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WO2018193387A1 - Composés hétérocycliques ayant des propriétés microbiocides - Google Patents

Composés hétérocycliques ayant des propriétés microbiocides Download PDF

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Publication number
WO2018193387A1
WO2018193387A1 PCT/IB2018/052681 IB2018052681W WO2018193387A1 WO 2018193387 A1 WO2018193387 A1 WO 2018193387A1 IB 2018052681 W IB2018052681 W IB 2018052681W WO 2018193387 A1 WO2018193387 A1 WO 2018193387A1
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WO
WIPO (PCT)
Prior art keywords
piperidin
thiazol
dihydroisoxazol
pyridin
trifluoromethyl
Prior art date
Application number
PCT/IB2018/052681
Other languages
English (en)
Inventor
Gajanan SHANBHAG
Ranga Prasad DODDA
Ganesh Tatya KAMBLE
Yuvraj Navanath KALE
G. Renugadevi
Sulur G MANJUNATHA
Mohan Kumar S.P.
Santosh Shridhar AUTKAR
Ruchi GARG
Hagalavadi M VENKATESHA
Jagadeesh Nanjegowda MAVINAHALLI
Alexander G.M. KLAUSENER
Original Assignee
Pi Industries Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pi Industries Ltd. filed Critical Pi Industries Ltd.
Publication of WO2018193387A1 publication Critical patent/WO2018193387A1/fr

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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the present invention relates to compounds containing one or more heterocyclic rings and salts, metal complexes, N-oxides, enantiomers, stereoisomers and polymorphs thereof; compositions and methods of use for controlling or preventing phytopathogenic micro-organisms.
  • the compounds and compositions thereof of the present invention have the potential of overcoming drawbacks and are suitable for crop protection against phytopathogenic micro-organisms causing plant diseases.
  • compositions comprising, “comprising”, “includes”, “including”, “has”, “having”, “contains”, “containing”, “characterized by” or any other variation thereof, are intended to cover a nonexclusive inclusion, subject to any limitation is explicitly indicated.
  • a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.
  • the term "invertebrate pest” includes arthropods, gastropods and nematodes of economic importance as pests.
  • arthropod includes insects, mites, spiders, scorpions, centipedes, millipedes, pil l bugs and symphylans.
  • gastropod includes snails, sl ugs and other Stylommatophora.
  • nematode refers to a living organism of the Phylum Nematoda.
  • helminths includes roundworms, heartworms, phytophagous nematodes (Nematoda), flukes (Tematoda), acanthocephala and tapeworms (Cestoda).
  • invertebrate pest control means inhibition of invertebrate pest development (including mortality, feeding reduction, and/or mating disruption), and related expressions are defined analogously.
  • agronomic refers to the production of field crops such as for food and fiber and includes the growth of corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye, rice, maize), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (berries, cherries) and biofuel crops such as, jatropha, palm trees, other specialty crops (e.g., canola, sunflower, olives).
  • nonagronomic refers to other than field crops, such as horticultural crops (e.g., greenhouse, nursery or ornamental plants not grown in a field), residential, agricultural, commercial and industrial structures, turf (e.g., sod farm, pasture, golf course, lawn, sports field, etc.), wood products, stored product, agro-forestry and vegetation management, public health (i.e. human) and animal health (e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife) applications.
  • horticultural crops e.g., greenhouse, nursery or ornamental plants not grown in a field
  • turf e.g., sod farm, pasture, golf course, lawn, sports field, etc.
  • wood products e.g., stored product, agro-forestry and vegetation management
  • public health i.e. human
  • animal health e.g., domesticated animals such as pets, livestock and poultry, undomesticated animals such as wildlife
  • Nonagronomic applications include protecting an animal from an invertebrate parasitic pest by administering a parasiticidally effective (i.e. biologically effective) amount of a compound of the present invention, typically in the form of a composition formulated for veterinary use, to the animal to be protected.
  • a parasiticidally effective (i.e. biologically effective) amount of a compound of the present invention typically in the form of a composition formulated for veterinary use, to the animal to be protected.
  • parasiticidal i.e. biologically effective
  • Parasiticidally refers to observable effects on an invertebrate parasite pest to provide protection of an animal from the pest. Parasiticidal effects typical ly relate to diminishing the occurrence or activity of the target invertebrate parasitic pest.
  • Such effects on the pest include necrosis, death, retarded growth, diminished mobility or lessened ability to remain on or in the host animal, reduced feeding and inhibition of reproduction.
  • These effects on invertebrate parasite pests provide control (including prevention, reduction or elimination) of parasitic infestation or infection of the animal.
  • Stereoisomers of the present invention may be present either in pure form or as mixtures of different possible isomeric forms such as stereoisomers or constitutional isomers.
  • the various stereoisomers include enantiomers, diastereomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, optical isomers, polymorphs, and geometric isomers. Any desired mixtures of these isomers fall within the scope of the claims of the present invention.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other isomer(s) or when separated from the other isomer(s). Additional ly, the person ski lled in the art knows processes or methods or technology to separate, enrich, and/or to selectively prepare said isomers.
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” or -N(aikyl) or alkylcarbonylalkyl or alkylsuphonylamino includes straight-chain or branched C, to C 24 alkyl, preferably C
  • 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 -dimethylbutyi, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,2- dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1 , 1 , 1
  • the 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 C 2 to C 24 alkenes, preferably C 2 to C J5 alkenes, more preferably C 2 to C 10 alkenes, most preferably C 2 to C 6 alkenes.
  • alkenes include ethenyl, 1 -propenyl, 2-propenyl, 1 -methylethenyl, 1 -butenyl,
  • 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.
  • alkynes used either alone or in compound words include ethynyl, 1 -propynyl, 2-propynyl, 1 -butynyl, 2-butynyl, 3-butynyl, l -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, l -methyl-2- pentynyl, l-methyl-3-pentynyl,
  • 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.
  • Cycloalkyl means alkyl closed to form a ring. Representative examples include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. This definition also applies to cycloalkyl as a part of a composite substituent, for example cycloalkylalkyl etc., unless specifically defined elsewhere.
  • Cycloalkenyl means alkenyl closed to form a ring including monocyclic, partially unsaturated hydrocarbyl groups. Representative examples include but are not limited to cyclopropenyl, cyclobutenyl, cyclopentenyl and cyclohexenyl. This definition also applies to cycloalkenyl as a part of a composite substituent, for example cycloalkenylalkyl etc., unless specifically defined elsewhere.
  • 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 cycloalkoxyalkyl 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 examples include chloromethyl, bromomethyl, iodomethyl, 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, pentafiuoroetbyl, ] , l -dichloro-2,2,2-trifluoroethyl, and l , l , l l
  • haloalkenyl and “haloalkynyl” are defined analogously except that, instead of alkyl groups, alkenyl and alkynyl groups are present as a part of the substituent.
  • ha!oalkoxy means straight-chain or branched alkoxy groups where at least one up to all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above.
  • haloalkoxy include chloromethoxy, iodomethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromefhoxy, 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-trichloro
  • haloalkylthio means straight-chain or branched alkylthio groups where at least one up to all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above.
  • Non-limiting examples of haloalkylthio include chloromethylthio, iodomethylthio, 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-ch
  • haloalkylsulfinyl examples include CF 3 S(0), CC1 3 S(0), CF 3 CH 2 S(0) and CF 3 CF 2 S(0).
  • haloalkylsulfonyl examples include CF 3 S(0) 2 , CC1 3 S(0) 2 , CF 3 CH 2 S(0) 2 and CF 3 CF 2 S(0) 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(0) 2 .
  • alkoxy used either alone or in compound words included Cj to C 24 alkoxy, preferably C , to C is alkoxy, more preferably C
  • alkoxy include methoxy, ethoxy, propoxy, 1 -methyl ethoxy, butoxy, 1 -methylpropoxy, 2-methylpropoxy, 1 , 1 - dimethylethoxy, pentoxy, 1 -methyl butoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1 - ethylpropoxy, hexoxy, 1 , 1 -dimethylpropoxy, 1 ,2-dimethylpropoxy, 1 -methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methy I pentoxy, 1 , 1 -dimethylbutoxy, 1 ,2-dimethylbutoxy, 1 ,3-dimethylbutoxy, 2,2- dimethylbutoxy, 2,3
  • Alkoxyalkyl denotes alkoxy substitution on alkyl.
  • alkoxyalkyl include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • alkoxyalkoxy denotes alkoxy substitution on alkoxy.
  • alkylthio includes branched or straight-chain alkylthio 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-rnethylpentylthio, 1 , 1 -dimethylbutylthio, 1 ,2-di
  • Halocycloalkyl, halocycloalkenyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylcarbonyl, cycloalkylcarbonyl, haloalkoxylalkyl, and the like, are defined analogously to the above examples.
  • alkylthioalkyl denotes alkylthio substitution on alkyl.
  • Representative examples of “alkylthioalkyl” include -CH 2 SCH 2 , -CH 2 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 .
  • Alkylthioalkoxy denotes alkylthio substitution on alkoxy.
  • cycloalkylalkylamino denotes cycloalkyl substitution on alkyl amino.
  • alkoxyalkoxyalkyl alkylaminoalkyl, dialkylaminoalkyl, cycloalkylaminoalkyl, cycloalkylaminocarbonyl and the like, are defined analogously to "alkylthioalkyl” or cycloalkylalkylamino.
  • 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.
  • alkoxycarbonylalkylamino denotes alkoxy carbonyl substitution on alkyl amino.
  • Alkylcarbonylalkylamino denotes alkyl carbonyl substitution on alkyl amino.
  • alkylthioalkoxycarbonyl, cycloalkylalkylaminoalkyl and the like are defined analogously.
  • alkylsulfinyl examples include but are not limited to methylsulphinyl, ethylsulphinyl, propylsulphinyl, 1 -methylethylsulphinyl, butylsulphinyl, 1 -methylpropylsulphinyl, 2- methylpropylsulphinyl, 1 , 1 -dimethylethyIsulphinyl, pentylsulphinyl, 1 -methylbutylsulphinyl, 2- methylbutylsulphinyl, 3-methylbutylsulphinyl, 2,2-dimethylpropylsulphinyl, 1 -ethylpropylsulphinyl, hexylsu!phinyi, 1 , 1 -dimethylpropylsulphinyl, 1 ,2-dimethylpropylsulphinyl, 1 -methylpentylsulphinyl, 2- methylpentyl
  • arylsulfinyl includes Ar-S(O), wherein Ar can be any carbocyle or heterocylcle. This definition also appl ies to alkylsulphinyl as a part of a composite substituent, for example haloalkylsulphinyl etc., unless specifically defined elsewhere.
  • alkylsulfonyl examples include but are not l imited to methylsulphonyl, ethylsulphonyl, propylsulphonyl, 1 -methylethylsulphonyl, butylsulphonyl, 1 -methylpropylsulphonyl, 2- methylpropylsulphonyl, 1 , 1 -dimcthylethylsulphonyl, pentylsulphonyl, 1 -methylbutylsulphonyl, 2- methylbutylsulphonyl, 3-methy!butylsulphonyl, 2,2-dimethylpropylsulphonyl, 1 -ethylpropylsulphonyl, hexylsulphonyl, 1 , 1 -dimethylpropylsulphonyl, 1 ,2-dimethylpropylsulphonyl, 1 -methylpentylsulphonyl,
  • arylsulfonyl includes Ar-S(0) 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.
  • Alkylamino "dialkylamino”, and the like, are defined analogously to the above examples.
  • carrier or “carbocyclic” or “carbocyclyl” include “aromatic carbocyclic ring system” and “nonaromatic carbocylic ring system” or polycyclic or bicyclic (spiro, fused, bridged, nonfused) ring compounds in which the ring may be aromatic or non-aromatic (where aromatic indicates that the Hueckel rule is satisfied and non-aromatic indicates that the Hueckel rule is not statisfied).
  • non-aromatic heterocycle means three- to fifteen-membered, preferably three- to twelve- membered, saturated or partially unsaturated heterocycles containing one to four heteroatoms from the group of oxygen, nitrogen and sulphur: mono, bi- or tricyclic heterocycles which contain, in addition to carbon ring members, one to three n 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, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2- tetrahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl, 3-pyrrol idinyl, 3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl, 3-isothiazo
  • heteroaryl means 5 or 6-membered, fully unsaturated monocyclic ring system containing one to four heteroatoms from the group of oxygen, n and sulphur; if the ring contains more than one oxygen atom, they are not directly adjacent; 5-membered heteroaryl containing one to four n atoms or one to three n atoms and one sulphur or oxygen atom: 5-membered heteroaryl groups which, in addition to carbon atoms, may contain one to four n atoms or one to three n atoms and one sulphur or oxygen atom as ring members, for example (but not limited thereto) 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3- pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3- pyrazolyl
  • 6-membered heteroaryl which contains one to four n atoms: 6-membered heteroaryl groups which, in addition to carbon atoms, may contain, respectively, one to three and one to four n atoms as ring members, for example (but not limited thereto) 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4- pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, I,3,5-triazin-2-yl, l,2,4-triazin-3-yl and l,2,4,5-tetrazin-3-yl; benzofused 5-membered heteroaryl containing one to three n atoms or one n atom and one oxygen or sulphur atom: for example (but not limited to) indol-l-yl, indol-2-yl, indol-3-yl, indo
  • heteroaryl as a part of a composite substituent, for example heteroarylalkyl etc., unless specifically defined elsewhere.
  • Trialkylsilyl includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom such as trimethylsilyl, triethylsilyl and t-butyl-dimethylsilyl.
  • Hydrochalotrialkylsilyl denotes at least one of the three alkyl radicals is partially or fully substituted with halogen atoms which may be the same or different.
  • Alkoxytrialkylsilyl denotes at least one of the three alkyl radicals is substituted with one or more alkoxy radicals which may be the same or different.
  • Trialkylsilyloxy denotes a trialkylsilyl moiety attached through oxygen.
  • Examples of “a!kylcarbonyl” include C(0)CH 3 , C(0)CH 2 CH 2 CH 3 and C(0)CH(CH 3 ) 2 .
  • haloalkylsufonylaminocarbonyl, alkylsulfonylaminocarbonyl, alkylthioalkoxycarbonyl, alkoxycarbonylalkyl amino and the like are defined analogously
  • the total number of carbon atoms in a substituent group is indicated by the "Q-C " prefix where i and j are numbers from 1 to 21 .
  • C 1 -C 3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2
  • C 3 alkoxyalkyl designates, for example, CH 3 CH(OCH 3 ), CH 3 OCH 2 CH 2 or CH 3 CH 2 OCH 2
  • C 4 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 .
  • all substituents are attached to these rings through any available carbon or n by replacement of a hydrogen on said carbon or n
  • fragments 1 , 3 and 5 are capable of forming two double bonds inside the ring by tautomerization as shown below and exist in tautomeric forms 2, 4 and 6 respectively, fragments 1 , 3 and 5 and tautomers thereof i.e., 2, 4 and 6 are included within the definition of the term "fragments and tautomeric forms thereof having two double bonds inside the ring".
  • pest for the purpose of the present invention includes but is not limited to fungi, stramenopiles (oomycetes), bacteria, nematodes, mites, ticks, insects and rodents.
  • Plant is understood here to mean all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants).
  • Crop plants may be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the transgenic plants and including the plant cultivars which are protectable and non-protectable by plant breeders' rights.
  • plant includes a living organism of the kind exemplified by trees, shrubs, herbs, grasses, ferns, and mosses, typically growing in a site, absorbing water and required substances through its roots, and synthesizing nutrients in its leaves by photosynthesis.
  • plant for the purpose of the present invention include but are not limited to agricultural crops such as wheat, rye, barley, triticale, oats or rice; beet, e.g. sugar beet or fodder beet; fruits and fruit trees, such as pomes, stone fruits or soft fruits, e.g.
  • leguminous plants such as lenti ls, peas, alfalfa or soybeans; oil plants, such as rape, mustard, olives, sunflowers, coconut, cocoa beans, castor oil plants, oil palms, ground nuts or soybeans; cucurbits, such as squashes, cucumber or melons; fiber plants, such as cotton, flax, hemp or jute; citrus fruit and citrus trees, such as oranges, lemons, grapefruits or mandarins; any horticultural plants, vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, cucurbits or paprika; lauraceous plants, such as avocados, cinnamon or camphor; cucurbitaceae; oleaginous plants; energy and raw material plants, such as cereals, corn, soybean, other leguminous plants, rape, sugar cane or oil palm; tobacco; nuts;
  • the plant for the purpose of the present invention include but is not limited to cereals, corn, rice, soybean and other leguminous plants, fruits and fruit trees, grapes, nuts and nut trees, citrus and citrus trees, any horticultural plants, cucurbitaceae, oleaginous plants, tobacco, coffee, tea, cacao, sugar beet, sugar cane, cotton, potato, tomato, onions, peppers and vegetables, ornamentals, any floricultural plants and other plants for use of human and animals.
  • plant parts is understood to mean all parts and organs of plants above and below the ground.
  • plant parts includes but is not limited to cuttings, leaves, twigs, tubers, flowers, seeds, branches, roots including taproots, lateral roots, root hairs, root apex, root cap, rhizomes, slips, shoots, fruits, fruit bodies, bark, stem, buds, auxiliary buds, meristems, nodes and internodes.
  • locus thereof includes soil, surroundings of plant or plant parts and equipment or tools used before, during or after sowing/planting a plant or a plant part.
  • compositions optionally comprising other compatible compounds to a plant or a plant material or locus thereof include application by a technique known to a person skilled in the art which include but is not limited to spraying, coating, dipping, fumigating, impregnating, injecting and dusting.
  • adhered means adhered to a plant or plant part either physically or chemically including impregnation.
  • the present invention relates to a compound of Formula I,
  • the present invention is inclusive of salts, metal complexes, N-oxides, isomers, and polymorphs of the compound of Formula I.
  • compound of formula I containing fragment of Formula II and tautormeric forms of such fragments having two double bonds inside the ring of Formula II when v is 1 are excluded from the scope of the present invention.
  • the compound X is excluded from the scope of the present invention since the compound X undergoes tautomerization to have two double bonds as shown in Y.
  • v is an integer ranging from 0 to 3.
  • the fragment of Formula II is a four membered ring.
  • the fragment of Formula II is a five, six and seven membered ring respectively.
  • the subsequent ring members of the fragment of Formula II being added as a result of definition of "v" have the same meaning as defined for X 1 , X 2 , X 3 and X 4 .
  • X 4a is the new ring member and has the same meaning as defined for X', X 2 , X 3 and X 4 .
  • v is an integer ranging from 0 to 2.
  • p is an integer ranging from 0 to 10. Particularly, p is an integer ranging from 0 to 8.
  • the indication for example for the purpose of this invention shall mean to include the rings with all the single bonds or all the possible double bonds, depending on the valency of the ring member or the possible combinations of single and double bonds.
  • T is selected from Tl to Tl 17
  • Non-limiting representative examples of T are depicted herein below wherein the bond at the right is attached to A as shown.
  • the substituent R' may be attached to at least one possible position.
  • the substituent R" has the same meaning as R' excluding hydrogen.
  • A is C(R I 5 ) 2 or C(R 15 ) 2 -C(R l5 ) 2 or NR 16 .
  • the substituent R 15 is independently selected from hydrogen, halogen, cyano, hydroxy, -CHO, C 1 - C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 2 -C 4 alkoxyalkyl, C 2 -C 4 alkylthioalkyl, C 2 -C 4 alkylsulfinylalkyl, C 2 -C 4 alkylsulfonylalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl, C 2 -C 5 alkoxycarbonyl, C 3 -C 5 alkoxycarbonylalkyl, C 2 -C 5 alkylaminocarbonyl, C 3 -C 5 dialkylaminocarbonyl
  • the substituent R 15 is hydrogen, halogen, cyano, hydroxy, -CHO, C 1 -C 4 alkyl, C 1 - C 4 haloalkyl or C 2 -C 5 alkoxycarbonyl.
  • the substituent R 16 is hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 2 -C 4 alkoxyalkyl, C 2 -C 4 alkylthioalkyl, C 2 -C 4 alkylsulfinylalkyl, C 2 - C 4 alkylsulfonylalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl, C 2 -C 5 alkoxycarbonyl, C 3 - C 5 alkoxycarbonylalkyl, C 2 -C 5 alkylaminocarbonyl, C 3 -C 5 dialkylaminocarbonyl, C 1 -C 4 alkylsulfonyl and C
  • the substituent R 16 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl or C 2 -C 4 alkoxycarbonyl.
  • W is O or S.
  • R 2 is independently hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, halogen, cyano or hydroxyl .
  • R 2 are taken together as C 1 -C 4 alkylene or C 2 -C 4 alkenylene to form a bridged bicyclic or fused bicyclic ring system.
  • R 2 independently is selected from C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, halogen, cyano and hydroxy.
  • Z is C or N.
  • n is an integer ranging from 0 to 9 with a proviso that when Z is N, "n” is an integer ranging from 0 to 8; and when the presentation in ring D is a double bond then "n" is an integer
  • G is an optionally substituted 5- or 6- membered heteroaromatic ring or 5- or 6-membered saturated or partially saturated or unsaturated heterocyclic ring.
  • G is a 5- or 6 membered heteroaromatic ring or 5- or 6- membered saturated or partially saturated or unsaturated heterocyclic ring, each ring optionally substituted with up to 2 substituents in case of 5- membered ring and up to 3 substituents in case of 6- membered ring, each substituent selected from R 3 on carbon ring members and R 1 1 on n ring members.
  • G is a 5- or 6 membered heteroaromatic ring each ring optionally substituted with up to 2 substituents in case of 5- membered ring and up to 3 substituents in case of 6- membered ring, wherein in at least one of the hetero atoms is N; and the other heteroatom is N or S or O.
  • the substituents on G are R 3 on carbon ring members and R l ! on n ring members.
  • G is a 5- membered heteroaromatic ring each ring optionally substituted with up to 1 substituents, wherein in at least one of the hetero atoms is N; and the other heteroatom is S or O.
  • G is selected from the G l to G62 as de icted herein below:
  • each R 3a is independently H or R 3 and each R l l a is independently H or R".
  • R 3 and R" may be attached to any or all of the possible position/s.
  • the substituent R 3 is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with 1 to 2 substituents independently selected from R 4a on carbon ring members and R 4b on n ring members.
  • R 3 is independently C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or halogen.
  • the substituent R 4a is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 - Cio cycloalkylalkyl, C 4 -C 10 alkylcycloalkyl, C 5 -C 10 alkylcycloalkylalkyl, C 1 -C 6 haloalkyl, C 2 - C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, C 1 - C 4 alkoxy, Ci-C 4 haloalkoxy, C 1 -C 4 alkyl thio, C 1 -C 4 alkyl sulfinyl, C 1 -C 4 alkylsulfonyl, C 1 - C 4 haloalky
  • the substituent R 4b is independently C 1 -C 6 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 - C 6 haloalkyl, C 3 -C 6 haloalkenyl, C 3 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl or C 2 -C 4 alkoxyalkyl .
  • the substituent R" is independently C 1 -C 3 alkyl.
  • J is a 5- or 6- membered ring, wherein ring members are selected from carbon, up to 3 N and up to 2 O.
  • J is a 5- or 6- membered ring, wherein ring members are selected from carbon, 1 N and 1 O.
  • J is selected from J l to J86 as depicted herein below:
  • bond on the left is attached to Z 1 and R 3 may be substituted at any or all of the possible position/s and is a single or a double bond.
  • J is selected from and wherein W is C(R 5 ) 2 or CO or O or S or SO or S0 2 or NR 5 .
  • R 5 is -Z 2 Q.
  • the substituents R 25 and R 26 are independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 haloalkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 haloalkoxycarbonyl.
  • R 25 and R 26 can be -Z 4 Q.
  • the carbon to which Q is attached may be chiral or non-chiral carbon.
  • the substituents R 17 and R 18 are independently C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 3 - C 5 cycloalkyl, C 3 -C 6 halocycloalkyl, C 4 -C 10 cycloalkylalkyl, C 4 -C 7 alkylcycloalkyl, C 5 - C 7 alkylcycloalkylalkyl, C 1 -C 5 haloalkyl, C 1 -C 5 alkoxy and C 1 -C 5 haloalkoxy.
  • Q are depicted herein below wherein the bond at the left is attached to J or Z as the case may be.
  • the substituent R 7 may be attached to any possible position/s and the presentation " is a single or a double bond.
  • J & Q together forms aryl or heterocyclic dioxepine ring system.
  • J & Q together forms a fragment selected from M l and M2.
  • the substituents R 5 , R 7 and R 12 may be attached at one or more possible position/s.
  • x is an integer ranging from 0 to 2 and Y is selected from O, S & N.
  • Two R' of Formula II may form a bridged ring system.
  • X' and X 3 may be connected through for example either of -CH 2 -, -CH 2 CH 2 -, -CH 2 CH 2 CH 2 - or -CH 2 CH 2 CH 2 CH 2 - to form a bridged ring system.
  • X 2 and X 3 may be connected to either of -CH 2 -, -CH 2 -, -CH 2 CH 2 -, -CH 2 CH 2 CH 2 -, -CH 2 CH 2 CH 2 CH 2 -, -CH 2 CH 2 (CH 3 )CFI 2 -, or -CH 2 (CH 3 )CH 2 (CH 3 )-.
  • the substituent R 8 is independently selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 - C 6 cycloalkyl, C 4 -C 10 cycloalkylalkyl, C 4 -C 10 alkylcycloalkyl, C 5 -C 10 alkylcycloalkylalkyl, C 1 - C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloal
  • the substituent R 20 is independently hydrogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.
  • the substituent R 21 is independently hydrogen, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 3 -C 8 cycloalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 8 haloalkylcarbonyl, C 2 -C 8 alkoxycarbonyl or C 2 -C 8 haloalkoxycarbonyl.
  • a is an integer independently ranging from 0 to 2.
  • Non-limiting compounds of the present invention comprise:
  • Compound No.360 l-(2-(4-(4-(5-(2,5-difluorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-l- yl)-2-oxoethyl)-3-isocyano-5-(trifluoiOmethyl)pyridin-2(lH)-one;
  • Compound No.361 3-bromo-l-(2-(4- (4-(l,5-dihydrobenzo[e][l,3]dioxepin-3-yl)thiazol-2-yl)piperidin-l-yl)-2-oxoethyl)-5- (trifluoromethyl)pyridin-2(lH)-one;
  • Compound No.360 l-(2-(4-(4-(4-(5-(2,5-difluorophenyl)-4,5-dihydroisoxazol-3-
  • Compound No. 402 l-(2-(4-(4-(5-(2-bromo-5-fluorophenyl)-4,5-dihydroisoxazol-3- yl)thiazol-2-yl)piperidin-l-yl)-2-oxoethyl)-3-(trifluoromethyl)pyridin-2(lH)-one;
  • Compound No.403 1- (2-(4-(4-(4-(5-(3,5-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-l-yl)-2-oxoethyl)-5- (trif]uoromethyl)pyridin-2(lH)-one; Compound No.
  • Compound No. 506 l-(2-(4-(4-(3-(2,6-difluorophenyl)-lH-pyrazol-l-yl)thiazol-2-yl)piperidin-l-yl)-2- oxoethyl)-3-(trifluoromethyl)pyridin-2(lH)-one;
  • Compound No. 507 5-chloro-l-(2-(4-(4-(4-(3-(2,6- difluorophenyl)-! H-pyrazol-l-yl)thiazol-2-yl)piperidin-l-yl)-2-oxoethyl)-3-(trifluoromethyl)pyridin-
  • 641 6-chloro-l-(2-(4-(4-(5-(2,6- difluorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-l-yl)-2-oxoethyl)-3- (trifluoromethyl)pyridin-2(lH)-one; Compound No.
  • 642 6-chloro-l-(2-(4-(4-(5-(2,6-dichlorophenyl)- 4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-l-yl)-2-oxoethyl)-3-(trifluoromethyl)pyridin-2(
  • R 22 is hyrdoxy, bromine, chlorine, iodine or O- C 1 -C 4 alkyl.
  • corresponding C 1 -C 3 alkyl ester or acyl chloride can prepared by alkylating 2-oxo compound (equivalent to C of example 16) using C 1 -C 3 alkyl 2-haloacetate to obtain C 1 -C 3 alkylated 2-oxo compound (equivalent to D of example 16).
  • C 1 -C 3 alkylated 2-oxo compound is then optionally hydrolyzed to obtain an acid (equivalent to E of example 16).
  • the C 1 -C 3 alkylated 2-oxo compound obtained in the first step or the acid obtained in the second step is halogenated using suitable halogenating agent to obtain acyl halide.
  • novel and inventive compounds of the present invention are effective in preventing against and controlling phytopathogenic micro-organisms.
  • An anion part of the salt in case the compound of Formula I is cationic or capable of forming a cation can be inorganic or organic.
  • a cation part of the salt in case the compound of Formula I is an anionic or capable of forming anion can be inorganic or organic.
  • inorganic anion part of the salt examples include but are not limited to chloride, bromide, iodide, fluoride, sulfate, phosphate, nitrate, nitrite, hydrogen carbonates, hydrogen sulfate.
  • organic anion part of the salt examples include but are not limited to formate, alkanoates, carbonates, acetates, trifluoroacetate, trichloroacetate, propionate, glycolate, thiocyanate, lactate, succinate, malate, citrates, benzoates, cinnamates, oxalates, alkylsulphates, alkylsulphonates, arylsulphonates aryldisulphonates, alkylphosphonates, arylphosphonates, aryldiphosphonates, p-toluenesulphonate, and salicylate.
  • inorganic cation part of the salt examples include but are not limited to alkali and alkaline earth metals.
  • organic cation part of the salt include but are not limited to pyridine, methyl amine, imidazole, benzimidazole, hitidine, phosphazene, tetramethyl ammonium, tetrabutylammonium, choline and tri methyl amine.
  • Metal ions in metal complexes of the compound of Formula I are especially the ions of the elements of the second main group, especially calcium and magnesium, of the third and fourth main group, especially aluminium, tin and lead, and also of the first to eighth transition groups, especially chromium, manganese, iron, cobalt, nickel, copper, zinc and others. Particular preference is given to the metal ions of the elements of the fourth period and the first to eighth transition groups.
  • the metals can be present in the various valencies that they can assume.
  • the present invention also relates to the compound of Formula I, in the composition with one or more inert carriers for controlling or preventing against phytopathogenic micro-organisms.
  • the compound of Formula I of the present invention in the composition can be agriculturally acceptable salts, metal complexes, constitutional isomers, stereo-isomers. diastereoisomers, enantiomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, optical isomers, polymorphs, geometric isomers, or N-oxides thereof.
  • the excipient can be an inert carrier or any other essential ingredient such as surfactants, additives, solid diluents and liquid diluents.
  • the present invention also relates to the compound of Formula I in the composition comprising at least one active compatible compound selected from fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertiliers and nutrients.
  • active compatible compounds selected from fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertiliers and nutrients.
  • active compatible compounds selected from fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertiliers and nutrients.
  • the concentration of the compound of present invention in the composition ranges from 1 to 90% by weight with respect to the total weight of the composition, preferably from 5 to 50% by weight with respect to the total weight of the composition.
  • fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics and nutrients can be combined with at least one compound of the Formula I of the present invention.
  • fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients disclosed and reported in WO2016156129 can be combined with at least one compound of the Formula I of the present invention.
  • fungicides insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients reported in WO20161 56129 are incorporated herein by way of reference as non-limiting examples to be combined with at least one compound of the Formula I of the present invention.
  • the present invention also relates to a use of the compound of Formula 1 or of the compound of Formula 1 in the composition for control ling or preventing against phytopathogenic micro-organisms such as fungi, stramenopiles, bacteria, insects, nematodes, mites in agricultural crops and or horticultural crops.
  • phytopathogenic micro-organisms such as fungi, stramenopiles, bacteria, insects, nematodes, mites in agricultural crops and or horticultural crops.
  • the present invention also relates to a use of the compound of Formula I or of the compound of Formula I in the composition for controlling or preventing against phytopathogenic fungi and oomycetes in agricultural crops and or horticulture crops.
  • the compound of Formula I or the compound of Formula I in the composition may be used to treat several fungal pathogens.
  • pathogens of fungal diseases include:
  • Albugo species for example Albugo Candida
  • Bremia species for example Bremia lactucae
  • Peronospora species for example Peronospora pisi or P. brassicae
  • Phytophthora species for example Phytophthora infestans
  • Plasmopara species for example Plasmopara viticola
  • Pseiidoperonospora species for example Pseudoperonospora hiimuli or Pseiidoperonospora cubensis
  • Pythium species for example Pythhim 8%
  • Blumeria species for example Blumeria graminis
  • Podosphaera species for example Podosphaera leucotricha
  • Sphaerotheca species for example Sphaerotheca fuliginea
  • Uncinula species for example Uncinula necator
  • Erysiphe species for example Erysiphe cichoracearu
  • Gymnosporangium species for example Gymnosporangium sabinae
  • Hemileia species for example Hemileia vastatrix
  • Phakopsora species for example Phakopsora pachyrhizi or Phakopsora meibomiae
  • Puccinia species for example Puccinia recondita, Puccinia graminis oder Puccinia striiformis
  • Uromyces species for example Uromyces appendiculatus
  • ear and panicle diseases caused, for example, by Alternaria species, for example Alternaria spp.; Aspergillus species, for example Aspergillus flavus; Cladosporium species, for example Cladosporium cladosporioides; Claviceps species, for example Claviceps purpurea; Fusarium species, for example Fusarium culmorum; Gibberella species, for example Gibberella zeae; Monographella species, for example Monographella nivalis; Stagnospora species, for example Stagnospora nodorum; diseases caused by smut fungi, for example Sphacelotheca species, for example Sphacelotheca reiliana; Tilletia species, for example Tilletia caries or Tilletia controversa; Urocystis species, for example Urocystis occulta; Ustilago species, for example Ustilago nuda;
  • Alternaria species for example Alternaria brassicicola
  • Aphanomyces species for example Aphanomyces euteiches
  • Ascochyta species for example Ascochyta lends
  • Aspergillus species for example Aspergillus flavus
  • Cladosporium species for example Cladosporium herbarum
  • Cochliobolus species for example Cochliobolus sativus (conidial form: Drechslera, Bipolaris Syn: Helminthosporium);
  • Colletolrichum species for example Colletolrichum coccodes
  • Fusarium species for example Fusarium culmorum
  • Gibberella species for example Gibberella zeae
  • Macrophomina species for example Macrophomina phaseolina
  • Microdochium species for example Microdochium nivale
  • Monographella species for example,
  • wi lt diseases caused, for example, by Monilinia species, for example Monilinia laxa;
  • Exobasidium species for example Exobasidium vexans
  • Taphrina species for example Taphrina deformans
  • degenerative diseases in woody plants caused, for example, by Esca species, for example Phaeomoniella chlamydospora, Phaeoacremonhim aleophilum or Fomitiporia mediterranea; Ganoderma species, for example Ganoderma boninense;
  • Botrytis species for example Botrytis cinerea
  • diseases of plant tubers caused, for example, by Rhizoctonia species, for example Rhizoctonia solani
  • Helminthosporhim species for example Helminthosporium solani
  • diseases caused by bacterial pathogens for example Xanthomonas species, for example Xanthomonas campestris pv. oryzae; Pseiidomonas species, for example Pse domonas syringae pv. lachrymans; Erwinia species, for example Erwinia amylovora; Ralstonia species, for example Ralstonia solanacearam;
  • phytophthora rot (Phytophthora megasperma), brown stem rot ⁇ Phialophora gregata), pythium rot (Pythium aphanidermatum, Pythium irregulare, Pythium debaryanum, Pythium myriotylum, Pythium ultimum), rhizoctonia root rot, stem decay, and damping-off (Rhizoctonia solani), sclerotinia stem decay (Sclerotmia sclerotiorum), sclerotinia southern blight (Sclerotinia rolfsii), thielaviopsis root rot (Thielaviopsis basicola).
  • Plants which can be treated in accordance with the invention include the following: Rosaceae sp (for example pome fruits such as apples, pears, apricots, cherries, almonds and peaches), Ribesioidae sp. , Juglandaceae sp. , Betulaceae sp. , Anacardiaceae sp., Fagaceae sp., Moraceae sp. , Oleaceae sp. , Actinidaceae sp. , Lauraceae sp. , Musaceae sp. (for example banana trees and plantations), Rubiaceae sp. (for example coffee), Tlteaceae sp.
  • Rosaceae sp for example pome fruits such as apples, pears, apricots, cherries, almonds and peaches
  • Ribesioidae sp. Juglandaceae sp.
  • Sterculiceae sp. for example lemons, oranges and grapefruit
  • Vitaceae sp. for example grapes
  • Solanaceae sp. for example tomatoes, peppers
  • Liliaceae sp. Aster aceae sp.
  • Umbelliferae sp. for example lettuce
  • Cibashaceae sp. for example cucumber
  • Alliaceae sp. for example leek, onion
  • Papilionaceae sp. for example peas
  • major crop plants such as PoaceaelGramineae sp.
  • Asteraceae sp. for example sunflower
  • Brassicaceae sp. for example white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radishes, and oilseed rape, mustard, horseradish and cress
  • Fabacae sp. for example bean, peanuts
  • Papilionaceae sp. for example soya bean
  • Solanaceae sp. for example potatoes), Chenopodiaceae sp.
  • the agricultural crops are cereals, corn, rice, soybean and other leguminous plants, fruits and fruit trees, nuts and nut trees, citrus and citrus trees, any horticultural plants, cucurbitaceae, oleaginous plants, tobacco, coffee, tea, cacao, sugar beet, sugar cane, cotton, potato, tomato, onions, peppers and other vegetables, and ornamentals.
  • the present invention further relates to the use of the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound for treating seeds with the purpose of protecting the seeds, the germinating plants and emerged seedlings against phytopathogenic micro-organisms.
  • the present invention further relates to seeds which have been treated with the compound of the Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound for protection from phytopathogenic micro-organisms.
  • the present invention also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic micro-organisms in agricultural crops and or horticultural crops wherein the compound of Formula I or the compound of Formula 1 in the composition optionally comprising at least one active compatible compound, is applied to the plants, to parts thereof or the locus thereof.
  • the effective amount of compound of Formula 1 or the compound of Formula I in the composition optionally comprising at least one active compatible compound ranges from 1 gai to 5000 gai per hectare in agriculture or horticulture crops.
  • the present invention relates to the compound of the Formula I or the compound of the Formula I in the composition optionally comprising at least one active compatible compound applied to a plant, plant parts or locus thereof.
  • the present invention furthermore includes a method for treating seed, particularly seeds (dormant, primed, pregerminated or even with emerged roots and leaves) treated with the compound of the Formula I or the compound of the Formula I in the composition optionally comprising at least one active compatible compound.
  • seed particularly seeds (dormant, primed, pregerminated or even with emerged roots and leaves) treated with the compound of the Formula I or the compound of the Formula I in the composition optionally comprising at least one active compatible compound.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound is applied to the seeds of plants for controlling or preventing infestation of useful plants by phytopathogenic micro-organisms in agricultural and or horticultural corps.
  • methods for the treatment of seed should also take into consideration the intrinsic phenotypes of transgenic plants in order to achieve optimum protection of the seed and the germinating plant with a minimum of crop protection compositions being employed.
  • One of the advantages of the present invention is that the treatment of the seeds with the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound not only protects the seed itself, but also the resulting plants after emergence, from animal pests and/or phytopathogenic harmful micro-organisms. In this way, the immediate treatment of the crop at the time of sowing or shortly thereafter protect plants as well as seed treatment in prior to sowing. It is likewise considered to be advantageous that the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound can be used especially also for transgenic seed, in which case the plant which grows from this seed is capable of expressing a protein which acts against pests, herbicidal damage or abiotic stress.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound are suitable for protection of seed of any plant variety which is used in agriculture, in the greenhouse, i n forests or in horticulture. More particularly, the seed is that of cereals (such as wheat, barley, rye, millet and oats), oilseed rape, maize, cotton, soybeen, rice, potatoes, sunflower, beans, coffee, beet (e.g. sugar beet and fodder beet), peanut, vegetables (such as tomato, cucumber, onions and lettuce), lawns and ornamental plants. Of particular significance is the treatment of the seed of wheat, soybean, oi lseed rape, maize and rice. ;
  • transgenic seed with the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound
  • heterologous genes in transgenic seeds may originate, for example, from microorganisms of the species Bacillus, Rhizobhim, Pseitdomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladiiim.
  • These heterologous genes preferably originate from Bacillus sp., in which case the gene product is effective against the European corn borer and/or the Western corn rootworm.
  • the heterologous genes originate from Bacillus thuringiensis.
  • the compound of Formula I or the compound of Formula I in the composition optional ly comprising at least one active compatible compound is applied to seeds.
  • the seed is treated in a state in which it is sufficiently stable for no damage to occur in the course of treatment.
  • seeds can be treated at any time between harvest and some time after sowing. It is customary to use seed which has been separated from the plant and freed from cobs, shells, stalks, coats, hairs or the flesh of the fruits. For example, it is possible to use seed which has been harvested, cleaned and dried down to a moisture content of less than 15% by weight.
  • seed which, after drying, for example, has been treated with water and then dried again or seeds just after priming, or seeds stored in primed conditions or pre-germinated seeds, or seeds sown on nursery trays, tapes or paper.
  • the amount of the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound applied to the seed and/or the amount of further additives is selected such that the germination of the seed is not impaired, or that the resulting plant is not damaged.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound can be applied directly, i.e. without containing any other components and without having been diluted.
  • the compounds of the Formula I can be converted to the customary Formulations relevant to on-seed applications, such as solutions, emulsions, suspensions, powders, foams, slurries or combined with other coating compositions for seed, such as film forming materials, pelleting materials, fine iron or other metal powders, granules, coating material for inactivated seeds, and also ULV Formulations.
  • seeds can be coated with polymer.
  • the polymer coating is comprised of a binder, a wax and a pigment, and one or more stabilizers in an amount effective to stabilize the suspension.
  • the binder can be a polymer selected from the group consisting of vinyl acetate- ethylene copolymer, vinyl acetate homopolymer, vinyl acetate-acrylic copolymer, vinylacrylic, acrylic, ethylene-vinyl chloride, vinyl ether maleic anhydride, or butadiene styrene. Other similar polymers can be used.
  • Formulations are prepared in a known manner, by mixing the active ingredients or active ingredient combinations with customary additives, for example customary extenders and solvents or diluents, dyes, wetting agents, dispersants, emulsifiers, antifoams, preservatives, secondary thickeners, adhesives, gibberellins, and also water.
  • customary additives for example customary extenders and solvents or diluents, dyes, wetting agents, dispersants, emulsifiers, antifoams, preservatives, secondary thickeners, adhesives, gibberellins, and also water.
  • Useful dyes which may be present in the seed dressing Formulations usable in accordance with the invention are all dyes which are customary for such purposes. It is possible to use either pigments, which are sparingly soluble in water, or dyes, which are soluble in water. Examples include the dyes known by the names Rhodamine B, C.I. Pigment Red 1 12 and C.I. Solvent Red 1 .
  • Useful wetting agents which may be present in the seed dressing Formulations usable in accordance with the invention are all substances which promote wetting and which are conventionally used for the Formulation of active agrochemical ingredients.
  • Usable with preference are alkylnaphthalenesulphonates, such as diisopropyl- or diisobutylnaphthalenesulphonates.
  • Useful dispersants and/or emulsifiers which may be present in the seed dressing Formulations usable in accordance with the invention are all nonionic, anionic and cationic dispersants conventionally used for the Formulation of active agrochemical ingredients. Usable with preference are nonionic or anionic dispersants or mixtures of nonionic or anionic dispersants.
  • Useful nonionic dispersants include especially ethylene oxide/propylene oxide block polymers, alkylphenol polyglycol ethers and tristryrylphenol polyglycol ether, and the phosphated or sulphated derivatives thereof.
  • Suitable anionic dispersants are especially lignosulphonates, polyacrylic acid salts and arylsulphonate/formaldehyde condensates.
  • Antifoams which may be present in the seed dressing Formulations usable in accordance with the invention are all foam-inhibiting substances conventionally used for the Formulation of active agrochemical ingredients. Silicone antifoams and magnesium stearate can be used with preference.
  • Preservatives which may be present in the seed dressing Formulations usable in accordance with the invention are all substances usable for such purposes in agrochemical compositions. Examples include dichlorophene and benzyl alcohol hemiformal.
  • Secondary thickeners which may be present in the seed dressing Formulations usable in accordance with the invention are all substances usable for such purposes in agrochemical compositions.
  • Preferred examples include cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and finely divided silica.
  • Adhesives which may be present in the seed dressing Formulations usable in accordance with the invention are all customary binders usable in seed dressing products.
  • Preferred examples include polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose.
  • the Formulations for on-seed applications usable in accordance with the invention can be used to treat a wide variety of different kinds of seed either directly or after prior dilution with water.
  • the concentrates or the preparations obtainable therefrom by dilution with water can be used to dress the seed of cereals, such as wheat, barley, rye, oats, and triticale, and also seeds of maize, soybean, rice, oilseed rape, peas, beans, cotton, sunflowers, and beets, or else a wide variety of different vegetable seeds.
  • the Formulations usable in accordance with the invention, or the di lute preparations thereof can also be used for seeds of transgenic plants. In this case, enhanced effects may also occur in interaction with the substances formed by expression.
  • the application rate of the Formulations usable in accordance with the invention can be varied within a relatively wide range. It is guided by the particular content of the active ingredients in the Formulations and by the seeds.
  • the application rates of each single active ingredient are generally between 0.001 and 15 gai per kilogram of seed, preferably between 0.01 and 5 gai per kilogram of seed.
  • the application rate of the compound of Formula I or the compound of Formula 1 in a composition optionally comprising at least one active compatible compound is: in the case of treatment of plant parts, for example leaves: from 0. 1 to 10000 gai/ha, preferably from 5 to 1000 gai/ha, more preferably from 5 to 100 gai/ha (in the case of application by watering or dripping, it is even possible to reduce the application rate, especially when inert substrates such as rockwool or perlite are used);
  • the compound of the Formula I can, at particular concentrations or application rates, also be used as safeners, growth regulators or agents to improve plant properties, or as microbicides, for example as fungicides, antimycotics, bactericides, viricides (including compositions against viroids) or as compositions against phytoplasmas ML O (Mycoplasma-like organisms) and RLO (Rickettsia-like organisms).
  • the compounds of the Formula I intervene in physiological processes of plants and can therefore also be used as plant growth regulators.
  • Plant growth regulators may exert various effects on plants. The effect of the substances depends essentially on the time of application in relation to the developmental stage of the plant, the plant variety and also on the amounts of active ingredient applied to the plants or their environment and on the type of application. In each case, growth regulators should have a particular desired effect on the crop plants.
  • Growth regulating effects comprise earlier germination, better emergence, more developed root system and/or improved root growth, increased ability of tillering, more productive tillers, earl ier flowering, increased plant height and/or biomass, shorting of stems, improvements in shoot growth, number of kernels/ear, number of ears/m 2 , number of stolons and/or number of flowers, enhanced harvest index, bigger leaves, less dead basal leaves, improved phyllotaxy, earlier maturation/ earlier fruit finish, homogenous riping, increased duration of grain filling, better fruit finish, bigger fruit/vegetable size, sprouting resistance and reduced lodging.
  • Increased or improved yield is referring to total biomass per hectare, yield per hectare, kernel/fruit weight, seed size and/or hectolitre weight as well as to improved product quality, comprising:
  • improved marketability relating to improved fruit/grain quality, size distribution (kernel, fruit, etc.), increased storage/shelf-life, firmness /softness, taste (aroma, texture, etc.), grade (size, shape, number of berries, etc.), number of berries/fruits per bunch, crispness, freshness, coverage with wax, frequency of physiological disorders, colour, etc.;
  • decreased undesired ingredients such as e.g. less mycotoxines, less aflatoxines, geosmin level, phenol ic aromas, lacchase, polyphenol oxidases and peroxidases, nitrate content etc.
  • Plant growth-regulating compounds can be used, for example, to slow down the vegetative growth of the plants.
  • Such growth depression is of economic interest, for example, in the case of grasses, since it is thus possible to reduce the frequency of grass cutting in ornamental gardens, parks and sport facilities, on roadsides, at airports or in fruit crops.
  • Also of significance is the inhibition of the growth of herbaceous and woody plants on roadsides and in the vicinity of pipelines or overhead cables, or quite generally in areas where vigorous plant growth is unwanted.
  • growth regulators for inhibition of the longitudinal growth of cereal. This reduces or completely eliminates the risk of lodging of the plants prior to harvest.
  • growth regulators in the case of cereals can strengthen the culm, which also counteracts lodging.
  • the employment of growth regulators for shortening and strengthening culms allows the deployment of higher fertilizer volumes to increase the yield, without any risk of lodging of the cereal crop.
  • vegetative growth depression allows denser planting, and it is thus possible to achieve higher yields based on the soil surface.
  • Another advantage of the smaller plants obtained in this way is that the crop is easier to cultivate and harvest.
  • Reduction of the vegetative plant growth may also lead to increased or improved yields because the nutrients and assimilates are of more benefit to flower and fruit formation than to the vegetative parts of the plants.
  • growth regulators can also be used to promote vegetative growth. This is of great benefit when harvesting the vegetative plant parts. However, promoting vegetative growth may also promote generative growth in that more assimilates are formed, resulting in more or larger fruits.
  • beneficial effects on growth or yield can be achieved through improved nutrient use efficiency, especially n (N)-use efficiency, phosphours (P)-use efficiency, water use efficiency, improved transpiration, respiration and/or C0 2 assimilation rate, better nodulation, improved Ca-metabolism etc.
  • growth regulators can be used to alter the composition of the plants, which in turn may result in an improvement in quality of the harvested products. Under the influence of growth regulators, parthenocarpic fruits may be formed. In addition, it is possible to influence the sex of the flowers. It is also possible to produce sterile pollen, which is of great importance in the breeding and production of hybrid seed.
  • growth regulators can control the branching of the plants.
  • by breaking apical dominance it is possible to promote the development of side shoots, which may be highly desirable particularly in the cultivation of ornamental plants, also in combination with an inhibition of growth.
  • side shoots which may be highly desirable particularly in the cultivation of ornamental plants, also in combination with an inhibition of growth.
  • the amount of leaves on the plants can be controlled such that defoliation of the plants is achieved at a desired time.
  • defoliation plays a major role in the mechanical harvesting of cotton, but is also of interest for facilitating harvesting in other crops, for example in viticulture.
  • Defoliation of the plants can also be undertaken to lower the transpiration of the plants before they are transplanted.
  • growth regulators can modulate plant senescence, which may result in prolonged green leaf area duration, a longer grain filling phase, improved yield quality, etc.
  • Growth regulators can likewise be used to regulate fruit dehiscence. On the one hand, it is possible to prevent premature fruit dehiscence. On the other hand, it is also possible to promote fruit dehiscence or even flower abortion to achieve a desired mass ("thinning"). In addition, it is possible to use growth regulators at the time of harvest to reduce the forces required to detach the fruits, in order to allow mechanical harvesting or to facilitate manual harvesting.
  • Growth regulators can also be used to achieve faster or else delayed ripening of the harvested material before or after harvest. This is particularly advantageous as it allows optimal adjustment to the requirements of the market. Moreover, growth regulators in some cases can improve the fruit colour. In addition, growth regulators can also be used to synchronize maturation within a certain period of time. This establishes the prerequisites for complete mechanical or manual harvesting in a single operation, for example in the case of tobacco, tomatoes or coffee.
  • growth regulators By using growth regulators, it is additionally possible to influence the resting of seed or buds of the plants, such that plants such as pineapple or ornamental plants in nurseries, for example, germinate, sprout or flower at a time when they are normally not inclined to do so. In areas where there is a risk of frost, it may be desirable to delay budding or germination of seeds with the aid of growth regulators, in order to avoid damage resulting from late frosts.
  • growth regulators can induce resistance of the plants to frost, drought or high salinity of the soil. This allows the cultivation of plants in regions which are normally unsuitable for this purpose.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound also exhibit potent strengthening effect in plants. Accordingly, they can be used for mobilizing the defences of the plant against attack by undesirable micro-organisms.
  • Plant-strengthening (resistance-inducing) substances in the present context are substances capable of stimulating the defence system of plants in such a way that the treated plants, when subsequently inoculated with undesirable micro-organisms, develop a high degree of resistance to these microorganisms.
  • plant physiology effects comprise the following:
  • Abiotic stress tolerance comprising tolerance to high or low temperatures, drought tolerance and recovery after drought stress, water use efficiency (correlating to reduced water consumption), flood tolerance, ozone stress and UV tolerance, tolerance towards- chemicals like heavy metals, salts, pesticides etc.
  • Biotic stress tolerance comprising increased fungal resistance and increased resistance against nematodes, viruses and bacteria.
  • biotic stress tolerance preferably comprises increased fungal resistance and increased resistance against nematodes.
  • the compound of Formula 1 or the compound of Formula 1 in the composition optionally comprising at least one active compatible compound can reduce the mycotoxin content in the harvested material and the foods and feeds prepared therefrom.
  • Mycotoxins include particularly, but not exclusively, the following: deoxynivalenol (DON), nivalenol, 15-Ac-DON, 3-Ac-DON, T2- and HT2- toxin, fumonisins, zearalenon, moniliformin, fusarin, diaceotoxyscirpenol (DAS), beauvericin, enniatin, fusaroproliferin, fusarenol, ochratoxins, patulin, ergot alkaloids and aflatoxins which can be produced, for example, by the following fungi : Fusarium spec, such as F. acuminatum, F. asialicum, F. avenaceum, F.
  • Penicillium spec such as P. verrucosum, P. viridicatum, P. citrinum, P. expansum, P. claviforme, P. roqueforti, Claviceps spec, such as C. purpurea, C. fusiformis, C. paspali, C. africana, Stachybotrys spec, and others.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound can also be used in the protection of materials, for protection of industrial materials against attack and destruction by phytopathogenic micro-organisms.
  • the compounds of the Formula I can be used as antifouling compositions, alone or in combinations with other active ingredients.
  • Industrial materials in the present context are understood to mean inanimate
  • industrial materials which are to be protected by inventive compositions from microbial alteration or destruction may be adhesives, glues, paper, wallpaper and board/cardboard, textiles, carpets, leather, wood, fibers and tissues, paints and plastic articles, cooling lubricants and other materials which can be infected with or destroyed by micro-organisms.
  • Parts of production plants and buildings, for example cooling-water circuits, cooling and heating systems and ventilation and air- conditioning units, which may be impaired by the proliferation of micro-organisms may also be mentioned within the scope of the materials to be protected.
  • Industrial materials within the scope of the present invention preferably include adhesives, sizes, paper and card, leather, wood, paints, cooling lubricants and heat transfer fluids, more preferably wood.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound may prevent adverse effects, such as rotting, decay, discoloration, decoloration or formation of mould.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound may also be used against fungal diseases liable to grow on or inside timber.
  • the term "timber" means all types of species of wood, and all types of working of this wood intended for construction, for example solid wood, high-density wood, laminated wood, and plywood.
  • the method for treating timber according to the invention mainly consists in contacting a composition according to the invention; this includes for example direct application, spraying, dipping, injection or any other suitable means.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound can be used to protect objects which come into contact with saltwater or brackish water, especially hulls, screens, nets, buildings, moorings and signalling systems, from fouling.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound can also be employed for protecting storage goods.
  • Storage goods are understood to mean natural substances of vegetable or animal origin or processed products thereof which are of natural origin, and for which long-term protection is desired.
  • Storage goods of vegetable origin for example plants or plant parts, such as stems, leaves, tubers, seeds, fruits, grains, can be protected freshly harvested or after processing by (pre)drying, moistening, comminuting, grinding, pressing or roasting.
  • Storage goods also include timber, both unprocessed, such as construction timber, electricity poles and barriers, or in the form of finished products, such as furniture.
  • Storage goods of animal origin are, for example, hides, leather, furs and hairs.
  • the inventive compositions may prevent adverse effects, such as rotting, decay, discoloration, decoloration or formation of mould.
  • Micro-organisms capable of degrading or altering the industrial materials include, for example, bacteria, fungi, yeasts, algae and slime organisms.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound preferably act against fungi, especially moulds, wood-discoloring and wood-destroying fungi (Ascomycetes, Basidiomycetes, Deiiteromycetes and Zygomycetes), and against slime organisms and algae.
  • micro-organisms of the following genera Alternaria, such as Alternaria tenuis; Aspergillus, such as Aspergillus niger; Chaetomium, such as Chaetomium globosum; Coniophora, such as Coniophora puetana; Lentinus, such as Lenlinus tigriniis; Penicillium, such as Penicillium glaucum; Polyporus, such as Polyporus versicolor, Aureobasidium, such as Aureobasidium pullulans; Sclerophoma, such as Sclerophoma pityophila; Trichoderma, such as Trichoderma viride; Ophiostoma spp., Ceratocystis spp., Humicola spp., Petriella spp., Trichurus spp., Coriohis spp., Gloeophyllwn spp., Pleurotits spp.
  • the compound of Formula I or the compound of Formula 1 in the composition optionally comprising at least one active compatible compound also has very good anti mycotic effects.
  • the compound of Formula 1 or the compound of Formula I in the composition optionally comprising at least one active compatible compound can be used also to control important fungal pathogens in fish and Crustacea farming, e.g. saprolegnia diclina in trouts, saprolegnia parasitica in crayfish.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound can therefore be used both in medical and in non-medical applications.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound can be used as such, in the form of their Formulations or the use forms prepared therefrom, such as ready-to-use solutions, suspensions, wettable powders, pastes, soluble powders, dusts and granules.
  • Application is accomplished in a customary manner, for example by watering, spraying, atomizing, broadcasting, dusting, foaming, spreading-on and the like. It is also possible to deploy the active ingredients by the ultra-low volume method or to inject the active ingredient preparation/the active ingredient itself into the soil. It is also possible to treat the seed of the plants.
  • plants and their parts in accordance with the invention, preferably with wild plant species and plant cultivars, or those obtained by conventional biological breeding methods, such as crossing or protoplast fusion, and also parts thereof.
  • transgenic plants and plant cultivars obtained by genetic engineering methods if appropriate in combination with conventional methods (Genetically Modified Organisms), and parts thereof are treated.
  • the terms "parts” or “parts of plants” or “plant parts” have been explained above. More preferably, plants of the plant cultivars which are commercially available or are in use are treated in accordance with the invention.
  • Plant cultivars are understood to mean plants which have new properties ("traits") and have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. They can be cultivars, varieties, bio- or genotypes.
  • the method of treatment according to the invention can be used in the treatment of genetically modified organisms (GMOs), e.g. plants or seeds.
  • GMOs genetically modified organisms
  • Genetically modified plants are plants of which a heterologous gene has been stably integrated into genome.
  • the expression "heterologous gene” essentially means a gene which is provided or assembled outside the plant and when introduced in the nuclear, chloroplastic or mitochondrial genome gives the transformed plant new or improved agronomic or other properties by expressing a protein or polypeptide of interest or by downregulating or silencing other gene(s) which are present in the plant (using for example, antisense technology, cosuppression technology, RNA interference - RNAi - technology or microRNA - miRNA - technology).
  • a heterologous gene that is located in the genome is also called a transgene.
  • a transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.
  • Plants and plant cultivars which are preferably to be treated according to the invention include all plants which have genetic material which impart particularly advantageous, useful traits to these plants (whether obtained by breeding and/or biotechnological means).
  • Plants and plant cultivars which are also preferably to be treated according to the invention are resistant against one or more biotic stresses, i.e. said plants show a better defense against ani mal and microbial pests, such as against nematodes, insects, mites, phytopathogenic fungi, bacteria, viruses and/or viroids. Plants and plant cultivars which may also be treated according to the invention are those plants which are resistant to one or more abiotic stresses.
  • Abiotic stress conditions may include, for example, drought, cold temperature exposure, heat exposure, osmotic stress, flooding, increased soil salinity, increased mineral exposure, ozone exposure, high light exposure, limited availability of n nutrients, limited availability of phosphorus nutrients, shade avoidance.
  • Plants and plant cultivars which may also be treated according to the invention are those plants characterized by enhanced yield characteristics. Increased yield in said plants can be the result of, for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved n use, enhanced carbon assimilation, improved photosynthesis, increased germination efficiency and accelerated maturation.
  • Yield can furthermore be affected by improved plant architecture (under stress and non-stress conditions), including but not limited to, early flowering, flowering control for hybrid seed production, seedling vigor, plant size, internode number and distance, root growth, seed size, fruit size, pod size, pod or ear number, seed number per pod or ear, seed mass, enhanced seed filling, reduced seed dispersal, reduced pod dehiscence and lodging resistance.
  • Further yield traits include seed composition, such as carbohydrate content and composition for example cotton or starch, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
  • Plants that may be treated according to the invention are hybrid plants that already express the characteristic of heterosis or hybrid vigor which results in generally higher yield, vigor, health and resistance towards biotic and abiotic stresses).
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering which may be treated according to the invention are herbicide-tolerant plants, i.e. plants made tolerant to one or more given herbicides. Such plants can be obtained either by genetic transformation, or by selection of plants containing a mutation imparting such herbicide tolerance.
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering which may also be treated according to the invention are insect-resistant transgenic plants, i.e. plants made resistant to attack by certain target insects. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such insect resistance.
  • Plants or plant cultivars which may also be treated according to the invention are tolerant to abiotic stresses. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such stress resistance. Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention show altered quantity, quality and/or storage-stability of the harvested product and/or altered properties of specific ingredients of the harvested product.
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as cotton plants, with altered fiber characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered fiber characteristics.
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered oil profile characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered oil profile characteristics.
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered seed shattering characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered seed shattering characteristics and include plants such as oilseed rape plants with delayed or reduced seed shattering. Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as tobacco plants, with altered post-translational protein modification patterns.
  • a compound of Formula 3 is prepared by coupling corresponding acid of Formula 1 with an amine of Formula 2 (or its salt) in the presence of a dehydrative coupling reagent such as dicyclohexylcarbodiimide (DCC), l -(3-dimethy!aminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) 3- [Bis(dimethylamino)methyliumyl]-3FI-benzotriazol-l -oxide hexafluorophosphate (HBTU), or 1 - [Bis(dimethylamino)methylene]-l FI- l ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU).
  • DCC dicyclohexylcarbodiimide
  • EDC l -(3-dimethy!aminopropyl)-3-ethylcarbodiimide hydrochloride
  • Polymer-supported reagents are also useful here, such as polymer-bound cyclohexylcarbodiimide. These reactions are typically carried out at 0-40 °C in a solvent such as dichloromethane, acetonitrile or dimethylformamide in the presence of a base such as triethylamine or diisopropylethylamine.
  • amides of Formula 3 wherein W is O can be converted to thioamides of Formula 3a wherein W is S using a variety of standard thionating reagents such as phosphorus pentasulfide or 2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4- diphosphetane-2,4-disulfide (Lawesson's reagent).
  • standard thionating reagents such as phosphorus pentasulfide or 2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4- diphosphetane-2,4-disulfide (Lawesson's reagent).
  • R 2 CH 2 COOH where R 2 is a heterocyclic ring linked through n can be prepared by reacting the corresponding R 2 H compound with a haloacetic acid or ester in the presence of base; followed by hydrolysis.
  • the amine compound of Formula 2 can be prepared from the protected amine compound of Formula 4 where ⁇ ' is an amine-protecting group.
  • a compound of the Formula 4 is converted to a compound of the Formula 2 by suitable methods for removing protecting groups described in the literature (Protective Groups in Organic Synthesis; Theodora W. Greene, Peter G. M. Wilts; Wiley-lnterscience; Third Edition; 1999; 494-653).
  • tert-butoxycarbonyl and benzyloxycarbonyl protecting groups can be removed in an acidic medium (for example with hydrochloric acid or trifiuoroacetic acid).
  • Acetyl protecting groups can be removed under basic conditions (for example with potassium carbonate or caesium carbonate).
  • Benzylic protecting groups can be removed hydrogenolytically with hydrogen in the presence of a catalyst (for example palladium on activated carbon).
  • the compound of Formula 2 is separated from the reaction mixture by one of the customary separation techniques. If necessary, the compounds are purified by recrystallization or chromatography, or can, if desired, also be used in the next step without prior purification. It is also possible to isolate the compound of the general Formula 2 as a salt, for example as a salt of hydrochloric acid or of trifluoroacetic acid.
  • a compound of the general Formula 6 is obtained by condensation of an aldehyde of the Formula 5 with hydroxylamine and subsequent chlorination (see, for example, WO05/0040159, WO08/013622 and Synthesis, 1987, 1 1 , 998- 1001 ).
  • aldehyde 5 and hydroxylamine are first reacted to obtain corresponding oxime which is subsequently chlorinated in the presence of a suitable chlorinating agent.
  • a suitable chlorinating agent Preferred chlorinating reagents are N-chlorosuccinimide, NaOCl, HCIO and chlorine.
  • the step (a) is performed using one or more diluents preferably with protic solvents, for example ethanol.
  • the reaction mixture is diluted in step (b) with a further solvent, for example tetrahydrofuran, and then aqueous sodium hypochlorite is added.
  • the chlorination can likewise be effected with the aid of N-chlorosuccinimide in N,N-dimethyl formamide (DMF) or Ethyl acetate.
  • DMF N,N-dimethyl formamide
  • Ethyl acetate Ethyl acetate
  • alkenes and alkynes 7a and 7b are commercially available or can be prepared from commercially available precursors by methods described in the literature (for example from ketones or aldehydes by a Wittig or Horner-Wadsworth-Emmons olefination: Chem. Rev. 1989, 89, 863-927 and Julia olefination: Tetrahedron Lett., 1973, 14, 4833-4836; Peterson olefmation: J. Org. Chem. 1968, 33, 780; with the Bestmann-Ohira reagent: Synthesis 2004, 1 , 59-62).
  • a compound of the general Formula 4a is obtained from an alkyne of the general Formula 7a and and compound 6; and a compound of the general Formula 4b is obtained from an alkene of the general Formula 7b and compound 6 by a cycloaddition reaction (see, for example, WO 08/013622 and Synthesis, 1987, 1 1 , 998- 1001 ).
  • the step c is performed in the presence of a suitable base.
  • bases are tertiary amines (e.g. triethylamine), and alkali metal or alkaline earth metal carbonates (for example potassium or sodium carbonate), hydrogencarbonates and phosphates.
  • the step c is preferably performed using one or more diluents.
  • inert organic solvents are a preferred option (for example toluene and ethyl acetate). Water is likewise a possible solvent.
  • process can be performed in an excess of the alkene 7a or of the alkyne
  • the workup is carried out by customary methods. If necessary, the compounds are purified by recrystallization or chromatography.
  • a compound of Formula 5 is prepared (step a) by reducing corresponding ester 8 into the corresponding alcohol using NaBH -MeOH system.
  • the aromatic alcohols are obtained by the method explained in the ARKIVOC 2006, 128- 133, involving the reduction of aromatic ethyl, esters within 15 - 60 minutes after refluxing in THF.
  • the respective alcohol products were isolated after aqueous workup in good yield.
  • Corresponding alcohol is oxidized to aldehyde compound of Formula 5 (Scheme 4, Step b) using oxidizing agents like Mn0 2 , Dess-Martin periodinane, IBX, TEMPO.
  • Preferred solvents for the conversion were acetonitrile or dichloromethane.
  • a Compound of Formula 8 is prepared using the well-known Suzuki reaction involving Pd-catalyzed cross-coupling of Formula 10 with a boronic acid Formula 9 or corresponding ester.
  • Many catalysts are useful for this type of transformation; a typical catalyst is tetrakis(triphenylphosphine)palladium, or bis(triphenylphosphine)palladium chloride Solvents such as tetrahydrofuran, acetonitrile, diethyl ether and dioxane or dioxane: water mixture are suitable.
  • the Suzuki reaction and related coupling procedures offer many alternatives for creation of the C-G bond. For leading references see for example C. A. Zificsak and D. J.
  • Reduction of the compound of Formula 8 is carried out by catalytic hydrogenation to obtain compound of Formula 8a.
  • Pd/C, Pt/C, Raney Ni are the preferred catalyst.
  • For synthetic procedure refer Bioorganic & Medicinal Chemistry 23 (201 5) 2129-21 38.
  • Substituted compound of Formula 17 can be further functionalized using known methods in the literature like chlorionation, bromination, trifluromethylation to obtain appropriately substituted heterocyclic ring l ike pyridone (Formula 11).
  • References for the said transformations are Zhang, Pei-Zhi et al Tetrahedron, 72(23), 3250-3255; 2016 Canibano; Rodriguez; Santos; Sanz-Tejedor; Carreno; Gonzalez; Garcia-Ruano Synthesis, 2001 , 14,2175 - 2179, WO2004/50637.
  • the substituted functional ized heterocyclic ring containing a pyridone-like moiety can be acylated by reaction with an alkyl ester containing a suitable leaving group such as halogen, mesylate or tosylate, in the presence of a base such as potassium carbonate or cesium carbonate, in a polar solvent such as N,N- dimethyl formamide (DMF) or N-methyl-2-pyrrolidone (NMP), with or without heating to obtain the compound of Formula 12.
  • a polar solvent such as N,N- dimethyl formamide (DMF) or N-methyl-2-pyrrolidone (NMP)
  • DMF N,N- dimethyl formamide
  • NMP N-methyl-2-pyrrolidone
  • mixtures of O- and N-alkylated products are obtained, and the two regio-isomeric products can be separated by means of SiO z gel or reverse phase chromatography.
  • lithium salts for example LiCl
  • the addition of lithium salts, for example LiCl, to the reaction mixture can be employed to favor N- vs. O- alkylation.
  • the obtained alkyl ester can be further hydrolyzed to the corresponding acids by heating or stirring at room temperature in the presence of lithium hydroxide or sodium hydroxide in solvents like ethanol and water to obtain compound of Formula 1.
  • a compound of Formula 14 can be prepared by treating substituted acetoacetic ester with alkyl hydrazine of Formula 13. Compound of Formula 14 can then be selectively alkylated using alkyl halides with or without base to obtain compound of Formula 15.
  • Substituted compound of Formula 15 can be further functionalized using known methods in the literature l ike chlorionation, bromination and trifluromethylation to obtain appropriately substituted heterocyclic ring like pyrazolone of Formula 16.
  • the pyrazolone of Formula 16 can be further hydrolyzed to the corresponding acids by heating or stirring at room temperature in the presence of lithium hydroxide or sodium hydroxide in solvents like ethanol and water to obtain compound of Formula la.
  • a compound of Formula 6b can be prepared by reacting a compound of Formula 11 and a compound of Formula 10 in the presence of a base.
  • Suitable bases include sodium hydride or potassium carbonate, and the reaction is carried out in a solvent such as ⁇ , ⁇ -dimethylformamide or acetonitrile at 0 to 80 °C.
  • Suitable leaving groups Y 2 in the compound of Formula 11 include bromide, iodide, mesylate (OS(0) 2 CH 3 ), triflate (OS(0) 2 CF 3 ) and the like, and the compound of Formula 11 can be prepared from the corresponding compounds wherein Y is OH, using general methods known in the art.
  • a compound of Formula 3a wherein W is O involves coupling of an acid of Formula 1 or la with an amine of Formula 20 (or its acid salt) in the presence of a dehydrative coupling reagent such as dicyclohexylcarbodiimide (DCC), l -(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) O-benzotriazol-l-yl-tetramethyluronium hexafluoro-phosphate (HBTU), or 1 - [Bis(dimethylamino)methylene]- l H- l ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU).
  • DCC dicyclohexylcarbodiimide
  • EDC O-benzotriazol-l-yl-tetramethyluronium hexafluoro-phosphate
  • HATU 1 - [
  • Polymer-supported reagents are again useful here, such as polymer-bound cyclohexylcarbodiimide. These reactions are typically run at 0-40 °C in a solvent such as dichloromethane, acetonitrile or ⁇ , ⁇ -dimethylformamide in the presence of a base such as triethylamine or ⁇ , ⁇ -diisopropylethylamine.
  • amides of Formula 3a wherein W is O can be converted to thioamides of Formula 3a wherein W is S using a variety of standard thiating reagents such as phosphorus pentasulfide or 2, 4-bis(4-methoxyphenyl)-l,3-dithia-2,4-diphosphetane-2,4-disulfide (Lawesson's reagent).
  • standard thiating reagents such as phosphorus pentasulfide or 2, 4-bis(4-methoxyphenyl)-l,3-dithia-2,4-diphosphetane-2,4-disulfide (Lawesson's reagent).
  • a compound of Formula 3a can be prepared by reacting the compound of Formula 21 with compound of the formula 22 in the presence of an acid or a Lewis acid, preferably in the presence of an acid.
  • the acid which can be used in this step include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and the like, organic acids such as acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid and the like.
  • Lewis acid examples include zinc chloride, aluminum chloride, tin chloride, boron trichloride, boron trifluoride, trimethylsi lyltrifluoromethane sulfonate and the like.
  • the solvent which can be used in this step may be any solvent which does not inhibit the progress of this reaction and examples thereof include nitriles such as acetonitrile; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme, etc.; dichloromethane, dichloroethane , Halogenated hydrocarbons such as chloroform, carbon tetrachloride and tetrachloroethane; aromatic hydrocarbons such as benzene, chlorobenzene, nitrobenzene and toluene; amides such as N,N- dimethylformamide and ⁇ , ⁇ -dimethylacetamide; imidazolinones such as l ,3-dimethyl-2-imidazolinone, sulfur compounds such as dimethylsulfoxide and the like can be used, and mixed solvents thereof can also be used.
  • nitriles such as ace
  • the reaction temperature may be selected from the range of -20 °C to the boiling point of the inert solvent to be used, preferably in the range of 0 °C to 150 °C.
  • the reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount and the like, but is usually from 10 minutes to 48 hours.
  • the compound of Formula 22 can be prepared by reducing the compound of Formula 23 with a reducing agent in a solvent.
  • Reducing agent suitable in this step are lithium aluminum hydride, diisobutylaluminum hydride, borane and the like.
  • Preferred solvent that can be used in this step is tetrahydrofuran, dioxane or the like.
  • the reaction temperature may be selected from the range of from -20 °C to the boiling point range of the inert solvent to be used, preferably in the range of 0 °C to 100 °C.
  • the compound of Formula 22 can also be prepared by reducing the compound of Formula 24 with a reducing agent in a solvent.
  • Reducing agent suitable in this step are lithium aluminum hydride, diisobutylaluminum hydride, borane and the like.
  • Preferred solvent that can be used in this step is tetrahydrofuran, dioxane or the l ike.
  • the reaction temperature may be selected from the range of from -20 °C. to the boiling point range of the inert solvent to be used, preferably in the range of 0°C to 100 °C.
  • Synthesis of compounds of Formula 26 involves palladium-catalyzed cross-coupling reaction of terminal alkynes of Formula 25 and organic electrophiles such as alkyl bromides or chlorides. The most widely used of these is a cross between the Cu-promoted Castro-Stephens reaction and the Heck alkynylation, known as the Sonogashira reaction.
  • the compound of Formula 26 can also be obtained using palladium- based systems to catalyze the reaction of aryl halides and terminal alkynes.
  • alkynylation of aldehydes can be achieved by Corey-Fuchs reaction (Tetrahedron Lett, 1 972, 36, 3769) or a Seyferth-Gilbert homologization (see, for example, J. Org. Chem., 1 996, 61 , 2540).
  • the alkyne of Formula 19 can also be prepared from the aldehyde of Formula 5 with Bestmann-Ohira's reagent analogously to the literature instructions (see, for example, Synthesis, 2004, 59).
  • Alkynylation with Bestmann-Ohira's reagent in methanol or ethanol is preferably used in the equivalent of potassium carbonate or sodium carbonate.
  • the aldehyde of Formula 5 and the alkynylation reagent are used in equimolar amounts, but the Bestmann-Ohira's reagent can be used in excess if necessary.
  • the reaction is preferably carried out at from -100 °C to 60 °C and more preferably at from -78 °C to 40 °C.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a few minutes and 48 hours.
  • the compounds of Formula 25 are separated from the reaction mixture by one of the conventional separation techniques. If necessary, the compounds are purified by recrystallization, distillation or chromatography or, if desired, can also be used in the next step without prior purification.
  • Step A Preparation of ethyl 2-bromo-l,3-thiazole-4-carboxylate
  • Step B Preparation of ethyl 2-(l-(tert-butoxycarbonyl)-l,2,3,6-tetrahydropyridin-4-yI)thiazole-4- carboxylate
  • Step C Preparation of ethyl 2-(l-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylate
  • Step D Preparation of tert-butyl 4-(4-(hydroxymethyl)thiazol-2-yl)piperidine-l-carboxylate
  • Step E Preparation of tert-butyl 4-(4-formylthiazol-2-yl)piperidine-l-carboxylate
  • Step G Preparation of tert-butyl 4-(4-(5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2- yl)piperidine-l-carboxylate
  • Step Gl Alternate preparation of tert-butyl 4-(4-(5-(2,6-difIuorophenyl)-4,5-dihydroisoxazol-3- yl)thiazol-2-yl)piperidine-l-carboxylate
  • Step H Preparation of 5-(2,6-difluorophenyl)-3-(2-(piperidin-4-yI)thiazol-4-yl)-4,5- dihydroisoxazole
  • reaction mixture was concentrated under reduced pressure and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution and the ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated to obtain the 160 mg of 5-(2,6-difluorophenyl)-3- (2-(piperidin-4-yl)thiazol-4-yl)-4,5-dihydroisoxazole.
  • Step I Preparation of 3-chloro-l-(2-(4-(4-(5-(2,6-difIuorophenyl)-4,5-dihydroisoxazol-3-yl)thiazoI- 2-yl)piperidin-l-yl)-2-oxoethyl)-5-(trifluoromethyl)pyridin-2(lH)-one
  • the reaction mixture was diluted with dichloromethane (10 ml), and washed with IN aqueous Hydrogen chloride and saturated aqueous sodium bicarbonate solution.
  • the dichloromethane layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 3-chloro-l-(2-(4-(4-(5-(2,6-difluorophenyl)-4,5- dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-l-yl)-2-oxo (100 mg, 0.170 mmol, 36% yield).
  • Step A Preparation of 2-(l-(tert-butoxycarbonyl)piperidin-4-yl)thiazoIe-4-carboxylic acid
  • Step B Preparation of tert-butyl 4-(4-((l, 2, 3, 4-tetrahydronaphthalen-l-yl)carbamoyl)thiazol-2- yl)piperidine-l-carboxy!ate
  • the reaction mixture was diluted with dichloromethane ( 10 ml), and washed with 1 N aqueous Hydrogen chloride and saturated aqueous sodium bicarbonate solution.
  • the dichloromethane layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 2-( l -(2-(3-chloro-2-oxo-5- (trifluoromethyl)pyridin- l (2H)-yl)acetyl)piperidin-4-yl)-N-( l ,2,3,4-tetrahydronaphth ⁇
  • reaction mixture was diluted with water (20 ml) and extracted twice with dichloromethane (30 ml). The combined dichloromethane layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure which was purified by column chromatography using ethyl acetate and hexane (80:20) as eluents to obtain 5-(difluoromethyl)-2-(2-(4-(4-(5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3- yl)thiazol-2-yl)piperidin-l-yl)-2-oxoethyl)-l-methyl-l,2-dihydro-3H-pyrazol-3-one (0.075 g, 0.140 mmol, 24% yield).
  • Step A Preparation of tert-butyl (E)-4-(4-(((benzyloxy) imino) methyl) thiazol-2-yl) piperidine-1- carboxylate
  • Step B Preparation of (E)-2-(piperidin-4-yl) thiazole-4-carbaldehyde O-benzyl oxime
  • Step C Preparation of (E/Z)-2-(l-(2-(2-oxo-5-(trifluoromethyl) pyridin-l(2H)-yl) acetyl) piperidin- 4-yl) thiazole-4-carbaldehyde O-benzyl oxime
  • reaction mixture was allowed to stirr at room temperature for 3h.
  • the reaction mixture was quenched with water, extracted thrice with ethyl acetate (30 ml).
  • the ethyl acetate layer was dried over sodium sulphate filtered and concentrated under reduced pressure.
  • Step B Preparation of tert-butyl 4-(4-(3-(2, 6-difluorophenyI)-4, 5-dihydroisoxazol-5-yl) thiazoI-2- yl) piperidine-l-carboxylate
  • the resulting mixture was stirred at 60 °C for 3h.
  • the reaction mixture was diluted with water (50 ml) and extracted twice with ethyl acetate (20 ml). The comined ethyl acetate layers were dried over anhydrous sodium sulfate and evaporated.
  • Step C Preparation of 3-(2, 6-difluorophenyl)-5-(2-(piperidin-4-yl) thiazol-4-yl ⁇ -4, 5- dihydroisoxazole 2, 2, 2-trifluoroacetate
  • Step D Preparation of l-(2-(4-(4-(3-(2, 6-difluorophenyl)-4, 5-dihydroisoxazol-5-yl) thiazol-2-yl) piperidin-l-yl)-2-oxoethyl)-3-(trifluoromethyl) pyridin-2(lH)-one
  • the reaction mixture was stirred at room temperature for l h.
  • the reaction was quenched with cold water and the solid obtained was filtered.
  • the crude prodcut was purified by prep- chromatography to obtain l -(2-(4-(4-(3-(2, 6-difluorophenyl)-4, 5-dihydroisoxazol-5-yl) thiazol-2-yl) piperidin- l -yl)-2-oxoethyl)-3-(trifluoromethyl) pyridin-2( l H)-one ( 100 mg, 0.1 81 mmol, 34% yield).
  • Step 2 Preparation of 4-(l, 5-dihydrobenzo[e] [1,3] dioxepin-3-yl)-2-(piperidin-4-yi) thiazole
  • Step 3 Preparation of l-(2-(4-(4-(l, 5-dihydrobenzo[e] [1 ,3] dioxepin-3-yl) thiazol-2-yl) piperidin-1- yl)-2-oxoethyi)-3-(trifluoromethyl) pyridin-2(lH)-one
  • reaction mixture was stirred for 12h. After completion of the reaction, the reaction mixture was diluted with water (50 ml) and extracted twice with ethyl acetate ( 10 ml). The combined ethyl acetate layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure.
  • Step 1 Preparation of 2-(piperidin-4-yl) thiazole-4-carbaldehyde
  • Step 2 Preparation of 2-(l-(2-(2-oxo-5-(tritluoromethyl) pyridin-l(2H)-yl) acetyl) piperidin-4-yl) thiazole-4-carbaldehyde
  • Step 3 Preparation of l-(2-oxo-2-(4-(4-(3-phenyl-4,8-dihydro-[l,3]dioxepino[5,6-d]isoxazol-6- yl)thiazoI-2-yl)piperidin-l-yl)ethyl)-5-(trifluoromethyl)pyridin-2(l H)-one
  • 3-phenyl isoxazole-4,5-diyl)dimethanol (0. 185 g, 0.901 mmol) and p-toluene sulfonic acid monohydrate (0.071 g, 0.376 mmol) were dissolved in a solution of dry toluene (20 ml) and dry N,N-dimethyl formamide (5 ml) and stirred with odium sulfate under n atmosphere.
  • Step B Preparation of dimethyl 3-phenylisoxazole-4, 5-dicarboxylate
  • Step B l-chloro-2-ethenyl-3-(methoxymethoxy)benzene
  • Step D 3-chloro-2-ethenylphenyl methanesulfonate
  • Step B Preparation of ethyl 2-(3-(difluoromethyl)-2-methyI-5-oxo-2,5-dihydro-lH-pyrazol-l- yl)acetate
  • Step C Preparation of 2-(3-(difluoromethyl)-2-methyl-5-oxo-2,5-dihydro-lH-pyrazol-l-yl)acetic acid
  • Step A Preparation of ethyl 2-(4-bromo-3-(difluoromethyl)-2-niethyl-5-oxo-2,5-dihydro-lH- pyrazol-l-yl)acetate
  • Step B Preparation of 2-(4-bromo-3-(difluoroniethyl)-2-methyl-5-oxo-2,5-dihydro-lH-pyrazol-l- yl)acetic acid

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  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

La présente invention concerne un composé de formule I, dans laquelle les substituants T, A, W, R2, n, Z, G, Z1 et J sont tels que définis dans la description.
PCT/IB2018/052681 2017-04-19 2018-04-18 Composés hétérocycliques ayant des propriétés microbiocides WO2018193387A1 (fr)

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WO2022130188A1 (fr) 2020-12-15 2022-06-23 Pi Industries Ltd. Composition agrochimique comprenant des composés de pipéridine thiazole
CN114685481A (zh) * 2020-12-31 2022-07-01 南通泰禾化工股份有限公司 一种氟噻唑吡乙酮的制备方法
CN114761403A (zh) * 2019-11-11 2022-07-15 Pi工业有限公司 用作作物保护杀菌剂的1-(4-(4-(5-苯基-4,5-二氢异噁唑-3-基)噻唑-2-基)哌啶-1-基)-乙烷-1-酮衍生物及相关化合物
WO2022243810A1 (fr) 2021-05-15 2022-11-24 Pi Industries Ltd. Nouvelle composition agrochimique comprenant des composés de pipéridine thiazole
WO2023007426A1 (fr) 2021-07-29 2023-02-02 Pi Industries Ltd. Nouveaux composés styréniques et leur procédé de préparation
CN116041255A (zh) * 2022-12-10 2023-05-02 武威广达科技有限公司 一种2-氯-5-三氟甲基吡啶的制备方法
WO2024035686A1 (fr) * 2022-08-11 2024-02-15 Alexion Pharmaceuticals, Inc. Composés pharmaceutiques pour le traitement de troubles médiés par le complément
CN118754799A (zh) * 2024-06-26 2024-10-11 滕州市悟通香料有限责任公司 一种2,6-二氟苯乙烯的合成方法

Citations (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE506425C (de) * 1927-05-12 1930-09-05 Schering Kahlbaum Ag Verfahren zur Erhoehung der Loeslichkeit von halogensubstituierten Oxpyridinen in Wasser
US4112088A (en) * 1976-03-11 1978-09-05 Smithkline Corporation 7-Acyl-3-(sulfoalkyl substituted oxadiazolylthiomethyl) cephalosporins
WO2004050637A2 (fr) 2002-12-03 2004-06-17 Axys Pharmaceuticals, Inc. Derives de 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine utilises en tant qu'inhibiteurs du facteur viia
WO2005040159A1 (fr) 2003-10-17 2005-05-06 Astrazeneca Ab Derives de 4-(pyrazol-3-ylamino) pyrimidine qui s'utilisent dans le traitement du cancer
WO2007039563A1 (fr) 2005-09-30 2007-04-12 N.V. Organon Dérivés de 9-azabicyclo[3.3.1]nonane en tant qu'inhibiteurs du recaptage des monoamines
WO2008013925A2 (fr) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Amides azocycliques fongicides
WO2009094407A2 (fr) 2008-01-25 2009-07-30 E. I. Du Pont De Nemours And Company Amides fongicides
WO2009094445A2 (fr) 2008-01-25 2009-07-30 E. I. Du Pont De Nemours And Company Composés hétérocycliques fongicides
WO2010065579A2 (fr) 2008-12-02 2010-06-10 E. I. Du Pont De Nemours And Company Composés hétérocycliques fongicides
WO2011076699A1 (fr) 2009-12-21 2011-06-30 Bayer Cropscience Ag Bis(difluorométhyl)pyrazoles utilisés comme fongicides
WO2011085170A1 (fr) 2010-01-07 2011-07-14 E. I. Du Pont De Nemours And Company Composés hétérocycliques fongicides
WO2012025557A1 (fr) 2010-08-25 2012-03-01 Bayer Cropscience Ag Dérivés hétéroarylpipéridine et hétéroarylpipérazine en tant que fongicides
WO2012055837A1 (fr) 2010-10-27 2012-05-03 Bayer Cropscience Ag Hétéroarylpipéridine et dérivés d'hétéroarylpipéridine comme fongicide
WO2012104273A1 (fr) 2011-02-01 2012-08-09 Bayer Cropscience Ag Dérivés d'hétéroarylpipéridine et d'hétéroarylpipérazine utilisés comme fongicides
WO2013037768A1 (fr) 2011-09-15 2013-03-21 Bayer Intellectual Property Gmbh Pipéridinopyrazoles à action fongicide
WO2013098229A2 (fr) 2011-12-27 2013-07-04 Bayer Intellectual Property Gmbh Dérivés d'hétéroarylpipéridine et d'hétéroarylpipérazine utilisés comme fongicides
WO2013127808A1 (fr) 2012-03-02 2013-09-06 Syngenta Participations Ag Dérivés de pyrazole microbicides
WO2014071044A1 (fr) 2012-11-01 2014-05-08 Allergan, Inc. Dérivés de 6,7-dialcoxy-3-isoquinoline substitués à titre d'inhibiteurs de phosphodiestérase 10 (pde10a)
WO2014075874A1 (fr) 2012-11-13 2014-05-22 Syngenta Participations Ag Dérivés microbicides de pyrazole
WO2014206896A1 (fr) 2013-06-24 2014-12-31 Bayer Cropscience Ag Dérivés d'acide pipéridine-carboxylique à utiliser en tant que fongicides
WO2015028457A1 (fr) 2013-08-28 2015-03-05 Bayer Cropscience Ag Dérivés de type ester malonique d'hétéroaryl-pipéridines et -pipérazines à titre de fongicides
WO2015144571A1 (fr) 2014-03-24 2015-10-01 Bayer Cropscience Ag Dérivés phénylpipéridinecarboxamide utiles en tant que fongicides
WO2016024434A1 (fr) 2014-08-13 2016-02-18 株式会社エス・ディー・エス バイオテック Composé cyclique à 11 éléments condensé et fongicide pour l'agriculture et l'horticulture le comprenant
WO2016156129A1 (fr) 2015-04-02 2016-10-06 Basf Se Composés de quinoléine
WO2017109858A1 (fr) 2015-12-22 2017-06-29 株式会社エス・ディー・エス バイオテック Composé cyclique à 11 éléments condensé et germicide pour l'agriculture et l'horticulture le contenant
WO2017109855A1 (fr) 2015-12-22 2017-06-29 株式会社エス・ディー・エス バイオテック Composé thiazole et germicide agricole et horticole le comprenant
WO2017138069A1 (fr) 2016-02-08 2017-08-17 株式会社エス・ディー・エス バイオテック Composition germicide

Patent Citations (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE506425C (de) * 1927-05-12 1930-09-05 Schering Kahlbaum Ag Verfahren zur Erhoehung der Loeslichkeit von halogensubstituierten Oxpyridinen in Wasser
US4112088A (en) * 1976-03-11 1978-09-05 Smithkline Corporation 7-Acyl-3-(sulfoalkyl substituted oxadiazolylthiomethyl) cephalosporins
WO2004050637A2 (fr) 2002-12-03 2004-06-17 Axys Pharmaceuticals, Inc. Derives de 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine utilises en tant qu'inhibiteurs du facteur viia
WO2005040159A1 (fr) 2003-10-17 2005-05-06 Astrazeneca Ab Derives de 4-(pyrazol-3-ylamino) pyrimidine qui s'utilisent dans le traitement du cancer
WO2007039563A1 (fr) 2005-09-30 2007-04-12 N.V. Organon Dérivés de 9-azabicyclo[3.3.1]nonane en tant qu'inhibiteurs du recaptage des monoamines
WO2008013925A2 (fr) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Amides azocycliques fongicides
WO2008013622A2 (fr) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Amides azocycliques fongicides
WO2009094407A2 (fr) 2008-01-25 2009-07-30 E. I. Du Pont De Nemours And Company Amides fongicides
WO2009094445A2 (fr) 2008-01-25 2009-07-30 E. I. Du Pont De Nemours And Company Composés hétérocycliques fongicides
WO2010065579A2 (fr) 2008-12-02 2010-06-10 E. I. Du Pont De Nemours And Company Composés hétérocycliques fongicides
WO2011076699A1 (fr) 2009-12-21 2011-06-30 Bayer Cropscience Ag Bis(difluorométhyl)pyrazoles utilisés comme fongicides
WO2011085170A1 (fr) 2010-01-07 2011-07-14 E. I. Du Pont De Nemours And Company Composés hétérocycliques fongicides
WO2012025557A1 (fr) 2010-08-25 2012-03-01 Bayer Cropscience Ag Dérivés hétéroarylpipéridine et hétéroarylpipérazine en tant que fongicides
WO2012055837A1 (fr) 2010-10-27 2012-05-03 Bayer Cropscience Ag Hétéroarylpipéridine et dérivés d'hétéroarylpipéridine comme fongicide
WO2012104273A1 (fr) 2011-02-01 2012-08-09 Bayer Cropscience Ag Dérivés d'hétéroarylpipéridine et d'hétéroarylpipérazine utilisés comme fongicides
WO2013037768A1 (fr) 2011-09-15 2013-03-21 Bayer Intellectual Property Gmbh Pipéridinopyrazoles à action fongicide
WO2013098229A2 (fr) 2011-12-27 2013-07-04 Bayer Intellectual Property Gmbh Dérivés d'hétéroarylpipéridine et d'hétéroarylpipérazine utilisés comme fongicides
WO2013127808A1 (fr) 2012-03-02 2013-09-06 Syngenta Participations Ag Dérivés de pyrazole microbicides
WO2014071044A1 (fr) 2012-11-01 2014-05-08 Allergan, Inc. Dérivés de 6,7-dialcoxy-3-isoquinoline substitués à titre d'inhibiteurs de phosphodiestérase 10 (pde10a)
WO2014075874A1 (fr) 2012-11-13 2014-05-22 Syngenta Participations Ag Dérivés microbicides de pyrazole
WO2014206896A1 (fr) 2013-06-24 2014-12-31 Bayer Cropscience Ag Dérivés d'acide pipéridine-carboxylique à utiliser en tant que fongicides
WO2015028457A1 (fr) 2013-08-28 2015-03-05 Bayer Cropscience Ag Dérivés de type ester malonique d'hétéroaryl-pipéridines et -pipérazines à titre de fongicides
WO2015144571A1 (fr) 2014-03-24 2015-10-01 Bayer Cropscience Ag Dérivés phénylpipéridinecarboxamide utiles en tant que fongicides
WO2016024434A1 (fr) 2014-08-13 2016-02-18 株式会社エス・ディー・エス バイオテック Composé cyclique à 11 éléments condensé et fongicide pour l'agriculture et l'horticulture le comprenant
WO2016024350A1 (fr) 2014-08-13 2016-02-18 株式会社エス・ディー・エス バイオテック Composés cycliques à 11 éléments condensés et fongicides pour l'agriculture et l'horticulture les contenant
WO2016156129A1 (fr) 2015-04-02 2016-10-06 Basf Se Composés de quinoléine
WO2017109858A1 (fr) 2015-12-22 2017-06-29 株式会社エス・ディー・エス バイオテック Composé cyclique à 11 éléments condensé et germicide pour l'agriculture et l'horticulture le contenant
WO2017109855A1 (fr) 2015-12-22 2017-06-29 株式会社エス・ディー・エス バイオテック Composé thiazole et germicide agricole et horticole le comprenant
WO2017138069A1 (fr) 2016-02-08 2017-08-17 株式会社エス・ディー・エス バイオテック Composition germicide

Non-Patent Citations (25)

* Cited by examiner, † Cited by third party
Title
ARKIVOC, 2006, pages 128 - 133
BESTMANN-OHIRA, SYNTHESIS, vol. 1, 2004, pages 59 - 62
BIOORGANIC & MEDICINAL CHEMISTRY, vol. 23, 2015, pages 2129 - 2138
C. A. ZIFICSAK; D. J. HLASTA, TETRAHEDRON, vol. 60, 2004, pages 8991 - 9016
CANIBANO; RODRIGUEZ; SANTOS; SANZ-TEJEDOR; CARRENO; GONZALEZ; GARCIA-RUANO, SYNTHESIS, vol. 14, 2001, pages 2175 - 2179
CASTRO, C. E.; STEPHENS, R. D., J. ORG. CHEM., vol. 28, 1963, pages 2163
DE MEIJERE, A.; DIEDERICH, F.: "Metal-Catalyzed Cross-Coupling Reactions", vol. 2, 2004, WILEY-VCH
DESS, D. B.; MARTIN, J. C., J. AM. CHEM. SOC., vol. 113, 1991, pages 7277
DIECK, H. A.; HECK, F. R., J. ORGANOMET. CHEM., vol. 93, 1975, pages 259
EDWARDS M L ET AL: "beta latam antibiotics derived from nitrogen heterocyclic acetic acids", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 20, no. 4, 1 January 1977 (1977-01-01), pages 560 - 563, XP002503461, ISSN: 0022-2623, DOI: 10.1021/JM00214A020 *
J. J. LI AND G. W. GRIBBLE: "Palladium in Heterocyclic Chemistry: A Guide for the Synthetic Chemist", 2000, ELSEVIER
J. ORG. CHEM., vol. 61, 1996, pages 2540
JULIA OLEFINATION, TETRAHEDRON LETT., vol. 14, 1973, pages 4833 - 4836
LAVECCHIA; BERTEINA-RABOIN; GUILLAUMET, TETRAHEDRON LETTERS, vol. 45, 2004, pages 6633 - 6636
NAIK, N.; BRASLAU, R., TETRAHEDRON, vol. 54, 1998, pages 667
NEGISHI, E.; ANASTASIA, L., CHEM. REV., vol. 103, 2003, pages 1979
PETERSON OLEFINATION, J. ORG. CHEM., vol. 33, 1968, pages 780
QUESADA, E.; TAYLOR, R. J. K., TETRAHEDRON LETT., vol. 46, 2005, pages 6473 - 6476
SONOGASHIRA, K., J. ORGANOMET. CHEM., vol. 653, 2002, pages 46
SYNTHESIS, vol. 11, 1987, pages 998 - 1001
SYNTHESIS, vol. 59, 2004
TETRAHEDRON LETT, vol. 36, 1972, pages 3769
THEODORA W. GREENE; PETER G. M. WUTS: "Protective Groups in Organic Synthesis", 1999, WILEY-INTERSCIENCE, pages: 494 - 653
WITTIG; HORNER-WADSWORTH-EMMONS OLEFINATION, CHEM. REV., vol. 89, 1989, pages 863 - 927
ZHANG, PEI-ZHI ET AL., TETRAHEDRON, vol. 72, no. 23, 2016, pages 3250 - 3255

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