TW201309680A - Thienylpyri(mi)dinylpyrazole - Google Patents

Abstract

Thienylpyri(mi)dinylpyrazole of the formula (I) in which R1 to R8 and X1 have the meanings given in the description, and agrochemically active salts, to their use and to methods and compositions for controlling phytopathogenic harmful fungi in and/or on plants or in and/or on seed of plants and for reducing mycotoxins in plants and parts of the plants, to processes for preparing such compounds and compositions and treated seed and also to their use for controlling phytopathogenic harmful fungi in agriculture, horticulture, forestry, in animal husbandry, in the protection of materials, in the domestic and hygiene field and for the reduction of mycotoxins in plants and parts of the plants.

Description

Thienylpyrimidinylpyrazole

The present invention relates to novel thienylpyrimidinylpyrazoles and their agrochemically active salts, to their use, and to plant pathogens for controlling and/or plant or/and plant seeds. Method and composition for reducing harmful fungi and reducing mycotoxins in plants and plants, methods for preparing such compounds and compositions, and treating seeds and controlling them in agriculture, horticulture, forestry, animal husbandry, and material protection The use of phytopathogenic harmful molds in homes and health, and the use of mycotoxins in plants and plant parts.

Certain arylpyrazoles are known to be useful as fungicide crop protection agents (see WO 2009/076440, WO 2003/49542 and WO 2001/30154). However, the fungicidal activity of these compounds, especially at low application rates, is not entirely sufficient.

Due to the increasing ecological and economic needs of modern crop protection agents, for example regarding activity spectrum, toxicity, selectivity, application rate, formation of residues and advantageous manufacturing, and further problems such as resistance, continued need The development of novel crop protection agents, particularly fungicides, is advantageous over some areas, compared to known fungicides.

Surprisingly, it has now been found that the thienylpyrimidinylpyrazoles of the present invention solve at least some of the above problems and are suitable for use as crop protection agents, particularly as fungicides.

Certain aryl azoles are known as pharmaceutically active compounds (see, for example, WO 1998/52937, EP-A 1 553 096, WO 2004/29043, WO 1998/52940, WO 2000/31063, WO 1995/31451, WO 2002/ 57265 and WO 2000/39116), but not surprisingly the fungicidal activity.

The present invention provides a compound of formula (I) Wherein the symbols have the following meanings: X ¹ represents CH or N, R ¹ represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -alkane Oxy, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₈ -propadienyl, C ₃ -C ₈ -trialkyldecyl, C ₄ -C ₈ -cycloalkenyl, C ₁ -C ₆ -alkoxy-C ₁ -C ₆ -alkyl, decyloxy-C ₁ -C ₆ -alkyl, heteroaryl-C ₁ -C ₆ -alkyl, aryl-C ₁ -C ₆ - Alkyl, C ₁ -C ₆ -alkylthio-C ₁ -C ₆ -alkyl, C ₁ -C ₄ -alkyl-C(O)-C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl-C(O)-C ₁ -C ₄ -alkyl, heterocyclyl-C(O)-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkyl-C(O OC ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl-C(O)OC ₁ -C ₄ -alkyl,heterocyclyl-C(O)OC ₁ -C ₄ -alkyl, Heterocyclyl-C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, heterocyclyl, heteroaryl, each of which is mono- or more optionally substituted with the same or different substituents containing R ¹⁶ Substituted, or represents H,C(O)NR ¹⁷ R ¹⁸ ,C(O)R ¹⁷ ,C(O)OR ¹⁷ ,S(O) ₂ R ¹⁷ ,C(S)NR ¹⁷ R ¹⁸ ,C(S) _{^{R 17, S (O) 2}} NR 17 R 18, R 2 represents H, cyano, halogen, or represents C ₁ -C ₆ - alkyl, C ₃ -C ₆ - cycloalkyl, Heterocyclyl, C ₂ -C ₈ - alkenyl, C ₂ -C ₈ - alkynyl, C ₁ -C ₈ - alkoxy, C ₂ -C ₈ - alkynyl group, C ₁ -C ₈ - alkoxy A thiol group, a C ₃ -C ₈ -trialkylsulfanyl group, wherein each of the substituents are mono- or polysubstituted by the same or different substituents: halogen, cyano, amine, dimethylamino Or methoxy, R ³ represents H, halogen, cyano, OR ¹¹ , C(O)OR ¹¹ , C(O)SR ¹¹ , C(S)OR ¹¹ , C(O)R ¹¹ , C(S) R ¹¹ , SR ¹¹ , NR ⁹ R ¹⁰ , C(O)NR ¹¹ R ²⁰ , C(S)NR ¹¹ R ²⁰ , N(R ¹⁷ )C(O)OR ¹¹ , N=CH-NR ¹⁷ R ¹⁸ , NH-CH-NR ¹⁷ R ¹⁸ , N=CR ¹⁷ R ¹⁸ , N(C ₁ -C ₆ -alkyl)-NHR ¹⁷ , N=C(H)OR ¹⁷ , N=C(OR ¹⁷ )R ¹⁸ , N=C(SR ¹⁷ )R ¹⁸ ,C(=NR ¹⁷ )NR ¹⁷ R ¹⁸ ,SO(=NR ¹⁷ )R ¹⁸ ,SO ₂ NR ¹¹ R ²⁰ ,SO ₂ R ¹¹ , or represent C ₁ -C ₆ - Alkyl, C ₃ -C ₈ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₈ -alkynyl, C ₆ -C ₁₄ -aryl, C ₂ -C ₉ -heterocyclyl, a C ₂ -C ₉ -heteroaryl group, wherein each of the substituents which are the same or different from R ¹⁶ is mono- or polysubstituted, and the excluded compound is wherein R ³ is a substituted NH-phenyl group, if X ¹ is N , R ⁴ and R ⁵ each independently represent H, F, Cl, Br, I, cyano, nitro, OH, SH, or represents C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₆ -C ₁₄ -aryl, C ₁ -C ₄ -alkoxy, O-(C ₆ -C ₁₄ -aryl), S-(C ₁ -C ₄ -alkyl), S(O)-(C ₁ -C ₆ -alkyl), C(O)-(C1-C ₆ -alkyl), C ₃ -C ₈ - a trialkylalkylene group, a heteroaryl group, a heterocyclic group, each of which is mono- or polysubstituted by the same or different substituents containing R ¹⁶ or formed by a carbon atom bonded thereto, and any Mono- or a plurality of the same or different halogen, oxygen, cyano or C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₆ -haloalkyl, C ₁ -C ₄ a haloalkoxy group substituted by a C ₃ -C ₆ -cycloalkyl group having 5 to 8 ring atoms, wherein the ring consists of carbon atoms but may also contain 1 to 4 selected from oxygen, sulfur or NR ^a hetero atom of ¹⁹ , R ⁶ represents C ₁ -C ₆ -alkyl, H, halogen, or represents C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₂ -C ₈ -alkenyl , C ₂ -C ₈ -alkynyl, C(O)-C ₁ -C ₆ -alkyl, C ₁ -C ₈ -alkoxy, C ₁ -C ₈ -alkylthio , C ₁ -C ₈ -haloalkoxy, C ₁ -C ₆ -alkylthioalkenyl, C ₁ -C ₆ -alkylthio, C ₃ -C ₈ -trialkyldecyl, C ₆ -C ₁₀ -aryl, heteroaryl, heterocyclic, C ₆ -C ₁₀ -aryloxy, each of which is mono- or polysubstituted by the same or different substituents containing R ¹⁶ , R ⁷ represents H, halogen, cyano, nitro, C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₅ - C ₁₀ -Aryl, heteroaryl, heterocyclyl, or R ⁶ and R ⁷ together form a 5- to 7-membered ring which may be optionally substituted with one or more substituents selected from the group consisting of C: _1- C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy, halogen, hydroxy, amine, cyano or nitro Wherein the ring consists of carbon atoms but may also contain from 1 to 4 heteroatoms selected from oxygen, sulfur or NR ¹⁹ , R ⁸ represents H, halogen, cyano, C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₆ -C ₁₀ -aryl, heteroaryl, heterocyclic, R ⁹ and R ¹⁰ represent H,C (S)R ¹⁴ , C(O)R ¹⁴ , SO ₂ R ¹⁴ , C(O)OR ¹⁴ ,OR ¹⁴ or C(O)NR ¹⁴ R ¹⁵ , or represents C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₈ -cycloalkyl, heterocyclyl or heteroaryl, each of which is mono- or polysubstituted by the same or different substituents: F, Cl, Br, OH, cyano, C ₁ -C ₆ -alkyl, OC(O)R ¹⁷ , OP(O)(OR ¹⁷ ) ₂ , OB(OR ¹⁷ ) ₂ or O-(C ₁ -C ₄ -alkyl), R ¹¹ and R ²⁰ represents H, C(S)R ¹² , C(O)R ¹² , SO ₂ R ¹² , C(O)OR ¹² , OR ¹² or C(O)NR ¹² R ¹³ , or represents C ₁ -C ₆ - Alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₄ -aryl, heterocyclyl or heteroaryl, each of which Any mono- or polysubstituted by the same or different substituents: F, Cl, Br, OH, cyano, C ₁ -C ₆ -alkyl, OC(O)R ¹⁷ , OP(O) (OR ¹⁷ ) ₂ , OB(OR ¹⁷ ) ₂ or O-(C ₁ -C ₄ -alkyl), R ¹² and R ¹³ represent H, or represent C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₄ -aryl, heterocyclyl or heteroaryl, Each of them is the same or With the following substituents contains mono - or substituted: F, Cl, Br, I , OH, carbonyl, cyano, C ₁ -C ₆ - alkyl or C ₁ -C ₄ - alkoxy, R ^14, and R ¹⁵ represents H, or represents C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₈ - a cycloalkyl group, a C ₆ -C ₁₄ -aryl group, a benzyl group, a phenethyl group, a phenoxymethyl group, a heterocyclic group or a heteroaryl group, each of which is independently or identically substituted with the following substituents - or polysubstituted: F, Cl, Br, I, OH, carbonyl, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second butyl (butyl ), tert-butyl, n-pentyl, cyclopropyl, or methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, methylsulfanyl , nitro, trifluoromethyl, difluoromethyl, C(O)R ¹⁷ , C(O)OR ¹⁷ , C(O)NR ¹⁷ R ¹⁸ , SO ₂ R ¹⁷ , OC(O)R ¹⁷ ,R ¹⁶ represents OH, F, Cl, Br, I, cyano, NH-C(O)R ¹⁷ , NR ¹⁷ R ¹⁸ , C(O)R ¹⁷ , C(O)OR ¹⁷ , C(O)NR ¹⁷ R _{^{18, SO 2 R 17, OC}} (O) R 17, or represents C ₁ -C ₆ - alkyl, C ₂ -C ₆ - Group, C ₂ -C ₆ - alkynyl, C ₃ -C ₈ - cycloalkyl, C ₁ -C ₄ - alkoxy, C ₁ -C ₄ - alkylthio, O- (C ₃ -C ₈ -cycloalkyl), S-(C ₃ -C ₈ -cycloalkyl), C ₆ -C ₁₄ -aryl, O-(C ₆ -C ₁₄ -aryl), S-(C ₆ -C ₁₄ -aryl),heterocyclyl or heteroaryl, each of which is mono- or polysubstituted by the same or different substituents: F, Cl, Br, I, OH, carbonyl, cyano, C ₁ -C ₆ -alkyl or C ₁ -C ₄ -alkoxy, R ¹⁷ and R ¹⁸ represent C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -ene a C ₂ -C ₆ -alkynyl group, a benzyl group, an aryl group, each of which is mono- or polysubstituted by the same or different substituents: F, Cl, Br, OH, cyano, or H, R ¹⁹ represents H, C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(S)R ¹⁴ , C(O)R ¹⁴ , SO ₂ R ¹⁴ , C(O)OR ¹⁴ , and agrochemically active salts thereof.

The invention also provides the use of a compound of formula (I) as a fungicide.

The thienylpyrimidinylpyrazole of the formula (I) according to the present invention and an agrochemically active salt thereof are highly suitable for controlling phytopathogenic harmful molds and for reducing mycotoxins. The above-mentioned compounds according to the present invention have strong fungicidal activity and are useful for crop protection in homes and sanitary fields for protecting substances and reducing mycotoxins in plants and plant parts.

The compounds of formula (I) may exist in pure form and in mixtures of various possible isomeric forms, especially stereoisomers such as E and Z, threo and erythro, and optical isomers such as R and S isomers or Isomerism, and, if appropriate, as well as tautomers. Requested are both E and Z isomers, and sulphate and erythro, as well as optical isomers, mixtures of these isomers, and possible tautomeric forms.

Preferred are compounds of formula (I) wherein one or more symbols have one of the following meanings: X ¹ represents CH, R ¹ represents H, methyl, ethyl, n-propyl, isopropyl, n-butyl , isobutyl, second butyl, tert-butyl, n-pentyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, -CH=CHCH ₃ ,-C≡CCH ₃ ,3-methylbut-2-en-1-yl,but-2-en-1-yl,but-3-en-2-yl,prop-2-yn-1-yl ,but-2-yn-1-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, 1-cyclopropylethyl, -CH=C=CH ₂ , trimethyl Base alkyl, tert-butyldimethylalkyl, cyclohexenyl, 2-methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, Tributoxy-methyl, cyanomethyl, 1-cyanoethyl, 2-cyanoethyl, 1-cyanopropan-2-yl, trifluoromethyl, difluoromethyl, 2-fluoro Ethyl, 2,2-difluoroethyl, 1,3-difluoropropan-2-yl, 2-chloroethyl, (2,2-dichlorocyclopropyl)methyl, trifluoromethoxy, Difluoromethoxy, 2-(trifluoromethoxy)ethyl, methyl acetate, ethyl acetate, pyridin-2-ylmethyl, pyridine-3 -ylmethyl, pyridin-4-ylmethyl, (1,3-thiazol-5-yl)methyl, (1,3-thiazol-4-yl)methyl, (1,3-thiazole-3- Methyl), (1,3- Azole-5-yl)methyl, (1,3- -4-yl)methyl, (1,3- 3-yl)methyl, phenylmethyl, phenylethyl, methylthio, ethylthio, n-propylthio, isopropylthio, tert-butylthio, n-butyl Thio, tert-butylthio, isobutylthio, methylthioalkyl, phenyl, benzyl, naphthyl, oxiranyl, aziridine, 2-tetrahydrofuranyl, 3- Tetrahydrofuranyl, tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-4-yl, 2-tetrahydrothiophenyl, 3-tetrahydro Thienyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-iso Zyridinyl, 4-iso Zyridinyl, 5-iso Zyridinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidine, 5-pyrazolidine, 2- Azolidinyl, 4- Zyridinyl, 5- Zyridinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 2-pyrroline-2-yl, 2-pyrroline-3- Base, 3-pyrolin-2-yl, 3-pyrroline-3-yl, 2-iso Oxazolin-3-yl, 3-iso Oxazolin-3-yl, 4-iso Oxazolin-3-yl, 2-iso Oxazolin-4-yl, 3-iso Oxazolin-4-yl, 4-iso Oxazolin-4-yl, 2-iso Oxazoline-5-yl, 3-iso Oxazoline-5-yl, 4-iso Oxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-iso Thiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2-hexa Hydropyridyl, 3-hexahydropyridyl, 4-hexahydropyridyl, 1,3-di Alkan-5-yl, 2-tetrahydropyranyl, 4-tetrahydropiperidyl, 2-tetrahydrothiophenyl, 3-hexahydro-indole Base, 4-hexahydroindole Base, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-hexahydropyridyl Base, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, iso Zin-3-yl, different Azole-4-yl, different Zyrid-5-yl, 1H-pyrrol-1-yl, 1H-pyrrol-2-yl, 1H-pyrrol-3-yl, Zin-2-yl, Azole-4-yl, Zyrid-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazole-1- , pyrazol-3-yl, pyrazol-4-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4- Base -3-base, 嗒 4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridyl -2-yl, morpholine, wherein each of the substituents which are identical or different from R ¹⁶ is mono- or polysubstituted, or represents H,C(O)NR ¹⁷ R ¹⁸ ,C(O)R ¹⁷ , C(O)OR ¹⁷ , S(O) ₂ R ¹⁷ , C(S)NR ¹⁷ R ¹⁸ , C(S)R ¹⁷ , S(O) ₂ NR ¹⁷ R ¹⁸ , R ² represents H, cyano group, Br, Cl, F, or represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropyl, cyclobutyl , cyclopentyl, cyclohexyl, -CH ₂ CH=CH ₂ , -C≡CH, -C≡CCH ₃ , -CH ₂ C≡CH, methoxy, ethoxy, n-propoxy, isopropyl Oxyl, n-butoxy, tert-butoxy, -O-CH ₂ C≡CH, methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl, Tributylsulfanyl, n-butylsulfanyl, t-butylsulfanyl, isobutylsulfanyl, trimethyldecyl, each of which is the same or different substituents Mono- or polysubstituted: F, Cl, Br, cyano, amine, dimethylamino or methoxy, R ³ represents H, F, Cl, Br, cyano, OR ¹¹ , C(O)OR ¹¹ , C(O)R ¹¹ , NR ⁹ R ¹⁰ , C(O)NR ¹¹ R ²⁰ , N=C(OR ¹⁷ )R ¹⁸ , N=C(SR ¹⁷ )R ¹⁸ ,SO(=NR ¹⁷ )R ¹⁸ ,N(C ₁ -C ₆ -alkyl )-NHR ¹⁷ , or represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropyl, cyclobutyl , cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, -CH=CHCH ₃ , -C≡CCH ₃ , but-2- Alken-1-yl, but-3-en-2-yl, but-2-yn-1-yl, phenyl, benzyl, each of which is mono- ordinarily substituted with the same or different substituents containing R ¹⁶ - Or polysubstituted, R ⁴ , R ⁵ each independently represent H, F, Cl, Br, cyano, nitro, OH, SH, or represents methyl, ethyl, cyclopropyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , —CH ₂ C≡CH, —C≡CH, phenyl, methoxy, each of which is mono- or polysubstituted by the same or different substituents containing R ¹⁶ , or the like The bonded carbon atoms are formed together, any one- or more of the same or different F, Cl, Br, oxygen, cyano or alkyl, cycloalkyl, heterocyclic, haloalkyl, alkoxy, An aryl group substituted with a heteroaryl group has 5 8 ring atoms, wherein the ring consists of carbon atoms, but may contain 1 to 4 heteroatoms selected from oxygen, sulfur or NR ¹⁹ hetero atoms of, R ⁶ representatives of H, Cl, F, methyl, ethyl, cyanomethyl , difluoromethyl, trifluoromethyl, or represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, methoxy, ethoxy, positive Propyloxy, isopropoxy, n-butoxy, tert-butoxy, methylthio, ethylthio, n-propylthio, isopropylthio, tert-butylthio, positive Butylthio, second butylthio, isobutylthio, each of which is mono- or polysubstituted by the same or different substituents containing R ¹⁶ and R ⁷ represents H, F, Cl, Br , cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropyl, cyclobutyl , cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, or R ⁶ and R ⁷ together A 5- to 7-membered ring may be formed which may be optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, trifluoromethyl, methoxy, trifluoromethoxy, F, Cl, Br, hydroxy, amine, cyano or nitro, wherein the ring consists of carbon atoms but may also contain from 1 to 4 heteroatoms selected from oxygen, sulfur or NR ¹⁹ and R ⁸ represents H, F, Cl ,Br,cyano,methyl,ethyl, n-propyl,isopropyl, n-butyl, isobutyl, second butyl, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, Cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, R ⁹ and R ¹⁰ represent H,C(S)R ¹⁴ ,C( O) R ¹⁴ , SO ₂ R ¹⁴ , C(O)OR ¹⁴ , OR ¹⁴ or C(O)NR ¹⁴ R ¹⁵ , R ¹¹ and R ²⁰ represent H, C(S)R ¹² , C(O)R ¹² , SO ₂ R ¹² , C(O)OR ¹² , OR ¹² or C(O)NR ¹² R ¹³ , or represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, Dibutyl, tert-butyl, n-pentyl, OC(O)Me, OC(O)Et, OP(O)(OMe) ₂ , OB(OMe) ₂ , OB(OEt) ₂ or, methoxy Base, ethoxy, n-propoxy, isopropoxy, n-butoxy, third butoxy Substituted methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, Cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, phenyl, each of which is singularly the same or different substituents containing the following - or Multiple substitution: F, Cl, Br, OH, cyano, R ¹² and R ¹³ represent H, or represent methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl , tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH , phenyl, each of which is mono- or polysubstituted by the same or different substituents: F, Cl, Br, I, OH, carbonyl, cyano, methyl, ethyl, n-propyl, Isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl or methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, Tributoxy, R ¹⁴ and R ¹⁵ represent H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, Second butyl, tert-butyl, n-pentyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ ,- CH ₂ C≡CH,-C≡CH,phenyl,naphthyl,benzyl,phenethyl,phenoxymethyl,pyridyl,pyridyl Base, pyrimidinyl, furyl, thienyl, thioantyl, Tenchyl, pyrazolyl, imidazolyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, pyrrolidinyl, hexahydropyridyl, hydroquinone, wherein each of the following is substituted by the same or different Mono- or poly-substitution: F, Cl, Br, I, OH, carbonyl, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, Tert-butyl, n-pentyl, cyclopropyl, or methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, methylsulfanyl, nitrate Base, trifluoromethyl, difluoromethyl, acetamidine, methoxycarbonyl, ethoxycarbonyl, or hydrogen, R ¹⁶ represents OH, F, Cl, Br, I, cyano, NH-C (O R ¹⁷ ,NR ¹⁷ R ¹⁸ ,C(O)R ¹⁷ ,C(O)OR ¹⁷ ,C(O)NR ¹⁷ R ¹⁸ ,SO ₂ R ¹⁷ , or represent methyl, ethyl, n-propyl, iso Propyl, n-butyl, isobutyl, t-butyl, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH =CH ₂ , -CH ₂ C≡CH, -C≡CH, phenyl, methoxy, ethoxy, tetrahydrofuranyl, 3-tetrahydrofuranyl, 2 -pyrrolidinyl, 3-pyrrolidinyl, 3-iso Zyridinyl, 4-iso Zyridinyl, 5-iso Zyridinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidine, 5-pyrazolidine, 2- Azolidinyl, 4- Zyridinyl, 5- Zyridinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 2-pyrroline-2-yl, 2-pyrroline-3- Base, 3-pyrolin-2-yl, 3-pyrroline-3-yl, 2-iso Oxazolin-3-yl, 3-iso Oxazolin-3-yl, 4-iso Oxazolin-3-yl, 2-iso Oxazolin-4-yl, 3-iso Oxazolin-4-yl, 4-iso Oxazolin-4-yl, 2-iso Oxazoline-5-yl, 3-iso Oxazoline-5-yl, 4-iso Oxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-iso Thiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2-hexa Hydropyridyl, 3-hexahydropyridyl, 4-hexahydropyridyl, 2-hexahydropyridyl Base, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, iso Zin-3-yl, different Azole-4-yl, different Zyrid-5-yl, 1H-pyrrol-1-yl, 1H-pyrrol-2-yl, 1H-pyrrol-3-yl, Zin-2-yl, Azole-4-yl, Zyrid-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazole-1- , pyrazol-3-yl, pyrazol-4-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4- Base -3-base, 嗒 4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridyl a 2-yl group, each of which is mono- or polysubstituted by the same or different substituents: F, Cl, Br, I, OH, carbonyl, cyano, methyl, ethyl, methoxy , R ¹⁷ and R ¹⁸ represent methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropyl, cyclobutyl , cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, benzyl, each of which is substituted by the same or different Mono- or poly-substituted: F, Cl, Br, OH, cyano, or represents H, R ¹⁹ represents H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, Second butyl, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, C(S)R ¹⁴ , C(O)R ¹⁴ , SO ₂ R ¹⁴ , C(O)OR ¹⁴ , and agrochemically active salts thereof.

Particularly preferred are compounds of formula (I) wherein one or more symbols have one of the following meanings: X ¹ represents CH, R ¹ represents H, methyl, ethyl, propyl, isopropyl, isobutyl, second Butyl, allyl, 3-methylbut-2-en-1-yl, prop-2-yn-1-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H -pyran-2-yl, tetrahydrofuran-3-yl, Tan-3-yl, thitan-3-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-4-yl, 2,2-difluoroethyl, 1,3- Difluoropropan-2-yl, 2-chloroethyl, 2-fluoroethyl, 2-(trifluoromethoxy)ethyl, cyanomethyl, 1-cyanoethyl, 2-cyanoethyl , 1-cyanopropan-2-yl, 2-methoxyethyl, 2-ethoxyethyl, 2-(methylsulfanyl)ethyl, cyclopropylmethyl, 1-cyclopropyl Ethyl, (2,2-dichlorocyclopropyl)methyl, 2-fluorobenzyl, 1-(2-fluorophenyl)ethyl, 3-cyanobenzyl, R ² represents H, methyl, Ethyl, n-propyl, methoxy, ethoxy, methylsulfanyl, methoxymethyl, difluoromethyl, 2-hydroxyprop-2-yl, hydroxymethyl, 2-hydroxyethyl , 2-cyanoethyl, R ³ represents H, amine, formamide, ethenyl, propionyl amine, isobutylguanidino, (2-methylbutylidene) amine , (3-methylbutyridinium)amino, (3,3-dimethylbutyryl)amino, (methoxyethyl hydrazide) amine, [(2-methoxyethoxy) acetyl] Amino, (3,3,3-trifluoropropanoyl)amine, (cyanoethenyl)amine, (lactoamine), (2-hydroxy-2-methylpropenyl) Amine, [(methyl sulphur) Alkyl)ethylamino, [2-(4-chlorophenoxy)propanyl]amino, (phenylethyl)amino, (3-phenylpropenyl)amine, [3 -(4-chlorophenyl)propanyl]amino, [2-(4-fluorophenyl)propanyl]amino, [2-(2-fluorophenyl)propanyl]amine, Cyclopentyl hydrazide), (cyclopropylethyl hydrazide) amine, (cyclopropylcarbonyl)amino, [(2-methylcyclopropyl)carbonyl]amino, [(1-chlorocyclopropane) Alkyl)carbonyl, (cyclobutylcarbonyl)amino, (2,3-dihydro-1H-indol-2-ylcarbonyl)amino, [(2-phenylcyclopropyl)carbonyl]amino , methacrylamidylamino, (3-methylbut-2-enyl)amino, (4-methylpent-3-enyl)amino, (benzamide), 4-fluorobenzhydrazide)amino, (3-thienylcarbonyl)amino, (2-thienylcarbonyl)amino, (tetrahydrofuran-2-ylcarbonyl)amino, (tetrahydrofuran-3-ylcarbonyl)amine , (tetrahydro-2H-pyran-4-ylcarbonyl)amino, (methoxycarbonyl)amino, (ethoxycarbonyl)amino, (isopropoxycarbonyl)amino, (third Butoxycarbonyl)amine,diethylammonium,dipropylamino,diisobutylamino, bis(methoxyethyl)amino, bis(3-methylbutyl)amino Bis(cyclopropylcarbonyl)amino, bis(cyclopropylcarbonyl)amino, acetamidine (isobutyl) amide, butyl fluorenyl (cyclopropylcarbonyl) amine, (cyclopropylcarbonyl) (propionyl)amine (cyclopropylcarbonyl)(methoxyethyl hydrazide)amine, (cyclopropylcarbonyl)(3-methylbutylidene)amino, (cyclopropylcarbonyl)(pentamethylene)amine, different Butyl (propyl) amine, (cyclopropylcarbonyl) (methoxycarbonyl) amine, (cyclopropylcarbonyl) (ethoxycarbonyl) amine, [(E)-(dimethylamino) Methyl]amino, methylaminoformamidine, (ethylaminomethylhydrazine) amine group, R ⁴ , R ⁵ represents H, F, Cl, or a carbon atom bonded thereto, optionally Single- or multiple identical or different F, Cl, Br, oxygen, cyano, methyl, ethyl, n-propyl, isopropyl, methoxy, trifluoromethyl, difluoromethyl, three a ring substituted with fluoromethoxy, cyclopropyl, cyclopropylmethyl, cyclobutyl, wherein they together represent -(CH=CH-N(R ¹⁹ ), -(CH=CH-CH=N) -, -(NH-CH=N)- or -(CH ₂ -C(O)-N(R ¹⁹ ), R ⁶ represents H, Cl, F, methyl, ethyl, cyano, difluoromethyl , trifluoromethyl, R ⁷ represents H, F, Cl, methyl, R ⁸ represents H, Cl, and R ¹⁹ represents H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropyl , cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, ethyl hydrazine, n-propionium, isobutyl fluorenyl, 2- Methyl butyl hydrazine, 3-methylbutyl hydrazine, 3,3-dimethylbutyl hydrazine, cyclopropyl carbonyl, and agrochemically active salts thereof.

Particularly preferred are compounds of formula (I) wherein one or more symbols have one of the following meanings: X ¹ represents CH, R ¹ represents H, methyl, ethyl, propyl, isopropyl, isobutyl, Dibutyl, cyclopropyl, 2,2-difluoroethyl, 1,3-difluoropropan-2-yl, 2-chloroethyl, 2-cyanoethyl, 1-cyanoprop-2- Base, 2-methoxyethyl, 2-ethoxyethyl, cyclopropylmethyl, R ² represents H, methyl, R ³ represents H, acetamino, n-propylamine, isobutyl fluorenyl Amino, (2-methylbutyridinium)amine, (3-methylbutyridinium)amine, (methoxyethyl)amino, (lactoamine), (2-hydroxy-2-methyl) Amino group, (phenyl acetamidine) amine group, (cyclopropyl acetamidine) amine group, (cyclopropylcarbonyl) amine group, [(2-methylcyclopropyl)carbonyl]amino group , (cyclobutylcarbonyl)amino, methacrylamidylamino, (3-methylbut-2-enyl)amino, (benzylamino), (3-thienylcarbonyl)amine , (2-thienylcarbonyl)amino group, R ⁴ represents H, R ⁵ represents H, F, R ⁶ represents H, F, Cl, methyl, R ⁷ represents H, R ⁸ represents H, and the like Agrochemical active salts.

Particularly preferred are also compounds of formula (I) wherein X ¹ represents CH, wherein the other substituents have one or more of the above-mentioned meanings, as well as agrochemically active salts thereof.

Very particularly preferred are compounds of formula (I) wherein R ¹ represents H, methyl, ethyl, propyl, isopropyl, isobutyl, second butyl, cyclopropyl, 2,2-difluoro. Ethyl, 1,3-difluoropropan-2-yl, 2-chloroethyl, 2-cyanoethyl, 1-cyanopropan-2-yl, 2-methoxyethyl, 2-ethoxy Alkylethyl, cyclopropylmethyl, wherein the other substituents have one or more of the above-mentioned meanings, as well as agrochemically active salts thereof.

Particularly preferred are also compounds of formula (I) wherein R ² represents H, methyl, wherein the other substituents have one or more of the above-mentioned meanings, as well as agrochemically active salts thereof.

Very particularly preferred are compounds of formula (I) wherein R ³ represents H, acetamido, n-propylamino, isobutyl decylamino, (2-methylbutyridinium) amine, (3-methyl Amino, (methoxyethyl) amine, (lactoamine), (2-hydroxy-2-methylpropanyl) amine, (phenylethyl) amine, (ring Acryl)amino, (cyclopropylcarbonyl)amino, [(2-methylcyclopropyl)carbonyl]amino, (cyclobutylcarbonyl)amino, methacrylamidoamine, 3-methylbut-2-enyl)amino, (benzylamino), (3-thienylcarbonyl)amino, (2-thienylcarbonyl)amino, wherein the other substituent has one Or a plurality of the above-mentioned meanings, and the agrochemically active salts thereof.

Very particularly preferred are compounds of formula (I) wherein R ⁴ represents H, wherein the other substituents have one or more of the above-mentioned meanings, as well as agrochemically active salts thereof.

Particularly preferred are also compounds of formula (I) wherein R ⁵ represents H, F, wherein the other substituents have one or more of the above-mentioned meanings, as well as agrochemically active salts thereof.

Particularly preferred are also compounds of formula (I) wherein R ⁶ represents H, F, Cl, methyl, wherein the other substituents have one or more of the above-mentioned meanings, as well as agrochemically active salts thereof.

Very particularly preferred are also compounds of formula (I) wherein R ⁷ represents H, wherein the other substituents have one or more of the above-mentioned meanings, as well as agrochemically active salts thereof.

Very particularly preferred are compounds of formula (I) wherein R ⁸ represents H, wherein the other substituents have one or more of the above-mentioned meanings, as well as agrochemically active salts thereof.

The definition of the above groups can be combined with the other. Furthermore, individual definitions may not apply.

Depending on the nature of the substituents defined above, the compounds of formula (I) have acidic or basic character and can form salts, if appropriate also form internal salts, or form adducts with inorganic or organic acids or with bases or metal ions. . If the compound of the formula (I) carries an amine group, an alkylamino group or other group which induces a basic character, these compounds can be reacted with an acid to obtain a salt, or the like can be directly salted in the synthesis method. The class gets. If the compound of formula (I) carries a hydroxyl group, a carboxyl group or other group which induces acidic characteristics, these compounds can be reacted with an alkali acid to obtain a salt. Suitable bases are, for example, alkali metal and alkaline earth metals, especially sodium, potassium, magnesium and calcium hydroxides, carbonates, hydrogencarbonates, further ammonia, having (C ₁ -C ₄ )-alkyl groups The first, second and third amines, (C ₁ -C ₄ )-alkanol mono-, di- and trialkanolamines, choline and choline.

Salts obtainable in this manner also have fungicidal properties.

Examples of inorganic acids are hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid and hydroiodic acid, sulfuric acid, phosphoric acid and nitric acid, and acidic salts such as NaHSO ₄ and KHSO ₄ . Suitable organic acids are, for example, formic acid, carbonic acid and alkanoic acids such as acetic acid, trifluoroacetic acid, trichloroacetic acid and propionic acid, and glycolic acid, thiocyanate, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid , oxalic acid, alkylsulfonic acid (sulfonic acid having a linear or branched alkyl group of 1 to 20 carbon atoms), arylsulfonic acid or aryl disulfonic acid (aromatic group such as phenyl and naphthyl, It carries one or two sulfonic acid groups), an alkylphosphonic acid (phosphonic acid having a linear or branched alkyl group of 1 to 20 carbon atoms), an arylphosphonic acid or an aryl diphosphonic acid (aromatic a group, such as phenyl and naphthyl, which carries one or two phosphonic acid groups, wherein the alkyl and aryl groups may carry other substituents, such as p-toluenesulfonic acid, salicylic acid, Aminosalicylic acid, 2-phenoxybenzoic acid, 2-ethoxylated benzoic acid, and the like.

Suitable metal ions are particularly ions of the second main group element, particularly calcium and magnesium, ions of the third and fourth main group elements, particularly aluminum, tin and lead, and ions of the first to eighth transition elements, Especially for chromium, manganese, iron, cobalt, nickel, copper, zinc and others. Particularly preferred is the metal ion of the fourth periodic element. Herein, the metal may exist in a variety of measurable valences.

Any substituted group may be mono- or polysubstituted, and when polysubstituted, the substituents may be the same or different.

In the definition of the symbols given in the above formula, collective terminology is used, which is usually represented by the following substituents: halogen: fluorine, chlorine, bromine and iodine; aryl: unsubstituted or optionally substituted 6 - to a 14-membered partially or fully unsaturated mono-, bi- or tricyclic ring system having at most 3 ring members selected from the group consisting of C(=O), (C=S), at least one of which The ring in the system is completely unsaturated, such as, but not limited to, benzene, naphthalene, tetrahydronaphthalene, anthracene, hydroquinone, phenanthrene, anthracene; alkyl: saturated, linear or branched having from 1 to 8 a hydrocarbyl group of a carbon atom, such as, but not limited to, a C ₁ -C ₆ -alkyl group such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl , 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropane Base, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl Base, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2 ,3-dimethyl Base, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-Ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl; alkenyl: unsaturated, straight-chain or branched hydrocarbon group having 2 to 8 carbon atoms and a double bond at any position For example, but not limited to, C ₂ -C ₆ -alkenyl, such as ethenyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-butenyl , 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentyl Alkenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1- Butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2- Methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2- Dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexyl Alkenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl 1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl , 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl- 3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butene Alkenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-di Methyl-2-butenyl, 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-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2- Propylene, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl; alkyne : Having from 2 to 8 carbon atoms and a triple bond in a straight or branched hydrocarbon chain of any location, such as (but not limited to) C ₂ -C ₆ - alkynyl, such as ethynyl, 1-propynyl, 2 -propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentyne Base, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butyne 1,1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl , 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl , 2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl- 2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-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-butynyl and 1-ethyl-1-methyl-2-propynyl; alkoxy: having a saturation of 1 to 8 carbon atoms Straight-chain or branched alkoxy, such as (but not limited to) C ₁ -C ₆ - alkoxy, such as methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy , 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3- Methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy , 1-methylpentyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethylbutoxy, 1,2-dimethyl Butyloxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1 -ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methyl Propyloxy and 1-ethyl-2-methylpropoxy; alkylthio: a saturated, straight-chain or branched alkylthio group having from 1 to 8 carbon atoms, such as, but not limited to, ) C ₁ -C ₆ - alkylthio, such as methylthio, ethylthio, propylthio, 1-methylethyl, butylthio, 1- Propyl propyl, 2-methylpropylthio, 1,1-dimethylethylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2- Dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1,1-dimethyl Butyl thio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutyl Thiothio, 3,3-dimethylbutylthio, 1-ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1, 2,2-Trimethylpropylthio, 1-ethyl-1-methylpropylthio and 1-ethyl-2-methylpropylthio; alkoxycarbonyl: 1 to 6 An alkoxy group of a carbon atom (as described above) which is attached to the backbone via a carbonyl group (-CO-); an alkylsulfinyl group: saturated with from 1 to 8 carbon atoms, straight or Branched alkylsulfinyl group, such as, but not limited to, a C ₁ -C ₆ -alkylsulfinyl group, such as methyl Sulfonyl, ethylsulfinyl, propylsulfinyl, 1-methylethylsulfinyl, butylsulfinyl, 1-methylpropylsulfinyl, 2-methyl Propyl sulfinyl, 1,1-dimethylethylsulfinyl, pentylsulfinyl, 1-methylbutylsulfinyl, 2-methylbutylsulfinyl , 3-methylbutylsulfinyl, 2,2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl, hexylsulfinyl, 1,1-dimethyl Propylsulfinyl, 1,2-dimethylpropylsulfinyl, 1-methylpentylsulfinyl, 2-methylpentylsulfinyl, 3-methylpentyl Sulfhydryl, 4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl, 1,2-dimethylbutylsulfinyl, 1,3-dimethyl Butylsulfinyl, 2,2-dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl, 3,3-dimethylbutylsulfinyl, 1 -ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfin Sulfhydryl, 1-ethyl-1-methylpropylsulfinyl and 1-ethyl-2-methylpropylsulfinyl; alkylsulfonyl: a saturated, straight or branched alkylsulfonyl group having from 1 to 8 carbon atoms, such as, but not limited to, a C ₁ -C ₆ -alkylsulfonyl group, such as methylsulfonyl, Sulfosyl, propylsulfonyl, 1-methylethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl, 2-methylpropylsulfonyl, 1,1 - dimethylethylsulfonyl, pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonyl, 3-methylbutylsulfonyl, 2,2- Dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, hexylsulfonyl, 1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl, 1-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentylsulfonyl, 1,1-dimethylbutylsulfonate Mercapto, 1,2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 2,3-dimethylbutyl Sulfosyl, 3,3-dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1,1,2-trimethylpropylsulfonate Indenyl, 1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropylsulfonyl and 1-ethyl-2- Methylpropylsulfonyl; cycloalkyl: a monocyclic ring having 3 to 10 carbon ring members, a saturated hydrocarbyl group such as, but not limited to, a cyclopropyl group, a cyclopentyl group and a cyclohexyl group; A straight or branched alkyl group having from 1 to 8 carbon atoms (as described above), wherein some or all of the hydrogen atoms in these groups may be replaced by a halogen atom as described above, for example ( But not limited to this) C ₁ -C ₃ -haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloro Fluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2 , 2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2, 2-trichloroethyl, pentafluoroethyl and 1,1,1-trifluoropropan-2-yl; haloalkoxy: a linear or branched alkoxy group having from 1 to 8 carbon atoms (as above a), where in these groups some or all of the hydrogen atoms may be replaced by halogen atoms as mentioned above, the example (but not limited to) C ₁ -C ₃ - alkoxy halo Such as chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoro Methoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2 , 2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and 1,1,1-trifluoroprop-2-yl; haloalkylthio: straight chain having from 1 to 8 carbon atoms or a branched alkylthio group (as described above) wherein some or all of the hydrogen atoms in these groups may be replaced by a halogen atom as described above, such as, but not limited to, C ₁ -C ₃ -haloalkylthio, such as chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethyl Thiothio, chlorofluoromethylthio, dichlorofluoromethylthio, chlorodifluoromethylthio, 1-chloroethylthio, 1-bromoethylthio, 1-fluoroethylthio , 2-fluoroethylthio, 2,2-difluoroethane Sulfuryl, 2,2,2-trifluoroethylthio, 2-chloro-2-fluoroethylthio, 2-chloro-2,2-difluoroethylthio, 2,2-dichloro- 2-fluoroethylthio, 2,2,2-trichloroethylthio, pentafluoroethylthio and 1,1,1-trifluoropropan-2-ylthio; heteroaryl: a 5 Or a 6-membered fully unsaturated monocyclic ring system containing one to four heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur; if the ring contains a plurality of oxygen atoms, these are not directly adjacent; Heteroaryl containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom: a 5-membered heteroaryl group which, in addition to a carbon atom, may contain one to four nitrogen atoms or one to three a nitrogen atom and a sulfur or oxygen atom as a ring element, such as, but not limited to, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-different Azolyl, 4-iso Azolyl, 5-iso Azyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2- Azolyl, 4- Azolyl, 5- Azyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 1,2,4- Diazol-3-yl, 1, 2, 4- Oxazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1, 3,4- Diazol-2-yl, 1,3,4-thiadiazol-2-yl and 1,3,4-triazol-2-yl; 5-membered heteroaryl, which are linked via nitrogen and contain one to four a nitrogen atom, or a benzo-fused 5-membered heteroaryl group, which is bonded via nitrogen and contains one to three nitrogen atoms: a 5-membered heteroaryl group which, in addition to a carbon atom, may contain one to four nitrogen atoms And one to three nitrogen atoms, respectively, as a ring member and two of the adjacent carbon ring members or nitrogen and an adjacent carbon ring member may be bridged by a butane-1,3-diene-1,4-diyl group One or two carbon atoms may be replaced by a nitrogen atom, wherein these rings are attached to the backbone via one of the nitrogen ring members, such as, but not limited to, 1-pyrrolyl, 1-pyrazolyl, 1,2,4-triazol-1-yl, 1-imidazolyl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl; 6-membered heteroaryl , which contains one to four nitrogen atoms: a 6-membered heteroaryl group which, in addition to a carbon atom, may contain one to three or one to four nitrogen atoms as ring members, such as, but not limited to, 2-pyridine Base, 3-pyridyl, 4-pyridyl, 3-anthracene Base, 4-嗒 Base, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyridyl Base, 1, 3, 5 - three -2-base, 1, 2, 4-three -3-yl and 1,2,4,5-four 3-yl; benzo-fused 5-membered heteroaryl containing one to three nitrogen atoms or a nitrogen atom and an oxygen or sulfur atom: for example, but not limited to, 1H-indol-1-yl ,1H-indol-2-yl, 1H-indol-3-yl, 1H-indol-4-yl, 1H-indol-5-yl, 1H-indol-6-yl, 1H-indole -7-yl, 1H-benzimidazol-1-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, benzimidazol-5-yl, 1H-carbazole-1- ,1H-indazol-3-yl, 1H-indazol-4-yl, 1H-indazol-5-yl, 1H-indazol-6-yl, 1H-carbazole-7-yl, 2H-indole Zin-2-yl, 1-benzofuran-2-yl, 1-benzofuran-3-yl, 1-benzofuran-4-yl, 1-benzofuran-5-yl, 1-benzo Furan-6-yl, 1-benzofuran-7-yl, 1-benzothiophen-2-yl, 1-benzothiophen-3-yl, 1-benzothiophen-4-yl, 1-benzo Thiophen-5-yl, 1-benzothiophen-6-yl, 1-benzothiophen-7-yl, 1,3-benzothiazol-2-yl and 1,3-benzo Zin-2-yl, benzo-fused 6-membered heteroaryl containing one to three nitrogen atoms: for example, but not limited to, quinolin-2-yl, quinolin-3-yl, quinoline 4-yl, quinoline-5-yl, quinoline-6-yl, quinoline-7-yl, quinoline-8-yl, isoquinolin-1-yl, isoquinolin-3-yl, iso Quinoline-4-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, and isoquinolin-8-yl; heterocyclic: tri- to fifteen- a saturated or partially unsaturated heterocyclic ring containing one to four heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur groups: mono-, di- or tricyclic heterocycles containing, in addition to carbon ring members, One to three nitrogen atoms and/or one oxygen or sulfur atom or one or two oxygen and/or sulfur atoms; if the ring contains a plurality of oxygen atoms, the atoms are not directly adjacent; for example, but not limited to , oxiranyl, aziridine, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothiophenyl, 3-tetrahydrothiophenyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3- different Zyridinyl, 4-iso Zyridinyl, 5-iso Zyridinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidine, 5-pyrazolidine, 2- Azolidinyl, 4- Zyridinyl, 5- Zyridinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1,2,4- Diazolidin-3-yl, 1, 2, 4- Diazolidin-5-yl, 1,2,4-thiadiazolidin-3-yl, 1,2,4-thiadiazolidin-5-yl, 1,2,4-triazolidine-3- Base, 1, 3, 4- Diazolidin-2-yl, 1,3,4-thiadiazolidin-2-yl, 1,3,4-triazolidine-2-yl, 2,3-dihydrofuran-2-yl, 2 ,3-dihydrofuran-3-yl, 2,4-dihydrofuran-2-yl, 2,4-dihydrofuran-3-yl, 2,3-dihydrothiophen-2-yl, 2,3 -dihydrothiophen-3-yl, 2,4-dihydrothiophen-2-yl, 2,4-dihydrothiophen-3-yl, 2-pyrolin-2-yl, 2-pyrolin-3-yl , 3-pyrolin-2-yl, 3-pyrroline-3-yl, 2-iso Oxazolin-3-yl, 3-iso Oxazolin-3-yl, 4-iso Oxazolin-3-yl, 2-iso Oxazolin-4-yl, 3-iso Oxazolin-4-yl, 4-iso Oxazolin-4-yl, 2-iso Oxazoline-5-yl, 3-iso Oxazoline-5-yl, 4-iso Oxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-iso Thiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2,3 -dihydropyrazol-1-yl, 2,3-dihydropyrazol-2-yl, 2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2 , 3-dihydropyrazol-5-yl, 3,4-dihydropyrazol-1-yl, 3,4-dihydropyrazol-3-yl, 3,4-dihydropyrazol-4-yl , 3,4-dihydropyrazol-5-yl, 4,5-dihydropyrazol-1-yl, 4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazole-4 -yl, 4,5-dihydropyrazol-5-yl, 2,3-dihydro Zin-2-yl, 2,3-dihydrogen Zyrid-3-yl, 2,3-dihydrogen Zin-4-yl, 2,3-dihydrogen Oxazol-5-yl, 3,4-dihydrogen Zin-2-yl, 3,4-dihydrogen Zyrid-3-yl, 3,4-dihydrogen Zin-4-yl, 3,4-dihydrogen Oxazol-5-yl, 3,4-dihydrogen Zin-2-yl, 3,4-dihydrogen Zyrid-3-yl, 3,4-dihydrogen Zin-4-yl, 2-hexahydropyridyl, 3-hexahydropyridinyl, 4-hexahydropyridinyl, 1,3-di Alkan-5-yl, 2-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothiophenyl, 3-hexahydroindole Base, 4-hexahydroindole Base, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-hexahydropyridyl Base, 1,3,5-hexahydrogen -2-yl and 1,2,4-hexahydro three -3-based; the composition that is not included is the one that touches the natural law and is excluded by the skilled person according to his professional knowledge. The exclusion is, for example, a ring structure having three or more contiguous oxygen atoms.

The invention further relates to a process for the preparation of the thienylpyrimidinylpyrazole of the formula [I] according to the invention.

Description of the process and intermediates

The thienylpyrimidinylpyrazole of the formula [I] according to the invention can be prepared according to different routes. In the following, the possible processes are first shown in the process and then detailed. Unless otherwise indicated, the indicated residue has the meaning given in the following scheme.

The thienylpyrimidinylpyrazole of the formula [I] according to the present invention can be produced by Process A according to the following scheme.

Met ¹ = such as -Sn(Bu) ₃ , -B(OR*) ₂ Met ² = such as -B(OR*) ₂ B(OR*) ₂ = such as -B(OiPr) ₂ , -B(OH) ₂ -B (pinacolato) Z ¹ = such as Cl, Br, I, -OTos, -OMs, -OH Z ² = such as Cl, Br Z ³ = such as Cl, -OH A ⁷ = R ¹⁵ , -OR ¹⁵ R ^3a = such as -NH-C(S)R ¹⁵ , -NH-C(O)R ¹⁵ , -NHC(O)OR ¹⁵ , -NH-C(O)NR ¹⁵ R ¹⁶ , PG= Tetrahydro-2H-pyran-2-yl, 2-(trimethyldecyl)ethoxy]methyl

Further, the intermediates of the formulae [VI] and [VII] can be produced by Process B (Scheme 2).

Z ⁴ = as CH ₃ , O alkyl Z ⁵ = such as NMe ₂ , OH, O alkyl Z ⁶ = such as Cl, Br, I

Further, the thienylpyrimidinylpyrazole of the formula [I-b] according to the present invention can also be produced by Process C (Scheme 3).

Met ³ = as Sn(n-Bu) ₃

Further, the intermediate of the formula [VII] can be produced by Process D (Scheme 4)

Compound of formula [III] Wherein the symbols R ¹ , R ² , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ¹⁸ and X ¹ have the above general, preferably, particularly preferred, quite excellent, optimal or especially preferred meanings, and salts thereof Class, is novel.

For example, the compounds of the formula [III] listed in the following table are novel: Wherein X ¹ represents =CH, and R ⁴ and R ⁵ represent H.

Compound of formula [IV] Wherein, the symbols R ¹ , R ² , R ⁶ , R ⁷ and R ⁸ have the above general, preferably, particularly preferred and very preferred meanings, and salts thereof, which are novel.

For example, the compounds of the formula [IV] listed in the following table are novel:

^{1 When} measuring the logP value, the following method was used.

² specified as having the highest intensity of the mass of [M ⁺ H] + ions of the isomeric forms of the peak; if detected [MH] ^- ion mass values indicated in line 2.

The preparation of the compound of the general formula [I] by the method A can be carried out as follows:

The compound of the formula [VII] is halogenated to give a compound of the formula [V]. This is converted to the compound of the formula [IV] by reaction with a substrate of the formula [VIII], thus forming a pyrazole positional isomeric mixture. These can be separated into individual positional isomers by conventional methods such as chromatography. Alternatively, the compound of the general formula [VII] can be converted to the compound of the formula [VI] by reaction with a substrate of the formula [VIII], whereby a pyrazole positional isomer mixture can be formed. Halogenation of a compound of formula [VI] provides a compound of formula [IV]. The compound of the formula [IV] and the substrate of the formula [IX-a] can be carried out in a C-C coupling reaction, thereby obtaining a compound of the formula [I] (Scheme 1).

Alternatively, the pyrazole compound of the general formula [IV] can be converted to the compound of the formula [III] by reaction with a boronic acid ester. These can be converted to the compound of the formula [I] (Scheme ¹ ) by carrying out a reaction in the CC coupling reaction of the formula [Xa].

Alternatively, the compound of the formula [IV] can be converted to the compound of the formula [II] by reacting with a C-C coupling reaction of the formula [IX-b] and then deprotecting. These compounds can likewise be converted to the compound of the formula [I-a] by reaction with a substrate of the formula [XI].

Further, the compound of the formula [III] can be converted into the formula [II] by reacting with the coupling of the formula [X-b] in the C-C coupling reaction and then deprotecting it. Compound (Scheme 1).

The synthesis of the general formula [VI] by Process B can be carried out as follows:

The compound of the general formula [XII] is converted into the structure of the formula [XIII] by a known method. The 1,3-diketone compound or the eneamine of the structure [XIII] can be converted into a structure of the formula [VII] together with hydrazine. Alternatively, the structure of the formula [XIII] can be converted to the compound of the formula [VI], whereby a mixture of pyrazole isomers can be obtained, depending on the nature of R ¹ (Scheme 2).

Further, the structural formula of the general formula [VI] can be obtained by reacting an alkyne of the general formula [XVI] with hydrazine. The intermediate of the general formula [XVI] can be formed by subjecting the general formula [XIV] mercapto halide to a transition metal catalytic coupling reaction or by reacting the compound of the general formula [XV] in the presence of carbon monoxide (Scheme 2). .

The preparation of the compound of the general formula [I-b] by Process C can be carried out as follows:

The compound of the general formula [XVII] can be reacted with a C-C coupling reaction of the formula [XVIII], thereby forming a compound of the formula [XIX]. Next, this compound is deprotected, thereby obtaining a compound of the general formula [XX]. The resulting pyrazole of the formula [XX] is immediately reacted with a substrate of the formula [VIII], thereby obtaining the formula [I-b]thienylpyrimidinylpyrazole according to the invention (Scheme 3).

The synthesis of the intermediate of the general formula [VII] by Process D can be carried out as follows:

The compound of the general formula [XXI] can be converted into Weinreb decylamine of the formula [XXII]. This compound is reacted with acetylene in the presence of a strong base and then treated with hydrazine, thus obtaining a pyrazole of the formula [VII-a] (Scheme 4).

Step (V1)

One possible synthetic method for a compound of formula [VI] is shown in Scheme 1.

A compound of the formula [VI], wherein R ¹ does not represent hydrogen, can be similarly illustrated in the literature (Bioorg. Med. Chem. Lett. 2000, 10, 1351-1356 or J. Am. Chem. Soc. 2007, 129 , 26,8064-8065), by reacting a compound of the formula [VII] with a formula of the formula [VIII] (wherein Z ¹ represents a release group such as Cl, Br, I, -OTos, -OMs, etc.), If necessary, the reaction is carried out in the presence of a solvent and an acid scavenger/base to synthesize.

A compound of the formula [VI], wherein R ¹ does not represent hydrogen, may also be similarly described in the literature (Mitsunobu, O. Synthesis 1981, 1-28), such as by formulating the compound of the formula [VII] with the formula [VIII] The acceptor (wherein Z ¹ represents -OH) is carried out in the presence of a phosphine such as triphenylphosphine and an azodicarboxylate such as diethyl azodicarboxylate and a solvent such as THF. Synthesis by reaction.

Similarly, these synthetic methods can also be used to convert a halogenated pyrazole of the formula [V] to a compound of the formula [IV].

The compound of the formula [VII] can be obtained, for example, from commercially available ethylbenzene by dimethylformamide dimethyl acetal and hydrazine by a method known in the literature (Tetrahedron, 2003, 59, 555-560). Prepared by reaction.

The compound of the formula [VIII] required for the reaction is commercially available or can be prepared by a literature method (RC Larock, Comprehensive Organic Transformations, 2nd edition, 1999, Wiley-VCH, page 690 and page 1929) And the literature cited therein).

A process for preparing a suitable compound of the formula [VIII] wherein R ^{1 is} in the case of an alkylation reaction, such as a substituted or unsubstituted alkyl or cycloalkyl residue, for example, an alcohol and methane Sulfonyl chloride and triethylamine are reacted (Org. Lett. 2008, 10, 4425-4428) or by Appel reaction with triphenylphosphine and CCl ₄ (as illustrated in Tetrahedron 2008, 64, 7247-7251) .

The preparation of a suitable compound of the formula [VIII] (wherein R ¹ , in the case of a oximation reaction of a carbonyl group, is directly bonded to Z ¹ ) is carried out by methods known in the literature (eg Jerry March, Advanced) Organic Chemistry, 4th edition, John Wiley & Sons, page 437 and the literature cited therein).

According to the chemical structure of the acceptor of the general formula [VIII], certain preferred compositions can be found in selecting a suitable solvent and a suitable base.

In the case of an alkylation reaction with a substrate of the formula [VIII] wherein R ^{1 is} in the case of an alkylation reaction, such as a substituted or unsubstituted alkyl or cycloalkyl residue, Use all solvents which are generally inert under the reaction conditions, such as cyclic or acyclic ethers (eg diethyl ether, tetrahydrofuran, two Alkane), aromatic hydrocarbons (such as benzene, toluene, xylene), halogenated hydrocarbons (such as dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (such as chlorobenzene, dichlorobenzene), nitrile Classes (such as acetonitrile), carboxylates (such as ethyl acetate), decylamine (such as N, N-dimethylformamide, N,N-dimethylacetamide), dimethyl hydrazine or 1 , 3-dimethyl-2-imidazolidinone, or the reaction can be carried out in a mixture of two or more such solvents. Preferred solvents are dimethylformamide and acetonitrile.

In the case of an alkylation reaction with a substrate of the formula [VIII] wherein R ^{1 is} in the case of an alkylation reaction, such as a substituted or unsubstituted alkyl or cycloalkyl residue, The base used in the present invention is, for example, lithium hexamethyldifluoride azide (LiHMDS), potassium carbonate, cesium carbonate and sodium hydride. A preferred base is sodium hydride. As usual, at least one equivalent of base is used.

In the case of a deuteration reaction with a substrate of the formula [VIII] wherein the carbonyl group is directly bonded to Z ¹ in R ¹ , all solvents which are generally inert under the reaction conditions, such as a ring, may be used. Or acyclic ethers (such as diethyl ether, tetrahydrofuran, two Alkane), aromatic hydrocarbons (such as benzene, toluene, xylene), halogenated hydrocarbons (such as dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (such as chlorobenzene, dichlorobenzene), nitrile The class (such as acetonitrile) and the aromatic heterocyclic amine (pyridine) or the reaction can be carried out in a mixture of two or more such solvents. Preferred solvents are tetrahydrofuran and dichloromethane.

When in the formula [VIII] by mass of (wherein R ¹ attached to the carbonyl group directly bonded to the lines Z ¹⁾ of the case of the acylation reaction, in relation to the general formula [V] or [VII] The starting material For example, one equivalent of acid scavenger/base (such as pyridine, diisopropylethylamine, triethylamine or a commercially available polymeric acid scavenger) can be used. If the starting material is a salt, at least two equivalents of acid scavenger are required. If pyridine is used as the solvent, similar to the description in the literature, the addition of other bases (EP-A-1 000 062) may be omitted in some cases.

The reaction is usually carried out at a temperature of from 0 ° C to 100 ° C and preferably from 20 ° C to 30 ° C, but it can also be carried out at the reflux temperature of the reaction mixture. The reaction time varies depending on the reaction scale and the reaction temperature, but usually In between a few minutes and 48 hours.

After completion of the reaction, the compound [VI] or [IV] is isolated from the reaction mixture by one of the general separation techniques. Depending on the nature of the acceptor of the formula [VIII] and the reaction conditions, the compounds of the formulae [VI] and [IV], wherein R ^{1 is} not hydrogen, may be a purely positional isomer or may be two possible positional isomers ( A mixture in which the group R ¹ can occupy two positions of the N atom of the pyrazole. In the case where a positional isomeric mixture is obtained, these can be purified by physical means (for example, crystallization or chromatography) or can be optionally used without first purification in the next step.

Step (V2)

A possible synthetic method for the compound of formula [V] is shown in Scheme 1.

Halogenated pyrazoles of the formula [V] are either commercially available or can be prepared by literature methods. One method of preparing a suitable halogenated pyrazole is, for example, the related pyrazole [VII] (as described in EP-A 1 382 603) by a bromination reaction with N-bromosuccinimide in acetic acid.

Step (V3)

A possible synthetic system for the compound of formula [III] is shown in Scheme 1.

The compound of the formula [III] can be used by the methods described, for example, via a halogen pyrazole [IV] with a boronic ester such as a dipinacol bis(B,4,4',4',5,5,5' , 5'-octamethyl-2,2'-bis-1,3,2-di Cyclopentane) in the presence of a base such as 1,1 '-bis(diphenyl-phosphino) ferrocene iron-palladium (II) dichloride in the presence of a base and a suitable solvent (see US Prepared by the reaction of 2009/0018156, WO 2007/024843 or EP-A 1 382 603).

As the solvent, all of the general solvents which are inert under the reaction conditions, such as anthraquinones (such as dimethyl hydrazine) and cyclic ethers (such as An alkane) and a guanamine (such as N,N-dimethylformamide) and the reaction can be carried out in a mixture of two or more such solvents. Preferred solvents are dimethyl hydrazine and two alkyl.

The reaction is generally carried out at a temperature of from 80 ° C to 120 ° C, and preferably the reaction temperature is from about 85 ° C to 90 ° C. The reaction time varies depending on the reaction scale and the reaction temperature, but is usually between 1 hour and 16 hours.

Compounds of formula [III] can also be prepared using other synthetic methods described in the literature. For example, a compound of the formula [III] can be obtained by metallation of a halogenated pyrazole [IV] with a base such as n-butyllithium and reaction with a boronic ester such as trimethylborate and subsequent pyrazole-boric acid and It is prepared by the reaction of tetramethyl glycol (see, for example, J. Het. Chem. 2004, 41, 931-940 or EP-A 1 382 603 and WO 2007/16392).

Step (V4)

A possible synthetic system for the compound of formula [I] is shown in Scheme 1.

The compound of the formula [I] can be, for example, by halogenating a pyrazole [IV] with a metal halide of the formula [IX-a] (wherein Met ¹ represents a boronic acid ester or a boronic acid such as B(OiPr) ₃ , B(OH) ₂ ) The catalyst, a base, is prepared by coupling with a ligand in the presence of a suitable solvent at a suitable temperature by known literature procedures (Top. Curr. Chem. 2002, 219, 11; Organomet. Chem. 1999, 28, 147 and the literature cited therein, 2005, 7, 21, 4753-4756). (Process 1)

Similarly, the synthesis of the azole [II] from the compound of the formula [IV] described in Scheme 1 is carried out according to this method.

The compound of the formula [I] can also be obtained, for example, by a halogenated pyrazole [IV] with a metal halide of the formula [IX-a] wherein Met ¹ represents a tin-compound such as Sn(n-Bu) ₃ , if It is desirable that the inorganic or organic halide salt be prepared if it is desired to be coupled at a suitable temperature in the presence of a ligand and a suitable solvent by known literature procedures (see Synthesis 1992, 803-815).

Compounds of the formula [IX-a1] wherein X ¹ represents CH are commercially available or can be prepared by processes in the literature. One method for preparing a suitable halogen heterocyclic ring [IX-a1] is the presence of a halogen heterocyclic ring of the formula [XXIII] and a diboralol diboron in a catalyst such as Pd(OAc) ₂ or PdCl ₂ (dppf). If necessary, a ligand (for example, 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroanthracene chloride), a base (such as potassium acetate or sodium acetate) and In the presence of a solvent such as tetrahydrofuran or dimethyl hydrazine by the methods described in the literature (Bioorg. Med. Chem. Lett. 2006, 16, 5, 1277-1281 and WO 2011/042389) (Scheme 5) get on.

Alternatively, a compound of the formula [IX-a1] wherein X ¹ represents CH can also be prepared by other known literature methods. One method for preparing a suitable heterocyclic ring [IX-a1] is the metallation of a halogen pyridine [XXIII] with a base such as n-butyllithium in a solvent such as diethyl ether or tetrahydrofuran and then with a boronic ester ( For example, B(i-PrO) ₃ or B(OMe) ₃ ) and tetramethyl glycol are reacted by methods known in the literature (Synthesis 2004, 4, 469-483 and the literature described therein) (Scheme 6) ).

Similarly, the compound of the formula [IX-b] can be pre-formed according to the method described in the literature (WO 2011/042389) by using a respective halogen heterocyclic ring (using Met ² in [IX-b] with Cl, Br , I instead) is synthesized by reacting with a double-frequency phenolic diboron in the presence of a catalyst.

Compounds of the formula [IX-a2] wherein X ¹ represents N are commercially available or can be prepared by the literature. One method for preparing a suitable halogen heterocyclic ring [IX-a2] is a halogen heterocyclic compound of the formula [XXIV] and a hexaalkylditin compound (for example, 1,1,1,2,2,2-hexabutylditin. In the presence of a catalyst such as bis(triphenylphosphine)palladium(II) acetate, if desired, in the presence of a source of monofluoride (eg, tetrabutylammonium fluoride) and a solvent (eg, tetrahydrofuran or diethyl ether) The reaction is carried out by the method described in the literature (WO 2003/095455 or WO 2007/104538) (Scheme 7).

Alternatively, the compound [IX-a2] wherein X ¹ represents N can also be prepared by other known literature methods. One method for preparing a suitable halogen heterocyclic ring [IX-a2] is a halogen pyridine [XXIV] using a metalating agent (alkyl lithium compound such as n-butyl lithium or Grignard reagent such as isopropylmagnesium chloride) in a solvent such as diethyl ether. Metallization in tetrahydrofuran and then with a trialkyltin halogen compound (for example Bu ₃ SnCl) by methods known in the literature (WO 2008/008747 or Tetrahedron 1994, 275-284 and the literature described therein) Scheme 8) The reaction is carried out.

The compounds of the formulae [XXIII] and [XXIV] are either commercially available or can be prepared, for example, by deuteration of the relevant amine (in the case of R ³ =-NH ₂ ) by methods known in the literature (eg J. Org. Chem. 2004, 69, 543-548). Another method of preparing the compounds of the formula [XXIII] and [XXIV] is the halogenation of the related hydroxyheterocyclic ring which is similar to the halogenation method specified in the synthesis of the compounds [X-a1] and [XXVII].

For the coupling of a halogen pyrazole [IV] and a metal halide of the formula [IX-a] (where Met represents a boronic acid ester or a boronic acid such as B(OiPr) ₃ or B(OH) ₂ ), the choice of solvent, base, The temperature, the catalyst and the added ligand, if desired, may vary depending on the boronate acceptor used and include the coupling of the compound of the formula [III] described in the step (V5) with the acceptor of the formula [Xa]. Possible variations.

When coupling a halogen pyrazole [IV] and a metal halide of the formula [IX-a] (where Met ¹ represents a group carrying an alkyl tin such as Sn(Bu) ₃ ), when a catalyst is selected, if necessary Inorganic or organic halide salts, if desired, and suitable solvents at appropriate temperatures may vary depending on the alkyltin species employed.

As the solvent in the reaction of the compound of the formula [IX-a], all solvents which are usually inert under the reaction conditions, such as a cyclic or acyclic ether (ether, dimethoxymethane, divinylethylene) can be used. Alcohol dimethyl ether, tetrahydrofuran, two Alkane, diisopropyl ether, tert-butyl methyl ether), aromatic hydrocarbons (such as benzene, toluene, xylene), decylamine (such as dimethylformamide, dimethyl-acetamide, N- Methylpyrrolidone) and anthraquinones (such as dimethyl hydrazine) or the reaction can be carried out in a mixture of two or more such solvents. A preferred solvent is dimethylformamide.

a halide salt in the reaction of a compound of the formula [IX-a], which is preferably a For use in the process according to the invention is, for example, a copper halide (e.g. CuBr or CuI), a cesium halide (CsF) and a tetraalkylammonium halide (TBAF).

The halide salt is preferably used in the process according to the present invention in an amount of from 1 to 400 mol% based on the organotin compound. However, mixtures of halide salts can also be used in a ratio of from 1 to 400 mole percent. It is particularly preferred that the mixture of copper iodide and cesium fluoride is added in a ratio of from 1 to 200 mol%.

With respect to the catalyst in the reaction of the compound of the formula [IX-a] with the halogenated pyrazole of the formula [IV], the compound of the formula [I] is prepared by following the procedure described in the step V5 by the following description of the compound of the formula [III] and [Xa]. The catalyst used in the reaction.

The amount of the catalyst is preferably from 0.001 to 0.5 mol% and particularly preferably from 0.01 to 0.2 mol%, based on the heteroaromatic [IX-a] carrying the release group Met ¹ .

The catalyst may contain a phosphorus-containing or arsenic-containing ligand, or a phosphorus- or arsenic-containing ligand may be added to the reaction mixture separately. As for the phosphorus-containing ligand, it is preferably a tri-n-alkylphosphine, a triarylphosphine, a dialkylaryl-phosphine, an alkyldiarylphosphine and/or a heteroarylphosphine such as a tripyridylphosphine and a trifuranyl group. a phosphine wherein the three substituents on the phosphorus may be the same or different and may be palm or non-palphalinic and one or more substituents may be attached to a plurality of phosphine phosphorus groups, wherein this is attached to a The fraction may also be a metal atom, which is suitable. Particularly preferred are phosphines such as triphenylphosphine, tri-tert-butylphosphine and tricyclohexyl-phosphine. As for the arsenic-containing ligands, such as tri-n-alkylarsenic and triarylarsenic, the three substituents on arsenic may be the same or different and are suitable.

The total concentration of the ligand is preferably from up to 1 mol%, particularly preferably from 0.01 to 0.5 mol%, based on the heteroaromatic [IX-a] carrying the release group Met ¹ .

In order to carry out the process according to the invention, it is advantageous to carry out the precipitation, the solvent, the base, the halide salt, the catalyst and, if necessary, the ligand thoroughly mixed and preferably at a temperature between 0 ° C and 200 ° C, particularly preferably 60- 150 ° C. The reaction time may vary depending on the scale of the reaction and the reaction temperature, but is usually between several minutes and 48 hours. In addition to the single-tank reaction, the reaction can be carried out in such a way that the various reactants are metered in in a controlled manner during the reaction, whereby different metering routes can be employed.

The process according to the invention is generally carried out under normal pressure. However, it can also be carried out under elevated pressure or reduced pressure. This reaction is usually carried out using a protective gas such as argon or nitrogen.

The molar ratio of the halogen pyrazole [IV] to the organotin compound [IX-a2] is preferably from 0.9 to 2.

After completion of the reaction, the solid-generating catalyst is removed by filtration, the crude product is removed from the solvent and then purified by methods known to those skilled in the art and suitable for the particular product, such as by Recrystallization, distillation, sublimation, zone melting, melt crystallization or chromatography.

Step (V5)

A possible synthesis of a compound of the formula [I] and a possible synthesis of a compound of the formula [III] are shown in Scheme 1.

The compound of the formula [I] can be, for example, by reacting a pyrazole boronic acid [III] with a heterocyclic ring of the formula [Xa] (wherein Z ² represents a cleavage group such as Cl or Br) in the presence of a catalyst, a base and a suitable solvent. Suitable temperatures are prepared by coupling by known literature procedures (Top. Curr. Chem. 2002, 219, 11; Organomet. Chem. 1999, 28, 147 and references cited therein).

In a similar manner, the compound of the formula [II] can be produced by coupling pyrazole boronic acid [III] with a heterocyclic compound of the formula [X-b].

The compound of the formula [Xa] (wherein X ¹ represents CH) is commercially available or can be prepared by a literature process (Scheme 9). One method for preparing the appropriate halogen heterocycle [X-a1] is to treat the pyridine N-oxide with a halogenating agent (such as PCl ₃ , POCl ₃ , SOCl ₃ or methane sulfonium chloride) (see Bioorg. Med. Chem. Lett. 2007, 17, 7, 1934-1937) The reaction was carried out.

Pyridine N-oxide [XXV] is known or can be related by pyridine (eg with H ₂ O ₂ , H ₂ O ₂ + methyltriketopoxime, m-chloroperoxybenzoic acid, dimethyl Base-ethylene oxide or H ₂ O ₂ + manganese tetrakis(2,6-dichlorophenyl)porphyrin) by the process described in the literature (ARKIVOC 2001 (i) 242-268 and the literature contained therein) It is prepared by oxidation.

Another method for preparing the appropriate halogen heterocyclic [X-a1] is to use a [XXVI] 4-hydroxypyridine compound with a halogenating agent (such as PCl ₃ , POCl ₃ ) by a known literature procedure (Pol. J. Chem. 1981, 55, 4, 925-929) (Scheme 10) The reaction is carried out.

Hydroxypyridine [XXVI] is known.

Alternatively, the [Xa] compound (wherein X ¹ represents CH) is commercially available or can be prepared by literature methods (Scheme 11). One method for preparing a suitable halogen heterocyclic ring [Xa-2] is to combine the amine heterocyclic ring of the formula [XXVII] with mercapto chloride in the presence of a base and a solvent (Synth. Commun. 1997, 27, 5, 861- 870) The reaction is carried out.

Aminoheterocyclic [XXVII] (wherein X ¹ represents CH) is known or can be obtained by the process described in the literature by the N-BOC protecting group (Aust. J. Chem. 1982, 35, 10, 2025- 2034 and the references contained therein are prepared by removal from a compound of formula [Xb-1].

Aminoheterocyclic [XXVII] (wherein X ¹ represents N) is known or can be obtained by the process of the hydroxy compound (Z ² =-OH) as described in the literature (eg according to J. Med. Chem. 2006, 49, 14, 4409-4424) was prepared by halogenation.

Compounds of the formula [Xb] wherein X ¹ represents CH are commercially available or can be prepared by literature methods (Scheme 12). One method for preparing a suitable N-Boc-halogen heterocyclic ring [Xb-1] is to treat a suitable acid (such as 4-bromo-pyridinecarboxylic acid) [XXIX] with diphenylphosphonium azide and a third-butyl group. The reaction is carried out with an alcohol (Aust. J. Chem. 1982, 35, 2025-2034, J. Med. Chem. 1992, 35, 15, 2761-2768 or US 5,112,837 A).

The carboxylic acid [XXIX] is known or can be obtained from commercially available precursors by the procedures described in the literature (see, e.g., EP-A 1 650 194), for example by commercially available pyridine-2-carboxylic acid by The sulfoxide (di) chloride is prepared by reacting it in dimethylformamide. Alternatively, the compound of the general formula [L] can also be obtained by a commercially available 4-halo-2-methyl-pyridine derivative by a known literature procedure (Aust. J. Chem. 1982, 35, 2025-2034). It is prepared by oxidation.

Compounds of the formula [Xb] wherein X ¹ represents N are commercially available or can be prepared by literature methods (Scheme 13). One method for preparing a suitable N-Boc-halogen heterocycle [Xb-2] is a hydroxy compound (such as (4-hydroxy-pyrimidin-2-yl) urethane) and phosphonium chloride (Chem. Pharm. Chlorination of Bull. 2003, 51, 8, 975-977).

The hydroxy compound [XXX] is known or can be prepared from commercially available precursors by the procedure described in the literature (Chem. Pharm. Bull. 2003, 51, 8, 975-977).

As the solvent in the synthesis method of the compound of the formula [I] and [II], all solvents which are usually inert under the reaction conditions, such as an alcohol (e.g., methanol, ethanol, 1-propanol, 2-propanol, ethylene) can be used. Ethylene glycol, 1-butanol, 2-butanol, third-butanol), cyclic or acyclic ethers (ether, dimethoxymethane, divinyl glycol dimethyl ether, Tetrahydrofuran, two Alkane, diisopropyl ether, tert-butyl methyl ether), aromatic hydrocarbons (such as benzene, toluene, xylene), hydrocarbons (such as hexane, iso-hexane, heptane, cyclohexane), ketone Classes (such as acetone, ethyl methyl ketone, isobutyl methyl ketone), nitriles (such as acetonitrile, propionitrile, butyronitrile) and guanamine (such as dimethylformamide, dimethylacetamide, N- Methylpyrrolidone) and water or the reaction can be carried out in a mixture of two or more such solvents. The preferred solvent is two alkyl.

In the process according to the invention, the bases which are preferably used are alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates, alkali metal hydrogencarbonates, alkali metal and alkaline earth metal acetates, alkali metals and alkaline earth metals. An alkoxide, and first, second and third amines. Preferred bases are alkali metal carbonates such as cesium carbonate, sodium carbonate and potassium carbonate.

In the process according to the invention, based on the aromatic boronic acid, the base is preferably Use in a ratio of 100 to 1000 mol%. A preferred ratio is from 600 to 800 mol%.

As the catalyst, for example, metal palladium, a palladium compound and/or a nickel compound can be used. The catalyst can also be applied to a solid support such as activated carbon or alumina. Palladium catalyst is preferred, wherein the palladium is present in an oxidized state (0) or (II), such as tetrakis(triphenylphosphine)-palladium, bis(triphenylphosphine)palladium dichloride, bis(diphenyl) -phosphinyl) ferrocene, iron, palladium dichloride, palladium keto acid salt, palladium acetonate pyruvate (eg palladium acetonate pyruvate), nitrile palladium halide (eg bis-(benzonitrile) Palladium dichloride, bis(acetonitrile)-palladium dichloride), palladium halide (PdCl ₂ , Na ₂ PdCl ₄ , Na ₂ PdCl ₆ ), allyl palladium halide, palladium dicarboxylate (eg palladium - II acetate) and tetrachloropalladium acid. The most preferred catalysts are tetrakis(triphenylphosphine)-palladium, bis(triphenylphosphine)-palladium dichloride and bis-(diphenylphosphino) ferrocene iron palladium dichloride. The palladium compound can also be formed in situ, such as palladium (II) acetate from palladium (II) chloride and sodium acetate.

The amount of the catalyst is preferably from 0.001 to 0.5 mol% and particularly preferably from 0.01 to 0.2 mol%, based on the heteroaromatic [Xa] and [Xb] carrying the release group Z ² .

The catalyst may contain a phosphorus-containing ligand or the phosphorus-containing ligand may be separately added to the reaction mixture. More suitable phosphorus-containing ligands are tri-n-alkylphosphines, triarylphosphines, dialkylarylphosphines, alkyldiarylphosphines and/or heteroarylphosphines such as tripyridylphosphine and trifurylphosphine. Wherein the three substituents on the phosphorus may be the same or different, and one or more of the substituents may be attached to a plurality of phosphine phosphorus groups, wherein one part of the linkage may also be a metal atom. Particularly preferred are phosphines such as triphenylphosphine, tri-tert-butylphosphine and tricyclohexylphosphine.

The total concentration of the phosphorus-containing ligands is preferably from 0.01 to 0.5 mol%, based on the heteroaromatic groups [Xa] and [Xb] carrying the release group Z ² .

In order to carry out the process according to the invention, it is convenient to carry out the precipitation, the solvent, the base, the catalyst and, if appropriate, the ligand thoroughly, preferably at a temperature of from 0 ° C to 200 ° C, particularly preferably from 100 to 170 ° C. The reaction time may vary depending on the scale of the reaction and the reaction temperature, but is usually between several minutes and 48 hours. In addition to the single-tank reaction, the reaction can also be carried out such that the various reactants are metered in in a controlled manner during the reaction, which can be in different metering routes.

The molar ratio of the heteroaromatic [X-a] and [X-b] to the organoboron compound [III] is preferably from 0.9 to 1.5.

The process according to the invention is generally carried out under normal pressure. However, it can also be carried out under elevated or reduced pressure. This reaction is usually carried out using a protective gas such as argon or nitrogen. After completion of the reaction, the catalyst produced as a solid is removed by filtration, the crude product is removed from the solvent, and then purified by methods known to those skilled in the art and suitable for the particular product, such as By recrystallization, distillation, sublimation, zone melting, melt crystallization or chromatography.

Step (V6)

A possible synthetic method for the compound of the formula [I-a] is shown in Scheme 1.

The compounds of the general formula [Ia] can be similarly described in the literature (see, for example, WO 2004/052880 and, for example, TW Greene, PGM Wuts, Protective Groups in Organic Synthesis, 1999, John Wiley & Sons, Inc.), by the relevant general formula [II] Synthesis of a compound with a coupling of a compound of the general formula [XI] (wherein Z ³ such as =Cl, Br, F or -OH), if necessary in the presence of an acid scavenger/base, in the above scheme The definitions of residues, R ¹ , R ² , R ^3a , R ⁴ , R ⁵ and X ¹ are related to the definitions above.

The mercapto halide [XI] (Z ³ = Cl) or the related carboxylic acid [XI] (Z ³ = OH) is commercially available or can be prepared by the methods described in the literature. Furthermore, the acceptor of the general formula [XI], wherein Z ³ = Cl, can be prepared from the related acid (Z ³ = OH) by chlorination by a known literature method (RC Larock, Comprehensive Organic Transformations, 2nd edition, 1999, Wiley-VCH, starting on page 1929 and the literature cited therein).

As the solvent, all solvents which are generally inert under the reaction conditions, such as cyclic or acyclic ethers (e.g., diethyl ether, tetrahydrofuran, Alkanes, aromatic hydrocarbons (such as benzene, toluene, xylene), halogenated hydrocarbons (such as dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (such as chlorobenzene, dichlorobenzene) and nitrile The class (such as acetonitrile) or the reaction can be carried out in a mixture of two or more such solvents. Preferred solvents are tetrahydrofuran and dichloromethane.

With respect to the starting materials of the general formula [II], at least one equivalent of an acid scavenger/base (for example, a Hünig base, triethylamine or a commercially available polymerized acid) is used. Scavenger). If the starting material is a salt, at least 2 equivalents of acid scavenger are required.

The reaction is usually carried out at a temperature of from 0 ° C to 100 ° C and preferably at from 20 ° C to 30 ° C, but it can also be carried out at the reflux temperature of the reaction mixture. The reaction time may vary depending on the scale of the reaction and the reaction temperature, but is usually between several minutes and 48 hours.

In order to carry out the process (V6) according to the invention for the preparation of the compound of the formula [Ia], usually 0.2 to 2 moles, preferably 0.5 to 0.9 moles of the amine group [II] per mole of the [XI]carboxylic acid halide is used. derivative. The operation was carried out by evaporating the volatile constituents in vacuo and treating the crude material with a solution of ammonia in methanol (7 mol).

After completion of the reaction, the compound [I-a] is separated from the reaction mixture by one of the usual separation techniques. If necessary, the compound is purified by recrystallization, distillation or chromatography.

Alternatively, the compound of the formula [Ia] can be similarly described in the literature by the related compound of the formula [II] and the formula [XI] of Z ³ =-OH in the presence of a coupling agent (eg Tetrahedron 2005, 61, 10827). -10852, and the literature cited therein) to synthesize.

Suitable coupling agents are, for example, peptide couplers (for example, N-(3-dimethyl-aminopropyl)-N'-ethyl-carbodiimide mixed with 4-dimethylamino-pyridine, N-(3-dimethylamino-propyl)-N'-ethyl-carbodiimide mixed with 1-hydroxy-benzotriazole, bromo-tripyrrolidinium-quinone hexafluorophosphate, O -(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyl Hexafluorophosphate, etc.).

If necessary, a base such as triethylamine or Hünig base can be used in the reaction.

As the solvent, all solvents which are usually inert under the reaction conditions, such as alcohols (e.g., methanol, ethanol, propanol), cyclic or acyclic ethers (e.g., diethyl ether, tetrahydrofuran, Alkane), aromatic hydrocarbons (such as benzene, toluene, xylene), halogenated hydrocarbons (such as dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (such as chlorobenzene, dichlorobenzene), nitrile The compounds (such as acetonitrile) and guanamines (such as N,N-dimethylformamide, N,N-dimethylacetamide) or the reaction can be carried out in a mixture of two or more such solvents. A preferred solvent is dichloromethane.

The reaction is usually carried out at a temperature of from 0 ° C to 100 ° C and preferably at from 0 ° C to 30 ° C, but it can also be carried out at the reflux temperature of the reaction mixture. The reaction time may vary depending on the scale of the reaction and the reaction temperature, but usually it is between several minutes and 48 hours.

After completion of the reaction, the compound [I-a] is isolated from the reaction mixture by one of the usual separation techniques. If necessary, the compound is purified by recrystallization, distillation or chromatography.

In the compound of the general formula [Ia], R ^3a represents -NR ¹² R ^12' (symmetric or asymmetric bis-guanidinium aminopyridine) can be directly obtained from the compound of the general formula [Ia] by the above method, wherein R ^3a represents -NHR ¹² (monodecylaminopyridine) is obtained by reacting with a mercapto halide of the formula [XI] (Z ³ = such as Cl, F).

Step (V7)

A possible synthetic system for the compound of formula [XIII] is shown in Scheme 2.

A compound of the general formula [XIII] wherein Z ⁴ represents NMe ₂ , Oalkyl can be obtained according to known literature methods (US 2002/19404 A1; Bioorg. Med. Chem. 2009, 17, 5, 2091-2100; J. Het .Chem. 2007, 44, 2, 355-361) by using a compound of the general formula [XII] (wherein Z ³ represents a methyl group) and a formazanizing agent such as an alkyl formate (such as a methyl formate), A trialkyl orthoformate such as trimethyl orthoformate or an acetal of N,N-dialkylformamide is obtained by reaction. The solvent can be optionally used. Typical solvents include alcohols (such as ethanol), esters (such as ethyl acetate), ethers (such as THF), and more polar solvents such as DMF or NMP. The reaction temperature can be varied from room temperature to the boiling point of the reaction mixture. The reaction time may vary depending on the scale of the reaction and the reaction temperature, but usually it is between several minutes and 48 hours.

Alternatively, the compound of the formula [XIII] (wherein Z ⁴ represents OH) can be obtained by a known compound method (J. Org. Chem. 2001, 66, 24, 8000-8009) by a compound of the formula [XII] (wherein Z ³ represents an O-alkyl group which is obtained by reacting a methyl ketone of the formula CH ₃ COR ² with a base such as sodium hydride, lithium diisopropyl decylamine or potassium t-butoxide and a solvent. Typical solvents include alcohols (such as ethanol) or ethers (such as THF).

Alternatively, the compound of the formula [XIII] wherein Z ⁴ represents OH can be obtained by a known literature method (Bioorg. Med. Chem. Lett. 2004, 14, 2, 343-346) by the formula [XII] methyl ketone. (wherein Z ³ represents CH ₃ ) and a carboxylic acid ester of the formula R ² COO alkyl is reacted in the presence of a base such as sodium hydride, lithium diisopropyl decylamine or potassium t-butoxide, and a solvent to obtain . Typical solvents include alcohols (such as ethanol) or ethers (such as THF).

After the end of the reaction, the compound [XII] is used from the reaction mixture. One of the common separation techniques to remove. If necessary, the compound is purified by recrystallization, distillation or chromatography, or the like, if appropriate, may be used in the next step without purification.

The compound of the formula [XII] is commercially available or can be synthesized according to known synthetic methods (for example, in Monatshefte Chem. 1989, 120, 53-63 or J. Am. Chem. Soc. 1947, 69, 3096-3098). .

Step (V8)

A possible synthetic system for the compound of formula [VII] is shown in Scheme 2.

The compound of the formula [VII] can be obtained according to known literature methods (Tetrahedron 1995, 51, 41, 11251-11256; J. Med. Chem. 2003, 46, 25, 5416-5427; WO 2008/108602 A1 or J. Med. Chem. 1998, 41, 13, 2390-2410) is obtained by reacting a compound of the formula [XIII] with hydrazine or a hydrated form thereof. An inert solvent such as a cyclic or acyclic ether (e.g., diethyl ether, tetrahydrofuran, Alkanes), alcohols (such as methanol or ethanol). The reaction can be carried out in a mixture of two or more such solvents. If desired, a base such as triethylamine can be used. The reaction temperature can be varied from 10 ° C to 50 ° C but is preferably room temperature. The reaction time may vary depending on the scale of the reaction and the reaction temperature, but is usually between several minutes and 48 hours. The reaction can be carried out in a microwave device of elevated temperature (e.g., CEM Explorer) which reduces reaction time. After the end of the reaction, the compound [VII] is removed from the reaction mixture by one of the usual separation techniques. If necessary, the compound is purified by recrystallization, distillation or chromatography.

Step (V9)

A possible synthetic system for the compound of formula [VI] is shown in Scheme 2.

The compound of the general formula [VI] can be obtained by a compound of the formula [XIII] and a compound of the formula R ¹ -NH-NH ₂ according to known literature methods (J. Med. Chem. 1998, 41, ¹³ , 2390-2410). It is obtained by reacting it or its hydration type. An inert solvent such as a cyclic or acyclic ether (e.g., diethyl ether, tetrahydrofuran, Alkanes), alcohols (such as methanol or ethanol). The reaction can be carried out in a mixture of two or more such solvents. If desired, a base such as triethylamine can be used. The reaction temperature can be changed from 10 ° C to 50 ° C, but room temperature is preferred. The reaction time may vary depending on the scale of the reaction and the reaction temperature, but is usually between several minutes and 48 hours. The reaction can be carried out in a microwave device (such as CEM Explorer) at an elevated temperature, which can shorten the reaction time. After the end of the reaction, the compound [VII] is removed from the reaction mixture by one of the usual separation techniques. If necessary, the compound is purified by recrystallization, distillation or chromatography.

Step (V10)

A possible synthetic method for the compound of formula [XVI] is shown in Scheme 2.

The alkynyl ketone [XVI] can be reacted by, for example, transition metal catalysis by mercapto chloride [XIV] as described in Tetrahedron Lett. 2006, 47, 5527-5530 or in Synthesis 2003, 18, 2815-2826. Prepared.

The compound of the general formula [XIV] is commercially available or can be synthesized according to known synthetic methods (e.g., J. Heterocycl. Chem. 1966, 3, 184-186 or J. Med. Chem. 2001, 44, 863- 872).

Step (V11)

A possible synthetic method for the compound of formula [XVI] is shown in Scheme 2.

Alternatively, alkyne ketone [XVI] can be coupled by carbonylation of a thiophene halide [XV] with an alkyne by carbon monoxide, as described, for example, in Synlett 2008, 6, 886-888 or J. Org. Chem. 2005, 70. Prepared by 6097-6100.

The compound of the general formula [XV] is commercially available or can be synthesized according to known synthetic methods (e.g., in EP 1424333 A1 or Acta Chemica Scandinavica B, 1976, 30, 439-449).

Step (V12)

A possible synthetic system for the compound of formula [VI] is shown in Scheme 2.

The compound of the formula [VI] can be treated by using an anthracene derivative under the conditions used in the specified method (e.g., Eur. J. Org. Chem. 2008, 4157-4168 or Tetrahedron Lett. 2008, 49, 3805-3809). [XVI] alkyne prepared.

Step (V13)

A possible synthetic method for the compound of formula [XIX] is shown in Scheme 3.

The compound of the formula [XIX] can be, for example, by a pyrazole of the formula [XVII] (wherein Met represents a boronic acid ester or a boronic acid such as B(OiPr) ₃ or B(OH) ₂ ) and a compound of the formula [XVIII] (wherein Z ⁴ represents a Release of a radical such as Cl, Br, I, methanesulfonate or triflate) by a known literature process in the presence of a catalyst, a base, a ligand, and a suitable solvent at an appropriate temperature (Top) . Curr. Chem. 2002, 219, 11; Organomet. Chem. 1999, 28, 147 and the literature cited therein, Org. Lett. 2005, 7, 21, 4753-4756) were produced by coupling.

Further, the compound of the formula [XIX] can be, for example, by a pyrazole of the formula [XVII] (wherein Met ³ represents a group carrying an alkyl tin, such as -Sn(Bu) ₃ ) and a compound of the formula [XVIII] (wherein Z ⁴ represents a release group such as Cl, Br, I, methanesulfonate or triflate) on the catalyst, if necessary, an inorganic or organic halide salt, if a ligand is required and a suitable solvent is present The appropriate temperature is produced by coupling by known literature procedures (see Synthesis 1992, 803-815).

Compounds of the formula [XVIII] such as 3-bromothiophene are known and are commercially available. A compound of the formula [XVII] such as 4-[1-(tetrahydro-2H-pyran-2-yl)-5-(tributylstannyl)-1H-pyrazol-4-yl]pyridine can be described according to the literature. The synthesis method is prepared (WO 2011/042389).

In the coupling of pyrazole [XVII] with the compound of the formula [XVIII], the choice of the solvent, the base, the temperature, the catalyst, the halide salt and the added ligand, if necessary, may vary depending on the pyrazole [XVII] used. And includes possible changes described in (V4).

The process according to the invention is generally carried out under normal pressure. However, it can also be carried out under elevated pressure or reduced pressure.

This reaction is usually carried out using a protective gas such as argon or nitrogen.

The molar ratio of pyrazole [XVII] to the compound of the formula [XVIII] is preferably from 0.9 to 2.

After completion of the reaction, the catalyst produced as a solid is removed by filtration, the crude product is removed from the solvent, and then purified by methods known to those skilled in the art and suitable for the particular product, such as By recrystallization, distillation, sublimation, zone melting, melt crystallization or chromatography.

Step (V14)

A possible synthetic method for the compound of formula [XX] is shown in Scheme 3.

The compound of the formula [XIX] is converted into a compound of the formula [XX] by removing the protecting group by an appropriate method, which is described in the literature ("Protective Groups in Organic Synthesis"; 3rd edition; Theodora W. Greene, Peter GMWuts; 1999, Wiley-VCH, pp. 494-653, and references cited therein).

The 2-(trimethyldecyl-ethoxy)methyl and tetrahydropyran-2-yl protecting groups can be, for example, in an acidic medium (such as methanolic HCl or trifluoroacetic acid) by known literature procedures ( Removed from WO 03/099822 and J. Org. Chem. 2008, 73, 4309-4312 and the literature contained therein. The benzyl protecting group can be used in the presence of a hydrogen source (such as hydrogen, ammonium formate, formic acid or cyclohexene) in a catalyst such as palladium activated carbon or palladium hydroxide on activated carbon by known literature procedures (EP- A 1 228 067) is removed by hydrolysis.

As the solvent, all solvents which are usually inert under the reaction conditions, such as alcohols (e.g., methanol, ethanol, propanol), cyclic or acyclic ethers (e.g., diethyl ether, tetrahydrofuran, Alkane), aromatic hydrocarbons (such as benzene, toluene, xylene), halogenated hydrocarbons (such as dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (such as chlorobenzene, dichlorobenzene), nitrile Classes (such as acetonitrile), carboxylates (such as ethyl acetate), decylamine (such as N, N-dimethylformamide, N,N-dimethylacetamide), dimethyl hydrazine, 1, 3-Dimethyl-2-imidazolidinone, water and acetic acid or the reaction can be carried out in a mixture of two or more such solvents.

The reaction is usually carried out at a temperature of from 0 ° C to 150 ° C and preferably at room temperature, but it can also be carried out at the reflux temperature of the reaction mixture. The reaction time may vary depending on the scale of the reaction and the reaction temperature, but is usually between half an hour and 72 hours.

After completion of the reaction, the compound [XX] is isolated from the reaction mixture by one of the usual separation techniques. If necessary, the compound is purified by recrystallization, distillation or chromatography, or if desired, may be used in the next step without purification. Furthermore, it is possible to separate the compound of the formula [XX] with a salt such as a salt of hydrochloric acid or trifluoroacetic acid.

Step (V15)

A possible synthetic system for the compound of formula [XXII] is shown in Scheme 4.

The compound of the formula [XXI] is converted to the compound of the formula [XXII] by conversion of the acid to N,O-dimethyl-hydroxylamine using a guanamine formation method, which is described in the literature (US 6,562,811 A, US 2003) /158185 A1 or J. Med. Chem. 2001, vol. 44, 6, 863-872).

Step (V16)

A possible synthetic system for the compound of formula [VII-a] is shown in Scheme 4.

The compound of the formula [XXII] is converted to the compound of the formula [VII-a] by converting the weinreb amide to an intermediate decyl alkyne according to a known literature method (J. Org. Chem. 2000, Vol. 5, 17, 5114-5119) was then treated with hydrazine and cyclized to pyrazole according to literature methods (US 6,310,049 A).

Another subject of the invention relates to the non-medical use of the thienylpyrimidinylpyrazole or mixtures thereof according to the invention for controlling unwanted microorganisms and reducing mycotoxins in plants and plant parts.

Another subject of the invention relates to an agent for controlling unwanted microorganisms and mycotoxins which are reduced in plants and plant parts, comprising at least one thienylpyrimidinylpyrazole according to the invention.

Furthermore, the present invention relates to a method for controlling undesired microorganisms and reducing mycotoxins in plants and plant parts, characterized in that the thienylpyrimidinylpyrazole according to the present invention is applied to microorganisms and/or In its environmental zone.

The substances according to the invention have potent bactericidal activity and can be used to control unwanted microorganisms such as molds and bacteria, in crop protection and in the protection of substances.

The invention further relates to crop protection compositions for controlling unwanted microorganisms, in particular unwanted molds, which comprise the active compounds according to the invention. These are preferably fungicidal compositions which include agrochemically suitable adjuvants, solvents, carriers, surfactants or extenders.

Furthermore, the invention relates to a method for controlling unwanted microorganisms, characterized in that the active compound according to the invention is applied to phytopathogenic molds and/or to its environmental zones.

According to the invention, the carrier is a natural or synthetic organic or inorganic material with which the active compound is mixed or bonded for better applicability, in particular for application to plants or plant parts or seeds. The carrier, which may be solid or liquid, is generally inert and should be suitable for agricultural use.

Suitable solid or liquid carriers are, for example, ammonium salts and ground natural ores such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic ore, Such as extremely dispersed cerium oxide, aluminum oxide and natural or synthetic silicates, resins, waxes, solid fertilizers, water, alcohols, especially butanol, organic solvents, mineral oils and vegetable oils and derivatives thereof. Mixtures of such carriers can also be used. Suitable solid carriers for the granules are, for example, pulverized and graded natural rocks such as calcite, marble, pumice, sepiolite, dolomite, and synthetic particles of inorganic and organic powders, as well as particles of organic matter such as saws. Sawdust, coconut shell, maize cob and tobacco stem.

Suitable liquefied gaseous extenders or carriers are liquids which are gaseous at ambient ambient temperature and atmospheric pressure, such as aerosol propellants, such as halogenated hydrocarbons, and butane, propane, nitrogen and carbon dioxide.

Thickeners such as carboxymethylcellulose and natural and synthetic polymers in powder, granule or latex form, such as acacia, polyvinyl alcohol and polyvinyl acetate, or natural phospholipids such as cephalins and lecithins and synthetic phospholipids, Can be used in the formulation. Other possible additives are mineral oils and vegetable oils.

If the extender used is water, it is possible to use, for example, an organic solvent as an auxiliary solvent. Essentially, suitable liquid solvents are: aromatics such as xylene, toluene or alkylnaphthalene, chlorinated aromatic and chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride or methylene chloride, aliphatic hydrocarbons such as cyclohexane Alkanes or paraffins, such as mineral oil fractions, mineral oils and vegetable oils, alcohols such as butanol or ethylene glycol and the like, ethers and esters, ketones such as acetone, methyl ethyl Ketones, methyl isobutyl ketone or cyclohexanone, strong polar solvents such as dimethylformamide and dimethyl hydrazine, and water.

According to the invention, the composition may further comprise other constituents, for example, a surfactant. Suitable surfactants are emulsifiers and/or foam formers, dispersants or wetting agents having ionic or nonionic character, or mixtures of these surfactants. Examples of such are polyacrylic acid salts, salts of lignosulfonic acid, salts of phenolsulfonic acid or naphthalenesulfonic acid, polycondensates of ethylene oxide and fatty alcohols or with fatty acids or with fatty amines. Substituted phenol (preferably alkyl phenol or aryl phenol), salts of thiosuccinic acid esters, taurine derivatives (preferably alkyl taurate), polyethoxylated alcohols or phenol Phosphate esters, fatty esters of polyhydric alcohols, and derivatives of compounds containing sulfates, sulfonates and phosphates, such as alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, Aryl sulfonate, protein hydrolysate, lignin sulfite waste liquid and methyl cellulose. If one of the active compounds and/or one of the inert carriers is insoluble in water and when the application is carried out in water, a surfactant is required. The proportion of surfactant is between 5 and 40 weight percent based on the weight of the composition according to the invention.

It can use coloring agents such as inorganic pigments such as iron oxide, titanium dioxide and Prussian blue, and organic dyes such as halogen dyes, azo dyes and metal phthalocyanine dyes, and micronutrients such as iron and manganese. , boron, copper, cobalt, molybdenum and zinc salts.

If appropriate, other additional components may also be present, such as protective sols, adhesives, binders, thickeners, thixotropic substances, infiltration Agent, stabilizer, chelating agent, complex forming agent. Generally, the active compound can be combined with any solid or liquid additive conventionally used for the purpose of formulation.

The compositions and formulations according to the invention generally comprise between 0.05 and 99% by weight, 0.01 and 98% by weight, preferably between 0.1 and 95% by weight, particularly preferably between 0.5 and 90%. The active compound, most particularly preferably between 10 and 70% by weight.

The active compounds or compositions according to the invention may be used as such or, depending on their individual physical and/or chemical characteristics, in the form of their formulations or their use, such as aerosols, capsule suspensions , cold mist concentrate, warm mist concentrate, encapsulated granules, fine granules, fluid concentrate for seed treatment, ready-to-use solution, powder for dispersion, emulsifiable concentrate, oil-in-water emulsion, Water-in-oil emulsion, large granules, granules, oil-dispersible powder, oil-miscible fluid concentrate, oil-miscible liquid, foam, paste, insecticide-embedded seed, suspension Concentrate, suspension emulsion concentrate, soluble concentrate, suspension, wettable powder, soluble powder, dust and granules, water-soluble granules or lozenges, water-soluble powder for seed treatment, wettable powder, The natural products and synthetic substances impregnated with the active compound, as well as the microcapsules for the seeds in the polymeric substance and in the embedding material, and the ULV cold fogging and warm fogging formulations.

The formulations mentioned may be prepared in a manner known per se, for example by wetting the active compound with at least one conventional extender, solvent or diluent, emulsifier, dispersant, and/or adhesive or fixative. Agent, Moisture repellent, if appropriate, desiccant and UV stabilizer and, if appropriate, dyes and pigments, defoamers, preservatives, secondary thickeners, binders, gibberellins and other handling aids.

Compositions in accordance with the present invention include not only ready-to-use formulations and can be applied to plants or seeds with suitable equipment, but also include commercially available concentrates which must be diluted with water prior to use.

The active compounds according to the invention may be present as such or in their (commercially available) formulations and in the use forms prepared from such formulations, to contain other (known) active compounds, such as insecticides. , a mixture of traps, disinfectants, bactericides, acaricides, nematicides, fungicides, growth regulators, herbicides, fertilizers, safeners and/or chemical carriers.

The treatment of plants and plant parts with the active compound or composition according to the invention is carried out directly or by conventional treatment methods, for example by soaking, spraying, spraying, irrigating, steaming, dusting, fogging, spreading, foaming, Smearing, spreading, sprinkling (irrigating), drip irrigation and acting on its environment, habitat or storage space, and in the case of propagating substances, especially in the case of seeds, also by dry seed treatment, seed treatment The solution is used to treat the raw material with a water-soluble powder, to form a clam shell, to be embedded with a single- or multi-layer coating, and the like. It can also be applied to the soil by ultra low volume methods or by injection of the active compound preparation or the active compound itself into the soil.

The invention further includes a method of treating seeds.

The invention further relates to seeds treated by one of the methods described in the preceding paragraph. The seed according to the invention is used to protect seeds from In a method that does not want microorganisms. In these methods, seeds which have been treated with at least one active compound according to the invention are used.

The active compounds or compositions according to the invention are also suitable for the treatment of seeds. Most of the damage caused by pests to crop plants is caused by seed infections at the time of storage or after sowing, and at and after the germination of the plants. This period is particularly important because the roots and shoots of growing plants are particularly sensitive and even minor damage can lead to plant death. Therefore, it is of great benefit to protect the seed and the germinated plant by using appropriate compositions.

Controlling plant pathogenic molds by treating the seeds of plants has been known for a long time and is the subject of continuous improvement. However, there are still many problems with the handling of seeds, which may not be solved in a satisfactory manner. Therefore, it is desirable to develop methods for protecting seeds or plants that are germinated, which are omitted after planting or after plant germination, or at least significantly reduce the additional application of crop protection agents. It also wants to optimize the amount of active compound used so that the seed and the plant in the germination are optimally protected against phytopathogenic mold attack without harming the plant itself by the active compound used. In particular, the method of treating seeds should also take into account the fungicidal properties of the genetically modified plant itself in order to achieve optimal protection of the seed and the plant in the germination with a minimum amount of crop protection agent.

Accordingly, the present invention also relates to a method for protecting seeds and germinated plants from attack by phytopathogenic molds by treating the seeds with the composition according to the present invention. The invention also relates to the use of a composition according to the invention for treating seed to protect the seed and the germinated plant from phytopathogenic mold. Further, the present invention relates to a seed treated with the composition according to the present invention to protect against phytopathogenic mold.

Plant pathogenic mold damage The control of plants after germination is mainly carried out by treating the soil and the shoots of plants with a substance protection agent. Since it is considered that crop protection agents may affect the environment and the health of humans and animals, efforts are still being made to reduce the amount of active compound applied.

One of the advantages of the present invention is the specific systemic characteristics of the active compounds and compositions according to the present invention, meaning that when the seeds are treated with such active compounds and compositions, they not only protect the seeds themselves, but also protect them after germination. Plants are free of plant pathogenic molds. In this way, crops can be dispensed with directly during the sowing period or immediately afterwards.

It is also considered to be advantageous for the active compounds or compositions according to the invention to be used in particular for gene-transplanting seeds, wherein the plants from which the seeds are grown are capable of exhibiting proteins which are resistant to pests. By treating such seeds with the active compound or composition according to the invention, specific pests can be controlled, even by expression, for example, insecticidal proteins. Surprisingly, other synergistic effects can be observed here, which additionally enhance the protective effect against pest attacks.

The composition according to the invention is suitable for protecting seeds of any cultivar plant used in agronomy, greenhouses, forests or horticulture and viticulture. In particular, this is cereals (such as wheat, barley, rye, black wheat, sorghum / millet and oats), maize, cotton, soybeans, rice, potatoes, sunflowers, beans, coffee, beets (such as beets and fodder beets), Seeds of peanuts, canola, poppy, olives, coconut, cocoa, sugar cane, tobacco, vegetables (such as tomatoes, cucumbers, onions and lettuce), turf and ornamental plants (see also below). Treating cereals (such as wheat, barley, rye, black wheat and oats), the seeds of maize and rice are the most important.

It is also important to treat gene-transferred seeds using the active compounds or compositions according to the invention, as also indicated below. This relates to seeds of plants containing at least one heterologous gene capable of expressing a multi-peptide or protein having insecticidal properties. The heterologous gene in the gene-transferred seed may be derived from, for example, a microorganism of the genus Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Ring Rot, Glomus or Mycobacterium. This difference The gene is preferably derived from Bacillus, and the gene product is effective against European maize and/or western maize rootworm. The heterologous gene is particularly preferably derived from Bacillus thuringiensis.

In the context of the present invention, the compositions according to the invention are applied separately or to the seed in a suitable formulation. Preferably, the seed is treated in a sufficiently stable state so that no damage occurs during processing. Typically, the seed can be processed at any time between harvest and sowing. The commonly used seed has been isolated from plants and does not contain the hard shaft, shell, stalk, skin, hair or fruit flesh. Thus, it can be used, for example, a seed that has been harvested, cleaned and dried to a moisture content of less than 15% by weight. Alternatively, seeds which have been dried, for example, treated with water and then dried, may also be used.

In the treatment of seeds, it must generally be noted that the amount of the composition according to the invention applied to the seed and/or the amount of other additives is selected such that the germination of the seed does not adversely affect, or the resulting plant is not subject to damage. Of particular note is the fact that the active compound has a phytotoxic effect at a particular rate of application.

The composition according to the invention can be applied directly, i.e. without any other constituents and without dilution. Generally, the compositions are preferably applied to the seed in a suitable formulation. Suitable formulations and methods for treating seeds are known to those skilled in the art and are described, for example, in the following documents: US 4,272,417 A, US 4,245,432 A, US 4,808,430 A, US 5,876,739 A, US 2003/ 0176428 A1, WO 2002/080675 A1, WO 2002/028186 A2.

The active compounds which can be used according to the invention can be converted into conventional seed dressing formulations, such as solutions, emulsions, suspensions, powders, foams, raw materials or other embedding compositions for seed, and ULV Compounding.

These formulations are in a known manner by the active compound with conventional additives, for example, conventional extenders and solvents or diluents, dyes, wetting agents, dispersing agents, emulsifiers, antifoaming agents, preservatives Prepared by mixing a secondary thickener, a binder, a stressant, and water.

Useful dyes which may be present in the seed dressing formulations which can be used in accordance with the invention are all dyes customary for this purpose. In this context, it is possible to use not only a slightly water-soluble pigment but also a water-soluble dye. Examples include known dyes known as Rhodamine B, C.I. Pigment Red 112 and C.I. Solvent Red 1.

Suitable wetting agents which may be present in the seed dressing formulations which may be employed in accordance with the invention are those which promote wetting and which are customary in the formulation of agrochemical active compounds. It is preferred to use an alkylnaphthalenesulfonate such as diisopropyl- or diisobutylnaphthalenesulfonate.

Suitable dispersing agents and/or emulsifiers which may be present in the seed dressing formulations which may be employed in accordance with the invention are all nonionic, anionic and cationic dispersing agents which are customary in the formulation of agrochemical active compounds. Preferred are nonionic or anionic dispersing agents or mixtures of nonionic or anionic dispersing agents. Suitable nonionic dispersants which may be mentioned are, in particular, ethylene oxide/propylene oxide block polymers, alkylphenyl polyethylene glycol ethers and tristyrylphenol polyglycol ethers, and the like phosphates or Sulfate derivatives. Suitable anionic dispersants are, in particular, lignosulfonates, polyacrylates and arylsulfonate/formaldehyde condensates.

May be present in a seed dressing formulation that can be used in accordance with the present invention Defoamers are all suds suppressing substances which are conventionally used in agrochemically active compound formulations. Preferably, an anthrone defoamer and magnesium stearate can be used.

Preservatives which may be present in the seed dressing formulations which can be used in accordance with the invention are all materials which can be used for such purposes in agrochemical compositions. Examples include dichlorophenol and benzyl alcohol hemiformal.

Secondary thickeners which may be present in the seed dressing formulations which may be used in accordance with the present invention are all materials which may be used for such purposes in agrochemical compositions. Preferred examples include cellulose derivatives, acrylic acid derivatives, xanthan gum, modified clays and extremely dispersed vermiculite.

Binders which may be present in the seed dressing formulations which may be used in accordance with the present invention are all conventional adhesives which may be used in the product of the seed dressing. Preferred examples include polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and sodium cellulose acetate.

The geranin which may be present in the seed dressing formulations which can be used according to the invention is preferably sirolimus A1, A3 (= gibberellic acid), A4 and A7; particularly preferred is gibberellic acid. It is known (see R. Wegler "Chemie der Pflanzenschutz-und Schädlingsbekämpfungsmittel" [Chemistry of Crop Protectants and Pesticides], Vol. 2, Spengeg Villac, 1970, pp. 401-412).

Seed dressing formulations which can be used in accordance with the present invention can be used directly or after dilution with water to treat a wide range of seeds, including seeds of genetically transformed plants. In this paper, the additive multiplication effect also occurs by performance in interaction with the formed substance.

All mixers used in seed dressing operations are suitable for use The seed dressing formulation used in accordance with the present invention, or a formulation made therefrom by adding water, treats the seed. In the preparation of the seed dressing, in particular, the process is during the seed dressing operation, wherein the seed is placed in the mixer, and the seed dressing formulation of such a particular amount or diluted with water is added, and The contents were mixed until the formulation was evenly distributed on the seeds. If appropriate, then carry out the drying operation.

The active compounds or compositions according to the invention have potent microbicidal activity in crop protection and substance protection and can be used to control unwanted microorganisms such as molds and bacteria.

The fungicide can be used in crop protection to control Rhizopus, Oomycetes, Chytrix, Arbuscular Mycoplasma, Ascomycetes, Basidiomycetes and Deuteromycetes.

Bactericides can be used in crop protection to control Pseudomonas, Rhizobium, Enterobacteriaceae, Corynebacterium and Streptomyces.

The fungicidal composition according to the invention can be used for the therapeutic or protective control of phytopathogenic molds. Accordingly, the present invention relates to a method for the therapeutic or protective control of phytopathogenic molds using the active compounds or compositions according to the invention, which are applied to seeds, plants or plant parts, fruits or plants grown soil.

The composition according to the invention for controlling plant pathogenic molds on crop protection comprises an effective, but non-phytotoxic amount of the active compound according to the invention. "Effective, but non-phytotoxic amount" means a root sufficient to control a plant fungal disease in a satisfactory manner or to completely remove a fungal disease, and at the same time, does not cause any significant phytotoxicity symptoms. The amount of the composition according to the invention. Generally, this application rate can vary over a considerable range. It depends on a number of factors, for example, depending on the mold, plant, climatic conditions and constituents of the composition according to the invention to be controlled.

The fact that the active compound is sufficient to tolerate the plant to the concentration required to control plant diseases allows for the treatment of shoots, shoots and seeds, and soil.

All plants and plant parts can be treated in accordance with the present invention. It is to be understood that the term "plant" as used herein refers to all plants and flora, such as desired and unwanted wild plants or crop plants (including naturally grown crop plants). The crop plant may be a plant obtained by conventional cultivation and preferred methods or by biotechnological and genetic engineering methods or a combination of such methods, including genetically transformed plants and including cultivar plants, which are protected by plant breeder rights. And unprotected. It should be understood that plant parts refer to all parts and organs of the above and below ground parts of plants, such as buds, leaves, flowers and roots. Examples may be leaves, needles, stalks, stems, flowers, fruit bodies, Fruits, seeds, roots, bulbs and roots. Part of the plant also includes harvested plants and nutritive and reproductive reproductive material such as seedlings, bulbs, roots, cuttings and seeds.

When the active compound according to the present invention is sufficiently tolerated by plants, has favorable toxicity to warm-blooded animals and is environmentally friendly, it is suitable for protecting plants and plant organs to increase the yield and improve the quality of the harvested crops. It is preferably used as a crop protection agent. It is equivalent to combating general sensitivities and resistance classes and is active against all or some stages of development.

The following plants may be mentioned as plants which can be treated according to the invention: cotton, flax, grapes, fruits, vegetables, such as Rosaceae (for example pear fruits such as apples and pears, and stone fruits such as apricots, cherries, almonds and peaches, And berries such as strawberries), gooseberry, walnut, birch, lacquer, genus Fagaceae, mulberry, oleaceae, kiwi, carp, musa (such as banana plants and banana plantations), valerian (eg Coffee), tea family, sycamore family, Rutaceae (eg lemon, citrus and grapefruit); Solanaceae (eg tomato), Liliaceae, Compositae (eg lettuce), Umbelliferae, Cruciferae, Polygonaceae, Gourd Branch (eg gherkin), onion (eg leek, onion), pteridophyte (eg pea); main crop plants such as Gramineae sp. (eg maize, turf, cereals such as wheat, rye, Rice, barley, oats, millet and triticale), Poaceae sp. (eg sugar cane), Compositae (eg sunflower), cruciferous (eg apricot milk cabbage, red cabbage, broccoli, broccoli, Ball cabbage, cabbage, broccoli Radish, as well as canola, mustard, horseradish and cress), legumes (eg beans, peanuts), pteridophyte (eg soybean), Solanaceae (eg potato), alfalfa (eg beet, fodder beet, alfalfa) Vegetables, beetroots; useful plants and ornamental plants in gardens and forests; and genetically modified species of such plants in each case.

As is premise, it is possible to treat all plants and parts thereof in accordance with the present invention. In a preferred embodiment, wild plant species and cultivated plants can be treated, or those obtained by conventional biological cultivation methods, such as hybridization or protoplast fusion, and parts thereof. In other preferred embodiments, the processing is by genetic engineering methods, if appropriate with the practitioner The method (genetically modified organism) combines the obtained gene transfer plants and cultivated plants, and parts thereof. The term "partial" or "plant part" or "plant part" has been explained before. Particularly preferred according to the invention is the treatment of plants of various commercially available or used cultivars. It should be understood that a cultivated plant refers to a plant that has new properties ("features") and has been obtained by conventional cultivation, by mutagenesis or by recombinant DNA techniques. They may be cultivars, varieties, organisms or genotypes.

The treatment method according to the invention can be used to treat genetically modified organisms (GMOs), such as plants or seeds. A genetically modified plant (or a gene transfer plant) is a plant in which a heterologous gene has been stably integrated into a genome. "Heterogeneous gene" means essentially a gene that is provided or combined outside the plant and, when introduced into the nucleus, chloroplast or mitochondrial genome, by expressing a protein or multi-success Peptides or new or improved agronomic or other properties of transformed plants by down-regulating or suppressing other genes present in plants (using, for example, antisense technology, synergistic inhibition mechanism technology or RNAi technology [RNA interference]) . The heterologous gene present in the chromosome is also referred to as a transgenic gene. A transgene that is defined by its specific location in the plant genome is called a transformation or gene transfer event.

Depending on the plant species or the cultivar plant, its location and growth conditions (soil, climate, growing season, nutrient uptake), the treatment according to the invention may also produce a super-additive ("co-multiply") effect. Thus, for example, the following effects may exceed the actual expected efficacy: reducing the rate of application and/or expanding the spectrum of activity and/or increasing the active compounds which may be used in accordance with the invention and The activity of the composition, the plant growth is better, the tolerance to high temperature or low temperature is improved, the tolerance to drought or water or soil salt content is improved, the flowering performance is improved, the harvest is easier, the ripening is accelerated, and the yield is higher. The fruit is larger, the plant is higher, the leaf color is greener, the flowering is earlier, the quality of the harvested product is higher and/or the nutritional value is higher, the sugar concentration in the fruit is higher, and the storage stability and/or processability of the harvest product are obtained. Preferably.

The active compounds according to the invention may also have a strong benefit in plants at a particular application rate. Therefore, they are also suitable for stabilizing plant defense systems against unwanted plant pathogenic molds and/or microbial and/or viral attacks. If appropriate, this may be one of the reasons for the enhanced activity of the composition according to the invention, for example against mold. It should be understood that herein, a plant-strong (resistance-induced) substance also refers to a composition of substances or substances capable of stimulating a plant defense system, in such a manner, when an unwanted plant pathogenic mold is immediately inoculated. The plants treated exhibit a substantial degree of resistance to these unwanted plant pathogenic molds. Thus, the substance according to the invention can be used to protect plants from attack by the mentioned pathogen for a specific period of time after treatment. After treatment with the active compound, the extension of the protection period reached from 1 to 10 days, preferably from 1 to 7 days.

Plants and cultivar plants which are suitable for treatment according to the invention comprise plants having all of the genetic material conferring particularly advantageous and useful characteristics to such plants, whether obtained by cultivation and/or biotechnological means.

It is also preferred that the plants and cultivars treated according to the invention are Resistant to one or more bio-stress factors, ie, the plant has better defense against animal and microbial pests, such as against nematodes, insects, mites, phytopathogenic molds, bacteria, viruses and/or viroids. force.

Plants and cultivar plants which are also suitable for treatment according to the invention are those which are resistant to one or more abiotic pressure factors. Abiotic stress conditions can include, for example, drought, cold temperature exposure, heat exposure, osmotic pressure, water immersion, increased soil salinity, increased exposure to minerals, exposure to ozone, exposure to glare, limited nitrogen nutrient availability, limited Phosphorus nutrient availability or lack of shelter.

Plants and cultivar plants which are also suitable for treatment according to the invention are those which are characterized by improved yield characteristics. Increasing yield in such plants can be, for example, improving plant physiology, improving plant growth and development outcomes such as water use efficiency, water stagnation benefits, improving nitrogen use, enhancing carbon assimilation, improving photosynthesis, and improving germination efficiency. And accelerate maturity. Yield can also be affected by improved plant architecture (under stress and non-stress conditions), including early flowering, flowering control in mixed seed production, seedling growth, plant size, internode number and internode length, root growth , seed size, fruit size, pod size, pod number or number of spikes, number of seeds per pod or per ear, seed weight, increase seed satiety, reduce seed dispersal, reduce split pods and resist lodging. Other yield characteristics include seed compositions such as carbohydrate content, protein content, oil content and composition, nutritional value, reduced anti-nutritional compounds, improved processability and better storage stability.

Plants that can be treated in accordance with the present invention are mixed plants that have exhibited mixed seed characteristics, or mixed effects, which generally result in higher yields, are robust, healthy, and resistant to biotic and abiotic stress factors. Such plants are typically obtained by heterozygous male-infertile parental (female kinship) mated by a close relative and male-bred parental (male brood) mated by another close relative. Mixed seeds are typically harvested from male sterile plants and sold to growers. Male sterile plants can sometimes be produced (eg in maize) by removing spike-like male flowers (ie mechanical removal of male reproductive organs or male flowers); however, more typically, male sterile lines are derived from plant genomes. Caused by genetic factors. In this case, and especially when the seed is the desired product from the mixed plant, it is typically advantageous for the male fertilization rate in the mixed plant containing the genetic factors responsible for male sterility. Completely repaired. This can be accomplished by convincing a male fertile having a fertilization rate repair gene capable of repairing a male fertilization rate in a mixed plant capable of repairing a male fertilization rate in a mixed plant containing a genetic factor responsible for male sterility. Male sterility genetic factors can be located in the cytoplasm. Examples of cytoplasmic male sterility (CMS) are, for example, those described in Brassica. However, genetic factors for male sterility can also be located in the nuclear genome. Male sterile plants can also be obtained by plant biotechnology methods such as genetic engineering. A particularly useful method for obtaining male sterile plants is described in WO 89/10396, wherein, for example, a ribonuclease, such as a barnase, is selectively expressed in the stamen cells in the stamen. The fertilization rate can then be mediated by a ribonuclease inhibitor, such as a choroidal cell of a bacillus RNase inhibitor (barstar) Repaired in performance.

Plants or cultivar plants (obtained by plant biotechnology methods such as genetic engineering) which can be treated according to the invention are herbicide-tolerant plants, i.e. plants which are tolerant to one or more given herbicides. Such plants can be obtained by genetic transformation or by selection of plants containing mutations conferring tolerance to such herbicides.

The herbicide-tolerant plant is, for example, a glyphosate-tolerant plant, that is, a plant that is tolerant to the herbicide glyphosate or a salt thereof. For example, a glyphosate-tolerant plant can be obtained by transforming a plant having the gene encoding the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Examples of such EPSPS genes are the AroA gene of Salmonella typhimurium (mutant CT7), the CP4 gene of Agrobacterium tumefaciens, the genetically encoded Petunia EPSPS, tomato EPSPS, or Goosegrass EPSPS. It can also be a mutated EPSPS. Glyphosate-tolerant plants can also be obtained by expressing genes encoding glyphosate oxidoreductase enzymes. Glyphosate-tolerant plants can also be obtained by expressing a gene encoding a glyphosate acetamyltransferase enzyme. Glyphosate-tolerant plants can also be obtained by selecting plants containing naturally occurring mutations of the above genes.

Other herbicide-resistant plants are, for example, plants which are tolerant to insecticides which inhibit the enzyme glutamine synthetase, such as dipropylamine, phosphinothricin or glufosinate. Such plants can be obtained by an enzyme which detoxifies a herbicide or a mutant glutamine synthetase enzyme which exhibits resistance to inhibition. An enzyme that is effective for detoxification, for example, an enzyme encoding a phosphetine acetyltransferase (such as a chain) a bar or pat protein of the genus Mycoplasma. Plants exhibiting an exogenous phosphetine-inhibitor converting enzyme have been described.

Other herbicide-tolerant plants are also plants that are tolerant to herbicides that inhibit the enzyme hydroxyphenylpyruvate dioxygenase (HPPD). Hydroxyphenylpyruvate dioxygenase is an enzyme that catalyzes the reaction of conversion of p-hydroxyphenylpyruvate (HPP) to homogentisate. Plants that are tolerant to HPPD inhibitors can be transformed with genes encoding naturally occurring resistant HPPD enzymes, or genetically encoded mutant HPPD enzymes. Tolerance to HPPD inhibitors can also be obtained by transforming plants that have genes encoding specific enzymes capable of forming gentisate, although HPPD inhibitors inhibit native HPPD enzymes. The tolerance of plants to HPPD inhibitors can also be improved by transforming plants with the gene encoding the enzyme pre-phenylate dehydrogenase and the gene encoding the HPPD-tolerant enzyme.

Other herbicide-resistant plants are plants that are tolerant to acetamidine acetate synthase (ALS) inhibitors. Known ALS inhibitors include, for example, sulfonylurea, imidazolinone, triazolopyrimidine, pyrimidinyloxy(thio)benzoate and/or sulfonylaminocarbonyltriazolyl ketone herbicide. Different mutations in ALS enzymes (also known as acetamidine hydroxyacid synthase, AHAS) are known to confer tolerance to different herbicide and herbicide groups. The production of sulfonylurea-resistant plants and imidazolinone-tolerant plants has been described in International Publication WO 1996/033270. Other sulfonylurea- and imidazolinone-tolerant plants have also been described, for example, in WO 2007/024782.

Other plants that are tolerant to imidazolinones and/or sulfonylureas Induced mutagenesis is obtained by selection in cell culture in the presence of a herbicide or by mutational cultivation.

Plants or cultivated plants (obtained by plant biotechnology methods such as genetic engineering) which can also be treated according to the invention are insect-resistant gene-transgenic plants, i.e., plants are rendered resistant by attack by specific target insects. Such plants can be obtained by genetic transformation or by selection of plants containing mutations conferring such insect resistance.

As used herein, "insect-resistance gene transfer plant" includes any plant comprising at least one of a transgenic gene comprising a coding sequence: 1) an insecticidal crystalline protein from Bacillus thuringiensis or an insecticidal portion thereof, such as Insect crystalline protein listed online: http://www.lifesci.sussex.ac.uk/Home/Neil_Crickmore/Bt/, or its insecticidal fraction, for example, Cry protein grade Cry1Ab, Cry1Ac, Cry1F, Cry2Ab a protein of Cry3Ae, or Cry3Bb or an insecticidal fraction thereof; or 2) a crystalline protein from Bacillus thuringiensis or a part thereof, which is a second crystalline protein of Bacillus thuringiensis or a part thereof, such as An insecticidal activity in the presence of a binary toxin composed of Cry34 and Cry35 crystalline proteins; or 3) a mixed insecticidal protein comprising two different insecticidal crystalline proteins of Bacillus thuringiensis, such as a protein mixture of the above 1) or a protein mixture of the above 2), such as the Cry1A.105 protein produced by the maize event MON98034 (WO 2007/027777); 4) Any of the proteins of any of the preceding paragraphs 1) to 3), some of which, in particular, 1 to 10, the amino acid being replaced by another amino acid to give a higher insecticidal activity against the target insect species, and / Or to expand the range of insect species affected by the target, and/or because of the changes induced in the coding DNA during colonization or transformation, such as the Cry3Bb1 protein in the maize event MON863 or MON88017, or the Cry3A protein in the maize event MIR604 Or 5) an insecticidal hidden protein from Bacillus thuringiensis or Bacillus cereus, or an insecticidal part thereof, as listed at: http://www.lifesci.sussex.ac.uk/Home/Neil_Crickmore/Bt a plant-based insecticidal protein (VIP) in /vip.html, such as a protein from the VIP3Aa protein grade; or 6) a hidden protein from Bacillus thuringiensis or Bacillus cereus, which is Bacillus thuringiensis or Bacillus cereus The second hidden protein, such as the binary toxin composed of VIP1A and VIP2A proteins, is insecticidal in the presence; 7) mixed insecticidal protein, including Bacillus thuringiensis or wax a part of different concealed proteins of Bacillus, such as a mixture of proteins in the above 1) or a mixture of proteins in the above 2); or 8) any of the proteins of the foregoing 1) to 3), wherein Certain, in particular, 1 to 10, the amino acid has been replaced by another amino acid to give a higher insecticidal activity against the target insect species, and/or to expand the range of affected insect species, and / or because of the changes induced in the coding DNA during colonization or transformation (although still encoding insecticidal Protein), such as the VIP3Aa protein in cotton event COT102.

Of course, insect-resistant gene transgenic plants, as used herein, also include any plant comprising a combination of genes encoding any of the above 1 to 8 proteins. In one embodiment, an insect-resistant plant line contains more than one transgenic gene encoding a protein of any of the above 1 to 8 grades, by using different protein insecticides on the same but different target modes of insects. Species, for example, bind to different receptor binding sites in insects to expand the range of insect species affected, or to delay the development of insect resistance to plants.

Plants or cultivated plants (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are those which are tolerant to abiotic stress factors. Such plants can be obtained by genetic transformation or by selection of plants containing mutations conferring such stress resistance. Particularly useful stress-tolerant plants include the following: a. plants containing planting cells or plants that are capable of reducing the expression and/or activity of multiple (ADP-ribose) polymerase (PARP) genes; Plants that reduce the expression and/or activity of a PARG-encoding gene of a plant or plant cell containing a stress-tolerant-enhancing gene; c. containing a stress-tolerant-enhancing transgene encoding a tobacco indoleamine adenine dinucleotide Plant-functional enzymes that rescue biosynthetic pathways, including tobacco glutaminase, tobacco hydrazide phosphoribosyltransferase, niacin-nucleoadenosyltransferase, tobacco guanamine adenine dinucleotide synthase or A plant of tobacco indole phosphoribosyltransferase.

Plants or cultivated plants (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention exhibit a change in the amount, quality and/or storage stability of the product of the harvest and/or the nature of the particular constituent of the product of the harvest. Changes, for example:

1) The genetically modified starch of the genetically transformed plant, compared with the starch synthesized in the wild type plant cell or plant, its physicochemical characteristics, especially the starch sugar content or the starch sugar/starch pectin ratio, the degree of branching, The average chain length, side chain distribution, viscous properties, gel resistance, starch particle size and/or granule morphology are altered such that the modified starch is more suitable for a particular application.

2) Gene-transplanting plants which synthesize non-starch carbohydrate polymers or their synthesis of non-starch carbohydrate polymers with altered properties do not require alteration of the gene when compared to wild-type plants. Examples are plants which produce polyfructose, in particular inulin and levan-type, plants which produce alpha-1,4-polyglucose, plants which produce alpha-1,6 branched alpha-1,4-polyglucose, and Produce alternating plants.

3) Gene transfer plants that produce acetaminophen hyaluronic acid.

Plants or cultivated plants (obtained by plant biotechnology methods such as genetic engineering) which can also be treated according to the invention are plants having altered fiber properties, such as cotton plants. Such plants may be obtained by gene transformation, or by selecting a plant containing a mutation that confers such altered fiber characteristics and comprising: a) a plant, such as a cotton plant, containing a modified version of the cellulase enzyme gene; b) plants containing altered rsw2 or rsw3 homologous nucleic acids, such as cotton plants; c) plants having enhanced sucrose phosphate synthase expression, such as cotton plants; d) plants having enhanced sucrose synthase expression, such as cotton plants; e) plants, such as cotton plants, in which the timing of intercellular filaments in the fibroblast matrix is altered, for example via downward regulation of fiber-selective beta 1,3-polyglucose; f) altered reactive fibers A plant, such as a cotton plant, is expressed, for example, via an N-acetylglucosamine invertase gene comprising a nodC and a chitin synthase gene.

Plants or cultivated plants (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants having altered oil-like properties, such as canola or related canola plants. Such plants may be obtained by genetic transformation, or by selecting plants containing mutations that confer such altered oil characteristics and comprising: a) plants which produce oils having a high oleic acid content, such as canola plants; b) A plant having an oil having a low linoleic acid content, such as a canola plant; c) a plant producing an oil having a low saturated fatty acid content, such as a canola plant.

Particularly useful gene transfer plants which can be treated according to the invention are plants comprising one or more genes which encode one or more toxins which are genetically modified plants and are sold under the following trade names: YIELD GARD ^® (eg maize) , cotton, soy), KnockOut ^® (eg maize), BiteGard ^® (eg maize), BT-Xtra ^® (eg maize), StarLink ^® (eg maize), Bollgard ^® (cotton), Nucotn ^® (cotton), Nucotn 33B ^® (cotton), NatureGard ^® (eg maize), Protecta ^® and NewLeaf ^® (potato). Examples of herbicide-tolerant plants that may be mentioned are maize cultivars, cotton cultivars and soybean cultivars, which are available under the trade name Roundup Ready ^® (tolerant to glyphosate, such as maize, cotton, soybeans) ), Liberty Link ^® (tolerant to phosphinone, such as canola), IMI ^® (tolerant to imidazolinone) and SCS ^® (tolerant to sulfonylurea, such as maize). Which may be mentioned of herbicide - resistant plants (in a conventional manner for herbicide tolerance of cultivated plants) comprising cultivars to Clearfield ^® (e.g. maize) sold the name.

Particularly useful genetically transformed plants that can be treated in accordance with the present invention are plants that contain a transformation event, or a combination of transformation events, and are listed, for example, in a database of national or regional regulatory agencies (see, for example, http://gmoinfo.jrc. Ec.europa.eu/).

Furthermore, in the case of substance protection, the active compounds or compositions according to the invention can be used to protect industrial substances against attack and destruction by unwanted microorganisms such as molds and insects.

Furthermore, the compounds according to the invention may be used alone or in combination with other active compounds as anti-scaling compositions.

It should be understood that the term "industrial material" as used herein refers to an inanimate substance that has been prepared for use in industry. For example, protected by the active compound of the invention An industrial substance that is free of microbial changes or destruction. It can be adhesives, glues, paper, wallpaper, and wood, fabrics, carpets, leather, wood, paints and plastics, cooling lubricants and can be infected or destroyed by microorganisms. Other substances. Plants and building parts that can be damaged by the proliferation of microorganisms, such as cooling water circuits, cooling and heating systems, and ventilation and air conditioning units are also mentioned in the scope of the substances to be protected. Industrial materials within the scope of the present invention preferably include binders, glues, paper and cardboard, leather, wood, paints, cooling lubricants and heat exchange fluids, particularly wood. The active compounds or compositions according to the invention can avoid adverse effects such as decay, erosion, fading, discoloration or mold. Furthermore, the compounds according to the invention can be used to protect objects in contact with sea water or alkaline water, in particular hulls, screens, nets, buildings, moorings and signalling systems from fouling.

The method according to the invention for controlling unwanted molds can also be used to protect stored items. In this context, it should be understood that a stored item is a natural substance of vegetable or animal origin or a processed product thereof, which is a natural source and is intended to be a long-term protector. Vegetable sources, such as plants or plant parts, such as stems, leaves, bulbs, seeds, fruits, grains, can be freshly harvested or dried (pre-), wetted, ground, ground, crushed or baked. Protected after baking. Stored items also include wood, unprocessed, such as construction timber, poles and fences, or finished versions, such as furniture. Storage items of animal origin are, for example, hides, leather, fur and animal hair. The active compounds according to the invention avoid adverse effects such as decay, erosion, fading, discoloration or mold.

Non-limiting examples of pathogens of certain fungal diseases that may be treated according to the present invention include: diseases caused by powdery mildew pathogens, such as powdery mildew, such as wheat powdery mildew; A genus of the genus Mycelia; a genus of the genus Monochamus, such as the genus Mycelium; a genus of the genus H. genus, such as the genus Mycelium; a disease caused by a rust pathogen, such as a rust fungus, such as rust fungus (Gymnosporangium sabinae); genus Ralstonia, such as R. solani; Puccinia, such as Phakopsora pachyrhizi and P. sylvestris; Puccinia genus, such as Puccinia striiformis, wheat Puccinia serrata, Puccinia triticina; Puccinia triticina; Pseudomonas, such as P. sylvestris; diseases caused by pathogens of the genus Oomycetes, such as white rust Genus, such as white rust; genus Potentilla, such as the genus Potentilla; genus Downy, such as Phytophthora or Brassica oleracea; Phytophthora, such as pathogenic plague; Trichoderma; genus Pseudomonas, such as Pseudomonas sinensis or C. sinensis; Genus, such as Pythium ultimum; leaf spot and leaf blight, for example, from Alternaria, such as Alternaria alternata; Cercospora, such as Eucalyptus genus, Cladosporium, such as Melon (Cladiosporium cucumerinum); genus Helicobacter, such as Helminthosporium (conidia: Dexterella, total: Helminthosporium) or Helminthosporium; Cycloconium, such as Cycloconium oleaginum; genus, such as the citrus compartment Phytophthora, such as the genus Cysticercus, such as the genus Cysticercus; the genus Phytophthora, such as the genus Pseudosporium; the genus genus, such as the small plexus; the genus Coccidia, such as Coccidioides; small Phytophthora, such as Leptosphaeria maculans or C. sphaeroides; Magnaporthe, such as M. oxysporum; Glomus, such as Cochlear, M. fijiensis; genus M. fijiensis; genus genus, such as Helminthosporium; genus genus, such as nucleus or chlorophyll; Genus, for example, Ramularia collo-cygni or Helminthosporium leucocephala; Fusarium, such as Fusarium sinensis; Neurospora, such as the mustard or the Italian tomato shell Acupuncture; a genus of the genus Rhizopus, such as Rhizopus genus; a genus of the genus of the genus, such as the bacterium of the genus Arthrobacter; a disease of the roots and stems, such as a genus of the genus Fusarium, such as the genus A genus of the genus Streptomyces, such as Streptomyces fuliginea; a genus of the genus Capsular genus, such as Capreolaceae; a genus of the genus Rhizopus, such as Rhizopus genus; Rhizoctonia Genus, such as Rhizoctonia solani; Sarocladium species, for example, Sarocladium oryzae; Phytophthora, for example, Rhizoctonia solani; Tapese, such as Tapesia acuformis; Genus, such as caused by Rhizopus oryzae; ear and panicle disease (including maize cob), for example, from Alternaria, such as Alternaria, Aspergillus, such as Aspergillus oryzae; , for example, Cladosporium fulvum; ergots such as ergot; genus Streptomyces, such as Streptomyces megacephala; Gibberella, such as Gibberella zeae; Monographella, for example Wheat leaf fungus Caused by (Monographella nivalis); by smut mold, such as A. sphaeroides, such as sphaerotheca fuliginea; genus genus, such as wheat smut, black smut, wheat black smut; a genus of genus, such as the genus Helminthosporium; a genus of the genus Phytophthora, such as the genus Phytophthora, a disease caused by the genus Pseudomonas sphaeroides; the fruit rot is caused by, for example, Aspergillus, for example, Aspergillus oryzae; Genus, for example, Botrytis cinerea; Penicillium, such as Penicillium sp. and Penicillium chrysogenum; Sclerotinia, such as Sclerotinia; Verticillium, such as Verticillium dahliae; Seed-and soil - rot and wilting disease of the vector, and diseases of the seedlings, for example, Alternaria species, such as Alternaria brassicicola; Aphanomyces species, such as root rot Aphanomyces euteiches; Ascochyta species, for example, Ascochyta lentis; Aspergillus species, for example, Aspergillus flavus; Cladosporium species , for example, lentils (Cladospo) Rium herbarum); Cochliobolus species, for example, Cochliobolus sativus (conidia type: Dexelella, creeping: Helminthosporium); Colletotrichum species, for example, (Colletotrichum coccodes); Fusarium species, for example, Fusarium culmorum; Gibberella species, for example, Gibberella zeae; Macrophomina species, for example, bean shell Macrophomina phaseolina; Microdochium species, for example, Microdochium nivale; Monographella species, for example, Monographella nivalis Penicillium species, for example, Penicillium expansum; Phoma species, for example, Phoma lingam; Phomopsis species, for example , Phomopsis sojae; Phytophthora species, for example, Phytophthora cactorum; Pyrenophora species, for example, Pyrenophora graminea; Pyricularia species, for example, Pyricularia oryzae; Pythium species, for example, Pythium ultimum; Rhizoctonia species, for example Rhizoctonia solani; Rhizopus species, for example, Rhizopus oryzae; Sclerotium species, for example, sclerotium (Scleroti) Um rolfsii); Septoria species, for example, Septoria nodorum; Typhula species, for example, caused by Typhula incarnate; Sporozoites, for example, Verticillium dahlia; cancer, ticks and arbuscular diseases caused by, for example, the genus Clam, for example, the red crust of the scorpion; The disease is caused by, for example, the genus Streptococcus, for example, Sclerotinia sclerotiorum; the deformity of leaves, flowers and fruits is, for example, from the genus Fusarium, such as the genus of the outer bacterium; A genus of bacteria, for example, caused by a deformed outer bacterium; a degenerative disease of a woody plant is, for example, an Esca species, for example, Phaeomoniella chlamydospora, Aspergillus oryzae ( Phaeoacremonium aleophilum) or Fomitiporia mediterranea; caused by Ganoderma, for example, Ganoderma boninense; diseases of flowers and seeds are caused, for example, by Botrytis, for example, Botrytis cinerea; The disease of the plant bulb is caused, for example, by Rhizoctonia, for example, Rhizoctonia solani; Helminthosporium, for example, by Helminthosporium fulvum; by bacterial pathogens, for example, Xanthomonas, For example, Xanthomonas campestris variety; Pseudomonas, such as Pseudomonas syringae melon-causing species; Erwinia, such as diseases caused by Erwinia amylovora. It is preferred to control the following soybean diseases: fungal diseases on leaves, stems, pods and seeds, for example, from Alternaria specs (Alternaria spec. atrans tenuissima) ), anthracnose (Colletotrichum gloeosporoides dematium var. truncatum), brown spot (S. soy), Cercospora brown spot and disease (C. cerevisiae), Fusarium leaf blight ( Fungus Trichosporon (Syn.), hairy nucleus Mycorrhizal leaf spot (Sclerotium genus), Phytophthora (Northeast Phytophthora), Helminthosporium rot (S. cerevisiae), Soybean ash leaf spot (Soybean cerevisiae), small light shell Leaf spot (Clover small Phytophthora), leaf spot of the genus Phaeocystis (Soybean fuliginea), pod and stem blight (Soybean spp.), powdery mildew (Soybean powdery mildew), Trichosporon Spot (C. oxysporum), Rhizoctonia genus, leaf and reticular plague (Rhizobacter serrata), rust (Pested potato rust fungus, Hawthorn rust fungus), 痂 (Soybean 痂 round Spore), caused by the leaf blight of the genus Rhizoctonia (Phaeocystis), and the small round shield (S. serrata).

The fungal diseases on roots and stems are, for example, black root rot (Calonectria crotalariae), black rot (coccidial), streptomyces or wilting, root rot , and pod and collar rot (Fusarium oxysporum, Fusarium solani, Fusarium oxysporum, Fusarium oxysporum), root rot (soybean brown necrosis), new genus (invasive new red shell), Pod and stem blight (R. sylvestris), stem ulcer (Diaporthe phaseolorum var. caulivora), Phytophthora rot (Pythium aureus), brown stalk rot (soybean stem brown rot) Pathogen), Pythium rot (Pythium oleifera, Pythium pyogenes, Pythium bacillus, Pythium genus, Pythium ultimum), Rhizoctonia root rot, Stem rot, and rickets (Rhizobacter serrata), Sclerotium stalk rot (Secretaria), sclerotium sclerotium (simple nucleus), caused by Rhizopus genus root rot (Candida).

Microorganisms capable of decomposing or changing industrial substances include, for example, bacteria, molds, yeasts, algae, and cohesive organisms. The active compound according to the invention is suitable for combating fungi, especially molds, wood fading and wood-destroying basidiomycetes, and anti-adhesive Quality organisms and algae. Microorganisms of the following genera may be mentioned as examples: Alternaria, such as the spores of the genus Aspergillus; Aspergillus, such as Aspergillus niger; Chaetomium, such as Chaetomium; Chaeococcus, such as powder Phytophthora; genus Lentinus, such as tiger skin mushroom; Penicillium, such as Penicillium citrifolia; porous genus, such as polychromic fungi; Phytophthora, such as Aureobasidium; Phytophthora such as Phytophthora (Sclerophoma) Pityophila); Trichoderma, such as Trichoderma viride; Escherichia, such as Escherichia coli; Pseudomonas, such as Pseudomonas aeruginosa; Staphylococcus, such as Staphylococcus aureus.

Furthermore, the active compounds according to the invention also have excellent antifungal activity. They have a very broad spectrum of antifungal activity, especially against dermatophytes and yeasts, molds and biphasic molds (such as against Candida, such as Candida albicans, Candida glabrata), and C. oxysporum, Aspergillus, such as Aspergillus niger and Aspergillus fumigatus, Trichophyton, such as Trichophyton, Microsporum, such as Microsporum canis and Auduinii. The list of such molds is in no way intended to limit the anti-fungal spectrum it covers, but only for clarification.

Thus, the active compounds according to the invention are useful in both medical and non-medical applications.

When the active compound according to the invention is used as a fungicide, the application rate can vary within a relatively wide range depending on the type of application. The application rate of the active compound according to the invention is from 0.1 to 10,000 g/ha, preferably from 10 to 1000 g/ha, particularly preferably from 50 to 300, when treating plant parts, such as leaves g/ha (in the case of irrigation or drip irrigation, the application rate can even be reduced, especially when using inert substances such as rockwool or perlite); when treating seeds: from 2 to 200 grams per 100 kg of seed, It should be from 3 to 150 grams per 100 kilograms of seed, particularly preferably from 2.5 to 25 grams per 100 kilograms of seed, most preferably from 2.5 to 12.5 grams per 100 kilograms of seed; from 0.1 to 10,000 grams per hectare when treated with soil. It should be from 1 to 5000 g/ha.

The dosages indicated herein are by way of example to illustrate the method according to the invention. Those skilled in the art will understand how to use the dosage, especially depending on the nature of the plant or crop to be treated.

The compositions according to the invention can be used to protect plants against phytopathogenic molds and/or microorganisms over a specific time frame after treatment. When the protection therein is effective, the period of protection provided is usually from 1 to 28 days, preferably from 1 to 14 days, more preferably from 1 to 10 days, and most preferably from 1 to 7 days, or from 1 to 7 days after treatment of the plant with the composition, or It is up to 200 days after treatment with plant propagation material.

Furthermore, the compositions and compositions according to the present invention can also be used to reduce the amount of mycotoxins in plants and harvested plant material and foods and animal feeds made therefrom. In particular, but not limited to the following, mycotoxins: deoxynivalenol (DON), Fusarium oxysporum, 15-Ac-DON, 3-Ac-DON, T2- and HT2- Toxin, fumaran, japonin, beads, sputum, valerian diacetate (DAS), beauverin, encephalosporin, layer Fusarium, Fusarenol, ochratoxin, patulin, ergot alkaloid and aflatoxin, and which can be produced, for example, by the following molds: Fusarium, such as sharp Fusarium oxysporum, Fusarium oxysporum, Fusarium oxysporum, Fusarium oxysporum, Fusarium graminearum (S. citrinum), Fusarium oxysporum, F. fujikoroi, F.musarum, tip Fusarium, Fusarium oxysporum, Fusarium oxysporum, F. pseudoidinearum, Fusarium oxysporum, Fusarium oxysporum, Fusarium oxysporum, Fusarium oxysporum, Fusarium oxysporum, Lang F. langsethiae, F. subglutinans, Fusarium oxysporum, F. verticillioides and others, from Aspergillus, Penicillium, Chromium, Grape genus and others.

The active compounds are also useful in the veterinary world and are toxic to warm-blooded animals against animal husbandry and parasitic protozoa found in livestock breeding, breeding, zoos, laboratory and laboratory animals and pets. It is equivalent to being active against all or some stages of the pest.

Animals raised or produced in agriculture include mammals such as sheep, goats, horses, scorpions, camels, buffalos, rabbits, and especially cattle and pigs or birds such as turkeys, ducks, geese and chickens, especially, or even insects. Such as B. bees.

Pets are, for example, mammals such as hamsters, guinea pigs, large mice, small mice, especially dogs and cats or caged birds.

A preferred embodiment is for use in birds. Other preferred specific examples are for use in mammals.

When applied to diseases (such as meat, milk, wool, hides, Eggs, honey, etc., can avoid or reduce death, so the use of active compounds can simplify the livestock industry.

The novel active compounds are administered in a conventional manner, either directly or in a suitable formulation, gastrointestinally, parenterally, transdermally, nasally in the veterinary field and in animal husbandry. For enteral administration, the active ingredient is administered, for example, as a powder, a suppository, a lozenge, a capsule, a paste, a drink, a granule, a medicinal preparation, a bolus, a medicated feed or drinking water. Transdermal application is carried out, for example, by dip coating, spraying, bathing, rinsing, casting (injection and pouring) and dusting. Parenteral administration, for example, is by injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implantation.

In parasitic protozoa:

Mastigophora (Flagellata), such as Trypanosomatidae, such as Trypanosoma b. Brucei, TbGambiense, Rhodsia Trypanosoma (Tb Rhodesiense), T. Congolense, T. cruzi, T. Evansi, T. Equinum, Trypanosoma cruzi (T. Lewisi), T. Percae, T. Simiae, T.Vivax, Leishmania brasiliensis, L. Donovani, L. Tropica, such as Trichomonadidae, such as Giardia lamblia, G. canis.

Sarcomastigophora (Rhizopoda), Such as the amoeba (Entamoebidae), such as Entamoeba histolytica, Hartmanellidae, such as Acanthamoeba sp., Harmanella Sp.)

Apicomplexa (Sporozoa), such as Eimeridae, such as Eimeria acervulina, E. Adenoides, E. Alabahmensis, E. Anatis, E. Anserina, E. Arloingi, Akhsa E.Ashata, E.Auburnensis, E.Bovis, E.Brunetti,Canine Emerald E. Canis, E. Chinchillae, E. Clupearum, E. Columbae, E. Contorta , E. Crandalis, E. Debliecki, E. Dispersa, E. Ellipsoidales, 镰E.Falciformis, E.Faurei, E.Flavescens, E.Gallopavonis,Haas Ai E. Hagani, E. Intestinalis, E. Iroquoina, Eimeria without Eimeria ( E.Irresidua), pigeon E.Labbeana, E.Leucarti, E.Magna, Eimeria (E. .Maxima), E. Media, E. Meleagridis, turkey and slow E.Meleagrimitis, E.Mitis, E.Necatrix, E.Ninakohlyakimovae,Emmy E. Ovis, E. Parva, E. Pavonis, E. Perforans, E. coli (E) .Phasani), E. Piriformis, E. Praecox, E. Residua, E. Scabra, Ai E.spec., E.Stiedai, E.Suis, E.Tenella, Truncate Amy Coccidia (E.Truncata), E.Truttae, E.Zuernii, (Globidium spec.), Issopora belli, canine, etc. I. Canis, I.Felis, I.Ohioensis, I.Rivolta, Isospora (I.Rivolta) I.spec.), I. Suis, Cystisospora spec., Cryptosporidium spec. (especially Cryptosporidium) Such as Toxoplasmadidae, such as Toxoplasma gondii, Hammondia heydornii, Neospora caninum, Besnoitia besnoitii, such as arch Sarcocystidae, such as Sarcocystis bovicanis, S. Bovihominis, S. Ovicanis, S. Ovifelis, cat muscle S. Neuron, S. spec., S. shohominis, such as blood-borne protozoa (Leucozoidae), such as Leukozytozoon simondi, such as Plasmodiidae, such as Plasmodium berghei, P. falciparum, three days Plasmodium (P. Malariae), P. Ovale, P. vivax, P. spec., such as Piroplasmea Such as Babesia argentina, B. Bovis, B. Canis, B. spec., Theileria parva, Tyler ( Theileria spec.), such as Adeleina, such as Hepatozoon canis, H. spec.

The preparation of the active substance of the formula [I] according to the present invention is as follows. However, the invention is not limited to these examples.

Preparation of intermediate of formula [XIII]:

3-(Dimethylamino)-1-(3-thienyl)prop-2-en-1-one [XIII-1]

13.94 g of 1-(thiophen-3-yl)ethanone (110.5 mmol) and 21.9 ml of N,N-dimethylformamide dimethyl acetal (165.7 mmol) were heated under reflux overnight. . After cooling to room temperature, all volatile components were evaporated in vacuo. 19.27 g (96%) of 3-(dimethylamino)-1-(3-thienyl)prop-2-en-1-one as a light brown solid was obtained and used in the next step without further purification in.

logP (pH 2.7): 1.23

MS (ESI): 182.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.17 (dd, 1H), 8.62 (d, 1H), 7.50 (m, 2H), 5.73 (d, 1H), 3.12 (s, 3H, Br), 2.89 (s, 3H, br) ppm

1-(5-chloro-3-thienyl)-3-(dimethylamino)prop-2-en-1-one [XIII-2]

18.60 g of 1-(5-chloro-3-thienyl)ethanone (115.8 mmol) and 23.0 ml of N,N-dimethylformamide dimethyl acetal (173.7 mmol) were refluxed Heat in 5 hours. After cooling to room temperature, all volatile components were evaporated in vacuo. 24.86 g (99%) of 1-(5-chloro-3-thienyl)-3-(dimethylamino)prop-2-en-1-one as a brown solid was obtained without further purification In the next step.

logP (pH 2.7): 1.82

MS (ESI): 216.0 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.04 (d, 1H), 7.66 (d, 1H), 7.49 (d, 1H), 5.68 (d, 1H), 3.13 (s, 3H, Br), 2.90 (s, 3H, br) ppm

1-(2,5-dichloro-3-thienyl)-3-(dimethylamino)prop-2-en-1-one [XIII-3]

15.70 g of 1-(2,5-dichloro-3-thienyl)ethanone (80.5 mmol) and 21.3 ml of N,N-dimethylformamide dimethyl acetal (161.0 mmol) ) heated overnight in reflux. After cooling to room temperature, all volatile components were evaporated in vacuo. 20.22 g (100%) of 1-(2,5-dichloro-3-thienyl)-3-(dimethylamino)prop-2-en-1-one as a brown solid was obtained without further purification Even if used in the next step.

logP (pH 2.7): 2.27

MS (ESI): 250.0 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.63 (d, 1H), 7.34 (s, 1H), 5.48 (d, 1H), 3.14 (s, 3H, br), 2.88 (s, 3H, br) ppm

The following compounds can be prepared by the same method:

3-(Dimethylamino)-1-(2,5-dimethyl-3-thienyl)prop-2-en-1-one [XIII-4]

logP (pH 2.7): 1.92

MS (ESI): 210.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.54 (d, 1H), 7.00 (s, 1H), 5.44 (d, 1H), 3.09 (s, 3H, br), 2.84 (s, 3H, br), 2.54 (s, 3H), 2.35 (s, 3H) ppm

Preparation of intermediates of formula [XIX]:

4-[5-(5-methyl-3-thienyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]pyridine [XIX-1]

100 mg (0.19 mmol) of 4-[1-(tetrahydro-2H-pyran-2-yl)-5-(tributylstannyl)-1H-pyrazol-4-yl]pyridine and 68 Milligram (0.38 mmol) of 4-bromo-2-methylthiophene was stirred in 1 ml of dimethylformamide. 33 mg of tetrakis(triphenylphosphine)-palladium(0) (0.02 mmol, 15 mol%) and 3 mg of copper (I) iodide (0.01 mmol, 10 mol%) were added thereto The mixture was degassed with a blanket gas for 5 minutes. Thereafter, the mixture was heated at 45 ° C for 2 hours. Next, the crude mixture was filtered through a cartridge with a hydrazine salt and the volatile components were removed in vacuo. The crude product was purified by chromatography on EtOAc (hexanehexane / ethyl acetate) to afford <RTI ID=0.0> Base-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]pyridine (41%).

4-[5-(5-methyl-3-thienyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]pyridine [XIX-1]

logP (pH 2.7): 1.34

MS (ESI): 326.03 ([M+H] ⁺ )

Preparation of intermediates of formula [XX]:

4-[3-(5-methyl-3-thienyl)-1H-pyrazol-4-yl]pyridine [XX-1]

The intermediates prepared in the general procedure V13 can also be used in the deprotection reaction without further purification.

The protected thienylpyrazole [XIX-1] (26.2 mg, 0.08 mmol) crude product was dissolved in 2 ml of methanol and used with 800 μL of HCl. Alkane (4 moles) treatment. The solution was stirred at room temperature for 1 hour and then concentrated. The obtained solid was washed with aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. After drying and evaporation of the solvent, 25.6 mg of 4-[3-(5-methyl-3-thienyl)-1H-pyrazol-4-yl]pyridine (54%).

4-[3-(5-methyl-3-thienyl)-1H-pyrazol-4-yl]pyridine [XX-1]

logP (pH 2.7): 0.67

MS (ESI): 242.04 ([M+H] ⁺ )

Preparation of intermediate of formula [XXII]:

N-methoxy-N,5-dimethylthiophene-3-carboxamide [XXII-1]

To a solution of 5-methylthiophene-3-carboxylic acid (20 g, 140.8 mmol) in CH ₂ Cl ₂ (200 mL) was added EtOAc (2. (4.0 mL) and the reaction mixture was stirred at room temperature for 4 hr. The solvent was evaporated, and diluted with CH ₂ Cl ₂ was co-distilled residue with CH ₂ Cl ₂ (200 ml) was added at 0 ℃ DIPEA (73.5 mL, 422.4 mmol), followed by N, O- dimethyl Base-hydroxylamine (20.5 g, 211.2 mmol) was stirred at room temperature for 16 h. The reaction mixture was diluted with CH ₂ Cl ₂ (200 mL), washed with 1N HCl solution, followed by washing with H ₂ O, the organic layer was separated dried (Na ₂ SO ₄₎ and concentrated. The residual compound was purified by column chromatography (EtOAc, 5-10%EtOAc / petroleum ether) to afford N-methoxy-N,5-dimethylthiophene-3-carboxyindole as a liquid. Amine (12 g, 46.1%).

MS (ESI): 185 ([M+H] ⁺ )

¹ H-NMR (400 MHz, CDCl ₃ ): δ = 7.80 (d, 1H), 7.20 (s, 1H, br), 3.65 (s, 3H), 3.33 (s, 3H), 2.47 (s, 3H) Ppm.

Preparation of the intermediate of the formula [VII] by the production method (V8):

3-(3-thienyl)-1H-pyrazole [VII-1]

18.00 g of 3-(dimethylamino)-1-(3-thienyl)prop-2-en-1-one (99.3 mmol) and 9.66 ml of hydrazine hydrate (198.6 mmol) were dissolved in ethanol. (100 ml) and heated under reflux for 15 hours. After cooling to room temperature, all volatile components were evaporated in vacuo. The residue was dissolved in ethyl acetate and washed with a half-saturated aqueous solution of ammonium chloride and brine. The organic phase was dried over MgSO4 and evaporated The crude material was triturated with hexane / EtOAc (EtOAc:EtOAc:EtOAc:

logP (pH 2.7): 1.39

MS (ESI): 151.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 12.90 (s, 1H, br), 7.81 - 7.37 (m, 4H, br), 6.58 (s, 1H, br)

3-(5-chloro-3-thienyl)-1H-pyrazole [VII-2]

23.00 g of 1-(5-chloro-3-thienyl)-3-(dimethylamino)prop-2-en-1-one (106.6 mmol) and 10.38 ml of hydrazine hydrate (213.3 mmol) Dissolved in ethanol (100 ml) and heated under reflux for 15 hours. After cooling to room temperature, all volatile components were evaporated in vacuo. The residue was dissolved in ethyl acetate and washed with a half-saturated aqueous solution of ammonium chloride and brine. The organic phase was dried over magnesium sulfate and concentrated to give a brown oil. The crude material was recrystallized from dichloromethane / hexane afforded 18.88 g (96%) of 3-(5-chloro-3-thiophenyl)-1H-pyrazole as an orange solid.

logP (pH 2.7): 2.04

MS (ESI): 185.0 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 13.00 (s, 1H, br), 7.75 (s, 1H, br), 7.64 (s, 1H, br), 7.47 (s, 1H, br ), 6.60 (s, 1H, br) ppm

3-(2,5-Dichloro-3-thienyl)-1H-pyrazole [VII-3]

20.00 g of 1-(2,5-dichloro-3-thienyl)-3-(dimethylamino)prop-2-en-1-one (80.0 mmol) and 7.78 ml of hydrazine hydrate (159.9) Monomolar was dissolved in ethanol (75 mL) and heated in reflux for 15 h. After cooling to room temperature, all volatile components were evaporated in vacuo. The residue was dissolved in ethyl acetate and washed with a half-saturated aqueous solution of ammonium chloride and brine. The organic phase was dried over magnesium sulfate and concentrated to give a ash White solid. The crude material was triturated with hexanes to yieldd.

logP (pH 2.7): 2.78

MS (ESI): 218.9 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 13.13 (s, 1H, br), 7.86 (s, 1H, br), 7.45 (s, 1H, br), 6.78 (s, 1H) ppm

3-(2,5-dimethyl-3-thienyl)-1H-pyrazole [VII-4]

2.16 g of 3-(dimethylamino)-1-(2,5-dimethyl-3-thienyl)prop-2-en-1-one (10.32 mmol) and 0.65 ml of hydrazine hydrate ( 13.42 mmoles were dissolved in ethanol (10 mL) and heated under reflux for 15 h. After cooling to room temperature, all the volatile components were evaporated in vacuo to give 821 mg (44%) of 3-(2,5-dimethyl-3-thienyl)-1H-pyrazole as a brown oil. It was used in the next step without further purification.

logP (pH 2.7): 2.07

MS (ESI): 179.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 12.80 (s, 1H, br), 7.68 (s, 1H, br), 6.98 (s, 1H), 6.42 (s, 1H), 2.50 ( s, 3H), 2.38 (s, 3H) ppm

Preparation of the intermediate of the formula [VII] by the production method (V16):

3-(5-methyl-3-thienyl)-1H-pyrazole [VII-a-1]

A stirred solution of TMS acetylene (9.6 ml) in THF (90 mL) was cooled to -78 °C, then EtOAc (EtOAc, EtOAc, Then, a solution (134 ml) containing N-methoxy-N,5-dimethylthiophene-3-carboxamide (5 g, 27.0 mmol) in THF was added dropwise to the reaction mixture. Stir at 78 ° C for 1 hour. Then, the solvent was evaporated and the reaction mixture was quenched with saturated NH ₄ Cl solution was cooled and concentrated. The residue was dissolved in of EtOH, _{NH 2 NH 2 x H 2 O} (3.1 ml) at 0 ℃ and stirred at room temperature for 16 hours. The residual compound was purified by column chromatography (EtOAc, 20%EtOAc/hexane) to afford 3-(5-methyl-3-thienyl)-1H-pyrazole as a solid (2 g , 45.1%).

MS (ESI): 165 ([M+H] ⁺ )

¹ H-NMR (400 MHz, CDCl ₃ ): δ = 7.58 (d, 1H), 7.28 (d, 1H), 7.08 (s, 1H), 6.44 (d, 1H), 2.49 (s, 3H) ppm.

Preparation of intermediates of formula [V]:

4-bromo-3-(5-methyl-3-thienyl)-1H-pyrazole [V-1]

Add NBS (106 mg, 0.6 m) to a solution of 3-(5-methyl-3-thienyl)-1H-pyrazole (50 mg, 0.3 mmol) in CCl ₄ (2 mL). Moore), stirred overnight at 70-75 ° C and monitored by TLC. The reaction mixture was diluted and the residue was diluted with CHCl ₃ and H ₂ O; the layers were separated, the aqueous layer was extracted twice with CHCl ₃ and washed with H ₂ O. The separated CHCl ₃ layer was distilled and the residue was purified by column chromatography (gelatin, 100-200 mesh) to give a liquid 4-bromo-3-(5-methyl-3-thiophene). Base)-1H-pyrazole (40 mg, 55.2%).

MS (ESI): 243, 245 ([M+H] ⁺ )

¹ H-NMR (400 MHz, CDCl ₃ ): δ = 7.61 (d, 1H), 7.60 (s, 1H), 7.18 (s, 1H), 2.53 (s, 3H) ppm.

Preparation of intermediates of formula [VI]:

1-isopropyl-3-(3-thienyl)-1H-pyrazole [VI-1]

Sodium hydride (1.50 g, 60% suspension in mineral oil, 37.4 mmol) was added portionwise to a solution containing 3.75 g of 3-(3-thienyl)-1H-pyrazole (25.0 m) under argon. Mole) in a solution of anhydrous N,N-dimethylformamide (50 mL). The mixture was stirred at room temperature for 15 minutes under argon and then cooled to -10 °C. Isopropyl iodide (3.74 mL, 37.4 mmol) was added dropwise at -10 °C, and the mixture was stirred at room temperature overnight. The yellow suspension was poured into water (100 mL) and extracted with EtOAc EtOAc. The combined organic phases were washed with EtOAc EtOAc m. The crude product was purified by silica gel chromatography (eluent: methylene chloride / EtOAc) to afford 3. (3-Thienyl)-1H-pyrazole and 676 mg (14%) of 1-isopropyl-5-(3-thienyl)-1H-pyrazole as a brown oil.

Main isomer: 1-isopropyl-3-(3-thienyl)-1H-pyrazole [VI-1]:

logP (pH 2.7): 2.56

MS (ESI): 193.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.75 (d, 1H), 7.70 (m, 1H), 7.55 (m, 1H), 7.46 (dd, 1H), 6.55 (d, 1H) , 4.50 (m, 1H), 1.43 (d, 6H) ppm

Minor isomer: 1-isopropyl-5-(3-thienyl)-1H-pyrazole:

logP (pH 2.7): 2.52

MS (ESI): 193.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.70 (m, 2H), 7.48 (d, 1H), 7.27 (dd, 1H), 6.32 (d, 1H), 4.62 (m, 1H) , 1.38 (d, 6H) ppm

3-(5-chloro-3-thienyl)-1-isopropyl-1H-pyrazole [VI-2]

Sodium hydride (2.46 g, 60% suspension in mineral oil, 61.6 mmol) was added portionwise to a solution containing 7.58 g of 3-(5-chloro-3-thienyl)-1H-pyridinium under argon. The azole (41.1 mmol) was dissolved in anhydrous N,N-dimethylformamide (100 mL). The mixture was stirred at room temperature for 15 minutes and then cooled to -10 ° C under argon. Isopropyl iodide (6.15 ml, 61.6 mmol) was added dropwise at -10 °C, and the mixture was stirred at room temperature overnight. The brown reaction mixture was poured into water (400 mL) andEtOAcEtOAc. The combined organic phases were washed with EtOAc EtOAc m. The crude product was purified by silica gel chromatography (eluent: methylene chloride/methyl-tert-butyl ether) to give 5.14 g (55%) of 3-(5-chloro-3) as pale yellow oil. -Thienyl)-1-isopropyl-1H-pyrazole and 863 mg (9%) of 5-(5-chloro-3-thienyl)-1-isopropyl-1H-pyrazole as a brown oil.

Main isomer: 3-(5-chloro-3-thienyl)-1-isopropyl-1H-pyrazole [VI-2]

logP (pH 2.7): 3.51

MS (ESI): 227.0 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.77 (d, 1H), 7.60 (d, 1H), 7.44 (d, 1H), 6.57 (d, 1H), 4.50 (m, 1H) , 1.42(d,6H)ppm

Minor isomer: 5-(5-chloro-3-thienyl)-1-isopropyl-1H-pyrazole

logP (pH 2.7): 3.30

MS (ESI): 227.0 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.60 (d, 1H), 7.49 (d, 1H), 7.33 (d, 1H), 6.36 (d, 1H), 4.61 (m, 1H) , 1.38 (d, 6H) ppm

3-(2,5-Dichloro-3-thienyl)-1-isopropyl-1H-pyrazole [VI-3]

Sodium hydride (0.92 g, 60% suspension in mineral oil, 22.9 mmol) was added portionwise to hexane containing 2.51 g of 3-(2,5-dichloro-3-thienyl)-1H. Pyrazole (11.5 mmol) in a solution of anhydrous N,N-dimethylformamide (25 mL). The mixture was stirred at room temperature for 15 minutes and then cooled to -10 ° C under argon. Isopropyl iodide (2.29 ml, 22.9 mmol) was added dropwise at -10 °C, and the mixture was stirred at room temperature overnight. The brown reaction mixture was poured into water (200 mL) andEtOAc. The combined organic phases were washed with EtOAc EtOAc m. The crude product was purified by silica gel chromatography (eluent: hexane/ethyl acetate) to give 2.39 g (yield: 80%) of 3-(2,5-dichloro-3- Thienyl)-1-isopropyl-1H-pyrazole and 134 mg (4%) of 5-(2,5-dichloro-3-thienyl)-1-isopropyl-1H-pyrene as a yellow oil Oxazole.

Main isomer: 3-(2,5-dichloro-3-thienyl)-1-isopropyl-1H-pyrazole [VI-3]

logP (pH 2.7): 4.85

MS (ESI): 261.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.88 (d, 1H), 7.41 (s, 1H), 6.74 (d, 1H), 4.54 (m, 1H), 1.44 (d, 6H) Ppm

Minor isomer: 5-(2,5-dichloro-3-thienyl)-1-isopropyl-1H-pyrazole

logP (pH 2.7): 4.01

MS (ESI): 261.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.57 (d, 1H), 7.30 (s, 1H), 6.35 (d, 1H), 4.30 (m, 1H), 1.35 (d, 6H) Ppm

3-(2,5-dimethyl-3-thienyl)-1-isopropyl-1H-pyrazole [VI-4]

Sodium hydride (274 mg, 60% suspension in mineral oil, 6.8 mmol) was added portionwise to 829 mg of 3-(2,5-dimethyl-3-thienyl)- under argon. 1H-pyrazole (4.6 mmol) in a solution of anhydrous N,N-dimethylformamide (10 mL). The mixture was stirred at room temperature for 15 minutes and then cooled to -10 ° C under argon. Isopropyl iodide (0.68 ml, 9.1 mmol) was added dropwise at -10 °C, and the mixture was stirred at room temperature overnight. The yellow suspension was poured into water (50 mL) and extracted with EtOAc EtOAc. The combined organic phases were washed with EtOAc EtOAc m. The crude product was purified by silica gel chromatography (eluent: methylene chloride/methyl-tert-butyl ether) to afford y. Methyl-3-thienyl)-1-isopropyl-1H-pyrazole and 300 mg (30%) of 5-(2,5-dimethyl-3-thienyl)-1-iso in yellow oil Propyl-1H-pyrazole.

Main isomer: 3-(2,5-dimethyl-3-thienyl)-1-isopropyl-1H-pyrazole [VI-4]

logP (pH 2.7): 3.72

MS (ESI): 221.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.75 (d, 1H), 6.96 (s, 1H), 6.39 (d, 1H), 4.49 (m, 1H), 2.51 (s, 3H) , 2.37(s,3H), 1.43(d,6H)ppm

Minor isomer: 5-(2,5-dimethyl-3-thienyl)-1-isopropyl-1H-pyrazole

logP (pH 2.7): 3.46

MS (ESI): 221.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 7.50 (d, 1H), 6.67 (s, 1H), 6.17 (d, 1H), 4.29 (m, 1H), 2.41 (s, 3H) , 2.23 (s, 3H), 1.32 (d, 6H) ppm

1-isopropyl-3-(5-methyl-3-thienyl)-1H-pyrazole [VI-5]

KOH (37.6 mg, 0.67 m) with a solution of 3-(5-methyl-3-thienyl)-1H-pyrazole (100 mg, 0.61 mmol) in THF (3 mL). Add, followed by the addition of isopropyl bromide (147.5 mg, 1.2 mmol), the temperature of the reaction was raised to 60-65 ° C and stirred overnight. The solvent was evaporated and the residue was extracted with EtOAc, washed with H ₂ O and concentrated. The residual compound was purified by column chromatography (gelatin, 30% MDC / n-hexane) to afford 1-isopropyl-3-(5-methyl-3-thienyl) as an oil. 1H-pyrazole.

¹ H-NMR (400 MHz, CDCl ₃ ): δ=7.38 (d, 1H), 7.26 (s, 1H), 7.14 (s, 1H), 6.37 (d, 1H), 4.51 (m, 1H), 2.50 (s, 3H), 1.52 (d, 6H) ppm.

Preparation of the intermediate of the formula [IV] by the production method (V1):

4-iodo-1-isopropyl-3-(3-thienyl)-1H-pyrazole [IV-1]

N-iodosuccinimide (4.03 g, 17.9 mmol) was added to 3.13 g of 1-isopropyl-3-(3-thienyl)-1H-pyrazole in argon at -10 °C. (16.3 mmol) in a solution of anhydrous N,N-dimethylformamide (50 mL). The reaction mixture was stirred at room temperature for 2 days. Aqueous 5% sodium thiosulfate (100 ml) and a saturated aqueous solution of sodium carbonate (70 ml) were added and the mixture was stirred at room temperature for 1 hour and then extracted with MTBE (3 x 80 ml). The combined organic phases were washed with EtOAc EtOAc m. The crude product was purified by silica gel chromatography (eluent: hexane/ethyl acetate) to afford 4.78 g (90%) of 4-iodo-1-isopropyl-3- as pale oil. (3-Thienyl)-1H-pyrazole.

logP (pH 2.7): 3.67

MS (ESI): 319.0 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.04 (s, 1H), 7.93 (dd, 1H), 7.61 (m, 1H), 7.54 (dd, 1H), 4.52 (m, 1H) , 1.43 (d, 6H) ppm

3-(5-chloro-3-thienyl)-4-iodo-1-isopropyl-1H-pyrazole [IV-2]

N-iodosuccinimide (5.08 g, 22.6 mmol) was added to 5.00 g of 3-(5-chloro-3-thienyl)-1-isopropyl- in argon at -10 °C. 1H-pyrazole (20.5 mmol) in anhydrous N,N-dimethylformamide (50 ml) in solution. The reaction mixture was stirred at room temperature for 2 days. Aqueous 5% sodium thiosulfate (150 ml) and a saturated aqueous solution of sodium carbonate (100 ml) were added and the mixture was stirred at room temperature for 1 hour and then extracted with MTBE (3 x 120 ml). The combined organic phases were washed with EtOAcq. The crude product was purified by silica gel chromatography (eluent: cyclohexane / ethyl acetate) to afford 7.43 g (100%) of 3-(5-chloro-3-thiophenyl) as pale oil. 4-iodo-1-isopropyl-1H-pyrazole.

logP (pH 2.7): 4.76

MS (ESI): 352.9 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.05 (s, 1H), 7.84 (d, 1H), 7.46 (d, 1H), 4.51 (m, 1H), 1.43 (d, 6H) Ppm

3-(2,5-Dichloro-3-thienyl)-4-iodo-1-isopropyl-1H-pyrazole [IV-3]

N-iodosuccinimide (4.42 g, 19.7 mmol) was added to 4.69 g of 3-(2,5-dichloro-3-thienyl)-1-iso in argon at -10 °C. Propyl-1H-pyrazole (17.9 mmol) in a solution of anhydrous N,N-dimethylformamide (50 mL). The reaction mixture was stirred at room temperature for 2 days. The reaction mixture was heated to 105 °C for 4 hours and then cooled to room temperature. Another portion of N-iodosuccinimide (1.00 g, 4.4 mmol) was added and the mixture was stirred at 105 ° C overnight. After cooling to room temperature, aqueous 5% sodium thiosulfate (150 ml) and saturated aqueous sodium carbonate (100 ml) was added and the mixture was stirred at room temperature for 1 hour and then extracted with MTBE (3 x 150 ml). The combined organic phases were washed with water (100 mL) brine brine The crude product of the color oil. The crude product was purified by silica gel chromatography (eluent: hexane/ethyl acetate) to afford 6.78 g (97%) of 3-(2,5-dichloro-3- Thienyl)-4-iodo-1-isopropyl-1H-pyrazole.

logP (pH 2.7): 5.03

MS (ESI): 386.9 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.10 (s, 1H), 7.25 (s, 1H), 4.54 (m, 1H), 1.42 (d, 6H)

4-bromo-1-isopropyl-3-(5-methyl-3-thienyl)-1H-pyrazole [IV-4]

KOH (18 mg) was added to a solution of 4-bromo-3-(5-methyl-3-thienyl)-1H-pyrazole (40 mg, 0.16 mmol) in THF (2 mL). , 0.32 mmol, isopropyl bromide (29 mg, 0.24 mmol) and the temperature of the reaction mixture was taken to 55-60 ° C, stirred overnight and monitored by TLC. The solvent was evaporated, EtOAc in was added, followed by addition of H ₂ O, dried (Na ₂ SO ₄₎ and concentrated. The residual compound was purified by column chromatography to give 4-bromo-1-isopropyl-3-(5-methyl-3-thienyl)-1H-pyrazole as a liquid. (10 mg, 22.2%) (isomeric mixture at 88:12 position).

logP (pH 2.7): 4.15

MS (ESI): 285, 287 ([M+H] ⁺ )

¹ H-NMR (400 MHz, CD ₃ CN): δ = 7.71 (s, 1H), 7.67 (d, 1H), 7.29 (s, 1H), 4.49 (m, 1H), 2.52 (s, 3H), 1.48 (d, 6H) ppm.

3-(2,5-Dimethyl-3-thienyl)-4-iodo-1-isopropyl-1H-pyrazole [IV-5]

N-iodosuccinimide (651 mg, argon at 0 ° C, 2.90 mmol) was added to contain 580 mg of 3-(2,5-dimethyl-3-thienyl)-1-isopropyl-1H-pyrazole (2.63 mmol) in anhydrous N,N-di In a solution of methylformamide (10 ml). The reaction mixture was stirred at room temperature overnight. Another portion of N-iodosuccinimide (118 mg, 0.53 mmol) was added and the mixture was stirred at room temperature overnight. Aqueous 5% sodium thiosulfate (100 mL) and aq. EtOAc (EtOAc) (EtOAc) The combined organic phases were washed with EtOAcq. The crude product was purified by silica gel chromatography (eluent: hexane/ethyl acetate) to afford 890 mg (93%) of 3-(2,5-dimethyl-3 -Thienyl)-4-iodo-1-isopropyl-1H-pyrazole.

logP (pH 2.7): 4.43

MS (ESI): 347.0 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.00 (s, 1H), 6.87 (s, 1H), 4.50 (m, 1H), 2.40 (s, 3H), 2.37 (s, 3H) , 1.42 (d, 6H) ppm

Preparation of the intermediate of the formula [II] by the production method (V4):

4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-amine [II-1]

Will be 1,4-two The alkane and 2M aqueous sodium carbonate solution was degassed by passing an argon bubble through the solution for 10 minutes. 2.06 g of 4-iodo-1-isopropyl-3-(3-thienyl)-1H-pyrazole (6.15 mmol) was weighed and added to a 100 ml 3-neck equipped with a reflux condenser and an internal thermometer. In a round bottom flask. 36.8 ml degassed 1,4-two Alkane, 2.36 g of tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-di Cyclopentaborin-2-yl)pyridin-2-yl]carbamate (7.38 mmol), 454 mg bis(tricyclohexylphosphine)palladium(II) dichloride (0.62 mmol) and 12.3 ml of degassed 2M sodium carbonate solution was added quickly. The reaction mixture was again degassed by argon gas for 1 minute and then heated to reflux for 3 hours under argon. After cooling to room temperature, the mixture was concentrated to one half of its original volume and filtered through ethyl acetate via a short pad of silica gel. The filtrate was extracted with ethyl acetate. The combined organic layers were washed with a saturated aqueous The residue was dissolved in tri-butanol (10 mL) and dichloromethane (10 mL). The reaction mixture was evaporated in vacuo and purified eluting eluting eluting eluting eluting eluting -[1-Isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}carbamate.

1.49 g of tert-butyl {4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}carbamate (3.87 mmol) The ears were dissolved in 35 ml of dichloromethane and cooled to 0 °C. Trifluoroacetic acid (1.19 ml, 15.46 mmol) was added at 0 ° C and the mixture was stirred at room temperature overnight. Another portion of trifluoroacetic acid (1.50 mL, 19.47 mmol) was added and the mixture was stirred overnight. Another portion of trifluoroacetic acid (0.50 mL, 6.49 mmol) was added and the mixture was stirred for 2h. A saturated aqueous solution of sodium carbonate was added and the mixture was extracted with dichloromethane. The combined organic layers were treated with saturated aqueous sodium bicarbonate and brine Washed, dried over MgSO4, and evaporated tolulujjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj 99%).

4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-amine [II-1]

logP (pH 2.7): 1.06

MS (ESI): 285.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ=8.02 (s, 1H), 7.83 (d, 1H), 7.54 (m, 1H), 7.46 (m, 1H), 7.17 (dd, 1H) , 6.40 (d, 1H), 5.85 (s, 2H, br), 4.52 (m, 1H), 1.47 (d, 6H) ppm

The intermediate tert-butyl {4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}carbamate can be isolated and The characterization is as follows:

logP (pH 2.7): 2.93

MS (ESI): 385.2 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ=9.70 (s, 1H), 8.16 (s, 1H), 8.13 (dd, 1H), 7.81 (d, 1H), 7.55 (m, 1H) , 7.47 (m, 1H), 7.14 (dd, 1H), 6.87 (dd, 1H), 4.56 (m, 1H), 1.48 (d, 6H), 1.45 (s, 9H) ppm

Preparation of the compound of the formula [I] by the production method (V4):

4-[3-(5-chloro-3-thienyl)-1-isopropyl-1H-pyrazol-4-yl]pyridine [I-1] {Example 143}

Will be 1,4-two The alkane and 2M aqueous sodium carbonate solution was degassed by passing an argon bubble through the solution for 10 minutes. Will be 123.0 mg of 4-(4,4,5,5-tetramethyl-1,3,2-di Cyclopentane-2-yl)pyridine (0.60 mmol) and 36.9 mg of bis(tricyclohexylphosphine)-palladium(II) dichloride (0.05 mmol) were weighed into a microwave oven (2-5) Milliliter reaction volume). 176.3 mg of 3-(5-chloro-3-thienyl)-4-iodo-1-isopropyl-1H-pyrazole (0.50 mmol) was dissolved in 3.3 ml of degassed 1,4-two The alkane is transferred to the reaction tank. 1.1 ml of degassed 2M sodium carbonate solution was quickly added. The reaction mixture was again degassed by argon gas flow for 20 seconds. The microwave bath was sealed with a septum cap and the reaction mixture was irradiated with radiation in a microwave oven to a temperature of 140 ° C for 20 minutes. After cooling to room temperature, the orange-brown reaction mixture was diluted with ethyl acetate (3 mL) and filtered th The combined filtrates were evaporated in vacuo and purified by silica gel chromatography (eluent: hexane/ethyl acetate) to give 99.1 g (61%) of 4-[3- (5-Chloro-3-thienyl)-1-isopropyl-1H-pyrazol-4-yl]pyridine.

logP (pH 2.7): 1.48

MS (ESI): 304.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.51 (dd, 2H), 8.25 (s, 1H), 7.37 (d, 1H), 7.31 (dd, 2H), 7.12 (d, 1H) , 4.54 (m, 1H), 1.48 (d, 6H) ppm

4-[3-(5-chloro-3-thienyl)-1-isopropyl-1H-pyrazol-4-yl]-3-fluoropyridine [I-2] {Example 31}

Will be 1,4-two The alkane and 2M aqueous sodium carbonate solution was degassed by passing an argon bubble through the solution for 10 minutes. Will be 167.0 mg 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-di Cyclopentane-2-yl)pyridine (0.75 mmol) and 36.6 mg 1,1'-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (0.05 mmol) Ear) Weighed into a microwave bath (2-5 ml reaction volume). 186.0 mg of 3-(5-chloro-3-thienyl)-4-iodo-1-isopropyl-1H-pyrazole (0.50 mmol) was dissolved in 3.0 mL of degassed 1,4-di The alkane is transferred to the reaction tank. 1.0 ml of degassed 2M sodium carbonate solution was added quickly. The reaction mixture was again degassed by argon gas flow for 1 minute. The microwave bath was sealed with a septum cap and the reaction mixture was irradiated with radiation in a microwave oven to a temperature of 140 ° C for 12 minutes. After cooling to room temperature, the black reaction mixture was used The alkane (5.0 mL) was diluted and filtered through ethyl acetate (3 x 5 mL). The combined filtrates were evaporated in vacuo and purified by EtOAc (EtOAc:EtOAc:EtOAc) (5-Chloro-3-thienyl)-1-isopropyl-1H-pyrazol-4-yl]-3-fluoropyridine.

logP (pH 2.7): 3.35

MS (ESI): 322.0 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.60 (d, 1H), 8.39 (dd, 1H), 8.17 (d, 1H), 7.35 (dd, 1H), 7.28 (d, 1H) , 7.12 (d, 1H), 4.59 (m, 1H), 1.48 (d, 6H) ppm

Preparation of the compound of the formula [I-a] by the production method (V6):

N-{4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}cyclopropanecarboxamide [Ia-1] {Example 25} And N-(cyclopropylcarbonyl)-N-{4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}cyclopropanecarboxylate Amine [Ia-2] {Example 42}

0.18 ml of cyclopropanecarbonium chloride (1.94 mmol) was added dropwise to a solution containing 183.4 mg of 4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridine. 2-Amine (0.65 mmol) and 0.27 mL of triethylamine (1.94 mmol) in dichloromethane (2.5 mL). The mixture was stirred at room temperature overnight and diluted with 2.5 mL dichloromethane. 2.0 ml of the reaction mixture was taken up to diatomaceous earth and purified by gelatin chromatography (eluent: cyclohexane / ethyl acetate) to give 89.2 mg (31%) of N- (cyclopropyl) as a white solid. -Carbocarbonyl)-N-{4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}cyclopropanecarboxamide.

N-(cyclopropylcarbonyl)-N-{4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}cyclopropanecarboxamide [Ia-2]{Instance 42}

logP (pH 2.7): 3.31

MS (ESI): 421.2 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ=8.47 (dd, 1H), 8.36 (s, 1H), 7.60 (m, 1H), 7.51 (m, 1H), 7.37 (dd, 1H) , 7.33 (d, 1H), 7.17 (dd, 1H), 4.54 (m, 1H), 1.95 (m, 2H), 1.49 (d, 6H), 0.95 (m, 4H), 0.90 (m, 4H) ppm

The remaining reaction solution was evaporated in vacuo and dried over EtOAc EtOAc EtOAc EtOAc EtOAc After concentrating the reaction mixture, the residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate) to afford 102.9 mg (44%) of N-{4-[1 -Isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}cyclopropanecarboxamide.

N-{4-[1-isopropyl-3-(3-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}cyclopropanecarboxamide [I-a-1] {Example 25}

logP (pH 2.7): 1.91

MS (ESI): 353.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 10.75 (s, 1H), 8.19 (dd, 1H), 8.12 (s, 1H), 8.11 (m, 1H), 7.54 (m, 1H) , 7.47 (m, 1H), 7.14 (dd, 1H), 6.91 (dd, 1H), 4.55 (m, 1H), 2.00 (m, 1H), 1.48 (d, 6H), 0.80 (m, 4H) ppm

Preparation of the compound of the formula [I-b] by the production method (V1):

4-[1-isopropyl-3-(5-methyl-3-thienyl)-1H-pyrazol-4-yl]pyridine [I-b-1]

21 mg (0.08 mmol) of 4-[5-(5-methyl-3-thienyl)-1H-pyrazol-4-yl]pyridine was dissolved in 0.3 ml of N,N-dimethylformamide in. 5 mg of sodium hydride (1.3 eq) was added to the oil in a 60% suspension and the mixture was stirred at 25 ° C for 20 min. Next, 22 mg of isopropyl iodide (0.12 mmol) was added and the reaction mixture was stirred at 25 ° C overnight. To facilitate the reaction, acetic acid (concentrated) was slowly added (0.2 eq) and then all volatile components were removed in a high vacuum. The residue was dissolved in water and extracted several times with ethyl acetate. Next, the organic phase was dried (Na ₂ SO ₄ ) and concentrated. Purification was carried out by gelatin chromatography using cyclohexane (A) / ethyl acetate (B) (0% B to 100% B). 7 mg of 4-[1-isopropyl-3-(5-methyl-3-thienyl)-1H-pyrazol-4-yl]pyridine [Ib-1] and a positional isomer (66:34) mixture of 4-[1-isopropyl-5-(5-methyl-3-thienyl)-1H-pyrazol-4-yl]pyridine.

4-[1-isopropyl-3-(5-methyl-3-thienyl)-1H-pyrazol-4-yl]pyridine [I-b-1] {instance number 6}

logP (pH 2.7): 1.38

MS (ESI): 284.1 ([M+H] ⁺ )

¹ H-NMR (400 MHz, d ₆ -DMSO): δ = 8.48 (dd, 2H), 8.22 (s, 1H), 7.31 (dd, 2H), 7.18 (d, 1H), 6.87 (d, 1H) , 4.52 (m, 1H), 2.44 (s, 3H), 1.48 (d, 6H) ppm

The compounds of the formula [I] set forth in the following Tables I and II are also obtained by the aforementioned methods.

[c] Examples 1, 2, 3 and 4 are hydrochlorides.

Method A Note the determination of the logP value and the quality test: the indicated logP value is performed on a reverse phase column (C18) by HPLC (High Performance Liquid Chromatography) according to EEC-Directive 79/831 Annex V.A8. measuring. Agilent 1100 LC system; 50*4.6 Zorbax Eclipse Plus C18 1.8 micron; eluent A: acetonitrile (0.1% formic acid); eluent B: water (0.09% formic acid); linear gradient from 10% acetonitrile to 95% acetonitrile 4.25 minutes, then 1.25 minutes at 95% acetonitrile; oven temperature 55 ° C; flow rate: 2.0 ml / min. Mass determination was performed using an Agilend MSD system.

Method B Note the determination of the logP value and the quality test: the indicated logP value is performed on a reverse phase column (C18) by HPLC (High Performance Liquid Chromatography) according to EEC-Directive 79/831 Annex V.A8. measuring. HP1100; 50*4.6 Zorbax Eclipse Plus C18 1.8 μm; eluent A: acetonitrile (0.1% formic acid); eluent B: water (0.08% formic acid); linear gradient from 5% acetonitrile to 95% acetonitrile at 1.70 min. It was then 1.00 min at 95% acetonitrile; oven temperature 55 ° C; flow rate: 2.0 ml/min. The mass measurement was carried out from water using a ZQ2000 mass spectrometer.

Method C Note the determination of the logP value and the quality test: The indicated logP value is based on EPLC-Directive 79/831 Annex V.A8 by UPLC (Super Efficient Liquid Chromatography) on a reverse phase column (C18). measuring. HP1100; 50*2.1 Zorbax Eclipse Plus C18 1.8 micron; eluent A: acetonitrile (0.09% formic acid); eluent B: water (0.1% formic acid); linear gradient from 10% A to 95% A at 3.25 minutes; Furnace temperature 40 ° C; flow rate: 0.8 ml / min. The mass measurement is carried out from water using a Premier or SQD mass spectrometer.

The calibration is carried out with unbranched alkan-2-ones (having from 3 to 16 carbon atoms) with a logP value known (logP values are based on retention time by linear interpolation between two consecutive alkanones) And measurement).

The λ-maximum is measured from the maximum value of the chromatographic signal from a UV spectrum from 200 nm to 400 nm.

Use case Example A

Phytophthora test (tomato) / preventive

Solvent: 49 parts by weight of N,N-dimethylformamide

Emulsifier: 1 part by weight of alkyl aryl polyglycol ether

1 part by weight of the active compound is mixed with a specified amount of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration to prepare a suitable active compound preparation.

To test for prophylactic activity, plant young plants are sprayed with the active compound formulation at the indicated application rates. One day after this treatment, the plants were inoculated with an aqueous spore suspension of Phytophthora infestans. The plants were placed in an incubation chamber at approximately 22 ° C and 100% relative atmospheric humidity for 1 day. The plants are then placed in an incubation chamber at about 20 ° C and 96% relative atmospheric humidity.

The test was evaluated 7 days after the inoculation. 0% refers to the efficacy associated with the untreated control group; 100% efficacy means no disease is observed.

In this test, the following compounds according to the invention showed 70% or even higher efficacy at a concentration of 500 ppm active ingredient: 1 (80%), 6 (70%), 9 (70%), 16 (95%) ), 19 (80%), 21 (80%), 22 (90%), 27 (90%), 28 (80%), 26 (90%), 23 (95%), 24 (90%), 25 (80%), 31 (70%).

Instance B

Monofilament test (courgette) / preventive

Solvent: 49 parts by weight of N,N-dimethylformamide

Emulsifier: 1 part by weight of alkyl aryl polyglycol ether

1 part by weight of the active compound is mixed with a specified amount of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration to prepare a suitable active compound preparation.

To test for prophylactic activity, plant young plants are sprayed with the active compound formulation at the indicated application rates. One day after this treatment, the plants were inoculated with an aqueous spore suspension of the monofilament shell. The plants are then placed in a greenhouse at about 23 ° C and 70% relative atmospheric humidity.

The test was evaluated 7 days after the inoculation. 0% refers to the efficacy associated with the untreated control group; and 100% efficacy means no disease is observed.

In this test, the following compounds according to the invention showed 70% or even higher efficacy at a concentration of 500 ppm active ingredient: 10 (90%), 12 (93%), 16 (80%), 19 (90%) ), 22 (70%), 29 (70%), 26 (93%), 23 (95%), 24 (95%), 25 (93%), 31 (85%).

Example C

Nuclear cavity test (barley) / preventive

Solvent: 49 parts by weight of N,N-dimethylformamide

Emulsifier: 1 part by weight of alkyl aryl polyglycol ether

1 part by weight of the active compound is mixed with a specified amount of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration to prepare a suitable active compound preparation.

To test for prophylactic activity, plant young plants are sprayed with the active compound formulation at the indicated application rates. One day after this treatment, the plants were inoculated with an aqueous spore suspension of the bacterium. The plants were placed in an incubation chamber at approximately 22 ° C and 100% relative atmospheric humidity for 48 hours. The plants are then placed in a greenhouse at about 20 ° C and 80% relative atmospheric humidity.

The test was evaluated 7-9 days after inoculation. 0% refers to the efficacy associated with the untreated control group; and 100% efficacy means no disease is observed.

In this test, the following compounds according to the invention showed 70% or even higher efficacy at a concentration of 500 ppm active ingredient: 6 (100%), 8 (95%), 9 (100%), 10 (100%) ), 11 (100%), 12 (95%), 16 (100%), 19 (100%), 21 (80%), 22 (100%), 30 (95%), 27 (100%), 28 (100%), 29 (94%), 26 (95%), 23 (100%), 24 (95%), 25 (90%), 31 (100%).

Example D

Alternaria test (tomato) / preventive

Solvent: 49 parts by weight of N,N-dimethylformamide

Emulsifier: 1 part by weight of alkyl aryl polyglycol ether

1 part by weight of the active compound is mixed with a specified amount of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration to prepare a suitable active compound preparation.

To test for prophylactic activity, plant young plants are sprayed with the active compound formulation at the indicated application rates. One day after this treatment, the plants were inoculated with an aqueous spore suspension of Alternaria alternata. The plants were placed in an incubation chamber at approximately 22 ° C and 100% relative atmospheric humidity for 1 day. The plants are then placed in an incubation chamber at about 20 ° C and 96% relative atmospheric humidity.

The test was evaluated 7 days after the inoculation. 0% refers to the efficacy associated with the untreated control group; and 100% efficacy means no disease is observed.

In this test, the following compounds according to the invention showed 70% or even higher efficacy at a concentration of 500 ppm active ingredient: 1 (95%), 6 (95%), 7 (90%), 8 (80%) ), 9 (95%), 10 (95%), 11 (70%), 12 (95%), 16 (90%), 18 (80%), 19 (95%), 21 (70%), 22 (95%), 30 (90%), 27 (80%), 28 (95%), 26 (90%), 23 (80%), 24 (80%), 25 (70%), 31 ( 90).

Claims (8)

A thienylpyrimidinylpyrazole derivative of formula (I) Wherein X ¹ represents CH or N, R ¹ represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₈ -propadienyl, C ₃ -C ₈ -trialkyldecyl, C ₄ -C ₈ -cycloalkenyl, C ₁ -C ₆ -alkoxy -C ₁ -C ₆ -alkyl, decyloxy-C ₁ -C ₆ -alkyl, heteroaryl-C ₁ -C ₆ -alkyl, aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylthio-C ₁ -C ₆ -alkyl, C ₁ -C ₄ -alkyl-C(O)-C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl -C(O)-C ₁ -C ₄ -alkyl,heterocyclyl-C(O)-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkyl-C(O)OC ₁ -C ₆ -Alkyl, C ₃ -C ₆ -cycloalkyl-C(O)OC ₁ -C ₄ -alkyl,heterocyclyl-C(O)OC ₁ -C ₄ -alkyl,heterocyclyl-C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, heterocyclyl, heteroaryl, wherein each of the substituents of the group consisting of the same or different R ¹⁶ is mono- or more Substituted, or represents H,C(O)NR ¹⁷ R ¹⁸ ,C(O)R ¹⁷ ,C(O)OR ¹⁷ ,S(O) ₂ R ¹⁷ ,C(S)NR ¹⁷ R ¹⁸ ,C(S) _{^{R 17, S (O) 2}} NR 17 R 18, R 2 represents H, cyano, halogen, or represents C ₁ -C ₆ - alkyl, C ₃ -C ₆ - cycloalkyl, heterocyclyl C ₂ -C ₈ - alkenyl, C ₂ -C ₈ - alkynyl, C ₁ -C ₈ - alkoxy, C ₂ -C ₈ - alkynyl group, C ₁ -C ₈ - alkylthio, a C ₃ -C ₈ -trialkylsulfanyl group, wherein each of the substituents which are the same or different groups consisting of the following are mono- or polysubstituted: halogen, cyano, amine, dimethylamine Or methoxy, R ³ represents H, halogen, cyano, OR ¹¹ , C(O)OR ¹¹ , C(O)SR ¹¹ , C(S)OR ¹¹ , C(O)R ¹¹ , C(S R ¹¹ , SR ¹¹ , NR ⁹ R ¹⁰ , C(O)NR ¹¹ R ²⁰ , C(S)NR ¹¹ R ²⁰ , N(R ¹⁷ )C(O)OR ¹¹ , N=CH-NR ¹⁷ R ¹⁸ , NH-CH-NR ¹⁷ R ¹⁸ , N=CR ¹⁷ R ¹⁸ , N(C ₁ -C ₆ -alkyl)-NHR ¹⁷ , N=C(H)OR ¹⁷ , N=C(OR ¹⁷ )R ¹⁸ , N=C(SR ¹⁷ )R ¹⁸ , C(=NR ¹⁷ )NR ¹⁷ R ¹⁸ ,SO(=NR ¹⁷ )R ¹⁸ ,SO ₂ NR ¹¹ R ²⁰ ,SO ₂ R ¹¹ , or represents C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₈ -alkynyl, C ₆ -C ₁₄ -aryl, C ₂ -C ₉ -heterocyclyl a C ₂ -C ₉ -heteroaryl group, wherein each of the substituents which are the same or different groups consisting of R ¹⁶ is mono- or polysubstituted, and the excluded compound is wherein, if X ¹ is N , R ³ is Substituted NH-phenyl, R ⁴ and R ⁵ each independently represent H, F, Cl, Br, I, cyano, nitro, OH, SH, or represents C ₁ -C ₆ -alkyl, C ₃ - C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₆ -C ₁₄ -aryl, C ₁ -C ₄ -alkoxy, O-(C ₆ - C ₁₄ -aryl), S-(C ₁ -C ₄ -alkyl), S(O)-(C ₁ -C ₆ -alkyl), C(O)-(C ₁ -C ₆ -alkyl a C ₃ -C ₈ -trialkylalkylene group, a heteroaryl group, a heterocyclic group, each of which is mono- or polysubstituted by a substituent of the group consisting of R ¹⁶ of the same or different, or Formed with its otherwise bonded carbon atom, any mono- or multiple identical or different halogens, oxygen, cyano or C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₆ -haloalkyl, C ₁ -C ₄ -haloalkoxy, substituted by C ₃ -C ₆ -cycloalkyl, having 5 to 8 ring atoms, wherein the ring consists of carbon atoms but It may contain from 1 to 4 heteroatoms selected from oxygen, sulfur or NR ¹⁹ , R ⁶ represents C ₁ -C ₆ -alkyl, H, halogen, or represents C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₂ -C ₈ -alkenyl, C ₂ -C ₈ -alkynyl, C(O)-C ₁ -C ₆ -alkyl, C ₁ -C ₈ -alkoxy, C ₁ -C ₈ -alkylthio, C ₁ -C ₈ -haloalkoxy, C ₁ -C ₆ -alkylthioalkenyl, C ₁ -C ₆ -alkyl Thio group, C ₃ -C ₈ -trialkyldecylalkyl, C ₆ -C ₁₀ -aryl, heteroaryl, heterocyclic, C ₆ -C ₁₀ -aryloxy, each of which is the same or The substituents of the group consisting of R ¹⁶ are mono- or polysubstituted, and R ⁷ represents H, halogen, cyano, nitro, C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl , C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₅ -C ₁₀ -aryl, heteroaryl, heterocyclic, or R ⁶ and R ⁷ together form a 5- to 7 a member ring which may be optionally substituted with one or more substituents selected from the group consisting of C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy, halogen, hydroxy, amine, cyano or nitro, wherein the ring consists of carbon atoms but may also contain from 1 to 4 heteroatoms selected from oxygen, sulfur or NR ¹⁹ , R ⁸ represents H, halogen, cyano, C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₆ - C ₁₀ - aryl, heteroaryl, heterocyclyl, R ⁹ and R ¹⁰ represents H ^{C (S) R 14, C} (O) R 14, SO 2 R 14, C (O) OR 14, OR 14 or ^{C (O) NR 14 R 15} , or represents C ₁ -C ₆ - alkyl, C _3- C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₈ -cycloalkyl, heterocyclyl or heteroaryl, each of which is arbitrary Mono- or polysubstituted by the same or different substituents: F, Cl, Br, OH, cyano, C ₁ -C ₆ -alkyl, OC(O)R ¹⁷ , OP(O) (OR ¹⁷ ₂ , OB(OR ¹⁷ ) ₂ or O-(C ₁ -C ₄ -alkyl), R ¹¹ and R ²⁰ represent H, C(S)R ¹² , C(O)R ¹² , SO ₂ R ¹² , C(O)OR ¹² , OR ¹² or C(O)NR ¹² R ¹³ , or represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₄ -aryl, heterocyclyl or heteroaryl, each of which is mono- or polysubstituted by a substituent of the group consisting of the following or different :F, Cl, Br, OH, cyano, C ₁ -C ₆ -alkyl, OC(O)R ¹⁷ , OP(O)(OR ¹⁷ ) ₂ , OB(OR ¹⁷ ) ₂ or O-(C ₁ -C ₄ -alkyl), R ¹² and R ¹³ represent H, or represent C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ - alkynyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₄ An aryl group, a heterocyclic group or a heteroaryl group, each of which is mono- or polysubstituted by a substituent of the same or different group consisting of F, Cl, Br, I, OH, carbonyl, Cyano, C ₁ -C ₆ -alkyl or C ₁ -C ₄ -alkoxy, R ¹⁴ and R ¹⁵ represent H, or represent C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl , C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₄ -aryl, benzyl, phenethyl, phenoxymethyl Or a heterocyclic group or a heteroaryl group, wherein each of the substituents which are the same or different from the group consisting of: mono- or polysubstituted: F, Cl, Br, I, OH, carbonyl, cyano, Methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, tert-butyl, n-pentyl, cyclopropyl, or methoxy, ethoxy, positive Propyloxy, isopropoxy, n-butoxy, tert-butoxy, methylsulfanyl, nitro, trifluoromethyl, difluoromethyl, C(O)R ¹⁷ , C(O) OR ¹⁷ , C(O)NR ¹⁷ R ¹⁸ , SO ₂ R ¹⁷ , OC(O)R ¹⁷ , R ¹⁶ represents OH, F, Cl, Br, I, cyano, NH-C(O)R ¹⁷ , NR ¹⁷ R ¹⁸ , C(O)R ¹⁷ , C(O)OR ¹⁷ , C(O)NR ¹⁷ R ¹⁸ , SO ₂ R ¹⁷ , OC(O)R ¹⁷ , or represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl , C ₃ -C ₈ -cycloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkylthio, O-(C ₃ -C ₈ -cycloalkyl), S-(C _3- C ₈ -cycloalkyl), C ₆ -C ₁₄ -aryl, O-(C ₆ -C ₁₄ -aryl), S-(C ₆ -C ₁₄ -aryl), heterocyclic or hetero An aryl group, each of which is mono- or polysubstituted by the same or different substituents: F, Cl, Br, I, OH, carbonyl, cyano, C ₁ -C ₆ -alkyl or C ₁ -C ₄ -alkoxy, R ¹⁷ and R ¹⁸ represent C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl , benzyl, aryl, each of which is mono- or polysubstituted by the same or different substituents: F, Cl, Br, OH, cyano, or represents H, R ¹⁹ represents H, C ₁ - C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(S)R ¹⁴ ,C(O)R ¹⁴ ,SO ₂ R ¹⁴ , C(O)OR ¹⁴ , and agrochemically active salts thereof. A thienylpyrimidinylpyrazole of the formula (I) as claimed in claim ¹ wherein X ¹ represents CH and R ¹ represents H, methyl, ethyl, n-propyl, isopropyl , n-butyl, isobutyl, second butyl, tert-butyl, n-pentyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH,- CH=CHCH ₃ ,-C≡CCH ₃ ,3-methylbut-2-en-1-yl,but-2-en-1-yl,but-3-en-2-yl,prop-2-yne -1-yl,but-2-yn-1-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, 1-cyclopropylethyl, -CH=C=CH ₂ , trimethyldecyl, tert-butyldimethylalkyl, cyclohexenyl, 2-methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2-ethoxy Ethyl, tert-butoxy-methyl, cyanomethyl, 1-cyanoethyl, 2-cyanoethyl, 1-cyanopropan-2-yl, trifluoromethyl, difluoromethyl ,2-fluoroethyl, 2,2-difluoroethyl, 1,3-difluoropropan-2-yl, 2-chloroethyl, (2,2-dichlorocyclopropyl)methyl, trifluoro Methoxy, difluoromethoxy, 2-(trifluoromethoxy)ethyl, methyl acetate, ethyl acetate, pyridin-2-ylmethyl, pyridin-3-yl Methyl, pyridin-4-ylmethyl, (1,3-thiazol-5-yl)methyl, (1,3-thiazol-4-yl)methyl, (1,3-thiazol-3-yl) Methyl, (1,3- Azole-5-yl)methyl, (1,3- -4-yl)methyl, (1,3- 3-yl)methyl, phenylmethyl, phenylethyl, methylthio, ethylthio, n-propylthio, isopropylthio, tert-butylthio, n-butyl Thio, tert-butylthio, isobutylthio, methylthioalkyl, phenyl, benzyl, naphthyl, oxiranyl, aziridine, 2-tetrahydrofuranyl, 3- Tetrahydrofuranyl, tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-4-yl, 2-tetrahydrothiophenyl, 3-tetrahydro Thienyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-iso Zyridinyl, 4-iso Zyridinyl, 5-iso Zyridinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidine, 5-pyrazolidine, 2- Azolidinyl, 4- Zyridinyl, 5- Zyridinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 2-pyrroline-2-yl, 2-pyrroline-3- Base, 3-pyrolin-2-yl, 3-pyrroline-3-yl, 2-iso Oxazolin-3-yl, 3-iso Oxazolin-3-yl, 4-iso Oxazolin-3-yl, 2-iso Oxazolin-4-yl, 3-iso Oxazolin-4-yl, 4-iso Oxazolin-4-yl, 2-iso Oxazoline-5-yl, 3-iso Oxazoline-5-yl, 4-iso Oxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-iso Thiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2-hexa Hydropyridyl, 3-hexahydropyridyl, 4-hexahydropyridyl, 1,3-di Alkan-5-yl, 2-tetrahydropyranyl, 4-tetrahydropiperidyl, 2-tetrahydrothiophenyl, 3-hexahydro-indole Base, 4-hexahydroindole Base, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-hexahydropyridyl Base, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, iso Zin-3-yl, different Azole-4-yl, different Zyrid-5-yl, 1H-pyrrol-1-yl, 1H-pyrrol-2-yl, 1H-pyrrol-3-yl, Zin-2-yl, Azole-4-yl, Zyrid-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazole-1- , pyrazol-3-yl, pyrazol-4-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4- Base -3-base, 嗒 4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridyl -2-yl, morpholine, wherein each of the substituents which are identical or different from R ¹⁶ is mono- or polysubstituted, or represents H,C(O)NR ¹⁷ R ¹⁸ ,C(O)R ¹⁷ , C(O)OR ¹⁷ , S(O) ₂ R ¹⁷ , C(S)NR ¹⁷ R ¹⁸ , C(S)R ¹⁷ , S(O) ₂ NR ¹⁷ R ¹⁸ , R ² represents H, cyano group, Br, Cl, F, or represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropyl, cyclobutyl Base, cyclopentyl, cyclohexyl, -CH ₂ CH=CH ₂ , -C≡CH, -C≡CCH ₃ , -CH ₂ C≡CH, methoxy, ethoxy, n-propoxy, isopropyl Oxyl, n-butoxy, tert-butoxy, -O-CH ₂ C≡CH, methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl, Tributylsulfanyl, n-butylsulfanyl, t-butylsulfanyl, isobutylsulfanyl, trimethyldecyl, each of which is the same or different substituents Mono- or polysubstituted: F, Cl, Br, cyano, amine, dimethylamino or methoxy, R ³ represents H, F, Cl, Br, cyano, OR ¹¹ , C(O)OR ¹¹ , C(O)R ¹¹ , NR ⁹ R ¹⁰ , C(O)NR ¹¹ R ²⁰ , N=C(OR ¹⁷ )R ¹⁸ , N=C(SR ¹⁷ )R ¹⁸ ,SO(=NR ¹⁷ )R ¹⁸ ,N(C ₁ -C ₆ -alkyl -NHR ¹⁷ or represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropyl, cyclobutyl, Cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, -CH=CHCH ₃ , -C≡CCH ₃ , but-2-ene 1-yl, but-3-en-2-yl, but-2-yn-1-yl, phenyl, benzyl, each of which is substituted by the same or different group consisting of R ¹⁶ The mono- or poly-substitution, R ⁴ , R ⁵ each independently represent H, F, Cl, Br, cyano, nitro, OH, SH, or represents methyl, ethyl, cyclopropyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, phenyl, methoxy, each of which is a substituent of the same or different group consisting of R ¹⁶ Mono- or poly-substituted, or formed with its otherwise bonded carbon atom, any single- or multiple identical or different F, Cl, Br, oxygen, cyano or alkyl, cycloalkyl, heterocyclic ,haloalkyl, alkoxy, aryl, hetero Substituted with a cycloalkyl group of 5 to 8 ring atoms, wherein the ring consists of carbon atoms, but may contain 1 to 4 heteroatoms selected from oxygen, sulfur or NR ¹⁹ hetero atoms of, R ⁶ representatives of H, Cl, F, Methyl, ethyl, cyano, difluoromethyl, trifluoromethyl, or represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, third Butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, methoxy , ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, methylthio, ethylthio, n-propylthio, isopropylthio, Tributylthio, n-butylthio, t-butylthio, isobutylthio, each of which is mono- or more of any substituents of the same or different group consisting of R ¹⁶ Substituted, R ⁷ represents H, F, Cl, Br, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl , n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, or R ⁶ and R ⁷ together may form a 5- to 7-membered ring which may be optionally substituted with one or more substituents selected from the group consisting of methyl, B. Base, trifluoromethyl, methoxy, trifluoromethoxy, F, Cl, Br, hydroxy, amine, cyano or nitro, wherein the ring consists of carbon atoms but may also contain from 1 to 4 From oxygen, sulfur or a hetero atom of NR ¹⁹ , R ⁸ represents H, F, Cl, Br, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second Base, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡ CH, R ⁹ and R ¹⁰ represent H, C(S)R ¹⁴ , C(O)R ¹⁴ , SO ₂ R ¹⁴ , C(O)OR ¹⁴ , OR ¹⁴ or C(O)NR ¹⁴ R ¹⁵ , R ¹¹ And R ²⁰ represents H, C(S)R ¹² , C(O)R ¹² , SO ₂ R ¹² , C(O)OR ¹² , OR ¹² or C(O)NR ¹² R ¹³ , or represents methyl, B Base, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, tert-butyl, n-pentyl, OC(O)Me, OC(O)Et, OP(O)(OMe _{) 2, OB (OMe) 2} , OB (OEt) 2 or by methoxy, ethoxy, n-propoxy , isopropoxy, n-butoxy, tert-butoxy substituted methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, tert-butyl, N-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, phenyl, each of which Any one of the substituents of the same or different group consisting of the following: mono- or polysubstituted: F, Cl, Br, OH, cyano, R ¹² and R ¹³ represent H, or represent methyl, ethyl , n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, phenyl, each of which is mono- or polysubstituted by a substituent of the same or different group consisting of :F, Cl, Br, I, OH, carbonyl, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second butyl, tert-butyl, n-pentyl Or methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, R ¹⁴ and R ^{1 5} represents H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropyl, cyclopropylmethyl, Cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, Phenyl, naphthyl, benzyl, phenethyl, phenoxymethyl, pyridyl, pyridyl Base, pyrimidinyl, furyl, thienyl, thioantyl, Tenchyl, pyrazolyl, imidazolyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, pyrrolidinyl, hexahydropyridyl, hydroquinone, wherein each of the following is composed of the same or different Substituents of the group are mono- or polysubstituted: F, Cl, Br, I, OH, carbonyl, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, Second butyl, tert-butyl, n-pentyl, cyclopropyl, or methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, methyl Sulfhydryl, nitro, trifluoromethyl, difluoromethyl, ethyl hydrazino, methoxycarbonyl, ethoxycarbonyl, or hydrogen, R ¹⁶ represents OH, F, Cl, Br, I, cyano , NH-C(O)R ¹⁷ , NR ¹⁷ R ¹⁸ , C(O)R ¹⁷ , C(O)OR ¹⁷ , C(O)NR ¹⁷ R ¹⁸ ,SO ₂ R ¹⁷ , or represent methyl, ethyl , n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, phenyl, methoxy, ethoxy, tetrahydrofuranyl, 3- Tetrahydrofuranyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-iso Zyridinyl, 4-iso Zyridinyl, 5-iso Zyridinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidine, 5-pyrazolidine, 2- Azolidinyl, 4- Zyridinyl, 5- Zyridinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 2-pyrroline-2-yl, 2-pyrroline-3- Base, 3-pyrolin-2-yl, 3-pyrroline-3-yl, 2-iso Oxazolin-3-yl, 3-iso Oxazolin-3-yl, 4-iso Oxazolin-3-yl, 2-iso Oxazolin-4-yl, 3-iso Oxazolin-4-yl, 4-iso Oxazolin-4-yl, 2-iso Oxazoline-5-yl, 3-iso Oxazoline-5-yl, 4-iso Oxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-iso Thiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2-hexa Hydropyridyl, 3-hexahydropyridyl, 4-hexahydropyridyl, 2-hexahydropyridyl Base, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, iso Zin-3-yl, different Azole-4-yl, different Zyrid-5-yl, 1H-pyrrol-1-yl, 1H-pyrrol-2-yl, 1H-pyrrol-3-yl, Zin-2-yl, Azole-4-yl, Zyrid-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazole-1- , pyrazol-3-yl, pyrazol-4-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4- Base -3-base, 嗒 4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridyl a -2- group wherein each of the substituents which are the same or different groups consisting of the following are mono- or polysubstituted: F, Cl, Br, I, OH, carbonyl, cyano, methyl, B , methoxy, R ¹⁷ and R ¹⁸ represent methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, n-pentyl, cyclopropane Base, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, benzyl, each of which is the same or The substituents of the group consisting of the following are mono- or polysubstituted: F, Cl, Br, OH, cyano, or represent H, R ¹⁹ represents H, methyl, ethyl, n-propyl, isopropyl Base, n-butyl, isobutyl, t-butyl, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH=CH ₂ , -CH ₂ CH= CH ₂ , -CH ₂ C≡CH, -C≡CH, C(S)R ¹⁴ , C(O)R ¹⁴ , SO ₂ R ¹⁴ , C(O)OR ¹⁴ , and agrochemically active salts thereof . A thienylpyrimidinylpyrazole of the formula (I) as claimed in claims 1 and 2, wherein X ¹ represents CH and R ¹ represents H, methyl, ethyl, propyl, isopropyl Base, isobutyl, second butyl, allyl, 3-methylbut-2-en-1-yl, prop-2-yn-1-yl, cyclopropyl, cyclobutyl, cyclopentyl , cyclohexyl, tetrahydro-2H-pyran-2-yl, tetrahydrofuran-3-yl, Tan-3-yl, thitan-3-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-4-yl, 2,2-difluoroethyl, 1,3- Difluoropropan-2-yl, 2-chloroethyl, 2-fluoroethyl, 2-(trifluoromethoxy)ethyl, cyanomethyl, 1-cyanoethyl, 2-cyanoethyl , 1-cyanopropan-2-yl, 2-methoxyethyl, 2-ethoxyethyl, 2-(methylsulfanyl)ethyl, cyclopropylmethyl, 1-cyclopropyl Ethyl, (2,2-dichlorocyclopropyl)methyl, 2-fluorobenzyl, 1-(2-fluorophenyl)ethyl, 3-cyanobenzyl, R ² represents H, methyl, Ethyl, n-propyl, methoxy, ethoxy, methylsulfanyl, methoxymethyl, difluoromethyl, 2-hydroxyprop-2-yl, hydroxymethyl, 2-hydroxyethyl , 2-cyanoethyl, R ³ represents H, amine, formamidine, acetamido, n-propylamino, isobutyl decylamino, (2-methylbutylidene) amine, (3 -methylbutyric acid)amino, (3,3-dimethylbutyryl)amine, (methoxyethyl)amino, [(2-methoxyethoxy)ethyl]amino, (3,3,3-trifluoropropenyl)amine, (cyanoethenyl)amine, (lactoamine), (2-hydroxy-2-methylpropionyl)amine, [( Methylsulfanyl)ethylamino]amine, [2-(4-Chlorophenoxy)propanyl]amino, (phenylethyl)amino, (3-phenylpropenyl)amine, [3-(4-chlorophenyl)propene Amidino, [2-(4-fluorophenyl)propanyl]amino, [2-(2-fluorophenyl)propanyl]amino, (cyclopentylethyl)amino, (cyclopropylethylhydrazine)amine, (cyclopropylcarbonyl)amino, [(2-methylcyclopropyl)carbonyl]amino, [(1-chlorocyclopropyl)carbonyl]amino, (ring Butylcarbonyl)amino, (2,3-dihydro-1H-indol-2-ylcarbonyl)amino, [(2-phenylcyclopropyl)carbonyl]amino, methacrylamidoamine, (3-methylbut-2-enyl)amino, (4-methylpent-3-enyl)amino, (benzylamino), (4-fluorobenzhydrazide) amine ,(3-Thienylcarbonyl)amino, (2-thienylcarbonyl)amino, (tetrahydrofuran-2-ylcarbonyl)amino, (tetrahydrofuran-3-ylcarbonyl)amino, (tetrahydro-2H-pyridyl) Alkyl-4-ylcarbonyl)amino, (methoxycarbonyl)amino, (ethoxycarbonyl)amino, (isopropoxycarbonyl)amino, (t-butoxycarbonyl)amine, Ethylamino, dipropylamine, diisobutylamino, bis(methoxyethyl)amino, bis(3-methylbutyl)amino, bis(cyclopropylcarbonyl) , bis(cyclopropylcarbonyl)amino, acetamidine (isobutyl decyl) amine, butyl fluorenyl (cyclopropylcarbonyl) amine, (cyclopropylcarbonyl) (propyl) amine, (cyclopropylcarbonyl) (methoxy) an amine group, (cyclopropylcarbonyl) (3-methylbutyl fluorene) amine group, (cyclopropylcarbonyl) (pentamethylene) amine group, isobutyl fluorenyl (propyl) amino group, (cyclopropylcarbonyl)(methoxycarbonyl)amino, (cyclopropylcarbonyl)(ethoxycarbonyl)amino,[(E)-(dimethylamino)methyl]amine, A Aminomethylmercapto, (ethylaminomethylhydrazine) amine group, R ⁴ , R ⁵ represents H, F, Cl, or a carbon atom bonded thereto, and any single- or multiple identical Or different F, Cl, Br, oxygen, cyano, methyl, ethyl, n-propyl, isopropyl, methoxy, trifluoromethyl, difluoromethyl, trifluoromethoxy, cyclopropane a ring substituted with a cyclopropylmethyl group and a cyclobutyl group, wherein they together represent -(CH=CH-N(R ¹⁹ ), -(CH=CH-CH=N)-, -(NH-CH =N)- or -(CH ₂ -C(O)-N(R ¹⁹ ), R ⁶ represents H, Cl, F, methyl, ethyl, cyano, difluoromethyl, trifluoromethyl, R ⁷ represents H, F, Cl, methyl, and R ⁸ represents H, Cl, R ^{1 9} represents H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, tert-butyl, n-pentyl, cyclopropyl, cyclobutyl, cyclopentane , cyclohexyl, -CH=CH ₂ , -CH ₂ CH=CH ₂ , -CH ₂ C≡CH, -C≡CH, ethyl hydrazino, n-propyl decyl, isobutyl fluorenyl, 2-methylbutyl fluorenyl, 3 -methylbutydenyl, 3,3-dimethylbutyryl, cyclopropylcarbonyl, and agrochemically active salts thereof. A composition for controlling a pathogenic fungus of a plant and a mycotoxin-producing mold, characterized by comprising at least one thiophenepyridinylpyrazole of the formula (I) according to any one of claims 1 to 3. , as well as extenders and / or surfactants. A use of the thiophenylpyrylpyrazole of the formula (I) according to any one of claims 1 to 3, for controlling microorganisms which are not desired. A method for controlling a pathogenic fungus of a plant and a mold for producing a mycotoxin, characterized in that the thienylpyrimidinylpyrazole of the formula (I) according to any one of claims 1 to 3 is applied to the microorganism And/or its environmental zones. A method for preparing a composition for controlling an undesirable microorganism, which is characterized in that the thiophenylpyrylpyrazole of the formula (I) according to any one of claims 1 to 3 of the patent application is supplemented with Mixing agents and/or surfactants. A use of a thiophenyl or pyrithionepyrazole of the formula (I) according to any one of claims 1 to 3 for the treatment of a genetically transgenic plant.