminomethyl Preparation of ester (intermediate I-53)

[0761]

[0762] 3-Chlorobenzoic acid (0.7 g, 4 mmol) was added to a solution of tert-butyl N-[5-(1-cyano-1-methyl-ethoxy)-3-ethylthioalkyl-2-pyridyl]carbamate (prepared as described above) (1.5 g, 4.2 mmol) in ethanol (15 mL) at 15 °C–20 °C. The reaction mixture was stirred at room temperature for 12 hours. The reaction was quenched with saturated sodium sulfite (5 mL), and the resulting mixture was then added to an ice-cold solution of sodium carbonate (0.4 g, 4 mmol) in water (200 mL) and stirred for 30 minutes. The resulting white precipitate was filtered through a Buchner funnel, and the solid residue was washed with cold water, then with cyclohexane, and dried under vacuum to give tert-butyl N-[5-(1-cyano-1-methyl-ethoxy)-3-ethylsulfonyl-2-pyridyl]carbamate (I-53) as a white solid. The crude product was used as is in the next step. LCMS (Method 2): Rt = 1.37 min, m / z = 314[(M+H)-56] + .

[0763] Table I: Examples of Intermediates

[0764]

[0765]

[0766]

[0767]

[0768]

[0769]

[0770]

[0771]

[0772]

[0773]

[0774]

[0775]

[0776]

[0777]

[0778] The activity of the compositions according to the invention can be significantly broadened and adapted to general conditions by adding other insecticidal, acaricidal, and / or fungicidal ingredients. Mixtures of compounds of Formula I with other insecticidal, acaricidal, and / or fungicidal ingredients can also have additional unexpected advantages, which can be described more broadly as synergistic activity. For example, better plant tolerance, reduced phytotoxicity, control of insects at different developmental stages, or better behavior during their production (e.g., during grinding or mixing, during storage, or during use).

[0779] Here, the appropriate active ingredients are representative of the following categories of active ingredients: organophosphorus compounds, nitrophenol derivatives, thiourea, juvenile hormones, formamidin, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylurea, pyridylmethylene amino derivatives, macrolides, neonicotinoids, and Bacillus thuringiensis preparations.

[0780] The following mixtures of compounds having Formula I and active ingredients are preferred (the abbreviation "TX" means "a compound selected from the group consisting of compounds described in Tables A-1 to A-12, D-1 to D-12, E-1 to E-12 and G1 to G-12 and Table P of the present invention"):

[0781] The auxiliary agent is selected from the following group of substances: petroleum (alias) (628) + TX;

[0782] Insect control active substances selected from abamectin + TX, miticide + TX, acetamiprid + TX, acetamiprid + TX, flufenoxuron + TX, acynonapyr + TX, bispyrifos + TX, afralanar + TX, pyrethroid + TX, α-cypermethrin + TX, lambda-cyhalothrin + TX, sulfadiazine + TX, methamidophos + TX, triazophos + TX, chlorpyrifos + TX, benzoyl permethrin + TX, Benzpyrimoxan + TX, β-cypermethrin + TX, β-cypermethrin + TX, bifenazate + TX, bifenthrin + TX, chlorfenapyr + TX, bio-allethrin + TX, S-bio-allethrin + TX, bio-benzylfenoxuron + TX, and more. Triflufenoxam + TX, Broflanilide + TX, Broflufenoxam + TX, Bromothion-Ethyl + TX, Thiamethoxam + TX, Butanil + TX, Thiamethoxam + TX, Carbaryl + TX, Sevin + TX, Thiamethoxam + TX, Bataan + TX, CAS No.: 1632218-00-8+TX, CAS No.: 1808115-49-2+TX, CAS No.: 2032403-97-5+TX, CAS No.: 2044701-44-0+TX, CAS No.: 2128706-05-6+TX, CAS No.: 2095470-94-1+TX, CAS No.: 2377084-09-6+TX, CAS No.: 14 45683-71-5+TX, CAS No.: 2408220-94-8+TX, CAS No.: 2408220-91-5+TX, CAS No.: 1365070-72-9+TX, CAS No.: 2171099-09-3+TX, CAS No.: 2396747-83-2+TX, CAS No.: 2133042-31-4+TX, CAS No.: 2133042-44-9+TX, CAS No.: 1445684-82-1+TX, CAS No.: 1445684-82-1+TX, CAS No.: 1922957-45-6+TX, CAS No.: 1922957-46-7+TX, CAS CAS Nos: 1922957-47-8+TX, 1922957-48-9+TX, 2415706-16-8+TX, 1594624-87-9+TX, 1594637-65-6+TX, 1594626-19-3+TX, 1990457-52-7+TX, 1990457-55-0+TX, 1990457-57-2+TX, 1990457-77-6+TX, 1990457-66-3+TX, 1990457-85-6+TXCAS No.: 2220132-55-6+TX, CAS No.: 1255091-74-7+TX, Chlorantraniliprole +TX, Chlordane +TX, Bromoxynil +TX, Cyprodinil +TX, Clenbuterol +TX, Cloethocarb +TX, Thiamethoxam +TX, 2-Chlorophenyl N-methylcarbamate (CPMC) +TX, Benzoate +TX, Bromoxynil +TX, Cyclobutrifluram +TX, Pyrethroids +TX, Ethoxyfen +TX, Cyclobutrifluram +TX, Cyprodinil +TX, Cyclobutrifluram +TX, Fluorochlor Cypermethrin + TX, Cyhalodiamide + TX, Trifluralin + TX, Cypermethrin + TX, Phenylebin + TX, Cyproflanilide + TX, Cyromazine + TX, Deltamethrin + TX, Acaricide + TX, Chlorimuron + TX, Dibrom + TX, Dichlorvos + TX, Flufenoxuron + TX, Diflubenzuron + TX, Difenoconazole + TX, Difenoconazole + TX, Difenoconazole + TX, Fipronil + TX, Emafenoxam (or Emafenoxam benzoate) + TX, D-cyclohexylpyridinium +TX, ε-momfluorothrin+TX, ε-methoxybenzylfluthrin+TX, cypermethrin+TX, ethion +TX, acetamiprid +TX, etoxazole +TX, phosmet +TX, quinfenoxam +TX, pendimethalin +TX, fenmezoditiaz +TX, fenitrothion +TX, methyl parathion +TX, fenthion +TX, fenoxycarb +TX, cypermethrin +TX, fenpyroximate +TX, fensodium +TX, fenthion +TX, cypermethrin +TX, flumetoquinone +TX, flupyradifurone +TX, pyrimethanil +TX, fluazaindolizine +TX, pyrimethanil +TX, flufenoxuron +TX, flufenoxuron +TX, fluchlordiniliprole +TX, flucitrinate +TX, flufenoxuron +TX, flufenoxuron +TX, flufenoxuron +TX, pyrimethanil +TX, trifluralin +TX, butenpyram +TX, fluhexafon +TX, flupyridaben +TX, flupyradifurone +TX, flupentiofenox +TX, flupyrflufenoxuron +TX, flupyrflufenoxuron +TXFlupyrimin + TX, fluralaner + TX, lambda-cyhalothrin + TX, fluxametamide + TX, thiazophos + TX, γ-trifluorocypermethrin + TX, Gossyplure, TM+TX, imidacloprid +TX, chlorfenapyr +TX, benzylfentanyl +TX, heptafluthrin +TX, thiamethoxam +TX, flufenoxuron +TX, imidacloprid +TX, imidacloprid +TX, indazapyroxamet +TX, indoxacarb +TX, iodomethacin +TX, iprodione +TX, isocycloseram +TX, isopyram +TX, ivermectin +TX, κ-bifenthrin +TX, κ-heptafluthrin +TX, lambda-cyhalothrin +TX, rapamycin +TX, lotilanar +TX Chlorfenapyr + TX, Cyfluthrin + TX, Metformin + TX, Mefenoxam + TX, Metformin + TX, Methoxyfenozide + TX, Methoxyfenozide + TX, Mefenoxam + TX, Mefenoxam + TX, Acaricide + TX, Momfluorothrin + TX, Dimethoate + TX, Nicofluprole + TX; Acetaminophen + TX, Nitrothiamethoxam + TX, Omethoate + TX, Cypermethrin + TX, Oxazosulfyl + TX, Parathion-ethyl + TX, Permethrin + TX, Difenoconazole + TX, Calcium oxychloride + TX, Piperazine + TX, Pyrimethanil-ethyl + TX, Pyrimethanil-methyl + TX, Polyhexene Virus + TX, propargite + TX, profenofos + TX, fenfluroxyfen + TX, chlorfenapyr + TX, acetamiprid + TX, propoxur + TX, fenthion + TX, protrifenbute + TX, pyflubumide + TX, pymetrozine + TX, pyrazophos + TX, pyrafluprole + TX, pyridaben + TX, acetamiprid + TX, pyrifluquinazon + TX, pyrimethanil + TX, pyrimethanil + TX, pyrazophos + TX, pyridaben + TX, fenfluroxyfen + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX, pyrimethanil + TX , Flufenoxam + TX, Ethyl spinosad + TX, Spinosad + TX, Spiropidion + TX, Spirotetramethrin + TX, Spiropidone + TX, Sulfadiazine + TX, Tebufenozide + TX, Pyridaben + TX, Tebupirimiphos + TX, Heptamethrin + TX, Dimethoate + TX, Tetrachlorfenapyr + TX, Tetradiphon + TX, Pyrethroid + TX, Tetrafluthrin + TX, Acaricide + TX, Flufenoxuron + TX, θ-Cypermethrin + TX, Thiamethoxam + TX, Thiamethoxam + TX, Cypermethrin + TX, Thiamethoxam + TX, Dichlorvos + TX, Thiamethoxam + TX, Dichlorvos + TX, Thiamethoxam + TX, Dichlorvos + TX, Methion + TX, Pyridaben + TXTioxazafen+TX, acetamiprid+TX, toxaphene+TX, tetrabromopyr+TX, tetrafluorobenzylpyr+TX, pymetrozine+TX, triazophos+TX, trichlorfon+TX, cypermethrin+TX, trichlorfon+TX, triflumezopyrim+TX, tyclopyrazoflor+TX, ζ-cypermethrin+TX, seaweed extract and fermented products derived from glycoyl +TX, seaweed extract and fermented products derived from glycoyl (including urea+TX, amino acids+TX, potassium and molybdenum, and EDTA chelated manganese)+TX, seaweed extract and fermented plant products+TX, seaweed extract and fermented plant products (including plant hormones+TX, vitamins+TX, EDTA chelated copper+TX, zinc+TX, and iron+TX), azadirachtin+TX, Bacillus aizawai+TX, Bacillus chitinosa Bacillus chitinosporus AQ746 (NRRL Registry No. B-21618) + TX, Bacillus sturdier + TX, Bacillus kurstaki + TX, Bacillus mycosis fungoides AQ726 (NRRL Registry No. B-21664) + TX, Bacillus pumilus (NRRL Registry No. B-30087) + TX, Bacillus pumilus AQ717 (NRRL Registry No. B-21662) + TX, Bacillus species AQ178 (ATCC Registry No. 53522) + TX, Bacillus species AQ175 (ATCC Registry No. 55608) + TX, Bacillus species AQ177 (ATCC Registry No. 55609) + TX, Bacillus subtilis (unspecified) + TX, Bacillus subtilis AQ153 (ATCC Registry No. 55614) +TX, Bacillus subtilis AQ30002 (NRRL Registry No. B-50421) +TX, Bacillus subtilis AQ30004 (NRRL Registry No. B-50455) +TX, Bacillus subtilis AQ713 (NRRL Registry No. B-21661) +TX, Bacillus subtilis AQ743 (NRRL Registry No. B-21665) +TX, Bacillus thuringiensis AQ52 (NRRL Registry No. B-21619) +TX, Bacillus thuringiensis BD#32 (NRRL Registry No. B-21530) +TX, Bacillus thuringiensis Kurstaki subsp. BMP 123+TX, Beauveria bassiana +TX, D-limonene +TX, Granulovirus +TX, Harpin +TX, Cotton bollworm nucleopolyhedrovirus +TX, Gramineae nucleopolyhedrovirus +TX, Tobacco budworm nucleopolyhedrovirus +TX, Australian cotton bollworm nucleopolyhedrovirus +TX, Metarhizium species +TX,Muscodor albus 620 (NRRL Registry No. 30547) +TX, Muscodor roseus A3-5 (NRRL Registry No. 30548) +TX, neem-based products +TX, *Paecilomyces rosenbergii* +TX, *Paecilomyces lilacinus* +TX, *Paecilomyces szawa* +TX, *Paecilomyces punctata* +TX, *Paecilomyces mycoides* +TX, *Paecilomyces thornei* +TX, *Paecilomyces* +TX, p-cymene +TX, diamondback moth granulovirus +TX, diamondback moth nucleopolyhedrovirus +TX, polyhedrovirus +TX, pyrethrum +TX, QRD 420 (terpene blend) +TX, QRD 452 (terpene blend) +TX, QRD 460 (terpene blend) + TX, *Saponaria spp.* + TX, *Rhodococcus spherulites* AQ719 (NRRL registry number B-21663) + TX, *Fall Armyworm* nucleopolyhedrovirus + TX, *Streptomyces flavus* (NRRL registry number 30232) + TX, *Streptomyces* species (NRRL registry number B-30145) + TX, terpene blend + TX, and *Verticillium* species;

[0783] Algicide selected from the following groups of substances: bethoxazin [CCN]+TX, copper dioctanoate (IUPAC name) (170)+TX, copper sulfate (172)+TX, 2-tert-butylamino-4-cyclopropylamino-6-methylthio-s-triazine [CCN]+TX, dichlone (1052)+TX, dichlorophenol (232)+TX, fentin (295)+TX, fentin (347)+TX, quicklime [CCN]+TX, sodium mancozeb (566)+TX, quinoclamine (714)+TX, quinonamid (1379)+TX, simazine (730)+TX, tin triphenylacetate (IUPAC name) (347) and tin triphenyl hydroxide (IUPAC name) (347)+TX;

[0784] The anthelmintic is selected from the group of substances consisting of: abamectin (1)+TX, chlorfenapyr (1011)+TX, cyclobutyral+TX, doxorubicin (alias) [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, irinotecan (alias) [CCN]+TX, ivermectin (alias) [CCN]+TX, milbemycin oxime (alias) [CCN]+TX, moxicillin (alias) [CCN]+TX, piperazine [CCN]+TX, slakine (alias) [CCN]+TX, spinosad (737) and thiophanate (1435)+TX;

[0785] Bird killers selected from the following groups of substances: chloralose (127) + TX, isodrin (1122) + TX, fenthion (346) + TX, pyridine-4-amine (IUPAC name) (23) and strychnine (745) + TX;

[0786] Bactericides selected from the following groups of substances: 1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222)+TX, 4-(quinoxalo-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, 8-hydroxyquinoline sulfate (446)+TX, bromonitrile (97)+TX, copper dioctanoate (IUPAC name) (170)+TX, copper hydroxide (IUPAC name) (169)+TX, cresol [CCN]+TX, dichlorophenol (232)+TX, dipyrithione (1105)+TX, doxycycline (1112)+TX, fenaminosulfonate (1144)+TX, formaldehyde (404)+TX, mercaptophenone ( (Alternative names) [CCN]+TX, Kasugamycin (483)+TX, Kasugamycin hydrochloride hydrate (483)+TX, Di(dimethyldithiocarbamate) nickel (IUPAC name) (1308)+TX, Nitropyrin (580)+TX, Octhilinone (590)+TX, Oxytetracycline (606)+TX, Oxytetracycline (611)+TX, Potassium hydroxyquinoline sulfate (446)+TX, Probenazole (658)+TX, Streptomycin (744)+TX, Streptomycin sesquisulfate (744)+TX, Phthalate (766)+TX, and Thimerosal (alternative name) [CCN]+TX;

[0787] Biological reagents, selected from the following groups of substances: Cotton Brown Leaf Roller GV (alias) (12)+TX, *Agrobacterium radiata* (alias) (13)+TX, *Amblyseius spp.* (alias) (19)+TX, Celery Noctuid Moth NPV (alias) (28)+TX, *Anagrus atomus* (alias) (29)+TX, *Aphelinus adominalis* (alias) (33)+TX, Cotton Aphid Parasitic Wasp (Aphidius colemani) (alias) (34)+TX, Aphidoletes aphidimyza (alias) (35)+TX, Alfalfa Silver-striped Noctuid Moth NPV (alias) (38)+TX, *Bacillus firmus* (alias) (48)+TX, *Bacillus sphaericus* Neide)(scientific name)(49)+TX, Bacillus thuringiensis Berliner)(scientific name)(51)+TX, Bacillus thuringiensis subsp. aizawai)(scientific name)(51)+TX, Bacillus thuringiensis subsp. israelensis)(scientific name)(51)+TX, Bacillus thuringiensis subsp. japonensis)(scientific name)(51)+TX, Bacillus thuringiensis subsp. kurstaki)(scientific name)(51)+TX, Bacillus thuringiensis subsp. truncatella)(scientific name)(51)+TX, Bacillus thuringiensis subsp.tenebrionis (scientific name) (51)+TX, Beauveria bassiana (synonym) (53)+TX, Beauveria brongniartii (synonym) (54)+TX, Chrysoperla carnea (synonym) (151)+TX, Cryptolaemus montrouzieri (synonym) (178)+TX, Codling moth GV (synonym) (191)+TX, Dacnusa sibirica (synonym) (212)+TX, Diglyphusisaea (synonym) (254)+TX, Encarsia formosa (scientific name) (293)+TX, Eretmocerus eremicus (alias) (300)+TX, Grainworm NPV (alias) (431)+TX, Heterorhabditis bacteriophora and H. megidis (alias) (433)+TX, Hippodamia convergens (alias) (442)+TX, Leptomastixdactylopii (alias) (488)+TX, Macrophorus caliginosus (alias) (491)+TX, Cabbage moth NPV (alias) (494)+TX, Metaphycus helvolus (alias) (522)+TX, Metarhizium anisopliae var. acridum (scientific name) (523)+TX, Metarhizium anisopliae var. anisopliae (scientific name) (523)+TX, Neodiprionsertifer NPV and Neodiprionsertifer (N.lecontei)NPV (synonyms) (575)+TX, Species of the genus *Lecontei* (synonyms) (596)+TX, *Paecilomyces fumosoroseus* (synonyms) (613)+TX, *Phytoseiulus persimilis* (synonyms) (644)+TX, *Spodopteraexigua multicapsid nuclear polyhedrosis virus* (scientific name) (741)+TX, *Steinernema bibionis* (synonyms) (742)+TX, *Steinernema carpocapsae* (synonyms) (742)+TX, *Steinernema glaseri* (synonyms) (742)+TX, *Steinernema rubescens* (synonyms) (742)+TX, *Steinernema glaseri* (synonyms) (742)+TX, *Steinernema rubescens* riobrave)(synonyms)(742)+TX, Steinernema riobravis)(synonyms)(742)+TX, Steinernema scapterisci)(synonyms)(742)+TX, Steinernema spp.)(synonyms)(742)+TX, Trichogramma spp.(synonyms)(826)+TX, Typhlodromus occidentalis(synonyms)(844) and Verticillium lecanii(synonyms)(848)+TX;

[0788] Soil disinfectant, selected from the following group of substances: iodomethane (IUPAC name) (542) and bromomethane (537) + TX;

[0789] Chemical sterilizing agents are selected from the following groups of substances: apholate [CCN]+TX, bisazir [CCN]+TX, busulfan [CCN]+TX, diflubenzuron (250)+TX, dimatif [CCN]+TX, hemel [CCN]+TX, hempa [CCN]+TX, metepa [CCN]+TX, methyl thiophanate... Methiotepa [CCN]+TX, methylapholate [CCN]+TX, morzid [CCN]+TX, penfluron (alias) [CCN]+TX, tepa [CCN]+TX, thiohempa (alias) [CCN]+TX, thiotepa (alias) [CCN]+TX, tratamine (alias) [CCN], and urethaneimine (alias) [CCN]+TX;

[0790] Insect pheromones are selected from the following groups of substances: (E)-dec-5-en-1-yl acetate and (E)-dec-5-en-1-ol (IUPAC name) (222)+TX, (E)-tetadecarbon-4-en-1-yl acetate (IUPAC name) (829)+TX, (E)-6-methylheptane-2-en-4-ol (IUPAC name) (541)+TX, (E,Z)-tetradecane-4,10-dien-1-yl acetate (IUPAC name) (779)+TX, (Z)-dodecane-7-en-1-yl acetate (IUPAC name) (285)+TX, (Z)-hexadecane-11-enal (IUPAC name) (436)+TX, (Z)-hexadecane-11-en-1-yl acetate (IUPAC name) (437)+T X, (Z)-hexadec-13-en-11-yn-1-yl acetate (IUPAC name) (438)+TX, (Z)-eicosero-13-en-10-one (IUPAC name) (448)+TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782)+TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783)+TX, (Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784)+TX, (7E,9Z)-dodec-7,9-dien-1-yl acetate (IUPAC name) (283)+TX, (9Z,11E)-tetradec-9,11-dien-1-yl acetate (IUPAC name) (780)+TX, (9Z,12E)-tetradec-9,12-Dien-1-ylacetate (IUPAC name) (781)+TX, 14-Methyloctadec-1-ene (IUPAC name) (545)+TX, 4-Methylnon-5-ol and 4-Methylnon-5-one (IUPAC name) (544)+TX, alpha-multistriatin (alias) [CCN]+TX, brevicomin (alias) [CCN]+TX, codlelure (alias) [CCN]+TX, codlelure (alias) [CCN]+TX, codlelure (alias) mone)(alias)(167)+TX, cuelure)(alias)(179)+TX, disparlure)(277)+TX, dodecano-8-en-1-yl acetate (IUPAC name))(286)+TX, dodecano-9-en-1-yl acetate (IUPAC name))(287)+TX, dodecano-8+TX, 10-dien-1-yl acetate (IUPAC name))(284)+TX, dominicalure(alias)[CCN]+TX, ethyl 4-methyloctanoate (IUPA) C Name)(317)+TX, Eugenol (Alias) [CCN]+TX, Frontalin (Alias) [CCN]+TX, Gossyplure (Alias) (420)+TX, Grandlure (421)+TX, Grandlure I (Alias) (421)+TX, Grandlure II (Alias) (421)+TX, Grandlure III (Alias) (421)+TX, Grandlure IV (Alias) (421)+TX, Hexalure [CCN]+TX, ipsdienol (alias) [CCN]+TX, ipsenol (alias) [CCN]+TX, japonilure (alias) (481)+TX, lineatin (alias) [CCN]+TX, litlure (alias) [CCN]+TX, looplure (alias) [CCN]+TX, medlure (alias) [CCN]+TX, megatomoic acid (alias) [CCN]+TX, methyl eugenol (alias) (540)+TX, muscalure (563)+TX, octadec-2,13-dien-1-yl acetate (IUPAC name) (588)+TX, octadec-3,13-Dien-1-ylacetate (IUPAC name) (589)+TX, Orfralure (alias) [CCN]+TX, Oryctalure (alias) (317)+TX, Ostramone (alias) [CCN]+TX, Siglure (CCN)+TX, Sordidin (alias) (736)+TX, Sulcatol (Alias) [CCN]+TX, tetradec-11-en-1-yl acetate (IUPAC name) (785)+TX, Mediterranean fruit fly attractant (839)+TX, Mediterranean fruit fly attractant A (alias) (839)+TX, Mediterranean fruit fly attractant B1 (alias) (839)+TX, Mediterranean fruit fly attractant B2 (alias) (839)+TX, Mediterranean fruit fly attractant C (alias) (839) and trunc-call (alias) [CCN]+TX;

[0791] Insect repellents selected from the group consisting of the following substances: 2-(octylthio)ethanol (IUPAC name) (591)+TX, butopyronoxyl (933)+TX, butoxy (polypropylene glycol) (936)+TX, dibutyl adipate (IUPAC name) (1046)+TX, dibutyl phthalate (1047)+TX, dibutyl succinate (IUPAC name) (1048)+TX, DEET [CCN]+TX, dimethyl carbate [CCN]+TX, dimethyl phthalate [CCN]+TX, ethylhexanediol (1137)+TX, hexourea [CCN]+TX, methoquin-butyl (1276)+TX, methylneodecanamide [CCN]+TX, oxamate [CCN], and picaridin [CCN]+TX;

[0792] Molluscicides selected from the group consisting of the following substances: di(tributyltin)oxide (IUPAC name) (913)+TX, bromoacetamide [CCN]+TX, calcium arsenate [CCN]+TX, chlorpyrifos (999)+TX, copper acetylacetate [CCN]+TX, copper sulfate (172)+TX, triphenyltin (347)+TX, ferric phosphate (IUPAC name) (352)+TX, metaldehyde (518)+TX, cypermethrin (530)+TX, niclosamide (576)+TX, niclosamide-ethanolamine (576)+TX, pentachlorophenol ( 623)+TX, sodium pentachlorophenoxide (623)+TX, tazimcarb (1412)+TX, thiamethoxam (799)+TX, tributyltin oxide (913)+TX, trifenmorph (1454)+TX, trimethacarb (840)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX, pyriprole [394730-71-3]+TX;

[0793] Nematicides selected from the following groups of substances: AKD-3088 (compound code) + TX, 1,2-dibromo-3-chloropropane (IUPAC / Chemical Abstracts name) (1045) + TX, 1,2-dichloropropane (IUPAC / Chemical Abstracts name) (1062) + TX, 1,2-dichloropropane and 1,3-dichloropropene (IUPAC name) (1063) + TX, 1,3-dichloropropene (233) + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC / Chemical Abstracts name) Abstract Name)(1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980)+TX, 5-methyl-6-thio-1,3,5-thiadiazin-3-ylacetic acid (IUPAC name) (1286)+TX, 6-isopentenylaminopurine (synonym) (210)+TX, avermectin (1)+TX, acetaminophen [CCN]+TX, basil (15)+TX, aldicarb (16)+TX, aldicarb (863)+TX, AZ 60541 (compound code) + TX, benclothiazide [CCN] + TX, benomyl (62) + TX, butylpyridaben (synonym) + TX, chlorpyrifos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, thiocarbofuran (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, [unclear text - possibly a compound code] Viagra (999) + TX, Cyclobutrazol + TX, Cytokinin (alias) (210) + TX, Dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, Diamidafos (1044) + TX, Diamidafos (1051) + TX, Diclophos (alias) + TX, Dimethoate (262) + TX, Dolactin (alias) [ [CCN]+TX, Emamectin (291)+TX, Emamectin Benzoate (291)+TX, Irinokine (alias) [CCN]+TX, Phosphate (312)+TX, Dibromoethane (316)+TX, Phosphate (326)+TX, Fenpyrad (alias)+TX, Fonsodium (1158)+TX, Thiazolium (408)+TX, Butylthionine (1196)+TX, Fenpyroxene Aldehyde (synonyms) [CCN]+TX, GY-81 (research code) (423)+TX, phosmet [CCN]+TX, iodomethane (IUPAC name) (542)+TX, isamidophos (1230)+TX, chlorpyrifos (1231)+TX, ivermectin (synonyms) [CCN]+TX, kinetin (synonyms) (210)+TX, methyl pymetrozine (1258)+TX,Vibrio (519)+TX, Vibrio potassium salt (alias) (519)+TX, Vibrio sodium salt (519)+TX, Methyl bromide (537)+TX, Methyl isothiocyanate (543)+TX, Milbexime (alias) [CCN]+TX, Moxifloxacin (alias) [CCN]+TX, Myrothecium verrucaria composition (alias) (565)+TX, NC-184 (compound code)+TX, chlorpyrifos (602)+TX, phorate (636)+TX, phosphatidylcholine (639)+TX, phosmet [CCN]+TX, chlorpyrifos (alias)+TX, silachlor (alias) [CCN]+TX, spinosad (737)+TX, tert-butylcarbate (synonym)+TX, terbufos (773)+TX, tetrachlorothiophene (IUPAC / Chemical Abstracts name) (1422)+TX, thiafenox (synonym)+TX, phosmet (1434)+TX, triazophos (820)+TX, triazophos (synonym)+TX, xylenol [CCN]+TX, YI-5302 (compound code) and zeatin (synonym) (210)+TX, fluensulfone [318290-98-1]+TX, fluopyram+TX;

[0794] The nitration inhibitor is selected from the group consisting of potassium ethyl xanthate [CCN] and nitrapyrin (580) + TX;

[0795] Plant activator selected from the following group of substances: acibenzolar (6)+TX, acibenzo-S-methyl (6)+TX, probenazole (658) and Reynoutria sachalinensis extract (synonym) (720)+TX;

[0796] Rodenticide selected from the group consisting of the following substances: 2-isovaleryl indan-1,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalo-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, α-chlorool [CCN] + TX, aluminum phosphide (640) + TX, antagonist (880) + TX, arsenic trioxide (882) + TX, barium carbonate (891) + TX, daridin (912) + TX, bromadiolone (89) + TX, and bromodiphenyl ether. Bromadiolone (including α-bromadiolone) + TX, bromadiolone (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorpyrifos (140) + TX, cholecalciferol (synonym) (850) + TX, chlorpyrifos (1004) + TX, cyproheptadine (1005) + TX, bromadiolone (175) + TX, pyrimidine (1009) + TX, cyproheptadine (246) + TX, thiamethoxam (249) + TX, bromadiolone (273) + TX, calciferol (301) + T X, fluoroacetamide (357) + TX, fluoroacetamide (379) + TX, fluoroacetidine (1183) + TX, fluoroacetidine hydrochloride (1183) + TX, γ-HCH (430) + TX, HCH (430) + TX, hydrogen cyanide (444) + TX, iodomethane (IUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (IUPAC name) (640) + TX, methyl bromide (537) + TX, phosmet (1318) + TX, phosmet ( 1336)+TX, Phosphine (IUPAC name) (640)+TX, Phosphine [CCN]+TX, Warfarin (1341)+TX, Potassium Arsenite [CCN]+TX, Warfarin (1371)+TX, Onion Glycoside (1390)+TX, Sodium Arsenite [CCN]+TX, Sodium Cyanide (444)+TX, Sodium Fluoroacetate (735)+TX, Strychnine (745)+TX, Thallium Sulfate [CCN]+TX, Warfarin (851) and Zinc Phosphide (640)+TX;

[0797] Synergists selected from the group consisting of the following substances: 2-(2-butoxyethoxy)ethyl piperitate (IUPAC name) (934)+TX, 5-(1,3-benzodioxane-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903)+TX, farnesol with nerolidol (alias) (324)+TX, MB-599 (research code) (498)+TX, MGK 264 (research code) (296)+TX, piperonyl butoxide (649)+TX, piperonal (1343)+TX, propyl isomer (1358)+TX, S421 (research code) (724)+TX, sesamex (1393)+TX, sesasmolin (1394) and sulfoxide (1406)+TX;

[0798] Animal repellents selected from the following groups of substances: anthraquinone (32)+TX, chloralose (127)+TX, copper naphthenate [CCN]+TX, copper oxychloride (171)+TX, diazinon (227)+TX, dicyclopentadiene (chemical name) (1069)+TX, guazatine (422)+TX, guazatine (422)+TX, cypermethrin (530)+TX, pyridine-4-amine (IUPAC name) (23)+TX, silane (804)+TX, trimethacarb (840)+TX, zinc naphthenate [CCN], and zinc thiram (856)+TX;

[0799] The antiviral agent is selected from the following group of substances: Imanin (also known as CCN) and Ribavirin (also known as CCN) + TX;

[0800] The wound protectant is selected from the following group of substances: mercuric oxide (512) + TX, octhilinone (590) and methyl thiophanate (802) + TX;

[0801] Bioactive substances selected from 1,1-bis(4-chloro-phenyl)-2-ethoxyethanol + TX, 2,4-dichlorophenylbenzenesulfonate + TX, 2-fluoro-N-methyl-N-1-naphthylacetamide + TX, 4-chlorophenylphenyl sulfone + TX, acetamiprid + TX, aldicarb + TX, cypermethrin + TX, phosmet + TX, methamidophos + TX, ammonium oxalate + TX, amitraz + TX, dicofol + TX, arsenic trioxide + TX, azobenzene + TX, azophos + TX, benomyl + TX, benzyl benzoate + TX, bifenthrin + TX, bromopyr + TX, and bromopyr + TX. Bromothion + TX, Bromodifen + TX, Thiamethoxam + TX, Butanone + TX, Butanone Sulfonate + TX, Butylpyridinium + TX, Calcium Polysulfide + TX, Camphene Octadec + TX, Chlorfenapyr + TX, Trithion + TX, Acaricide + TX, Dimethoate + TX, Acaricide + TX, Acaricide + TX, Acaricide Hydrochloride + TX, Dichlorvos + TX, Acaricide + TX, Dichlorvos + TX, Ethyl Acetate + TX, Chlormebuform + TX, Diflubenzuron + TX, Propyl Acetate + TX, Chlorpyrifos + TX, Ciprofloxacin I + TX, Ciprofloxacin II + TX, Ciprofloxacin + TX, Clofenac + TX, Phoxim + TX, Clomid + TX, phosmet + TX, thiophanate-methyl + TX, phosmet + TX, DCPM + TX, DDT + TX, phosmet + TX, phosmet-O + TX, phosmet-S + TX, phosmet-S + TX, phosmet-S-methyl + TX, demeton-S-methylsulfon + TX, phosmet + TX, dichlorvos + TX, dichlorvos + TX, chlorpyrifos + TX, methylflufenoxam + TX, dinex + TX, dinex-diclexine + TX, diclexine-4 + TX, diclexine- 6+TX, chlorpyrifos +TX, amyl nitrate +TX, nitroglycerin +TX, nitrate +TX, dichlorvos +TX, sulfadiazine +TX, disulfiram +TX, DNOC +TX, dofenapyn +TX, dofenapyn +TX, phosmet +TX, phosmet +TX, phenoxyacetic acid +TX, fenpyrad +TX, fenpyroximate +TX, fenpyroximate +TX, fenpyroximate +TX, fenpyroximate +TX, fenpyroximate +TX, fentrifanil +TX, flufenoxuron +TX, flufenoxuron +TX, fenpyroximate ...Benzyl ether + TX, cetylcyclopropane carboxylate + TX, methamidophos + TX, jasmine ester I + TX, jasmine ester II + TX, iodophos + TX, lindane + TX, propiconazole + TX, phosmet + TX, dithiamethoxam + TX, methiophene + TX, chlorfenapyr + TX, methyl bromide + TX, methamidophos + TX, milbemime + TX, propanil + TX, phosmet + TX, methamidophos + TX, moxifloxacin + TX, naled + TX, 4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazine-3-one + TX, flufenoxuron + TX, nicotinamide + TX, cyanamide + TX, cyanamide 1:1 zinc chloride complex +TX, Omethoate +TX, Sulfonate +TX, Phosphate +TX, pp'-DDT +TX, Parathion +TX, Permethrin +TX, Fenthion +TX, Phosphate +TX, Phosphamidon +TX, Phosphamidon +TX, Polychloroterpenes +TX, Polynactins +TX, Prochloraz +TX, Carbendazim +TX, Prochloraz +TX, Ethiazophos +TX, Phosphate +TX, Pyrethrin I +TX, Pyrethrin II +TX, Pyrethrin +TX, Pyridaben +TX, Pyrazophos +TX, Pyrimethanil +TX, Pyrimethanil +TX, Quinalphos +TX, Quintiofos +TX, R-149 2+TX, glyphosate+TX, rotenone+TX, octamethrin+TX, chlorpyrifos+TX, silachlor+TX, thiophanate-methyl+TX, SSI-121+TX, sufil+TX, fipronil+TX, thiophanate-methyl+TX, sulfur+TX, flufenoxam+TX, t-flufenoxam+TX, TEPP+TX, terbufos+TX, tetrachlorfon+TX, chlorfenapyr+TX, thiafenoxam+TX, chlorpyrifos+TX, methyl methamidophos+TX, chlorpyrifos+TX, thiamethoxam+TX, chlorpyrifos+TX, fenpyroxetine+TX, triazophos+TX, trichlorfon+TX, trichlorfon+TX, chlorpyrifos+TX, fenpyroxetine+TX, vanil iprole)+TX, cybutanol+TX, copper dioctanoate+TX, copper sulfate+TX, cybutryne+TX, dichloronaphthoquinone+TX, dichlorophenol+TX, cybutanol+TX, triphenyltin+TX, quicklime+TX, sodium mancozeb+TX, cybutanol+TX, cybutanol+TX, cybutanol+TX, cybutanol+TX, simazine+TX, triphenyltin acetate+TX, triphenyltin hydroxide+TX, cypermethrin+TX, piperazine+TX, thiophanate-methyl+TX, chloralose+TX, phosmet+TX, pyridine-4-amine+TX, strychnine+TX, 1-hydroxy-1H-pyridine-2-thione+TX, 4-(quinoxalo-2-ylamino)benzenesulfonamide+TX, 8-hydroxyquinoline sulfate+TX, bromonitrile+TX, copper hydroxide+TXCresol + TX, Dipyridamole + TX, Doxorubicin + TX, Sodium Dichlorophenate + TX, Formaldehyde + TX, Mercuroquine + TX, Kasugamycin + TX, Kasugamycin Hydrochloride Hydrate + TX, Di(Dimethyldithiocarbamate) Nickel + TX, Trichloromethylpyridine + TX, Octethiazoline + TX, Oxytetracycline + TX, Potassium Hydroxyquinoline Sulfate + TX, Thiamethoxam + TX, Streptomycin + TX, Streptomycin Sesquisulfate + TX, Leaf Blight + TX, Thimerosal + TX, Cotton Brown Leaf Roller GV + TX, Agrobacterium radiata + TX, Amblyseius species + TX, Celery Noctuid moth NPV + TX, Protoceratops spp. + TX, Short-spurred Aphids + TX, Cotton Aphid Parasitic Wasp + TX, Aphid Gall Moth + TX, Alfalfa Silver-striped Noctuid moth NPV + TX, Bacillus spheroides + TX, Beauveria bassiana + TX, common lacewing + TX, *Cryptocoryne mongolica* + TX, codling moth GV + TX, *Siberian chastes parasitic wasp* + TX, pea leafminer wasp + TX, *Encarsia formosa* + TX, *Aphidius spp.* + TX, *Heterotrophic nematode* and *Heterotrophic nematode* + TX, *Spotted long-legged ladybug* + TX, *Citrus citrus scale parasitic wasp* + TX, mirid bug + TX, *Calophyllum noctuid moth* NPV + TX, *Broad-stalked flea wasp* + TX, *Metarhizium anisopliae* + TX, *Metarhizium anisopliae* microsporum variety + TX, *Neopyrhinus cerana* NPV and *Neopyrhinus rubescens* NPV + TX, *Stereophora* species + TX, *Paecilomyces flavus* + TX, *Physeieus chiaretus* + TX, hairy nematode + TX, *Stereophora stylosa* + TX, *Stereophora stylosa* + TX, *Nematophora griseus* + TX, *Stereophora stylosa ... riobravis+TX, *Strombus stearothermiae* +TX, *Strombus stearothermiae* species +TX, *Trichogramma* species +TX, *Vibrio vulnificus* +TX, *Verticillium clavatum* +TX, azirphosphazine +TX, bis(aziridine)methylaminophosphonate sulfide +TX, busulfan +TX, dimeltifol +TX, hexamethylmelamine +TX, hexamethylphosphine +TX, methylthiophosphine +TX, methylthiophosphine +TX, methylazirphosphazine +TX, styramine +TX, flufenoxuron +TX, thiophosphine +TX, thiophosphine +TX, tratamine +TX, urethaneimine +TX, (E)-dec-5-en-1-ylacetate and (E)-dec-5-en-1-ol +TX, (E)-tetrate-4-en-1-yl acetate +TX, (E)-6-methylhept-2-en-4-ol +TX, (E,Z)-tetradecane-4,10-dien-1-yl acetate +TX, (Z)-dodecane-7-en-1-yl acetate +TX, (Z)-hexadecane-11-enal +TX, (Z)-hexadecane-11-en-1-yl acetate +TX, (Z)-hexadecane-13-en-11-ynyl acetate +TX, (Z)-eicosode-13-en-10-one +TX, (Z)-tetradecane-7-en-1-al +TX, (Z)-tetradecane-9-en-1-ol +TX(Z)-Tetradecano-9-en-1-yl acetate + TX, (7E,9Z)-Dodeca-7,9-dien-1-yl acetate + TX, (9Z,11E)-Tetradecano-9,11-dien-1-yl acetate + TX, (9Z,12E)-Tetradecano-9,12-dien-1-yl acetate + TX, 14-Methyloctadecano-1-ene + TX, 4-Methylnon-5-ol and 4-Methylnon-5-one + TX, α-polystyrin + TX, western pine bark beetle pheromone + TX, dodecadienol + TX, cyproterone + TX, cyclohexane + TX, cyclohexane + TX, dodecano-8-en-1-yl acetate + TX, dodecano- -9-en-1-yl acetate + TX, dodecano-8 + TX, 10-dien-1-yl acetate + TX, dominicalure + TX, ethyl 4-methyloctanoate + TX, eugenol + TX, Southern pine bark beetle pheromone + TX, attractant ene mixture + TX, attractant ene mixture I + TX, attractant ene mixture II + TX, attractant ene mixture III + TX, attractant ene mixture IV + TX, hexane attractant + TX, bark beetle dienol + TX, small beetle enol + TX, scarab beetle sex pheromone + TX, trimethyldioxane + TX, litlure + TX, white armyworm sex pheromone + TX, attractant ester + TX, megatomoic Acid + TX, Insecticidal Ether + TX, Insecticidal Enzyme + TX, Octadec-2,13-dien-1-yl Acetate + TX, Octadec-3,13-dien-1-yl Acetate + TX, Hecombi + TX, Coconut Beetle Aggregating Pheromone + TX, Filacon + TX, Insecticidal Ring + TX, Sordidin + TX, Fungicidal Entrainer + TX, Tetradecano-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 C + TX, Trunc-Call + TX, 2-(Octylthio)-ethanol + TX, DEET + TX, Butoxy(polypropylene glycol) + TX, Dibutyl Adipate + TX, dibutyl phthalate + TX, dibutyl succinate + TX, DEET + TX, mosquito repellent + TX, dimethyl phthalate + TX, ethylhexanediol + TX, hexane + TX, methylquinoline + TX, methylneodecanamide + TX, oxaloate + TX, picaridin + TX, 1-dichloro-1-nitroethane + TX, 1,1-dichloro-2,2-di(4-ethylphenyl)-ethane + TX, 1,2-dichloropropane and 1,3-dichloropropene + TX, 1-bromo-2-chloroethane + TX, 2,2,2-trichloro-1-(3,4-dichloro-phenyl)ethyl acetate + TX, 2,2-dichlorovinyl-2-ethylsulfinyl ethyl methyl phosphate + TX, 2-(1,3-dithiopentane-2-yl)phenyl dimethyl carbamate + TX,2-(2-Butoxyethoxy)ethyl thiocyanate + TX, 2-(4,5-dimethyl-1,3-dioxolane-2-yl)phenylmethylcarbamate + TX, 2-(4-chloro-3,5-dimethylmethyloxy)ethanol + TX, 2-chlorovinyl diethyl phosphate + TX, 2-imidazolinone + TX, 2-isovaleryl indan-1,3-dione + TX, 2-methyl(prop-2-ynyl)aminophenylmethylcarbamate + TX, 2-cyanothioethyl laurate + TX, 3-bromo-1-chloroprop-1-ene + TX, 3-methyl-1-phenylpyrazole-5-yldimethylamino Carbamate + TX, 4-methyl(prop-2-ynyl)amino-3,5-xylylmethylcarbamate + TX, 5,5-dimethyl-3-oxocyclohex-1-enyldimethylcarbamate + TX, asethion + TX, acrylonitrile + TX, aldrin + TX, chlorpyrifos + TX, α-decanoic acid + TX, aluminum phosphide + TX, chlorpyrifos + TX, neonicotinoid + TX, ethyl phosphide + TX, methyl pyridinium + TX, Bacillus thuringiensis δ-endotoxin + TX, barium hexafluorosilicate + TX, barium polysulfide + TX Cypermethrin + TX, Bayer 22 / 190 + TX, Bayer 22408 + TX, β-cyhalothrin + TX, β-cypermethrin + TX, bioethanomethrin + TX, permethrin + TX, bis(2-chloroethyl) ether + TX, borax + TX, bromophenylenephos + TX, bromo-DDT + TX, cypermethrin + TX, chlorpyrifos + TX, butathiofos + TX, butyl phosphate + TX, calcium arsenate + TX, calcium cyanide + TX, carbon disulfide + TX, carbon tetrachloride + TX, batamethrin hydrochloride + TX Cevadine + TX, Borneol + TX, Chlordane + TX, Decachlorophenone + TX, Chloroform + TX, Chloropicrin + TX, Chloronitrile Oxime + TX, Chlorprazophos + TX, Cis-resmethrin + TX, Cismethrin + TX, Clocythrin (another name) + TX, Copper Acetate Arsenite + TX, Copper Arsenate + TX, Copper Oleate + TX, Coumithoate + TX, Cryolite + TX, CS 708+TX, benzoylphos +TX, fenitrothion +TX, pyrethrum +TX, cypermethrin +TX, d-methoxyfenozide +TX, DAEP +TX, dazomet +TX, decarbofuran +TX, chlorpyrifos +TX, isochlorpyrifos +TX, chlorpyrifos +TX, dicresyl +TX, cyclopyrronium +TX, dieldrin +TX, diethyl-5-methylpyrazol-3-yl phosphate +TX, dior +TX, tetrafluoromethrin +TX, dimethoate +TX,Benzylpyrethrin + TX, Methyl chlorpyrifos + TX, Difenoconazole + TX, Pronitrophenol + TX, Pentylnitrophenol + TX, Diphenoxyethanol + TX, Benzylphos + TX, Phosphate + TX, Thiamethoxam + TX, DSP + TX, Ecstatone + TX, EI 1642 + TX, EMPC + TX, EPBP + TX, Etaphos + TX, Ethyl formate + TX, Dibromoethane + TX, Dichloroethane + TX, Ethylene oxide + TX, EXD + TX, Fenoxacrim + TX, Ethyl carbendazim + TX, Fenitrothion + TX, Fenoxacrim + TX, Cypermethrin + TX, Fonsophos + TX, Ethyl thion + TX, Flucofuron + TX, Butylphosphide + TX, Phosphate + TX, Butylphosphide + TX, Furazolidone + TX, Pyrethroids +TX, Biguanide Octyl Salt +TX, Biguanide Octyl Acetate +TX, Sodium Tetrathiocarbonate +TX, Benzylfentanyl +TX, HCH +TX, HEOD +TX, Heptachlor +TX, Phosphate +TX, HHDN +TX, Hydrogen Cyanide +TX, Quinoline +TX, IPSP +TX, Chlorpyrifos +TX, Carbochlor +TX, Isofenphos +TX, Isofenphos +TX, Transplanting Agent +TX, Isoprothiolane +TX, Oxadiazon +TX, Juvenile Hormone I +TX, Juvenile Hormone II +TX, Juvenile Hormone III +TX, Chlorpentine +TX, Acetaminophen +TX, Lead Arsenate +TX, Bromobenzyl + TX, Acetaminophen + TX, Thiazolium + TX, m-isopropylphenyl methyl carbamate + TX, Magnesium phosphide + TX, Azoxystrobin + TX, Methyl phosphonate + TX, Phosphorus + TX, Mercurous chloride + TX, Methyl sulfoxide + TX, Potassium phosphonate + TX, Sodium phosphonate + TX, Methylsulfonyl fluoride + TX, Butenyl phosphonate + TX, Methoprene + TX, Permethrin + TX, Methoxydextrin + TX, Methyl isothiocyanate + TX, Methyl chloroform + TX, Dichloromethane + TX, Pyrimethanil + TX, Miperazine + TX, Naphthalene + TX, NC-1 70+TX, Nicotine+TX, Nicotine Sulfate+TX, Nitrothiazide+TX, Protonicine+TX, O-5-Dichloro-4-iodophenyl O-ethyl ethyl thiophosphonate+TX, O,O-Diethyl O-4-methyl-2-oxo-2H-benzopyran-7-yl thiophosphonate+TX, O,O-Diethyl O-6-methyl-2-propylpyrimidin-4-yl thiophosphonate+TX, O,O,O',O'-Tetrapropyl dithiopyrophosphate+TX, Oleic Acid+TX, p-Dichlorobenzene+TX, Methyl parathionine+TX, Pentachlorophenol+TX, Pentachlorophenyl Laurate+TX, pH 60-38+TX, fenthion+TX, parachlorpyrifos+TX, phosphine+TX, methyl phoxim+TX, methamidophos+TX, polychlorinated dicyclopentadiene isomer+TX, potassium arsenite+TX, potassium thiocyanate+TX, precocious pruning agent I+TX, precocious pruning agent II+TX,Precocious Pruning Agent III + TX, Aminopyrimidine Phosphate + TX, Procymidone + TX, Mancozeb + TX, Propyridaben + TX, Pyraclostrobin + TX, Pyrethrum + TX, Quassia Extract + TX, Quinalphos-Methyl + TX, Phoxim + TX, Iodophos + TX, Benzylfuran + TX, Rotenone + TX, Thiamethoxam + TX, Rianodine + TX, Sabadilla + TX, Octylphosphide + TX, Ketoconazole + TX, SI-0009 + TX, Thiamethoxam + TX, Sodium Arsenite + TX, Sodium Cyanide + TX, Sodium Fluoride + TX, Sodium Hexafluorosilicate + TX, Sodium Pentachlorophenolate + TX, Sodium Selenate + TX, Sodium Thiocyanate + TX, Sulfobenzyl Oxide (su 1, ... X, tebufenozide + TX, veratrine + TX, veratrine + TX, XMC + TX, zetamethrin + TX, zinc phosphide + TX, pyraclostrobin + TX, chlorpyrifos + TX, tetrafluoromethrin + TX, bis(tributyltin)oxide + TX, bromoacetamide + TX, ferric phosphate + TX, niclosamide-ethanolamine + TX, tributyltin oxide + TX, pyrmorpholine + TX, serotonin + TX, 1,2-dibromo-3-chloropropane + TX, 1,3-dichloropropene + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide + TX, 3-(4-chlorophenyl)-5-methylrhodanine + TX, 5-methyl-6-thio-1,3,5-thiadiazin-3-ylacetic acid + TX, 6-isopentenyl Aminopurine +TX, anisiflupurin +TX, phenylchlorothiazide +TX, cytokinin +TX, DCIP +TX, furfural +TX, isoamylphosphine +TX, kinetin +TX, *Lysimachia christinae* composition +TX, tetrachlorothiophene +TX, xylenol +TX, zeatin +TX, potassium ethyl xanthate +TX, aramidoylbenzene +TX, aramidoylbenzene-S-methyl +TX, Polygonum cuspidatum extract +TX, α-chlorool +TX, antagonist +TX, barium carbonate +TX, dimethomorph +TX, bromadiolone +TX, bromadiolone +TX, bromadiolone +TX, bromadiolone +TX, chlorpyrifos +TX, cholecalciferol +TX, chlorpyrifos +TX, cymoxanil +TX, cymoxanil +TX, cymoxanil +TX, cymoxanil +TX, cymoxanil +TXFiberam + TX, Fiberam + TX, Calcium alcohol + TX, Fluorine + TX, Fluoroacetamide + TX, Fluorine + TX, Fluorine hydrochloride + TX, Fiberam + TX, Rat parathion + TX, Phosphate + TX, Rat chlorpyrifos + TX, Rat chlorpyrifos + TX, Rat chlorpyrifos + TX, Onion glycoside + TX, Sodium fluoroacetate + TX, Thallium sulfate + TX, Fiberam + TX, 2-(2-butoxyethoxy)ethyl piperine + TX, 5-(1,3-benzodioxane-5-yl)-3-hexylcyclohex-2-enone + TX, Farnesol with nerolidol + TX, Synergistic alkyne + TX, MGK 264+TX, Piperyl Butyl Ether+TX, Synergistic Aldehyde+TX, Propyl Isomer+TX, S421+TX, Synergistic Powder+TX, Sesamin+TX, Sulfoxide+TX, Anthraquinone+TX, Copper Naphthenate+TX, Copper Oxide+TX, Dicyclopentadiene+TX, Ciprofloxacin+TX, Zinc Naphthenate+TX, Zinc Ferroxetine+TX, Imanin+TX, Ribavirin+TX, Chlorindolehydrazine+TX, Mercuric Oxide+TX, Methyl Thiophanate+TX, Azaconazole+TX, Bifenthrin+TX, Fenoxacillin+TX, Cycloconazole+TX, Difenoconazole+TX, Tebuconazole+TX, Fluorocyclic Azoxystrobin + TX, cyproconazole + TX, fluquinazole + TX, flusilazole + TX, tebuconazole + TX, furazolidone + TX, hexaconazole + TX, imazalil + TX, imazalil + TX, tebuconazole + TX, cyproconazole + TX, paclobutrazol + TX, isoprothiolane + TX, tebuconazole + TX, prothioconazole + TX, pyrifenoxam + TX, prochloraz + TX, propiconazole + TX, pyraclostrobin + TX, simeconazole + TX, tebuconazole + TX, flufenoxuron + TX, triadimefon + TX, triadimefon + TX Fluopyram + TX, tebuconazole + TX, pyrimidinol + TX, chlorophenylpyrimidinol + TX, fluphenylpyrimidinol + TX, bupirimate + TX, dimethirimol + TX, ethirimol + TX, dodecyl morpholine + TX, fenpropidin + TX, butyl morpholine + TX, spirocyclam + TX, tridemorpholine + TX, azoxystrobin + TX, azoxystrobin + TX, pyrimethanil + TX, seed dressing + TX, fludioxonil + TX, benalaxyl+TX, furaxyl+TX, metalaxyl+TX, R-metalaxyl+TX, furazolidone+TX, oxadixyl+TX, carbendazim+TX, debacarb+TX, tebuconazole+TX, thiabendazole+TX, chlozolinate+TX, dichlozoline+TX, myclozoline+TX, procymidone+TXVinclozoline + TX, boscalid + TX, carbendazim + TX, methomyl + TX, flutolanil + TX, oxadiazon + TX, oxychloride + TX, penthiopyrad + TX, thifluzamide + TX, doxycycline + TX, biguanidine + octylamine + TX, azoxystroburin + TX, ethoxystroburin + TX, fluopyram + TX, fluopyram + TX, ethoxystroburin + TX, azoxystroburin + TX, fenoxystroburin + TX, azoxystroburin + TX, azoxystroburin + TX, azoxystroburin + TX, azoxystroburin + TX, azoxystroburin + TX, pyraclostroburin +TX, azoxystrobin +TX, ferrous sulfate +TX, mancozeb +TX, mancozeb +TX, mancozeb +TX, methyl mancozeb +TX, mancozeb +TX, captan +TX, captan +TX, fenvalerate +TX, fenvalerate +TX, fenvalerate +TX, methyl thiophanate +TX, Bordeaux mixture +TX, copper oxide +TX, mancozeb +TX, quinoline copper +TX, phthalimide +TX, chlorpyrifos +TX, isoprothiolane +TX, chlorpyrifos +TX, methyl thiophanate +TX, fenpyroximate +TX, benomyl +TX, blasticidin +TX, chloroneb +TX, chlorothalonil +TX, cyclobutr +TX, cymoxanil +TX, cyclobutr ifluram+TX, diclocymet+TX, diclomezine+TX, dicloran+TX, diethofencarb+TX, dimethomorph+TX, flumorph+TX, dithianon+TX, ethaboxam+TX, etridiazole+TX, oxadiazon+TX, fenamidone+TX, fenoxanil+TX, ferimzone+TX, fluazinam+TX Flumetylsulforim + TX, fluopicolide + TX, fluoxytioconazole + TX, flusulfamide + TX, fluoxetine + TX, cyclophosphamide + TX, fosetyl-aluminium + TX, hymexazol + TX, propineb + ​​TX, cyazofamid + TX, methasulfocarb + TX, benomyl + TX, pencycuron + TX, phthalide + TX, polyoxins + TXPropamocarb + TX, Pyrafenoxam + TX, Proquinazid + TX, Pyroquilon + TX, Pyriofenone + TX, Quinoxal + TX, Pentachloronitrobenzen + TX, Thiamethoxam + TX, Triazol + TX, Tricyclazole + TX, Azoxystrobin + TX, Enteromycin + TX, Valamid + TX, Zoxamide + TX, Mandipropamid + TX, Flubeneteram + TX, Isopyrazam + TX, Fluoxetine Sedaxane + TX, Benzylfluopyram + TX, Fluopyram + TX, 3-Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro-biphenyl-2-yl)-amide + TX, Isoflucypram + TX, Isothiazine + TX, Dipymetitrone + TX, 6-Ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithia[1,2-c]isothiazolidin-3-carboxynitrile + 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-Formonitrile + 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-pyrazole-3-amine + TX, 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine + TX, fluindapyr + TX, jiaxiangjunzhi + TX, lvbenmixianan + TX, dichlobentiazox + TX, mandestrob In addition to TX, the following are also listed: 3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinoline-1-yl)quinolone + TX, 2-[2-fluoro-6-[(8-fluoro-2-methyl-3-quinolinyl)oxy]phenyl]prop-2-ol + TX, oxathiapiprolin + TX, N-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]tert-butyl carbamate + TX, piraziflumid + TX, inpyrfluxam + TX, trolprocarb + TX, chlorfluazuron + TX, and 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-formamidin + TX, N'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidin + TX, [2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazole-1-yl]acetyl]-4-piperidinyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chloro-phenyl]methanesulfonate + TX, N-[6-[[(Z)-[(1-methyltetrazole-5-yl)- [Phenylene-methylene]amino]oxymethyl]-2-pyridyl]carbamate butyl-3-yne ester + TX, N-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamate methyl ester + TX, 3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine + TX, pyridachlometyl + TX, 3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 1-[2-[[1-(4-chlorophenyl)pyrazole-3-yl]oxymethyl]-3-methyl-phenyl]-4-methyl-tetrazol-5-one + TX, 1-methyl-4-[3- Methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]tetrazole-5-one+TX, aminopyrifen+TX, azoxystrobin+TX, indazolesulfonamide+TX, fluopyram-aniline+TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamine+TX, florylpicoxamid+TX, fenpicoxamid+TX, metarylpicoxamid+TX, isobutylethoxyquinoline+TX, ipflufenoquin+TX, quinofum Elin+TX, Isoprothiamethoxam+TX, N-[2-[2,4-dichloro-phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide+TX, N-[2-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide+TX, Benzothiamethoxam+TX, Cyazofamid+TX, 5-amino-1,3,4-thiadiazole-2-thiol zinc salt (2:1)+TX, Fluopyram+TX, Flufenoxadiazam+TX, Flufenoxadiazam+TX, Fluopyram+TX, Pyrapropoyne+TX, Piperazon+TX2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indane-4-yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylindane-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, 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylindane-4-yl) α-(1,1-dimethylethyl)-α-[4'-(trifluoromethoxy)[1,1'-diphenyl]-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-(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-thioalkyl-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-thio-4H-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, anti-dampness ester + TX, eugenol + TX, kasugamycin + TX, thiamethoxam + TX, thiamethoxam + TX, metronidazole zinc + TX, amectotractin + TX, iprodione + TX, octochlor + TX; N'-[5-bromo-2-methyl-6-[(1S)-1 [-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidin + TX, N'-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidin + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidin + TX, N'-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidin + TX,N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-isopropyl-N-methyl-formamidin + TX (these compounds can be prepared by the method described in WO2015 / 155075); N'-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidin + TX (this compound can be prepared by IPCOM00) Prepared by the method described in 0249876D); N-isopropyl-N'-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidin + TX, N'-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidin + TX (these compounds can be prepared by WO Prepared by the method described in 2018 / 228896); N-ethyl-N'-[5-methoxy-2-methyl-4-[(2-trifluoromethyl)oxetane-2-yl]phenyl]-N-methyl-formamidin + TX, N-ethyl-N'-[5-methoxy-2-methyl-4-[(2-trifluoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidin + TX (these compounds can be prepared by WO (Prepared by the method described in 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-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 + TXN-((1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide + TX (these compounds can be prepared by the method described in 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-dimethylpyra...

Claims

1. A compound having formula (I): (I)， in Q is a group selected from the group consisting of: formulas Qa, Qb, and Qc. ， The arrow indicates the attachment point to the nitrogen atom in the tricyclic ring; And where A represents N; X is SO2; R1 is a C1-C4 alkyl group; Where Q is Qa: R2 is hydrogen; Q1 is hydrogen, halogen, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, C1-C6 cyanoalkyl, C1-C6 cyanoalkoxy, C1-C6 haloalkoxy, -N(R3)2, -N(R3)COR4, -N(R3)CON(R3)2, (oxazolidin-2-one)-3-yl or 2-pyridinyloxy; Each R3 is independently hydrogen or C1-C4 alkyl; R4 is a C1-C6 alkyl or a C3-C6 cycloalkyl; Q1 is a five- to six-membered aromatic ring system with a ring carbon atom connected to a ring containing a substituent A, wherein the ring system is unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and the ring system may contain one or two cyclic nitrogen atoms; or Q1 is a five-membered aromatic ring system in which a ring containing a substituent A is attached via a cyclic nitrogen atom, the ring system being unsubstituted or monosubstituted with substituents selected from the group consisting of halogens and C1-C4 haloalkyl groups; and the ring system containing 2 or 3 cyclic nitrogen atoms; Where Q is Qb: R2 is hydrogen; Q1 is cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl; C1-C6 haloalkoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl that can be monosubstituted by cyanocyclopropyl; N-linked pyrazolyl that can be monosubstituted by chlorine; C-linked pyrazolyl that is N-substituted by cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole that can be monosubstituted by cyclopropyl; and C-linked isoxazole that can be monosubstituted by cyclopropyl; and Where Q is Qc: R5 is a C1-C4 alkyl group; R6 is hydrogen, halogen, C3-C6 cycloalkyl, C1-C6 haloalkoxy, -CO(NR3R4), or -NR3COR4; wherein each R3 is independently C1-C4 alkyl; and R4 is independently C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 haloalkoxy; or R6 is a five-membered heteroaromatic ring system connected to an imidazole ring via a ring nitrogen atom. This imidazole ring is connected to a substituent R5. The ring system is unsubstituted or monosubstituted by substituents selected from the group consisting of: Halogen, C3-C6 cycloalkyl or C1-C4 haloalkyl, wherein the ring system contains two cyclic nitrogen atoms; or R6 is a five- to six-membered partially saturated, aromatic or heteroaromatic ring system connected to an imidazole ring via a ring carbon atom, the imidazole ring being connected to a substituent R5, the ring system being unsubstituted or monosubstituted by substituents selected from the group consisting of: C1-C4 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl monosubstituted with cyano, (C3-C8)cycloalkyl-(C1-C6)alkyl-, or (C3-C8)cycloalkyl monosubstituted with cyano-(C1-C6)alkyl-, and the ring system may contain two cycloheteratomes selected from the group consisting of nitrogen and oxygen, wherein the ring system may not contain more than one epoxy atom; Or an agriculturally chemically acceptable salt of a compound having formula I.

2. The compound having formula I according to claim 1, wherein the compound is represented by: compounds having formula I-A1: Wherein A, R1, R2, X, Q1, R3 and R4 are as defined in Formula I as claimed in claim 1, and Q is Qa, or are chemically acceptable salts thereof.

3. The compound having formula I according to claim 1, wherein the compound is represented by: compounds having formula I-A2: Wherein A, R1, R2, X, Q1, R3 and R4 are as defined in Formula I as claimed in claim 1, where Q is Qb, or are chemically acceptable salts thereof.

4. The compound having formula I according to claim 1, wherein the compound is represented by: a compound having formula I-B1: X, R1, R3, R4, R5 and R6 are as defined in Formula I and Q is Qc as claimed in claim 1, or are chemically acceptable salts thereof.

5. The compound according to claim 1, wherein R5 is methyl or ethyl.

6. The compound according to claim 1, wherein: R1 is an ethyl group.

7. The compound according to any one of claims 1 or 2, wherein: Q is Qa; and Q1 is selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl; C1-C6 haloalkoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl monosubstituted by cyanocyclopropyl; N-linked pyrazolyl monosubstituted by chlorine; C-linked pyrazolyl monosubstituted by cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole monosubstituted by cyclopropyl; and C-linked isoxazole monosubstituted by cyclopropyl.

8. The compound according to any one of claims 1 or 3, wherein: Q is Qb; Q1 represents cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-(1-cyanocyclopropyl)phenyl ; 3-chloro-pyrazole-1-yl; 4-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

9. The compound according to any one of claims 1 or 4, wherein: Q stands for Qc; R6 is selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl; C1-C6 haloalkoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl monosubstituted with cyanocyclopropyl; N-linked pyrazolyl monosubstituted with chlorine; C-linked pyrazolyl monosubstituted with cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole monosubstituted with cyclopropyl; and C-linked isoxazole monosubstituted with cyclopropyl.

10. The compound according to claim 1, wherein: R6 is hydrogen, cyclopropyl, 2,2,2-trifluoroethoxy, -CONCH3(CH2CF3), -N(CH3)COCH2CF3, or a substituent selected from J1 to J12. 。 11. The compound having formula I according to claim 1, wherein the compound is represented by: a compound having formula I: (I-C), in Q is a group selected from the following groups: formulas Qa-1, Qb-1, and Qc-1. ， The arrow indicates the attachment point to the nitrogen atom in the tricyclic ring; And among them R5 is a C1-C6 alkyl group; and Q1 and R6 are each independently selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; C1-C6 haloalkyl; C1-C6 haloalkoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl monosubstituted with cyanocyclopropyl; N-linked pyrazolyl monosubstituted with chlorine; C-linked pyrazolyl monosubstituted with cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole monosubstituted with cyclopropyl; and C-linked isoxazole monosubstituted with cyclopropyl.

12. The compound having formula I according to claim 11, wherein R5 is methyl or ethyl; and Q1 and R6 are each independently selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; trifluoromethyl; difluoroethyl; trifluoroethoxy; difluoropropoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl monosubstituted with cyanocyclopropyl; N-linked pyrazolyl monosubstituted with chlorine; C-linked pyrazolyl monosubstituted with cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole monosubstituted with cyclopropyl; and C-linked isoxazole monosubstituted with cyclopropyl.

13. The compound having formula I according to claim 11, wherein R5 is a methyl group; and Q1 and R6 are each independently selected from the group consisting of: cyclopropyl; cyanocyclopropyl; cyanoisopropyl; cyanoisopropoxy; trifluoromethyl; difluoroethyl; trifluoroethoxy; difluoropropoxy; -N(CH3)COCH3; N-linked triazolyl; C-linked pyrimidinyl; phenyl monosubstituted with cyanocyclopropyl; N-linked pyrazolyl monosubstituted with chlorine; C-linked pyrazolyl monosubstituted with cyclopropyl, -CHF2, -CH2CHF2, -CH2CF3, -(CH2)-cyclopropyl or -(CH2)-cyanocyclopropyl; C-linked dihydroisoxazole monosubstituted with cyclopropyl; and C-linked isoxazole monosubstituted with cyclopropyl.

14. The compound according to any one of claims 1, 2, 3, 5, 6 or 11, wherein: Q1. Choose from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3- Chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

15. The compound according to any one of claims 1, 2, 3, 5, 6 or 11, wherein: Q1 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; 1,2,4-triazol-4-yl; pyrimidin-5-yl; and pyrimidin-2-yl.

16. The compound according to any one of claims 1, 4, 5, 6 or 11, wherein: R6 is selected from the group consisting of: cyclopropyl; 1-cyanocyclopropyl; 1-cyano-1-methyl-ethyl; 1-cyano-1-methyl-ethoxy; trifluoromethyl; 1,1-difluoroethyl; 2,2,2-trifluoroethoxy; 2,2-difluoropropoxy; -N(CH3)COCH3; 1,2,4-triazol-1-yl; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3- Chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

17. The compound according to any one of claims 1, 4, 5, 6 or 11, wherein: R6 is selected from the group consisting of: cyclopropyl; 2,2,2-trifluoroethoxy; pyrimidin-5-yl; pyrimidin-2-yl; 4-(1-cyanocyclopropyl)phenyl; 3-(1-cyanocyclopropyl)phenyl; 3-chloro-pyrazole-1-yl; 4-chloro-pyrazole-1-yl; 1-cyclopropylpyrazole-4-yl; 1-difluoromethylpyrazole-4-yl; 1-(2,2-difluoroethyl)pyrazole-4-yl; 1-(2,2,2-trifluoroethyl)pyrazole-4-yl; 1-cyclopropylmethylpyrazole-4-yl; 1-(1-cyanocyclopropylmethyl)pyrazole-4-yl; 3-cyclopropyl-4,5-dihydro-isoxazole-5-yl; and 3-cyclopropyl-isoxazole-5-yl.

18. The compound having formula I according to claim 1, wherein the compound is selected from the group consisting of: 1-[6-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindol-6-yl)-5-ethylsulfonyl-3-pyridyl]cyclopropanecarboxylon (compound P1); 1-[4-[4-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindol-6-yl)-5-ethylsulfonyl-1-methyl-imidazol-2-yl]phenyl]cyclopropanecarboxylon (compound P2); 6-[2-(3-cyclopropyl-4,5-dihydroisooxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindol-6 ... Heterocyclopentenzo[4,5-f]isoindole-7-one (compound P3); 6-[2-[1-(2,2-difluoroethyl)pyrazol-4-yl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopentenzo[4,5-f]isoindole-7-one (compound P4); 1-[[4-[4-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopentenzo[4,5-f]isoindole-6-yl)-5-ethylsulfonyl-1-methyl-imidazol-2-yl]pyrazol-1-yl]methyl]cyclopropanecarboxylate (compound P5); 6-[5-ethylsulfonyl-1-methyl- 2-(2,2,2-trifluoroethoxy)imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P6); 6-(5-ethylsulfonyl-1-methyl-2-pyrimidin-5-yl-imidazol-4-yl)-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P7); 6-[3-ethylsulfonyl-5-(2,2,2-trifluoroethoxy)-2-pyridyl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P8); 6-[2-[1 -(cyclopropylmethyl)pyrazol-4-yl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P9); 6-(6-cyclopropyl-3-ethylsulfonyl-2-pyridyl)-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P10); 6-[3-ethylsulfonyl-6-(1,2,4-triazol-1-yl)-2-pyridyl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P11).6-[5-(2,2-difluoropropoxy)-3-ethylsulfonyl-2-pyridyl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P12); 6-[3-ethylsulfonyl-5-(trifluoromethyl)-2-pyridyl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P13); 6-[5-ethylsulfonyl-1-methyl-2-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P) 14); 6-(5-ethylsulfonyl-1-methyl-2-pyrimidin-2-yl-imidazol-4-yl)-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P15); 6-(3-ethylsulfonyl-6-pyrimidin-2-yl-2-pyridyl)-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P16); 6-[2-(1-cyclopropylpyrazol-4-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenten[4,5-f]isoindole-7-one (compound P17); N-[6-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindole-6-yl)-5-ethylsulfonyl-3-pyridyl]-N-methyl-acetamide (compound P18); 6-(5-cyclopropyl-3-ethylsulfonyl-2-pyridyl)-2,2-difluoro-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindole-7-one (compound P19); 6-[2-[1-(difluoromethyl)pyrazol-4-yl]-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindole-7-one (compound P20). 6-[2-(3-chloropyrazol-1-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopentenon[4,5-f]isoindole-7-one (compound P21); 2-[6-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopentenon[4,5-f]isoindole-6-yl)-5-ethylsulfonyl-3-pyridyl]-2-methyl-propionitrile (compound P22); 6-[5-(1,1-difluoroethyl)-3-ethylsulfonyl-2-pyridyl]-2,2-difluoro-5H-[1,3]m-dioxacyclopentenon[4,5-f]isoindole-7-one (compound P23);6-(2-Cyclopropyl-5-ethylsulfonyl-1-methyl-imidazol-4-yl)-2,2-difluoro-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindol-7-one (compound P24); 2-[[6-(2,2-difluoro-7-oxo-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindol-6-yl)-5-ethylsulfonyl-3-pyridinyl]oxy]-2-methyl-propionitrile (compound P25); and 6-[2-(3-Cyclopropylisoxazol-5-yl)-5-ethylsulfonyl-1-methyl-imidazol-4-yl]-2,2-difluoro-5H-[1,3]m-dioxacyclopenteno[4,5-f]isoindol-7-one (compound P26).

19. A composition comprising an effective amount of an insecticidal, acaricidal, nematicidal, or molluscicidal compound having formula (I) as defined in any one of claims 1-18, or an agriculturally chemically acceptable salt thereof, and optionally, an adjuvant or diluent.

20. A method for non-therapeutic purposes of combating and controlling insects, mites, nematodes or mollusks, the method comprising applying to the pest, the site of the pest, or plants susceptible to pest attack an effective amount of an insecticidal, acaricidal, nematicidal or molluskalidal compound of formula (I) as defined in any one of claims 1-18, or an agriculturally chemically acceptable salt thereof, or a composition as defined in claim 19.

21. A method for protecting plant propagation material from insects, mites, nematodes, or mollusks, the method comprising treating the propagation material or the site where the propagation material is grown with the composition of claim 19.

22. A compound having the formula IX-a (IX-a), in R1 and X are as defined under formula I of claim 1; and Q 1a It is trifluoromethyl, 1,1-difluoroethyl or -N(CH3)COCH3.

23. A compound having formula VI (WE), in LG2 is a leaving group; and R is a C1-C6 alkyl, benzyl, or phenyl.

24. The compound having formula VI according to claim 23, wherein LG2 is bromine or chlorine; and R is methyl or ethyl.

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