WO2007113322A2 - 5-hétarylpyrimidines substituées - Google Patents

5-hétarylpyrimidines substituées Download PDF

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Publication number
WO2007113322A2
WO2007113322A2 PCT/EP2007/053332 EP2007053332W WO2007113322A2 WO 2007113322 A2 WO2007113322 A2 WO 2007113322A2 EP 2007053332 W EP2007053332 W EP 2007053332W WO 2007113322 A2 WO2007113322 A2 WO 2007113322A2
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WIPO (PCT)
Prior art keywords
het
alkyl
compounds
methyl
hetarylpyrimidines
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PCT/EP2007/053332
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German (de)
English (en)
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WO2007113322A3 (fr
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Joachim Rheinheimer
Thomas Grote
Bernd Müller
Sarah Ulmschneider
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Basf Se
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Publication of WO2007113322A3 publication Critical patent/WO2007113322A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to the use of 5-hetarylpyrimidines for controlling phytopathogenic fungi, novel 5-hetarylpyrimidines and pesticides containing at least one such compound as an active ingredient.
  • WO 01/96314, WO 02/074753, WO 03/070721, WO 03/043993, WO 2004/103978 and WO 2005/019187 disclose 5-phenyl-4-aminopyrimidines and their use for controlling phytopathogenic fungi (phytopathogenic fungi) known.
  • the 5-phenyl-4-aminopyrimidines known from the prior art are in some cases unsatisfactory with regard to their fungicidal action or have undesired properties, such as a low compatibility with crops.
  • the present invention is therefore based on the object of providing compounds with better fungicidal activity and / or a better crop tolerance.
  • the present invention thus relates to the use of 5-hetarylpyrimidine compounds of the general formula I.
  • R 1 is d-C ⁇ -alkyl, C 3 -C 8 cycloalkyl, C 5 -C 0 bicycloalkyl, C 2 -C 8 alkenyl, C 4 -C 0 - alkadienyl, C 3 -C 6 cycloalkenyl, C C 2 -C 8 -alkynyl, phenyl, naphthyl, or a C-bound five- or six-membered saturated, partially unsaturated or aromatic heterocycle having one, two, three or four heteroatoms from the group O, N or S as ring members;
  • R 11 cyano, nitro, amino, hydroxy, C (O) NH 2, C (S) NH 2, carboxyl, C r C 6 - alkylcarbonyl, C 3 -C 6 cycloalkyl, Ci-C 6 -alkoxy, CrC 6 alkoxycarbonyl, d-Ce-alkylthio, C r C 6 alkylamino, di-C r C 6 alkylamino, C r C 6 -
  • R 11 wherein the aliphatic, alicyclic, heterocyclic and aromatic groups in R 11 may in turn be partially or completely halogenated or may carry one, two or three groups R 12 :
  • R 12 is cyano, nitro, hydroxyl, mercapto, amino, carboxyl, aminocarbonyl, aminothiocarbonyl, alkyl, haloalkyl, alkenyl, alkadienyl, alkenyloxy, alkynyloxy, alkoxy, haloalkoxy, alkylthio, alkylamino, dialkylamino, formyl, alkylcarbonyl, alkylsulfonyl, Alkylsulfoxyl, alkoxycarbonyl, alkylcarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminothiocarbonyl, dialkylaminothiocarbonyl, where the alkyl groups in these radicals contain 1 to 6 carbon atoms and said alkenyl, alkadienyl or alkynyl groups in these radicals contain 2 to 8 carbon atoms;
  • Z is O, S, NR 33 , NOR 34 or N-NR 35 R 36 ;
  • Z ' is a chemical bond, oxygen, a carbonyl group, a group
  • R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 32a , R 33 , R 34 , R 35 and R 36 independently of one another are hydrogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C -alkynyl, C 3 -C 8 -cycloalkyl or C 4 -C 8 -cycloalkenyl;
  • R 23a has, except for hydrogen, one of the meanings given for R 21 ;
  • R 22 , R 28 and R 32 may additionally denote -CO-R 25 ;
  • R 22 can furthermore be -CO-OR 21 or -CO-NR 23 R 23b , where R 23b has one of the meanings given for R 21 ;
  • R 22 and R 23 or R 22 and R 23a may also together form a C 3 -C 6 alkylene group which may be interrupted by an oxygen atom or may have a double bond;
  • R 31 , R 32 , R 32a , R 33 , R 34 or R 35 with another radical R 21 , R 22 , R 23 , R 24 , R 25 or R 31 can also together form a C 1 -C 6 -alkylene group which in the Case of C 2 -C 6 alkylene may have a double bond;
  • R 26 and R 22 , R 26 and R 27 , R 26 and R 28 or R 29 and R 30 may also together form a C 3 -C 6 -alkylene group which may be interrupted by an oxygen atom or may have a double bond;
  • R w is halogen, cyano, C r C 8 alkyl, C 2 -C 0 alkenyl, C 2 -C 0 alkynyl, C r C 6 - alkoxy, C 2 -C 0 alkenyloxy, C 2 -C 0 - Alkynyloxy, C 3 -C 6 -cycloalkyl, C 3 -C 6 -
  • R 2 is a cyclic radical selected from C 3 -C 0 cycloalkyl, phenyl and five-, six- or seven-membered saturated, partially unsaturated or aromatic heterocycles see which one, two, three or four heteroatoms from the group O .
  • R 3 is hydrogen, OH, halogen, cyano, C r C 8 alkyl, C r C 8 alkoxy, C r C 8 alkylthio, C r Cs-alkylsulfinyl, C r C 8 alkylsulfonyl, C 2 -C 8 - alkenyl or C 2 -C 8 -alkynyl, where the 7 last-mentioned radicals may be partially or fully halogenated and / or one, two or three substituents selected from nitro, cyano, OH, -C 2 - alkoxy, -C 4 alkoxycarbonyl, amino , Ci-C 4 -alkylamino and Di-CrC 4 -
  • Alkylamino can carry
  • Het is a substituted C- or N-linked, 5- or 6-membered aromatic heterocycle having 1, 2, 3 or 4 heteroatoms selected from nitrogen, oxygen and sulfur as ring members and having the general formula:
  • # indicates the binding site to the 5-position of the pyrimidine ring;
  • X is N, N- (C 1 -C 4 -alkyl), S, O or CR 4 ;
  • Y is C or N;
  • k is 1, 2 or 3 and when X is N- (C r C 4 alkyl) or CR 4 , also
  • 0 can be
  • R 4 represents halogen, cyano, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C 4 -alkoxy, or C is 4 -haloalkoxy;
  • L is selected from halogen, cyano, hydroxy, cyanato (OCN), nitro, d- C ⁇ alkyl, C 2 -Cio-alkenyl, C 2 -C 0 alkynyl, C r C 6 haloalkyl, C 2 -C 0 -
  • R 5 are independently selected from hydrogen, d-C ⁇ -alkyl, C 2 -C 0 alkenyl, C 2 -C 0 alkynyl, C 3 -C 6 cycloalkyl or C 3 - C 6 cycloalkenyl, where the 5 last-mentioned radicals to be partially or fully halogenated and / or one, two, three or four groups selected from cyano, CrC 4 -Alkoximino, C 2 -C 4 -
  • a 1 is hydrogen, hydroxy, C 1 -C 6 -alkyl, amino, C 1 -C 6 -alkylamino or di- (C 1 -C 8 -alkyl) amino;
  • n O, 1 or 2;
  • a 2 is C 2 -C 8 alkenyl, C r C 8 alkoxy, C r C 6 haloalkoxy, C 2 -C 0 - alkenyloxy, C 2 -C 0 alkynyloxy or one of said at A 1 group- pen stands;
  • a 3 and A 4 are each independently -C 8 alkyl, C 2 -C 8 -alkenyl, CrC 8 -
  • Haloalkyl C 2 -C 8 haloalkenyl, C 3 -C 6 cycloalkyl, dC 8 alkoxy, C
  • R 7 , R 8 , R 9 , R 10 and R 11 are independently selected from
  • R 8 and R 9 and / or R 10 and R 11 together with the nitrogen atom to which they are attached form a four-, five- or six-membered saturated or partially unsaturated ring which is one, two, three or four, independently of one another under R a may carry selected substituents;
  • R a is halo, OH, C r C 8 alkyl or C r C 8 alkoxy
  • the present invention further provides an agent for controlling harmful fungi, comprising at least one compound of general formula I and / or an agriculturally useful salt thereof and at least one liquid or solid carrier.
  • the present invention furthermore relates to novel 5-hetaryl-4-aminopyrimidines of the general formula I in which Het, W, R 1 , R 2 and R 3 have the meanings mentioned above, except compounds of the formula I in which R 2 is C 6 -C 6 -alkoxy means.
  • the invention also provides the salts of 5-hetaryl-4-aminopyrimidines of the general formula I, in particular their agriculturally useful salts and their pharmaceutically suitable salts.
  • the present invention furthermore relates to the use of 5-hetaryl-4-aminopyrimidines of the general formula I and / or a pharmaceutically suitable salt thereof as medicaments, in particular for the treatment of cancers.
  • the present invention furthermore relates to pharmaceutical compositions comprising at least one 5-hetaryl-4-aminopyrimidine of the general formula I and / or a pharmaceutically suitable salt thereof and a pharmaceutically acceptable carrier.
  • the present invention furthermore relates to the use of 5-hetaryl-4-aminopyrimidines of the general formula I and / or pharmaceutically suitable salts thereof for the production of a medicament for the treatment of cancers.
  • the present invention furthermore relates to a method for the treatment of cancers in mammals, comprising administering to the mammal in need thereof an effective amount of a 5-hetaryl-4-aminopyrimidine of the general formula I and / or a pharmaceutically acceptable salt thereof.
  • the compounds of the formula I can have one or more centers of chirality and are then present as enantiomer or diastereomer mixtures.
  • the invention relates to both the pure enantiomers or diastereomers and mixtures thereof.
  • Suitable compounds of general formula I also include all possible stereoisomers (cis / trans isomers) and mixtures thereof.
  • Suitable agriculturally useful salts are, in particular, the salts of those cations or the acid addition salts of those acids whose cations or anions have the pesticidal activity, e.g. the fungicidal, insecticidal or nematicidal action which does not adversely affect compounds I.
  • the ions of the alkali metals preferably sodium and potassium, the alkaline earth metals, preferably calcium, magnesium and barium, and the transition metals, preferably manganese, copper, zinc and iron, and the ammonium ion, the desired one to four Ci-C4 Alkyl substituents and / or a phenyl or benzyl substituent, preferably diisopropylammonium, tetramethylammonium, tetrabutylammonium, trimethylbenzylammonium, furthermore phosphonium ions, sulfonium ions, preferably tri (C 1 -C 4 -alkyl) sulfonium and sulfoxonium ions, preferably tri (C 1 -C 4 -alkyl) alkyl) sulfoxonium, into consideration.
  • the alkali metals preferably sodium and potassium
  • the alkaline earth metals preferably calcium, magnesium and barium
  • the transition metals preferably manganes
  • Anions of useful acid addition salts are primarily chloride, bromide, fluoride, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, phosphate, nitrate, bicarbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate, and the anions of C 1 -C 4 alkanoic acids, preferably formate, acetate , Propionate and butyrate.
  • You can by reaction of I with an acid of the corresponding Anions preferably hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid or nitric acid, are formed.
  • Suitable pharmaceutically suitable salts are, in particular, physiologically tolerated salts of compound I, in particular the acid addition salts with physiologically tolerated acids.
  • suitable, physiologically compatible organic and inorganic acids are hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, C 1 -C 4 -alkylsulfonic acids such as methanesulfonic acid, cycloaliphatic sulfonic acids such as S - (+) - 10-camphorsulfonic acid, aromatic sulfonic acids such as benzenesulfonic acid , cis- and cinnamic acid, fluorescein and toluenesulfonic acid, C 2 -C 10 -hydroxycarboxylic acids such as glycolic acid, di- and tri-C 2 -C 10 -carboxylic acids and -hydroxycarboxylic acids such as oxalic acid, malonic acid, maleic acid, fumaric acid, lactic acid
  • physiologically tolerated salts of the compounds I can be present as mono-, bis-, tris- and tetrakis salts, i. H. they may have 1, 2, 3 or 4 of the aforementioned acid molecules per molecule of formula I.
  • the acid molecules may be in protonated form or as anions.
  • Halogen fluorine, chlorine, bromine and iodine
  • Alkenyl and the alkenyl moieties in alkenyloxy monounsaturated, straight-chain or branched hydrocarbon radicals having 2 to 4, 2 to 6, 2 to 8 or 2 to 10 carbon atoms and a double bond in any position, e.g.
  • C2-C6 alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1 Methyl 2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 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-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-ethyl-1-propen
  • Alkadienyl diunsaturated, straight-chain or branched hydrocarbon radicals having 4 to 10 carbon atoms and two double bonds in any position, for example 1, 3-butadienyl, 1-methyl-1,3-butadienyl, 2-methyl-1,3-butadienyl, penta- 1, 3-dien-1-yl, hexa-1, 4-dien-1-yl, hexa-1, 4-dien-3-yl, hexa-1, 4-dien-6-yl, hexa-1, 5-dien-1-yl, hexa-1, 5-dien-3-yl, hexa-1, 5-dien-4-yl, hepta-1, 4-dien-1-yl, hepta-1, 4 dien-3-yl, hepta-1, 4-dien-6-yl, hepta-1, 4-dien-7-yl, hepta-1, 5-dien-1-yl, hepta-1, 5-diene 3-y
  • Haloalkenyl unsaturated, straight-chain or branched hydrocarbon radicals having 2 to 10 carbon atoms and a double bond in any position (as mentioned above), wherein in these groups, the hydrogen atoms partially or completely replaced by halogen atoms as mentioned above, in particular fluorine, chlorine and bromine could be;
  • Alkynyl and the alkynyl moieties in alkynyloxy straight or branched hydrocarbon groups having 2 to 4, 2 to 6, 2 to 8 or 2 to 10 carbon atoms and one or two triple bonds in any position, e.g.
  • 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-pentynyl, 4- Pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1, 1-dimethyl-2-propynyl, 1-ethyl-2- propynyl, 1-hexynyl, 2-hexynyl, 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-p
  • Cycloalkyl and the cycloalkyl moieties in cycloalkoxy monocyclic saturated hydrocarbon groups having 3 to 8 carbon ring members such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl;
  • Cycloalkenyl monocyclic monounsaturated hydrocarbon groups having 3 to 8, preferably 5 to 6 carbon ring members such as cyclopenten-1-yl, cyclopenten-3-yl, cyclohexen-1-yl, cyclohexen-3-yl, cyclohexen-4-yl and the like ;
  • Bicycloalkyl bicyclic hydrocarbon radical having 5 to 10 carbon atoms such as bicyclo [2.2.1] hept-1-yl, bicyclo [2.2.1] hept-2-yl, bicyclo [2.2.1] hept-7-yl, Bicyclo [2.2.2] oct-1-yl, bicyclo [2.2.2] oct-2-yl, bicyclo [3.3.0] octyl, bicyclo [4.4.0] decyl and the like; CrC 4 -alkoxy: for an oxygen-bonded alkyl group having 1 to 4 C atoms: z. Methoxy, ethoxy, n -propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy or 1, 1-dimethylethoxy;
  • d-Cs-alkoxy for Ci-C 4 -Akoxy, as mentioned above, and z.
  • Pentoxy 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1, 1-dimethylpropoxy, 1, 2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3- Methylpentoxy, 4-methylpentoxy, 1, 1-dimethylbutoxy, 1, 2-dimethylbutoxy, 1, 3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1, 1, 2-trimethylpropoxy, 1, 2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy or 1-ethyl-2-methylpropoxy;
  • C 1 -C 4 -haloalkoxy a C 1 -C 4 -alkoxy radical as mentioned above which is partially or completely substituted by fluorine, chlorine, bromine and / or iodine, preferably by fluorine, eg OCH 2 F, OCHF 2 , OCF 3 , OCH 2 Cl, OCHCl 2 , OCCl 3 , chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, OC 2 F 5 , 2-fluoropropoxy, 3-fluor
  • Ci-C ⁇ -haloalkoxy for Ci-C4-haloalkoxy, as mentioned above, as well as e.g. 5-fluoropentoxy, 5-chloropentoxy, 5-bromopentoxy, 5-iodopentoxy, undecafluoropentoxy, 6-fluorohexoxy, 6-chlorohexoxy, 6-bromohexoxy, 6-iodohexoxy or dodecafluorohexoxy;
  • Alkenyloxy alkenyl as mentioned above, which is bonded via an oxygen atom, for example C 3 -C 6 -alkenyloxy such as 1-propenyloxy, 2-propenyloxy, 1-methylethenyloxy, 1-butenyloxy, 2-butenyloxy, 3-butenyloxy, 1-methyl- 1 -propenyloxy, 2-methyl-1-propenyloxy, 1-methyl-2-propenyloxy, 2-methyl-2-propenyloxy, 1-pentenyloxy, 2-pentenyloxy, 3-pentenyloxy, 4-pentenyloxy, 1-methyl-1 - butenyloxy, 2-methyl-1-butenyloxy, 3-methyl-1-butenyloxy, 1-methyl-2-butenyloxy, 2-methyl-2-butenyloxy, 3-methyl-2-butenyloxy, 1-methyl-3-butenyloxy, 2-methyl-3-butenyloxy, 3-methyl-3-butenyl, 1, 1-dimethyl-2-propeny
  • Alkynyloxy alkynyl as mentioned above, which is bonded via an oxygen atom, e.g. C 3 -C 6 -alkynyloxy, such as 2-propynyloxy, 2-butynyloxy, 3-butynyloxy, 1-methyl-2-propynyloxy, 2-pentynyloxy, 3-pentynyloxy, 4-pentynyloxy, 1-methyl-2-butynyloxy, 1-methyl 3-butynyloxy, 2-methyl-3-butynyloxy, 1-ethyl-2-propynyloxy, 2-hexynyloxy, 3-hexynyloxy, 4-hexynyloxy, 5-hexynyloxy, 1-methyl-2-pentynyloxy, 1-methyl-3 pentynyloxy and the like;
  • C 3 -C 6 -alkynyloxy such as 2-propynyloxy, 2-butynyloxy, 3-buty
  • Alkylthio Alkyl as defined above attached via an S atom.
  • Alkylsulfinyl alkyl as defined above bonded through an SO group.
  • Alkylsulfonyl Alkyl as defined above attached via an S (O) 2 group.
  • heterocyclyl Five- or six-membered saturated or partially unsaturated heterocycle (hereinafter also heterocyclyl) containing one, two, three or four heteroatoms from the group oxygen, nitrogen and sulfur as ring members: for example, monocyclic saturated or partially unsaturated heterocycles containing one to three nitrogen atoms in addition to carbon ring members and / or an oxygen or sulfur atom or one or two oxygen and / or sulfur atoms, eg 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isoxazolidinyl, 4- isoxazolidinyl, 5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl
  • Seven-membered saturated or partially unsaturated heterocycle containing one, two, three or four heteroatoms from the group consisting of oxygen, nitrogen and sulfur as ring members e.g. mono- and bicyclic heterocycles having 7 ring members, 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, for example tetra-. and hexahydroazepinyl like
  • Alkylene divalent unbranched chains of 1 to 6 CH 2 groups, eg CH 2 , CH 2 CH 2 , CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 and CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ;
  • Oxyalkylene divalent unbranched chains of 2 to 4 CH 2 groups, wherein a valence is bonded to the skeleton via an oxygen atom, for example OCH 2 CH 2 , OCH 2 CH 2 CH 2 and OCH 2 CH 2 CH 2 CH 2 ;
  • Oxyalkylenoxy divalent unbranched chains of 1 to 3 CH 2 groups, both valences being bonded to the skeleton via an oxygen atom, eg OCH 2 O, OCH 2 CH 2 O and OCH 2 CH 2 CH 2 O.
  • Het is bound via N, i. in the case of N-linked heteroaromatic radicals, Y in formula Q stands for N and in the case of C-linked heteroaromatic radicals for C.
  • Het carries at least one substituent, ie in formula Q k is 1, 2 or 3 and / or X is CR 4 .
  • Het has 1, 2, 3 or 4 heteroatoms selected from nitrogen, oxygen and sulfur as ring members. These heteroatoms may be however, Het may also have other heteroatoms as ring members, where the total number of all ring atoms is 5 or 6 and the total number of all heteroatom ring atoms is 1, 2, 3 or 4.
  • W is oxygen
  • R 1 is in particular d-C ⁇ -alkyl, C 2 -C 8 -alkenyl, C 2 -C 8 kinyl -alkyl, C 3 -C 8 -cycloalkyl which contains 1, 2, 3, 4, 5 or 6 under Halogen and CrC 4 -AlkVl can carry selected substituents, or Ci-C 8 haloalkyl.
  • a particularly preferred embodiment relates to compounds of the general formula I in which R 1 is a group B:
  • Z 1 is hydrogen, fluorine or C 1 -C 4 -fluoroalkyl
  • Z 2 is hydrogen or fluorine
  • R 42 is hydrogen or methyl.
  • radicals B examples include 2,2,2-trifluoroethyl, 1-methyl-2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, 3,3,4,4,4-pentafluorobutyl, 2,2,3,3,3-pentafluoro-1-methylpropyl, and 2,3,3-trifluoro-2-propenyl.
  • a further preferred embodiment relates to compounds of the formula I in which R 1 represents branched C 3 -C 8 -alkyl, such as 1-methylpropyl, 1-methylbutyl, 2-methylpropyl, 1,2-dimethylpropyl or 1,2,2-trimethylpropyl or C3-Cs alkenyl such as 2-propenyl, 2-methyl-2-propenyl.
  • R 1 represents branched C 3 -C 8 -alkyl, such as 1-methylpropyl, 1-methylbutyl, 2-methylpropyl, 1,2-dimethylpropyl or 1,2,2-trimethylpropyl or C3-Cs alkenyl such as 2-propenyl, 2-methyl-2-propenyl.
  • a further preferred embodiment relates to compounds of the formula I in which R 1 is C 3 -C 6 -cycloalkyl which may be substituted by C 1 -C 4 -alkyl.
  • R 2 is a 5- or 6-membered heterocyclic radical. Particularly preferred are compounds I in which R 2 is selected from pyrrolyl, pyrazolyl, imidazolyl, 1, 2,3-triazolyl, 1, 2,4-triazolyl, tetrazolyl, oxazolyl, isoxazolyl, 1, 3,4-oxadiazolyl, furyl , Thienyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1, 2,3-triazinyl, 1, 2,4-triazinyl, 1, 3,5-triazinyl, 1-pyridine (1, 2-dihydro) - 2-one, pyrazol-3-one-1-yl, imidazol-2-one-1-yl, pyrazolin-3-one-1-yl, imidazolin-2-one-1-yl, 1, 2,
  • heterocyclic radical is unsubstituted.
  • R x which are halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 4 -alkoxy, C 2 hal
  • R 2 is an aromatic five-membered heterocycle which is preferably bonded via N and / or may be substituted by one, two or three radicals R x , where R x preferably has the meanings mentioned as being preferred.
  • R x preferably has the meanings mentioned as being preferred.
  • R 2 is 1-pyrazolyl, [1, 2,4] triazol-1-yl or [1, 2, 3] triazol-1-yl, where the abovementioned radicals unsubstituted or by 1, 2 or 3 radicals R x can be substituted.
  • R 2 is one of the following radicals:
  • NR 32 OR 21 such as N (C (OO) CH 3 ) (O-C 1 -C 4 -alkyl),
  • radicals NR 32 NR 22 R 23 are NHNHC (OO) OCH 3 , NHNHC (OO) OC 2 H 5 , NHNHC (OO) OC 3 H 7 , NHNHC (OO) OC 4 H 9 .
  • R 3 is preferably halogen, cyano, Ci -C4 -alkyl, Ci-C 4 haloalkyl, Ci-C 4 - alkoxy or C 2 -haloalkoxy.
  • compounds of general formula I are preferred in which R 3 is halogen, C 1 -C 2 -alkyl, cyano or C 1 -C 2 -
  • Alkoxy such as chlorine, fluorine, bromine, methyl, cyano, methoxy or ethoxy.
  • R 3 is halogen and especially chlorine.
  • R 3 is methoxy.
  • R 3 is methyl.
  • R 3 is cyano.
  • X in formula Q is N, N-C 1 -C 4 -alkyl, O or S, in particular N, ie one of the heteroatoms of the heteroaromatic radical Het is ortho to the point of attachment of Het to the pyrimidine skeleton arranged.
  • Preferred substituents L in the ortho position are fluorine, chlorine, bromine, C 1 -C 2 -alkyl, such as methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, C 1 -C 2 -alkoxy, such as methoxy and C 1 -C 2 -haloalkoxy, such as difluoromethoxy and trifluoromethoxy ,
  • X is CR 4 , in which R 4 has the abovementioned meanings and in particular represents fluorine, chlorine, bromine, C 1 -C 2 -alkyl, such as methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, C 1 -C 2 -cycloalkyl, Alkoxy such as methoxy or Ci-C2 haloalkoxy such as difluoromethoxy or trifluoromethoxy.
  • Preferred substituents L in the formula Q are halogen, cyano, nitro, NH2, Ci-C ⁇ alkyl, d-C ⁇ -haloalkyl, Ci-C 6 alkoxy, Ci-C 6 -alkylamino, di-Ci-C 6 -alkylamino, NH-C (O) -Ci-C ⁇ -alkyl, a group C (S) A 2 and a group C (O) A 2 .
  • a 2 has the abovementioned meanings and is preferably C 1 -C 4 -alkoxy, NH 2, C 1 -C 4 -alkylamino or C 1 -C 4 -alkylamino.
  • L groups are independently selected from fluorine, chlorine, bromine, cyano, nitro, Ci-C4-alkyl, Ci-C 4 - haloalkyl, Ci-C4-alkoxy and Ci-C4 alkoxycarbonyl, most preferably below Fluorine, chlorine, C 1 -C 2 -alkyl, such as methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, C 1 -C 2 -alkoxy, such as methoxy, or C 1 -C 2 -alkoxycarbonyl, such as methoxycarbonyl.
  • Preferred substituents R 4 are fluorine, chlorine, bromine, C 1 -C 2 -alkyl, such as methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, C 1 -C 2 -alkoxy, such as methoxy and C 1 -C 2 -haloalkoxy, such as difluoromethoxy and trifluoromethoxy.
  • Het is a substituted 5-membered heteroaromatic radical containing at least one nitrogen atom and optionally 1 or 2 further heteroatoms selected from O, S and N as Has ring members.
  • Examples thereof are compounds of formula I wherein Het is selected from substituted pyrrolyl, pyrazolyl, imidazolyl, 1, 2,3-triazolyl, 1, 2,4-triazolyl, oxazolyl, thiazolyl, isoxazolyl and isothiazolyl.
  • Het is in particular one of the radicals Het-1 to Het-31 given below:
  • R 4a , R 4b are hydrogen or have one of the meanings given for R 4 , with the proviso that in the formulas Het-4, Het-6, Het-10, Het-13 and Each of at least one of R 4a or R 4b is other than hydrogen;
  • R is C 1 -C 4 -alkyl, in particular methyl or ethyl; # denotes the point of attachment to the 5-position of the pyrimidine ring; and L 1 , L 2 , and L 3 independently of one another are hydrogen or have one of the meanings given for L, with the proviso that in the formulas Het-1, Het-7, Het-8, Het-9, Het- 11, Het-12, Het-14 to Het-18, Het-23, Het-24 and Het-25 each of at least one of L 1 , L 2 or L 3 is other than hydrogen.
  • the radicals L 1 , L 2 and L 3 are independently selected from hydrogen, halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, especially C 1 -C 2 -fluoroalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkyl. C 4 alkoxycarbonyl.
  • L 1 , L 2 and L 3 are independently selected from hydrogen, nitro, cyano, fluoro, chloro, bromo, methyl, ethyl, isopropyl, trifluoromethyl, fluoromethyl, methoxy and methoxycarbonyl.
  • R 4a and R 4b are in particular selected from fluorine, chlorine, bromine, C 1 -C 2 -alkyl, such as methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, C 1 -C 2 -alkoxy, such as methoxy and C 1 -C 2 -haloalkoxy, such as difluoromethoxy and trifluoromethoxy ,
  • Het-1 examples are 3,5-dimethylpyrazol-1-yl, 3,5-diisopropylpyrazol-1-yl, 3-methyl-5-isopropyl-pyrazol-1-yl, 3-isopropyl-5-methyl-pyrazole 1 -yl, 3-ethyl-5-methyl-pyrazol-1-yl, 3,4,5-trimethyl-pyrazol-1-yl, 3-chloro-pyrazol-1-yl, 3-methyl-pyrazole-1 - yl, 3-methyl-4-chloro-pyrazol-1-yl, 3-trifluoromethyl-pyrazol-1-yl, 3-trifluoromethyl-5-methoxy-pyrazol-1-yl, 3-trifluoromethyl-5-methyl-pyrazole 1 -yl, 3-methyl-5-methoxypyrazol-1-yl, 3,5-dichloro-4-methyl-pyrazol-1-yl, 3,5-dimethyl-4-chloro-pyrazol-1-yl, 3, 5-d
  • Het-2 are 1, 3-dimethylpyrazol-5-yl and 1-methyl-3-trifluoromethylpyrazol-5-yl.
  • Het-3 are 1, 5-dimethylpyrazol-3-yl and 1-methyl-5-methoxypyrazol-3-yl.
  • Het-4 examples include 1, 3-dimethylpyrazol-4-yl, 1, 5-dimethylpyrazol-4-yl, 1, 3,5-trimethylpyrazol-4-yl, 1-methyl-3-trifluoromethylpyrazol-4-yl and 1-methyl-5-trifluoromethylpyrazole-4-yl.
  • Het-5 are 1-methylpyrrol-2-yl, 1, 4-dimethylpyrrol-2-yl, 1-methyl-5-chloropyrrol-2-yl and 1-methyl-3,5- dichloropyrrole-2-yl.
  • Het-6 is 1, 4-dimethylpyro-3-yl.
  • Het-7 2-methyl-thiazol-4-yl
  • Het-10 are 3-methyl-isothiazol-4-yl and 3-methyl-5-chloro-isothiazol-4-yl.
  • het-13 examples include 3,5-dimethylisoxazol-4-yl, 3-methylisoxazol-4-yl and 3-chloro-isoxazol-4-yl.
  • Het-16 examples include 2-methyl-oxazol-4-yl and 2,5-dimethyloxazol-4-yl.
  • Het-19 examples include 4,5-dichloro-imidazol-1-yl and 4,5-dimethyl-imidazol-1-yl.
  • Het-20 is 1-methyl-imidazol-4-yl.
  • Het-21 is 1-methylimidazol-2-yl.
  • Het-22 is 1-methylimidazol-5-yl.
  • het-23 examples include 3-chloro-1, 2,4-triazol-1-yl, 3-fluoro-1, 2,4-triazol-1-yl,
  • Het-24 examples include 4,5-dimethyl-1,2,3-triazol-1-yl,
  • Het-26 is 1-methyl-1,2,4-triazol-5-yl.
  • Het-27 is 1-methyl-1,2,3-triazol-5-yl.
  • Het-28 is 2-methyl-1,2,3-triazol-4-yl.
  • Het-29 is 1-methyl-1,2,4-triazol-3-yl.
  • Het-30 is 1-methyl-1,2,3-tiazol-4-yl.
  • Het-31 is 2-methyl-1,2,3-triazol-5-yl.
  • Het is substituted thienyl. Accordingly, Het is one of the following residues Het-32 or Het-33:
  • R 4a , R 4b are hydrogen or have one of the meanings given for R 4 , with the proviso that at least one of the radicals R 4a or R 4b is different from hydrogen;
  • # denotes the point of attachment to the 5-position of the pyrimidine ring;
  • L 1 , L 2 , and L 3 independently of one another are hydrogen or have one of the meanings given for L, with the proviso that in the formula Het-32 at least one of the radicals L 1 , L 2 or L 3 is different from hydrogen is.
  • the radicals L 1 , L 2 and L 3 are independently selected from hydrogen, halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, especially C 1 -C 2 -fluoroalkyl, C 1 -C 4 -alkoxy and C 1 C 4 alkoxycarbonyl.
  • L 1 , L 2 and L 3 are independently selected from hydrogen, nitro, cyano, fluoro, chloro, bromo, methyl, ethyl, isopropyl, trifluoromethyl, fluoromethyl, methoxy and methoxycarbonyl.
  • R 4a and R 4b are in particular selected from fluorine, chlorine, bromine, C 1 -C 2 -alkyl, such as methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, C 1 -C 2 -alkoxy, such as methoxy and C 1 -C 2 -haloalkoxy, such as difluoromethoxy and trifluoromethoxy ,
  • Het-32 are 5-methylthiophene-2-yl, 4-methylthiophene-2-yl, 5-chlorothiophene-2-yl, 3-cyanothiophene-2-yl, 5-acetylthiophene-2-yl, 5-bromothiophene 2-yl, 3,5-dichlorothiophen-2-yl, and 3,4,5-trichlorothiophen-2-yl.
  • Het-33 examples are 2-methylthiophen-3-yl, 2,5-dichlorothiophen-3-yl, 2,4,5-trichloro-thiophen-3-yl and 2,5-dibromothiophene-3-yl. According to a further embodiment of the invention, Het is substituted fu- ryl. Accordingly, Het is one of the following residues Het-34 or Het-35:
  • R 4a , R 4b are hydrogen or have one of the meanings given for R 4 , with the proviso that at least one of the radicals R 4a or R 4b is different from hydrogen;
  • # denotes the point of attachment to the 5-position of the pyrimidine ring;
  • L 1 , L 2 , and L 3 independently of one another represent hydrogen or have one of the meanings given for L, with the proviso that in the formula Het-34 at least one of the radicals L 1 , L 2 or L 3 is different from hydrogen is.
  • the radicals L 1 , L 2 and L 3 are independently selected from hydrogen, halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, especially C 1 -C 2 -fluoroalkyl, C 1 -C 4 -alkoxy and C 1 C 4 alkoxycarbonyl.
  • L 1 , L 2 and L 3 are independently selected from hydrogen, nitro, cyano, fluoro, chloro, bromo, methyl, ethyl, isopropyl, trifluoromethyl, fluoromethyl, methoxy and methoxycarbonyl.
  • R 4a and R 4b are in particular selected from fluorine, chlorine, bromine, C 1 -C 2 -alkyl, such as methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, C 1 -C 2 -alkoxy, such as methoxy and C 1 -C 2 -haloalkoxy, such as difluoromethoxy and trifluoromethoxy ,
  • Het-34 are 5-methylfuran-2-yl, 5-chlorofuran-2-yl, 4-methylfuran-2-yl, 3-cyanofuran-2-yl, 5-acetyl-furan-2-yl, 5-bromofuran 2-yl, 3,5-dichloro-furan-2-yl and 3,4,5-trichlorofuran-2-yl.
  • Het-35 examples are 2-methylfuran-3-yl, 2,5-dimethylfuran-3-yl and 2,5-dibromofuran-3-yl.
  • a further preferred embodiment of the invention relates to compounds of general formula I wherein Het is a substituted 6-membered heteroaromatic radical having 1, 2 or 3 nitrogen atoms as ring members.
  • Het preferably stands for substituted pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl, in particular substituted pyridinyl, or pyrimidinyl.
  • compounds of general formula I wherein Het is substituted pyridinyl
  • compounds of the formula I in which Het is 2-pyridinyl which has 1 or 2 substituents L.
  • those compounds are particularly preferred in which one of the substituents L is located in the 5-position of the pyridinyl ring.
  • most preferred are compounds I wherein one of the substituents L is located in the 3-position of the pyridinyl ring.
  • L has in particular the meanings given as preferred.
  • Also preferred among the compounds of this embodiment are compounds of general formula I, wherein Het is 4-pyridinyl, which carries a substituent R 4 and optionally has 1 or 2 substituents L.
  • compounds of this embodiment further preferred are compounds of the general formula I in which Het is substituted pyrimidinyl and in particular 2- or 4-pyrimidinyl which has 1, 2 or 3 substituents L.
  • Het is substituted pyrimidinyl and in particular 2- or 4-pyrimidinyl which has 1, 2 or 3 substituents L.
  • compounds of the formula I in which Het is 2-pyrimidinyl or 4-pyrimidinyl which has 1 or 2 substituents L particularly preferred are those compounds wherein one of the substituents L is located in the 5-position of the pyrimidinyl ring. L has in this case in particular the meanings given as preferred.
  • a further preferred embodiment of the invention relates to compounds of general formula I wherein Het is 2-pyrazinyl having 1, 2 or 3 substituents L.
  • a further preferred embodiment of the invention relates to compounds of the general formula I in which Het is 4-pyridazinyl which has 1, 2 or 3 substituents L.
  • a further preferred embodiment of the invention relates to compounds of the general formula I in which Het is 1,3,5-triazinyl which has 1 or 2 substituents L.
  • heterocyclic radicals Het of this embodiment are the radicals Het-36 to Het-41 given below:
  • R 4a , R 4b are hydrogen or have one of the meanings given for R 4 , with the proviso that in the formulas Het-37, Het-38 and Het-40 at least one of R 4a or R 4b is different from hydrogen ;
  • L 1 , L 2 , L 3 and L 4 independently of one another are hydrogen or have one of the meanings given for L, with the proviso that in the formulas Het-36, Het-39 and Het-41 in each case at least one of the radicals L 1 , L 2 , L 3 or L 4 is different from hydrogen.
  • the radicals L 1, L 2, L 3 and L 4 are independently selected from hydrogen, halogen, nitro, cyano, -C 4 alkyl, dC 4 -haloalkyl, especially Cr C 2 fluoroalkyl, Ci-C 4 -alkoxy and dC 4 alkoxycarbonyl.
  • L 1 , L 2 , L 3 and L 4 are independently selected from hydrogen, nitro, cyano, fluoro, chloro, bromo, methyl, ethyl, isopropyl, trifluoromethyl, fluoromethyl, methoxy and methoxycarbonyl.
  • R 4a and R 4b are in particular selected from fluorine, chlorine, bromine, C 1 -C 2 -alkyl, such as methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, C 1 -C 2 -alkoxy, such as methoxy, and C 1 -C 2 -haloalkoxy, such as difluoromethoxy and trifluoromethoxy.
  • Het-36 are 3-fluoro-pyidin-2-yl, 3-chloro-pyridine-in-2-yl, 3-bromo-2-pyridin-2-yl, 3-trifluoromethyl-pyridin-2-yl, 3-methylpyridin-2-yl, 3-ethyl-pyridin-2-yl, 3,5-difluoro-pyridin-2-yl, 3,5-dichloro-pyridin-2-yl, 3,5-dibromo pyridin-2-yl, 3,5-dimethylpyridin-2-yl, 3-fluoro-5-trifluoromethylpyridin-2-yl, 3-chloro-5-fluoropyridin-2-yl, 3-chloro 5-methyl-pyridin-2-yl, 3-fluoro-5-chloro-pyridin-2-yl, 3-fluoro-5-methyl-pyridin-2-yl, 3-methyl-5-fluoro-pyridine-2-yl yl, 3-methyl-5-flu
  • Het-37 examples are 2-chloro-pyridin-3-yl, 2-bromo-pyridin-3-yl, 2-fluoro-pyridin-3-yl, 2-methyl-pyridin-3-yl, 2,4-dichloro-pyridine 3-yl, 2,4-dibromopyridin-3-yl, 2,4-difluoropyridin-3-yl, 2-fluoro-4-chloropyridin-3-yl, 2-chloro-4- fluoropyridin-3-yl, 2-chloro-4-methylpyridin-3-yl, 2-methyl-4-fluoropyridin-3-yl, 2-methyl-4-chloropyridin-3-yl, 2,4-dimethyl-pyridin-3-yl, 2,4,6-trichloropyridin-3-yl, 2,4,6-tribromopyridin-3-yl, 2,4,6-trimethyl-pyridin-3-yl, 2-chloro-6-methyl-pyridin
  • Het-38 examples include 3-chloro-pyridin-4-yl, 3-bromo-pyridin-4-yl, 3-methyl-pyridin-4-yl, 3,5-dichloro-pyridin-4-yl, 3, 5-dibromo-pyridin-4-yl and 3,5-dimethyl-pyridin-4-yl.
  • Het-39 examples include 5-chloropyrimidin-4-yl, 5-fluoropyrimidin-4-yl, 5-fluoro-6-chloropyrimidin-4-yl, 2-methyl-6-trifluoromethyl-pyrimidin-4-yl,
  • Het-40 examples include 4-methyl-pyrimidin-5-yl, 4,6-dimethyl-pyrimidin-5-yl, 2,4,6-trimethyl-pyrimidin-5-yl and 4-trifluoromethyl-6-methyl-pyrimidine. 5-yl.
  • Het-41 examples include 4,6-dimethyl-pyrimidin-2-yl, 4,5,6-trimethyl-pyrimidin-2-yl, 4,6-ditrifluoromethyl-pyrimidin-2-yl and 4,6-dimethyl-5-chloro pyrimidin-2-yl.
  • R 5 and R 6 independently of one another preferably represent hydrogen or C 1 -C 4 -alkyl.
  • R 7 is preferably hydrogen or in particular Ci-C ⁇ -alkyl.
  • R 8 and R 9 independently of one another preferably represent hydrogen or C 1 -C 6 -alkyl.
  • R 10 and R 11 are preferably independently selected from hydrogen or C 1 -C 6 -alkyl.
  • a 1 is preferably hydrogen, C 1 -C 6 -alkyl or amino.
  • the index n is preferably 0, 1 or 2.
  • a 2 is preferably C 1 -C 4 -alkoxy, NH 2, C 1 -C 4 -alkylamino or C 1 -C 4 -alkylamino.
  • Z is preferably O, S or NOR 34 .
  • Z ' is preferably a direct bond.
  • R 2 I 1 R 2 S 1 R 24j R 2 S 1 R 26i R 2 T 1 R 2 S 1 R 2 R 3 O 1 R 3 R 32 R 33j R 34 R 35 and R 36 are preferably for hydrogen or C 1 -C 4 -alkyl.
  • R 22 is preferably hydrogen, C 1 -C 4 -alkyl, -CO-OR 21 or -COR 25 .
  • R 1 , R 3 and Het have the abovementioned meanings, in particular the meanings mentioned as being preferred.
  • R is C 1 -C 4 -alkyl, in particular methyl
  • Het 1 is methyl-5-trifluoromethylpyrazol-4-yl and the combination of R 1 and R 3 for a connection corresponds in each case to one row of Table A.
  • Table 103 Compounds of the formulas 1.1, I.2, I.3, I.4, I.5, I.6, I.7, I.8, I.9, 1.10, 1.11, 1.12, 1.13,
  • Table 109 Compounds of the formulas 1.1, I.2, I.3, I.4, I.5, I.6, I.7, I.8, I.9, 1.10, 1.11, 1.12, 1.13,
  • Table 1 14 Compounds of the formulas 1.1, I.2, I.3, I.4, I.5, I.6, I.7, I.8, I.9, 1.10, 1.11, 1.12, 1.13,
  • Table 141 Compounds of the formulas 1.1, I.2, I.3, I.4, I.5, I.6, I.7, I.8, I.9, 1.10, 1.11, 1.12, 1.13,
  • Trimethylpyrimidin-5-yl and the combination of R 1 and R 3 for a compound corresponds in each case to one row of Table A.
  • Table 151 Compounds of the formulas 1.1, I.2, I.3, I.4, I.5, I.6, I.7, I.8, I.9, 1.10, 1.11, 1.12, 1.13,
  • Table 152 Compounds of the formulas 1.1, I.2, I.3, I.4, I.5, I.6, I.7, I.8, I.9, 1.10, 1.11, 1.12, 1.13,
  • Examples of compounds of the general formula I are also those compounds of the formula I which correspond to the compounds mentioned in Tables 1 to 154, in which W is sulfur instead of oxygen.
  • novel compounds of the formula I can be prepared analogously to known processes of the prior art.
  • the compounds of the formula I can be prepared by reacting appropriately substituted 5-halopyrimidines II with correspondingly substituted organometallic compounds III (see Scheme 1)
  • Y, L, k, R 1 , R 2 , R 3 and X have the meanings given above, R 3 typically not being OH, Br or I.
  • R 3 is in particular hydrogen, alkyl, alkoxy, fluorine or chlorine; Hal is halogen, preferably bromine or iodine.
  • W is oxygen or sulfur, in particular for oxygen.
  • the reaction is carried out in the presence of catalytically active amounts of a transition metal of group 10 of the periodic table (group 10 according to IUPAC), z.
  • a transition metal of group 10 of the periodic table group 10 according to IUPAC
  • nickel palladium or platinum, especially in the presence of a palladium catalyst.
  • Suitable catalysts are, for example, palladium-phosphine complexes such as tetrakis (triphenylphosphine) palladium (0), PdCl2 (o-tolyl3P) 2, bis (triphenylphosphine) -palladium (II) chloride, [1, 1'-bis (diphenylphosphino) ferrocene] palladium (II) chloride-dichloromethane complex, bis [1,2-bis (diphenylphosphine) ethane] palladium (0) and [1,4-bis (diphenylphosphine) butane] palladium (II) chloride, palladium on activated charcoal in the presence of phosphine compounds and palladium (II) compounds such as palladium (II) chloride or bis (acetonitrile) palladium (II) chloride, in the presence of phosphine compounds such as triphenylphosphine,
  • Hetaryllithium compounds can in turn be prepared by direct metallation of CH-acidic heteroaromatics with lithium bases such as lithium diisopropylamide or butyllithium, or by lithiation of halo-hetaryl compounds with alkyllithium such as n-butyllithium.
  • the reaction then takes place under the conditions of a Stille coupling, as described, for example, by D. Milstein, JK Stille, J. Am. Chem. Soc. 1978, 100, pp. 3636-3638 or V. Farina, V. Krishnamurthy, WJ Scott, Org. React. 1997, 50, 1-652 are known.
  • Hetarylstannanes IM can be prepared analogously to known processes by reacting hetaryllithium compounds with RaSnCl.
  • the reaction then takes place under the conditions of a Kumada coupling, as described, for. From Kumada, Tetrahedron, 1982, 38, 3347 or A.C. Frisch, N. Shaikh, A. Zapf, M. Beller, Angew. Chem., 2002, 114, 4218-4221.
  • the reaction then takes place under the conditions of a Negishi coupling, as described for. From A. Lützen, M. Hapke, Eur. J. Org. Chem., 2002, 2292-2297.
  • Hetarylzincitatien can fertilize in a conventional manner from the Hetaryllithiumverbin- or be prepared from the HetarylmagnesiumENSen by reaction with zinc salts such as zinc chloride.
  • Suitable bases are alkali metal carbonates and alkali metal bicarbonates, such as sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, alkaline earth metal carbonates and alkaline earth metal hydrogencarbonates, such as magnesium carbonate or magnesium hydrogencarbonate or tertiary amines, such as triethylamine, trimethylamine, triisopropylamine or N-ethyl-N-diisopropylamine.
  • solvents are organic solvents such as ethers, z. B. 1, 2-dimethoxyethane, cyclic ethers such as tetrahydrofuran or 1, 4-dioxane, polyalkylene glycols such as diethylene glycol, carbonitriles such as acetonitrile, propionitrile, Carbon Text- suitable as dimethylformamide or dimethylacetamide.
  • organic solvents such as ethers, z. B. 1, 2-dimethoxyethane, cyclic ethers such as tetrahydrofuran or 1, 4-dioxane, polyalkylene glycols such as diethylene glycol, carbonitriles such as acetonitrile, propionitrile, Carbon Tar- suitable as dimethylformamide or dimethylacetamide.
  • the aforementioned solvents can also be used in admixture with water, for.
  • the ratio of organic solvent to water may range from 5: 1 to 1: 5.
  • R 1 , R 2 , R 3 and Hal have the meanings given above.
  • R 3 is in particular alkyl or halogen.
  • R ' is Ci-C ⁇ -alkyl, and Hal is halogen, preferably bromine or iodine.
  • W stands for oxygen or sulfur, in particular for oxygen.
  • the sulfones of the formula IV are reacted with compounds V usually under basic conditions. For practical reasons, it is possible to use directly the alkali metal, alkaline earth metal or ammonium salt of compound V. Alternatively, the addition of base is possible.
  • This reaction typically occurs under the conditions of nucleophilic substitution; usually at 0 to 200 ° C, preferably at 10 to 150 ° C.
  • a phase transfer catalyst for. B. 18-crown-6, perform.
  • the reaction takes place in the presence of a dipolar aprotic solvent such as N, N-dialkylated carboxylic acid amides, for.
  • N, N-dimethylformamide, cyclic ethers e.g. As tetrahydrofuran or carbonitriles such as acetonitrile [cp. DE-A 39 01 084; Chimia, Vol. 50, pp. 525-530 (1996); Khim. Geterotsikl. Soedin, Vol. 12, pp. 1696-1697 (1998)].
  • compounds IV and V are used in approximately stoichiometric amounts.
  • the reaction is carried out in the presence of a base, which can be used equimolar or in excess.
  • Suitable bases are alkali metal carbonates and bicarbonates, for example sodium carbonate and sodium hydrogencarbonate, nitrogen bases, such as triethylamine, tributylamine and pyridine, alkali metal alcoholates, such as sodium methoxide or potassium tert-butoxide, alkali metal amides, such as sodium amide or alkali metal hydrides, such as lithium hydride or sodium hydride , in question.
  • nitrogen bases such as triethylamine, tributylamine and pyridine
  • alkali metal alcoholates such as sodium methoxide or potassium tert-butoxide
  • alkali metal amides such as sodium amide or alkali metal hydrides, such as lithium hydride or sodium hydride , in question.
  • Suitable solvents are halogenated hydrocarbons, ethers, such as diethyl ether, diisopropyl ether, tert-butyl ether, 1,2-dimethoxyethane, dioxane, anisole and tetrahydrofuran, and also dimethyl sulfoxide, N, N-dialkylated carboxamides, such as dimethylformamide or dimethylacetamide. Particularly preferred are ethanol, dichloromethane, acetonitrile and tetrahydrofuran. It is also possible to use mixtures of the solvents mentioned.
  • CR 26 R 27 - NR 22 R 23 can be advantageously obtained from compounds II in which R 2 is cyano, according to standard methods for the derivatization of CN groups.
  • R 2 CN
  • R 2 COOH
  • W, R 1 , R 3 , R 22 , R 23 have the meanings given above.
  • R 3 is in particular alkyl or halogen
  • Hal is halogen, preferably bromine or iodine.
  • the saponification of the nitrile II is usually carried out in inert polar solvents, such as water or alcohols, preferably with inorganic bases, such as alkali or alkaline earth metal hydroxides, in particular NaOH.
  • the saponification of the nitrile II is carried out by reaction with hydrogen peroxide under alkaline conditions.
  • the reaction of the acid II (R 2 is COOH) with the amine VI is advantageously carried out under the conditions known from Chem. And Pharm. Bull. 1982, Vol. 30, N12, page 4314. If appropriate, it may be advantageous to activate the acid II before the reaction with the amine VI, for example to convert it into its acid chloride. In the case of carboxylic acids II, which tend to decarboxylate, it may be advantageous not to isolate the free acid but their alkali metal salt directly with conventional halogenating agents, for example, transfer with oxalyl chloride in the acid chloride and the latter with the amine, optionally in To implement the presence of an auxiliary base.
  • the substituted hydroxylamines can be used as free base or preferably in the form of their acid addition salts.
  • the halides such as chlorides or sulfates come into consideration.
  • Suitable alkylating agents are, for example, C 1 -C 6 -alkyl halides, di-C 1 -C 6 -alkyl sulfates or phenolsulfonic acid C 1 -C 6 -alkyl esters, where the phenyl radical optionally has one or two radicals selected from nitro and C 1 -C 6 -alkyl. te wears.
  • the alkylation is carried out in the presence of a base. Basically, all compounds which are capable of deprotonating the amide nitrogen are suitable as the base.
  • Suitable bases are, for example, alkali metal or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide or lithium hydroxide.
  • W, R 1 , R 3 , R 22 , R 23 , R 34 have the meanings given above, R 3 is in particular alkyl or halogen and Hal is halogen, preferably bromine or iodine.
  • OR 21 can be obtained by esterification of the compounds II (R 2 is COOH) under acidic or basic conditions.
  • R 3 is in particular alkyl or halogen
  • Hal is halogen, preferably bromine or iodine.
  • the cyano compound II is reacted in the presence of a solvent or diluent with hydrogen sulfide gas.
  • Suitable solvents or diluents are, for example, aromatic amines such as pyridine, substitutu ized pyridines, such as collidine and lutidine, or tertiary amines, such as trimethylamine, triethylamine, triisopropylamine and N-methylpiperidine.
  • the resulting aminothiocarbonyl compounds II (R 2 is C (SS) NH 2 ) can then optionally be alkylated once or twice on the amide nitrogen.
  • suitable methods for alkylation reference is made to the above.
  • suitable sulfurizing agents are organophosphorus sulfides such as Lawesson's reagent, (2,2-bis (4-methoxyphenyl) -1, 3,2,4-dithiodiphosphetane-2,4-disulfide, organotin sulfides such as bis (tricyclohexyltin) sulfide or phosphorus pentasulfide (see also J. March, Advanced Organic Chemistry, 4th Ed., Wiley Interscience 1992, p.893f and the literature cited therein).
  • R 1 and R 3 have the meanings given above.
  • R 3 is in particular alkyl or halogen.
  • Hal is halogen, preferably bromine or iodine, and R 'is C 1 -C 6 -alkyl.
  • Suitable oxidizing agents are, for example, hydrogen peroxide, selenium dioxide [cf. WO 02/88127] or organic carboxylic acids such as 3-chloroperbenzoic acid.
  • the oxidation is preferably carried out at from 10 to 50 ° C. in the presence of protic or aprotic solvents [cf. B. Cor. Chem. Soc., Vol. 16, pp. 489-492 (1995); Z. Chem., Vol. 17, p. 63 (1977)].
  • Compounds VII in which Hal represents halogen, in particular bromine or iodine are obtainable, for example, according to the synthetic route outlined in Scheme 4.
  • R 1 and R 3 have the meanings given above.
  • R 3 is in particular alkyl or halogen, R 'is C 1 -C 6 -alkyl.
  • Hal is halogen, preferably bromine or iodine.
  • Suitable halogenating agents are preferably chlorinating agents, brominating agents and iodinating agents.
  • a suitable chlorinating agent is, for example, N-chlorosuccinimide.
  • Suitable brominating agents are bromine and N-bromosuccinimide.
  • the bromination takes place in the presence of a solvent.
  • Suitable solvents for the bromination are, for example, carboxylic acids such as acetic acid.
  • Suitable iodinating agents are hydrogen iodide, chloroiodide or N-iodosuccinimide. The iodination is usually carried out in a solvent.
  • Suitable solvents are chlorinated hydrocarbons such as dichloromethane using hydrogen iodide, C 1 -C 4 -alcohols such as methanol or carboxylic acids such as acetic acid when using chloroiodide and halogenated carboxylic acids such as trifluoroacetic acid when using N-iodosuccinimide.
  • the halogenation is usually carried out between 10 ° C and the boiling point of the solvent.
  • Ether compounds VIII can be prepared starting from 4-halopyrimidine compounds IX by reaction with HOR 1 , compound X (see Scheme 5).
  • R 1 and R 3 have the meanings given above.
  • R 3 is in particular halogen or alkyl
  • R ' is C 1 -C 6 -alkyl
  • Hal' is halogen, in particular chlorine.
  • a base such as tertiary amines, for example triethylamine, or inorganic bases such as alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal hydrogencarbonates, alkali metal hydrides or alkaline earth metal hydrides such as sodium hydride or calcium hydride.
  • the reaction can be carried out in a solvent which is inert under the reaction conditions.
  • the compound X used in the excess is used as solvent.
  • the reaction is advantageously carried out at 0 ° C to the boiling point of the reaction mixture, for example 10 to 35 ° C.
  • 4-halopyrimidines IX in which R 3 is alkyl are advantageously obtained by reacting 4,6-dihalopyrimidines XI with a Grignard reagent R 3 -MgCl under the conditions of a Kumada coupling, as described in Scheme 6.
  • Hal ' are independently halogen, preferably chlorine.
  • 4,6-Dihalogenpy ⁇ imidine Xl are advantageously obtained, for example, by reacting 4,6-dihydroxypyrimidines XII with halogenating agents, in particular chlorinating agent or brominating agent; as described in Scheme 7.
  • Hal ' is independently halogen, preferably chlorine.
  • Suitable chlorinating agents for the conversion of the dihydroxy compound XII into the compounds XI are in particular POCb, PCI3 / CI2 or PCI5, or mixtures of these reagents.
  • the reaction can be carried out in excess of chlorinating agent (POCb) or an inert solvent such as carbonitriles, e.g. Acetonitrile or propionitrile, aromatic hydrocarbons, e.g. As toluene, chlorinated hydrocarbons, eg. B. 1, 2-dichloroethane or chlorinated aromatic hydrocarbons such as chlorobenzene can be performed.
  • the reaction usually takes place between 10 and 180 ° C.
  • the process is advantageously carried out with the addition of N, N-dimethylformamide in catalytic or sub-catalytic amounts or nitrogen bases, such as N, N-dimethylaniline.
  • 4,6-dihydroxypyrimidines XII can be obtained by the route outlined in Scheme 8.
  • the malonic acid ester XIII is converted with thiourea into the 2-mercaptopyrimidine compound XIIIa.
  • the subsequent alkylation with an alkylating agent gives the compound XII.
  • alkylating agents come z.
  • B. Ci-C ⁇ -alkyl halides, preferably alkyl bromides and alkyl chlorides, di-Ci-C ⁇ - alkyl sulfates or phenolsulfonic Ci-C6-alkyl esters into consideration.
  • the reaction of the malonic esters of the formula XIII with thiourea can be carried out in the presence or absence of solvents. It is advantageous to use those solvents to which the starting materials are largely inert and in which they are completely or partially soluble.
  • the malonic acid ester XIII can also be reacted with an S-alkylisothiourea to give directly the thioether XII; see Scheme 8.
  • R * is alkyl, preferably C 1 -C 6 -alkyl and R 'is C 1 -C 6 -alkyl.
  • R * is alkyl, preferably Ci-C ⁇ -alkyl
  • R ' is Ci-C ⁇ -alkyl
  • Hal' is halogen, preferably chlorine.
  • a ⁇ -ketoester of formula XIV is converted to a 2-thioether compound XV either by reaction with an S-alkylisothiourea or by reaction with thiourea and subsequent alkylation, as described in Scheme 8. Thereafter, the thioether XV is reacted with a halogenating agent under the conditions described in Scheme 7 to give a 4-halopyrimidine of the formula IX.
  • R 1 , X, Y, (L) k have the meanings given above, R * is alkyl, preferably Ci-C ⁇ -alkyl, R 'is Ci-C ⁇ -alkyl and Hal' is halogen.
  • step i) hetarylmalonates of the general formula XVI are reacted with thiourea and subsequently with an alkylating agent to give the thioether XVII, or the hetarylmalonate XVI is reacted directly with the S-alkylisothiourea to give the compound XVIII.
  • the reaction takes place as described in Scheme 8.
  • the compounds XVII thus obtained can then be converted into the dihalogen compounds XVIII in step ii) by the processes described in Scheme 7.
  • the dihalo compounds XVIII can then be converted to the ether compound XIX in step iii) according to the procedures described in Scheme 5.
  • step iv) The thiol group in the 2-position of the compound XIX is oxidized to the alkylsulfonyl group in step iv) according to the process described in Scheme 3 and thus converted into a good leaving group for further exchange reactions.
  • the introduction of the radical R 2 (step v) can be carried out, for example, as described in step 2.
  • step v) further transformations follow, as described above, for example in schemes 2a, 2b or 2c.
  • Scheme 1 1 skiziiert Another route for the preparation of compound I in which R 3 is alkyl is shown in Scheme 1 1 skiziiert.
  • R 1 , X, Y, (L) k have the abovementioned meaning
  • R * is alkyl, preferably Ci-C ⁇ -alkyl
  • R ' is Ci-C ⁇ -alkyl
  • Hal' is halogen.
  • the halopyridmidine compound of the formula XIX is converted in step vi) into the corresponding alkylpyrimidine compound XXI as described in scheme 6.
  • the thiol group in the 2-position of compound XXI is oxidized to the alkylsulfonyl group in step vii) according to the procedure described in Scheme 3 and thus converted into a good leaving group for further exchange reactions.
  • the introduction of the radical R 2 (step vi) may, for example, be carried out as described in step 2. If appropriate, further conversions follow step v), as described above, for example in schemes 2a, 2b or 2c.
  • X, Y, (L) k have the abovementioned meaning
  • R * is alkyl, preferably C 1 -C 6 -alkyl
  • R ' is C 1 -C 6 -alkyl
  • R 3 is alkyl.
  • step ix the substituted ⁇ -ketoester XXIII is reacted with thiourea and subsequently with an alkylating agent to give the thioether XXI, or the hetaryl substituted ⁇ -ketoester is reacted directly with the S-alkylisothiourea to give the compound XXI.
  • the reactions are carried out as described in Scheme 9.
  • the cation M 1 in formula XXIV has little significance; For practical reasons, ammonium, tetraalkylammonium salts such as tetramethylammonium or tetraethylammonium salts or alkali or alkaline earth metal salts are usually preferred (Scheme 13).
  • the reaction temperature is 0 to 120 ° C, preferably at 10 to 40 0 C [cp. J. Heterocycl. Chem., Vol. 12, pp. 861-863 (1975)].
  • Suitable solvents include ethers, such as dioxane, diethyl ether, methyl tert-butyl ether and, preferably, tetrahydrofuran, halogenated hydrocarbons, such as dichloromethane or dichloroethane, aromatic hydrocarbons, such as toluene, and mixtures thereof.
  • the reaction is preferably carried out in the presence of catalytic or in particular at least equimolar amounts of transition metal salts and / or compounds, in particular in the presence of Cu salts such as Cu (l) halides and especially Cu (I) iodide.
  • the reaction is carried out in an inert organic solvent, for example one of the abovementioned ethers, in particular tetrahydrofuran, an aliphatic or cycloaliphatic hydrocarbon such as hexane, cyclohexane and the like, an aromatic hydrocarbon such as toluene or in a mixture of these solvents.
  • the required temperatures are in the range of -100 to +100 ° C and especially in the range of - 80 ° C to + 40 ° C. Methods for this are known, for. B. from WO 03/004465
  • the reaction mixtures are worked up in the usual way, e.g. by mixing with water, separation of the phases and optionally chromatographic purification of the crude products.
  • the intermediate and end products are z.T. in the form of colorless or pale brownish, viscous oils, which are freed or purified under reduced pressure and at moderately elevated temperature from volatile constituents. If the intermediate and end products are obtained as solids, the purification can also be carried out by recrystallization or trituration.
  • Hetarylmalonates of the formula XVI can be prepared starting from hetaryl compounds of the formula XXV by reaction with one or two equivalents of a carbonic acid ester or a chloroformate (compound XXVI) in the presence of a strong base (see Scheme 14).
  • R z is hydrogen or a Q is halogen or C 1 -C 4 -alkoxy, in particular methoxy or ethoxy.
  • X, Y, (L) k have the meanings given above and R is Ci-C 4 -AlkVl.
  • R z H, at least 2 equivalents of Compound XXVI must be used to achieve complete conversion of XXV.
  • the reaction shown in Scheme 14 is usually in the presence of strong bases.
  • R z is hydrogen, it is usual to use alkali metal amides such as sodium amide or lithium diisopropylamide, or lithium organic compounds such as phenyl lithium or butyl lithium as base. In this case, the base will be used at least equimolar, based on the compound XXV, in order to achieve complete conversion.
  • R z is an alkoxycarbonyl group, it is preferable to use an alkali metal alcoholate, for example sodium or potassium ethanolate, sodium or potassium butoxide, sodium or potassium methoxide as the base.
  • reaction of XXV with XXVI can be carried out in one stage or in two separate stages, in which case the intermediate XXVI in which R z is an alkoxycarbonyl group is obtained as intermediate.
  • the reaction of XXV with XXVI can be carried out in analogy to the method described in J. Med. Chem. 25, 1982, p. 745.
  • malonates of the formula XVI is also advantageously achieved by reaction of corresponding bromine-hetaryl compounds Br-Het with dialkylmalonates under Cu (I) catalysis [cf. Chemistry Letters, pp. 367-370, 1981; EP-A 10 02 788].
  • substituted .beta.-keto esters of the formula XXIII is advantageously achieved, for example, by reaction of corresponding bromo-hetaryl compounds Br-Het with unsubstituted .beta.-ketoesters under Cu (I) catalysis.
  • the compounds I are suitable as fungicides. They are distinguished by outstanding activity against a broad spectrum of phytopathogenic fungi from the classes of the Ascomycetes, Deuteromycetes, Oomycetes and Basidiomycetes, in particular from the class of the Oomycetes. They are partially systemically effective and can be used in crop protection as foliar, pickling and soil fungicides.
  • fungi are particularly important for the control of a variety of fungi on various crops such as wheat, rye, barley, oats, rice, corn, grass, bananas, cotton, soy, coffee, sugar cane, wine, fruit and ornamental plants and vegetables such as cucumbers. Beans, tomatoes, potatoes and pumpkins, as well as the seeds of these plants. They may also be used in cultures tolerant of insect or fungal growth by breeding, including genetic engineering methods. In addition, they are suitable for the control of Botryosphaeria species, Cylindrocarpon species, Eutypa lata, Neonectria liriodendri and Stereum hirsutum, which attack, among other things, the wood or the roots of grapevines.
  • Ascochyta species on cereals and vegetables e.g. Ascochyta tritici (leaf drought) on wheat,
  • Bipolaris and Drechslera species on maize, cereals, rice and turf eg D. maydis on maize, D. teres on barley, D. tritci-repentis on wheat), - Blumeria graminis (powdery mildew) on cereals (eg wheat or barley )
  • Botrytis cinerea (gray mold) on strawberries, vegetables, flowers, wheat and vines
  • Cercospora species on corn, soybeans, rice and sugar beets and e.g. Cercospora sojina (leaf spot) or Cercospora kikuchii (leaf spot) on soybeans ,
  • Macrophomina phaseolina root / stem rot
  • Michrodochium nivale on cereals (eg wheat or barley)
  • Microsphaera diffusa powdery mildew
  • Mycosphaerella species on cereals
  • bananas and peanuts M. graminicola on wheat, M. fijiesis Banana
  • Peronospora species on cabbage e.g., P. brassicae
  • bulbous plants e.g., P. destructor
  • Peronospora manshurica downy mildew
  • Phakopsara pachyrhizi and Phakopsara meibomiae on soybeans
  • Phialophora gregata stalk disease
  • - Phomopsis species on soybeans
  • sunflowers and vines P. viticola on vines, P. helianthii on sunflowers
  • Phytophthora species on various plants for example P. capsici on paprika, Phytophthora megasperma (leaf rot rot) on soybeans, Phytophthora indans on potatoes and tomatoes, Plasmopara viticola on vines,
  • Pseudoperonospora species on hops and cucurbits e.g., P. cubenis on cucumber or P. humili on hops
  • Puccinia species on various plants e.g. P. triticina, P. striformins, P. hordei or P. graminis on cereals (for example wheat or barley) or asparagus
  • Ramularia collo-cygni (Ramularia / sunburn complex / Physiological leaf spots) on barley
  • Rhizoctonia species e.g., R. solani
  • Rhizoctonia solani root / stem rot
  • Rhizoctonia cerealis Spitzer
  • Sclerotinia species on oilseed rape, sunflowers and other plants e.g. Sclerotinia sclerotiorum (stem disease) or Sclerotinia rolfsii (stem disease)
  • Venturia species scab on apple and pear (eg V. inaequalis on apple).
  • they are suitable for controlling harmful fungi from the class of Peronosporomycetes (syn.Oomyceten), such as Peronospora species, Phytophthora species, Plasmopara viticola, Pseudoperonospora species and Pythium species.
  • the compounds I are also suitable for controlling harmful fungi in the protection of materials (for example wood, paper, paint dispersions, fibers or fabrics) and in the protection of stored products.
  • harmful fungi ascomycetes such as Ophiostoma spp., Ceratocystis spp., Aureobasidium pullulans, Sciophoma spp., Chaetomium spp., Humicola spp., Petriella spp., Trichurus spp .; Basidiomycetes such as Coniophora spp., Coriolus spp., Gloeophyllum spp., Lentinus spp., Pleu- rotus spp., Poria spp., Serpula spp.
  • Tyromyces spp. Deuteromycetes such as Aspergillus spp., Cladosporium spp., Penicillium spp., Trichoderma spp., Alternaria spp., Paecilomyces spp. and Zygomycetes such as Mucor spp., moreover, in the protection of the following yeasts: Candida spp. and Saccharomyces cerevisae.
  • the compounds I are used by treating the fungi or the plants, seeds, materials or the soil to be protected against fungal attack with a fungicidally effective amount of the active ingredients.
  • the application can be done both before and after the infection of the materials, plants or seeds by the fungi.
  • the fungicidal compositions generally contain between 0.1 and 95, preferably between 0.5 and 90 wt .-% of active ingredient.
  • the application rates in the application in crop protection depending on the nature of the desired effect between 0.01 and 2.0 kg of active ingredient per ha.
  • active ingredient in general, amounts of active ingredient of 1 to 1000 g / 100 kg, preferably 5 to 100 g / 100 kg of seed are needed.
  • the application rate of active ingredient depends on the type of application and the desired effect. Usual application rates are, for example, 0.001 g to 2 kg, preferably 0.005 g to 1 kg of active ingredient per cubic meter of material treated in the material protection.
  • the compounds of the formula I can be present in various crystal modifications, which may differ in their biological activity. They are also the subject of the present invention.
  • the compounds I can be converted into the customary formulations, for example solutions, emulsions, suspensions, dusts, powders, pastes and granules.
  • the application form depends on the respective purpose; she should be in everyone Case to ensure a fine and uniform distribution of the compound of the invention.
  • the formulations are prepared in a known manner, e.g. by stretching the active ingredient with solvents and / or carriers, if desired using emulsifiers and dispersants.
  • Suitable solvents / auxiliaries are essentially:
  • aromatic solvents eg Solvesso products, xylene
  • paraffins eg petroleum fractions
  • alcohols eg methanol, butanol, pentanol, benzyl alcohol
  • ketones eg cyclohexanone, gamma-butyrolactone
  • pyrrolidones NMP, NOP
  • glycol diacetate glycols, dimethyl fatty acid amides, fatty acids and fatty acid esters.
  • solvent mixtures can also be used
  • Excipients such as ground natural minerals (e.g., kaolins, clays, talc, chalk) and ground synthetic minerals (e.g., fumed silica, silicates); Emulsifiers such as non-ionic and anionic emulsifiers (for example polyoxyethylene
  • the surface-active substances are alkali metal, alkaline earth metal, ammonium salts of lignin sulfonic acid, naphthalenesulfonic acid, phenolsulfonic acid, dibutylnaphthalenesulfonic acid,
  • mineral oil fractions of medium to high boiling point such as kerosine or diesel oil, coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, e.g. Toluene, xylene, paraffin, tetrahydronaphthalene, alkylated naphthalenes or their derivatives, methanol, ethanol, propanol, butanol, cyclohexanol, cyclohexanone, isophorone, strong polar solvents, e.g. Dimethylsulfoxide, N-methylpyrrolidone or water into consideration.
  • mineral oil fractions of medium to high boiling point such as kerosine or diesel oil, coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, e.g. Toluene, xylene, paraffin, tetrahydronaphthalene, alkylated naphthalenes or their derivative
  • Powders, dispersants and dusts may be prepared by mixing or co-grinding the active substances with a solid carrier.
  • Granules for example coated, impregnated and homogeneous granules, can be prepared by binding the active compounds to solid carriers.
  • Solid carriers are, for example, mineral earths, such as silica gels, silicates, talc, kaolin, attaclay, limestone, lime, chalk, bolus, loess, clay, dolomite, diatomaceous earth, calcium and magnesium sulfate, magnesium oxide, ground plastics, fertilizers, such as ammonium sulfate , Ammonium phosphate, ammonium nitrate, ureas and vegetable products such as cereal flour, bark, wood and nutshell flour, cellulose powder and other solid carriers.
  • mineral earths such as silica gels, silicates, talc, kaolin, attaclay, limestone, lime, chalk, bolus, loess, clay, dolomite, diatomaceous earth, calcium and magnesium sulfate, magnesium oxide, ground plastics, fertilizers, such as ammonium sulfate , Ammonium phosphate, ammonium nitrate, ureas and vegetable products such as cereal flour
  • the formulations generally contain between 0.01 and 95 wt .-%, preferably between 0.1 and 90 wt .-% of the active ingredient.
  • the active ingredients are used in a purity of 90% to 100%, preferably 95% to 100% (according to NMR spectrum).
  • a Water Soluble Concentrates 10 parts by weight of the active ingredients are dissolved with 90 parts by weight of water or a water-soluble solvent. Alternatively, wetting agents or other adjuvants are added. When diluted in water, the active ingredient dissolves. This gives a formulation with 10 wt .-% active ingredient content.
  • the active compounds 20 parts by weight are dissolved in 70 parts by weight of cyclohexanone with the addition of 10 parts by weight of a dispersant, e.g. Polyvinylpyrrolidone dissolved. Dilution in water gives a dispersion.
  • a dispersant e.g. Polyvinylpyrrolidone dissolved. Dilution in water gives a dispersion.
  • the active ingredient content is 20% by weight
  • the active ingredients 20 parts by weight of the active ingredients are comminuted with the addition of 10 parts by weight of dispersants and wetting agents and 70 parts by weight of water or an organic solvent in a stirred ball mill to a fine active substance suspension. Dilution in water results in a stable suspension of the active ingredient.
  • the active ingredient content in the formulation is 20% by weight.
  • Water-dispersible and water-soluble granules 50 parts by weight of the active compounds are finely ground with the addition of 50 parts by weight of dispersing and wetting agents and prepared by means of industrial equipment (for example extrusion, spray tower, fluidized bed) as water-dispersible or water-soluble granules. Dilution in water results in a stable dispersion or solution of the active ingredient.
  • the formulation has an active ingredient content of 50% by weight.
  • the active ingredients 75 parts by weight of the active ingredients are ground with the addition of 25 parts by weight of dispersing and wetting agents and silica gel in a rotor-Strator mill. Dilution in water results in a stable dispersion or solution of the active ingredient.
  • the active ingredient content of the formulation is 75% by weight.
  • I dusts (DP, DS) 5 parts by weight of the active ingredients are finely ground and intimately mixed with 95 parts by weight of finely divided kaolin. This gives a dust with 5 wt .-% active ingredient content.
  • J Granules 0.5 parts by weight of the active ingredients are finely ground and combined with 99.5 parts by weight of carriers. Common processes are extrusion, spray drying or fluidized bed. This gives a granulate for direct application with 0.5 wt .-% active ingredient content.
  • LS water-soluble concentrates
  • FS suspensions
  • DS dusts
  • WS water-dispersible and water-soluble powders
  • ES emulsions
  • EC emulsifiable concentrates
  • gel formulations GF
  • the active compounds may be used as such, in the form of their formulations or the forms of use prepared therefrom, e.g. in the form of directly sprayable solutions, powders, suspensions or dispersions, emulsions, oil dispersions, pastes, dusts, litter, granules by spraying, misting, dusting, scattering or pouring.
  • the forms of application depend entirely on the purposes of use; In any case, they should ensure the finest possible distribution of the active compounds according to the invention.
  • Aqueous application forms can be prepared from emulsion concentrates, pastes or wettable powders (spray powders, oil dispersions) by addition of water.
  • the substances as such or dissolved in an oil or solvent, can be homogenized in water by means of wetter, tackifier, dispersant or emulsifier.
  • concentrates which are active substance, adhesion, dispersant or emulsifier and, if appropriate, solvent or oil, concentrates which are suitable for dilution with water.
  • the active compound concentrations in the ready-to-use preparations can be varied within wide ranges. In general, they are between 0.0001 and 10%, preferably between 0.01 and 1%.
  • the active ingredients can also be used with great success in the ultra-low-volume (ULV) process, it being possible to apply formulations containing more than 95% by weight of active ingredient or even the active ingredient without additives.
  • UUV ultra-low-volume
  • wetting agents To the active ingredients oils of various types, wetting agents, adjuvants, herbicides, fungicides, other pesticides, bactericides, possibly also just immediately before use (tank mix), are added. These agents can be added to the compositions according to the invention in a weight ratio of 1: 100 to 100: 1, preferably 1:10 to 10: 1.
  • organically modified polysiloxanes eg Break Thru S 240 ®
  • Alcohol alkoxylates eg. B. Atplus 245 ®, Atplus MBA 1303 ®, Plurafac LF 300 ® and Lutensol ON 30 ®
  • EO-PO block polymers eg. B. Pluro- nic RPE 2035 ® and Genapol B ®
  • Alcohol ethoxylates eg. As Lutensol XP 80 ®
  • sodium dioctylsulfosuccinate e. B. Leophen RA ®.
  • the agents according to the invention in the form of application as fungicides, may also be present together with other active substances, e.g. with herbicides, insecticides, growth regulators, fungicides or with fertilizers.
  • other active substances e.g. with herbicides, insecticides, growth regulators, fungicides or with fertilizers.
  • Azoxystrobin dimoxystrobin, enestroburine, fluoxastrobin, kresoxim-methyl, metominostrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, orysastrobin, (2-chloro-5- [1- (3-methyl-benzyloxyimino) -ethyl] -benzyl) -carbamic acid methyl ester, (2-Chloro-5- [1- (6-methyl-pyridin-2-ylmethoxyimino) -ethyl] -benzyl) -carbamic acid methyl ester, 2- (ortho- (2,5-dimethylphenyl-oxymethylene) -phenyl) -3- methoxy-methyl acrylate;
  • Benzoic acid amides flumetover, fluopicolide (picobenzamide), zoxamide;
  • Other carboxamides carpropamide, diclocymet, mandipropamide, N- (2- (4- [3- (4-chloro-phenyl) -prop-2-ynyloxy] -3-methoxyphenyl) -ethyl) -2-methanesulfonylamino 3-methyl-butyramide, N- (2- (4- [3- (4-chloro-phenyl) -prop-2-ynyloxy] -3-methoxy-phenyl) -ethyl) -2-ethanesulfonyl-amino-3-methyl- butyramide;
  • bitertanol bromuconazoles, cyproconazole, difenoconazole, diniconazole, enilconazole, epoxiconazole, fenbuconazole, flusilazole, fluquinconazole, flutria folic acid, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triadimefon, triticonazole;
  • - imidazoles cyazofamide, imazalil, pefurazoate, prochloraz, triflumizole; Benzimidazoles: benomyl, carbendazim, fuberidazole, thiabendazole;
  • Pyridines fluazinam, pyrifenox, 3- [5- (4-chlorophenyl) -2,3-dimethylisoxazolidin-3-yl] pyridine;
  • Pyrimidines bupirimate, cyprodinil, ferimzone, fenarimol, mepanipyrim, nuarimol, pyrimethanil;
  • Dicarboximides iprodione, procymidone, vinclozolin;
  • acibenzolar-S-methyl anilazine, captan, captafol, dazomet, diclomethine, fenoxanil, folpet, fenpropidin, famoxadone, fenamidone, octhilinone, probenazole, proquinazide, pyroquilon, quinoxyfen, tricyclazole, 5-chloro-7- ( 4-methyl-piperidin-1-yl) -6- (2,4,6-trifluorophenyl) - [1,2,4] triazolo [1,5-a] pyrimidine, 2-butoxy-6- iodo-3-propyl-chromen-4-one, 3- (3-bromo-6-fluoro-2-methylindol-1-sulfonyl) - [1, 2,4] triazole-1-sulfonic acid dimethylamide;
  • Carbamates and Dithiocarbamates - Dithiocarbamates Ferbam, Mancozeb, Maneb, Metiram, Metam, Propineb, Thiram, Zineb, Ziram;
  • guanidines dodine, iminoctadine, guazatine
  • Sulfur-containing heterocyclyl compounds isoprothiolanes, dithianone;
  • Organophosphorus compounds edifenphos, fosetyl, fosetyl-aluminum, Iprobenfos, pyrazophos, tolclofos-methyl, phosphorous acid and their salts;
  • Organochlorine compounds thiophanates methyl, chlorothalonil, dichlofluanid, toiylfluanid, flusulfamides, phthalides, hexachlorobenzene, pencycuron, quintozene;
  • Nitrophenyl derivatives binapacryl, dinocap, dinobuton;
  • - Inorganic active substances Bordeaux broth, copper acetate, copper hydroxide, copper oxychloride, basic copper sulphate, sulfur;
  • the compounds of the formula I according to the invention and their salts, in particular their agriculturally acceptable salts, are furthermore suitable for controlling arthropodic plant pests, in particular plant-damaging insects and arachnids. Furthermore, the compounds of the formula I according to the invention and their salts, in particular their agriculturally acceptable salts, are suitable for combating nemathodes, in particular plant-damaging nematodes.
  • phytopathogenic arthropods are insects
  • the order Lepidoptera e.g. Agrotis ypsilon, Agrotis segetum, Alabama argillacea, Anticarsia gemmatalis, Argyresthia conjugella, Autographa gamma, Bupalus piniarius, Cacoecia murinana, Capua reticulana, Cheimatobia brumata, Choristoneura fumiferana, Choristoneura occidentalis, Cirphis unipuncta, Cydia pomonella, Dendrolimus pini, Diaphania nitidalis, Diatraea grandiosella, Earias insulana, Elasmopalpus lignosellus, Eupoecilia ambiguella, Evetria bouliana, Feltia subterranea, Galleria mellonella, Grapholitha funebrana, Grapholitha molesta, Heliothis armigera,
  • Heliothis virescens Heliothis zea, Heliuta undalis, Hibernia defoliaria, Hyphantria cunea, Hyponomeuta malinellus, Keiferia lycopersicella, Lambdina fiscellaria, Laphygma exigua, Leucoptera coffeella, Leucoptera scitella, Lithocolletis blancardel Ia, Lobesia botrana, Loxostege sticticalis, Lymantria dispar, Lymantria monacha, Lyonetia clerkella, Malacosoma neustria, Mamestra brassicae, Orgyia pseudotsugata, Ostrinia nubilalis, Panolis flammea, Pectinophora gossypiella, Peridroma saucia, Phalera bucephala, Phthorimaea operculella, Phyllocnistis citrella, Pieris brassica
  • the order Coleoptera (beetle), e.g. Agrilus sinuatus, Agriotes lineatus, Agriotes obscurus, Amphimallus solstitialis, Anisandrus dispar, Anthonomus grandis, Anthomorphus pomorum, Atomaria linearis, Blastophagus piniperda, Blitophaga undata,
  • the order Diptera e.g. Aedes aegypti, Aedes vexans, Anastrepha ludens, Anopheles maculipennis, Ceratitis capitata, Chrysomia bezziana, Chrysomya hominivorax, Chrysomia macellaria, Contarina sorghicola, Cordylobia anthropophaga, Culex pipiens, Dacus cucurbitae, Dacus oleae, Dasineura brassicae, Fannia canicularis , Gasterophilus intestinalis, Glossina morsitans, Haematobia irritans, Haplodipis equestris, Hylemyia platura, Hypoderma lineata, Liriomyza sativae, Liriomyza trifolii, Lucilia caprina, Lucilia cuprina, Lucilia sericata, Lycoria pectoralis, Mayetiola de
  • Thysanoptera e.g. Dichromothrips spp., Frankliniella fusca, Frankliniella occidentalis, Frankliniella tritici, Scirtothrips citri, Thrips oryzae, Thrips palmi and Thrips tabaci,
  • Hymenoptera e.g. Athalia rosae, Atta cephalotes, Atta sexdens, Atta texana, Hoplocampa minuta, Hoplocampa testudinea, Monomorium pharaonis, Solenopsis geminata and Solenopsis invicta,
  • Heteroptera e.g. Acrosternum hilare, Blissus leucopterus, Cyrtopeltis notatus, Dysdercus cingulatus, Dysdercus intermedius, Eurygaster integriceps,
  • the order Homoptera e.g. Acyrthosiphon onobrychis, Adelges laricis, Aphidula nasturtii, Aphis craccivora, Aphis fabae, Aphis forbesi, Aphis pomi, Aphis gossypii,
  • the order Isoptera (termites), e.g. Calotermes flavicollis, Leucotermes flavipes, Reticulitermes lucifugus and Termes natalensis, and
  • Orthoptera e.g. Acheta domestica, Blatta orientalis, Blattella germanica, Forficula auricularia, Gryllotalpa gryllotalpa, Locusta migratoria, Melanoplus bivittatus, Melanoplus femur-rubrum, Melanoplus mexicanus, Melanoplus sanguinipes, Melanoplus spretus, Nomadacris septemfasciata, Periplaneta americana, Schistocerca americana, Schistocerca peregrina , Stauronotus maroccanus and
  • arachnids such as Acaria (Acarina), for example the families Argagridae, Ixodidae and Sarcoptidae, such as Amblyomma americanum, Amblyomma variegatum, Argas persicus, Boophilus annulatus Boophilus decoloratus, Boophilus micro-plus, Dermacentor silvarum, Hyalomma truncatum, Ixodes ricinus, Ixodes rubicundus, Ornithodorus moubata, Otobius megnini, Dermanyssus gallinae, Psoroptes ovis, Rhipicephalus appendiculatus, Rhipicephalus evertsi, Sarcoptes scabiei, and Eriophyida spp.
  • Arachnoidea such as Acaria (Acarina)
  • Amblyomma americanum Amblyomma variegatum
  • Tetranychus cinabarinus Tetranychus kanzawai, Tetranychus pacificus, Tetranychus telarius and Tetranychus urticae, Panonychus ulmi, Panonychus citri, and Oligonychus pratensis.
  • the compounds of the formula I and their salts are also suitable for combating nematodes, for example root-gland nematodes, for example Meloidogyne hapla, Meloyndyne incognita, Meloidogyne javanica, cyst-forming nematodes, eg Globodera rostochiensis, Heterodera avenae, Heterodera glycines, Heterodera schachtii, Het- erodera trifolii, stem and leaf nematodes, eg, Belonolaimus longicaudatus, Ditylenchus destructor, Ditylenchus dipsaci, Heliocotylenchus multicinctus, Longidorus eligatus, Radopholus similis, Rotylenchus robustus, Trichodorus primitivus, Tylenchorhynchus claytoni, Tylenchorhynchus dubius,
  • the invention also relates to a method for controlling the aforementioned animal pests, which comprises treating the animal plant pests or the plants, seeds, materials or the soil to be protected against attack by these harmful organisms with an effective amount of the compounds of formula I or their salts ,
  • the application can be carried out both before and after the infestation of the materials, plants or seeds by the harmful organisms.
  • 5-hetarylpyrimidines of the general formula I in particular the 5-hetarylpyrimidines of the formula I described in the preceding description, and their pharmaceutically suitable salts effectively inhibit the growth and / or proliferation of tumor cells, as in standard tests on tumor cell lines , such as HeLa, MCF-7 and COLO 205, can be shown.
  • pyrimidines of the invention exhibit the general formula I in IC 5 o values ⁇ 10 "6 mol / l (ie ⁇ 1 uM), preferably IC 50 values ⁇ 10" 7 mol / l (ie ⁇ 100 nM) for Zellzyklusinhi- beer in HeLa cells.
  • the 5-hetarylpyrimidines of the formula I are therefore suitable for the treatment, inhibition or control of the growth and / or proliferation of tumor cells and associated diseases suitable. Accordingly, they are for cancer therapy in warm-blooded vertebrates, ie of mammals and birds, especially in humans, but also in other mammals, especially in domestic and domestic animals such as dogs, cats, pigs, ruminants (cattle, sheep, goats, bison, etc.). ), Horse and birds such as chicken, turkey, duck, goose, guinea fowl and the like.
  • 5-hetarylpyrimidines of the formula I are suitable for the treatment of cancer or cancerous diseases of the following organs: breast, lung , Intestine, prostate, skin (melanoma), kidney, bladder, mouth, larynx, esophagus, stomach, ovaries, pancreas, liver and brain.
  • the invention further relates to the pharmaceutical use of the 5-hetarylpyrimidines of the formula I and their pharmaceutically suitable salts, in particular the use of the preferred 5-hetarylpyrimidines of the formula I and their pharmaceutically acceptable salts, and especially their use for the manufacture of a medicament for the treatment of cancer.
  • the present invention relates to a pharmaceutical composition containing at least one 5-hetarylpyrimidine of the formula I and / or a pharmaceutically acceptable salt thereof and optionally at least one pharmaceutically acceptable carrier.
  • a pharmaceutical composition containing at least one 5-hetarylpyrimidine of the formula I and / or a pharmaceutically acceptable salt thereof and optionally at least one pharmaceutically acceptable carrier.
  • pharmaceutical compositions which contain at least one (that is to say novel) 5-hetarylpyrimidine of the formula I according to the invention and / or a pharmaceutically suitable salt thereof.
  • those pharmaceutical compositions which contain at least one previously mentioned as preferred 5-hetaryl-pyrimidine of the formula I and / or a pharmaceutically suitable salt thereof.
  • compositions according to the invention contain, in addition to a 5-hetarylpyrimidine of the formula I and / or a pharmaceutically suitable salt thereof, optionally at least one suitable carrier.
  • suitable carriers include, for example, the solvents, carriers, excipients, excipients and the like commonly used for pharmaceutical formulations, which are exemplified below for single modes of administration.
  • the compounds of the formula I according to the invention or used according to the invention can be administered in the usual way, for.
  • oral intravenous, intramuscular or subcutaneous.
  • the active ingredient may be mixed with an inert diluent or with an edible carrier; it can be embedded in a hard or soft gelatin capsule, pressed into tablets or mixed directly with the food / feed.
  • the active ingredient may be mixed with excipients and administered in the form of indigestible tablets, buccal tablets, troches, pills, capsules, suspensions, juices, syrups and the like.
  • Such preparations should contain at least 0.1% active ingredient.
  • the composition of the preparation may of course vary. It usually contains from 2 to 60% by weight of active compound, based on the total weight of the particular preparation (dosage unit).
  • Preferred preparations of the compound I according to the invention or used according to the invention contain 10 to 1000 mg of active ingredient per oral dosage unit.
  • the tablets, troches, pills, capsules and the like may also contain the following ingredients: excipients such as tragacanth, acacia, corn starch or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch, potato starch, alginic acid and the like, lubricants such as magnesium stearate, sweetener, such as sucrose, lactose, or saccharin, and / or flavorants such as peppermint, vanilla, and the like.
  • Capsules may also contain a liquid carrier.
  • Other substances which change the nature of the dosing unit can also be used. be set. For example, tablets, pills and capsules may be coated with shellac, sugar or mixtures thereof.
  • Syrups or juices may contain, in addition to the active ingredient, also sugar (or other sweetening agents), methyl or propylparaben preservatives, a dye and / or a flavoring agent.
  • sugar or other sweetening agents
  • methyl or propylparaben preservatives e.g., a dye and / or a flavoring agent.
  • the constituents of the active compound preparations in the quantities used must be pharmaceutically pure and non-toxic.
  • the active compounds may be used as controlled-release preparations, e.g. As a sustained-release preparations formulated.
  • the active substances can also be administered parenterally or intraperitoneally. Solutions or suspensions of the active compounds or their salts can be prepared with water using suitable wetting agents such as hydroxypropylcellulose. Dispersions can also be made with glycerin, liquid polyethylene glycols, and mixtures thereof in oils. Often these preparations also contain a preservative to prevent the growth of microorganisms.
  • Preparations for injections include sterile aqueous solutions and dispersions as well as sterile powders for the preparation of sterile solutions and dispersions.
  • the preparation must be sufficiently liquid so that it is injectable. It must be stable under the conditions of manufacture and storage and be protected against microbial contamination.
  • the carrier can be a solvent or a dispersion medium, e.g. Water, ethanol, polyols (e.g., glycerol, propylene glycol, or liquid polyethylene glycol), mixtures thereof, and / or vegetable oils.
  • the active ingredients were formulated separately as a stock solution in dimethylsulfoxide at a concentration of 10,000 ppm.
  • the stock solution is pipetted into a microtiter plate (MTP) and diluted with an aqueous malt-based fungal nutrient medium to the stated active substance concentration. This was followed by the addition of an aqueous spore suspension of Pyricularia oryzae.
  • MTP microtiter plate
  • the plates were placed in a water vapor saturated chamber at temperatures of 18 ° C. With an absorbance photometer, the MTP's were measured at 405 nm on the 7th day after inoculation. The measured parameters were compared with the growth of the drug-free control variant and the fungus- and drug-free blank to determine the relative growth in% of the pathogens in the individual drugs.
  • Example 3 the sample treated with 125 ppm of the compound from Example 1, Example 2 or Example 3 showed a maximum of 5% relative growth of the pathogen.
  • the respective active ingredient was prepared as a stock solution with 25 mg of active ingredient, which in a mixture of acetone and / or dimethyl sulfoxide (DMSO) and the emulsifier Wettol EM 31 (wetting agent with emulsifying and dispersing action based on ethoxylated alkylphenols) in the volume ratio solvent Emulsifier from 99 to 1 ad 10 ml was filled. It was then made up to 100 ml with water. This stock solution was diluted with the described solvent-emulsifier-water mixture to the drug concentration given below.
  • DMSO dimethyl sulfoxide
  • Wettol EM 31 wetting agent with emulsifying and dispersing action based on ethoxylated alkylphenols
  • Leaves of potted tomato plants were sprayed to drip point with an aqueous suspension in the drug concentration below. The following day, the leaves were infected with an aqueous spore suspension of Alternaria solani in 2% biomalt solution with a density of 0.17 x 10 6 spores / ml. Subsequently, the plants were placed in a water vapor-saturated chamber at temperatures between 20 and 22 0 C. After 5 days, the disease on the untreated, but infected control plants had developed so strongly that the infestation could be determined visually in%.

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Abstract

La présente invention concerne des 5-hétaryl-4-pyrimidines de formule (I) et leur sels ainsi que des agents de protection végétale qui contiennent un composé de ce type en tant que principe actif. Dans ladite formule : W est oxygène, soufre, un groupe S=O ou S(=O)2; R1 est alkyle en C1-C8, cycloalkyle en C3-C8, bicycloalkyle en C5-C10, alcényle en C2-C8, alcadiényle en C4-C10, cycloalcényle en C3-C6, alcinyle en C2-C8, phényle, naphthyle éventuellement substitué, ou un hétérocycle lié à C, comprenant cinq ou six éléments, saturé, partiellement insaturé ou aromatique qui présente un, deux, trois ou quatre hétéroatomes choisis dans le groupe comprenant O, N et S en tant qu'éléments du cycle; R2 est halogène cyano, hydroxy, mercapto, N3, alkyle en C1-C6, alcényle en C2-C8, alcinyle en C2-C8, halogénalkyle en C1C6, alcoxy en C1C6, alcényloxy en C3-C8, alcinyloxy en C3-C8, halogénalcoxy en C1C6, alkylthio en C1-C6, alcénylthio en C3-C8, alcinylthio en C3-C8, halogénalkylthio en C1-C6, ou un radical ayant l'une des formules suivantes C(=Z)OR21, C(=Z)NR22R23, C(=Z)NR24-NR22R23, C(=Z)R25, CR26R27-OR28, CR26R27-NR22R23, ON(=CR29R30), O-C(=Z)R25, NR22R23a, NR31(C(=Z)R25), NR31(C(=Z)OR21), NR31(C(=Z)-NR22R23), NR32a(N=CR29R30), NR32NR22R23, NR32OR21, ou C(=N-Z'-R25)SR21; ou un radical cyclique; R3 est hydrogène, OH, halogène, cyano, NR37R38, alkyle en C1-C8, alcoxy en C1-C8, alkylthio en C1-C8, alkylsulfinyle en C1-C8, alkylsulfonyle en C1-C8, alcényle en C2-C8 ou alcinyle en C2-C8, les 7 derniers radicaux cités pouvant être halogénés partiellement ou complètement et/ou pouvant porter un deux ou trois substituants choisis entre nitro, cyano, OH, alcoxy en C1-C2, alcoxycarbonyle en C1-C4, amino, alkylamino en C1-C4 et di-C1-C4-alkylamino; Het est un hétérocycle aromatique à 5 ou 6 éléments, lié à C ou N, substitué qui comprend 1, 2, 3 ou 4 hétéroatomes sélectionnés entre azote, oxygène et soufre en tant qu'éléments du cycle. L'invention concerne également l'utilisation de 5-hétaryl-4-pyrimidines de formule (I) et de leurs sels pour lutter contre des champignons nuisibles.
PCT/EP2007/053332 2006-04-05 2007-04-04 5-hétarylpyrimidines substituées WO2007113322A2 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009007187A1 (fr) * 2007-07-09 2009-01-15 Basf Se 5-hétarylpyrimidines substituées

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