WO2023007429A1 - Preparation of phenyl sulfilimines or sulfoximines containing thiazolyl-piperidinyl compounds and intermediates thereof - Google Patents

Preparation of phenyl sulfilimines or sulfoximines containing thiazolyl-piperidinyl compounds and intermediates thereof Download PDF

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WO2023007429A1
WO2023007429A1 PCT/IB2022/057001 IB2022057001W WO2023007429A1 WO 2023007429 A1 WO2023007429 A1 WO 2023007429A1 IB 2022057001 W IB2022057001 W IB 2022057001W WO 2023007429 A1 WO2023007429 A1 WO 2023007429A1
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formula
compound
salts
alkyl
cycloalkyl
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PCT/IB2022/057001
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French (fr)
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Sanjay Maruti MADURKAR
Dipak Jaysing DHAWADE
Anup Manikrao JAWALEKAR
Pranab Kumar Patra
Alexander Guenther Maria KLAUSENER
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Pi Industries Ltd.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • the present invention relates to a process for the preparation of phenyl sulfilimines or sulfoximines containing thiazolyl-piperidinyl compounds or salts thereof.
  • the present invention relates to a process for the preparation of thiazolyl-piperidinyl compounds of formula (I) or salts thereof.
  • the present invention further relates to a process for the preparation of the intermediates of formula (II) and (III), which are useful in the preparation of a compound of formula (I) or salts thereof.
  • a process for the preparation of the intermediates of formula (II) and (III) which are useful in the preparation of a compound of formula (I) or salts thereof.
  • the thiazolyl-piperidinyl class of heterocyclic compounds are known to display a broad fungicidal activity and are useful as crop protecting agents. Some of these compounds are known from several prior arts, for example, WO2008013925, WO2012020060 and WO2016024434. Therefore, it appears that thiazolyl-piperidinyl heterocyclic compounds have a huge potential as prospective fungicidal crop protection agents.
  • WO2021094904 describes phenyl sulfilimines or sulfoximines containing thiazolyl-piperidinyl compounds having an improved fungicidal activity.
  • the present invention provides a simple, environment-friendly, and cost- effective process for the preparation of phenyl sulfilimines or sulfoximines containing thiazolyl- piperidinyl compounds and intermediates thereof, based on easily available starting materials.
  • the main objective of the present invention is to provide a simple, environment-friendly and cost- effective process for the preparation of phenyl sulfilimines or sulfoximines containing thiazolyl- piperidinyl compound of formula (I) or salts thereof, based on easily available starting materials.
  • Another objective of the present invention is to provide a process for the preparation of the oxazoline of formula (III) or salts thereof.
  • the present invention provides a process for preparing a phenyl sulfilimines or sulfoximines containing thiazolyl-piperidinyl compound of formula (I) or salts thereof wherein, the substituents Q, R 1 , R 2 , R a , n and m are defined in the detailed description.
  • the present invention provides a process for preparing an oxazoline of formula (III) that contain phenyl sulfilimines or sulfoximines substituent, or salts thereof.
  • the present invention provides a process for preparing a compound of formula (II) or salts thereof.
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” or - N(alkyl) or alkylcarbonylalkyl or alkylsuphonylamino includes straight-chain or branched C1 to C12 alkyl, preferably C1 to C6 alkyl.
  • Non limiting examples of alkyl include methyl, ethyl, propyl, 1- methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2- methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 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-methyl
  • alkyl is at the end of a composite substituent, as, for example, in alkylcycloalkyl
  • the part of the composite substituent at the start for example, the cycloalkyl
  • other radicals for example, alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy and the like, are at the end.
  • alkenyl used either alone or in compound words includes straight-chain or branched C2 to C12 alkenes, preferably C2 to C6 alkenes.
  • Non limiting examples of alkenes include ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-l- propenyl, l-methyl-2 -propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2- propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2 -propenyl, 1-ethyl-1-propenyl,
  • alkenyl also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. This definition also applies to alkenyl as a part of a composite substituent, for example, haloalkenyl and the like, unless defined specifically elsewhere.
  • alkynyl used either alone or in compound words includes branched or straight-chain C2 to C12 alkynes, preferably C2 to C6 alkynes.
  • Non limiting examples of alkynes include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, l-methyl-2-butynyl, l-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-l-butynyl, 1,1- dimethyl-2-propynyl, 1-ethyl -2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1- methyl-2-pentynyl, l-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-
  • alkynyl as a part of a composite substituent, for example, haloalkynyl etc., unless specifically defined elsewhere.
  • Alkynyl can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
  • alkoxy used either alone or in compound words included C1 to C12 alkoxy, most preferably C1 to C6 alkoxy.
  • alkoxy includes branched or straight-chain alkoxy ("-O-alkyl”) moieties.
  • alkoxy examples include methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2- methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2- dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1- methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2- dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1- ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy and l-ethyl-2-methylpropoxy and the different isomers.
  • alkoxy as a part of a composite substituent, for example, haloalkoxy, alkynylalkoxy, etc., unless specifically defined elsewhere.
  • alkylthio used either alone or in compound words included C 1 to C 12 alkylthio, most preferably C 1 to C 6 alkylthio.
  • alkylthio includes branched or straight-chain alkylthio ("-S- alkyl") moieties such as methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1- methylpropylthio, 2-methylpropylthio, 1,1-dimethylethylthio, pentylthio, 1-methylbutylthio, 2- methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1- dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3- methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3- dimethylbutylthio, 2,
  • alkylsulfinyl (“-S(O)-alkyl”) include methylsulphinyl, ethylsulphinyl, propylsulphinyl, 1-methylethylsulphinyl, butylsulphinyl, 1-methylpropylsulphinyl, 2- methylpropylsulphinyl, 1,1-dimethylethylsulphinyl, pentylsulphinyl, 1-methylbutylsulphinyl, 2- methylbutylsulphinyl, 3-methylbutylsulphinyl, 2,2-dimethylpropylsulphinyl, 1-ethylpropylsulphinyl, hexylsulphinyl, 1,1-dimethylpropylsulphinyl, 1,2-dimethylpropylsulphinyl, 1-methylpentylsulphinyl, 2-methylpentylsulphinyl, 3-methylp
  • arylsulfinyl includes Ar-S(O), wherein Ar can be any carbocyle or heterocylcle. This definition also applies to alkylsulphinyl as a part of a composite substituent, for example, haloalkylsulphinyl etc., unless specifically defined elsewhere.
  • alkylsulfonyl (“-S(O) 2 -alkyl”) include methylsulphonyl, ethylsulphonyl, propylsulphonyl, 1-methylethylsulphonyl, butylsulphonyl, 1-methylpropylsulphonyl, 2- methylpropylsulphonyl, 1,1-dimethylethylsulphonyl, pentylsulphonyl, 1-methylbutylsulphonyl, 2- methylbutylsulphonyl, 3-methylbutylsulphonyl, 2,2-dimethylpropylsulphonyl, 1- ethylpropylsulphonyl, hexylsulphonyl, 1,1-dimethylpropylsulphonyl, 1,2-dimethylpropylsulphonyl, 1- methylpentylsulphonyl, 2-methylpentylsulphonyl
  • arylsulfonyl includes Ar-S(O) 2 , wherein Ar can be any carbocyle or heterocylcle. This definition also applies to alkylsulphonyl as a part of a composite substituent, for example, alkylsulphonylalkyl etc., unless defined elsewhere.
  • cyclic alkyl or “cycloalkyl” means alkyl closed to form a ring. Non limiting examples include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • cycloalkylalkyl means cycloalkyl substituent on alkyl, for example, cyclopropyl or cyclobutyl or cyclopentyl are substituted on any carbon of C 1 -C 6 alkyl.
  • Representative examples of cycloalkylalkyl include cyclopropyl methyl, cyclopropyl ethyl.
  • cycloalkoxy “cycloalkenyloxy” and the like are defined analogously.
  • Non limiting examples of cycloalkoxy include cyclopropyloxy, cyclopentyloxy and cyclohexyloxy. This definition also applies to cycloalkoxy as a part of a composite substituent, for example, cycloalkoxy alkyl etc., unless specifically defined elsewhere.
  • halogen either alone or in compound words such as “haloalkyl”, includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different.
  • haloalkyl include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 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, 1,1-dichloro-2,2,2-trifluoroethyl, and 1,1,1- trifluoroprop-2-yl.
  • haloalkyl as a part of a composite substituent, for example, haloalkylaminoalkyl etc., unless specifically defined elsewhere.
  • haloalkenyl haloalkynyl
  • halocycloalkyl are defined analogously except that, instead of alkyl groups, alkenyl and alkynyl groups are present as a part of the substituent.
  • haloalkoxy means straight-chain or branched alkoxy groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above.
  • Non-limiting examples of haloalkoxy include chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 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 and l,l,l-trifluoroprop-2-oxy.
  • haloalkylthio or haloalkylsulfanyl means straight-chain or branched alkylthio groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above.
  • Non-limiting examples of haloalkylthio include chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, dichlorofluoromethylthio, chlorodifluoromethylthio, 1-chloroethylthio, 1- bromoethylthio, 1- fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2- chloro-2- fluoroethylthio, 2-chloro-2,2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2- trichloroethylthio, pentafluoroethylthio and l,l,l
  • haloalkylthio as a part of a composite substituent, for example, haloalkylthioalkyl etc., unless specifically defined elsewhere.
  • haloalkylsulfinyl include CF 3 S(O), CCl 3 S(O), CF 3 CH 2 S(O) and CF 3 CF 2 S(O).
  • haloalkylsulfonyl include CF 3 S(O) 2 , CCl 3 S(O) 2 , CF 3 CH 2 S(O) 2 and CF 3 CF 2 S(O) 2 .
  • hydroxy means —OH
  • amino means —NRR, wherein R can be H or any possible substituent such as alkyl
  • carbonyl means -C(O)-
  • carbonyloxy means -OC(O)-
  • sulfinyl means SO
  • sulfonyl means S(O) 2 .
  • alkylcarbonyl is an alkyl group bonded to a skeleton via a carbonyl group (-CO-). This definition also applies to alkylcarbonyl as a part of a composite substituent, for example, cycloalkylalkylcarbonyl and the like, unless specifically defined elsewhere.
  • alkylcarbonyl examples include C(O)CH 3 , C(O)CH 2 CH 2 CH 3 and C(O)CH(CH 3 )2.
  • Cycloalkylcarbonyl, and the like, are defined analogously to the above examples.
  • alkoxycarbonyl is an alkoxy group bonded to a skeleton via a carbonyl group (-CO-). This definition also applies to alkoxycarbonyl as a part of a composite substituent, for example, cycloalkylalkoxycarbonyl and the like, unless specifically defined elsewhere.
  • ring or “ring system” as a component of formula I is carbocyclyl or heterocyclyl.
  • ring system denotes one or more rings.
  • non-aromatic heterocycle or “non-aromatic heterocyclic” means three- to fifteen-membered, preferably three- to twelve-membered, saturated or partially unsaturated heterocycle containing one to four heteroatoms from the group of oxygen, nitrogen and sulphur: mono, bi- or tricyclic heterocycles 15 which contain, in addition to carbon ring members, one to three nitrogen atoms and/or one oxygen or sulphur atom or one or two oxygen and/or sulphur atoms; if the ring contains more than one oxygen atom, they are not directly adjacent; for example, (but not limited to) oxiranyl, aziridinyl, oxetanyl, azetidinyl, thietanyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazo
  • C 1 -C 3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2
  • C3 alkoxyalkyl designates, for example, CH 3 CH(OCH 3 ), CH 3 OCH 2 CH 2 or CH 3 CH 2 OCH 2
  • C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH 3 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • a compound of formula (I) when a compound of formula (I) is comprised of one or more heterocyclic rings, all substituents are attached to these rings through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • suitable leaving group refers to a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage.
  • Non-limiting examples of suitable leaving groups include halo groups selected from chloro, iodo, or bromo, aryl or alkyl sulfonates such as tosylate (p- toluenesulfonate), triflate (trifluoromethanesulfonate), nosylate or mesylate (methanesulfonate) and the like.
  • halo groups selected from chloro, iodo, or bromo
  • aryl or alkyl sulfonates such as tosylate (p- toluenesulfonate), triflate (trifluoromethanesulfonate), nosylate or mesylate (methanesulfonate) and the like.
  • reacting or “treating” or “combining” refers to the act of “mixing”, “intermixing” or “putting together” for the purposes of bringing two or more chemical compounds in close contact so as to promote a chemical reaction.
  • inventive compound of the present invention may, if appropriate, be present as mixtures of different possible isomeric forms, especially of stereoisomers, for example, E and Z, threo and erythro, and also optical isomers, but if appropriate also of tautomers. Both the E and the Z isomers, and also the threo and erythro isomers, and the optical isomers, any desired mixtures of these isomers and the possible tautomeric forms are disclosed and claimed.
  • the present invention provides a process for the preparation of phenyl sulfilimine or sulfoximine containing thiazolyl-piperidinyl of formula (I) or salts thereof.
  • the present invention provides a process for preparing a compound of formula (I) wherein, R 1 is selected from the group consisting of hydrogen, halogen, cyano, hydroxy, C 1 -C 6 alkyl, C1- C6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylsulfinyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl or C 3 -C 6 cycloalkyl; n is an integer selected from 0 to 3; R a is selected from the group consisting of hydrogen or C 1 -C 4 alkyl; R 2 is selected from the group consisting of halogen, cyano,
  • the present invention provides a process for preparing a compound of formula (I) or salts thereof wherein, Q, R 1 , R 2, R a , m and n are as defined above; comprising the steps of: a) reacting an oxazoline of formula (III) or salts thereof wherein, X is halogen; Q, R 2 and m are as defined above; with a compound of formula (II) or salts thereof, wherein, R 1 , R a and n are as defined above; optionally in the presence of a suitable reagent and a solvent; and wherein, the compound of formula (III) or salts thereof is obtained by following step: b) reacting a styrene of formula (V) or salts thereof wherein, Q, R 2 and m are as defined above, with an oxime of formula (IV) or salts thereof wherein, X is halogen, in the presence of a suitable base and a solvent, to obtain a compound of formula (III)
  • the present invention provides a process for preparing the compound of formula (VA) or salts thereof further comprising the steps of: I.
  • the compound of formula (II) or salts thereof is represented by a compound of formula (IIa) .
  • the present invention provides a process for preparing a compound of formula (IIa) or salts thereof comprising the following steps: i) reacting a compound of formula (VIIIa) with a sulphur source and optionally in the presence of a suitable reagent and a solvent to obtain a compound of formula (IIa ) or salts thereof, as shown in the scheme below: ii) the compound of formula (VIIIa) was obtained by reacting a compound of formula (X) with a compound of formula (IXa) or (IXa-a), optionally in the presence of a suitable base and a solvent, to obtain a compound of formula (VIIIa), as shown in the scheme below: wherein, M + represent metal ion; iii) the compound of formula (X) was obtained by reacting a compound of formula (XII) with a compound of formula (
  • the compound of formula (II) can be synthesized by using any of the methods known in the prior art. For instance, the process for the synthesis of a compound of formula (II) is disclosed in WO2008013925, WO2008013622, J. Org. Chem.22, 984 (1957). The compounds of formula (IV) are known and can be prepared as described in J. Org. Chem.45, 3916 (1980). The compound of formula (IX) can be synthesized by using any of the methods known in the prior art. For instance, the process for the synthesis of a compound of formula (VIII) is disclosed in Journal of Fluorine Chemistry, 139 (2012) 53-57).
  • the suitable solvents/diluents for carrying out the process according to the invention are all inert organic solvents.
  • These preferably include aliphatic, alicyclic or aromatic hydrocarbons such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons such as, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2- dimethoxyethane, 1,2-diethoxyethane or anisole; ketones, such as
  • the present invention provides a process for preparing a compound of formula (I) or salts thereof, comprising following reaction step (a) by reacting a styrene of formula (III) or salts thereof, with a compound of formula (II) or salts thereof, optionally in the presence of a suitable reagent and a solvent under suitable reaction conditions.
  • the suitable reagent used for the reaction step (a), step (c) and step (e) is selected from the group consisting of acidic reagents, basic reagents, quaternary ammonium salts or organometallic salts.
  • the acidic reagent includes but is not limited to hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulphuric acid, nitric acid, phosphoric acid, perchloric acid, barium fluoride, zinc chloride, aluminium chloride, magnesium chloride, formic acid, acetic acid, trifluoroacetic acid, sulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid, methanesulphonic acid.
  • the basic reagent includes but is not limited to lithium hydride, sodium hydride, potassium hydride, calcium hydride, sodium bicarbonate, sodium carbonate, calcium carbonate, cesium carbonate, lithium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, calcium hydroxide, sodium diphosphate, sodium phosphate, potassium diphosphate and potassium phosphate; amines, such as ethylamine, triethylamine, pyridine, piperidine, N,N-(dimethylamino)pyridine (DMAP), tetramethylammonium hydroxide tetrabutylammonium hydroxide and choline hydroxide; organometallic compounds or metal catalyst such as sodium methoxide, sodium ethoxide, sodium tert- butoxide, potassium tert-butoxide, magnesium tert-butoxide, aluminium isopropoxide, titanium (IV)isopropoxide lithium diisopropy
  • the quaternary ammonium salt reagents include but is not limited to salts of different alkyl cations such as tetrapropylammonium (TPA+), tetrabutylammonium (TBA+), tetrahexylammonium (THA), tetraoctylammonium (TOA+), tetradodecylammonium (TDodA+) with different anions such as iodide ion, chloride ion, bromide ion, fluoride ion, and hydroxide ion.
  • TPA+ tetrapropylammonium
  • TSA+ tetrabutylammonium
  • TAA tetrahexylammonium
  • TOA+ tetraoctylammonium
  • TDodA+ tetradodecylammonium
  • the suitable reagent is selected from tetrabutylammonium bromide (TBAB) or aq HCl.
  • the solvent used for the reaction step (a) and step (i) is selected from the group consisting of aliphatic, alicyclic or aromatic hydrocarbons, for example, petroleum ether, n-hexane, n-heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene and decalin or a mixture thereof; halogenated hydrocarbons, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane and trichloroethane or a mixture thereof; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane
  • the solvent is selected from the group consisting of alcohol and ethers or a mixture thereof. Most preferably, the solvent is selected from ethanol, isopropanol, tetrahydrofuran, 2- methyltetrahydrofuran or a mixture thereof.
  • the reaction step (a) is carried out at a suitable temperature and duration, optionally under an inert atmosphere which allows sufficient formation of a compound of formula (I) or salts thereof.
  • the suitable reaction temperature and period for completing the reaction step (a) may vary from 0 °C to 150 °C for duration of a few minutes to several hours, optionally under an inert atmosphere.
  • the reaction temperature ranges from 0 °C to 100 °C for a period of a few minutes to 24 h under atmospheric pressure, but can also be carried out under increased or reduced pressure.
  • the present invention provides a process for preparing the compound of formula (I) or salts thereof, comprising the further steps: obtaining the compound of formula (III) as per the reaction step (b) in the presence of a suitable base and a solvent under suitable reaction conditions, optionally under an inert atmosphere which allows for sufficient formation of the compound of formula (III) or salts thereof.
  • the suitable base used for the reaction step (b), step (ii) and (iii) is selected from the group consisting of organic bases, inorganic bases and organometallic bases or a mixture thereof.
  • the inorganic base is selected from metal hydride, metal hydroxide, metal carbonate metal bicarbonate, metal phosphate, wherein the metal is lithium, sodium, potassium, calcium, magnesium, cesium and the like.
  • the example of inorganic base includes but is not limited to lithium hydride, sodium hydride, potassium hydride, calcium hydride, sodium bicarbonate, sodium carbonate, calcium carbonate, cesium carbonate, lithium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, calcium hydroxide, sodium diphosphate, sodium phosphate, potassium diphosphate and potassium phosphate or a mixture thereof.
  • the organic base is selected from amines, which includes but is not limited to ethylamine, triethylamine, pyridine, piperidine, N,N-(dimethylamino)pyridine (DMAP), tetramethylammonium hydroxide tetrabutylammonium hydroxide and choline hydroxide or a mixture thereof.
  • amines which includes but is not limited to ethylamine, triethylamine, pyridine, piperidine, N,N-(dimethylamino)pyridine (DMAP), tetramethylammonium hydroxide tetrabutylammonium hydroxide and choline hydroxide or a mixture thereof.
  • the organometallic base is selected from metal alkoxide or metal amide, which include but is not limited to, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert- butoxide, magnesium tert-butoxide, aluminium isopropoxide, titanium (IV)isopropoxide lithium diisopropylamide (LDA), lithium tetramethylpiperidide (LiTMP), and lithium hexamethyldisilazide (LiHMDS) or a mixture thereof.
  • the base is selected from a group consisting of metal hydroxide, metal carbonate, metal bicarbonate, and amines, or a mixture thereof.
  • the base is selected from sodium bicarbonate, sodium carbonate, cesium carbonate, lithium carbonate or potassium carbonate.
  • the suitable solvent used for the reaction step (b), (ii) and (iii) is selected from the solvents as provided for the reaction step (a).
  • the solvent is selected from group consisting of aliphatic, alicyclic or aromatic hydrocarbons, ethers, amides, halogenated hydrocarbons and nitriles or a mixture thereof. More preferably, the solvent is selected from acetonitrile, 2-methyl tetrahydrofuran, tetrahydrofuran, N,N-dimethylformamide or mixture thereof.
  • the suitable reaction temperature and period for completing the reaction step (b) may vary from 0 °C to 70 °C for duration of a few minutes to several hours, optionally under an inert atmosphere.
  • the reaction temperature ranges from 10 °C to 30 °C for a period of a few minutes to 24 h under atmospheric pressure, but can also be carried out under increased or reduced pressure.
  • the suitable ligand used for the reaction step (I) is selected from the group consisting of 1,1- Bis(diphenylphosphino)methane (DPPM), 1,2-Bis(dimethylphosphino)ethane (DMPE), 1,2- Bis(diisopropylphosphino)ethane (DIPPE), 1,2-Bis(diphenylphosphino)ethane (DPPE), derivative of phenylanisylmethylphosphine (DIPAMP), Bis(dicyclohexylphosphino)ethane (DCPE), 1,3- Bis(diphenylphosphino)propane (DPPP), 1,4-Bis(diphenylphosphino)butane (DPPB), (S,S)-DIOP (O- isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane) (DIOP), 2,3- Bis(diphenylphosphino)
  • the ligand is selected from 2,2'- Bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), 1,2-dimethylethylenediamine (DMEDA) or 1,10-phenanthroline.
  • BINAP 2,2'- Bis(diphenylphosphino)-1,1'-binaphthyl
  • Xantphos 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene
  • DMEDA 1,2-dimethylethylenediamine
  • 1,10-phenanthroline 1,10-phenanthroline
  • the organometallic compounds or metal catalyst used for the reaction step (I) may be selected from the group consisting of organolithium compounds, organosodium compounds, organopotassium compounds organomagnesium, organoaluminum compounds, organocopper compounds, organonickel compounds, organozinc compounds, organoplatinum(II) complexes and organopalladium.
  • organometallic compounds includes palladium acetate, Bis(dibenzylideneacetone)palladium(0) [(Pd(dba) 2 )], tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3], CuI, CuBr, CuCl, Cu2O, Cu(OAc)2 and CuSO4.H2O and the like.
  • the metal catalyst is selected from organocopper or organopalladium compound.
  • the metal catalyst is selected from CuI, Cu(OAc) 2 , CuSO 4 .H 2 O, palladium acetate or tris(dibenzylideneacetone)dipalladium(0) [Pd 2 (dba) 3 ].
  • the suitable base used for the reaction step (I) is selected from bases as provided for the reaction step (a) above.
  • the base is selected from a metal alkoxide or metal carbonates. More preferably, the base is selected from sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, cesium carbonate or potassium carbonate.
  • the suitable solvent used for the reaction step (I) is selected from solvent as provided for the reaction step (a) above.
  • aliphatic, alicyclic or aromatic hydrocarbons such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons such as, for example, chlorobenzene, ethers such as dioxane, amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformanilide, N- methylpyrrolidone.
  • aliphatic, alicyclic or aromatic hydrocarbons such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin
  • halogenated hydrocarbons such as, for example, chlorobenzene, ethers such as dioxane,
  • the solvent is selected from N,N-dimethylformamide, N,N- dimethylacetamide, N-methylformanilide, N-methylpyrrolidone, toluene, xylene or dioxane
  • the suitable reaction temperature and period for completing the reaction step (I) may vary from 0 °C to 250 °C for duration of a few minutes to several hours, optionally under an inert atmosphere.
  • the reaction temperature ranges from 20 °C to 150 °C for a period of a few minutes to 24 h under atmospheric pressure, but can also be carried out under increased or reduced pressure.
  • reaction step (b) Successively, converting the compound of formula (V) or salts thereof, to a compound of formula (I) or salts thereof by following the reaction step (b) and then reaction step (a).
  • the suitable reaction temperature and period for completing the reaction step (d) and (e) may vary from 0 °C to 150 °C for duration of a few minutes to several hours, optionally under an inert atmosphere.
  • the reaction temperature ranges from 20 °C to 100 °C for a period of a few minutes to 24 h under atmospheric pressure, but can also be carried out under increased or reduced pressure.
  • the compound of formula R 5 SH or R 5 S-M is wherein; M represents a metal and R 5 represent C 1 -C 4 alkyl, C 2 -C 6 alkenyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl-C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 3 -C 6 halocycloalkyl.
  • a preferred compound of formula R 5 S-M is an alkali metal salt of thioalkoxide, wherein R 5 is C 1 -C 4 -alkyl and M is selected from sodium, potassium or lithium.
  • the metal salt of thioalkoxide is selected from a group consisting of lithium thioalkoxides, sodium thioalkoxides, or potassium thioalkoxides.
  • lithium thioalkoxides include but are not limited to lithium thiomethoxide, lithium thioethoxide, lithium thiopropoxide and the like.
  • sodium thioalkoxides include but are not limited to sodium thiomethoxide, sodium thioethoxide, sodium thiopropoxide and the like.
  • potassium thioalkoxides include but are not limited to potassium thiomethoxide, potassium thioethoxide, potassium thiopropoxide and the like.
  • the suitable oxidizing agent useful for performing the reaction step (d) is selected from a group consisting of fluorine; chlorine; hydrogen peroxide; nitric acid or nitrate compounds; sulfuric acid; peroxydisulfuric acid; peroxy mono sulfuric acid; chlorite, chlorate, perchlorate and other analogues of halogen compounds; hypochlorite and other hypohalite compounds such as sodium hypochlorite; hexavalent chromium compounds such as chromic and dichromic acids, chromium trioxide, pyridinium chlorochromate, chromate/dichromate compounds; permanganate compounds such as potassium permanganate; sodium perborate; nitrous oxide, nitrogen dioxide, dinitrogen tetroxide; potassium nitrate; sodium bismuthate, iodine, iodine pentoxide, iodobenzene dichloride, iodosobenzene bis(trifluoroacetate),
  • the oxidizing agent is selected from hydrogen peroxide, sodium hypochlorite, pyridinium chlorochromate, iodine pentoxide, iodobenzene dichloride, iodosobenzene bis(trifluoroacetate), iodosobenzene diacetate, N-iodosuccinimide, or iodosylbenzene.
  • the source of ammonium ion for the reaction step (d) is selected from a group consisting of ammonium carbamate, ammonium hydroxide, ammonium carbonate, ammonium chloride, ammonium nitrate, ammonium formate, ammonium acetate and the like.
  • the sulphur source(s) in the reaction step (i) selected from but is not limited to sulphur powder, hydrogen sulphide, ammonium sulphide, thioacetic acid, phosphorus pentasulfide, sodium sulphide, sodium hydrosulfide, like and combination thereof.
  • sulphur source(s) in the reaction step (i) selected from sulphur powder, hydrogen sulphide or a mixture thereof.
  • the suitable reagent used for the reaction step (i) is selected from reagents as provided for the reaction step (a) above.
  • the reagent is selected from diethylamine, triethylamine or aq ammonia.
  • the present invention provides a process for the preparation of a compound of formula (IA) or salts thereof Formula (IA) wherein, R 1 , R 2 , R a , R 4 , R 5 , n and m are as defined above.
  • the present invention provides a process for the synthesis of a compound of formula (IB) or salts thereof Formula (IB) wherein, R 1 , R 2 , R a , R 6 , R 7 , n and m are as defined above.
  • the present invention provides a compound of formula (III) or salts thereof wherein, X is halogen, R 2 , Q and m are as defined above.
  • the present invention provides a compound of formula (III) or salts thereof is selected from: .
  • the present invention provides a compound of formula (V) or salts thereof wherein, R 2 , Q and m are as defined above.
  • the present invention provides a compound of formula (VA) or salts thereof wherein, R 2 , R 6 , R 7 and m are as defined above.
  • the present invention provides a compound of formula (VB) or salts thereof wherein, R 2 , R 5 , R 6 and m are as defined above.
  • present invention provides process for preparing the compound of formula (I) or salts thereof wherein, preferred substitutions:
  • R 1 is selected from the group consisting of halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 3 -C 6 cycloalkyl.
  • n is an integer selected from 1 to 2. More preferred R 1 is selected from the group consisting of C 1 -C 6 alkyl and C 1 -C 6 haloalkyl. Most preferred R 1 is selected from the group consisting of CHF2 and CF 3 .
  • R a is selected from the group consisting of hydrogen and C1-C4 alkyl. More preferred R a is hydrogen.
  • R 2 is selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkyl and C 3 -C 6 cycloalkyl.
  • m is an integer selected from 1 to 2. More preferred R 2 is halogen.
  • R 4 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C 3 -C 6 cycloalkyl and C 3 -C 6 cycloalkyl-C1-C4 alkyl;
  • R 5 and R 6 are independently selected from the group consisting of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl-C 1 -C 4 alkyl, and C 3 -C 6 halocycloalkyl;
  • R 7 is independently selected from the group consisting of C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl-C 1 -C 4 alkyl, C 1 -C 4 haloal
  • R 4 , R 5 and R 6 are C 1 -C 4 alkyl.
  • the preparation of compounds of formula (I), (II), (III) may involve the isolation of respective reaction intermediates after the completion of the reaction. However, the reaction steps can also proceed to the next steps without isolation of the respective reaction intermediates.
  • the processes as disclosed in the present invention are preferably carried out batch-wise. However, semi-continuous or continuous reaction passages, for example, under flow conditions, are also possible.
  • the processes as disclosed in the present invention can be run in the absence of a solvent or in the presence of one or more suitable solvents.
  • the optional solvent should be stable against oxidation (i.e.
  • a solvent will be preferred whose rate of oxidation is substantially lower than that of the compounds of formula I to XV) and suitable for suspending, or preferably dissolving the reactants.
  • Any person skilled in the art knows the best work-up of the reaction mixtures after the end of the respective reactions.
  • the work-up is usually carried out by isolation of the product by filtration, and optionally washing with solvent, further optionally drying of the product if required.
  • the isolation of the reaction product can also be carried out by a technique which includes but is not limited to decantation, centrifugation, evaporation, liquid-liquid extraction, distillation, recrystallization, chromatography and the like.
  • the process steps according to the invention are generally carried out under atmospheric pressure.
  • Example 1 Preparation of ((2-(3-(2-(1-(2-(3,5-bis(trifluoromethyl)-1H-pyrazol-1- yl)acetyl)piperidin-4-yl)thiazol-4-yl)-4,5-dihydroisoxazol-5-yl)-3-fluorophenyl)imino)dimethyl- ⁇ 6 -sulfanone (Ia)
  • Step-1 Preparation of ((3-fluoro-2-vinylphenyl)imino)dimethyl- ⁇ 6 -sulfanone
  • Method A Pd catalyzed synthesis from bromo styrene VIIa To a stirred suspension of 1-bromo-3-fluoro-2-vinylbenzene (VIIa, 100 g, 497 mmol), iminodimethyl- ⁇ 6 -sulfanone (VIa, 51 g, 547 mmol) and sodium tert-but
  • reaction mixture was cooled to 25°C, diluted with water (25 mL), ethyl acetate (EtOAc) (25 mL) and filtered through a celite bed. The bed was washed with ethyl acetate (2 ⁇ 50 mL) and the combined filtrate was washed with water (50 mL) and brine solution (50 mL). Organic layer was dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure to afford ((3-fluoro-2- vinylphenyl)imino)dimethyl-l6-sulfanone (VIIa, 0.51 g, 67% purity) as a gummy material.
  • VIa ((3-fluoro-2- vinylphenyl)imino)dimethyl-l6-sulfanone
  • Method C Cu catalyzed synthesis from iodo styrene
  • VIPa1 1-iodo-3-fluoro-2-vinylbenzene
  • VIa iminodimethyl- ⁇ 6 -sulfanone
  • CuI 0.384 g, 2.016 mmol
  • DMF dry N,N dimethylformamide
  • DMEDA 1,2- dimethylethylenediamine
  • reaction mixture was stirred at 25-30 °C for 5 min.
  • Potassium tert-butoxide (1.357 g, 12.09 mmol) was added to the reaction mixture and the mixture was heated to 110 0C and stirred for 12 h under argon atmosphere.
  • the reaction mixture was filtered through a celite bed and washed with ethyl acetate (2 ⁇ 100 mL). Filtrate was washed with water (250 mL) and brine solution (250 mL).
  • Step-2 Preparation of ((2-(3-(2-chloroacetyl)-4,5-dihydroisoxazol-5-yl)-3-fluorophenyl)imino) dimethyl- ⁇ 6 -sulfanone (IIIa)
  • Method A To a stirred solution of ((3-fluoro-2-vinylphenyl) imino) dimethyl- ⁇ 6 -sulfanone (Va, 2 g, 9.38 mmol) and sodium bicarbonate (1.576 g, 18.76 mmol) in acetonitrile (20 mL), 3-chloro-N-hydroxy-2- oxopropanimidoyl chloride (IVa, 1.682 g, 10.78 mmol) was added at 25-30 °C and stirred for 4 h.
  • Step-3 Preparation of ((2-(3-(2-(1-(2-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)acetyl)piperidin-4- yl)thiazol-4-yl)-4,5-dihydroisoxazol-5-yl)-3-fluorophenyl)imino)dimethyl- ⁇ 6 -sulfanone (Ia)
  • Method A To a solution of ((2-(3-(2-chloroacetyl)-4,5-dihydroisoxazol-5-yl)-3-fluorophenyl) imino) dimethyl- ⁇ 6 - sulfanone (IIIa, 200 mg, 0.601 mmol) in ethanol (2 mL), 1-(2-(3,5-bis(trifluoromethyl)-1H-pyrazol-1- yl) acetyl)piperidine-4-carbothi
  • reaction mixture was heated to 50 ⁇ 5°C and stirred for 12 h under nitrogen atmosphere. After completion of the reaction, the mixture was concentrated, water (30.0 mL, 3.0v) was added in dropwise manner at 50 ⁇ 5°C. The reaction mass was allowed to cool to 25 ⁇ 5 °C and stirred at 25 ⁇ 5 °C for 12 h.
  • Step 1a Preparation of 1-(2-chloroacetyl)piperidine-4-carbonitrile (3)
  • Method-1 A mixture of piperidine-4-carbonitrile (XIIa, 15 g, 136 mmol) and 40 % aqueous solution of K2CO3 (25.9 g, 74.9 mmol) in dichloromethane (75 mL) was cooled to 0-5 °C.
  • Step-2a Preparation of 1-(2-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)acetyl)piperidine-4- carbonitrile (5) To a solution of 1-(2-chloroacetyl) piperidine-4-carbonitrile (Xa, 100 g, 536 mmol) in N,N- dimethylformamide (1000 mL), 3,5-bis(trifluoromethyl)-1H-pyrazole (IXa, 109 g, 536 mmol) and potassium carbonate (148 g, 1072 mmol) were added at 20-25 °C.
  • reaction mixture was heated at 60 °C and stirred for 4 h. After completion of the reaction, the reaction mixture was diluted with water (500 mL) and extracted with ethyl acetate (2 x 500 mL). The combined organic extract was washed with water (2 x 200 mL), brine solution (500 mL) and concentrated under reduced pressure to afford a colourless gummy oil. To this gummy oil, water (500 mL) was added and stirred at 25-30 °C for 16 h.
  • Step-3a Preparation of 1-(2-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)acetyl)piperidine-4- carbothioamide (IIa)
  • Method A Hydrogen sulfide (gas) was purged through a solution of 1-(2-(3,5-bis(trifluoromethyl)-1H-pyrazol-1- yl)acetyl)piperidine-4-carbonitrile (VIIIa, 100 g, 282 mmol) and diethylamine (31 g, 423 mmol) in ethanol (1000 mL), for 30 min at 50 °C.
  • reaction mixture was further stirred for 10 h at 50 °C. After completion of the reaction, excess hydrogen sulfide gas from the reaction mixture was purged out. The reaction mixture was concentrated under reduced pressure to get a brown coloured residue. The resulting residue was stirred in water (400 mL) overnight at 25-30 °C to afford a solid which was filtered, washed with water (200 mL), dried under reduced pressure to obtain 1-(2-(3,5- bis(trifluoromethyl)-1H-pyrazol-1-yl)acetyl)piperidine-4-carbothioamide (IIa, 92 g, 237 mmol, 84% yield).
  • reaction mixture was stirred for 12 h at 70 °C under pressure (2.0 bar). After completion of the reaction, excess hydrogen sulfide gas from the reaction mixture was safely purged out. The resulting reaction mixture was concentrated under reduced pressure. Toluene (500 mL) was added at 60°C. The reaction mass was gradually cooled to 5-10 °C. The solid obtained was filtered, dried under reduced pressure to afford 1-(2-(3,5-bis(trifluoromethyl)-1H-pyrazol- 1-yl)acetyl)piperidine-4-carbothioamide (IIa, 103 g, 93.9% yield).
  • reaction mixture was extracted with ethyl acetate and concentrated under reduced pressure to obtain a crude residue which was purified by column chromatography to afford 1-(2-(3,5- bis(trifluoromethyl)-1H-pyrazol-1-yl)acetyl)piperidine-4-carbothioamide (IIa, 220 mg, 40% yield) as an off white solid.
  • reaction mixture was stirred for 1.5 h at 0-5 °C. After completion of the reaction, the reaction mixture was charged with additional potassium carbonate (62.7 g, 454 mmol) and a solution of 3,5-bis(trifluoromethyl)-1H-pyrazole (IXa, 46.3 g, 227 mmol) in acetonitrile (50 mL). The reaction temperature was warmed up to 50 °C and stirred further for 4 h. After completion of the reaction, the reaction mixture was cooled to 25-30 °C and filtered. The obtained wet cake was washed with acetonitrile (150 mL). The combined filtrate was concentrated to afford a gummy oil.
  • reaction mixture was charged with 2-chloroacetyl chloride XIa (18.05 mL, 227 mmol) at 0 ⁇ 5 °C and stirred further for 2 h.
  • second lot of dry powdered potassium carbonate (47.0 g, 340 mmol) was charged at 0 ⁇ 5 °C and stirred for 5 min followed by the addition of freshly prepared solution of 3,5-bis(trifluoromethyl)-1H-pyrazole IXa (46.3 g, 227 mmol) in acetonitrile (50 mL).
  • the reaction mixture was heated to 50 ⁇ 5 °C and stirred for 4 h. After completion of the reaction, the mixture was cooled to 25 ⁇ 5 °C, and filtered.

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2012020060A1 (de) 2010-08-11 2012-02-16 Bayer Cropscience Ag Heteroarylpiperidin und -piperazinderivate als fungizide
WO2016024434A1 (ja) 2014-08-13 2016-02-18 株式会社エス・ディー・エス バイオテック 縮合１１員環化合物及びそれらを含有する農園芸用殺菌剤
US20160242416A1 (en) * 2015-02-23 2016-08-25 E I Du Pont De Nemours And Company Fungicidal isoxazoline carbinols
WO2021094904A2 (en) 2019-11-11 2021-05-20 Pi Industries Ltd. Novel sulfilimines or sulfoximines containing fungicidal heterocyclic compounds

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008013925A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2012020060A1 (de) 2010-08-11 2012-02-16 Bayer Cropscience Ag Heteroarylpiperidin und -piperazinderivate als fungizide
WO2016024434A1 (ja) 2014-08-13 2016-02-18 株式会社エス・ディー・エス バイオテック 縮合１１員環化合物及びそれらを含有する農園芸用殺菌剤
US20160242416A1 (en) * 2015-02-23 2016-08-25 E I Du Pont De Nemours And Company Fungicidal isoxazoline carbinols
WO2021094904A2 (en) 2019-11-11 2021-05-20 Pi Industries Ltd. Novel sulfilimines or sulfoximines containing fungicidal heterocyclic compounds

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GUPTA SURABHI ET AL: "Copper-Catalyzed N-Arylation of Sulfoximines with Arylboronic Acids under Mild Conditions", SYNTHESIS, vol. 51, no. 10, 30 May 2019 (2019-05-30), STUTTGART, DE., pages 2171 - 2182, XP055959884, ISSN: 0039-7881, DOI: 10.1055/s-0037-1612216 *
J. ORG. CHEM., vol. 22, 1957, pages 984
J. ORG. CHEM., vol. 45, 1980, pages 3916
JOURNAL OF FLUORINE CHEMISTRY, vol. 139, 2012, pages 53 - 57

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