piperidine-pyrazole fungicidal compounds, their uses, method and composition for controlling harmful

专利摘要:
patent summary for: "piperidine pyrazoles as fungicides". The invention relates to derivatives of heteroaryl piperidine and piperazine, their agrochemical active salts, their use and also to methods and compositions for the control of pathogenic phytopathic fungi in and / or on plants or in plants. and / or plant seeds, methods for producing such compositions and treated seeds, as well as their use for the control of harmful plant pathogenic plants in agriculture, horticulture and forests, animal health, material protection and in the household and hygiene sectors. The present invention further relates to a method for producing heteroaryl piperidine and piperazine derivatives.
公开号:BR112014005989B1
申请号:R112014005989-6
申请日:2012-09-11
公开日:2019-11-05
发明作者:Peter Schmidt Jan；Benting Jürgen；Cristau Pierre；Wasnaire Pierre；Hoffmann Sebastian；Hillebrand Stefan；Seitz Thomas；Tsuchiya Tomoki；Wachendorff-Neumann Ulrike
申请人:Bayer Ip Gmbh；
IPC主号:

专利说明:

PIPERIDINE-PIRAZOLES FUNGICID COMPOUNDS, THEIR USES, METHOD AND COMPOSITION TO CONTROL HARMFUL PHYTOPATOGENIC FUNGI, AND METHOD FOR PRODUCTION OF COMPOSITIONS [001] The invention concerns derivatives of heteroaryl-piperidine and piperazine, its active ingredients, its active ingredients their use and also methods and compositions for the control of harmful phytogenic fungi in and / or on plants or in and / or on plant seeds, methods for producing such compositions and treated seeds, as well as their use for the control of harmful phytopathogenic plants in agriculture, horticulture and forests, animal health, material protection and also in the domestic and hygiene sectors. The present invention also relates to a method for the production of heteroarylpiperidine and -piperazine derivatives.
[002] It is already known that certain heterocyclic-substituted thiazoles can be used as fungicidal agents for crop protection (see documents WO 07/014290, WO 08/013925,
WO 08/013622,
WO 08/091594,
WO 09/094445,
WO 08/091580,
WO 09/132785,
WO 09/055514,
WO 10/037479,
WO 09/094407,
WO 10/065579,
WO10 / 066353, WO10 / 123791, WO 10/149275, WO 11/051243, WO 11/085170, WO 11/076699, WO 12/020060, WO 12/025557, WO 12/082580, WO 12/055837). However, in particular at relatively low application rates, the fungicidal activity of these compounds is not always sufficient.
[003] Due to the continuous increase in environmental and economic requirements imposed on crop protection compositions today, with respect, for example, to the activity spectrum, toxicity, selectivity, application rate, formation of residues and the convenience of production, and since, in addition, problems may arise, for example, with resistance, there is a constant objective of developing new compositions for the protection of crops, in particular fungicides, which have advantages in relation to your
Petition 870190062787, of 07/05/2019, p. 11/17
2/114 known counterparts, at least in certain areas.
[004] Surprisingly, it has now been concluded that the present heteroaryl-piperidine and -piperazine derivatives achieve the stated objectives, at least in some respects, and are therefore suitable for use as crop protection compositions, in particular as fungicides.
[005] The invention provides compounds of structural formula (I),
F
F ^F (I) where the definitions of the radicals have the following meanings:
the symbol Y represents oxygen or sulfur, the symbol R ² represents hydrogen or halogen, the symbol Q represents where the bond identified by "x" is directly linked to the thiazole and the bond identified by "y" is directly linked to the symbol L ¹ or R ¹ , the symbol R ⁵ represents hydrogen, cyano, alkyl (C1-C3) or haloalkyl (C1-C3), the symbol L ¹ represents a direct bond, -CH ₂ -, - (C = O) -, sulfur or oxygen,
3/114 the symbol R ¹ represents phenyl containing at least one substituent Z ⁴ and, in addition, two, three or four other substituents that are independently selected from the substituents Z ⁴ and Z ¹ , or the symbol R ¹ represents naphthyl, di -hydronaphthalenyl, tetrahydronaphthalenyl, hexahydronaphthalenyl, octahydronaphthalenyl or indenyl, which contains at least one substituent Z ⁵ and, in addition, two, three or four other substituents that are independently selected from the substituents Z ⁵ and Z ¹ or the symbol R ¹ represents a 5- or 6-membered optionally substituted and benzofused heteroaryl that contains at least one substituent Z ⁶ and additionally contains two, three or four other substituents, which on carbon are selected independently from each other, among the substituents Z ⁶ and Z ¹ and which in nitrogen are independently selected from the substituents Z ⁶ and Z ² or the symbol R ¹ represents ta a cycloalkyl (C3-C8) or represents a cycloalkenyl (C ₅ -C ₈ ), which contains at least one Z7 substituent and additionally contains two, three or four other substituents which are independently selected from each other, between the substituents Z ⁷ and Z ¹ , the symbol Z ¹ represents hydrogen, halogen, hydroxyl, nitro, cyano, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, haloalkoxy, haloalkoxy, alkoxycarbonyl, alkyl, cycloalkoxyalkyl, cycloalkylamino, alkylthio, haloalkylthio, cycloalkylthio, cycloalkylalkyl, alkylcarbonyloxy, alkylcarbonylamino, haloalquilcarbonilamino, alquilcarboniltio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyloxy, haloalquilsulfoniloxi, alkylcycloalkylalkyl, -C (= O) NR ³ R ^4, -NR ³ R ⁴ , tri- ((C1-C2) alkyl) - silyl or L ³ Z ³ ,
4/114 the symbol Z ² represents hydrogen, halogen, hydroxyl, nitro, cyano, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, haloalkoxy, alkoxyalkyl, alkoxyalkyl, alkoxyalkyl, alkoxyalkyl, alkoxyalkyl, cycloalkylamino, alkylthio, haloalkylthio, cycloalkylthio, cycloalkylalkyl, alkylcarbonyloxy, alkylcarbonylamino, haloalquilcarbonilamino, alquilcarboniltio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyloxy, haloalquilsulfoniloxi, alkylcycloalkylalkyl, -C (= O) NR ³ R ^4, -NR ³ R ⁴ or tri (alkyl ( C ₁ -C ₂ )) - silyl, the symbol Z ³ represents a phenyl radical, a naphthalenyl radical or a 5- or 6-membered heteroaryl radical, which in each case may contain 0, 1, 2 or 3 substituents, being the substituents selected, independently of each other, from the following listing:
carbon substituents: halogen, cyano, nitro, hydroxyl, amino, SH, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkoxyalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxyalkoxy, alkoxyalkoxy, alkoxyalkoxy, alkoxyalkoxy, alkoxyalkoxy alkynyloxy, alkoxyalkoxy, alkylamino, dialkylamino, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, trisylylalkyl or phenyl, substitutents in nitrogen: hydrogen, -C (= O) halo, alkyl, alkenyl, alkyl, alkenyl, alkyl, alkenyl, alkyl, alkenyl, alkyl, alkyl, alkyl cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkoxyalkyl, halocycloalkyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, phenylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, cycloalkoxycarbonyl, C (= O) NR ³ R ^4, phenyl or benzyl, the symbol Z ⁴ represents SH, C (= O) H, cycloalkyl (C7-C8), halocycloalkyl (C ₇ -C ₈ ), cycloalkyl ylcycloalkyl, halocycloalkylalkyl, cycloalkenyl, halocycloalkenyl, (C5-C6) alkoxyalkyl, alkoxyalkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkylaminoalkyl, alkylalkylaminoalkyl, alkylaminoalkyl, alkylaminoalkyl, haloalkyl, alkylaminoalkyl,
Cej-carbonyl, haloalkylcarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, cycloalkylalkoxycarbonyl, cycloalkylaminocarbonyl, haloalkoxyalkyl, hydroxyalkyl (C ₅ -C ₆ ), alkoxy (C ₅ -C ₆ ), haloalkoxy (C ₅ -C ₆ , cycloalkoxy, cycloalkyl, cycloalkoxy, , haloalkenyloxy, alkynyloxy, haloalciniloxi, alkoxyalkoxy, haloalquilcarboniloxi, cycloalkylcarbonyloxy, alquilcarbonilalcoxi alkyl, (C5-C6) alkylthio, halo (C5-C6) alkylthio, (C5-C6) alkylsulfinyl, halo (C ₅ -C ₆₎ - sulfinyl, alkylsulfonyl, halo (C ₁ -C ₄ ) -sulfonyl, cycloalkylsulfonyl, tri- (C3-C4) alkyl - silyl, alkylsulfonylamino or haloalkylsulfonylamino, the symbol Z ⁵ represents tri- ((C2-C4) alkyl) - silyl, benzyl, phenyl, SH, alkoxy (C5-C6), haloalkoxy (C5-C6), alkenyloxy (C2-C6), alkynyloxy (C2-C6), alkyl (C5C6) -thio or haloalkyl (C5-C6) - uncle, the symbol Z ⁶ represents substituents on carbon: SH, cycloalkylcycloalkyl or tri ((C3C4) alkyl) - silyl, substituents on nitrogen: alkenyl, alkyn yl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, alkylsulfonyl, C (= O) H, benzyl or phenyl, Z7 represents cyano, halogen, hydroxy, oxo, (C1C ₄₎ -alkyl, (C1-C ₄ ), alkoxy (C1-C ₄ ), haloalkoxy (C1-C ₄ ), alkyl (C1-C ₄ ) -thio, halo (C1-C4) -thio or phenyl, the symbol L ³ represents a direct bond, -CH2-, -C (= O) -, sulfur, oxygen, -C (= O) O-, -C (= O) NH-, -OC (= O) - or -NHC (= O ) -, the symbols R ³ and R ⁴ , the same or different, independently represent hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, benzyl or phenyl, and also salts, complexes with metals and N- oxides of the compounds of structural formula (I).
[006] The use of compounds of structural formula (I) as fungicides is also provided.
6/114 [007] The heteroaryl-piperidine and -piperazine derivatives of structural formula (I) of the invention, as well as their salts, complexes with metals and Noxides, are extremely suitable for the control of harmful phytogenic fungi. The aforementioned compounds of the invention exhibit, in particular, a strong fungicidal activity and can be used for the protection of crops, in the domestic and hygiene sectors, as well as in the protection of materials.
[008] The compounds of structural formula (I) can occur in pure form and also in a mixture form of different possible isomeric forms, in particular, of stereoisomers, such as E and Z isomers, threus and erythro isomers and also optical isomers, such as R and S isomers or atropic isomers, and possibly also in the form of tautomers. E and Z isomers are also claimed, as well as threo and erythro isomers, as well as optical isomers, any desired mixtures of these isomers, as well as possible tautomeric forms.
[009] The definitions of the radicals for the compounds of formula (I) according to the invention preferably have, more preferably and even more preferably, the following meanings:
the symbol Y, preferably, represents oxygen or sulfur and, more preferably, represents oxygen, the symbol R ² , preferably, represents hydrogen or halogen, more preferably, represents hydrogen or fluorine and, even more preferably, represents hydrogen, the symbol Q preferably represents Q-1, Q-2, Q-3, Q-4, Q-5 and Q-6 and, more preferably, represents Q-3 and Q-4, where the bond identified by “ x ”is directly linked to the thiazole and the bond identified by“ y ”is directly linked to the symbol L ¹ or R ¹ , the symbol R ⁵ preferably represents hydrogen, cyano, methyl, ethyl, trifluoromethyl or difluoromethyl or
7/114 the symbol R ⁵ , more preferably, represents hydrogen, cyano, methyl, trifluoromethyl or difluoromethyl or the symbol R ⁵ , even more preferably, represents hydrogen, the symbol L ¹ , preferably, represents a direct bond or oxygen, the the symbol L ¹ , more preferably, represents a direct bond, the symbol R ¹ , preferably, represents phenyl which contains at least one substituent Z ⁴ and additionally contains two or three other substituents that are selected, independently of each other , between the substituents Z ⁴ and Z ¹ or the symbol R ¹ , more preferably, represents phenyl which contains at least one substituent Z ⁴ and contains, in addition, two other substituents which are independently selected from the substituents Z ⁴ and Z ¹ or the symbol R ¹ preferably represents naphthyl, dihydronaphthalenyl, tetrahydronaphthalenyl, hexahydronaphthalenyl, octahydronaphthalenyl or indenyl o, which contains at least one substituent Z ⁵ and additionally contains two or three other substituents that are independently selected from the substituents Z ⁵ and Z ¹ or the symbol R ¹ , more preferably, represents naphthyl , dihydronaphthalenyl, tetrahydronaphthalenyl or hexahydronaphthalenyl which contains at least one substituent Z ⁵ and which contains, in addition two other substituents which are selected independently from each other, between the substituents Z ⁵ and Z ¹ or the symbol R ¹ preferably represents a 5- or 6-membered optionally substituted and benzofused heteroaryl that contains at least one Z ⁶ substituent and additionally contains two or three other substituents, which on the carbon are independently selected from each other , between the substituents Z ⁶ and Z ¹ and which in nitrogen are selected independently from each other, between the substituents Z ⁶ and Z ² or
8/114 the symbol R ¹ , more preferably, represents furan-2-yl, furan-3-yl, thiophene-2-yl, thiophene-3-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazole- 5yl, pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-1-yl, imidazol- 2-yl, imidazol-4yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,4thiadiazole- 3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 1,2,3-triazol-1-yl, 1,2,3triazol-2-yl, 1,2,3-triazol-4-yl, 1,2,4-triazol-1-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol4-yl, pyridine-2- yl, pyridine-3-yl, pyridine-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidine-2-yl, pyrimidine-4-yl, pyrimidine-5-yl or pyrazine-2-yl, which contain at least one substituent Z6 and additionally contain two other substituents, which on carbon are selected in a independently of each other, between the substituents Z ⁶ and Z ¹ and in nitrogen, independently selected from each other, between the substituents Z ⁶ and Z ² or the symbol R ¹ , even more preferably, represents furan-2-yl, furan-3-yl, thiophene-2-yl, thiophene-3-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5yl, pyrrol-1-yl, pyrrol-2-yl, pyrrole-3- yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4yl, 1,2,4-oxadiazol-3- yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,4thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1, 3,4-thiadiazol-2-yl, 1,2,3-triazol-1-yl, 1,2,3triazol-2-yl, 1,2,3-triazol-4-yl, 1,2,4- triazol-1-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol4-yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyridazine-3- yl, pyridazine-4-yl, pyrimidine-2-yl, pyrimidine-4-yl, pyrimidine-5-yl or pyrazine-2 -ilo, which may contain, in each case, 1 or 2 substituents, one substituent selected from the Z ⁶ substituent and, optionally, another substituent selected from the following list:
substituents on carbon: fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1,1-dimethylethyl, 1,2
9/114 dimethylethyl, ethylene, ethynyl, trifluoromethyl, difluoromethyl, trichloromethyl, dichloromethyl, cyclopropyl, methoxy, ethoxy, n-propoxy, 1-methylethoxy, 1,1-dimethylethoxy, methylcarbonyl, ethylcarbonyl, trifluoromethoxycarbonyl, propylcarbonyl, methylcarbonyl, carbonyl , 1-methylethoxycarbonyl, 1,1dimetiletoxicarbonilo, 1-ethenyloxy, 2-propenyloxy, 2-propynyloxy, methylcarbonyloxy, trifluoroalquilcarboniloxi, clorometilcarboniloxi, methylcarbonylamino, trifluoroalquilcarbonilamino, clorometilcarbonilamino, methylthio, ethylthio, methylsulfinyl, methylsulfonyl, methylsulfonyloxy, trifluoroalquilsulfoniloxi, methylsulfonylamino or trifluorometilsulfonilamino substituents in nitrogen: methyl, ethyl, n-propyl, -C (= O) H, methylcarbonyl, trifluoromethylcarbonyl, chloromethylcarbonyl, methylsulfonyl, trifluoromethylsulfonyl, phenylsulfonyl, phenyl or 2-propynyl or the symbol R ¹ , more preferably, represents indol-1- yl, indol-2yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, i ndol-7-yl, benzimidazol-1-yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazol-5-yl, indazol-1-yl, indazol-
3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, indazol-7-yl, indazol-2-yl, 1benzofuran-2-yl, 1-benzofuran-3-yl, 1- benzofuran-4-yl, 1-benzofuran-5yl, 1-benzofuran-6-yl, 1-benzofuran-7-yl, 1-benzothiophene-2-yl, 1benzothiophene-3-yl, 1-benzothiophene-4-yl, 1-benzothiophene-5-yl, 1-benzothiophene-6yl, 1-benzothiophene-7-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3benzothiazole-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1,3-benzoxazol-2yl, 1,3-benzoxazol-4-yl, 1,3-benzoxazol-5-yl, 1, 3-benzoxazol-6-yl, 1,3benzoxazol-7-yl, quinoline-2-yl, quinoline-3-yl, quinoline-4-yl, quinoline-5-yl, quinoline-6-yl, quinoline-7- yl, quinoline-8-yl, isoquinoline-1-yl, isoquinoline-3yl, isoquinoline-4-yl, isoquinoline-5-yl, isoquinoline-6-yl, isoquinoline-7-yl or isoquinoline-8-yl, which contain at least one substituent Z ⁶ and additionally contain two other substituents, which on carbon are selected, independently from each other, among the The substituents Z ⁶ and Z ¹ and nitrogen are selected independently from each other, between the substituents Z ⁶ and Z ² or
10/114 the symbol R ¹ , more preferably, represents indol-1-yl, indol-2yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7- yl, benzimidazol-1-yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazol-5-yl, indazol-1-yl, indazol3-yl, indazol-4-yl, indazol-5-yl, indazol- 6-yl, indazol-7-yl, indazol-2-yl,
1-benzofuran-2-yl, 1-benzofuran-3-yl, 1-benzofuran-4-yl, 1-benzofuran-5yl, 1-benzofuran-6-yl, 1-benzofuran-7-yl, 1-benzothiophene- 2-yl, 1benzothiophene-3-yl, 1-benzothiophene-4-yl, 1-benzothiophene-5-yl, 1-benzothiophene-6yl, 1-benzothiophene-7-yl, 1,3-benzothiazole-2-yl, 1,3-benzothiazol-4-yl, 1,3benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1,3-benzoxazol-2yl, 1,3- benzoxazol-4-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3benzoxazol-7-yl, quinoline-2-yl, quinoline-3-yl, quinoline-4- yl, quinoline-5-yl, quinoline-6-yl, quinoline-7-yl, quinoline-8-yl, isoquinoline-1-yl, isoquinoline-3yl, isoquinoline-4-yl, isoquinoline-5-yl, isoquinoline- 6-yl, isoquinoline-7-yl or isoquinoline-8-yl, which, in each case, can contain up to two substituents, the substituents being selected independently from each other, from the following list:
substituents on carbon: fluorine, chlorine, bromine, iodine, methyl, methoxy,
2-propynyloxy, 2-propenyloxy, substituents on nitrogen: methyl, ethyl, n-propyl, -C (= O) H, methylcarbonyl, trifluoromethylcarbonyl, chloromethylcarbonyl, methylsulfonyl, trifluoromethylsulfonyl, phenylsulfonyl, phenyl or 2-propynyl, the symbol R ² preferably represents a (C3-Cs) cycloalkyl or a (C5-C8) cycloalkenyl, which contain at least one Z ⁷ substituent and additionally contain two or three other substituents that are independently selected from each other , between the substituents Z ⁷ and Z ¹ or the symbol R ¹ , more preferably, represents a cycloalkyl (C3C8) or a cycloalkenyl (C5-C8), which contain at least one substituent Z ⁷ and additionally contain two other substituents which are independently selected from the substituents Z ⁷ and Z ¹ or the symbol Z ¹ preferably represents hydrogen, halogen,
11/114 cyano, hydroxyl, nitro, -C (= O) NR ³ R ⁴ , -NR ³ R ⁴ , (C1-Ce) alkyl, alkenyl (C2-C6), alkynyl (C2-C6), haloalkyl (C1 -C6), haloalkenyl (C2-C6), haloalkynyl (C2-C6), cycloalkyl (C ₃ -C ₆ ), halocycloalkyl (C ₃ -C8), alkoxy (C ₁ -C ₆ ) -alkyl (C ₁ -C) ₆₎ alkyl, (C ₁ -C ₆₎ carbonyl, alkoxy (C ₁ -C ₆₎ alkoxycarbonyl, _(C1-C4) haloalkoxy, _(C1-C4) alkyl, (C1-C6) alkylcarbonyloxy, alkyl (C1-C4) -thio, haloalkyl (C1-C4) -thio, cycloalkyl (C3Ce) -thio, tri- (alkyl (C1-C2)) - silyl or -L ³ Z ³ , the symbol Z ¹ , more preferably, it represents hydrogen, chlorine, fluorine, bromine, cyano, nitro, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, CH2CH2CH2CH3, -CH (CH3) CH2CH3, -CH2CH (CH3) CH3, -C ( CH3) 3, -CH = CH2, CH = CHCH3, -CH2CH = CH2, -CH = CHCH2CH3, CH2CH = CHCH3, -CH2CH2CH = CH2, -CeCH, -CECCH3, -CH2CECH, CECCH2CH3, -CH2CECCH3, -CH2CH2CECH, - CF3, -CFH2, -CF2H, -CF2CF3, CCl3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH2OCH3, CH2OCH2CH3, -CH2CH2OCH3, -CH2OCH2CH2CH3, -CH2CH2OCH2CH3, CH2CH2 O) CH3, -C (= O) CH2CH3, C (= O) CH2CH2CH3, C (= O) CH (CH3) 2, -C (= O) CF3, -C (= O) OCH3, -C (= O) OCH2CH3, C (= O) OCH2CH2CH3, -C (= O) OCH (CH3) 2, -OCH3, -OCH2CH3, -OCH2CH2CH3, OCH (CH3) 2, -OCH2CH2CH2CH3, -OCH2CH (CH3) 2, -OCH (CH3) CH2CH3, OC (CH3) 3, -OCF3, -OCF2H, -OCH2CF3, -OCF2CF3 O-cyclohexyl, O-cyclopentyl, O-cyclopropyl, -SCH3, -SCH2CH3, -SCH2CH2CH3, -SCH (CH3) 2, SCH2CH2CH2CH3, -SCH2CH (CH3) 2, -SCH (CH3) CH2CH3, -SC (CH3) 3, SCF3, -SCF2H, -SCH2CF3, -SCF2CF3, -S (= O) Me, -S (O) CF3 , -S (= O) 2Me, S (O) 2CF3, -OCH2CH = CH2, -OCH2CECH, -OCH2OCH3, -OCH2OCH2CH3, OCH2CH2OCH3, -OCH2OCH (CH3) 2, trimethylsilyl or phenyl, which may contain 0, 1 or 2 substituents selected, independently of each other, from the following listing:
chlorine, fluorine, bromine, cyano, nitro, -CH3, -CH2CH3, -CH2CH2CH3, CH (CH3) 2, -CH2CH2CH2CH3, -CH (CH3) CH2CH3, -CH2CH (CH3) CH3, -C (CH3) 3, CH = CH2, -CH2CH = CH2, -CH2CH = CHCH3, -CH2CH2CH = CH2, -CeCH, CECCH3, -CH2CECH, -CF3, -CF2H, -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3,
11/124
-CH2OCH2CH2CH3, -CH2CH2OCH2CH3, -CH2CH2CH2OCH3, -C (= O) CH2CH3, C (= O) CH2CH2CH3, C (= O) CH2CH2CH3, C (= O) CH (CH3) 2, -C (= O) CF3, -C (= O) OCH3, C (= O) OCH2CH3, -C (= O) OCH2CH2CH3, -C (= O) OCH (CH3) 2, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH (CH3) 2 , -OCH2CH2CH2CH3, -OCH2CH (CH3) 2, OCH (CH3) CH2CH3, -OC (CH3) 3, -OCF3, -OCF2H, -OCH2CF3, -OCF2CF3 O-SCH3, -SCH2CH3, -OCH2CECH, -OCH2OCH, Z ² preferably represents hydrogen, halogen, cyano, hydroxyl, nitro, -C (= O) NR ³ R ⁴ , -NR ³ R ⁴ , (C1-C6) alkyl, alkenyl (C ₂ -C6), alkynyl (C2-C6), halo (C1-C6), haloalkenyl (C2-C6), haloalkynyl (C2-C6), cycloalkyl (C3-C6), halocycloalkyl (C3-C8), alkoxy (C1-C6) -alkyl ( C1-C6) alkyl, _(C1-C6) alkoxycarbonyl, _(C1-C4) haloalkoxy, _(C1-C4) alkyl, (C 1 -C ₆₎ alkylcarbonyloxy, (C1-C4) alkylthio, haloalkyl (C1-C4) -thio, cycloalkyl (C3-C6) -thio or tri ((C1-C2 alkyl)) - silyl, the symbol Z ² , more preferably, represents hydrogen, chlorine, fluorine, bromine, cyano, nitro, -CH3, -CH2CH3, -CH2CH2CH3, -CH (CH3) 2, CH2CH2CH2 CH3, -CH (CH3) CH2CH3, -CH2CH (CH3) CH3, -C (CH3) 3, -CH = CH2, CH = CHCH3, -CH2CH = CH2, -CH = CHCH2CH3, CH2CH = CHCH3, -CH2CH2CH = CH2 , -CeCH, -CECCH3, -CH2CECH, CECCH2CH3, -CH2CECCH3, -C ^ C ^ CeCH, -CF3, -CFH2, -CF2H, -CF2CF3, CCl ₃ , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH ₂ OCH ₃ , CH2OCH2CH3, -CH2CH2OCH3, -CH2OCH2CH2CH3, -CH2CH2OCH2CH3, CH2CH2CH2OCH3, -C (= O) CH3, -C (= O) CH2CH3, C (= O) CH2CH2CH3,
C (= O) CH (CH3) 2, -C (= O) CF3, -C (= O) OCH3, -C (= O) OCH2CH3, C (= O) OCH2CH2CH3, -C (= O) OCH ( CH3) 2, -OCH3, -OCH2CH3, -OCH2CH2CH3, OCH (CH3) 2, -OCH2CH2CH2CH3, -OCH2CH (CH3) 2, -OCH (CH3) CH2CH3, OC (CH3) 3, O-cyclohexyl, O- cyclopentyl, O-cyclopropyl, -OCH2CH = CH2, OCH2CECH, -OCH2OCH3, -OCH2OCH2CH3, -OCH2OCH2CHH, -OCH2CH2OCH3, OCH2OCH (CH3) 2, trimethylsilyl, the symbol Z ³ preferably represents a phenyl radical, naphthalenyl or a hetero radical or 6 members, which can contain up to two
13/114 substituents, the substituents being selected, independently from each other, from the following list:
substituents on carbon: halogen, cyano, nitro, hydroxyl, amino, SH, alkyl (C ₁ -C ₄ ), alkenyl (C ₂ -C ₄ ), alkynyl (C ₂ -C ₄ ), haloalkyl (C1-C ₄ ) , haloalkenyl (C2-C4), haloalkynyl (C2-C4), alkoxyalkyl (C2-C4), alkyl (CrCe) carbonyl, halo-alkyl (C1-C6) -carbonyl, alkoxy (C1-C6) -carbonyl, alkoxy ( C 1 -C ₄₎ haloalkoxy, _(C1-C4) alkenyloxy, (C ₂ -C ₆₎ alkynyloxy (C ₂ -C ₆₎ alkyl, _(C1-C4) alkylthio, (C1-C4) -alkylthio , (C1-C4) alkylsulfonyl, (C1-C4) haloalkyl-sulfonyl, (C1-C4) alkylamino or di ((C1-C4) alkyl) amino, substituents on nitrogen: alkylofCrCe), alkenyl (C2 C6), alkynyl (C2-C6), haloalkyl _(C1-C6) haloalkenyl, (C ₂ -C ₆₎ haloalkynyl (C ₂ -C ₆₎ alkyl, _(C1-C4) alkyl _(C1-C4 ), phenyl, benzyl, halo (C1-C ₄ ) -sulfonyl, alkoxy (C1-C ₆ ) carbonyl, halo (C1-C6) -carbonyl, phenylsulfonyl, (C1-C4) alkylsulfonyl, C (= O) H or (C1-C3) alkylcarbonyl and the symbol Z ³ , more preferably, represents a phenyl radical which can contain up to two substituents s, with the substituents being independently selected from the following list:
chlorine, bromine, iodine, fluorine, cyano, nitro, hydroxyl, amino, -SH, methyl, ethyl, n-propyl, 1-methylethyl, 1,1-dimethylethyl, ethylene, propene-2-yl, ethynyl, propine-2 -yl, trifluoromethyl, difluoromethyl, methoxymethyl, methylcarbonyl, ethylcarbonyl, trifluoromethylcarbonyl, methoxycarbonyl, ethoxycarbonyl, npropoxycarbonyl, 1-methylethoxycarbonyl, 1,1-dimethylethoxycarbonyl, methoxy, ethoxy, n-propoxy, 1-methyloxy , ethylenoxy, 2-propenyloxy, ethynyloxy, 2-propynyloxy, methylthio, ethylthio, trifluoromethylthio, methylsulfonyl, ethylsulfonyl, propylthionyl, 1-methylethylthio, trifluoromethylsulfonyl, methylamino, ethylamino, methylpropylamino, methylpropylamino, methylpropylamino, symbol Z ⁴ preferably represents C (= O) H, cycloalkyl (C7-C8), cycloalkyl (C3-C6) -cycloalkyl (C3-C6), cycloalkenyl (C3-C6), alkoxy (C4-C6) alkyl (C1-C ₄ ), (C3-C6) alkoxy (C2-C4) alkyl, (C1-C3) alkoxy (C5-C6) alkoxy (C1-C3) alkyl, (C1-C4) alkylthio- (C1-C2) alkyl, alkyl useful (C1-C ₄ ) -sulfinyl-alkyl (C114 / 114
C2), (C1-C4) alkylsulfonyl-alkyl (C1-C2), alkyl (C1-C4) -amino-alkyl (C1-C2), dialkyl (C1-C2) -amino-alkyl (C1-C2) , halo (C1-C4) -amino-alkyl (C1-C2), cycloalkyl (C ₃ -C ₆ ) -amino-alkyl (C ₁ -C ₂ ), alkyl (C ₅ -C ₆ ) -carbonyl, haloalkyl ( C ₁ -C ₄ ) -carbonyl, (C ₃ -C ₆ ) -carbonyl, cycloalkoxy (C ₃ -C ₆ ) carbonyl, (C3-C6) cycloalkyl (C1-C2) -carbonyl, cycloalkyl (C3-) C6) aminocarbonyl, haloalkoxy (C1-C4) -alkyl (C1-C2), hydroxyalkyl (C5-C6), alkoxy (C5-C6), haloalkoxy (C5-C6), cycloalkoxy (C3-C6), halocycloalkoxy (C3- C6), cycloalkyl (C3-C6) -alkoxy, alkenyloxy (C2-C6), haloalkenyloxy (C2-C6), alkynyloxy (C2C6), haloalkynyloxy (C2-C6), alkoxy (C1-C4) -alkoxy (C1-C4) ), halo (C1-C4) carbonyloxy, (C3-C6) cycloalkyl-carbonyloxy, (C1-C4) alkyl-carbonyl-alkoxy (C1-C4), (C5-C6) alkylthio, halo (C5-C6) alkyl -thio, (C5-C6) alkylsulfinyl, (C5-C6) haloalkylsulfinyl, (C ₁ -C ₄ ) alkylsulfonyl, halo (C ₁ -C ₄ ) -sulfonyl, (C ₃ -C ₆ ) cycloalkyl sulfonyl, tri (here 1 (C3-C4)) - silyl, (C1-C4) alkylsulfonylamino or halo (C1-C4) sulfonylamino, the symbol Z ⁴ , more preferably, represents C (= O) H, cycloheptyl, 2-cyclopropylcyclopropyl, cycle hexenyl, n-butoxymethyl, n-propoxyethyl, methoxyethoxymethyl, ethoxyethoxymethyl, methylthiomethyl, ethylthiomethyl, methylsulfinylmethyl, ethylsulfinylmethyl, methylsulfonylmethyl, ethylsulfonylmethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, trifluorometilaminometilo, n-butylcarbonyl, cyclopropyl-carbonyl, cyclopentyloxycarbonyl, ciclopentilaminocarbonilo, n-pentylcarbonyl , cyclohexylcarbonyl, cyclohexyloxycarbonyl, cyclohexylaminocarbonyl, halogen-n-pentoxy, cyclopropylamino-methyl, trifluoromethylcarbonyl, cyclopropoxycarbonyl, cycloproylaminocarbonyl, difluoromethoxymethyl, cyclohexoxymethyl, cyclooxymethyl, cyclooxymethyl, cyclooxy, -methylbut-2eno-1-yloxy, prop-2-yn-1-yloxy, but-2-yn-1-yloxy, pent-2-yn-1-yloxy, haloalkynyloxy, met oxyethoxy, methoxypropoxy, ethoxyethoxy, 3,3,3-trifluoropropanyloxy, trifluoromethylcarbonyloxy, cyclopropylcarbonyloxy, cyclopentylcarbonyloxy, cyclohexylcarbonyloxy, methylcarbonylmethoxy, pentylsulfonyl, methylsulfonyl, methylsulfonyl, methylsulfonyl, methylsulfonyl, methyl
15/114 trifluoromethylsulfonylamino, the symbol Z ⁵ preferably represents benzyl, phenyl, alkoxy (C5C ₆ ), haloalkoxy (C ₅ -C ₆ ), alkenyloxy (C ₂ -C ₄ ), alkynyloxy (C ₂ -C ₄ ) , (C ₅ -C ₆ ) alkylthio or halo (C ₅ -C ₆ ) -thio, the symbol Z ⁶ preferably represents substituents on the carbon: (C3-C6) cycloalkyl-cyclopropyl, (C ₃ - cycloalkyl) C ₆ ) -cyclohexyl or tri- (C ₃ -C ₄ alkyl)) - silyl, substituents on nitrogen: alkenyl (C ₂ -C ₆ ), alkynyl (C ₂ -C ₆ ), haloalkyl (C1Ce), (C3-C6) cycloalkyl, (C1-C4) alkyl (C3-C6) cycloalkyl, (C3-C6) cycloalkyl cyclopropyl, (C3-C6) cycloalkyl-cyclohexyl, (C3-C6) cycloalkyl (C1) alkyl -C4), (C1-C ₄ ) alkylsulfonyl, C (= O) H, benzyl or phenyl, the symbol L ³ preferably represents a direct bond, -CH ₂ -, sulfur or oxygen and, most preferably , represents a direct bond, the symbols R ³ and R ⁴ are preferably the same or different and, independently of each other, represent hydrogen, alk uyl (C1-C ₄ ), alkenyl (C ₂ -C ₄ ), alkynyl (C ₂ -C ₄ ), haloalkyl (C1-C ₄ ), cycloalkyl (C ₅ -C ₆ ), benzyl or phenyl, the symbols R ³ and R ⁴ , more preferably, are the same or different, and, independently of each other, represent hydrogen, methyl, ethyl, propyl, prop-2-yne-1-yl, 1,1,1-trifluoroethyl, cycle -hexyl, benzyl or phenyl.
[010] The general definition for the heteroaryl-piperidine and piperazine derivatives that can be used according to the invention is provided by structural formula (I). The radical definitions in the previous radical definitions of structural formula (I) and those specified below apply to the final products of structural formula (I) and to all intermediates (see also below in the section “Explanation of methods and intermediaries ”), likewise.
[011] The definitions and explanations of the radicals presented before and after, in general or at intervals of preference, can also be
11/164 arbitrarily combined with each other; in other words, between the respective intervals and preference intervals. Likewise, these apply to final products and also to precursors and intermediates. It is also possible for individual definitions to be omitted.
[012] Preferred compounds of structural formula (I) are those in which all radicals, in each case, have the preferred definitions specified above.
[013] The most preferred compounds of structural formula (I) include those in which all radicals, in each case, have the most preferred definitions specified above.
[014] As even more preferred compounds of structural formula (I) are those in which all radicals, in each case, have the even more preferred definitions specified above.
[015] As additionally preferred compounds are the compounds of structural formula (I), as well as their salts, complexes with metals and Nitrides effective from an agrochemical point of view, in which:
the symbol Y represents oxygen;
the symbol R ² represents hydrogen;
Q represents Q-3;
the symbol R ⁵ represents hydrogen;
the symbol L ¹ represents a direct connection;
R ¹ represents 4,5-dimethyl-2- (prop-2-yn-1-yloxy) -phenyl or R ¹ represents 2,6-difluoro-3- (prop-2-yn-1-yloxy ) -phenyl or the symbol R ¹ represents 2,6-difluoro-4- (prop-2-yne-1-yloxy) -phenyl or the symbol R ¹ represents 2,6-difluoro-4 - [(methylsulfonyl) -amino ] -phenyl or R ¹ represents 3- (allyloxy) -2,6-difluorophenyl.
[016] The above definitions of radicals can be combined in any desired way. It is also possible for individual definitions to be omitted.
17/114 [017] According to the type of substituents defined above, the compounds of formula (I) have acidic or basic properties and can form salts, possibly also internal or adult salts, with acids or with inorganic or organic bases or with metal ions. If the compounds of structural formula (I) support an amino group, alkylamino or other groups that induce basic properties, these compounds can be subjected to reaction with acids to obtain salts or are obtained directly as salts by synthesis. If the compounds of structural formula (I) support a hydroxyl, carboxyl or other groups that induce acidic properties, then these compounds can be subjected to reaction with bases to obtain salts. Suitable bases include, for example, hydroxides, carbonates, hydrogen carbonates of alkali metals and alkaline earth metals, in particular those of sodium, potassium, magnesium and calcium, as well as ammonia, primary, secondary and tertiary amines that have groups alkyl (C ₁ -C ₄ ), mono-, di- and tri-alkanolamines of alkanols (C1-C ₄ ), choline and chlorocholine.
[018] The salts obtained in this way also have fungicidal properties.
[019] Examples of inorganic acids include hydrohalic acids, such as hydrogen fluorestry, hydrogen chloride, hydrogen bromide and hydrogen iodide, sulfuric acid, phosphoric acid and nitric acid, and acidic salts, such as NaHSO4 and KHSO4 . Useful organic acids include, for example, formic acid, carbonic acid and alkanoic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid and propionic acid, as well as glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid , benzoic acid, cinnamic acid, oxalic acid, saturated or mono- or di-unsaturated fatty acids (C6-C ₂₀ ), alkyl sulfuric monoesters, alkyl sulfonic acids (sulfonic acids that have straight or branched chain alkyl radicals that have 1 to 20 carbon atoms), arylsulfonic or aryldisulfonic acids (aromatic radicals, such as
18/114 as phenyl and naphthyl, which support one or two sulfonic acid groups), alkylphosphonic acids (phosphonic acids that have straight or branched chain alkyl radicals that have 1 to 20 carbon atoms), arylphosphonic acids or arildiphosphonic acids (aromatic radicals , such as phenyl and naphthyl, which support one or two phosphonic acid radicals), in which the alkyl and aryl radicals can further support substituents, for example, ptoluenesulfonic acid, salicylic acid, p-amino-salicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid, etc.
[020] Useful metal ions refer in particular to the ions of elements from the second main group, in particular calcium and magnesium, from the third and fourth main groups, in particular aluminum, tin and lead, and also from the fifth to the eighth transition groups, in particular, chromium, manganese, iron, cobalt, nickel, zinc and others. Metal ions of the elements of the fourth period are particularly preferred. Metals can be present in the different valences they can assume.
[021] The optionally substituted groups can be mono- or polysubstituted, where the substituents, in the case of poly-substitutions, can be the same or different.
[022] In the definitions of the symbols presented in the previous structural formulas, collective terms were used, which are usually representative of the following substituents.
[023] Halogen: fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine, bromine and, more preferably, fluorine, chlorine.
[024] Alkyl: saturated straight or branched chain hydrocarbyl radicals having 1 to 8, preferably 1 to 6 and, more preferably, 1 to 3 carbon atoms, for example (but without limitation), alkyl (C1-C ₆ ), such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl,
3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1
19/114 dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1 , 2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl. This definition also applies to alkyl radicals as part of a compound substituent, for example, cycloalkylalkyl, hydroxyalkyl, etc., unless otherwise defined, such as, for example, alkylthio, alkylsulfinyl, alkylsulfonyl, haloalkyl or haloalkylthio. If the alkyl is at the end of a compound substituent, such as, for example, in alkylcycloalkyl, then the part of the compound substituent at the beginning, for example, cycloalkyl, can be mono- or polysubstituted, in the same or different way, and , independently, with alkyl. The same also applies to compound substituents in which other radicals, for example, alkenyl, alkynyl, hydroxyl, halogen, formyl, etc., are at the end.
[025] Alkenyl: unsaturated straight or branched chain hydrocarbyl radicals having 2 to 8 and preferably 2 to 6 carbon atoms and a double bond in any position, for example (but without limitation), alkenyl (C2-C6), such as ethylenyl, 1-propenyl, 2propenyl, 1-methylethyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl,
2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl- 1-butenyl, 3methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1methyl-3-butenyl, 2-methyl-3-butenyl, 3- methyl-3-butenyl, 1,1-dimethyl-2-propenyl,
1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2pentenyl, 2-methyl-2-pentenyl, 3- methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1dimethyl-2-butenyl, 1,1, -dimethyl-3-butenyl, 1,2-dimethyl-1 -butenyl, 1,2-dimethyl-2-butyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl,
11/20
1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-
2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl,
1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2butenyl, 2-ethyl-3-butenyl, 1,1, 2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl. This definition also applies to alkenyl as part of a compound substituent, for example, haloalkenyl, etc., unless otherwise defined.
[026] Alkynyl: straight or branched chain hydrocarbyl groups having 2 to 8 and preferably 2 to 6 carbon atoms and a triple bond in any position, for example (but without limitation), alkynyl ( C2-C6), such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4pentinyl, 1 -methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl , 2-hexynyl, 3hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4pentinyl, 2-methyl-3-pentynyl, 2-methyl-4 -pentinyl, 3-methyl-1-pentynyl, 3-methyl-4pentinyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1dimethyl-3-butynyl , 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3 -butinyl and 1-ethyl-1-methyl-2propynyl. This definition also applies to alkynyl as part of a compound substituent, for example, haloalkynyl, etc., unless otherwise defined.
[027] Alkoxy: saturated straight or branched chain alkoxy radicals having 1 to 8, preferably 1 to 6 and more preferably 1 to 3 carbon atoms, for example (but without limitation), alkoxy (C1-C6), such as methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3methylbutoxy, 2,2- dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1,1-dimethylpropoxy, 1,2dimethylpropoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy,
1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3
21/114 dimethylbutoxy, 3,3-dimethyl-butoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy,
1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy. This definition also applies to alkoxy as part of a compound substituent, for example, haloalkoxy, alkynylalkoxy, etc., unless otherwise defined.
[028] Alkylthio: saturated straight or branched chain alkylthio radicals having 1 to 8, preferably 1 to 6 and, more preferably, 1 to 3 carbon atoms, for example (but without limitation), alkyl (C ₁ -C ₆ ) -thio, 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, 1,1dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3methylpentylthio, 4-methylpentylthio, 1,1-dimethylthio, 1,1-dimethyl 1,2-dimethylbutylthio, 1,3dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio, 1ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio, 1-ethyl-1methylpropylthio and 1-ethyl-2-methylpropylthio. This definition also applies to alkylthio as part of a compound substituent, for example, haloalkylthio, etc., unless otherwise defined.
[029] Alkoxycarbonyl: an alkoxy group that has 1 to 6 and preferably 1 to 3 carbon atoms (as specified above) and is attached to the main structure through a carbonyl group (-CO-). This definition also applies to alkoxycarbonyl as part of a compound substituent, for example, cycloalkylalkoxycarbonyl, etc., unless otherwise defined.
[030] Alkylsulfinyl: saturated straight or branched chain alkylsulfinyl radicals having 1 to 8, preferably 1 to 6 and, more preferably, 1 to 3 carbon atoms, for example (but without limitation), alkyl (C ₁ -C ₆ ) -sulfinyl, such as methylsulfinyl, ethylsulfinyl, propylsulfinyl, 1-methylethylsulfinyl, butylsulfinyl, 1-methylpropylsulfinyl, 2methylpropylsulfinyl, 1,1-dimethylethylsulfinyl, pentylsulfinyl, 1-methylbutylsulfinyl, 2-methylsulfinyl, 2-methylsulfinyl, 2-methyl 2-dimethylpropylsulfinyl, 1
22/114 ethylpropylsulfinyl, hexylsulfinyl, 1,1-dimethylpropylsulfinyl, 1,2-dimethylpropylsulfinyl,
1-methylpentylsulfinyl, 2-methyl-pentylsulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl, 1,2-dimethylbutylsulfinyl, 1,3dimethylbutylsulfinyl, 2,2-dimethylbutylsulfinyl, 3-dimethyl, 3-dimethyl ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl, 1-ethyl-1-methylpropylsulfinyl and 1ethyl-2-methylpropylsulfinyl. This definition also applies to alkylsulfinyl as part of a compound substituent, for example, haloalkylsulfinyl, etc., unless otherwise defined.
[031] Alkylsulfonyl: saturated straight-chain or branched alkylsulfonyl radicals having 1 to 8, preferably 1 to 6 and more preferably 1 to 3 carbon atoms, for example (but without limitation), alkyl (C1-C6) -sulfonyl, such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, 1-methylethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl, 2-methylpropylsulfonyl, 1,1-dimethylethylsulfonyl, pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylsulfonyl, 2-methyl 2-dimethylpropylsulfonyl, 1-ethylpropyl sulfonyl, hexylsulfonyl, 1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl, 1methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentylsulfonyl, 1,1-dimethylbutyl, 1,1-dimethyl , 3dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1,1,2trimethylpropylsulfonyl, 1,2,2-trimethyl-propyl sulfonyl, 1-ethyl-1-methylpropylsulfonyl and 1-ethyl-2-methylpropylsulfonyl. This definition also applies to alkylsulfonyl as part of a compound substituent, for example, alkylsulfonylalkyl, etc., unless otherwise defined.
[032] Cycloalkyl: monocyclic saturated hydrocarbyl groups having 3 to 10, preferably 3 to 8 and, more preferably, 3 to 6 carbon ring members, for example (but not limited to), cyclopropyl, cyclopentyl and cyclohexyl. This definition also applies to cycloalkyl as part of a compound substituent, for example
23/114 example, cycloalkylalkyl, etc., unless otherwise defined.
[033] Cycloalkenyl: partially unsaturated monocyclic hydrocarbyl groups having 3 to 10, preferably 3 to 8 and, more preferably, 3 to 6 carbon ring members, for example (but without limitation), cyclopropenyl, cyclopentenyl and cyclohexenyl. This definition also applies to cycloalkenyl as part of a compound substituent, for example, cycloalkenylalkyl, etc., unless otherwise defined.
[034] Cycloalkoxy: monocyclic saturated cycloalkyloxy radicals having 3 to 10, preferably 3 to 8 and, more preferably, 3 to 6 carbon ring members, for example (but without limitation), cyclopropyloxy, cyclopentyloxy and cyclohexyloxy. This definition also applies to cycloalkoxy as part of a compound substituent, for example, cycloalkoxyalkyl, etc., unless otherwise defined.
[035] Haloalkyl: straight or branched chain alkyl groups having 1 to 8, preferably 1 to 6 and, more preferably, 1 to 3 carbon atoms (as specified above), where some or all of the hydrogen atoms in these groups may be substituted by halogen atoms, as specified above, for example (without limitation), halo (C1-C3) alkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl , dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2 , 2-dichloro-2-fluoroethyl, 2,2,2trichloroethyl, pentafluoroethyl and 1,1,1-trifluoroprop-2-yl. This definition also applies to haloalkyl as part of a compound substituent, for example, haloalkylaminoalkyl, etc., unless otherwise defined.
[036] The haloalkenyl and haloalkynyl groups are defined in a similar way to haloalkyl, with the exception that, instead of alkyl groups, alkenyl and alkynyl groups are present as part of the substituent.
24/114 [037] Haloalkoxy: straight or branched chain alkoxy groups having 1 to 8, preferably 1 to 6 and, more preferably, 1 to 3 carbon atoms (as specified above), in which some or all hydrogen atoms in these groups may be substituted by halogen atoms, as specified above, for example (but without limitation), haloalkoxy (CrC3), such as chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, trifluoromethoxy chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2 2,2-dichloro-2-fluoroethoxy, 2,2,2trichloroethoxy, pentafluoroethoxy and 1,1,1-trifluoroprop-2-oxy. This definition also applies to haloalkoxy as part of a compound substituent, for example, haloalkoxyalkyl, etc., unless otherwise defined.
[038] Haloalkylthio: straight or branched chain alkylthio groups having 1 to 8, preferably 1 to 6 and, more preferably, 1 to 3 carbon atoms (as specified before), in which some or all of the atoms of hydrogen in these groups can be replaced by halogen atoms, as specified above, for example (but without limitation), halo (C1-C ₃ ) -thio, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, dichlorofluoromethylthio, chlorodifluoromethylthio, 1-chloroethylthio, 1-bromoethylthio, 1-fluoroethylthio, 2-fluoroethylthio,
2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2-fluoroethylthio, 2-chloro-2,2difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2-trichlorethylthio, pentafluoroethylthio and 1,1,1-trifluoroprop-2-ylthium. This definition also applies to haloalkylthio as part of a compound substituent, for example, haloalkylthioalkyl, etc., unless otherwise defined.
[039] Heteroaryl: monocyclic ring system totally unsaturated with 5 or 6 members that contains one to four heteroatoms of the set consisting of oxygen, nitrogen and sulfur; if the ring contains more than
25/114 an oxygen atom, so these are not directly adjacent.
[040] 5-membered heteroaryl that contains one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom: 5-membered heteroaryl ring groups that, in addition to carbon atoms, may contain one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom as members in the ring, for example (but without limitation), 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, 4-pyrazolyl, 5-pyrazolyl, 2oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 2
4-imidazolyl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-thiadiazol-3-yl,
1,2,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1,3,4-oxadiazol-2-yl, 1,3,4-thiadiazol-2-yl and 1, 3,4-triazol-2-yl.
[041] 5-membered nitrogen-bonded heteroaryl that contains one to four nitrogen atoms or 5-membered nitrogen-bonded heteroaryl that contains one to three nitrogen atoms: 5-membered heteroaryl ring groups that, in addition to the atoms of carbon, can contain one to four nitrogen atoms or one to three nitrogen atoms as ring members and where two adjacent carbon ring members or a nitrogen atom and an adjacent carbon ring member can be bridged by means of a buta-1,3-diene-1,4-diyl group, in which one or two carbon atoms can be replaced by nitrogen atoms, where these rings are attached to the main structure through one of the ring members nitrogen, for example (but without limitation), 1pyrrolyl, 1-pyrazolyl, 1,2,4-triazol-1-yl, 1-imidazolyl, 1,2,3-triazol-1-yl and 1 , 3,4 triazol-1-yl.
[042] 6-membered heteroaryl that contains one to four nitrogen atoms: 6-membered heteroaryl ring groups that, in addition to the carbon atoms, can contain one to three or one to four nitrogen atoms as ring members, for example example (but without this constituting any
26/114 limitation), 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazine-2- yl, 1,2,4 triazine-3-yl and 1,2,4,5-tetrazine-3-yl.
[043] Benzofused 5-membered heteroaryl that contains one to three nitrogen atoms or a nitrogen atom and an oxygen or sulfur atom: for example (but without limitation), indole-1yl, indole-2-yl , indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, benzimidazol-1-yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazole -5-yl, indazol-1-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, indazol-7-yl, indazol-2-yl, 1-benzofuran -2-yl, 1-benzofuran-3-yl, 1-benzofuran-4-yl, 1benzofuran-5-yl, 1-benzofuran-6-yl, 1-benzofuran-7-yl, 1-benzothiophene-2yl, 1 -benzothiophene-3-yl, 1-benzothiophene-4-yl, 1-benzothiophene-5-yl, 1benzothiophene-6-yl, 1-benzothiophene-7-yl, 1,3-benzothiazol-2-yl, 1,3 -benzothiazol-4yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1,3benzoxazol-2-yl, 1,3-benzoxazol-4 -yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6yl and 1,3-benzoxazol-7-yl.
[044] 6-membered benzofused heteroaryl that contains one to three nitrogen atoms: for example (but not limited to), quinoline-2-yl, quinoline-3-yl, quinoline-4-yl, quinoline-5 -yl, quinoline-6-yl, quinoline-7-yl, quinoline-8-yl, isoquinoline-1-yl, isoquinoline-3yl, isoquinoline-4-yl, isoquinoline-5-yl, isoquinoline-6-yl, isoquinoline -7-yl and isoquinoline-8-yl.
[045] This definition also applies to heteroaryl as part of a compound substituent, for example, heteroarylalkyl, etc., unless otherwise defined.
[046] Heterocyclyl: saturated or partially unsaturated heterocycle with three to fifteen members and, preferably, three to nine members, containing one to four heteroatoms of the set consisting of oxygen, nitrogen and sulfur: mono-, bi- or tri-heterocycles cyclic which contain, in addition to the carbon ring members, one to three nitrogen atoms and / or one oxygen atom or
27/114 sulfur or one or two oxygen atoms and or sulfur; if the ring contains more than one oxygen atom, then they are not directly adjacent; for example (but not limited to), oxiranyl, aziridinyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isoxazolidinyl, 4isoxazolidinyl, 5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl,
5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 2-oxazolidinyl,
4-oxazolidinyl, 5-oxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1,2,4-oxadiazolidine-3-yl, 1,2,4-oxadiazolidine-
5-yl, 1,2,4-thiadiazolidine-3-yl, 1,2,4-thiadiazolidine-5-yl, 1,2,4-triazolidine-3-yl,
1,3,4-oxadiazolidine-2-yl, 1,3,4-thiadiazolidine-2-yl, 1,3,4-triazolidine-2-yl, 2,3dihydrofur-2-yl, 2,3- dihydrofuro-3-yl, 2,4-dihydrofuro-2-yl, 2,4-dihydrofuro-3-yl, 2,3-dihydrothieno-2-yl, 2,3-di- hydrothieno-3-yl, 2,4-dihydrothieno-2-yl, 2,4-dihydrothieno-3-yl, 2-pyrroline-2-yl, 2-pyrroline-3-yl, 3-pyrroline-2 -yl, 3-pyrroline-3yl,
2-isoxazoline-3-yl,
3-isoxazoline-3-yl,
4-isoxazoline-3-yl,
2-isoxazoline-4yl,
3-isoxazoline-4-yl,
4-isoxazoline-4-yl,
2-isoxazoline-5-yl,
3-isoxazoline-5yl,
4-isoxazoline-5-yl,
2-isothiazoline-3-yl,
3-isothiazoline-3-yl,
4-isothiazoline-3yl,
2-isothiazoline-4-yl,
3-isothiazoline-4-yl,
4-isothiazoline-4-yl,
2-isothiazoline-5yl,
3-isothiazoline-5-yl, 4-isothiazoline-5-yl, hydropyrazol-2-yl, hydropyrazol-5-yl, hydropyrazol-4-yl, hydropyrazol-3-yl,
2.3- dihydropyrazol-3-yl,
3.4- dihydropyrazol-1-yl,
3.4- dihydropyrazol-5-yl,
4.5- dihydropyrazol-4-yl,
2.3- dihydropyrazol-1-yl,
2.3- dihydropyrazol-4-yl,
3.4- dihydropyrazol-3-yl,
4.5- dihydropyrazol-1-yl,
4.5- dihydropyrazol-5-yl,
2,3-di2,3-di3,4-di4,5-di2,3-dihydrooxazol-2-yl, 2,3-dihydro-oxazol-3-yl, 2,3-dihydro-oxazole- 4-yl, 2,3-dihydroxazol-5-yl, 3,4-dihydro-oxazol-2-yl, 3,4-dihydro-oxazol-3-yl, 3,4-di -hydro oxazol-4-yl, 3,4-dihydro-oxazol-5-yl, 3,4-dihydro-oxazol-2-yl, 3,4-dihydro oxazol-3-yl, 3 , 4-dihydro-oxazol-4-yl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl,
1,3-dioxane-5-yl, 2-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl,
3-hexahydropyridazinyl, 4-hexahydropyridazinyl, 2-hexahydropyrimidinyl,
4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-piperazinyl, 1,3,5-hexah
28/114 hydrotriazine-2-yl and 1,2,4-hexahydrotriazine-3-yl. This definition also applies to heterocyclyl as part of a compound substituent, for example, heterocyclylalkyl, etc., unless otherwise defined.
[047] Removable group: removable group for S _N 1 or S _N 2, for example, chlorine, bromine, iodine, alkylsulfonates (-OSO ₂ -alkyl, eg, -OSO ₂ CH ₃ , -OSO ₂ CF ₃ ) or arulsulfonates (-OSO ₂ -aryl, eg, -OSO ₂ Ph, -OSO ₂ PhMe).
[048] Those combinations that are contrary to the laws of nature and that experts in the field would therefore discard based on their expert knowledge are not included. Ring structures with three or more adjacent oxygen atoms, for example, are excluded.
[049] Explanation of preparation processes and intermediates [050] The piperidine-pyrazoles of structural formula (I) can be prepared in different ways. First, the possible processes are presented below in a schematic way. Unless otherwise indicated, each of the specified radicals has the meanings defined above.
[051] The processes according to the invention for the preparation of the compounds of formula (I) are optionally carried out using one or more reaction aids.
[052] Useful reaction aids include, if necessary, acceptors of inorganic or organic acids or bases. These preferably comprise acetates, amides, carbonates, hydrogen carbonates, hydrides, hydroxides or alkoxides of alkali metals or alkaline earth metals, for example, sodium acetate, potassium acetate or calcium acetate, lithium amide, amide sodium, potassium amide or calcium amide, sodium carbonate, potassium carbonate or calcium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate or calcium hydrogen carbonate, lithium hydride, sodium hydride potassium or calcium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, methoxide, ethoxide, n- or i-propoxide, n-, i-, s- or sodium t-butoxide or
29/114 methoxide, ethoxide, n- or i-propoxide, n-, i-, s- or potassium t-butoxide; as well as basic organic nitrogen compounds, for example, trimethylamine, triethylamine, tripropylamine, tributylamine, ethyldiisopropylamine, N, N-dimethylcyclohexylamine, dicyclohexylamine, ethyl dicyclohexylamine, N, N-dimethylaniline, N, Ndimethylbenzylamine, pyridine -, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-,
3,4-dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl-2-methylpyridine, 4-dimethylaminopyridine, Nmethylpiperidine, 1,4-diazabicyclo [2.2.2] -octane (DABCO), 1,5-diazabicyclo [4.3.0] non-5-ene (DBN) or 1,8-diaza-bicycles [5.4.0] -undec-7-ene (DBU).
[053] The processes according to the invention are optionally carried out using one or more diluents. Useful diluents include virtually all inert solvents. These preferably comprise optionally halogenated aliphatic and aromatic hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, benzene, toluene, xylene, methylene chloride, ethylene chloride, chloroform, tetrachloride carbon, chlorobenzene and o-dichlorobenzene, ethers, such as diethyl ether and dibutyl ether, dimethylglycolic ether and dimethyldiglycolic ether, tetrahydrofuran and dioxane, ketones, such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, esters, such as methyl acetate and ethyl acetate, nitriles, for example, acetonitrile and propionitrile, amides, for example, dimethylformamide, dimethylacetamide and N-methylpyrrolidone, and also dimethyl sulfoxide, tetramethylene sulfone, hexamethylphosphoramide and DMPU.
[054] The reaction temperature in the process according to the invention can vary over a relatively wide range. In general, the temperature used is between 0 ° C and 250 ° C and, preferably, the temperature is between 10 ° C and 185 ° C.
[055] The reaction time varies depending on the scale of the reaction and the reaction temperature, but is usually between a few minutes and 48 hours.
[056] In general, the processes according to the invention are
30/114 carried out under normal pressure. However, it is also possible to use high pressure or reduced pressure.
[057] For the execution of the processes according to the invention, the starting materials needed in each case are normally used in approximately equimolar amounts. However, it is also possible to use one of the components used in each case in a relatively high excess.
Process A
Scheme 1: process A
[058] The symbols W ¹ and W ² represent functional groups suitable for the formation of the desired isoxazoles or isoxazoline [059] In general, it is possible to prepare the compounds of structural formula (I) from the corresponding compounds (IV) and (V) with suitable functional groups W ¹ and W ² (I) (see diagram 1, process A). The possible functional groups for W ¹ and W ² are able to form, under suitable reaction conditions, the desired isoxazole or isoxazoline Q ring (eg, aldehydes, esters, carboxylic acids, amides, nitriles, alcohols, oximes, oxime chlorides, halides, alkynes, alkenes, alkyl halides, methanesulfonates, boronic acids and boronates). In the literature there are several methods for preparing isoxazoles or isoxazolines (see, WO 2008/013622; Comprehensive Heterocyclic Chemistry Vol. 4-6, AR Katritzky and CW Rees editors, Pergamon Press, New York, 1984; Comprehensive Heterocyclic Chemistry //, Vol 2-4, AR Katritzky, CW Rees and E. F: Scriven editors, Pergamon Press, New York, 1996; The Chemistry of Heterocyclic Compounds, EC Taylor, editor, Wiley, New York; Rodd's Chemistry of Carbon Compounds , Vol. 2-4, Elsevier, New York; Synthesis,
11/314
1982, 6, 508-509; Tetrahedron, 2000, 56, 1057-1094; and literature cited there).
Process B
Scheme 2: process B
(VU) [060] A particular possibility for the preparation of compounds of formula (I) from the corresponding compounds (IVa) by reaction with compounds (VI) or (VII) is presented in scheme 2.
[061] A compound of structural formula (IVa) is obtained by condensing an aldehyde of structural formula (XIX) with hydroxylamine and subsequent chlorination (see, for example, WO 05/0040159, WO 08/013622 and
Synthesis, 1987, 11,998-1001). First, the aldehyde (XIX) and hydroxylamine (scheme 3, step (a)) are reacted. The corresponding oxime (XVIII) is subsequently subjected to chlorination in the presence of a suitable chlorination agent. Preferred chlorinating reagents are N-chloro15 succinimide, HCIO, NaOCl and chlorine. After step (a), the reaction mixture can be further processed by conventional methods or directly subjected to the reaction in step (b).
Layout 3
11/32
[062] Alkenes (VI) and alkynes (VII) are either commercially available or can be prepared from commercially available precursors by procedures described in the literature (eg, from ketones or aldehydes by Wittig or Horner- Wadsworth-Emmons: Chem. Rev. 1989, 89, 863-927 and Julia olefination: Tetrahedron Lett., 1973, 14, 4833-4836; Peterson olefin: J. Org. Chem. 1968, 33, 780; with reagent Bestmann-Ohira: Synthesis 2004, 1.59-62).
[063] A compound of structural formula (I) is obtained from an alkene of structural formula (VI) or from an alkene of structural formula (VII) and a compound (IVa) by means of a cycloaddition reaction (see, for example, WO 08/013622 and Synthesis, 1987, 11,998-1001).
[064] Process B is carried out in the presence of an adequate base. Preferred bases include tertiary amines (e.g., triethylamine), carbonates, hydrogen carbonates and phosphates of alkali metals or alkaline earth metals (e.g., sodium carbonate or potassium carbonate).
[065] Preferably, process B is carried out using one or more diluents. When process B is carried out, as contemplated solvents, preferably inert organic solvents (such as, for example, ethyl acetate, tetrahydrofuran and DMF) are referred to. Another solvent contemplated is water. Alternatively, process B can be carried out in an excess of alkene
33/114 (VI) or alkaline (VII).
[066] Further processing is carried out by conventional methods.
If necessary, the compounds are purified by recrystallization or chromatography.
Process C
Scheme 4: process C
^w (IX) —B or
: the symbol [067] The symbol W ³ represents -B (OH) ₂ , V
W ⁴ represents bromine or chlorine [068] A particular possibility for the preparation of the compounds of structural formula (I) from the corresponding compounds (IVb) by reaction with the compounds (VIII) or (IX) through coupling reactions catalyzed with palladium, such as, for example, the Suzuki reaction (Angew. Chem. Int. Ed. Engl., 1998, 27, 2046; Syn. Commun., 1981, 11.7, 513), is shown in scheme 4 (process C).
[069] The intermediate of structural formula (IVb) is obtained by a boron reaction or by metal-halogen exchange with subsequent transmetallation of boron from compounds of structural formula (XXII) (see, for example, Chemical Communications, 2011, 460 -462; European Journal of Organic Chemistry, 2007, 3212-3218; Tetrahedron, 2010, 8051-8059). The compounds of structural formula (XXII) can be prepared from commercially available precursors using procedures described in the literature (see, for example, WO 2011/076699).
11/34
ο ο [070] Ο symbol W represents -Β (ΟΗ) ₂ , f or I; the symbol W ¹⁰ represents bromine or iodine [071] Isoxazoles or isoxazolines of structural formula (VIII) can be prepared from commercially available precursors (eg, from hydroxycarbonimido dibromide or (hydroxyimino) -acetic acid) using a cycloaddition reaction with an alkene (VI) or an alkaline (VII) (see, Organic Letters, 2009, 1159-1162; Liebigs Annalen derChemie, 1989, 985-90).
[072] As solvents for process C, it is possible to use all the usual solvents that are inert under the reaction conditions and the reaction can be carried out in mixtures of two or more of these solvents. Preferred solvents include Ν, Ν-dimethylformamide, dichloromethane, DMSO and tetrahydrofuran.
[073] The reaction can be carried out in the presence of the following additives: phosphines, such as 2-dicyclohexylphosphinobiphenyl, drying agents, eg, 4 Å molecular sieve, and suitable bases, eg, triethylamine, pyridine, sodium carbonate, sodium ethoxide or potassium phosphate.
[074] In the reaction, it is possible to use several copper (ll) catalysts, palladium (O) catalysts or commercially available palladium (ll) catalysts, although it is preferred to use copper (ll) acetate, tetraquistriphenylphosphine in the reaction. -paladium (O), [1,1 -bi s- (d if eni If osphine) -ferrocene] -dichloropalladium (II) or palladium (II) acetate. The amount of catalyst used is at least 1% to an excess, depending on the starting compound (IVb).
[075] Further processing is carried out using conventional methods. If necessary, the compounds are purified by recrystallization
35/114 or by chromatography.
Process D
Figure 5: Process D
[076] The symbol W ⁵ represents iodine, bromine, chlorine, p-toluene-sulfonyloxy or methylsulfonyloxy [077] A particular possibility for the synthesis of compounds of structural formula (I) from compounds (X) with compounds (XI) or (XII) is shown in the diagram (process D).
[078] Thiocarboxamides (X) are obtained by methods known from the literature, such as, for example, by thionation of the corresponding commercially available carboxamide, using, for example, Lawesson's reagent (WO 2008/013622, Org. Synth. Vol. 7, 1990, 372).
[079] α-halocetones or the corresponding equivalents (e.g., ptoluenesulfonyloxy) are also obtained by methods known from the literature (for example, see WO 2008/013622), (scheme 6).
Layout 6
36/114
(XII)
Reagent
Grignard ^^ L ^L R ¹ (VII) ^{, r}
Ι_ί-β 'N Grignard reagent wM
O
o (XI) [080] The symbol W ⁹ represents Ν, Ν-dimethylamino, N-methoxy-N-methylamino or morpholine-1-yl [081] Thiazoles (I) are obtained through a thiazole synthesis of
Hantzsch from thiocarboxamides (X) and α-halocetones or corresponding equivalents (XI) or (XII) (see, for example, “Comprehensive heterocyclic Chemistry”, Pergamon Press, 1984; Vol 6, pages 235-363, “ Comprehensive heterocyclic Chemistry II ”, Pergamon Press, 1996; Vol 3, pages 373-474 and references cited therein and WO 07/014290).
[082] Preferably, process D is carried out using one or more diluents. When carrying out process D, contemplated solvents are preferably inert organic solvents (such as, for example, Ν, Ν-dimethylformamide and ethanol).
[083] The use of an auxiliary base, such as, for example, triethylamine, is optional.
[084] If necessary, the compounds are purified by recrystallization or chromatography or can be optionally used in the next step without prior purification.
Process E
Figure 7: Process E
37/114
[085] The amides (la) obtained during the execution of process E according to the invention (scheme 7) can be converted, by methods described in the literature, to the corresponding thioamides (Ib) (eg, Bioorganic & Medicinal Chemistry Letters , 2009, 19 (2), 462-468). In this case, the compounds of structural formula (Ia) are typically subjected to reaction with phosphorus pentasulfide or 2,4-bis (4-methoxyphenyl) -1,3ditia-2,4-diphosphethane 2,4-disulfide (reagent Lawesson).
[086] Preferably, process E according to the invention is carried out using one or more diluents. Preferred solvents include toluene, tetrahydrofuran and 1,2-dimethoxyethane.
[087] After the reaction is complete, the compounds (Ib) are separated from the reaction mixture using one of the conventional separation techniques. If necessary, the compounds are purified by recrystallization or chromatography.
Process F
[088] The symbol W ⁷ represents chlorine, bromine, iodine, p-toluene-sulfonyloxy or methylsulfonyloxy [089] A possibility for the preparation of compounds of structural formula (Ia) from the corresponding compounds (XIII) with the compounds (XV ) is shown in diagram 8 (process F).
38/114 [090] Starting materials (XIII), where the symbol W ⁷ represents a removable group (eg, chlorine, bromine, iodine, p-toluene-sulfonyloxy or methylsulfonyloxy) can be prepared by the methods described in the literature a from compounds (XX), (XXI) or (III) (see figure 1) (see, for example, mesylation: Organic Letters, 2003, 2539-2541; tosylation: JP 60156601; halogenation: Australian Journal of Chemistry, 1983 , 2095-2110). Typically, compounds of formula (XIIIa, W ⁷ = chlorine) are prepared starting from an amide of formula (III) and chloroacetyl chloride. Compounds (XX) in (figure 1) are prepared in a manner analogous to process F with glycolic acid or hydroxyacetyl chloride from compound (III) (see, for example, documents WO 2007103187, WO 2006117521, Bioorganic & Medicinal Chemistry Letters, 2007, 6326-6329).
Figure 1
q-l-r '
QLR ¹
q-l-r '
(XX) (III) (XXI) [091] 3,5-bis- (difluoromethyl) -1H-pyrazole (XV) is commercially available or can be prepared from precursors commercially available by the processes described in the literature (Zhurnal Vsesoyuznogo Khimicheskogo Obshchestva im. DI Mendeleeva, 1981, 1057).
[092] In process F, at least one equivalent of a base (e.g., sodium hydride, potassium carbonate) is used with respect to the starting material of structural formula (XIII).
[093] After finishing the reaction, the compounds (Ia) are separated from the reaction mixture using one of the conventional separation techniques. If necessary, the compounds are purified by recrystallization or chromatography.
Process G
Figure 9: Process G
39/114
F
N
N
F F, 2
(Ia) qlr '[094] The symbol W ⁶ represents fluorine, chlorine, bromine or iodine [095] A possibility for the preparation of compounds of structural formula (Ia) from the corresponding compounds (III) with the compounds (XIV) is shown in diagram 9 (process G).
[096] The compounds of formula XXIV are known or can be prepared by processes described in the literature for analogous compounds (see, for example, WO 2008/091580, WO 2007/014290 and WO 2008/091594).
[097] A compound having the structural formula (Ia) can be synthesized in a manner analogous to the procedures described in the literature (see, for example, WO 2007/147336) through a coupling reaction of a compound with the corresponding formula structural (III) with a substrate of structural formula (XIV), in which the symbol W ⁶ represents fluorine, chlorine, bromine or iodine, optionally in the presence of an acid / base acceptor.
[098] At least one equivalent of an acid / base acceptor (e.g., Hünig's base, triethylamine or commercially available polymeric acid acceptors) is used in relation to the starting material of structural formula (III). If the starting material is a salt, then at least two equivalents of acid acceptor are required.
[099] Alternatively, it is also possible to synthesize a compound of structural formula (Ia) from the corresponding compound of structural formula (III) with a substrate of structural formula (XIV), in which the symbol W ⁶ represents hydroxyl, in the presence of a coupling reagent, analogous to procedures described in the literature (eg, Tetrahedron
40/114
2005, 61, 10827-10852, and references cited there).
[100] Suitable coupling reagents include, for example, peptide coupling reagents, for example, N- (3-dimethylaminopropyl) N'-ethylcarbodiimide mixed with 4-dimethylaminopyridine, N- (3dimethylaminopropyl) -N'-ethylcarbodiimide mixed with 1-hydroxybenzotriazole, bromotripyrrolidine-phosphonium hexafluorophosphate, O- (7azabenzotriazol-1-yl) -N, N, N ', N'-tetramethyl-uronium hexafluorophosphate, etc.
[101] After completing the reaction, the compounds (Ia) are separated from the reaction mixture using one of the conventional separation techniques. If necessary, the compounds are purified by recrystallization or chromatography.
Process H
Figure 10: Process H
W — N elimination of r ² _N QL ^l R ¹ protecting group
HN (II) [102] The symbol W ⁸ represents acetyl, (C 1 -C ₄ ) alkoxycarbonyl, benzyl or benzyloxycarbonyl [103] A possibility for the preparation of compounds of formula (III) from the corresponding compounds (II ) is shown in diagram 10 (process H).
[104] A compound of structural formula (II) is converted to a compound of structural formula (III) by suitable methods for the removal of protective groups, which are described in the literature (“Protective Groups in Organic Synthesis; Theodora W. Greene, Peter GM Wuts; WileyInterscience; third edition; 1999; 494-653).
[105] The tert-butoxycarbonyl and benzyloxycarbonyl protecting groups can be removed in an acidic medium (e.g., with hydrochloric acid or trifluoroacetic acid). The acetyl protecting groups can be removed under
41/114 basic conditions (e.g., with potassium carbonate or cesium carbonate). The benzyl protecting groups can be removed hydrogenolytically with hydrogen in the presence of a catalyst (e.g., palladium on activated carbon).
[106] After finishing the reaction, compounds (III) are separated from the reaction mixture using one of the conventional separation techniques. If necessary, the compounds are purified by recrystallization or chromatography or they can also be used, if desired, in the subsequent step without prior purification. Another possibility is to isolate the compound of formula (III) in the form of a salt, e.g., the hydrochloric acid or trifluoroacetic acid salt.
Process I
Scheme 11: process I w — l — r ¹
OR ² N-.rW ¹ (V) r ² N QLR ¹ —w — n ¥ - < ^z li
S x __ / one or more steps - (XVI] (II] [107] The symbols W ¹ and W ² represent functional groups suitable for the formation of the desired isoxazole or isoxazoline [108] The symbol W ⁸ represents acetyl, alkoxy (Ci- C4) -carbonyl, benzyl or benzyloxycarbonyl [109] A possibility for the preparation of the intermediate of structural formula (II) from the corresponding compounds (XVI) is presented in scheme 11 (process I). The possible functional groups for W ¹ and W ² are capable of forming, under suitable reaction conditions, the desired isoxazole or isoxazoline ring Q (eg, aldehydes, esters, carboxylic acids, amides, nitriles, alcohols, oximes, oxime chloride, halides, alkanes, alkenes, halides of alkyl, methanesulfonates, trifluoromethane-sulfonates, boronic acids and boronates) Process I is carried out in a similar way to process A (scheme 1).
Process J
42/114
Figure 12: Process J
[110] The symbol W ⁸ represents acetyl, (C 1 -C 4) alkoxycarbonyl, benzyl or benzyloxycarbonyl [111] A particular possibility for the preparation of the intermediate of structural formula (II) from the corresponding compounds (XVIa) by reaction with compounds (VI) or (VII) are shown in scheme 12 (process J). Process J is carried out in a similar way to process B (scheme 2).
Process K
Figure 13: Process K
(ll)
The symbol W ³ represents -B (OH) ₂ ,
the symbol W ⁴ represents bromine or chlorine the symbol W ⁸ represents acetyl, (C 1 -C 4) alkoxycarbonyl, benzyl or benzyloxycarbonyl [112] Another particular possibility for the preparation of the intermediate of structural formula (II) from the corresponding compounds
43/114 (XVIb) by reaction with compounds (VIII) or (IX) is shown in scheme 13 (process K). process K is carried out in a similar way to process C (diagram 4).
Process L
Figure 14: Process L
(XVII)
(II)
[113] The symbol W ⁵ represents iodine, bromine, chlorine, p-toluene-sulfonyloxy or methylsulfonyloxy [114] A particular possibility for the preparation of the intermediate of structural formula (II) from the corresponding compounds (XVIa) by reaction with the compounds (XI) or (XII) is shown in scheme 14 (process L). Process L is carried out in a similar way to process D (diagram 5).
[115] It is recognized that certain reagents and reaction conditions, described above for the preparation of compounds of formula (I), may not be compatible with certain functionalities present in the intermediate compounds. In such cases, the incorporation of protection / deprotection sequences or mutual conversions of functional groups in the synthesis is useful to obtain the desired products. The use and selection of protecting groups is obvious to a specialist in the field of chemical synthesis (see, for example, “Protective Groups in Organic Synthesis”; third edition; 494-653, and literature cited there). It will be evident to a person skilled in the art that in certain cases, after the introduction of a particular reagent,
44/114 as presented in an individual scheme, it may be necessary to carry out additional routine synthesis steps, which are not described in detail, to complete the synthesis of the compounds of formula (I). Likewise, it will be apparent to a person skilled in the art that it may be necessary to perform a combination of steps, illustrated in the previous schemes, in a different order from the sequence implied by that specifically presented, to prepare the compounds of formula (I).
[116] Likewise, the present invention also provides compounds of structural formula (XIII)
Q-L-R '(XIII)
and also their salts, complexes with metals and N-oxides, in which the symbols W7, R ² , Q, L ¹ and R ¹ have the general, preferred, most preferred and even more preferred meanings indicated above.
[117] Likewise, the present invention also provides compounds of formula (II)
QLR ¹ (II) and also its salts, complexes with metals and N-oxides, in which the symbols W8, R ² , Q, L ¹ and R ¹ have the general, preferred, most preferred and even more preferred meanings indicated above.
[118]
Structural formula (III) compounds are new
QLR ¹ (III)
such as, for example, (IIIa), (IIIb), (IIIc) and (IIId),
45/114
and also their salts, complexes with metals and N-oxides, in which the symbols L ¹ , R ¹ and R ⁵ have the general, preferred, most preferred and even more preferred meanings indicated above.
[119] Likewise, the present invention provides the new compound of structural formula (XIV-1)
and also its salts, complexes with metals and N-oxides.
[120] The present invention also relates to a composition for the control of unwanted microorganisms, which comprises the active ingredients of the invention. Preferably, said composition is a fungicidal composition that comprises agriculturally suitable auxiliaries, solvents, vehicles, surfactants or fillers.
[121] The invention also relates to a method for the control of unwanted microorganisms, characterized in that the active ingredients of the invention are applied to phytogenic fungi and / or their habitat.
[122] According to the invention, a vehicle is an organic or inorganic substance, natural or synthetic, with which the active ingredients are mixed or combined to obtain a better applicability, in
46/114 particular for application to plants or parts of plants or seeds. The vehicle, which can be solid or liquid, is usually inert and should be suitable for use in agriculture.
[123] Useful solid or liquid vehicles include: for example, ammonium salts and natural rock dust, such as kaolin, clays, talc, chalk, quartz, atapulgite, montmorillonite or diatomaceous earth, and synthetic rock dust , such as finely divided silica, aluminum oxide and natural or synthetic silicates, resins, waxes, solid fertilizers, water, alcohols, in particular, butanol, organic solvents, mineral and vegetable oils and their derivatives. It is also possible to use mixtures of these vehicles. As solid vehicles useful for granules are: for example, broken and fractionated natural rocks, such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inorganic and organic flours and also granules of organic materials, such as sawdust , coconut shells, corn cobs and tobacco stems.
[124] Liquefied gaseous cargoes or vehicles include all liquids that are gaseous at normal temperature and under normal pressure, for example aerosol propellants such as halohydrocarbons, as well as butane, propane, nitrogen and carbon dioxide .
[125] In formulations, it is possible to use adhesives, such as carboxymethylcellulose, natural and synthetic polymers in the form of powders, granules or agglomerates, such as arabica, polyvinyl alcohol and polyvinyl acetate, or else natural phospholipids, such as like cephalins and lecithins and synthetic phospholipids. Like other additives, it is possible to mention mineral and vegetable oils.
[126] If the extender used is water, then it is also possible to use, for example, organic solvents as auxiliary solvents. Useful liquid solvents include essentially: aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalenes, chlorinated aromatic hydrocarbons or chlorinated aliphatic hydrocarbons, such as chlorobenzenes,
47/114 chloroethylenes or dichloromethane, aliphatic hydrocarbons, such as cyclohexane or paraffins, for example, fractions of mineral oils, mineral and vegetable oils, alcohols such as butanol or glycol, and their ethers and esters, ketones, such as acetone, methyl -ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents, such as dimethylformamide and dimethyl sulfoxide, as well as water.
[127] The compositions of the invention may further comprise other components, for example surfactants. Useful surfactants include emulsifiers and / or foaming agents, dispersants or wetting agents that have ionic or non-ionic properties, or mixtures of these surfactants. Examples of these include salts of polyacrylic acid, salts of lignosulfonic acid, salts of phenolsulfonic acid or naphthalene sulfonic acid, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols preferably alkylphenols or arylphenols), salts of sulfo-succinic esters, taurine derivatives (preferably alkyl taurates), phosphoric esters of alcohols or polyethoxylated phenols, fatty acid esters of polyols and derivatives of compounds containing sulphates, sulphonates and phosphates, for example, alkylarylpolyglycolic ethers, alkylsulfonates, alkylsulphates, arylsulphonates, protein hydrolysates, ligno-waste and methyl-cellulose. The presence of a surfactant and / or one of the inert vehicles is insoluble in water and if the application is carried out in water. The proportion of surfactants is between 5% and 40% by weight of the composition of the invention.
[128] It is possible to use dyes, such as inorganic pigments, for example, iron oxide, titanium oxide and Prussian blue, and organic dyes, such as alizarin dyes, azo dyes and metallic phthalocyanine dyes, and trace nutrients, such as iron, manganese, boron, copper, cobalt, molybdenum and zinc salts.
[129] If appropriate, it is also possible to have other additional components present, for example, protective colloids, binders,
48/114 adhesives, thickeners, thixotropic substances, penetrants, stabilizers, sequestrants, complexing agents. In general, the active ingredients can be combined with any solid or liquid additive commonly used for formulation purposes.
[130] In general, the compositions and formulations of the invention contain between 0.05% and 99% by weight, between 0.01% and 98% by weight, preferably between 0.1% and 95% by weight, more preferably between 0.5% and 90% by weight and even more preferably between 10% and 70% by weight of active ingredient.
[131] The active ingredients or compositions of the invention can be used as is or, depending on their physical and / or chemical properties, in the form of their formulations or forms of use prepared therefrom, such as aerosols, capsule suspensions, cold fog concentrates, hot fog concentrates, encapsulated granules, fine granules, fluidizable concentrates for seed treatment, ready-to-use solutions, dispersible powders, emulsifiable concentrates, oil-in-water emulsions, water-in-oil emulsions , macrogranules, microgranules, oil dispersible powders, oil miscible fluidizable concentrates, oil miscible liquids, foams, pastes, pesticide-coated seeds, suspension concentrates, suspo-emulsion concentrates, soluble concentrates, wettable powders, soluble powders, dust and water-soluble granules, granules or pills, water-soluble powders for seed treatment, wettable powders, natural and synthetic substances impregnated with active ingredient and also microencapsulations in polymeric substances and seed coating materials, as well as cold mist and hot mist ULV formulations.
[132] The above formulations can be prepared in a manner known per se, for example, by mixing the active ingredients with at least one filler, solvent or diluent, emulsifier, dispersant and / or
49/114 binder or fixing agent, wetting agent, water repellent, if appropriate desiccants and UV stabilizers and, if appropriate, dyes and pigments, defoamers, preservatives, secondary thickeners, adhesives, gibberellins and also processing aids.
[133] The compositions of the invention comprise not only formulations that are ready to use and that can be applied with devices suitable for plants or seeds, but also commercial concentrates that have to be diluted with water before use.
[134] The active ingredients of the invention may be present as such or in their (commercial) formulations and in forms of use prepared from these formulations, as a mixture with other (known) active ingredients, such as insecticides, tractors, sterilizers, bactericides , acaricides, nematicides, fungicides, growth regulators, herbicides, fertilizers, phytoprotective and / or semi-chemical agents.
[135] The treatment according to the invention of plants and parts of plants with the active ingredients or compositions is carried out directly or by acting on their surroundings, habitat or storage space using conventional treatment methods, for example , immersion, spraying, atomization, irrigation, evaporation, dusting, dusting, misting, dissemination, foam application, brushing, diffusion, rinsing (spraying), drip irrigation and, in the case of propagating material, in particular in in the case of seeds, by dry seed treatment, by wet seed treatment, by paste treatment, by incrustation, by coating with one or more layers, etc. It is also possible to apply the active ingredients by the ultra-volume method reduced or by injection of the active ingredient preparation or the active ingredient itself into the soil.
[136] The invention further comprises a method for treating seeds.
[137] The invention also relates to seeds treated with one of the
50/114 methods described in the previous paragraph. The seeds of the invention are used in methods for protecting seeds against unwanted microorganisms. In these methods, seeds treated with at least one active ingredient of the invention are used.
[138] The active ingredients or compositions of the invention are also suitable for seed treatment. A large part of the damage to crop plants caused by harmful organisms is triggered by the infection of the seed during storage or after cultivation, and also during and after the germination of the plant. This phase is particularly critical since the roots and shoots of the growing plant are particularly sensitive and even minor damage can cause the plant to die. Therefore, there is a great interest in protecting seeds and the germinating plant through the use of suitable compositions.
[139] The control of phyto-pathogenic fungi through the treatment of plant seeds has been known for a long time and is subject to constant improvements. However, seed treatment entails a set of problems that cannot always be satisfactorily solved. For example, it is desirable to develop methods to protect seeds and the germinating plant, which dispense with, or at least significantly reduce, the additional application of crop protection compositions after cultivation or after plant emergence. It is also desirable to optimize the amount of active ingredient used, in order to provide the best possible protection for the seed and for the germinating plant against attack by phytogenic fungi, without however damaging the plant itself by the active ingredient used. In particular, seed treatment methods should take into account the intrinsic fungicidal properties of transgenic plants to achieve optimum protection of the seed and the germinating plant with a minimum amount of crop protection compositions.
[140] Therefore, the present invention also concerns a method
51/114 for the protection of germinating seeds and plants against attack by phyto-pathogenic fungi by treating the seeds with a composition of the invention. The invention also relates to the use of the compositions of the invention for the treatment of seeds for the protection of seeds and germinating plants against phyto-pathogenic fungi. The invention also relates to seeds treated with a composition of the invention for protection against phyto-pathogenic fungi.
[141] Phyto-pathogenic fungi that damage post-emergence plants are mainly controlled by treating the soil and aerial parts of plants with crop protection compositions. Due to concerns about the possible influence of compositions for the protection of cultures on the environment and on the health of humans and animals, efforts are needed to reduce the applied amount of active ingredient.
[142] One of the advantages of the present invention is that, due to the particular systemic properties of the active ingredients and the compositions according to the invention, the treatment of the seeds with these active ingredients and compositions not only protects the seeds themselves, but also the resulting plants after emergence, against phyto-pathogenic fungi. In this way, immediate treatment of the crop at the time of cultivation or after a short time can be dispensed with.
[143] It is also considered advantageous that the active ingredients or compositions according to the invention can be used particularly in transgenic seeds, in which case the plant that grows from such seeds is capable of expressing a protein that acts against pests. The treatment of such seeds with the active ingredients or compositions of the invention, simply by expressing the protein, for example, an insecticidal protein, can provide control of certain pests. Surprisingly, it is possible to observe another synergistic effect in this case, which further increases the effectiveness of
52/114 protection against pest attack.
[144] The compositions of the invention are suitable for protecting seeds from any variety of plants used in agriculture, greenhouses, forests or horticulture and viticulture. In particular, this refers to cereal seeds (such as wheat, barley, rye, triticale, sorghum / millet and oats), maize, cotton, soy, rice, potatoes, sunflower, beans, coffee, beet (eg sugar beet and fodder beet), peanuts, rapeseed, poppy, olive, coconut, cocoa, sugar cane, tobacco, vegetables (such as tomatoes, cucumbers, onions and lettuce), grass and ornamental plants (see also below) . The treatment of cereal seeds (such as wheat, barley, rye, triticale and oats), corn and rice is particularly significant.
[145] As described below, the treatment of transgenic seeds with the active ingredients or compositions of the invention is of particular importance. This refers to plant seeds that contain at least one heterologous gene that allows the expression of a polypeptide or protein that has insecticidal properties.
[146] The heterologous gene in the transgenic seed may come, for example, from microorganisms of the species Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladium. Preferably, this heterologous gene comes from Bacillus sp., In which case the gene product is effective against the European corn borer and / or chrysomelid of the corn root system. Most preferably, the heterologous gene comes from Bacillus thuringiensis.
[147] In the context of the present invention, the composition of the invention is applied to the seed, either alone or in a suitable formulation. Preferably, the seed is treated in a state in which it is sufficiently stable to prevent damage during treatment. In general, the seed can be treated at any time between harvest and cultivation. It is customary to use seeds that have been separated from the plant and released from leaves, bark, stems, coatings, hair or flesh of the fruits. For example, it is
53/114 it is possible to use seeds that have been harvested, cleaned and dried to a moisture content of less than 15% by weight. Alternatively, it is also possible to use seeds that, after drying, for example, have been treated with water and then dried again.
[148] During seed treatment, it should normally be ensured that the amount of composition according to the invention applied to the seeds and / or the amount of other additives are selected in such a way that the germination of the seed is not impaired or that the resulting plant is not damaged. This should be particularly guaranteed in the case of active ingredients that exhibit phytotoxic effects for certain application rates.
[149] The compositions of the invention can be applied directly, that is, in the absence of any other components and without having to be diluted. In general, it is preferable to apply the compositions to the seeds in the form of a suitable formulation. Suitable formulations and methods for seed treatment are known to those skilled in the art and are described, for example, in the following documents: US 4 272 417, US 4 245 432, US 4 808 430, US 5 876 739, US 2003/0176428 A1, WO 2002/080675, WO 2002/028186.
[150] The active ingredients usable according to the invention can be converted into conventional seed coating formulations, such as solutions, emulsions, suspensions, powders, foams, pastes and other seed coating compositions, as well as ULV formulations.
[151] These formulations are prepared in a known way, by mixing the active ingredients with conventional additives, for example, fillers and solvents or diluents, dyes, wetting agents, dispersants, emulsifiers, defoamers, preservatives, secondary thickeners, adhesives, conventional gibberellins and also water.
[152] As useful dyes that may be present in seed coating formulations usable according to the invention are referred to
54/114 all dyes conventionally used for such purposes. It is possible to use pigments, which are poorly soluble in water, or dyes, which are soluble in water. Examples include dyes known by the names' Rhodamine B ',' C.I. Pigment Red 112 'and' C.I. Solvent Red 1 '.
[153] Useful wetting agents that can be present in seed coating formulations usable according to the invention include all substances that promote wetting and that are conventionally used for the formulation of active agrochemical ingredients. Preferably, alkylnaphthalene sulfonates, such as diisopropyl- or diisobutyl naphthalene sulfonates, are used.
[154] As useful dispersants and / or emulsifiers that may be present in seed coating formulations usable according to the invention are all nonionic, anionic and cationic dispersants conventionally used for the formulation of active agrochemical ingredients. Preferably, nonionic or anionic dispersants or mixtures of nonionic or anionic dispersants are used. In particular, useful non-ionic dispersants include blocking polymers of ethylene oxide / propyl oxide o, polyglycyl ethers of alkyls and poly-glycolic ether of tristrrylphenol, and their phosphate or sulfate derivatives. In particular, suitable anionic dispersants include lignosulfonates, polyacrylic acid salts and arylsulfonate / formaldehyde condensates.
[155] As defoamers that may be present in seed coating formulations usable according to the invention, all foam-inhibiting substances conventionally used for the formulation of active agrochemical ingredients are referred to. Preferably, silicone defoamers and magnesium stearate are used.
[156] As preservatives that can be present in seed coating formulations usable in accordance with the invention, all substances usable for such purposes in agrochemical compositions refer. Examples include dichlorophene and hemiformal benzyl alcohol.
55/114 [157] As secondary thickeners that can be present in seed coating formulations usable according to the invention, all substances usable for such purposes in agrochemical compositions are referred to. Preferred examples include cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and finely divided silica.
[158] As adhesives that may be present in seed coating formulations usable according to the invention are all conventional binders usable in seed coating products. Preferred examples include polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose.
[159] Preferably, the gibberellins which may be present in the seed coating formulations usable according to the invention may be gibberellins A1, A3 (= gibberellic acid), A4 and A7; the use of gibberellic acid is particularly preferred. Gibberellins are known (according to R. Wegler Chemie der Pflanzenschutz- und Schãdlingsbekãmpfungsmittel, vol. 2, Springer Verlag, 1970, pp. 401-412).
[160] The seed coating formulations usable according to the invention can be used to treat several different types of seeds, including the seeds of transgenic plants, either directly or after previous dilution with water. In this case, an additional synergistic effect may occur in the interaction with the substances formed by expression.
[161] For seed treatment with seed coating formulations usable according to the invention, or with preparations prepared therefrom by adding water, all mixing units conventionally used for seed coating are useful. In particular, the procedure for seed coating consists of placing the seeds in a mixer, adding the particular desired amount of seed coating formulations, either as or after
56/114 previous dilution with water, and mix everything until the formulation is evenly distributed over the seeds. If appropriate, after these steps, a drying operation follows.
[162] The active ingredients or compositions according to the invention have a potent microbicidal activity and can be used for the control of unwanted microorganisms, such as fungi and bacteria, for the protection of cultures and for the protection of materials.
[163] Fungicides can be used for crop protection to control plasmodioforomycetes, oomycetes, quitridiomycetes, zygomycetes, ascomycetes, basidiomycetes and deuteromycetes.
[164] Bactericides can be used for culture protection to control Pseudomonadaceae, Rhizobiaceae, Enterobacteriaceae, Corynebacteriaceae and Streptomycetaceae.
[165] The fungicidal compositions of the invention can be used for curative or protective control of phytogenic fungi. Therefore, the invention also concerns curative and protective methods for the control of phyto-pathogenic fungi through the use of the active ingredients or compositions of the invention, which are applied to seeds, plants or parts of plants, fruits or to the soil on which the plants grow.
[166] The compositions of the invention for the control of phyto-pathogenic fungi in crop protection comprise an effective but non-phytotoxic amount of the active ingredients of the invention. The term effective but non-phytotoxic amount means an amount of the composition of the invention that is sufficient to control fungal plant diseases in a satisfactory manner or to eradicate fungal disease completely and, at the same time, does not cause any significant symptoms of phytotoxicity. In general, such an application rate can vary over a relatively wide range. It depends on several factors, for example, the fungus to be controlled, the plant, the climatic conditions and the ingredients of the compositions of the invention.
57/114 [167] The fact that the active ingredients are well tolerated by plants in the concentrations necessary for the control of plant diseases, allows the treatment of aerial parts of plants, propagating material and seeds and soil.
[168] According to the invention, it is possible to treat all plants and parts of plants. The term "plants" used herein means all plants and plant populations, such as desired and unwanted wild plants or crop plants (including naturally occurring crop plants). As crop plants it is possible to refer to plants that can be obtained by conventional methods of cultivation and optimization or by methods of biotechnology and genetic engineering or by a combination of such methods, including transgenic plants and varieties of plants that may or may not be protected by plant variety rights. The term “plant parts” is intended to refer to all the aerial and underground parts and organs of plants, such as shoots, leaves, flowers and roots, being possible to mention as examples the leaves, needles, stems, trunks, flowers, carpophores, fruits, seeds, roots, tubers and rhizomes. The plant parts also comprise the harvest material and the vegetative and generative propagation material, for example, cuttings, tubers, rhizomes, rooted cuttings and seeds.
[169] The active ingredients of the invention, when well tolerated by plants, have a favorable homothermal toxicity and are well tolerated by the environment, are suitable for the protection of plants and plant organs, to increase the yield of the crop, to improve the quality of the material harvested. Preferably, they can be used as crop protection compositions. They are active against normally sensitive and resistant species and against all or some stages of development.
[170] According to the invention, the following main crop plants are referred to as plants that can be treated: corn, soybeans, cotton,
58/114 rapeseed oil seeds, such as Brassica napus (vg, canola), Brassica rapa, B. juncea (vg, mustard (field)) and Brassica carinata, rice, wheat, sugar beet, sugar cane, oats, rye, barley, millet and sorghum, triticale, flax, vines and various fruits and vegetables from different botanical classes, for example, Rosaceae sp. (for example, seeded fruits, such as apples and pears, but also stone fruits, such as apricots, cherries, almonds and peaches and berries, such as strawberries), 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. (e.g., coffee), Theaceae sp., Sterculiceae sp., Rutaceae sp. (for example, lemons, oranges and grapefruits); Solanaceae sp. (for example, tomatoes, potatoes, peppers, eggplants), Liliaceae sp., Compositae sp. (for example, lettuce, artichoke and chicory - including chicory root, endives or common chicory), Umbelliferae sp. (for example, carrot, parsley, celery and celeriac), Cucurbitaceae sp. (for example, cucumbers - including maxixeiro, pumpkins, watermelon, gourds and melons), Alliaceae sp. (for example, leek and onions), Cruciferae sp. (eg white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radish, bastard horseradish, watercress, mustard, rapeseed and Chinese cabbage), Leguminosae sp. (for example, peanuts, peas and beans - for example, common beans and broad beans), Chenopodiaceae sp. (eg Swiss cabbage, fodder beet, spinach, beet), Malvaceae (eg okra), Asparagaceae (eg asparagus); useful plants and ornamental plants in gardens and forests; and genetically modified varieties of each of these plants.
[171] As mentioned above, it is possible to treat all plants and their parts according to the invention. According to a preferred variant, species and varieties of plants and parts of wild plants or obtained by conventional biological culture methods are treated,
59/114 such as crossing or fusing protoplasts. According to a more preferred variant, the treatment of plants, plant varieties and parts of transgenic plants is carried out by genetic engineering methods, optionally in combination with conventional methods (Genetically Modified Organisms). The term plant parts or parts has been explained before. Particularly preferably, the plants that are treated according to the invention are plants of the varieties that are commercially available or in use. The term plant varieties is intended to refer to plants that have new characteristics (traits) and that were obtained by conventional culture, mutagenesis or by recombinant DNA techniques. They can be cultivars, biotypes or genotypes.
[172] The treatment method according to the invention can be used for the treatment of genetically modified organisms (GMO), for example, plants or seeds. Genetically modified plants (or transgenic plants) are plants in which a heterologous gene has been stably integrated into the genome. The term heterologous gene essentially designates a gene that comes from or is assembled outside the plant and that when introduced into the nuclear, chloroplastic or mitochondrial genome provides the transformed plant with new or improved agronomic or other properties through the expression of a protein or polypeptide relevant or by deregulation or silencing of other gene (s) that are present in the plant (using, for example, antisense technology, co-suppression technology or RNAi technology [RNA interference]). A heterologous gene that is present in the genome is called a transgene. A transgene that is defined by its particular location in the plant's genome is called a transgenic transformation or event.
[173] Depending on the species of the plant or the varieties of the plant, its location and growing conditions (soil, climate, vegetation period, diet), the treatment according to the invention can also
60/114 provide over-additive (“synergistic) effects. Thus, for example, it is possible to achieve a reduction in application rates and / or a broadening of the activity spectrum and / or an increase in the activity of the active compounds and compositions usable according to the invention, better plant growth, greater tolerance to high or low temperatures, greater tolerance to drought or salt content of water or soil, greater flowering performance, greater ease of harvesting, accelerated ripening, greater yields, larger fruits, greater height of plants, greener leaf coloration, faster flowering, better quality and / or a higher nutritional value of the harvested products, a higher concentration of sugar in the fruits, greater storage stability and / or an easier processing of the harvested products , effects that exceed the effects that could be predicted in reality.
[174] For certain application rates, combinations of active ingredients according to the invention can also have a strengthening effect on plants. Therefore, they are suitable for mobilizing the plant's defense system against attacks by unwanted phytogenic fungi and / or microorganisms and / or viruses. This may be one of the reasons for the increased activity of the combinations according to the invention, for example, against fungi. As plant-fortifying substances (resistance inducers) we intend to designate, in the present context, those substances or combinations of substances that are capable of stimulating the defense system of plants in such a way that treated plants, when subsequently inoculated with fungi unwanted phytogenic pathogens, develop a high degree of resistance against these unwanted phytogenic fungi. In the present case, as unwanted phyto-pathogenic fungi Thus, the substances according to the invention can be used to protect plants against attacks by the aforementioned pathogens after a certain period of time after the
61/114 treatment. The period of time during which protection is conferred is normally between 1 and 10 days and preferably between 1 and 7 days, after the treatment of the plants with the active ingredients.
[175] The plants and varieties of plants that are preferably treated according to the invention include all plants that have genetic material that gives useful and particularly advantageous traits to these plants (whether obtained by means of culture and / or biotechnological means) .
[176] Plants that are also preferably treated according to the invention are resistant to one or more biotic stresses, that is, said plants have a better defense against animal and microbial pests, such as against nematodes, insects, mites, fungi pathogens, bacteria, viruses and / or viroids.
[177] Examples of resistant plants and nematodes are described, for example, in the following North American patent applications: 11/765 491, 11/765 494, 10/926 819, 10/782 020, 12/032479,
10/783 417, 10/782 096, 11/657 964, 12/192 904, 11/396 808, 12/166253,
12/166 239, 12/166 124, 12/166 209, 11/762 886, 12/364 335, 11/763947,
12/252 453, 12/209 354, 12/491 396 and 12/497 221.
[178] The plants and plant varieties that can also be treated according to the invention are those plants that are resistant to one or more abiotic stressors. Abiotic stress conditions may include, for example, drought, exposure to cold temperatures, exposure to heat, osmotic stress, flooding, increased soil salinity, increased exposure to minerals, exposure to ozone, elevated exposure to light, limited availability nitrogen nutrients, limited availability of phosphorus nutrients, no shade.
[179] The plants and varieties of plants that can also be treated according to the invention are those plants characterized by increased yield characteristics. The increased yield on
62/114 said plants may be the result, for example, of an improvement in plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen utilization, improved carbon assimilation , improved photosynthesis, increased germination efficiency and accelerated maturation. In addition, yield may be affected by improved plant architecture (under stress conditions and in the absence of stress), including faster flowering, flowering control for hybrid seed production, seed vigor, plant size, number and internodal distance, root growth, seed size, fruit size, pod size, number of pods and ears, number of seeds per pod or ear, seed mass, increased seed filling, reduced seed dispersion, reduced dehiscence of pod and lodging resistance. Other yield traits include seed composition, such as carbohydrate content, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
[180] The plants that can be treated according to the invention are hybrid plants that already express the characteristics of heterosis or hybrid vigor that normally provides better performance, vigor, health and resistance to biotic and abiotic stress factors. Typically, such plants are prepared by crossing a sterile inbred male parent line (female parent) with another inbred male fertile parent line (male parent). Typically, hybrid seeds are harvested from sterile male plants and sold to producers. Sterile male plants can sometimes (for example, in maize) be produced by cutting the panicle (ie, mechanical removal of male reproductive organs or male flowers), although, more typically, male sterility is the result of genetic determinants in the plant genome. In this case, and particularly when the seed constitutes the product
63/114 that is intended to be harvested from hybrid plants, it is typically useful to ensure that male fertility in hybrid plants, which contain the genetic determinants responsible for male sterility, is fully restored. This can be done by ensuring that male parents have the appropriate fertility restoring genes, which are capable of restoring male fertility in hybrid plants that contain the genetic determinants responsible for male sterility. The genetic determinants for male sterility may be located in the cytoplasm. Examples of cytoplasmic male sterility (CMS) have been described, for example, for the species Brassica. However, the genetic determinants for male sterility can also be located in the nuclear genome. Plants with male sterility can also be obtained by plant biotechnological methods, such as genetic engineering. A particularly useful means of obtaining plants with male sterility is described in WO 89/10396, in which, for example, a ribonuclease, such as barnase, is selectively expressed in tapetum cells in the stamens. Fertility can then be restored by expression in the tapetum cells of a ribonuclease inhibitor, such as barstar.
[181] The plants or plant varieties (obtained by plant biotechnology methods, such as genetic engineering) that can be treated according to the invention are herbicide tolerant plants, that is, plants made tolerant to one or more specific herbicides . Such plants can be obtained by genetic transformation or by selecting plants that contain a mutation that gives them such tolerance to the herbicide.
[182] Herbicide-tolerant plants are, for example, glyphosate-tolerant plants, that is, plants made tolerant to the herbicide glyphosate or its salts. Plants can be made tolerant to glyphosate by various methods. For example, glyphosate-tolerant plants can be obtained by transforming the plant with a gene that encodes the enzyme 5
64/114 enolpyruvylshiquimato-3-phosphate synthase (EPSPS). Examples of such EPSPS genes include the AroA gene (CT7 mutant) of the bacterium Salmonella typhimurium (Comai et al., 1983, Science, 221, 370-371), the CP4 gene of the bacterium Agrobacterium sp. (Barry et al., 1992, Curr. Topics Plant Physiol. 7, 139-145), the genes encoding a petunia EPSPS (Shah et al., 1986, Science 233, 478-481), a tomato EPSPS ( Gasser et al., 1988, J. Biol. Chem. 263, 4280-4289) or an EPSPS of eleusina (WO 01/66704). They can also be a mutated EPSPS. Glyphosate-tolerant plants can also be obtained by expressing a gene that encodes a glyphosate oxidoreductase enzyme. Glyphosate-tolerant plants can also be obtained by expressing a gene that encodes a glyphosate acetyl transferase enzyme. Glyphosate-tolerant plants can also be obtained by selecting plants that contain naturally occurring mutations of the aforementioned genes. Plants have been described that express other genes that give them glyphosate tolerance, for example, decarboxylase genes.
[183] Other herbicide-resistant plants include, for example, plants that are made tolerant to herbicides that inhibit the enzyme glutamine synthase, such as bialafos, phosphinothricin or glufosinate. Such plants can be obtained by expressing a detoxifying enzyme from the herbicide or a mutant glutamine synthase enzyme that is resistant to inhibition. Such an effective detoxifying enzyme is, for example, an enzyme encoding a phosphinothricin acetyl transferase (for example, the bar or pat protein from the species Streptomyces). Plants that express an exogenous phosphinothricin acetyl transferase have already been described.
[184] In addition, other herbicide-tolerant plants are also plants that are made tolerant to herbicides that inhibit the enzyme hydroxyphenylpyruvate-dioxigenase (HPPD). Hydroxyphenylpyruvate-dioxigenases are enzymes that catalyze the reaction by which parahydroxyphenylpyruvate (HPP) is transformed into homogentisate. Plants tolerant to HPPD inhibitors
65/114 can be transformed with a gene encoding a naturally occurring resistant HPPD enzyme or a gene encoding a mutated or chimeric HPPD enzyme, as described in WO 96/38567, WO 99/24585, WO 99/24586, WO 2009/144079, WO 2002/046387 or US 6 768 044. Tolerance to HPPD inhibitors can also be obtained by transforming plants with genes that encode certain enzymes that allow the formation of homogentisate despite inhibition of the native HPPD enzyme by the HPPD inhibitor. Such plants are described in WO 99/34008 and WO 02/36787. The tolerance of plants to HPPD inhibitors can also be improved by transforming plants with a gene encoding a prefenate dehydrogenase enzyme in addition to a gene encoding an HPPD tolerant enzyme, as described in WO 2004/024928. In addition, plants can be made tolerant of HPPD inhibitors by inserting into their genome a gene encoding an enzyme that metabolizes or degrades HPPD inhibitors, for example, CYP450 enzymes (see WO 2007/103567 and WO 2008 / 150473).
[185] Other herbicide-resistant plants are plants that are made tolerant to acetolactate synthase (ALS) inhibitors. Known ALS inhibitors include, for example, the herbicides sulfonylurea, imidazolinone, triazolopyrimidines, pyrimidinyloxy (thio) -benzoates and / or sulfonylaminocarbonyltriazolinone. Different mutations in the ALS enzyme (also known as acetohydroxy acid synthase, AHAS) are known to confer tolerance to different herbicides and groups of herbicides, as described, for example, by Tranel and Wright (Weed Science 2002, 50, 700- 712). The production of plants tolerant to sulfonyl urea and plants tolerant to imidazolinone has been described. Other plants tolerant to sulfonylurea and imidazolinone are also described.
[186] Other imidazolinone and / or sulfonyl urea tolerant plants can be obtained by induced mutagenesis, selection in cell cultures in
66/114 presence of the herbicide or creation of the mutation (according to, for example, soy document US 5 084 082, for rice document WO 97/41218, for sugar beet documents US 5 773 702 and WO 99/057965, for lettuce document US 5 198 599 or for sunflower document WO 01/065922).
[187] The plants or varieties of plants (obtained by biotechnological methods of plants, such as genetic engineering) that can also be treated according to the invention are transgenic plants resistant to insects, that is, plants made resistant to attack by certain insects target. Such plants can be obtained by genetic transformation or by selecting plants that contain a mutation that gives plants such resistance to insects.
[188] In the present context, the term insect resistant transgenic plant includes any plant that contains at least one transgene that comprises a coding sequence that encodes:
1) an insecticidal crystal protein from Bacillus thuringiensis or an insecticidal portion thereof, such as the insecticidal crystal proteins compiled by Crickmore et al. (Microbiology and Molecular Biology Reviews 1998, 62, 807-813), updated by Crickmore et al. (2005) in the nomenclature of Bacillus thuringiensis toxin, described online at:
http://www.lifesci.sussex.ac.uk/Home/Neil_Crickmore/Bt/, or their insecticidal portions, for example, proteins of the Cry, Cry1Ab, Cry1Ac, Cry1B, Cry1C, Cry1D, Cry1F, Cry2Ab, Cry3Aa or Cry3Bb, or their insecticidal moieties (eg, EP-A 1999141 and WO 2007/107302), or those proteins encoded by synthetic genes, as described in US patent application 12/249 016 or [189] 2) a crystal protein from Bacillus thuringiensis or a portion thereof that is insecticidal in the presence of a second different crystal protein from Bacillus thuringiensis or a portion thereof, such as the binary toxin consisting of the crystal proteins Cy34 and Cy35 (Nat. Biotechnol.
67/114
2001, 19, 668-72; Applied Environm. Microbiol. 2006, 71, 1765-1774) or the binary toxin consisting of proteins Cry1A or Cry1F and proteins Cry2Aa or Cry2Ab or Cry2Ae (US patent application 12 / 214,022 and document EP08010791.5) or [190] 3) a hybrid insecticidal protein comprising parts of two different crystal insecticidal proteins from Bacillus thuringiensis, such as a hybrid of the proteins in the previous paragraph 1) or a hybrid of the proteins in the previous paragraph 2), for example, the Cry1A.105 protein produced by event in MON98034 corn (WO 2007/027777) or [191] 4) a protein of any of the preceding paragraphs 1) to 3), in which some, in particular, 1 to 10, amino acids have been replaced by other amino acids to obtain a superior insecticidal activity for a target insect species and / or to expand the range of affected target insect species and / or due to changes induced in the coding DNA during cloning and transformation, also l such as the Cry3Bb1 protein in the events in MON863 or MON88017 corn or the Cry3A protein in the event in MIR 604 corn or [192] 5) an insecticidal secreted protein from Bacillus thuringiensis or Bacillus cereus, or an insecticidal portion thereof, such as proteins vegetative insecticides (VIP) listed at: http://www.lifesci.sussex.ac.uk/Home/Neil_Crickmore/Bt/vip.html, for example, proteins of the VIP3Aa protein class or [193] 6) a secreted protein from Bacillus thuringiensis or Bacillus cereus which is an insecticide in the presence of a second secreted protein from Bacillus thuringiensis or B. cereus, such as the binary toxin made up of the VIP1A and VIP2A proteins (WO 94/21795) or [194] 7) a hybrid insecticidal protein comprising parts of different secreted proteins from Bacillus thuringiensis or Bacillus cereus, such as a hybrid of the proteins in paragraph 1) above or a hybrid of the proteins in a line 2) previous or
68/114 [195] 8) a protein of any of the preceding paragraphs 5) to 7), in which some, in particular, 1 to 10, amino acids have been replaced by other amino acids to obtain superior insecticidal activity for a species of target insect and / or to expand the reach of the affected target insect species and / or due to changes induced in the coding DNA during cloning or transformation (although they still encode an insecticidal protein), such as the VIP3Aa protein in the COT cotton event 102 or [196] 9) a secreted protein from Bacillus thuringiensis or Bacillus cereus that is insecticidal in the presence of a crystal protein from Bacillus thuringiensis, such as the binary toxin made up of the VIP3 and Cry1A or Cry1F proteins (invention patent applications) North American 61/126083 and 61/195019) or the binary toxin constituted by the VIP3 protein and only Cry2Aa or Cry2Ab or Cry2Ae proteins (patent application) North American Standard 12/214 022 and EP 08010791.5) or [197] 10) a protein according to paragraph 9) above, in which some, in particular 1 to 10, amino acids have been replaced by other amino acids to obtain superior insecticidal activity for a target insect species and / or to expand the reach of the affected target insect species and / or due to changes induced in the coding DNA during cloning or transformation (although they still encode an insecticidal protein.
[198] As is evident, a transgenic insect-resistant plant, as used herein, also includes any plant that comprises a combination of genes that encode the proteins of any of the previous classes 1 to 10. According to one variant, an insect-resistant plant contains more than one transgene that encodes a protein from any of the previous classes 1 to 10, to expand the range of affected target insect species or to delay the development of insect resistance to plants, using different insecticidal proteins for the same species of target insects, although presenting a way of
69/114 different action, such as binding to different binding sites to the receptor on the insect.
[199] Plants and plant varieties (obtained by biotechnological plant methods, such as genetic engineering) that can also be treated according to the invention are tolerant to abiotic stressors. Such plants can be obtained by genetic transformation or by selecting plants that contain a mutation that gives them such resistance to stress. Particularly useful stress-tolerant plants include:
plants containing a transgene capable of reducing the expression and / or activity of the poly (ADP-ribose) polymerase (PARP) gene in plant cells or plants;
plants that contain a transgene that enhances tolerance to stress capable of reducing the expression and / or activity of the genes encoding PARG of plants or plant cells;
plants that contain a transgene that enhances stress tolerance to a functional plant enzyme from the nicotinamide rescue pathway adenine dinucleotides, including nicotinamidase, nicotinate phosphoribosyltransferase, nicotinic acid, adenyltransferase, nicotinamide, adenyltransferase, nicotinamide and dinotinamide .
[200] Plants and plant varieties (obtained by biotechnological plant methods, such as genetic engineering) that can also be treated according to the invention have an altered quantity, quality and / or storage stability of the harvested product and / or altered properties of specific ingredients of the harvested product, such as, for example:
transgenic plants that synthesize a modified starch, which in its physical-chemical characteristics, in particular in the amylose content or in the amylose / amylopectin ratio, in the degree of branching, in the length of
70/114 medium chain, side chain distribution, viscosity behavior, gelling force, starch grain size and / or starch grain morphology, is altered compared to starch synthesized in plant cells or in wild type plants, so that this modified starch is better suited for special applications;
transgenic plants that synthesize polymers of carbohydrates other than starch or that synthesize polymers of carbohydrates other than starch with altered properties compared to wild type plants without genetic modification. Examples include plants that produce polyfructose, in particular the inulin and lead type, plants that produce alpha-1,4-glucans, plants that produce alpha-1,4
1,4-branched alpha-1,6 glucans and alternating producing plants;
transgenic plants that produce hyaluronan;
transgenic plants or hybrid plants, such as onions, with particular properties, such as “content of very soluble solids”, “reduced pungency” (LP) and / or “prolonged storage” (LS).
[201] The plants and plant varieties (obtained by biotechnological plant methods, such as genetic engineering) that can 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 selecting plants that contain a mutation that gives them such fiber characteristics, and comprise:
a) plants, such as cotton plants, that contain an altered form of cellulose synthase genes;
b) plants, such as cotton plants, that contain an altered form of homologous nucleic acids rsw2 or rsw3, such as cotton plants with an increased expression of sucrose phosphate synthase;
c) plants, such as cotton plants, with increased expression
71/114 sucrose synthase;
d) plants, such as cotton plants, in which the moment of plasmodesmatal activation at the base of the fiber cell is altered, e.g., by fiber-selective β-1,3-glucanase deregulation;
e) plants, such as cotton plants, that have fibers with altered reactivity, e.g., through the expression of the Nacetylglucosamine transferase gene, including the nodC and chitin synthase genes.
[202] The plants and plant varieties (obtained by biotechnological plant methods, such as genetic engineering) that can also be treated according to the invention are plants, such as rapeseed plants or plants associated with Brassica, with altered characteristics of the oil profile. Such plants can be obtained by genetic transformation or by selecting plants that contain a mutation that gives them such altered oil characteristics, and comprise:
a) plants, such as rapeseed plants, which produce oil with a high oleic acid content;
b) plants, such as rapeseed plants, which produce oil with a reduced content of linolenic acid;
c) plants, such as rapeseed plants, which produce oil with a low level of saturated fatty acids.
[203] The plants and plant varieties (obtained by plant biotechnological methods, such as genetic engineering) that can also be treated according to the invention are plants, such as potatoes, that are resistant to viruses, for example, viruses Potato Y (events SY230 and SY233 from Tecnoplant, Argentina) or that are resistant to diseases such as potato late blight (eg, RB gene) or that exhibit reduced cold-induced sweetness (which support the Nt-Inh genes, II-INV) or that exhibit the dwarf phenotype (oxidase gene A-20).
[204] Plants and plant varieties (obtained by methods
72/114 plant biotechnologies, such as genetic engineering) that can also be treated according to the invention are plants, such as rapeseed or plants associated with Brassica, with altered seed fracture characteristics. Such plants can be obtained by genetic transformation or by selecting plants that contain a mutation that gives plants such altered characteristics and comprises plants, such as rapeseed, with delayed or reduced seed fracture.
[205] As particularly useful transgenic plants that can be treated according to the invention are plants with transformation events or combinations of transformation events that are the subject of petitions granted or pending for unregulated status in the USA in the ' Animal and Plant Health Inspection Service '(APHIS) of the' United States Department of Agriculture '(USDA). Information regarding these is available at any time from APHIS (4700 River Road Riverdale, MD 20737, USA), for example, through the website http://www.aphis.usda.gov/brs/not_reg.html . On the date of delivery of the present invention patent application, the petitions with the following information were assigned or are pending in APHIS:
[206] - Petition: identification number of the petition. The technical description of the transformation event can be found in the specific petition document made available by APHIS on the website, through the petition number. These descriptions are hereby incorporated by reference.
- Extension of a petition: reference to a previous petition for which an extension of the scope or term is required.
- Institution: name of the person submitting the petition.
- Regulated article: the species of the plant in question.
- Transgenic phenotype: the trait given to the plant by the transformation event.
- Event or transformation line: the name of the event (s) (sometimes also referred to as line (s)) for which the status of non
Regulated 73/114 is required.
- APHIS documents: several documents that have been published by APHIS with respect to the petition or that can be obtained from APHIS upon request.
[207] Particularly useful transgenic plants that can be treated according to the invention include plants that comprise one or more genes encoding one or more toxins and transgenic plants that are marketed under the following trade names: YIELD GARD® (for corn, cotton, soybeans), KnockOut® (e.g. corn), BiteGard® (e.g. corn), BT-Xtra® (e.g. corn), StarLink® (e.g. corn), Bollgard® ( cotton), Nucotn® (cotton), Nucotn 33B® (cotton), NatureGard® (eg corn), Protecta® and NewLeaf® (potatoes). Examples of herbicide-tolerant plants that can be mentioned include maize varieties, cotton varieties and soybean varieties which are commercially available under the following trade names: Roundup Ready® (glyphosate tolerance, eg maize, cotton , soy), Liberty Link® (tolerance to phosphinothricin, for example, rapeseed), IMI® (tolerance to imidazolinone) and SCS® (tolerance to sulfonyl-urea), for example, corn. As herbicide-resistant plants (plants developed in a conventional way for herbicide tolerance) that can be mentioned are varieties marketed under the trade name Clearfield® (for example, maize).
[208] As particularly useful transgenic plants that can be treated according to the invention are plants that contain transformation events, or a combination of transformation events, and that are listed, for example, in databases of different national or regional regulatory agencies (see, for example, http://gmoinfo.jrc.it/gmp_browse.aspx and http://ceragmc.org/index.php evidcode=&hstIDXCode=&gType=&AbbrCode=&atCode=& stCode = & coIDCode = & action = gm_crop_database & mode = Submit).
74/114 [209] Active ingredients or compositions can also be used to protect materials, for example, to protect industrial materials from attack and destruction by unwanted microorganisms, for example, fungi and insects.
[210] In addition, the compounds of the invention can be used as antifouling compositions, either alone or in combination with other active ingredients.
[211] In the present context, the term "industrial materials" is intended to mean inanimate materials that have been prepared for industrial use. For example, as industrial materials that are intended to be protected with the active ingredients according to the invention against microbial modification or destruction, it is possible to refer to adhesives, glues, paper and cardboard, textiles, leather, wood, paints and plastics, soft materials and others materials that can be infected or destroyed by microorganisms. Among the materials to be protected, it is also possible to mention parts of factory facilities and buildings, for example, water cooling circuits, cooling and heating systems and ventilation and air conditioning systems, which can be damaged by proliferation. of microorganisms. Within the scope of the present invention, preferable industrial materials include adhesives, glues, paper and cardboard, leather, wood, paints, cooling materials and clear transfer fluids and, more preferably, wood. The active ingredients or compositions according to the invention can prevent adverse effects, such as rot, degradation, discoloration or mold formation. In addition, the compounds of the invention can be used to protect objects that come into contact with salt water and brackish water, in particular hulls, screens, nets, buildings, moorings and signaling systems, against fouling.
[212] The method according to the invention for controlling unwanted fungi can also be used to protect stored goods. Stored goods are intended to be designated natural substances of origin
75/114 animal or vegetable or its processed products that are of natural origin, and for which long-term protection is desired. Stored goods of plant origin, for example, plants or parts of plants, such as stems, leaves, tubers, seeds, fruits, grains, can be protected moments after harvest or after processing by (pre) drying, humidification, fragmentation, grinding, compression or roasting. Stored goods also comprise wood, whether unprocessed, such as construction timber, electricity poles and barriers, or in the form of finished products, such as furniture. Stored goods of animal origin include, for example, hides, skins and hair. The active ingredients of the invention can prevent adverse effects, such as rot, degradation, discoloration or mold formation.
[213] As non-limiting examples of pathogens of fungal diseases that can be treated according to the invention are:
diseases caused by pathogens of powdery mildew, for example, Blumeria species, for example, Blumeria graminis; of the species Podosphaera, for example, Podosphaera leucotricha; Sphaerotheca species, for example, Sphaerotheca fuliginea; the species Uncinula, for example, Uncinula necator, diseases caused by pathogens of rust disease, for example, the species of Gymnosporangium, for example, Gymnosporangium sabinae; of the Hemileia species, for example, Hemileia vastatrix; Phakopsora species, for example, Phakopsora pachyrhizi or Phakopsora meibomiae; of the Puccinia species, for example, Puccinia recondita or Puccinia triticina; Uromyces species, for example, Uromyces appendiculatus;
diseases caused by pathogens in the Oomycetes group, for example, 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; of the species Pseudoperonospora, for example, Pseudoperonospora humuli or Pseudoperonospora cubensis; gives
76/114 Pythium species, for example, Pythium ultimum;
leaf spot diseases and leaf wilt diseases caused, for example, by the Alternaria species, for example, Alternaria solani; Cercospora species, for example, Cercospora beticola; Cladosporium species, for example, Cladosporium cucumerinum; Cochliobolus species, for example, Cochliobolus sativus (conideal form: Drechslera, syn: Helminthosporium); Colletotrichum species, for example, Colletotrichum lindemuthanium; Cycloconium species, for example, Cycloconium oleaginum; Diaporthe species, for example, Diaporthe citri; Elsinoe species, for example, Elsinoe fawcettii; Gloeosporium species, for example, Gloeosporium laeticolor; Glomerella species, for example, Glomerella cingulata; Guignardia species, for example, Guignardia bidwelli; Leptosphaeria species, for example, Leptosphaeria maculans; Magnaporthe species, for example, Magnaporthe grisea; Microdochium species, for example, Microdochium nivale; Mycosphaerella species, for example, Mycosphaerella graminicola and M. fijiensis; Phaeosphaeria species, for example, Phaeosphaeria nodorum; Pyrenophora species, for example, Pyrenophora teres; Ramularia species, for example, Ramularia collo-cygni; Rhynchosporium species, for example, Rhynchosporium secalis; Septoria species, for example, Septoria apii; Typhula species, for example, Typhula incarnata; Venturia species, for example, Venturia inaequalis;
root and stem diseases caused, for example, by the species Corticium, for example, Corticium graminearum; Fusarium species, for example, Fusarium oxysporum; Gaeumannomyces species, for example, Gaeumannomyces graminis; Rhizoctonia species, for example, Rhizoctonia solani; Tapesia species, for example, Tapesia acuformis; Thielaviopsis species, for example, Thielaviopsis basicola;
ear and panicle diseases (including ears of corn) caused, for example, by the species Alternaria, for example, Alternaria spp .; Aspergillus species, for example, Aspergillus flavus; Cladosporium species,
77/114 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; Septoria species, for example, Septoria nodorum;
diseases caused by caries fungi, for example, Sphacelotheca species, for example, Sphacelotheca reiliana; Tilletia species, for example, Tilletia caries, T. controversa; Urocystis species, for example, Urocystis occulta; Ustilago species, for example, Ustilago nuda, U. nuda tritici;
fruit rot caused, for example, by Aspergillus species, for example, Aspergillus flavus; Botrytis species, for example, Botrytis cinerea; Penicillium species, for example, Penicillium expansum and P. purpurogenum; Sclerotinia species, for example, Sclerotinia sclerotiorum; Verticilium species, for example, Verticilium alboatrum;
rot and wilt diseases from seeds and soil, and also cuttings diseases, caused, for example, by the Alternaria species, for example, Fusarium species, for example, Fusarium culmorum; Phytophthora species, for example, Phytophthora cactorum; Pythium species, for example, Pythium ultimum; Rhizoctonia species, for example, Rhizoctonia solani; Sclerotium species, for example, Sclerotium rolfsii;
cancers, tumors and witches' broom disease caused, for example, by the species Nectria, for example, Nectria galligena;
wilting diseases caused, for example, by the species Monilinia, for example, Monilinia laxa;
deformations of leaves, flowers and fruits caused, for example, by the species Taphrina, for example, Taphrina deformans;
degenerative diseases of plants for wood caused, for example, by the species Esca, for example, Phaeomoniella chlamydospora and Phaeoacremonium aleophilum and Fomitiporia mediterranea;
flower and seed diseases caused, for example, by
78/114 Botrytis species, for example, Botrytis cinerea;
plant tuber diseases caused, for example, by the species Rhizoctonia, for example, Rhizoctonia solani; Helminthosporium species, for example, Helminthosporium solani;
diseases caused by bacterial pathogens, for example, of the species Xanthomonas, for example, Xanthomonas campestris pv. oryzae; Pseudomonas species, for example, Pseudomonas syringae pv. lachrymans; Erwinia species, for example, Erwinia amylovora.
[214] Preferably, it is possible to control the following diseases of soy: fungal diseases on leaves, stems, pods and seeds caused, for example, leaf spots by Alternaria (Alternaria spec. Atrans tenuissima), anthracnose (Colletotrichum gloeosporoides dematium var. truncatum), brown spots (Septoria glycines), spots and leaf degradation by cercospora (Cercospora kikuchii), leaf degradation by choanephora (Choanephora infundibulifera trispora (Syn.)), leaf spots by dactuliophora (Dactuliophora glycines), myld manshurica), degradation by drechslera (Drechslera glycini), frog's eye leaf spots (Cercospora sojina), leptosphaerulina (Leptosphaerulina trifolii) leaf spots, phyllostica (Phyllosticta soyecola) leaf spots, pod wilt and stem ), downy mildew (Microsphaera diffusa), leaf spotting by pyrenochaeta (Pyrenochaeta glycines), wilting of the aerial parts, leaf gem and structure by rhizoctonia (Rhizoctonia solani), rust (Phakopsora pachyrhizi, Phakopsora meibomiae), mange (Sphaceloma glycines), wilting of leaves by stemphylium (Stemphylium botryosum), target spots (Corynespora cassiicola).
[215] Fungal diseases at the base of the roots and stem caused, for example, by black root rot (Calonectria crotalariae), coal rot (Macrophomina phaseolina), pod and collar rot, root rot and fusarium degradation and wilting ( Fusarium oxysporum, Fusarium
79/114 orthoceras, Fusarium semitectum, Fusarium equiseti), root rot by mycoleptodiscus (Mycoleptodiscus terrestris), neocosmospora (Neocosmospora vasinfecta), stem and pod wilt (Diaporthe phaseolorum), stem cancer (Diaporthe phaseolorum var. Caul) caul. phytophthora rot (Phytophthora megasperma), brown stem rot (Phialophora gregata), pythium rot (Pythium aphanidermatum, Pythium irregulare, Pythium debaryanum, Pythium myriotylum, Pythium ultimum), dehumidification and degradation solani), stem degradation by sclerotinia (Sclerotinia sclerotiorum), southern wilting by sclerotinia (Sclerotinia rolfsii), root rot by thielaviopsis (Thielaviopsis basicola).
[216] Microorganisms capable of degrading or altering industrial materials include, for example, bacteria, fungi, yeasts, algae and mucilaginous organisms. Preferably, the active ingredients of the invention act against fungi, in particular molds, wood decolorizing fungi and wood destroying fungi (Basidiomycetes), as well as against mucilages and algae. As examples it is possible to mention the microorganisms 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 Lentinus tigrinus; 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; Escherichia, such as Escherichia coli; Pseudomonas, such as Pseudomonas aeruginosa; Staphylococcus, such as Staphylococcus aureus.
[217] In addition, the active ingredients of the invention also have very good antimycotic activity. They have a very broad spectrum of antimycotic activity, in particular against dermatophytes and yeasts, molds and diphasic fungi (for example, against the Candida species, such as Candida
80/114 albicans, Candida glabrata), and Epidermophyton floccosum, Aspergillus species, such as Aspergillus niger and Aspergillus fumigatus, Trichophyton species, such as Trichophyton mentagrophytes, Microsporon species, such as Microsporon canis and audouinii. The list of these fungi is not, in any way, a restriction of the mycotic spectrum covered, and has only an illustrative character.
[218] Therefore, the active ingredients can be used in medical and non-medical applications.
[219] When the active ingredients of the invention are used as fungicides, application rates can vary over a relatively wide range, depending on the type of application. The application rate of the active ingredients of the invention is included • in the case of the treatment of parts of plants, for example, leaves: between 0.1 and 10,000 g / ha, preferably between 10 and 1000 g / ha and, more preferably, between 50 and 300 g / ha (in the case of rinsing or dripping, it is even possible to reduce the application rate, in particular when using inert substrates, such as rock wool or perlite);
• in the case of seed treatment: between 2 and 200 g per 100 kg of seed, preferably between 3 and 150 g per 100 kg of seed, more preferably between 2.5 and 25 g per 100 kg of seed and, even more preferably, between 2.5 and 12.5 g per 100 kg of seed;
• in the case of soil treatment: between 0.1 and 10 000 g / ha and, preferably, between 1 and 5000 g / ha.
[220] These application rates are merely exemplary and are not limiting for the purpose of the invention.
[221] The active ingredients or compositions of the invention can thus be used to protect plants against attack by the mentioned pathogens for a certain period of time after treatment. Generally speaking, the period for which protection is conferred is
81/114 between 1 and 28 days, preferably between 1 and 14 days, more preferably between 1 and 10 days and, even more preferably, between 1 and 7 days, after treating the plants with the active ingredients, or up to 200 days after seed treatment.
[222] In addition, the treatment according to the invention can reduce the mycotoxin content in the harvested material and in the food and feed prepared from it. In particular, mycotoxins include, but are not limited to, the following: deoxynivalenol (DON), nivalenol, 15-Ac-DON, 3Ac-DON, T2- and HT2-toxin, fumonisins, zearalenone, moniliformine, fusarin, diaceotoxiscirpenol (DAS) , beauvericin, enniatin, fusaroproliferin, fusarenol, ochratoxins, patulin, ergot alkaloids and aflatoxins that can be produced, for example, by the following fungi: Fusarium species, such as Fusarium acuminatum, F. avenaceum, F. crookwellense, F. culmorum, F graminearum (Gibberella zeae), F. equiseti, F. fujikoroi, F. musarum, F. oxysporum, F. proliferatum, F. poae, F. pseudograminearum, F. sambucinum, F. scirpi, F. semitectum, F. solani , F. sporotrichoides, F. langsethiae, F. subglutinans, F. tricinctum, F. verticillioides, inter alia, and also by the Aspergillus species, Penicillium species, Claviceps purpurea, Stachybotrys species, inter alia.
[223] In some cases, the compounds of the invention may, for particular concentrations or rates of application, also be used as herbicides, phytoprotective agents, growth regulators or as compositions to improve the properties of plants, or as microbicides, for example, as fungicides, antimycotics, bactericides, viricides (including compositions against viroids) or as compositions against MLO (mycoplasma-like organisms) and RLO (rickettsia-like organisms). If appropriate, they can also be used as intermediates or precursors for the synthesis of other active ingredients.
[224] The active ingredients of the invention intervene in the metabolism of plants and, for this reason, can also be used as growth regulators.
82/114 [225] Plant growth regulators can have several effects on plants. The effects of substances depend essentially on the time of application in relation to the stage of development of the plant and the amounts of active ingredient applied to the plants and their environment and the type of application. In each case, the growth regulators should have a particular desired effect on the crop plants.
[226] Plant growth regulating compounds can be used, for example, to inhibit plant growth. Such inhibition of growth is interesting from an economic point of view, for example, in the case of grass, as it makes it possible to reduce the frequency of mowing in ornamental gardens, parks and sports facilities, on roadsides, in airports and in orchards. It is also important to inhibit the growth of herbaceous and wood plants on the edges of roads and in the vicinity of ducts or catenaries or, quite generally, in areas where vigorous plant growth is undesirable.
[227] It is also important to use growth regulators to inhibit longitudinal growth of cereals. This reduces or completely eliminates the risk of lodging the plants before harvest. In addition, in the case of cereals, growth regulators can strengthen the stem, which also prevents lodging. The use of growth regulators to reduce and strengthen stalks allows the development of higher volumes of fertilizers to increase yield, without presenting the risk of lodging the cereal crop.
[228] In many crop plants, inhibition of vegetative growth allows for denser planting, thus making it possible to obtain higher yields based on the surface of the soil. Another advantage of the smaller plants obtained in this way is that the crop is easier to grow and to harvest.
[229] Inhibiting plant growth can also provide increased yields, as nutrients and assimilates
83/114 are more beneficial for the formation of flowers and fruits than for the vegetative parts of plants.
[230] Often, growth regulators can also be used to promote vegetative growth. This is quite beneficial when harvesting vegetative parts of plants. However, the promotion of vegetative growth can also promote generative growth since they are more assimilated, providing more fruits or bigger fruits.
[231] In some cases, increases in yield can be achieved by manipulating the plant's metabolism without any detectable changes in vegetative growth. In addition, growth regulators can be used to change the composition of plants, which, in turn, can provide an improvement in the amount of products harvested. For example, it is possible to increase the sugar content in sugar beet, sugar cane, pineapples and citrus fruits, or to increase the protein content in soy or cereals. It is also possible, for example, to use growth regulators to inhibit the degradation of desirable ingredients, for example sugar in sugar beet or sugar cane, before or after harvest. It is also possible to positively influence the production or elimination of secondary plant ingredients. An example is the stimulation of latex flow in rubber trees.
[232] Under the influence of growth regulators, parthenocarpic fruits can be formed. In addition, it is possible to influence the sex of the flowers. It is also possible to produce sterile pollen, which is very important for the creation and production of hybrid seeds.
[233] The use of growth regulators can control the branching of plants. On the one hand, breaking the apical dominance, it is possible to promote the development of lateral shoots, which can be quite desirable, in particular, in the cultivation of ornamental plants, also in combination with a growth inhibition. On the other hand, however,
84/114 it is also possible to inhibit the growth of lateral shoots. This effect is particularly interesting, for example, in growing tobacco or growing tomatoes.
[234] Under the influence of growth regulators, it is possible to control the amount of leaves on the plants so that the defoliation of the plants is achieved in a desired period. Such defoliation plays a major role in the mechanical harvesting of cotton, but it is also interesting in other crops, for example, in viticulture. Defoliation of plants can be performed to decrease plant transpiration before transplanting.
[235] Likewise, growth regulators can be used to regulate fruit dehiscence. On the one hand, it is possible to prevent premature dehiscence of the fruits. On the other hand, it is also possible to promote the dehiscence of the fruits to reach a desired mass ("thinning"), to eliminate the alternation. The term “alternation” is intended to designate the characteristic of some species of fruit, for endogenous reasons, to present very different yields from year to year. Finally, it is possible to use growth regulators during the harvest period to reduce the forces required to pick the fruits, in order to allow mechanical harvesting or to facilitate manual harvesting.
[236] Growth regulators can also be used to achieve faster or delayed maturation of the harvested material, before or after harvest. This is particularly advantageous in that it allows an optimal adjustment to market requirements. In addition, in some cases, growth regulators can improve fruit color. In addition, growth regulators can also be used to concentrate maturation over a period of time. This establishes the prerequisites for a complete mechanical or manual harvest in a single operation, for example, in the case of tobacco, tomatoes or coffee.
[237] Through the use of growth regulators, it is still
85/114 possible to influence the resting of seeds or buds of plants, in such a way that plants, such as pineapples or ornamental plants in wards, for example, germinate, burst or give flowers in a period for which they are not inclined to do. it. In areas where there is a risk of frost, it may be desirable to delay the formation of buds or the germination of seeds with the aid of growth regulators, in order to avoid damage caused by frost.
[238] Finally, growth regulators can induce plant resistance to frost, drought or high soil salinity. This allows for the cultivation of plants in regions that are normally unsuitable for this purpose.
[239] The listed plants can be treated according to the invention in a particularly advantageous manner with the compounds of formula (I) and / or the compounds of the invention. The preferred ranges shown above for the active ingredients or compositions can also be applied for the treatment of these plants. It is particularly important to treat plants with the compounds or compositions referred to specifically in this text.
[240] The invention is illustrated by the following examples. However, the invention is not limited to the examples.
Examples [241] General note: unless otherwise stated, all chromatographic purification and separation steps are performed on silica gel and with a solvent gradient from 0: 100 ethyl acetate / cyclohexane to ethyl acetate / 100: 0 cyclohexane,
Preparation of compound I-1
Step 1
4- {4- [5- (2-Hydroxy-4,5-dimethylphenyl) -5-methyl-4,5-dihydro-1,2-oxazol-3-yl] -1,3thiazol-2-yl tert-butyl} -piperidine-1-carboxylate [242] A solution of 4- {4 - [(hydroxyimino) -methyl] -1,3-thiazol-2yl} -piperidine-1-carboxylate was mixed tert-butyl (400 mg) in ethyl acetate (6 ml)
86/114 with N-chlorosuccinimide (206 mg), 4,5-dimethyl-2- (prop-1-ene-2-yl) -phenol (1320 mg, purity: 50%), potassium hydrogen carbonate (643 mg) and subsequently a drop of water. The reaction mixture was stirred at reflux for 40 minutes. The reaction mixture was mixed, at room temperature, with ethyl acetate and water and extracted with ethyl acetate. The organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography. 4- {4- [5- (2hydroxy-4,5-dimethylphenyl) -5-methyl-4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazole was obtained Tert-butyl 2-yl} piperidine-1-carboxylate (293 mg).
¹ H NMR (DMSO-d6): 9.34 (s, 1H), 7.94 (s, 1H), 7.12 (s, 1H), 6.63 (s, 1H), 4.05-
3.95 (m, 2H), 3.52 (d, 1H), 3.48 (d, 1H), 3.25-3.15 (m, 1H), 2.88 (s lr, 2H), 2.09 (s, 6H), 2.05-1.96 (m, 2H), 1.66 (s, 3H), 1.58-1.46 (m, 2H), 1.40 (s, 9H).
Step 2
4- (4- {5- [4,5-Dimethyl-2- (prop-2-yn-1-yloxy) -phenyl] -5-methyl-4,5-dihydro-1,2oxazol-3- il} -1,3-thiazol-2-yl) -piperidine-1-carboxylate of tert-butyl (II-1) [243] At room temperature, a solution of 4- {4- [5- ( 2hydroxy-4,5-dimethylphenyl) -5-methyl-4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} piperidine-1-carboxylate butyl (150 mg) and potassium carbonate (132 mg) in acetone (3 ml) with 3-bromoprop-1-yne (42 mg, 80% in toluene). The reaction mixture was stirred at 60 ° C for 6 hours. Then, the mixture was mixed with water and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. Purified by column chromatography to obtain 4- (4- {5- [4,5-dimethyl-2- (prop-2-yn-1-yloxy) -phenyl] -5-methyl-4,5-dihydro- 1,2-oxazol-3-yl} -1,3-thiazol-2-yl) -piperidine-1 tert-butyl carboxylate (64 mg).
¹ H NMR (DMSO-de): 7.92 (s, 1H), 7.22 (s, 1H), 6.95 (s, 1H), 4.87 (s, 2H), 4.05-
3.95 (m, 2H), 3.55 (d, 1H), 3.46 (d, 1H), 3.30 (s, 1H), 3.27-3.17 (m, 1H), 2 , 88 (s lr, 2H), 2.19 (s, 3H), 2.15 (s, 3H), 2.04-1.96 (m, 2H), 1.66 (s, 3H), 1 , 58-1.46 (m, 2H), 1.40 (s, 9H).
Step 3
87/114
2- [3,5-Bis- (d if fluoromethyl) -1 H-pyrazol-1-yl] -1 - [4- (4- {5- [4,5-dimethyl-2- (prop-2ino -1-yloxy) -phenyl] -5-methyl-4,5-dihydro-1,2-oxazol-3-yl} -1,3-thiazol-2-yl) piperidine-1-yl] -ethanone (I-1) [244] At room temperature, mix, dropwise, 4- (4- {5- [4,5-dimethyl-2 (prop-2-yne-1-yloxy) -phenyl] -5 tert-butyl-methyl-4,5-dihydro-1,2-oxazol-3-yl} -1,3-thiazol-2-yl) piperidine-1-carboxylate (64 mg) with a 4 molar solution of hydrogen chloride (1.9 mL) in 1,4-dioxane. The solvent and excess hydrogen chloride were removed. 4- (4- {5- [4,5-dimethyl-2 (prop-2-yn-1-yloxy) -phenyl] -5-methyl-4,5-dihydro-1 chloride was obtained, 2-oxazol-3-yl} -1,3-thiazol-2-yl) piperidinium.
[245] At 0 ° C, a solution of [3,5-bis- (difluoromethyl) -1Hpyrazol-1-yl] -acetic acid (30 mg) in dichloromethane (20 ml) was mixed with oxalyl chloride (48 mg) and a drop of N, N-dimethylformamide. The reaction mixture was stirred at room temperature for 10 minutes. The solvent and excess reagent were removed under reduced pressure. The residue was redissolved in dichloromethane and added, dropwise and at room temperature, to a solution of 4- (4- {5- [4,5-dimethyl-2- (prop-2-yn) chloride -1-yloxy) -phenyl] -5-methyl-4,5dihydro-1,2-oxazol-3-yl} -1,3-thiazol-2-yl) -piperidinium and triethylamine (38 mg) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature. Then, it was mixed with a concentrated sodium hydrogen carbonate solution, the aqueous phase was separated and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. Purified by column chromatography to obtain 2- [3,5-bis- (difluoromethyl) -1Hpyrazol-1-yl] -1 - [4- (4- {5- [4,5-dimethyl-2- (prop -2-ino-1-yloxy) -phenyl] -5-methyl-4,5-dihydro-1,2-oxazol-3-yl} -1,3-thiazol-2-yl) -piperidine-1-yl ] -ethanone (53 mg).
¹ H NMR (DMSO-de): p.p. _m · 7.94 (s, 1H), 7.23 (s, 1H), 7.18 (t, 1H), 7.03 (t, 1H),
6.96 (s, 1H), 6.91 (s, 1H), 5.43 (d, 1H), 5.35 (d, 1H), 4.87 (s, 2H), 4.38-4 , 30 (m, 1H), 4.00-3.92 (m, 1H), 3.72-3.63 (m, 1H), 3.60-3.44 (m, 2H), 3.40 -3.20 (m, 2H), 2.86-2.78 (m, 1H), 2.19 (s, 3H), 2.15 (s, 3H), 2.13-2.00 (m , 2H), 1.82-1.70 (m, 1H), 1.67 (s, 3H), 1.60-1.58 (m, 1H).
88/114
Preparation of compound I-2
Step 1
4- {4- [5- (2,6-Difluoro-3-hydroxyphenyl) -4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2yl} -piperidine- Tert-Butyl 1-carboxylate [246] A solution of tert-butyl 4- {4 - [(hydroxyimino) -methyl] -1,3-thiazol-2yl} -piperidine-1-carboxylate ( 1278 g) in ethyl acetate (80 ml) with N-chlorosuccinimide (658 mg). The reaction mixture was stirred at reflux for 30 minutes. At room temperature, the reaction mixture was mixed with 2,4-difluoro-3-vinylphenol (705 mg) and potassium hydrogen carbonate (822 mg) and then with a drop of water. After stirring overnight at room temperature, the reaction mixture was mixed with ethyl acetate and water and extracted with ethyl acetate. The organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography. 4- {4- [5- (2,6-difluoro-3hydroxyphenyl) -4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} tert-butyl piperidine-1-carboxylate (680 mg).
¹ H NMR (DMSO-de): 9.92 (s, 1H), 8.01 (s, 1H), 7.02-6.90 (m, 2H), 5.96 (dd, 1H), 4 , 02 (d, 2H), 3.88 (dd, 1H), 3.51 (dd, 1H), 2.90 (s lr, 1H), 2.10-2.00 (m, 2H), 1 , 65-1.50 (m, 2H), 1.42 (s, 9H).
Step 2 2- [3,5-Bis- (difluoromethyl) -1H-pyrazol-1-yl] -1- (4- {4- [5- (2,6-difluoro-3-hydroxyphenyl) -4,5 -dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} -piperidine-1-yl) -ethanone [247] At 0 ° C, it was mixed dropwise , a solution of 4- {4- [5- (2,6difluoro-3-hydroxyphenyl) -4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl } tert-butyl piperidine-1 carboxylate (374 mg) in dichloromethane with a 4 molar solution of hydrogen chloride (4.0 equivalents) in 1,4-dioxane. The reaction mixture was stirred at 0 ° C and then slowly warmed to room temperature. After stirring for 5 hours, the solvent and excess hydrogen chloride were removed. 4- {4- [5- (2,6-difluoro-3-hydroxyphenyl) - chloride was obtained
4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} -piperidinium.
89/114 [248] At 0 ° C, a solution of [3,5-bis- (difluoromethyl) -1Hpyrazol-1-yl] -acetic acid (160 mg) in dichloromethane (20 ml) was mixed with chloride oxalyl (275 mg) and a drop of N, N-dimethylformamide. The reaction mixture was stirred at room temperature for 2 hours. The solvent and excess reagent were removed under reduced pressure. The solid residue was redissolved in dichloromethane and added dropwise at 0 ° C to a solution of 4- {4- [5- (2,6-difluoro-3-hydroxyphenyl) -4 chloride , 5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} piperidinium and triethylamine (10 equivalents) in dichloromethane (25 mL). The reaction mixture was stirred at room temperature overnight. Do, mixed with a concentrated sodium hydrogen carbonate solution, the aqueous phase was separated and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. Purified by column chromatography to obtain 2- [3,5-bis (difluoromethyl) -1H-pyrazol-1-yl] 1 - (4- {4- [5- (2,6-difluoro-3- hydroxy-phenyl) -4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2yl} -piperidine-1-yl) -ethanone (177 mg).
[249] ¹ H NMR (DMSO-de): 9.91 (s, 1H), 8.03 (s, 1H), 7.18 (t, 1H), 7.03 (t, 1H), 7, 01-6.88 (m, 3H), 5.96 (dd, 1H), 5.38 (q, 2H), 4.35 (d, 1H), 4.02-3.83 (m, 2H) , 3.51 (dd, 1H), 3.45-3.21 (m, 2H), 2.84 (t, 1H), 2.11 (t, 2H), 1.88-1.75 (m , 1H), 1.65-1.51 (m, 1H).
Step 3
2- [3,5-Bis- (difluoromethyl) -1 H-pyrazol-1-yl] -1 - [4- (4- {5- [2,6-difluoro-3- (prop-2ino-1- iloxy) -phenyl] -4,5-dihydro-1,2-oxazol-3-yl} -1,3-thiazol-2-yl) -piperidine-1-yl] ethanone (I-2) [250 ] At room temperature, a solution of 2- [3,5-bis (difluoromethyl) -1 H-pyrazol-1-yl] -1 - (4- {4- [5- (2,6-difluoro -3-hydroxyphenyl) -4,5-dihydro-
1,2-oxazol-3-yl] -1,3-thiazol-2-yl} -piperidine-1-yl) -ethanone (85 mg) and potassium carbonate (31 mg) in N, N-dimethylformamide (10 ml) with potassium iodide (13.5 mg) and 3-bromoprop-1-yne (35 mg (80% in toluene)). The reaction mixture was stirred at 80 ° C for 4 hours. Then, the mixture was mixed with water and extracted with ethyl acetate. The organic phases were dried
90/114 combined over sodium sulfate and concentrated. Purified by column chromatography to obtain 2- [3,5-bis- (difluoromethyl) -1H-pyrazol-1-yl] 1 - [4- (4- {5- [2,6-difluoro-3 - (prop-2-yne-1-yloxy) -phenyl] -4,5-dihydro-1,2-oxazol-3-yl} -
1,3-thiazol-2-yl) -piperidine-1-yl] -ethanone (60 mg).
¹ H NMR (DMSO-de): õpp. _m _: 8.03 (s, 1H), 7.38-7.26 (m, 1H), 7.18 (t, 1H), 7.207.10 (m, 1H), 7.03 (t, 1H ), 6.91 (s, 1H), 5.99 (dd, 1H), 5.40 (q, 2H), 4.89 (d, 2H), 4.35 (d, 1H), 4.03 -3.75 (m, 2H), 3.64 (t, 1H), 3.54 (dd, 1H), 3.47-3.20 (m, 2H), 2.84 (t, 1H), 2.12 (t, 2H), 1.88-1.74 (m, 1H), 1.65-1.50 (m, 1H).
Preparation of compound I-4 1- [4- (4- {5- [3- (Allyloxy) -2,6-difluorophenyl] -4,5-dihydro-1,2-oxazol-3-yl} - 1,3thiazol-2-yl) -piperidine-1-yl] -2- [3,5-bis- (difluoromethyl) -1 H-pyrazol-1-yl] -ethanone (I-4) [251] At temperature environment, a solution of 2- [3,5-bis (difluoromethyl) -1 H-pyrazol-1-yl] -1 - (4- {4- [5- (2,6-difluoro-3- hydroxyphenyl) -4,5-dihydro-
1,2-oxazol-3-yl] -1,3-thiazol-2-yl} -piperidine-1-yl) -ethanone (85 mg) and potassium carbonate (102 mg) in acetone (5 ml) with bromide allyl (72 mg). The reaction mixture was stirred at reflux for 5 hours. Then, the mixture was mixed with water and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. Purify by column chromatography to obtain 1- [4- (4- {5- [3- (allyloxy) -2,6-difluorophenyl] -
4,5-dihydro-1,2-oxazol-3-yl} -1,3-thiazol-2-yl) -piperidine-1-yl] -2- [3,5bis (difluoromethyl) -1H-pyrazole -1-yl] -ethanone (55 mg).
¹ H NMR (DMSO-de): 8.03 (s, 1H), 7.29-7.20 (m, 1H), 7.18 (t, 1H), 7.13-7.03 (m, 1H), 7.03 (t, 1H), 6.91 (s, 1H), 6.08-5.95 (m, 2H), 5.50-5.24 (m, 4H), 4.63 (dt, 2H), 4.35 (d, 1H), 4.05-3.85 (m, 2H), 3.53 (dd, 1H), 3.45-3.20 (m, 2H), 2.84 (t, 1H), 2.12 (t, 2H), 1.87-1.75 (m, 1H), 1.65-1.50 (m, 1H).
Preparation of compound I-5
Step 1
4- {4- [5- (4-Amino-2,6-difluorophenyl) -4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2yl} -piperidine- Tert-butyl 1-carboxylate
91/114 [252] A solution of tert-butyl 4- {4 - [(hydroxyimino) -methyl] -1,3-thiazol-2yl} -piperidine-1-carboxylate (500 mg) was mixed in N, N-dimethylformamide (2 ml) with N-chlorosuccinimide (257 mg). The reaction mixture was stirred at 50 ° C for 1 hour. At room temperature, the reaction mixture was mixed with 3,5-difluoro-4-vinylaniline (324 mg) and triethylamine (0.67 ml). Then and stirring at 50 ° C for 2 hours, the reaction mixture was mixed with ethyl acetate and water and extracted with ethyl acetate. The organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography. 4- {4- [5- (4-amino-2,6-difluorophenyl) -4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} tert-butyl piperidine-1-carboxylate (400 mg).
¹ H NMR (DMSO-d6): 7.95 (s, 1H), 6.21 (d, 2H), 5.89 (s, 2H), 5.79 (dd, 1H), 4.05-3 , 97 (m, 2H), 3.73 (dd, 1H), 3.39 (dd, 1H), 3.30-3.20 (m, 1H), 2.89 (s lr, 2H), 2 , 08-2.00 (m, 2H), 1.62-1.49 (m, 2H), 1.41 (s, 9H).
Step 2
4- [4- (5- {2,6-Difluoro-4 - [(methylsulfonyl) -amino] -phenyl} -4,5-dihydro-1,2-oxazole-
Tert-Butyl (II-2) 3-yl) -1,3-thiazol-2-yl] -piperidine-1-carboxylate [253] A solution of 4- {4- [5- (4- tert-butyl amino-2,6-difluorophenyl) -4,5dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} -piperidine-1-carboxylate (400 mg) in dichloromethane (10 ml) with methanesulfonyl chloride (109 mg) and pyridine (82 mg). The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed again at room temperature with pyridine (82 mg) and methanesulfonyl chloride (109 mg). After stirring at room temperature for 2 hours, the reaction mixture was mixed with a 1 N HCl solution and extracted with dichloromethane. The organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography. 4- [4- (5- {2,6-difluoro-4 - [(methylsulfonyl) -amino] -phenyl} -4,5-dihydro-1,2oxazol-3-yl) -1 was obtained, Tert-Butyl 3-thiazol-2-yl] -piperidine-1-carboxylate (380 mg).
¹ H NMR (DMSO-d6): 7.99 (s, 1H), 6.89 (d, 2H), 5.93 (dd, 1H), 4.05-3.97 (m,
92/114
2H), 3.75 (dd, 1H), 3.49 (dd, 1H), 3.30-3.20 (m, 1H), 3.14 (s, 3H), 2.89 (s Ir, 2H), 2.08-2.00 (m, 2H), 1.62-1.50 (m, 2H), 1.41 (s, 9H).
Step 3
4- [4- (5- {2,6-difluoro-4 - [(methylsulfonyl) -amino] -phenyl} -4,5-dihydro- chloride
1.2- oxazol-3-yl) -1,3-thiazol-2-yl] -piperidinium (III-1) [254] At room temperature, 4- [4- (5- { 2,6difluoro-4 - [(methylsulfonyl) -amino] -phenyl} -4,5-dihydro-1,2-oxazol-3-yl) -1,3-thiazol-2i] -piperidine-1-carboxy tert-butyl (380 mg) with a 4 moI solution of hydrogen chloride (2.6 mL) in 1,4-dioxane. The solvent and excess hydrogen chloride were removed. 4- [4- (5- {2,6-difluoro-4 [(methylsulfonyl) -amino] -phenyl} -4,5-dihydro-1,2-oxazol-3-yl) chloride was obtained -1,3-thiazol-2-yl] piperidinium (380 mg).
¹ H NMR (DMSO-d6): 9.19 (s lr, 1H), 8.94 (s lr, 1H), 8.04 (s, 1H), 6.92 (d, 2H), 5.94 (dd, 1H), 3.90-3.70 (m, 2H), 3.55-3.30 (m, 4H), 3.13 (s, 3H), 3.08-2.97 (m , 2H), 2.25-2.17 (m, 2H), 2.02-1.90 (m, 2H).
Step 4 N- (4- {3- [2- (1 - {[3,5-Bis- (difluoromethyl) -1H-pyrazol-1-yl] -acetyl} -piperidine-4-yl) -
1.3- thiazol-4-yl] -4,5-dihydro-1,2-oxazol-5-yl} -3,5-difluorophenyl) -methanesulfonamide (I-5) [255] Acid dissolved [3 , 5-bis- (difluoromethyl) -1 H-pyrazol-1-yl] -acetic (180 mg) and triethylamine (242 mg) in dichloromethane (10 ml) and stirred for 10 minutes. 4- [4- (5- {2,6-difluoro-4 - [(methylsulfonyl) amino] -phenyl} -4,5-dihydro-1,2-oxazol-3-yl) chloride was added -1,3-thiazol-2-yl] -piperidinium (380 mg) and bromotrispyrrolidine-phosphonium hexafluorophosphate (445 mg) and the reaction mixture was stirred at room temperature for 2 hours. Then, it was mixed with a concentrated sodium hydrogen carbonate solution, the aqueous phase was separated and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. Purified by column chromatography to obtain N- (4- {3- [2- (1 - {[3,5-bis- (difluoromethyl) -1Hpyazol-1-yl] -acetyl} -piperidine-4- il) -1,3-thiazol-4-yl] -4,5-dihydro-1,2-oxazol-5-yl} -3,5
93/114 difluorophenyl) -methane-sulfonamide (255 mg).
¹ H NMR (DMSO-de): 8.02 (s, 1H), 7.18 (t, 1H), 7.02 (t, 1H), 6.93-6.86 (m, 4H), 5 , 93 (dd, 1H), 5.43 (d, 1H), 5.35 (d, 1H), 4.40-4.32 (m, 1H), 4.01-3.95 (m, 1H ), 3.83 (dd, 1H), 3.50 (dd, 1H), 3.45-3.35 (m, 1H), 3.35-3.24 (m, 1H), 3.14 ( s, 3H), 2.89-2.80 (m, 1H), 2.16-2.05 (m, 2H), 1.86-1.75 (m, 1H), 1.63-1, 50 (m, 1H).
Preparation of compound XIV-1
[3,5-bis- (difluoromethyl) -1H-pyrazol-1-yl] -acetyl fluoride (XIV-1) [256] At 0 ° C, a solution of [3,5-bis- (difluoromethyl) -1Hpyazol-1-yl] -acetic (1.0 g) and pyridine (0.35 g) in dichloromethane (10 ml) with 2,4,6-trifluoro-1,3,5-triazine (0 , 60 g). After stirring overnight at 20 ° C, the reaction mixture was mixed with cyclohexane (10 ml) and filtered. The filtrate was concentrated under reduced pressure. [3,5-bis (difluoromethyl) -1H-pyrazol-1-yl] -acetyl fluoride (1.1 g) was obtained.
¹ H NMR (600 MHz, CDCU): p.p. _m .: 6.80 (s, 1H), 6.79 (t, 1H, J = 53.6 Hz), 6.68 (t, 1H, J = 54.7 Hz), 5.28 (d, 2H, J = 4.3 Hz).
¹⁹ F NMR (566 MHz, CDCU): p.p. _m 32.7 (t, J = 4.5 Hz), -113.3 (d, J = 53.3 Hz), -
113.5 (d, J = 54.6 Hz).
[257] The following compounds can be prepared using one or more of the processes specified above.
'R ¹ (I) [258] The structural element Q-3 shown in Table 1 is defined as follows:
<94/114
Table 1
For all compounds shown in Table 1, the symbol L ¹ represents a direct bond.
Ex. Y R ² Q R ⁵ R ¹ LogP I-1 O H Q-3 CH3 4,5-dimethyl-2- (prop-2-yne-1-yloxy) -phenyl 4.1 ^[a] ; 4.04 ^[b] I-2 O H Q-3 H 2,6-difluoro-3- (prop-2-yne-1-yloxy) -phenyl 3.26 ^[a] ; 3.18 ^[b] I-3 O H Q-3 H 2,6-difluoro-4- (prop-2-yne-1-yloxy) -phenyl 3.3 ^[a] ; 3.26 ^[b] I-4 O H Q-3 H 3- (allyloxy) -2,6-difluorophenyl 3.59 ^[a] ; 3.51 ^[b] I-5 O H Q-3 H 2,6-difluoro-4 - [(methylsulfonyl) -amino] -phenyl 2.63 ^[a] I-6 O H Q-3 H 6 - {[(2Z) -3-chloroprop-2-ene-1-yl] -oxy} -2,3-difluorophenyl 3.79 ^[a] ; 3.71 ^[b] I-7 O H Q-3 H 6 - [(2-chloroprop-2-ene-1-yl) -oxy] -2,3-difluorophenyl 3.68 ^[a] ; 3.69 ^[b] I-8 O H Q-3 H 2,3-difluoro-6- (prop-2-yne-1-yloxy) -phenyl 3.3 ^[a] ; 3.27 ^[b] I-9 O H Q-3 H 4 - [(cyclopropylcarbonyl) -oxy] -2,6-difluorophenyl 3.53 ^[a] I-10 O H Q-3 H 3,5-difluoro-2- (prop-2-yne-1-yloxy) -phenyl 3.58 ^[a] ; 3.51 ^[b] I-11 O H Q-3 H 4- (allyloxy) -2,6-difluorophenyl 3.7 ^[a] I-12 O H Q-3 H 3,6-difluoro-2- (prop-2-yne-1-yloxy) -phenyl 3.31 ^[a] ; 3.3 ^[b] I-13 O H Q-3 H 2,4-difluoro-6- (prop-2-yne-1-yloxy) -phenyl 3.32 ^[a]
95/114
Ex. Y R ² Q R ⁵ R ¹ LogP I-14 O H Q-3 H 2,6-difluoro-4-formylphenyl 2.93 ^[a] ; 2.87 ^[b] I-15 O H Q-3 H 2- (cyclopropylmethoxy) -4,6-difluorophenyl 3.81 ^[a] ; 3.76 ^[b] I-16 O H Q-3 H 2 - [(cyclopropylcarbonyl) -oxy] -4,6-difluorophenyl 3.5 ^[a] ; 3.42 ^[b] I-17 O H Q-3 H 6- (allyloxy) -2,3-difluorophenyl 3.53 ^[a] ; 3.56 ^[b] I-18 O H Q-3 H 2- (allyloxy) -4,6-dichlorophenyl 4.29 ^[a] ; _4j2 [ ^b ] I-19 O H Q-3 H 2 - [(2-chloroprop-2-ene-1-yl) -oxy] -4,6-difluorophenyl 3.79 ^[a] ; 3.7 ^[b] I-20 O H Q-3 H 2- (allyloxy) -4,6-difluorophenyl 3.67 ^[a] ; 3.58 ^[b] I-21 O H Q-3 H 2,4-dichloro-6- (prop-2-yne-1-yloxy) -phenyl 3.94 ^[a] ; 3.85 ^[b]
[259] The logP values have been determined in accordance with ‘EEC
Directive 79/831 Annex V.A8 'by HPLC (‘High Performance Liquid Chromatography') on reverse phase columns (C 18), using the following methods.
[260] ^[a] LC-MS determination in the acidic range is carried out at pH
2.7 using an aqueous solution of 0.1% formic acid and acetonitrile (containing 0.1% formic acid) as eluents; linear gradient from 10% acetonitrile to 95% acetonitrile.
[261] ^[b] Determination by LC-MS in the neutral range is carried out at pH
7.8, using a 0.001 molar aqueous ammonium hydrogen carbonate solution and acetonitrile as eluents; linear gradient from 10% acetonitrile to 95% acetonitrile.
[262] Calibration is performed using unbranched alkane-2-ones
96/114 (which have 3 to 16 carbon atoms), whose logP values are known (logP values determined based on retention times, by linear interpolation between two successive alkanones).
[263] The maximum lambda values were determined using the UV spectrum from 200 nm to 400 nm, at most of the chromatographic signals.
NMR data and selected examples
NMR peak listing method [264] The ¹ H-NMR data from examples I-2 to I-21 were recorded in the form of 1 H-NMR peak listings. For each signal peak, the δ value in
p.p.m. and signal strength are listed in parentheses.
Example I-2, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.0321 (10.80); 7.3369 (0.68); 7.3244 (0.70); 7.3139 (2.93); 7.3007 (1.44);
7.2901 (0.83); 7.2775 (0.83); 7.1806 (3.49); 7.1669 (1.70); 7.1516 (0.99);
7.1269 (1.61); 7.1079 (0.75); 7.1032 (0.78); 7.0475 (1.68); 7.0309 (4.13);
6.9059 (3.38); 6.8950 (2.03); 6.0178 (1.09); 5.9964 (1.30); 5.99872 (1.32);
5.9660 (1.19); 5.7554 (16.00); 5.4601 (0.75); 5.4189 (2.59); 5.3772 (2.57);
5.3351 (0.73); 4.8979 (7.50); 4.8919 (7.68); 4.3728 (0.77); 4.3379 (0.85);
4.0558 (0.51); 4.0379 (1.27); 4.0201 (1.38); 4.0025 (0.71); 3.9879 (0.70);
3.9553 (0.82); 3.9404 (0.94); 3.9099 (0.97); 3.8963 (1.14); 3.8672 (0.97);
3.6460 (2.31); 3.6401 (5.32); 3.6342 (2.33); 3.5740 (1.23); 3.5530 (1.15);
3.5309 (0.98); 3.5097 (1.00); 3.4298 (0.59); 3.4104 (0.63); 3.4014 (1.14);
3.3913 (0.72); 3.3821 (0.52); 3.3724 (0.63); 3.3642 (0.52); 3.3217 (441.54);
3.2982 (2.78); 3.2716 (1.08); 3.2428 (0.61); 2.8745 (0.55); 2.8477 (0.91);
2.8146 (0.55); 2.6748 (0.82); 2.6700 (1.07); 2.6655 (0.76); 2.5405 (0.58);
2.5236 (1.67); 2.5190 (2.60); 2.5055 (115.26); 2.5013 (157.77); 2.4975 (107.29); 2.3326 (0.84); 2.3278 (1.12); 2.3233 (0.82); 2.3191 (0.43); 2.1888 (0.67); 2.1166 (1.32); 2.0734 (1.55); 1.9884 (6.00); 1.8249 (0.63); 1.8037 (0.58); 1.5985 (0.66); 1.5885 (0.60); 1.5672 (0.59); 1.5566 (0.60); 1.2350 (0.58); 1.1922 (1.60); 1.1744 (3.24); 1.1567 (1.56); 0.0079 (0.44); -0,0002
97/114 (14.13); -0.0084 (0.43)
Example I-3, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.0257 (0.56); 8.0121 (14.18); 7.3097 (2.42); 7.1764 (5.60); 7.1594 (2.69);
7.0432 (2.77); 7.0234 (6.20); 6.9003 (5.53); 6.8875 (3.27); 6.8811 (0.99);
6.8646 (6.62); 6.8384 (6.44); 5.9498 (1.71); 5.9284 (2.08); 5.9200 (1.97);
5.8983 (1.73); 5.4549 (1.09); 5.4121 (4.09); 5.3707 (4.02); 5.3284 (1.08);
4.8880 (11.02); 4.8821 (10.88); 4.3687 (1.26); 4.3370 (1.29); 3.9899 (1.20);
3.9563 (1.33); 3.8847 (1.37); 3.8543 (1.59); 3.8417 (1.88); 3.8114 (1.63);
3.6502 (3.01); 3.6443 (6.39); 3.6384 (2.86); 3.5314 (2.07); 3.599 (2.15);
3.4880 (1.76); 3.4667 (1.80); 3.4363 (0.86); 3.4267 (1.28); 3.4173 (1.10);
3.4074 (1.56); 3.3983 (2.36); 3.3891 (1.73); 3.3782 (1.53); 3.3699 (2.00);
3.3592 (2.01); 3.3112 (736.95); 3.2456 (1.13); 2.8770 (0.87); 2.8500 (1.54);
2.8200 (0.87); 2.6741 (0.41); 2.6696 (0.54); 2.6654 (0.38); 2.5395 (0.76);
2.5094 (30.86); 2.5050 (57.09); 2.5006 (74.10); 2.4962 (51.38); 2.4918 (24.73); 2.3315 (0.34); 2.3272 (0.49); 2.3229 (0.36); 2.1495 (1.13); 2.1167 (2.29); 2.0808 (1.54); 2.0691 (16.00); 1.8528 (0.45); 1.8236 (1.01); 1.8000 (0.93); 1.7702 (0.38); 1.7632 (0.34); 1.6214 (0.47); 1.5997 (0.97); 1.5913 (1.01); 1.5709 (0.96); 1.5611 (0.92); 1.5416 (0.37); 0.0078 (0.32); -0,0002 (6.83)
Example I-4, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.0312 (10.33); 7.3143 (1.44); 7.2692 (0.57); 7.2561 (0.63); 7.2458 (1.27);
7.2329 (1.25); 7.2224 (0.78); 7.2094
7.1051 (0.87); 7.1005 (0.94); 7.0802
7.0524 (0.84); 7.0479 (1.67); 7.0312
6.0697 (0.49); 6.0563 (1.11); 6.0433
6.0133 (2.08); 6,0000 (1.33); 5,9942
5.9638 (1.12); 5.7558 (1.84); 5.4616
5.4189 (4.51); 5.3797 (3.63); 5.3758
5.2927 (1.94); 5.2887 (1.84); 5.2852
5.2623 (1.75); 5.2589 (0.70); 4.6453 (0.71); 7.1810 (3.32); 7.1672 (1.60) (1.40); 7.0766 (1.41); 7.0572 (0.73) (3.91); 6.9064 (3.12); 6.8954 (1.86) (1.03); 6.0301 (1.28); 6.0266 (0.69) (1.33); 5.99867 (2.19); 5.9736 (0.69) (0.69); 5.4271 (0.99); 5.4229 (3.18) (3.65); 5.3350 (0.69); 5.2961 (0.77) (0.76); 5.2699 (0.71); 5.2664 (1.77) (2.25); 4.6418 (3.99); 4.6381 (2.46)
98/114
4.6320 (2.37); 4.6284 (3.90); 4.6248
4.0558 (1.12); 4.0380 (3.54); 4.0202
3.9562 (0.68); 3.9382 (0.84); 3.9073
3.5690 (1.09); 3.5475 (1.13); 3.5255
3.4199 (0.33); 3.4101 (0.57); 3,4006
3.3717 (0.54); 3.3202 (94.97); 3.2965
2.8725 (0.46); 2.8451 (0.80); 2.8157 (2.29); 4.3719 (0.65); 4.3384 (0.68) (3.59); 4.0024 (1.44); 3.9916 (0.61) (0.86); 3.8947 (1.02); 3.8642 (0.88) (0.88); 3.5047 (0.91); 3.4294 (0.49) (1.03); 3.3915 (0.59); 3.3812 (0.37) (1.30); 3.2724 (0.86); 3.2432 (0.46) (0.47); 2.6704 (0.37); 2.5236 (0.61)
2.5055 (38.05); 2.5014 (52.03); 2.4980 (35.04); 2.3283 (0.36); 2.1882 (0.62); 2.1156 (1.18); 2.0738 (1.25); 1.9885 (16.00); 1.8250 (0.57); 1.8014 (0.47); 1.5985 (0.51); 1.5902 (0.56); 1.5692 (0.49); 1.5590 (0.49); 1.3975 (0.53);
1.1923 (4.37); 1.1745 (8.84); 1.1567 (4.26); -0,0002 (7.40)
Example I-5, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
10.3937 (2.73); 8.0149 (6.46); 7.3095 (1.10); 7.1762 (2.52); 7.1592 (1.22);
7.0429 (1.25); 7.0232 (2.80); 7.0162 (0.51); 6.9086 (3.56); 6,9007 (3.11);
6.8869 (2.75); 6.8831 (3.38); 5.9564 (0.78); 5.9351 (0.93); 5.9266 (0.88);
5.9049 (0.77); 5.7461 (8.38); 5.4548
5.3286 (0.49); 5.2173 (0.66); 4.3698
4.0215 (0.51); 4.0036 (0.40); 3.9908
3.8666 (0.73); 3.8538 (0.83); 3.8235 (0.51); 5.4119 (1.88); 5.3707 (1.85);
(0.58); 4.3367 (0.63); 4.0394 (0.49);
(0.58); 3.9571 (0.63); 3.8970 (0.62);
(0.73); 3.6198 (0.46); 3.5323 (0.94);
3.5226 (0.46); 3.5106 (1.09); 3.4889 (1.05); 3.4768 (0.42); 3.4748 (0.43);
3.4670 (0.89); 3.4256 (0.57); 3.4153 (0.49); 3.4058 (0.71); 3.3971 (1.06);
3.3875 (0.76); 3.3777 (0.67); 3.3683
3.2819 (1.10); 3.2761 (1.07); 3.2468
2.8494 (0.74); 2.8194 (0.41); 2.5396 (0.86); 3.3590 (0.78); 3.3090 (218.66);
(0.52); 3.1407 (16.00); 2.8775 (0.41);
(0.62); 2.5226 (1.59); 2.5093 (17.23);
2.5050 (31.09); 2.5006 (39.79); 2.4961
2.1151 (1.07); 2.0790 (0.63); 2.0693
1.8134 (0.48); 1.7954 (0.68); 1.5986 (27.48); 2.4918 (13.07); 2.1886 (0.52);
(0.52); 1.9868 (1.93); 1.8278 (0.50);
(0.46); 1.5916 (0.47); 1.5698 (0.45);
1.5604 (0.43); 1.1928 (0.54); 1.1750 (1.06); 1.1572 (0.53); -0,0002 (0.95)
Example I-6, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
7.9865 (12.73); 7.4770 (0.88); 7.4536 (2.07); 7.4284 (2.11); 7.4049 (0.93);
99/114
7.3138 (1.89); 7.1805 (4.51); 7.1668
6.9673 (1.06); 6.9630 (1.28); 6.9583
6.9395 (1.23); 6.9348 (1.17); 6.9312
6.4336 (1.25); 6.4298 (2.53); 6.4261
6.4081 (1.39); 6.0897 (1.48); 6.0692
6.0267 (1.22); 6.0116 (2.85); 5,9938
5.4656 (1.01); 5.4230 (3.22); 5.3782
4.7316 (4.12); 4.7169 (4.02); 4.3738
4.0200 (0.72); 4.0020 (0.67); 3.9922
3.8155 (1.36); 3.8037 (1.67); 3.7729
3.5296 (1.71); 3.572 (1.32); 3.4868
3.4081 (0.77); 3.3988 (1.40); 3.3895
3.3609 (0.37); 3.3213 (83.38); 3.2737 (1.22); 3.2451
2.8437 (1.12); 2.8171 (0.63); 2.6751 (0.50); 2.6706
2.5240 (1.60); 2.5192 (2.57); 2.5106 (41.11); 2.5060 (85.13); 2.5014 (115.73) (2.14); 7.0473 (2.15); 7.0308 (5.13) (1.21); 6.9539 (1.18); 6.9434 (1.04) (1.07); 6.9067 (4.30); 6.8950 (2.49) (1.30); 6.4156 (1.38); 6.4118 (2.74) (1.75); 6.0590 (1.68); 6.0383 (1.56) (2.68); 5.9788 (1.20); 5.7560 (16.00) (3.16); 5.3354 (1.00); 4.7347 (4.07) (0.89); 4.3407 (0.94); 4.0378 (0.69) (0.83); 3.9580 (0.92); 3.8464 (1.14) (1.44); 3.5679 (0.36); 3.5502 (1.68) (1.33); 3.4275 (0.62); 3.4180 (0.45) (0.78); 3.3792 (0.48); 3.3700 (0.73) (0.69); 2.8745 (0.62) (0.74); 2.6660 (0.51)
2.4968 (85.95); 2.4923 (41.91); 2.3328 (0.61); 2.3282 (0.83); 2.3236 (0.62);
2.3192 (0.32); 2.1887 (0.80); 2.1153 (1.65); 2.0803 (0.94); 1.9886 (3.13);
1.8525 (0.36); 1.8236 (0.73); 1.7978 (0.66); 1.6205 (0.39); 1.6002 (0.74);
1.5907 (0.81); 1.5690 (0.76); 1.5597 (0.72); 1.3357 (0.59); 1.2495 (0.76);
1.1926 (0.85); 1.1747 (1.66); 1.1569 (0.83); 0.0080 (0.64); -0,0002 (22.05);
0.0085 (0.77)
Example I-7, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.3197 (0.65); 7.9856 (16.00); 7.4879
7.4160 (1.28); 7.3159 (2.66); 7.1826
7.0344 (6.91); 6.9987 (2.18); 6,9945
6.9749 (2.08); 6.9710 (2.29); 6.9668
6.1198 (2.17); 6.0971 (2.92); 6.0893
5.7022 (6.95); 5.6982 (6.18); 5.4683
5.4259 (5.36); 5.3797 (5.13); 5.3376
4.7241 (0.57); 4.5089 (0.84); 4.3691 (1.28); 7.4644 (3.23); 7.4397 (3.13) (6.57); 7.1704 (3.06); 7.0494 (3.14) (2.47); 6,9900 (2.30); 6.9858 (2.03) (2.05); 6.9098 (7.03); 6.8986 (3.50) (2.52); 6.0669 (2.22); 5.7601 (15.24) (1.85); 5.4435 (8.54); 5.4390 (7.51) (1.75); 4.7945 (0.61); 4.7599 (13.49) (1.76); 4.3361 (1.83); 4.0372 (0.41)
100/114
4.0193 (0.46); 3.9893 (1.65); 3.9549 (1.79); 3.8680 (1.68); 3.8370 (2.07); 3.8253 (2.53); 3.7948 (2.21); 3.6188 (2.59); 3.5964 (2.61); 3.5759 (2.01); 3.5680 (1.20); 3.5537 (1.89); 3.4233 (1.18); 3.4140 (0.90); 3.4038 (1.53); 3.3950 (2.36); 3,3857 (1.44); 3.3749 (1.05); 3.3665 (1.44); 3.3563 (1.20); 3.3373 (20.72); 3.3328 (81.37); 3.3044 (1.38); 3.2731 (2.25); 3.2435 (1.28); 2.8904 (0.72); 2.8787 (1.07); 2.8742 (1.11); 2.8464 (2.18); 2.8161 (1.20); 2.7311 (0.42); 2.6759 (1.60); 2.6714 (1.91); 2.6669 (1.28); 2.5525 (2.03); 2.5110 (150.43); 2.5068 (249.11); 2.5023 (291.51); 2.4978 (204.83); 2.4936 (95.93); 2.3336 (1.86); 2.3291 (2.17); 2.3246 (1.56); 2.1444 (1.65); 2.1092 (3.36); 2.0752 (1.93); 1.9895 (1.78); 1.8551 (0.64); 1.8473 (0.72); 1.8253 (1.47); 1.8186 (1.49); 1.7956 (1.45); 1.7886 (1.29); 1.7657 (0.59); 1.6238 (0.64); 1.6127 (0.73); 1.5921 (1.48); 1.5832 (1.50); 1.5615 (1.49); 1.5530 (1.34); 1.5312 (0.61); 1.5218 (0.48); 1.3359 (2.56); 1.2980 (0.76); 1.2724 (0.37); 1.2582 (1.31); 1.2492 (3.17); 1.2351 (1.08); 1.1924 (0.61); 1.1746 (1.01); 1.1568 (0.58); 1.1377 (4.64); -0,0002 (36.52); -0.0085 (1.51)
Example I-8, solvent: DMSO-de, spectrometer: 399.95 MHz
7.9923 (11.58); 7.5087 (0.95); 7.4851 (2.36); 7.4605 (2.36); 7.4368 (0.95);
7.3140 (2.05); 7.1807 (4.71); 7.1670 (2.23); 7.0475 (2.29); 7.0310 (5.16);
7.0094 (1.55); 7.0048 (1.49); 7,0007 (1.43); 6.9860 (1.44); 6.9814 (1.34);
6.9059 (4.88); 6.8952 (2.64); 6.0729 (1.55); 6.0513 (1.86); 6.0426 (1.81);
6.0207 (1.62); 5.4625 (1.15); 5.4198 (3.83); 5.3779 (3.79); 5.3355 (1.14);
4.8879 (0.34); 4.8822 (0.35); 4.8478 (5.13); 4.8424 (8.89); 4.8371 (5.16);
4.8027 (0.36); 4.7968 (0.36); 4.3709 (1.11); 4.3372 (1.16); 3.9904 (1.04);
3.9561 (1.14); 3.9024 (16.00); 3.8624 (1.24); 3.8316 (1.41); 3.8195 (1.76);
3.7890 (1.54); 3.5683 (1.93); 3.5598 (2.71); 3.5539 (5.68); 3.5479 (4.11);
3.5256 (1.47); 3.5039 (1.45); 3.4343 (0.46); 3.4255 (0.76); 3.4159 (0.55);
3.4058 (0.92); 3.3968 (1.60); 3.3877 (0.94); 3.3774 (0.60); 3.3683 (0.86);
3.3596 (0.46); 3.3186 (55.10); 3.2727 (1.45); 3.2440 (0.80); 3.1746 (0.48);
3.1613 (0.45); 2.8903 (0.54); 2.8737 (0.78); 2.8443 (1.41); 2.8166 (0.78);
2.7310 (0.35); 2.6746 (1.14); 2.6702 (1.58); 2.6658 (1.17); 2.5233 (4.73);
101/114
2.5098 (90.48); 2.5056 (178.21); 2.5011 (234.80); 2.4967 (174.33); 2.3322 (1.22); 2.3279 (1.16); 1.8585 (0.81); 1.7711 (0.95); 1.5693 (1.65); 2.3236 (0.35); 1.8532 (0.33); 1.6310 (0.91); 1.5596 (1.24); 2.1526 (0.40); 1.8230 (0.35); 1.6204 (0.86); 1.5389 (1.00); 2.1168 (0.91); 1.8004 (0.44); 1.5994 (0.36); 1.3353 (2.04); 2.0816 (0.84); 1.7934 (0.89); 1.5901 (0.41); 1.2585 (0.38); 1.2494 (0.45); 0.0078 (1.46); -0,0002 (41.84); -0.0082 (1.76)
Example I-9, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.0348 (8.87); 7.3148 (1.29); 7.1815
7.1401 (3.74); 7.0484 (1.47); 7.0323
6.0081 (0.88); 5.99872 (1.05); 5.9779
5.4200 (2.17); 5.3784 (2.16); 5.3358
4.0554 (1.15); 4.0376 (3.55); 4.0199
3.9565 (0.64); 3.9330 (0.73); 3.9024
3.5813 (0.98); 3.5601 (1.01); 3.5377
3.4199 (0.33); 3.4099 (0.53); 3,4002
3.3715 (0.50); 3.3228 (57.43); 3.007 2.8710 (0.44); 2.8399 (0.76); 2.8133 (3.16); 7.1683 (2.30); 7.1628 (4.01);
(3.61); 6.9072 (2.88); 6.8965 (1.74);
(0.99); 5.9568 (0.90); 5.4627 (0.64);
(0.63); 4.3701 (0.59); 4.3378 (0.63);
(3.60); 4.0020 (1.43); 3.9900 (0.57);
(0.78); 3.8895 (0.92); 3.8592 (0.79);
(0.80); 3.5168 (0.80); 3.4290 (0.45);
(0.91); 3.3915 (0.53); 3.3806 (0.35);
(0.52); 3.2708 (0.80); 3.2420 (0.47);
(0.45); 2.6749 (0.37); 2.6704 (0.55);
2.6658 (0.39); 2.5646 (2.25); 2.5238 (1.62); 2.5191 (2.42); 2.5104 (30.49);
2.5059 (62.12); 2.5013 (81.90); 2.4967 (57.90); 2.4921 (27.04); 2.3328 (0.38);
2.3280 (0.53); 2.3236 (0.38); 2.1885 (0.60); 2.1144 (1.09); 2.0794 (0.63); 1.9887 (16.00); 1.9330 (0.43); 1.9211 (0.85); 1.9135 (1.00); 1.9086 (2.86); 1.9018 (1.61); 1.8967 (0.73); 1.8899 (0.90); 1.8823 (0.95); 1.8706 (0.55);
1.8253 (0.56); 1.8002 (0.44); 1.7957 (0.44); 1.5956 (0.47); 1.5870 (0.52);
1.5656 (0.51); 1.5570 (0.46); 1.4058 (0.78); 1.3974 (5.11); 1.1922 (4.31);
1.1744 (8.70); 1.1566 (4.21); 1.1187 (0.45); 1.1048 (1.62); 1.0972 (3.04);
1.0912 (1.62); 1.0848 (1.50); 1.0770 (2.88); 1.0711 (1.55); 1.0654 (1.93);
1.0594 (2.95); 1.0520 (2.63); 1.0484 (3.15); 1.0404 (1.61); 1.0266 (0.36);
0.0080 (0.85); -0,0002 (28.40); -0.0086 (0.84)
Example I-10, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.0353 (13.66); 7.3972 (1.40); 7.3896 (1.42); 7.3756 (1.54); 7.3683 (2.73);
102/114
7.3609 (1.53); 7.3470 (1.47); 7.3393 (1.44); 7.3116 (2.43); 7.1783 (5.57);
7.1667 (2.71); 7.0451 (2.71); 7.0306 (6.11); 7.0162 (1.67); 7.0119 (2.00);
6.9936 (1.71); 6.9894 (2.02); 6.9060 (5.82); 6.8949 (3.16); 5.9853 (1.96);
5.9667 (2.25); 5.9576 (2.25); 5.9386 (2.03); 5.7558 (16.00); 5.4588 (1.35);
5.4163 (4.61); 5.3744 (4.56); 5.3320 (1.37); 4.8270 (11.86); 4.8210 (12.23);
4.3634 (1.35); 4.3305 (1.41); 4.0559 (0.33); 4.0381 (1.05); 4.0203 (1.08);
4.0024 (0.49); 3.9789 (3.26); 3.9506 (3.67); 3.9355 (3.34); 3.9074 (2.39);
3.6710 (2.94); 3.6650 (6.17); 3.6591 (3.10); 3.4209 (0.46); 3.4119 (1.00);
3.4034 (3.18); 3.3928 (1.31); 3.3844 (4.34); 3.3746 (1.26); 3.3601 (2.86);
3.3415 (2.65); 3.3199 (50.52); 3.2951 (1.12); 3.2646 (1.78); 3.2360 (0.96);
2.8658 (0.92); 2.8357 (1.68); 2.8080 (0.94); 2.6753 (0.56); 2.6708 (0.81);
2.6663 (0.59); 2.5239 (1.87); 2.5061 (95.77); 2.5017 (127.50); 2.4973 (96.60);
2.3328
2.0642
1.8094
1.6139
1.5432
1.2497
0.0002 (34.59); -0.0083 (1.46) (0.71); 2.3284 (1.40); 1.9888 (1.17); 1.7867 (0.44); 1.6032 (1.07); 1.5222 (1.07); 1.1927 (0.93); 2.3244 (4.60); 1.8479 (1.07); 1.7793 (0.54); 1.5828 (0.45); 1.5115 (1.23); 1.1749 (0.73);
(0.44);
(1.01);
(1.08);
(0.37);
(2.39); 1.1571 (1.19); 0.0079 (1.10); 2,1327
1.8397
1.7572
1.5730
1.3360 (1.21); 2.0977 (0.53); 1.8172 (0.43); 1.7477 (1.18); 1.5519 (0.93); 1.2589 (2.49);
(1.06);
(0.36);
(1.10);
(0.38);
Example I-11, solvent: DMSO-de, spectrometer: 399.95 MHz
8.3939
7.1818
6,9974
6.8019
6.0236
5.9804
5.8891
5.4334
5.3863
5.2998 (0.50); 8.0195 (5.77); 7.1688 (0.36); 6.9076 (7.15); 6.7866 (1.93); 6.0203 (2.08); 5.9672 (1.86); 5.7992 (1.52); 5.4295 (3.83); 5.3819 (3.48); 5.2772 (16.00); 7.9523 (2.91);
(5.75);
(0.69);
(1.13);
(0.99);
(1.11);
(3.96);
(5.52);
(3.15);
7.0763
6.8969
6.0632
6.0103
5.9408
5.7576
5.4252
5.3785
5.2735 (0.43); 7.4270 (0.46); 7.0486 (3.38); 6.8441 (0.73); 6.0499 (1.07); 6.0068 (1.78); 5.9193 (2.26); 5.7219 (5.07); 5.4210 (5.54); 5.3360 (3.25); 4.6353 (0.41); 7.3150 (2.82); 7.0327 (0.70); 6.8286 (1.64); 6.0368 (2.10); 5.9936 (2.15); 5.9108 (0.52); 5.4631 (5.59); 5.3901 (1.31); 5.3035 (4.28); 4.6320 (2.46);
(6.70);
(7.12);
(1.58);
(1.84);
(2.09);
(1.31);
(1.56);
(3.45);
(7.26);
103/114
4.6285 (4.87); 4.6222 (4.70); 4.6187 (7.26); 4.6154 (4.55); 4.3715 (1.23);
4.3382 (1.30); 3.9892 (1.12); 3.9556 (1.26); 3.8790 (1.39); 3.8485 (1.60);
3.8358 (1.90); 3.8055 (1.66); 3.5154 (2.01); 3.4938 (2.07); 3.4721 (1.71);
3.4507 (1.68); 3.4357 (0.56); 3.4259 (0.94); 3.4170 (0.65); 3.4070 (1.06);
3.3974 (1.87); 3.3882 (1.10); 3.3784 (0.70); 3.3689 (0.99); 3.3600 (0.56);
3.3216 (94.65); 3,3001 (1.16); 3.2701 (1.67); 3.2420 (0.96); 2.9375 (0.93); 2.8901 (3.73); 2.8699 (0.86); 2.8396 (1.55); 2.8124 (0.91); 2.7305 (2.82);
2.6806 (2.46); 2.6749 (1.31); 2.6703 (1.75); 2.6658 (1.24); 2.6613 (0.53);
2.5236 (4.85); 2.5188 (8.09); 2.5102 (103.54); 2.5058 (208.03); 2.5012 (273.59); 2.4966 (198.03); 2.4922 (95.51); 2.3368 (0.75); 2.3325 (1.46);
2.3280 (1.96); 2.3234 (1.45); 2.3189 (0.76); 2.1470 (1.16); 2.1136 (2.34);
2.0789 (1.38); 1.8599 (0.46); 1.8503 (0.52); 1.8291 (1.01); 1.8214 (1.09);
1.7996 (0.98); 1.7908 (0.96); 1.7681 (0.43); 1.7594 (0.37); 1.6241 (0.42);
1.6153 (0.51); 1.5939 (1.01); 1.5854 (1.07); 1.5641 (1.01); 1.5546 (0.98);
1.5333 (0.44); 1.5239 (0.37); 1.2980 (0.56); 1.2584 (0.78); 1.2440 (0.42);
1.2339 (0.76); 0.1460 (0.65); 0.0079 (5.35); -0,0002 (159.14); -0.0084 (5.61);
0.0257 (0.38); -0.1497 (0.74)
Example I-12, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.3156 (0.33); 8.0077 (16.00); 7.4387
7.4120 (2.17); 7.4026 (2.14); 7.3994
7.3139 (2.92); 7.1807 (6.72); 7.1670
7.1094 (3.00); 7.0999 (2.97); 7.0856
7.0310 (7.20); 6.9065 (7.33); 6.8952
6.0303 (2.91); 6.0080 (2.54); 5.7560
5.3789 (5.65); 5.3363 (1.70); 4.8734
4.8278 (6.33); 4.8069 (5.95); 4.8010
4.3729 (1.75); 4.3403 (1.83); 4.0557
4.0018 (1.23); 3.9905 (1.65); 3.9562
3.8493 (2.23); 3.8190 (1.99); 3.6461
3.5426 (2.60); 3.5205 (2.62); 3.4994 (1.52); 7.4260 (1.68); 7.4151 (2.11);
(2.09); 7.3885 (1.82); 7.3758 (1.70);
(3.26); 7.1336 (1.78); 7.1240 (1.88);
(1.57); 7.0760 (1.49); 7.0475 (3.26);
(3.87); 6.0606 (2.42); 6.0386 (2.92);
(14.97); 5.4622 (1.70); 5.4196 (5.76);
(1.67); 4.8675 (1.74); 4.8338 (6.04);
(6.17); 4.7673 (1.62); 4.7614 (1.70);
(0.46); 4.0377 (1.38); 4.0200 (1.45);
(1.82); 3.8923 (1.61); 3.8616 (1.83);
(3.82); 3.6402 (7.80); 3.6344 (3.96);
(2.11); 3.4777 (2.08); 3.4345 (0.61);
104/114
3.4251 (1.17); 3.4160 (0.87); 3.4059 (1.40); 3.3967 (2.42); 3.3875 (1.48);
3.3776 (0.95); 3.3680 (1.33); 3.3590 (0.78); 3.3215 (59.77); 3.2719 (2.28);
3.2428 (1.22); 2.8720 (1.21); 2.8417 (2.19); 2.8144 (1.19); 2.6748 (0.82);
2.6705 (1.14); 2.6663 (0.88); 2.5058 (134.11); 2.5015 (175.63); 2.4972 (134.47); 2.3325 (0.92); 2.3283 (1.21); 2.3240 (0.97); 2.1491 (1.57); 2.1174 (3.23); 2.0818 (1.82); 1.9886 (5.76); 1.8629 (0.53); 1.8532 (0.66); 1.8314 (1.37); 1.8234 (1.52); 1.8009 (1.38); 1.7939 (1.31); 1.7716 (0.56); 1.7624 (0.47); 1.6308 (0.54); 1.6211 (0.70); 1.6006 (1.39); 1.5915 (1.53); 1.5696 (1.41); 1.5605 (1.36); 1.5393 (0.57); 1.5295 (0.47); 1.3358 (1.19); 1.2587 (0.37); 1.2496 (1.37); 1.2350 (0.45); 1.1925 (1.51); 1.1747 (2.97); 1.1570 (1.49); 0.0076 (1.19); -0,0002 (27.94)
Example I-13, solvent: DMSO-de, spectrometer: 399.95 MHz
8.0230 (0.42); 7.9766 (16.00); 7.3166 (2.62); 7.1833 (6.21); 7.1710 (3.10)
7.0502 (2.99); 7.0350 (7.08); 6.9724 (2.47); 6.9639 (2.17); 6.9575 (1.34)
6.9533 (1.89); 6.9447 (3.17); 6.9407 (3.16); 6.9372 (2.49); 6.9312 (1.60)
6.9102 (7.04); 6.8992 (3.60); 6.0215 (1.98); 5.9995 (2.40); 5.9910 (2.30)
5.9689 (2.05); 5.7596 (15.20); 5.4664 (1.51); 5.4237 (4.78); 5.3813 (4.71)
5.3387 (1.51); 4.9285 (0.41); 4.9226
4.8781 (6.12); 4.8440 (0.57); 4.8380
4.3391 (1.46); 4.0553 (0.53); 4.0374
3.9905 (1.27); 3.9562 (1.41); 3.8062
3.7319 (1.69); 3.5810 (3.07); 3.5751
3.4879 (2.20); 3.4772 (1.67); 3.4454
3.4116 (0.68); 3.4016 (1.14); 3.3926
3.3638 (1.08); 3.3548 (0.70); 3.3343
3.2414 (1.04); 2.8702 (0.96); 2.8398
2.6715 (0.67); 2.6671 (0.49); 2.5250 (0.44); 4.8885 (6.19); 4.8833 (10.07);
(0.44); 4.7531 (0.84); 4.3724 (1.35);
(1.61); 4.0196 (1.67); 4.0017 (1.10);
(1.29); 3.7745 (1.53); 3.7621 (1.86);
(6.98); 3.5692 (3.06); 3.5102 (2.15);
(1.70); 3.4305 (0.52); 3.4212 (0.93);
(1.94); 3.3832 (1.15); 3.3731 (0.76);
(63.61); 3,3003 (1.10); 3.2705 (1.82);
(1.75); 2.8129 (1.01); 2.6761 (0.45);
(1.73); 2.5202 (2.87); 2.5115 (39.45);
2.5071 (80.45); 2.5025 (106.22); 2.4980 (78.38); 2.4936 (39.34); 2.3338 (0.58); 2.3292 (0.78); 2.3247 (0.60); 2.1497 (1.21); 2.1145 (2.50); 2.0789 (1.45); 1.9896 (7.28); 1.8580 (0.45); 1.8507 (0.53); 1.8215 (1.15); 1.7982
105/114 (1.07); 1.7910 (0.54); 1.5948 (0.49); 1.5240 (1.03); 1.7700 (1.09); 1.5556 (0.38); 1.3973 (0.44); 1.7606 (1.20); 1.5643 (0.86); 1.3364 (0.37); 1.6249 (1.14); 1.5556 (0.68); 1.2586 (0.44); 1.6157 (1.09); 1.5346 (0.37); 1.2495 (0.89); 1.2347 (0.54); 1.1924 (1.98); 1.1747 (3.96); 1.1568 (1.97); -0,0002 (5.11)
Example I-14, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz (0.57); 8.3154 (0.32); 8.0576 (10.91);
(5.87); 7.6852 (0.93); 7.3144 (1.98);
(2.24); 7.0307 (5.04); 6.9066 (4.74);
(1.66); 6.0611 (1.62); 6.0401 (1.48);
(3.52); 5.3792 (3.61); 5.3368 (1.08);
(0.33); 4.0378 (1.00); 4.0199 (1.07);
(2.36); 3.9215 (1.40); 3.6330 (1.57);
(1.35); 3.4431 (0.37); 3.4337 (0.70);
(1.46); 3.3953 (0.87); 3.3857 (0.56);
(89.18); 3.2726 (1.41); 3.2440 (0.82);
(0.76); 2.6751 (0.66); 2.6707 (0.94);
9.9796 (4.86); 9.9008 (0.54); 8.6585
7.7244 (0.84); 7.7147 (5.87); 7.6945
7.1811 (4.70); 7.1668 (2.22); 7.0479
6.8949 (2.57); 6.0913 (1.41); 6.0706
5.7560 (16.00); 5.4629 (1.02); 5.4204
4.3743 (1.05); 4.3415 (1.09); 4.0557
3.9949 (2.01); 3.9647 (2.07); 3.9523
3.6121 (1.61); 3.5893 (1.31); 3.5684
3.4239 (0.52); 3.4143 (0.85); 3.4048
3.3763 (0.76); 3.3669 (0.42); 3.3219
2.8731 (0.73); 2.8420 (1.33); 2.8151
2.6662 (0.70); 2.5239 (2.72); 2.5104 (55.80); 2.5061 (112.26); 2.5017 (148.22); 2.4972 (109.34); 2.4928 (55.27); 2.3328 (0.76); 2.3284 (1.03);
2.3238 (0.79); 2.1512 (0.95); 2.1178
1.8568 (0.39); 1.8269 (0.85); 1.8049
1.5913 (0.88); 1.5703 (0.82); 1.5613
1.2983 (0.37); 1.2587 (0.54); 1.2496 (1.95); 2.0830 (1.12); 1.9887 (4.39);
(0.79); 1.6219 (0.41); 1.6006 (0.85);
(0.78); 1.5409 (0.35); 1.3358 (1.70);
(2.04); 1.2348 (0.55); 1.1926 (1.17);
1.1748 (2.28); 1.1570 (1.14); 0.0079 (0.70); -0,0002 (19.92); -0.0081 (0.85)
Example I-15, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
7.9638 (16.00); 7.3135 (2.67); 7.1803 (6.33); 7.1676 (3.03); 7.0472 (3.06); 7.0317 (6.94); 6.9073 (6.53); 6.8959 (3.48); 6.8640 (1.24); 6.8580 (1.73);6.8357 (7.52); 6.8101 (6.76); 6.0360 (2.24); 6.0152 (2.76); 6.0049 (2.58);5.9840 (2.36); 5.4767 (1.70); 5.4252 (4.81); 5.3719 (4.71); 5.3290 (1.81);4.3629 (1.49); 4.3316 (1.53); 4.0557 (0.64); 4.0378 (1.80); 4.0200 (1.88);
106/114
4.0024 (0.85); 3.9846 (1.39); 3.9500 (1.57); 3.9166 (2.34); 3.8997 (2.54);
3.8909 (3.26); 3.8741 (3.15); 3.7851 (1.71); 3.6700 (2.98); 3.7539 (2.55);
3.7418 (5.55); 3.7349 (2.71); 3.7145 (3.16); 3.5839 (2.65); 3.5629 (2.77);
3.5416 (1.93); 3.5208 (1.83); 3.4275 (0.70); 3.4181 (1.18); 3.4078 (0.90);
3.3984 (1.36); 3.3991 (2.37); 3.3808 (1.53); 3.3601 (2.29); 3.3507 (2.26);
3.3268 (446.42); 3.2902 (0.94); 3.2701 (2.16); 3.2422 (1.04); 2.8712 (1.05);
2.8397 (1.87); 2.8124 (1.08); 2.6752 (1.31); 2.6708 (1.75); 2.6662 (1.33);
2.5239 (5.68); 2.5105 (105.72); 2.5062 (210.23); 2.5017 (276.22); 2.4972 (205.17); 2.4929 (104.36); 2.3330 (1.29); 2.3285 (1.76); 2.3239 (1.28); 2.1225 (1.35); 2.0915 (2.77); 2.0560 (1.54);
(8.29); 1.8299 (0.55); 1.8098 (1.17);
(1.09); 1.7497 (0.44); 1.5959 (0.54);
(0.46); 1.3977 (1.17); 1.3356 (1.03);
(2.34); 1.1924 (2.17); 1.1746 (4.15);
(1.19); 0.9876 (1.08); 0.9753 (1.81);
(0.74); 0.8369 (0.33); 0.3767 (0.61);
(1.68); 0.3336 (2.37); 0.3216 (1.21);
(1.04); 0.1722 (2.53); 0.1621 (5.70);
(3.36); 0.1256 (2.35); 0.1167 (1.24); 0,
2.0275 (0.42); 2.0086 (0.62); 1.9889 1.8016 (1.25); 1.7801 (1.15); 1.7723 1.5689 (1.19); 1.5437 (1.12); 1.5124 1.2943 (0.38); 1.2493 (2.29); 1.2363 1.1568 (2.07); 1.0059 (0.60); 0.9922 0.9571 (1.49); 0.9421 (0.72); 0.8542 0.3674 (0.77); 0.3551 (1.80); 0.3466 0.3159 (0.91); 0.2094 (0.37); 0.1899 0.1550 (4.79); 0.1489 (4.84); 0.1364 082 (0.77); 0.0001 (2.70)
Example I-16, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.0268 (14.48); 7.3244 (1.39); 7.3178 (1.71); 7.3125 (2.87); 7.3014 (1.80);
7.2963 (2.50); 7.2911 (1.80); 7.2746 (1.43); 7.2682 (1.44); 7.1792 (5.89);
7.1660 (2.94); 7.1548 (1.89); 7.1501 (2.49); 7.1451 (1.79); 7.1312 (1.92);
7.1266 (2.48); 7.0460 (2.81); 7.0300 (6.49); 6.9059 (6.08); 6.8942 (3.34);
5.8657 (2.07); 5.8437 (2.49); 5.8351 (2.47); 5.8129 (2.16); 5.7556 (16.00);
5.4644 (1.49); 5.4218 (4.55); 5.3742 (4.52); 5.3317 (1.50); 4.3690 (1.38);
4.3358 (1.47); 4.0555 (0.76); 4.0377 (2.35); 4.0199 (2.42); 4.0020 (1.15);
3.9874 (1.29); 3.9525 (1.45); 3.8976 (1.65); 3.8667 (1.92); 3.8542 (2.20);
3.8235 (1.89); 3.4337 (2.66); 3.4236 (1.21); 3.4118 (2.82); 3.4048 (1.49);
3.3907 (2.94); 3.3779 (2.77); 3.3577 (0.78); 3.3217 (65.27); 3.2691 (1.83);
107/114
3.2411 (0.99); 3.1882 (0.41); 2.8695 (0.96); 2.8392 (1.76); 2.8121 (1.03); 2.6749 (0.55); 2.6704 (0.80); 2.6660 (0.60); 2.5237 (2.14); 2.5099 (45.65); 2.5058 (91.16); 2.5014 (120.94); 2.4969 (90.89); 2.4926 (47.44); 2.3326 (0.61); 2.3282 (0.85); 2.3237 (0.65); 2.1279 (1.22); 2.1042 (2.59); 2.0695 (1.44); 1.9885 (10.15); 1.8510 (0.44); 1.8412 (0.52); 1.8204 (1.09); 1.8118 (1.19); 1.7899 (1.09); 1.7821 (1.04); 1.7608 (0.45); 1.7493 (0.40); 1.7424(0.76); 1.7308 (1.41); 1.7226 (1.67); 1.7113 (2.97); 1.6999 (1.82); 1.6914(1.68); 1.6799 (0.84); 1.6159 (0.42); 1.6054 (0.51); 1.5841 (1.07); 1.5750(1.17); 1.5539 (1.08); 1.5451 (1.06); 1.5235 (0.44); 1.5176 (0.40); 1.3357(1.04); 1.2495 (1.26); 1.1925 (2.72); 1.1748 (5.43); 1.1569 (2.68); 1.0448(0.33); 1.0350 (0.92); 1.0210 (1.53); 1.0161 (1.70); 1.0112 (1.94); 1.0000(3.16); 0.9909 (2.45); 0.9814 (3.03); 0.9739 (1.47); 0.9618 (1.29); 0.9528(0.84); 0.9322 (0.97); 0.9222 (1.68); 0.9119 (1.46); 0.9067 (1.74); 0.8957(1.71); 0.8891 (1.79); 0.8813 (1.66); 0.8701 (2.61); 0.8613 (1.65); 0.8494(1.79); 0.8410 (1.16); 0.8295 (0.77); 0.8202 (0.45); 0.8154 (0.40); 0.8081(0.67); 0.7881 (0.67); 0.7832 (0.64); 0.7777 (0.69); 0.7702 (0.59); 0.7658(0.75); 0.75586 (0.33); 0.6934 (0.62); -0,0002 (6.53); -0.0084 (0.34)
Example I-17, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.3192
7.3884
7.0341
6.0780
5.8831
5.7596
5.2915
4.5772
4.5083
3.9901
3.7769
3.4287
7,9858
7.3160
6,9086
6.0564
5.8674 (16.00); 7.4606 (3.19); 7.1828 (10.84); 6.8986 (2.96); 5.9233 (2.27); 5.8536 (1.56); 7.4367 (4.09); 7.4123 (7.31); 7.1702 (7.19); 6.1083 (0.75); 5.9097 (1.91); 5.8404 (3.69); 7.0497 (2.81); 6.0869 (1.59); 5.8968 (1.99); 5.8272 (0.59);
(1.63);
(7.61);
(3.39);
(2.09);
(12.92); 5.4694 (2.35); 5.4267 (6.85); 5.3797 (6.78); 5.3372 (3.99);
(4.62);
(1.39);
(2.15);
(2.96);
(1.43);
5.1277
4.5648
4.3716
3.9563
3.5698
3.4197 (4.64);
(8.51);
(2.33);
(2.36);
(3.79);
(1.13);
5.1013
4.5519
4.3401
3.8503
3.5492
3.4092 (4.37); 4.6098 (4.63); 4.5334 (2.43); 4.0371 (2.27); 3.8194 (3.34); 3.5282 (1.81); 3.4000 (0.83); 4.5972 (0.97); 4.5192 (0.32); 4.0197 (2.67); 3.8076 (2.56); 3.5067 (2.96); 3.3917 (4.19);
(3.58);
(3.42);
(1.64);
(1.03);
(6.61);
(0.95);
(0.86);
(0.41);
(3.44);
(2.49);
(1.89);
108/114 (1.26); 3.3719 (1.72); 3.3322 (80.29); 3.3046 (2.09); 3.2739 (3.01); (1.60); 2.8900 (0.73); 2.8743 (1.52); 2.8441 (2.85); 2.8156 (1.54);
(0.42); 2.6715 (2.00); 2.5525 (2.69); 2.5025 (299.09); 2.3292 (2.27);
(2.12);
(0.89);
(0.75);
(2.01);
(1.62);
2.1112
1.8287
1.7606
1.5642
1.2981 (4.39); 2.0771 (1.83); 1.8219 (0.64); 1.6251 (1.86); 1.5557 (0.56); 1.2585 (2.51); 1.9895 (1.98); 1.7996 (0.72); 1.6155 (1.81); 1.5349 (0.77); 1.2494 (1.29); 1.8590 (1.83); 1.7923 (0.90); 1.5552 (0.77); 1.5251 (1.77); 1.2341 (0.74);
(1.74);
(1.81);
(0.63);
(0.61);
3.3809
3.2448
2.7311
2,1459
1.8508
1.7692
1.5861
1.3359
1.1930 (0.44); 1.1746 (0.70); 1.1571 (0.45); 1.1378 (6.70); -0,0002 (28.42)
Example I-18, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
7.9519
7.1970
6,9086
6.1620
5.7416
5.4267
5.2198
4.9885
4.5625
4.3368
3.9905
3.6939
3.4354
3,3884
3.3043
2.8185
2.5108 (24.96); 2.3332 (2.00); 2.0757 (0.88); 1.8173 i (6.60); 7,2018 (2.36); 7.0328 (2.40); 6.1853 (1.08); 5.7580 (16.00);
(0.61); 5.4693 (2.60); 5.2593 (2.45); 4.9917 (2.10); 4.5807 (0.72); 4.3691 (1.22); 4.0017 (1.90); 3.7249 (1.59); 3.4907 (0.93); 3.3976 (0.59); 3.3279 (75.26);
(0.78); 2.8461 (0.34); 2.5410 (5.62); 7.2546 (2.31); 7.0489 (1.88); 6.1931 (1.07); 5.7717 <
(1.25); 5.7017 (1.23); 5.2631 (2.44); 5.0149 (0.78); 4.5940 (0.78); 4.5165 (1.18); 4.0197 (1.49); 3.7359 (2.20); 3.5138 (0.57); 3.4066 (0.88); 3.3593 (0.75); 2.8765 (0.47); 2.6665 (5.65);
(5.52);
(2.22);
(12.77); 7.3153 (2.05); 7.2595 (5.00);
(4.64);
(1.95);
(1.38);
(3.60);
(2.20);
(2.27);
(2.07);
(1.13);
(1.01);
(2.04);
(0.40);
(0.94);
(2.20);
(0.76);
(26.24); 2.5064 (52.28); 2.5019 (69.42); 2.4974 (50.91);
(0.33); 2.3287 (0.47); 2.3240 (1.10); 1.9890 (5.16); 1.8563 (0.94); 1.7945 (0.87); 1.7859
7.1820
6.8970
5.7985
5.7284
5.3773
5.2160
4.6258
4.5483
4.0553
3.9562
3.5559
3.4259
3,3782
3.2757
2.6757 (4.90);
(2.70);
(0.50);
(1.10);
(3.53);
(2.25);
(2.01);
(0.40);
(1.11);
(2.19);
(0.76);
(0.62);
(1.43);
(0.34);
7.1688
6.2163
5.7847
5.7152
5.3349
5.0181
4,6123
4.5308
4.0375
3.7671
3.5327
3.4169
3.3690
3.2467
2.6709 (1.24);
(2.67);
(2.22);
(2.03);
(1.10);
(0.83);
(2.54);
(1.57);
(1.58);
(0.33); 2.1442 (0.34); 1.8468 (0.81); 1.7655 (0.95);
(0.41);
(0.34);
(1.36);
(0.37);
2.4929
2.1092
1.8255
1.6238
109/114 (0.34); 1.6133 (0.42); 1.5924 (0.87); 1.5834 (0.96); 1.5624 (0.88); 1.5534 (0.85); 1.5322 (0.35); 1.3358 (0.63); 1.2585 (0.41); 1.2491 (0.82); 1.2352 (0.45); 1.1924 (1.41); 1.1746 (2.79); 1.1568 (1.36); 0.0844 (0.53); 0.0707 (0.38); 0.0079 (2.33); -0,0002 (57.94); -0.0085 (2.34)
Example I-19, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.3189 (0.39); 7.9626 (12.22); 7.3152 (1.99); 7.1819 (4.72); 7.1696 (2.36);
7.0488 (2.27); 7.0335 (5.32); 7.0053 (1.86); 6.9775 (1.90); 6.9603 (1.25);
6.9544 (1.02); 6.9370 (1.56); 6.9326 (2.02); 6.9275 (1.31); 6.9094 (5.97);
6.8978 (2.82); 6.0590 (1.58); 6.0363 (1.96); 6.0286 (1.87); 6.0056 (1.69);
5.7591 (16.00); 5.7252 (4.35); 5.7230 (4.39); 5.7212 (4.45); 5.4675 (1.26); 5.4403 (5.36); 5.4358 (5.54); 5.4251 (3.89); 5.3782 (3.64); 5.3357 (1.24); 4.7896 (11.21); 4.3666 (1.10); 4.3338 (1.17); 4.0373 (0.84); 4.0194 (0.86); 4.0014 (0.57); 3.9869 (1.02); 3.9524 (1.13); 3.8054 (1.09); 3.7750 (1.31);
3.7632 (1.69); 3.7325 (1.50); 3.5684 (1.81); 3.5457 (1.82); 3.5258 (1.32);
3.5032 (1.30); 3.4276 (0.37); 3.4183 (0.72); 3.4085 (0.54); 3.3991 (0.93);
3.3899 (1.54); 3.3806 (0.95); 3.3705 (0.68); 3.3613 (0.95); 3.3332 (104.96); 3.3063 (0.96); 3.3010 (1.00); 3.2709 (1.49); 3.2423 (0.82); 2.8725 (0.77);
2.8414 (1.40); 2.8145 (0.79); 2.6805 (0.32); 2.6760 (0.66); 2.6714 (0.92);
2.6668 (0.67); 2.5414 (0.34); 2.5247 (2.44); 2.5111 (52.04); 2.5069 (104.57); 2.5023 (139.02); 2.4978 (104.39); 2.4936 (53.31); 2.3337 (0.75); 2.3291 (1.01); 2.3245 (0.76); 2.3992 (0.95); 2.1053 (2.03); 2.0705 (1.18); 1.9894 (3.75); 1.8525 (0.36); 1.8439 (0.45); 1.8229 (0.89); 1.8145 (0.97); 1.7919 (0.92); 1.7839 (0.84); 1.7627 (0.38); 1.6201 (0.35); 1.6095 (0.44); 1.5888 (0.87); 1.5790 (0.97); 1.5581 (0.92); 1.5492 (0.88); 1.5287 (0.39); 1.3358 (0.67); 1.2493 (0.83); 1.1925 (1.01); 1.1747 (1.98); 1.1569 (0.97); 0.1459 (0.36); 0.0080 (2.93); -0,0002 (85.86); -0.0084 (3.77); -0.1497 (0.39)
Example I-20, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
8.0177 (0.50); 7.9663 (12.01); 7.3158 (2.02); 7.1825 (4.88); 7.1699 (2.48);
7.0494 (2.29); 7.0339 (5.47); 6.9095 (5.64); 6.8981 (3.92); 6.8859 (2.24);
6.8775 (2.09); 6.8739 (1.98); 6.8680 (1.34); 6.8508 (1.36); 6.8450 (1.00);
110/114
6.0534 (1.62); 6.0320 (1.93); 6.0228
5.8872 (1.02); 5.8740 (0.98); 5.8607
5.8175 (1.31); 5.8044 (0.64); 5.7593
5.3790 (3.71); 5.3378 (3.52); 5.3342
5.1247 (2.30); 5.1214 (2.37); 5.0983
4.6201 (0.49); 4.6007 (2.35); 4.5972
4.5570 (0.64); 4.5436 (0.56); 4.5087
4.0371 (0.66); 4.0194 (0.71); 4.0010
3.7900 (1.12); 3.7589 (1.33); 3.7471
3.4935 (1.80); 3.4726 (1.39); 3.4511
3.4153 (0.54); 3.4052 (0.91); 3.3960
3.3673 (0.87); 3.3576 (0.63); 3.3337
3.2718 (1.47); 3.2434 (0.84); 2.8724
2.6757 (0.62); 2.6712 (0.86); 2.6668
2.5110 (49.52); 2.3335 (0.70); 2.3290 (2.06); 2.0752 (1.20); 1.9893 (2.96);
(0.91); 1.8184 (0.98); 1.7966 (0.91);
(0.38); 1.6129 (0.48); 1.5917 (0.91);
(0.89); 1.5317 (0.41); 1.5211 (0.33);
(0.82); 1.2491 (1.97); 1.2343 (0.97);
(1.87); 6.0011 (1.71); 5.9005 (0.48);
(1.23); 5.8441 (1.35); 5.8307 (1.20);
(16.00); 5.4690 (1.24); 5.4264 (3.71);
(3.48); 5.2948 (2.12); 5.2908 (2.18);
(2.16); 5.0950 (2.23); 4.6331 (0.50);
(1.88); 4.5882 (3.95); 4.5762 (2.34);
(0.38); 4.3711 (1.11); 4.3379 (1.18);
(0.64); 3.9893 (1.03); 3.9560 (1.13);
(1.67); 3.7166 (1.45); 3.5152 (1.76);
(1.36); 3.4338 (0.42); 3.4245 (0.72);
(1.56); 3.3865 (0.98); 3.3770 (0.62);
(91.42); 3.3088 (1.07); 3.3029 (1.05);
(0.76); 2.8416 (1.38); 2.8148 (0.81);
(0.64); 2.5525 (0.69); 2.5244 (2.32);
2.4934
2.1102
1.8579 (0.37); 1.8484 (0.48); 1.8267
1.7883 (0.85); 1.7671 (0.39); 1.6230
1.5829 (1.01); 1.5613 (0.94); 1.5518
1.3356 (1.57); 1.2979 (0.55); 1.2583
1.1924 (0.83); 1.1747 (1.56); 1.1569 (47.11); 2.5067 (94.65); 2.5022 (126.48); 2.4977 (95.53);
(0.94); 2.3244 (0.71); 2.1427 (0.98);
(0.81); 1.1378 (2.06); 0.0079 (2.38); -0,0002 (69.49); -0.0084 (3.56)
Example I-21, solvent: DMSO-d ₆ , spectrometer: 399.95 MHz
7.9640 (12.03); 7.3189 (5.52); 7.3141
7.1815 (4.70); 7.1691 (2.24); 7.0483
6.8973 (2.56); 6.1891 (1.86); 6.1649
5.7579 (16.00); 5.4636 (1.17); 5.4210
4.8995 (0.50); 4.8936 (0.51); 4.8596
4.8111 (0.49); 4.8052 (0.49); 4.3699
4.0374 (1.80); 4.0196 (1.85); 4.0018 (8.26); 7.2767 (5.84); 7.2720 (4.94) (2.25); 7.0331 (5.18); 6.9085 (4.76) (2.40); 6.1584 (2.24); 6.1340 (1.93) (3.78); 5.3793 (3.69); 5.3367 (1.14) (4.21); 4.8522 (5.90); 4.8451 (4.17) (1.11); 4.3371 (1.18); 4.0553 (0.59) (1.04); 3.9894 (1.03); 3.9552 (1.12)
111/114
3.7725 (1.46); 3.7415 (1.85); 3.7302 (2.45); 3.6992 (1.98); 3.5621 (2.19); 3.5378 (2.21); 3.5198 (1.61); 3.4956 (1.59); 3.4756 (2.42); 3.4698 (5.27); 3.4640 (2.36); 3.4266 (0.40); 3.4188 (0.78); 3.4090 (0.56); 3.3995 (0.93); 3.3900 (1.60); 3.3810 (0.95); 3.3706 (0.65); 3.3611 (0.91); 3.3524 (0.61); 3.3282 (59.14) ; 3.3043 (2.05) 3.2708 (1.45); 3.2418 (0.78); 2.8735 (0.81); 2.8426 (1.40); 2.8151 (0.78); 2.6756 (0.35); 2.6709 (0.47); 2.6666 (0.36); 2.5064 (50.45); 2.5019 (67.00); 2.4974 (49.25) 2.4931 (24.03) ; 2.3286 (0.44); 2.3241 (0.34); 2.1995 (0.99); 2.1164 (1.96); 2.0804 (1.10); 1.9890 (7.82); 1.8487 (0.39); 1.8255 (0.88); 1.8194 (0.91); 1.7963 (0.82); 1.6264 (0.34); 1.6162 (0.40); 1.5952 (0.85); 1.5862 (0.92); 1.5645 (0.85); 1.5568 (0.81); 1.5356 (0.33); 1.3357 (0.61); 1.2585 (0.35); 1.2492 (0.75); 1.1924 (2.17); 1.1746 (4.27); 1.1568 (2.09); 0.0844 ( 0.48); , 0707 ( 0.35); 0 , 0080 ( 2.15); - 0.0002 (54.96); -0.0085 (1.95)
[265] The intensity of the clearest signals is correlated with the weight of the signals in a printed example of an NMR spectrum in cm and shows the true proportions of the signal intensities. In the case of broad signals, the various peaks or the medium of the signal and their relative strength can be displayed in comparison to the most intense signal in the spectrum.
[266] The 1H-NMR peak listings are similar to conventional 1H-NMR impressions and thus contain all of the peaks listed in a conventional NMR interpretation.
[267] In addition, as with conventional 1H-NMR prints, 10 may show solvent signals, stereoisomeric signals from the target compounds, which are also provided by the invention, and / or impurity peaks.
[268] In the report of compound signals in the solvent and / or water delta range, these 1H-NMR peak listings show the usual solvent peaks, for example, DMSO peaks in DMSO-d6 and the peak of water, which normally has a high intensity on average.
[269] The stereoisomers peaks of the target compounds and / or the peaks of
112/114 impurities normally have a lower intensity on average than the peaks of the target compounds (for example, with a purity> 90%).
[270] Such stereoisomers and / or impurities may be characteristic of the particular preparation process. Therefore, their peaks can help to identify a reproduction of these preparation processes by reference to “fingerprints of by-products”.
[271] A specialized calculation of the peaks of the target compounds by known methods (MestreC, ACD simulation, or with expected values empirically evaluated) can, if necessary, isolate the peaks of the target compounds, using additional intensity filters, if appropriate. This isolation will be similar to the selection of relevant peaks in the interpretation of conventional 1H-NMR.
Usage examples
Example A
Phytophthora (tomato) / protective test
Solvent: 49 parts by weight of N, N-dimethylformamide
Emulsifier: 1 part by weight of alkylaryl-polyglycolic ether [272] A suitable preparation of active ingredient is prepared by mixing 1 part by weight of active ingredient with the specified amounts of solvent and emulsifier and diluting the concentrate with water to the desired concentration .
[273] To test for protective activity, spray young tomato plants with the active ingredient preparation at the specified application rate. One day after treatment, the plants are inoculated with a spore suspension of Phytophthora infestans and then kept at rest for 24 hours at 100% relative humidity and 22 ° C. Next, the plants are placed in an air-conditioned cell at about 96% relative atmospheric humidity and at a temperature of about 20 ° C.
[274] The evaluation takes place 7 days after inoculation. In this case, a value of 0% designates an efficiency that corresponds to that of the control, whereas
113/114 100% efficacy means that no infestation was observed.
[275] In this test, the compounds of the invention shown below showed an efficiency of 70% or greater for an active ingredient concentration of 100 p.p.m ..
Ex. Efficiency % I-1 98 I-2 94 I-3 98 I-4 95 I-5 95 I-18 95 I-21 95
Example B
Plasmopara (grape) / protective test
Solvent: 24.5 parts by weight of acetone
24.5 parts by weight of dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl-polyglycolic ether [276] A suitable preparation of active ingredient is prepared by mixing 1 part by weight of active ingredient with the specified amounts of solvent and emulsifier and diluting the concentrate with water to the desired concentration .
[277] To test for protective activity, spray young tomato plants with the active ingredient preparation at the specified application rate. After drying the sprayed coating, the plants are inoculated with an aqueous spore suspension of Plasmopara vitícola and then maintained for 1 day in an incubation chamber at about 20 ° C and 100% relative humidity. Subsequently, the plants are placed for 4 days in a greenhouse at about 21 ° C and about 90% atmospheric humidity.
The plants are then moistened and placed in an incubation chamber for 1 day.
114/114 [278] The evaluation takes place 6 days after inoculation. In this case, a value of 0% designates an efficacy that corresponds to that of the control, whereas an efficiency of 100% designates that no infestation was observed.
[279] In this test, the compounds of the invention shown below showed an efficiency of 70% or greater for an active ingredient concentration of 10 p.p.m ..
Ex. Efficiency % I-2 100 I-3 100 I-4 100 I-5 96 I-7 100 I-8 100 I-13 100 I-17 100 I-18 96 I-19 100 I-20 100 I-21 100
1/5

权利要求:
Claims (9)
[1]
1. Compounds of structural formula (I), to combat harmful phytopathogenic fungi

R ¹ (I) characterized in that the definitions of the radicals have the following meanings:
the symbol Y represents oxygen or sulfur, the symbol R2 represents hydrogen or halogen the symbol Q represents .5


O ^y R ⁵


Q-1 =
O, Q-2 =

where the bond identified by "x" is directly linked to the thiazole and the bond identified by "y" is directly linked to L ¹ or R ¹ , the symbol R ⁵ represents hydrogen, cyano, (C1-C3) alkyl or haloalkyl ( C1-C3), the symbol L ¹ represents a direct bond, -CH2-, - (C = O) -, sulfur or oxygen, the symbol R ¹ represents phenyl which contains at least one substituent Z4 and, in addition, two, three or four other substituents that are independently selected from the substituents Z4 and Z ¹ , the symbol Z ¹ represents halogen, hydroxyl, nitro, cyano, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, haloalkoxy, alkylcarbonyl, alkoxycarbonyl, alkylcycloalkyl, cycloalkoxyalkyl, cycloalkylamino, alkylthio, haloalkylthio, cycloalkylthio, cycloalkylalkyl, alkylcarbonyloxy,
Petition 870190062787, of 07/05/2019, p. 12/17
[2]
2/5 alkylcarbonylamino, haloalkylcarbonylamino, alkylcarbonylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyloxy, haloalkylsulfonyloxy, alkylcycloalkylalkyl, C (= O) NR ³ R ⁴ , -NR ³ R ⁴ , tri-alkyl ( ³⁾ Z ³ , the symbol Z ³ represents a phenyl radical, a naphthalenyl radical or a 5- or 6-membered heteroaryl radical, which may contain, in each case, 0, 1, 2 or 3 substituents, in which the substituents are selected, independently of each other, from the following listing:
- substituents on carbon: halogen, cyano, nitro, hydroxy, amino, SH, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkoxyalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxyalkoxy, alkoxyalkoxy, alkoxyalkoxy, alkoxyalkoxy , alkynyloxy, alkoxyalkoxy, alkylamino, dialkylamino, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, trisylylalkyl or phenyl,
- substituents on nitrogen: hydrogen, -C (= O) H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkylsulfonyl, haloalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl , haloalkoxycarbonyl, cycloalkoxycarbonyl, C (= O) NR ³ R ⁴ , phenyl or benzyl, the symbol Z ⁴ represents SH, C (= O) H, cycloalkyl (C7-C8), halocycloalkyl (C7-C8), cycloalkylcycloalkyl, halocycloalkylalkyl cycloalkenyl, halocycloalkenyl, alkoxyalkyl (C5C6) alkoxyalkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkylaminoalkyl, dialkylaminoalkyl, haloalquilaminoalquilo, cycloalkylaminoalkyl alkyl, (C5C6) alkoxycarbonyl, haloalkyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, cycloalkylalkoxycarbonyl, cycloalkylaminocarbonyl, haloalkoxyalkyl, hydroxyalkyl (C5-C6), alkoxy (C5-C6), haloalkoxy (C5-C6), cycloalkoxy, halocycloalkoxy, cycloalkylalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, haloalkynyloxy, alkoxyalkoxy, haloalkylcarbonyloxy, cycloalkylcarbonyloxy, alkylcarbonylalkoxy, (C5-C6-alkyl) -alkyl (halo-C6-alkyl) C5-C6) -sulfinyl, alkylsulfonyl, halo (C1-C4) -sulfonyl, cycloalkylsulfonyl, tri ((C3-C4) alkyl) - silyl, alkylsulfonylamino or haloalkylsulfonylamino,
Petition 870190062787, of 07/05/2019, p. 13/17
[3]
3/5 the L ³ symbol represents a direct bond, -CH2-, -C (= O) -, sulfur, oxygen, -C (= O) O-, -C (= O) NH-, -OC (= O) - or -NHC (= O) -, the symbols R ³ and R4 are the same or different and independently represent hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, benzyl or phenyl, and also salts, complexes with metals and N-oxides of the compounds of structural formula (I).
2. Compounds of structural formula (I), according to claim 1, characterized in that the symbol Y represents oxygen or sulfur, the symbol R ² represents hydrogen or halogen, the symbol Q represents Q-1, Q-2, Q- 3, Q-4, Q-5 and Q-6, where the connection identified by “x” is directly connected to the thiazole and the connection identified by “y” is directly connected to L ¹ or R ¹ , the symbol R ⁵ represent hydrogen, cyano, methyl, ethyl, trifluoromethyl or difluoromethyl, the symbol L ¹ represents a direct bond or oxygen, the symbol R ¹ represents phenyl that contains at least one substituent Z ⁴ and additionally contains two or three other substituents that are independently selected from the substituents Z ⁴ and Z ¹ , the symbol Z ³ represents a phenyl, naphthalenyl radical or a 5- or 6-membered heteroaryl radical, which may contain up to two substituents, where the substituents are selected, in a independently from the following list:
- substituents on carbon: halogen, cyan, nitro, hydroxyl, amino, -
SH, (C1-C4) alkyl, (C2-C4) alkenyl, (C2-C4) alkynyl, halo (C1-C4), haloalkenyl (C2-C4), haloalkynyl (C2-C4), alkoxy (C2-C4) alkoxy , (C1-C6) alkylcarbonyl, (C1-C6) haloalkyl-carbonyl, (C1-C6) alkoxycarbonyl, (C1-C4) alkoxy, (C1-C4) haloalkoxy, (C2-C6) alkenyloxy (alkynyloxy ( C2-C6), (C1-C4) alkylthio, halo (C1-C4) -thio, alkyl (C1-C4) -sulfonyl, halo (C1-C4) -sulfonyl, alkyl (C1-C4) -amino or di- ((C1-C4) alkyl) - amino,
- substituents on nitrogen: (C1-C6) alkyl, (C2-C6) alkenyl, (C2C6) alkynyl, (C1-C6) haloalkyl, (C2-C6) haloalkenyl, (C2-C6) haloalkyl (C1-C4) alkoxy )
Petition 870190062787, of 07/05/2019, p. 14/17
[4]
4/5 (C1-C4) alkyl, phenyl, benzyl, halo (C1-C4) -sulfonyl, (C1-C6) alkoxycarbonyl, halo (C1-C6) -carbonyl, phenylsulfonyl, (C1-C4) -sulfonyl , C (= O) H or (C1-C3) alkylcarbonyl, and the symbol Z ⁴ represents C (= O) H, cycloalkyl (C7-C8), cycloalkyl (C3-C6) cycloalkyl (C3-C6), cycloalkenyl (C3-C6), alkoxy (C4-C6) -alkyl (C1-C4), alkoxy (C3C6) -alkyl (C2-C4), alkoxy (C1 -C3) -alkoxy (C5-C6) -alkyl (C1 -C3), (C1-C4) alkyl (C1-C2) alkyl, (C1-C4) alkyl (C1-C2) alkyl, (C1-C4) alkyl (C1-C2) alkyl, (C1-C2) alkyl ( C1-C4) -amino-alkyl (C1-C2), dialkyl (C1-C2) -aminoalkyl (C1-C2), haloalkyl (C1-C4) -amino-alkyl (C1-C2), cycloalkyl (C3-C6) amino (C1-C2) alkyl, (C5-C6) alkylcarbonyl, halo (C1-C4) -carbonyl, cycloalkyl (C3-C6) -carbonyl, cycloalkoxy (C3-C6) -carbonyl, cycloalkyl (C3-C6) ) (C1-C2) alkoxy-carbonyl, (C3-C6) cycloalkyl-halocarbonyl, (C1-C4) alkyl (C1-C2) alkyl, (C5-C6) hydroxyalkyl, (C5-C6) alkoxy (C5-) C6), cycloalkoxy (C3-C6), halocyclone (C3-C6) alkoxy, (C3-C6) cycloalkyl-alkoxy, alkenyloxy (C2-C6), haloalkenyloxy (C2-C6), alkynyloxy (C2-C6), haloalkynyloxy (C2-C6), alkoxy (C1-C4) -C1 -C4 alkoxy, (C1 -C4) haloalkyl-carbonyloxy, (C3-C6) cycloalkyl carbonyloxy, (C1-C4) alkyl-carbonyl-alkoxy (C1-C4), (C5-C6) alkyl, halo (C5C6) -thio, (C5-C6) alkylsulfinyl, halo (C5-C6) -sulfinyl, alkyl (C1-C4) -sulfonyl, halo (C1-C4) -sulfonyl, (C3-C6) cycloalkyl sulfonyl, tri ((C3-C4) alkyl) - silyl, (C1-C4) alkylsulfonylamino or halo (C1-C4) -sulfonylamino, the symbol L ³ represents a direct bond, -CH2-, sulfur or oxygen, the R ³ and R ⁴ are the same or different and independently represent hydrogen, (C1-C4) alkyl, (C2-C4) alkenyl, (C2-C4) alkynyl, (C1-C4) haloalkyl, (C5-C6) cycloalkyl, benzyl or phenyl.
3. Compounds of structural formula (I), according to claim 1, characterized in that the symbol Y represents oxygen;
the symbol R ² represents hydrogen;
the symbol Q represents Q-3;
the symbol R ⁵ represents hydrogen;
the symbol L ¹ represents a direct connection;
the symbol R ¹ represents 4,5-dimethyl-2- (prop-2-yn-1-yloxy) -phenyl or the symbol R ¹ represents 2,6-difluoro-3- (prop-2-yn-1-yloxy ) -phenyl or R ¹ represents 2,6-difluoro-4- (prop-2-yne-1-yloxy) -phenyl or
Petition 870190062787, of 07/05/2019, p. 15/17
[5]
5/5 the symbol R ¹ represents 2,6-difluoro-4 - [(methylsulfonyl) -amino] -phenyl or the symbol R ¹ represents 3- (allyloxy) -2,6-difluorophenyl.
4. Method for controlling harmful phytopathogenic fungi, characterized in that the compounds of structural formula (I), as defined in claim 1, are applied to harmful phytopathogenic fungi and / or their habitat.
5. Composition to control harmful phytopathogenic fungi, characterized by the presence of at least one compound of structural formula (I), as defined in claim 1, in addition to fillers and / or surfactants.
[6]
6. Use of compounds of structural formula (I), as defined in claim 1, characterized by being to control harmful phytopathogenic fungi in agriculture, horticulture and in forests.
[7]
7. Method for producing compositions to control harmful phytopathogenic fungi, characterized in that the compounds of structural formula (I), as defined in claim 1, are mixed with fillers and / or surfactants.
[8]
8. Use of compounds of structural formula (I), as defined in claim 1, characterized by being for treating transgenic plants.
[9]
9. Use of compounds of structural formula (I), as defined in claim 1, characterized by being for treating seeds and also seeds of transgenic plants.

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US4272417A|1979-05-22|1981-06-09|Cargill, Incorporated|Stable protective seed coating|

---

US4245432A|1979-07-25|1981-01-20|Eastman Kodak Company|Seed coatings|

---

JPS60156601A|1984-01-26|1985-08-16|Mitsubishi Petrochem Co Ltd|Herbicide for paddy field|

---

US4808430A|1987-02-27|1989-02-28|Yazaki Corporation|Method of applying gel coating to plant seeds|

---

GB8810120D0|1988-04-28|1988-06-02|Plant Genetic Systems Nv|Transgenic nuclear male sterile plants|

---

US5084082A|1988-09-22|1992-01-28|E. I. Du Pont De Nemours And Company|Soybean plants with dominant selectable trait for herbicide resistance|

---

US5198599A|1990-06-05|1993-03-30|Idaho Resarch Foundation, Inc.|Sulfonylurea herbicide resistance in plants|

---

AU684068B2|1993-03-25|1997-12-04|Syngenta Participations Ag|Novel pesticidal proteins and strains|

---

FR2734842B1|1995-06-02|1998-02-27|Rhone Poulenc Agrochimie|DNA SEQUENCE OF A HYDROXY-PHENYL PYRUVATE DIOXYGENASE GENE AND OBTAINING PLANTS CONTAINING A HYDROXY-PHENYL PYRUVATE DIOXYGENASE GENE, TOLERANT TO CERTAIN HERBICIDES|

---

US5773704A|1996-04-29|1998-06-30|Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College|Herbicide resistant rice|

---

US5876739A|1996-06-13|1999-03-02|Novartis Ag|Insecticidal seed coating|

---

US5773702A|1996-07-17|1998-06-30|Board Of Trustees Operating Michigan State University|Imidazolinone herbicide resistant sugar beet plants|

---

FR2770854B1|1997-11-07|2001-11-30|Rhone Poulenc Agrochimie|DNA SEQUENCE OF A GENE OF HYDROXY-PHENYL PYRUVATE DIOXYGENASE AND PRODUCTION OF PLANTS CONTAINING SUCH A GENE, HERBICIDE TOLERANT|

---

FR2772789B1|1997-12-24|2000-11-24|Rhone Poulenc Agrochimie|PROCESS FOR THE ENZYMATIC PREPARATION OF HOMOGENTISATE|

---

DE19821614A1|1998-05-14|1999-11-18|Hoechst Schering Agrevo Gmbh|Sugar beet mutants which are tolerant to sulfonylurea herbicides|

---

US6503904B2|1998-11-16|2003-01-07|Syngenta Crop Protection, Inc.|Pesticidal composition for seed treatment|

---

ES2414438T3|2000-03-09|2013-07-19|E.I. Du Pont De Nemours And Company|Sunflower plants tolerant to sulfonylureas|

---

DE60111613T2|2000-03-09|2006-05-18|Monsanto Technology Llc.|METHOD FOR PRODUCING GLYPHOSATE TOLERANT PLANTS|

---

US6768044B1|2000-05-10|2004-07-27|Bayer Cropscience Sa|Chimeric hydroxyl-phenyl pyruvate dioxygenase, DNA sequence and method for obtaining plants containing such a gene, with herbicide tolerance|

---

US6660690B2|2000-10-06|2003-12-09|Monsanto Technology, L.L.C.|Seed treatment with combinations of insecticides|

---

FR2815969B1|2000-10-30|2004-12-10|Aventis Cropscience Sa|TOLERANT PLANTS WITH HERBICIDES BY METABOLIC BYPASS|

---

AU1415802A|2000-12-07|2002-06-18|Syngenta Ltd|Herbicide resistant plants|

---

US20020134012A1|2001-03-21|2002-09-26|Monsanto Technology, L.L.C.|Method of controlling the release of agricultural active ingredients from treated plant seeds|

---

FR2844142B1|2002-09-11|2007-08-17|Bayer Cropscience Sa|TRANSFORMED PLANTS WITH ENHANCED PRENYLQUINON BIOSYNTHESIS|

---

US7801797B2|2003-06-17|2010-09-21|Omx Technology Ab|Trading system supporting credit rating|

---

JP2007510626A|2003-10-17|2007-04-26|アストラゼネカアクチボラグ|4- pyrimidine derivatives for use in the treatment of cancer|

---

GB0508717D0|2005-04-29|2005-06-08|Astrazeneca Ab|Chemical compounds|

---

TW200738701A|2005-07-26|2007-10-16|Du Pont|Fungicidal carboxamides|

---

EA015908B1|2005-08-31|2011-12-30|Монсанто Текнолоджи, Ллс|Insecticidal protein b.thuringiensis cry1a.105, encoding polynucleotide thereof and use thereof|

---

MY145633A|2006-03-01|2012-03-15|Theravance Inc|8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists|

---

US20070214515A1|2006-03-09|2007-09-13|E.I.Du Pont De Nemours And Company|Polynucleotide encoding a maize herbicide resistance gene and methods for use|

---

CN101405296B|2006-03-21|2014-04-30|拜尔作物科学公司|Novel genes encoding insecticidal proteins|

---

EP2030974B1|2006-06-13|2016-02-17|Shanghai Institute of Materia Medica, Chinese Academy of Sciences|Thiazole non-nucleoside compounds, their preparation, pharmaceutical composition and their use as antiviral agents|

---

WO2008013622A2|2006-07-27|2008-01-31|E. I. Du Pont De Nemours And Company|Fungicidal azocyclic amides|

---

WO2008091594A2|2007-01-24|2008-07-31|E. I. Du Pont De Nemours And Company|Fungicidal mixtures|

---

JP5337711B2|2007-01-25|2013-11-06|イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー|Bactericidal amide|

---

CN101998988A|2007-05-30|2011-03-30|先正达参股股份有限公司|Cytochrome P450 genes conferring herbicide resistance|

---

TWI428091B|2007-10-23|2014-03-01|Du Pont|Fungicidal mixtures|

---

EP2260032A2|2008-01-25|2010-12-15|E. I. du Pont de Nemours and Company|Fungicidal hetercyclic compounds|

---

AU2009206522B2|2008-01-25|2013-12-19|E. I. Du Pont De Nemours And Company|Fungicidal amides|

---

US20110039706A1|2008-04-14|2011-02-17|Marco Busch|New mutated hydroxyphenylpyruvate dioxygenase, dna sequence and isolation of plants which are tolerant to hppd inhibitor herbicides|

---

US8569509B2|2008-04-30|2013-10-29|Bayer Intellectual Property Gmbh|Thiazole-4-carboxylic acid esters and thioesters as plant protection agents|

---

CN102216296B|2008-10-01|2015-03-18|拜耳作物科学公司|Heterocyclyl-substituted thiazoles as plant protection agents|

---

AU2009322486A1|2008-12-02|2010-06-10|E. I. Du Pont De Nemours And Company|Fungicidal heterocyclic compounds|

---

EP2376487B1|2008-12-11|2016-01-06|Bayer Intellectual Property GmbH|Thiazolyl oxime ether and hydrazones as plant protection agent|

---

TWI508962B|2009-04-22|2015-11-21|Du Pont|Solid forms of an azocyclic amide|

---

EP2272846A1|2009-06-23|2011-01-12|Bayer CropScience AG|Thiazolylpiperidine derivatives as fungicide|

---

WO2011051243A1|2009-10-29|2011-05-05|Bayer Cropscience Ag|Active compound combinations|

---

PT2516426E|2009-12-21|2015-12-01|Bayer Cropscience Ag|Bispyrazoles used as fungicides|

---

KR20120112755A|2010-01-07|2012-10-11|이 아이 듀폰 디 네모아 앤드 캄파니|Fungicidal heterocyclic compounds|

---

US20120122928A1|2010-08-11|2012-05-17|Bayer Cropscience Ag|Heteroarylpiperidine and -Piperazine Derivatives as Fungicides|

---

US8759527B2|2010-08-25|2014-06-24|Bayer Cropscience Ag|Heteroarylpiperidine and -piperazine derivatives as fungicides|

---

BR112013010497B1|2010-10-27|2018-07-17|Bayer Intellectual Property Gmbh|heteroaryl - piperidine and - piperazine derivatives as fungicides, a composition comprising them, as well as a process for the production of compositions for the control of noxious phytopathogenic fungi and a method for the control of noxious phytopathogenic fungi|

---

KR20140017520A|2010-12-17|2014-02-11|이 아이 듀폰 디 네모아 앤드 캄파니|Fungicidal azocyclic amides|

---

EP2532233A1|2011-06-07|2012-12-12|Bayer CropScience AG|Active compound combinations|US4711895A|1984-10-22|1987-12-08|Teijin Limited|4-hydroxy-2-cyclopentenone, process for production thereof, pharmaceutical composition comprising it|

---

AU615534B2|1988-04-19|1991-10-03|Teijin Limited|2-substituted-2-cyclopentenones|

---

US5216183A|1988-04-19|1993-06-01|Teijin Limited|Cyclopentanone/cyclopentenone derivative|

---

DK2921493T3|2011-12-27|2017-11-27|Bayer Ip Gmbh|HETEROARYLPIPERIDINE AND ¿PIPERAZINE DERIVATIVES|

---

AU2013216354B2|2012-02-02|2017-08-31|Idorsia Pharmaceuticals Ltd|4--thiazole compounds and related aza derivatives|

---

WO2014206896A1|2013-06-24|2014-12-31|Bayer Cropscience Ag|Piperidinecarboxylic acid derivatives as fungicides|

---

JP6330040B2|2013-07-22|2018-05-23|イドーシア ファーマシューティカルズ リミテッドＩｄｏｒｓｉａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｌｔｄ|1--2- -ethanone derivatives|

---

JP6408582B2|2013-08-28|2018-10-17|バイエル・クロップサイエンス・アクチェンゲゼルシャフト|Malonic acid ester derivatives of heteroarylpiperidine and heteroarylpiperazine as fungicides|

---

TWI647215B|2013-11-11|2019-01-11|德商拜耳作物科學股份有限公司|Method for preparing 3,5-dihaloalkylpyrazole derivatives from α,α-dihalamine|

---

KR20160134845A|2014-03-24|2016-11-23|바이엘 크롭사이언스 악티엔게젤샤프트|Phenylpiperidinecarboxamide derivatives as fungicides|

---

AR099789A1|2014-03-24|2016-08-17|Actelion Pharmaceuticals Ltd|DERIVATIVES OF 8--1,2,3,4-TETRAHYDRO-ISOQUINOLINE|

---

WO2016024350A1|2014-08-13|2016-02-18|株式会社エス・ディー・エス バイオテック|Condensed 11-membered ring compounds and agricultural and horticultural fungicide containing same|

---

AR103399A1|2015-01-15|2017-05-10|Actelion Pharmaceuticals Ltd|DERIVATIVES OF-2-METHYL-PIPERAZINE AS CXCR3 RECEIVER MODULATORS|

---

JP6337218B2|2015-01-15|2018-06-06|イドーシア ファーマシューティカルズ リミテッドＩｄｏｒｓｉａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｌｔｄ|Hydroxyalkyl-piperazine derivatives as CXCR3 receptor modulators|

---

WO2016202761A1|2015-06-17|2016-12-22|Bayer Cropscience Aktiengesellschaft|Active compound combinations|

---

AU2016392652B2|2016-02-08|2021-01-21|Gowan Company, L.L.C.|Fungicidal Composition|

---

WO2018193387A1|2017-04-19|2018-10-25|Pi Industries Ltd.|Heterocyclic compounds with microbiocidal properties|

---

EP3679035A1|2017-09-08|2020-07-15|PI Industries Ltd.|Novel fungicidal heterocyclic compounds|

---

WO2019048988A1|2017-09-08|2019-03-14|Pi Industries Ltd.|Novel fungidal heterocyclic compounds|

---

CN110818708A|2018-08-14|2020-02-21|华中师范大学|Compound containing fused heterocyclic structure, preparation method and application thereof, and bactericide|

---

CN111848612B|2019-07-31|2021-09-14|华中师范大学|Compound containing fused heterocyclic structure, preparation method and application thereof, and bactericide|

法律状态:
2019-04-30| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|

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2019-05-07| B06T| Formal requirements before examination|

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2019-08-27| B09A| Decision: intention to grant|

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2019-11-05| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 11/09/2012, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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EP11181383.8|2011-09-15|

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EP11181383|2011-09-15|

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PCT/EP2012/067728|WO2013037768A1|2011-09-15|2012-09-11|Piperidine pyrazoles as fungicides|

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