New derivatives of simple propargilovyh ether

 

(57) Abstract:

The invention relates to compounds of General formula I

including their optical isomers and mixtures of such isomers, where r1denotes hydrogen, C1-C6alkyl, C3-C6cycloalkyl or aryl, optionally substituted by 1-3 halogen atoms, R2and R3each independently of one another denote hydrogen or C1-C6alkyl, R4stands WITH1-C6alkyl or C3-C6quinil, R5, R6, R7and r8each denotes hydrogen and

,

r10denotes aryl, optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl,1-WITH4haloalkoxy,1-C4alkoxy, C1-C4alkyl, C1-C6alkylthio,3-C6alkyloxy, nitro and C1-C6alkoxycarbonyl or optionally substituted heteroaryl represents an aromatic ring system containing as the heteroatom is at least one oxygen atom or sulfur, r11denotes hydrogen, C1-C6alkyl or C316and R16stands WITH1-C6alkyl, -CH2-CO - C1-C6alkyl or phenyl. The technical result - derivative simple propargilovyh ether, which represents an bactericides that are used to control or prevent infestation of plants by phytopathogenic microorganisms. 5 C.p. f-crystals, 12 tab.

The present invention relates to new derivatives of simple propargilovyh ether of the following formula I. It relates to the production of these compounds and to agrochemical compositions containing as active ingredient at least one of these compounds. The invention relates also to receive these compositions and to the use of compounds or compositions for combating or preventing infestation of plants by phytopathogenic microorganisms, especially fungi.

The invention relates to a derivative of a simple propargilovyh ether of General formula I

including their optical isomers and mixtures of such isomers,

where R1denotes hydrogen, alkyl, cycloalkyl or optionally substituted aryl,

R2and R3each independently of one another denotes hydrogen or alkyl,

R4denotes alkyl, and a is hydrogen or alkyl and

R9refers to a group, or

R10denotes optionally substituted aryl or optionally substituted heteroaryl,

R11denotes hydrogen or optionally substituted alkyl, alkenyl or quinil,

Z represents hydrogen, -CO-R16, -COOR16, -CO-COOR16or-CONR16R17,

R12denotes hydrogen or optionally substituted alkyl, alkenyl or quinil,

R13denotes hydrogen or alkyl,

R14denotes hydrogen, alkyl, cycloalkyl or cycloalkenyl,

R15denotes alkyl, alkenyl, quinil, optionally substituted aryl or optionally substituted arylalkyl and

R16and R17independently of one another denote hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl.

The above term “aryl” includes aromatic hydrocarbon rings, such as phenyl, naphthyl, anthracene, phenanthrene and biphenyl, for example 1,3-biphenyl and 1,4-biphenyl, while preferred is phenyl.

Heteroaryl denotes an aromatic ring system, including mono-, bi -, or three of the nitrogen or sulfur. Examples are furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolin, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazines, indolyl, benzothiophene, benzofuran, benzimidazole, indazole, benzotriazole, benzothiazole, benzoxazole, chinoline, ethenolysis, phthalazine, honokalani, hintline, cinnoline and naphthyridine.

The above aryl and heteroaryl groups optionally can be substituted. This means that they can have one or more identical or different substituents. Typically, one to three substituents. Examples of the substituents of aryl or heteroaryl groups are alkyl, alkenyl, quinil, cycloalkyl, cycloalkenyl, phenyl and phenylalkyl, in turn, all of the above groups can bear one or more identical or different halogen atoms; alkoxy; alkenylamine; alkyloxy; alkoxyalkyl; haloalkoxy, alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkylamino; carboxy; alkoxycarbonyl; alkenylbenzenes or alkyloxyaryl is the input of one or more substituents, selected from the series comprising halogen, alkyl, alkoxy, alkylthio, nitro, cyano, hydroxy, mercapto, alkylsulphonyl or alkoxycarbonyl. Preferably the number of substituents does not exceed three with the exception of halogen, when the alkyl groups can be perhalogenated.

In the above definitions, the term "halogen" includes fluorine, chlorine, bromine and iodine.

Alkyl, alkanniny and alkynylaryl radicals can be straight or branched chain. This also applies to the alkyl, alkenyl or alkynylaryl fragments of other alkyl-, alkenyl or alkenylsilanes groups.

Depending on the number of the carbon atoms of the alkyl individually or as part of another substituent is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and their isomers such as isopropyl, isobutyl, tert-butyl or sec-butyl, isopentyl or tert-pentyl.

Cycloalkyl depending on the number of carbon atoms is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

Depending on the number of carbon atoms of alkenyl as a separate group or as structo-yl, penten-3-yl, HEXEN-1-yl, 4-methyl-3-pentenyl or 4-methyl-3-hexenyl.

Quinil as a separate group or as a structural element of other groups is, for example, ethinyl, propyne-1-yl, propyne-2-yl, butyn-1-yl, butyn-2-yl, 1-methyl-2-butenyl, hexyne-1-yl, 1-ethyl-2-butinyl or octen-1-yl.

Haloalkaline group may contain one or more (identical or different) halogen atoms and may represent, for example, l2CH2F, CCL3CH2CL, CHF2, CF3CH2CH2VG, WITH2CL5CH2Br, CHClBr, CF3CH2and so on

The presence of at least one asymmetric carbon atom in the compounds of formula I means that the compounds can be in the form of optical isomers and enantiomers. Due to the possible presence of aliphatic C=C double bond can take place as geometric isomerism. It should be understood that under the scope of compounds of formula I covered all the possible isomeric forms and mixtures thereof.

Preferred subgroups of compounds of formula I include compounds in which R1denotes hydrogen, alkyl, cycloalkyl, phenyl or naphthyl; phenyl and naphthyl optionally have substituents, select the group and in turn can be substituted by one or more halogen atoms; alkoxy, alkenylacyl, alkyloxy; alkoxyalkyl; haloalkoxy; alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; piano; nitro; amino; alkylamino; dialkylamino; carboxy; alkoxycarbonyl; alkenylbenzenes or alkyloxyalkyl, or

R1denotes hydrogen, C1-C8alkyl, C3-C8cycloalkyl, phenyl or naphthyl; phenyl and naphthyl optionally have 1-3 substituent selected from a range that includes WITH1-C8alkyl, C2-C8alkenyl,2-C8quinil,2-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio,1-C8alkylsulfonyl, halogen, cyano, nitro and C1-C8alkoxycarbonyl, or

R1denotes hydrogen, C1-C8alkyl, phenyl, optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio, halogen, cyano, nitro and C1-C8alkoxycarbonyl, or

R2and R3oboznachaya, or

R8represents C1-C6alkyl,

R4represents C1-C6alkyl, or

R8denotes methyl or ethyl, or

R4denotes methyl or ethyl, or

R10denotes aryl or heteroaryl, each of which is optionally substituted by substituents selected from the series comprising alkyl, alkenyl, quinil, cycloalkyl, cycloalkenyl, phenyl and phenylalkyl, where all these groups may be substituted by one or more halogen atoms; alkoxy, alkenylacyl, alkyloxy; alkoxyalkyl; haloalkoxy; alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkylamino; carboxy; alkoxycarbonyl; alkenylbenzenes and alkyloxyalkyl, or

R10denotes phenyl, naphthyl, 1,3-biphenyl or 1,4-biphenyl, each of which is optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C2-C8alkenyl,2-C8quinil,1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio,1-C8alkylsulfonyl, halogen, cyano, nitro, each of which optionally is substituted by 1-3 substituents, selected from a range that includes WITH1-C8alkyl, C1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy, C1-C8alkylthio,1-C8haloalkylthio, halogen, cyano, nitro and C1-C8alkoxycarbonyl, or

R11denotes hydrogen, C1-C4alkyl, C1-C4haloalkyl,3-C4alkenyl or3-C4quinil or

R11denotes hydrogen or C1-C4alkyl or

R11denotes hydrogen or

Z denotes hydrogen or-CO-R16where R16stands WITH1-C4alkyl or C3-C6cycloalkyl, or

Z denotes hydrogen or-CO-R16where R16stands WITH1-C4alkyl, or

Z denotes hydrogen or acetyl, or

Z denotes hydrogen or

R12denotes hydrogen, C1-C6alkyl, C1-C6haloalkyl,3-C6alkenyl or3-C6quinil or

R12denotes hydrogen, C1-C6alkyl, C3-C6alkenyl or3-C6quinil or

R12denotes hydrogen or C1-C3alkyl or

R13hereafter the means C1-C6alkyl or C3-C7cycloalkyl or

R14stands WITH2-C5alkyl or C3-C7cycloalkyl or

R15denotes alkyl, alkenyl, quinil; aryl or arylalkyl, with aryl and arylalkyl each optionally substituted with substituents selected from the series comprising alkyl, alkenyl, quinil, cycloalkyl, cycloalkenyl, phenyl and phenylalkyl, where all these groups may be substituted by one or more halogen atoms; alkoxy, alkenylacyl, alkyloxy; alkoxyalkyl; haloalkoxy; alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkylamino; carboxy; alkoxycarbonyl; alkenylbenzenes and alkyloxyaryl, or

R15stands WITH1-C8alkyl, C3-C8alkenyl,3-C8quinil; phenyl or benzyl, the phenyl and benzyl optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C2-C8alkenyl,2-C8quinil,1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio,1-C83-C6alkyl, C3-C6alkenyl or phenyl, optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio, halogen and cyano.

One preferred subgroup of compounds of formula I consists of compounds in which R11denotes hydrogen or alkyl, Z represents hydrogen or-CO-R16, R12denotes hydrogen, alkyl, alkenyl or quinil and R16denotes hydrogen or alkyl.

Other preferred subgroups of compounds of formula I include compounds in which

R1denotes hydrogen, alkyl, cycloalkyl, phenyl or naphthyl; phenyl and naphthyl optionally substituted with substituents selected from the series comprising alkyl, alkenyl, quinil, cycloalkyl, cycloalkenyl, phenyl and phenylalkyl, where all these groups in turn can be substituted by one or more halogen atoms; alkoxy, alkenylacyl, alkyloxy; alkoxyalkyl; haloalkoxy; alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkyl R10denotes aryl or heteroaryl, each of which is optionally substituted by substituents selected from the series comprising alkyl, alkenyl, quinil, cycloalkyl, cycloalkenyl, phenyl and phenylalkyl, where all these groups may be substituted by one or more halogen atoms; alkoxy, alkenylacyl, alkyloxy; alkoxyalkyl; haloalkoxy; alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkylamino; carboxy; alkoxycarbonyl; alkenylbenzenes and alkyloxyaryl, and Z denotes hydrogen or-CO-R16where R16represents C1-C4alkyl, and R15denotes alkyl, alkenyl, quinil; aryl or arylalkyl, with aryl and arylalkyl each optionally substituted with substituents selected from the series comprising alkyl, alkenyl, quinil, cycloalkyl, cycloalkenyl, phenyl and phenylalkyl, where all these groups may be substituted by one or more halogen atoms; alkoxy, alkenylacyl, alkyloxy; alkoxyalkyl; haloalkoxy; alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkylamino; carboxy; alkoxycarbonyl; alkenylbenzenes and alkyloxyaryl, Tyl; while the phenyl and naphthyl optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C2-C8alkenyl,2-C8quinil,1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio,1-C8alkylsulfonyl, halogen, cyano, nitro and C1-C8alkoxycarbonyl, and R2, R3, R5, R6and R7represent hydrogen, and R4and R8independently of one another denote C1-C6alkyl, and R10denotes phenyl, naphthyl, 1,3-biphenyl or 1,4-biphenyl, each of which is optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C2-C8alkenyl,2-C8quinil,1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio,1-C8alkylsulfonyl, halogen, cyano, nitro and C1-C8alkoxycarbonyl; and R11denotes hydrogen or C1-C4alkyl, and Z represents hydrogen or acetyl, and R12denotes hydrogen, C1-C6alkyl, C3-C6oznachaet C1-C6alkyl or C3-C7cycloalkyl, and R15stands WITH1-C8alkyl, C3-C8alkenyl,3-C8quinil; phenyl or benzyl, the phenyl and benzyl optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C2-C8alkenyl,2-C8quinil,1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio,1-C8alkylsulfonyl, halogen, cyano, nitro and C1-C8alkoxycarbonyl, or

R1denotes hydrogen, C1-C8alkyl, phenyl, optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio, halogen, cyano, nitro and C1-C8alkoxycarbonyl, and R2, R3, R5, R6and R7represent hydrogen and R4and R8each independently of one another denote methyl or ethyl, and R10denotes phenyl, naphthyl, 1,3-biphenyl or 1,4-biphenyl, each independently from SUB>-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio, halogen, cyano, nitro and C1-C8alkoxycarbonyl, and R11, Z and R13each represents hydrogen, and R12denotes hydrogen or C1-C3alkyl, and R14stands WITH2-C5alkyl or C3-C7cycloalkyl, and R15stands WITH3-C6alkyl, C3-C6alkenyl or phenyl, optionally substituted by 1-3 substituents chosen from the series, including1-C8alkyl, C1-C8haloalkyl,1-C8alkoxy, C1-C8haloalkoxy,1-C8alkylthio,1-C8haloalkylthio, halogen and cyano.

Preferred individual compounds are

2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-

injectively)ethyl]acetamide", she

2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-

injectively)ethyl]acetamide", she

2-(4-forfinal)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-bromophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-amide,

2-(4-were)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(2-naphthyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]-2-oxoacetate,

2-(4-chlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(4-bromophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(4-were)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(3,4-acid)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(1-methylethanolamine)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-3-methylbutyrate,

2-(1,1-dimethylethylenediamine)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-3-methylbutyrate,

2-(1,1-dimethylethylenediamine)-N-{2-[3-methoxy-4-(Penta-2-ynyloxy)phenyl]ethyl}-3-methylbutyrate,

2-(1,1-dimethylethylenediamine)-N-{2-[3-methoxy-4-(4-forgeryproof-2-ynyloxy)phenyl]ethyl}-3-methylbutyrate,

2-(1,1-dimethylethylenediamine)-N-{2-[3-methoxy-4-(4-chlorpheniram-2-ynyloxy)phenyl]ethyl}-3-methylbutyrate,

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-prop-2-inyl the>methoxybenzene,

2-(4-were)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide,

2-(4-bromophenyl)-2-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-

methoxybenzene,

2-(4-chlorophenyl)-2-hydroxy-N-[(R)2-(3-methoxy-4-prop-2-injectively)propyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-N-[(S) - 2-(3-methoxy-4-prop-2-injectively)propyl]acetamide", she

2-(4-chloro-2-nitrophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-

injectively)ethyl]acetamide", she

2-(4-ethylphenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-triptoreline)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-

injectively)ethyl]acetamide", she

2-(4-were)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]acetamide", she

2-(4-bromophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]acetamide", she

2-(4-were)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]acetamide", she

2-(4-triptoreline)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-(4-bromophenyl)-2-hydroxy-N-[2-(3-methoxy who]ndimethylacetamide,

2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-naphthyl-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-(4-triptoreline)-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-(4-biphenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-bromophenyl)-2-metallinoks-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-2-(prop-2-inyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]-2-oxoacetate,

2-(4-chlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide,

2-(4-were)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide and

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide.

To combat the damaging plants (pathogenic) fungi have been proposed some carbamates amino acids, derivatives almond acid and derivatives alkoxybenzenes acid (for example, in EP-A-398072, WO 94/29267 and WO 96/23763). However, these compounds are not satisfactory in all respects from the point of view selscohozaistvennaya formula I, are new types of bactericides, with a high level of activity.

Derived simple propargilovyh ether of the formula I can be obtained according to one of the processes represented in schemes 1-5 (see below).

Stage B

The acid of formula II or a derivative of the acid of formula II with an activated carboxyl function, where R9has the values specified for formula I, is subjected to the interaction with the amine of formula III, where R4, R5, R6, R7and R8have the meanings specified for formula I, optionally in the presence of a base and optionally in the presence of a diluent (stage A).

Derivatives of the acid of formula II with an activated carboxyl function are all compounds having an activated carboxyl group, such as gelegenheid, for example the acid chloride, such as symmetrical or mixed anhydrides, for example mixed anhydrides with O-alkalicarbonate, such as activated esters, such as complex pair-nitrophenolate esters or complex N-hydroxysuccinimide esters, and formed in situ activated forms of the amino acids of the formula II with condensing agents such as one, hexaphosphate O-benzotriazol-1-yl-N,N,N',N'-bis(pentamethylene)Urania, hexaflurophosphate O-benzotriazol-1-yl-N,N,N',N'-bis(tetramethylene)Urania, hexaflurophosphate O-benzotriazol-1-yl-N,N,N’,N’-tetramethylurea or hexaphosphate benzotriazol-1-electropermeabilization. Mixed anhydrides of the acids of formula II can be obtained by reacting the amino acid of formula II with esters of Harborview acid, such as alkalemia esters of Harborview acid, such as ethylchloride or isobutylparaben, optionally in the presence of organic or inorganic bases, such as tertiary amine, such as triethylamine, N,N-diisopropylethylamine, pyridine, N-methylpiperidine or N-methylmorpholine.

The above reaction is preferably carried out in a solvent such as an aromatic, non-aromatic or halogenated hydrocarbons, such as chlorinated hydrocarbons, for example dichloromethane or toluene; ketones, such as acetone; esters such as ethyl acetate; amides, for example N,N-dimethylformamide; NITRILES, for example acetonitrile, or ethers, for example diethyl ether, methyl tert-butyl ether, dioxane or tetrahydrofuran, or water. It is also possible to use mixtures of these rastvoriteleyj Amin, such as triethylamine, N,N-diisopropylethylamine, pyridine, N-methylpiperidine or N-methylmorpholine, such as a metal hydroxide or carbonate of a metal, preferably an alkali metal hydroxide or carbonate of an alkali metal such as lithium hydroxide, sodium hydroxide or potassium hydroxide, at temperatures in the range of -80 to 150 C, preferably at temperatures in the range -40 to 40C.

And finally, after that the compounds of formula I can be obtained by reacting a phenol of the formula IV, where R4, R5, R6, R7, R8and R9have the meanings specified for formula I, with a compound of formula V, where R1, R2and R3have the meanings specified for formula I, and where Y denotes a leaving group such as halide, for example chloride or bromide, or ether sulfonic acids, such as toilet, mesilate or triflate (stage B).

The reaction is preferably carried out in a solvent such as an aromatic, non-aromatic or halogenated hydrocarbons, such as chlorinated hydrocarbons, for example dichloromethane or toluene; ketones, for example acetone or 2-butanone; esters such as ethyl acetate; ethers, for example diethyl ether, methyl tert-butyl ARIMAR methanol, ethanol, isopropanol, n-butanol or tert-butanol, sulfoxidov, such as dimethylsulfoxide or water. It is also possible to use mixtures of these solvents. The reaction is carried out optionally in the presence of organic or inorganic bases, such as tertiary amine, such as triethylamine, N,N-diisopropylethylamine, pyridine, N-methylpiperidine or N-methylmorpholine, such as a metal hydroxide, a metal carbonate or a metal alkoxide, preferably a hydroxide of an alkali metal, a carbonate of an alkali metal or an alkali metal alkoxide such as lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, potassium methoxide, ethoxide sodium, atoxic potassium tert-piperonyl or sodium tert-piperonyl potassium, at temperatures in the range from -80 to 200C, preferably at temperatures in the range from 0 to 120C.

Stage b: Compound of formula VI, where R4, R5, R6, R7and R8have the meanings specified for formula I, alkylate using the compounds of formula V (see scheme 1), where R1, R2,R3and Y have the values listed for scheme 1, in the same manner described for stage B in figure 1.

Stage D: the Compound of formula VII, where RI, subjected to dehydration, getting isocyanic formula VIII, where R1, R2, R3, R4, R5, R6, R7and R8have the meanings specified for formula I, in well-known conditions (D. Seebach, G. Adam, T. Gees, M. Schiess, W. Weigang, Chem. Ber. 1988, 121, 507).

Stage D: Isocyanic formula VIII, where R1, R2, R3, R4, R5, R6, R7and R8have the meanings specified for formula I, is subjected to the interaction with the aldehyde or ketone of formula IX, where R10and R11have the meanings specified for formula I, in the presence of a carboxylic acid R16-COOH, where R16denotes hydrogen or lower alkyl, typically acetic acid, receiving O-acyl-hydroxyamide formula Ia, where R1, R2, R3, R4, R5, R6, R7, R8, R10and R11have the meanings specified for formula I, (three-component reaction of Passerini, J. March, Advanced Organic Chemistry, 4th ed., Wiley, 1992, page 980).

Alternatively, isocyanic formula VIII, where R1, R2, R3, R4, R5, R6, R7and R8have the meanings specified for formula I, is subjected to the interaction with the aldehyde or ketone of the formula IX in the presence of titanium tetrachloride, getting the>and R11have the above values) in a well-known conditions (Chem. Ber. 1988, 121, 507; O. Ort. and other Pesticide Sci. 1997, 50, 331).

Stage E: Compound of formula VII, where R1, R2, R3, R4, R5, R6, R7and R8have the meanings specified for formula I, is treated with one equivalent of phosgene (for example, triphosgene) and a base (e.g. triethylamine) and in the second stage, without isolating the intermediate product in the form of isocyanate is treated with titanium tetrachloride and an aldehyde or ketone of formula IX, where R10and R11have the meanings specified for formula I, in well-known conditions (WO 96/17840), getting hydroxyamide formula Ib, where R1, R2, R3, R4, R5, R6, R7, R8, R10and R11have the meanings specified for formula I.

Stage G: O-acyl-hydroxyamide formula Ia, where R1, R2, R3, R4, R5, R6, R7, R8, R10, R11and R16have the above meanings, is subjected to hydrolysis to obtain hydroxyamide formula Ib, where R1, R2, R3, R4, R5, R6, R7, R8, R10and R11have the meanings specified for formula I, in classic R3, R4, R5, R6, R7, R8, R10and R11have the meanings specified for formula I, are oxidized with an organic oxidant, such as alkylhydroperoxide, reagent on the basis of DMSO (T. T. Tidwell, Org. React., 1990, 29, 297-572), hypervalent iodine-containing reagent, dioxirane, nitroxyl radical, or inorganic oxidizing agent such as peroxides.

The interaction of the compounds of formula Ib with an oxidising agent is preferably carried out in an inert solvent, such as THF, dichloromethane, water or a ketone, for example acetone, or mixtures thereof in the presence of acid or without it, or in the presence of a base or without it at a temperature of from -80 to 150.

Stage I: Compound of formula IC, where R1, R2, R3, R4, R5, R6, R7, R8and R10have the meanings specified for formula I, is subjected to interaction with R12-O-NH2where R12has the above values, in classical terms oxymorphine (see, for example, J. March, Advanced Organic Chemistry, 4th ed., published by Wiley, 1992), obtaining the compound of formula Id where R1, R2, R3, R4, R5, R6, R7, R8, R10and R12have the above values. In addition, if R12Stage L: Dioxolane IX (obtained by condensation of almond acid with acetone in the presence of an acid catalyst (see EP-A-071568)) is treated sequentially base, such as diisopropylamide lithium (LDA) and alkylating agent R11-L according to known methods (THL 1994, 2891, Rec. Trav. Chim. Pays-Bas, DE 4319887).

Stage M and N: the Resulting dioxolane X or incubated with the appropriate amine XI at a temperature of 50-200C (stage M) or dioxalane first hydrolyzing dilute aqueous mineral acid (such as Hcl) or alkaline conditions (aqueous solution of sodium hydroxide (0-120C; stage N)) to obtain the substituted hydroxy acid II', which can then be subjected to amidation (according to the stage And scheme 1). Hydroxyacids II' can also be obtained by reacting the Grignard reagent R10-MgHal (using as initial products aryl halides and Mg) with the corresponding ether-keto-acid (Synthesis 1993,606).

Stage II: the Corresponding derivative of an ether carboxylic acid XII is subjected to interaction with alkylating oxidized (NaIO4) to gettimetolive ether, which in turn can be oxymoron to examinationby acid XVIII, as described in J. Med. Chem. 28, 1896.

Stage R stage With: Acetophenone derived XIV or a derivative of phenylacetic acid XVI to oxidize derived ketocarboxylic acid XIX with an oxidant, such as SeO2in an inert solvent, such as dioxane, pyridine, at a temperature in the range of 20-150C (J. Gen. Org. Chem. USSR, 21, 694, 1951).

Stage T: Derived ketocarboxylic acid XIX transform into the corresponding oxime XVIII using hydroxylamine derivative of H2NOR12in an inert solvent according to the method described for stage I (see scheme 2).

Stage I: Derived ether akriluksusnoy acid XVI eximious using Alternaria in alkaline or acidic conditions according to the method described in Org. reactions, volume 7, 327 (1953); Houben Weyl X/1, 911 and forth; ibid X/4, 44 and forth.

Stage X: Derived ketocarboxylic acid XIX restore using hydrogen in the presence of a catalyst, such as PtO2in an inert solvent, such as tetrahydrofuran, or with sodium borohydride at low temperature (-20 to 60°C) in a solvent such as alcohol (ethanol catalysts, allowing to obtain enantiomerically pure alcohols (Org. Synth. 63, 18 (1984; JACS 109, 5856; C. R. Stephenson, Advanced Asymm. Synthesis, London, 1996; M. Hudlicky. Reductions in Org. Chemistry, ACS Monogr. 188, Washington, 1996).

If necessary, the alcohol XX can be oxidized using an oxidizing agent (for example, DMSO/ll/tert-amine; J. Am. Chem. Soc. 108, 1035) to give the ketone XIX according to the method described for stage 3 (see scheme 2) (M. Hudlicky, Oxidations in Org. Chemistry, monograph 186 ACS, Washington, 1990).

Stage C: Aryl derivative XIII transform aired ketocarboxylic acid XIX by treatment derived ester of oxalic acid L2OC-Coolkill, where L2denotes a leaving group such as chlorine atom or alkoxygroup, in the presence of a Lewis acid, for example, ll3in an inert solvent, such as dichlorobenzene or CS2 (J. Med. Chem. 28, 1896).

Stage H: Aldehyde XV transform in the appropriate cyanhydrin by reacting with alkali metal cyanide (e.g., KCN) in the presence of sodium bisulfite (NaHSO3) in an inert solvent, such as water, or by interaction with trialkylsilanes in the presence of Lewis acid (ZnI2). Then cyanhydrin or trialkylsilyl ester hydrolyzing with mineral acids, such as water salanity XVI is subjected to hydroxylation with a derivative of hydrogen peroxide, for example bestemmelser derivative of hydrogen peroxide, in an inert solvent and in the presence of a base, such as diisopropylamide lithium (LDA) at temperatures from -90 up to 50C according to the method described in Synth. Comm. 18, 2141 (1988).

Stage G: Dichloroacetophenone XVII is treated with alkali metal hydroxide (NaOH) in water according to the method described in EP-A-071568.

Stage A': intermediates XVIII, XIX and XX, where R6' denotes alkyl, can be hydrolyzed with 1.0 to 1.5 equivalents. an aqueous solution of alkali metal hydroxide in water or in mixtures with alcohol or tetrahydrofuran, resulting in a gain corresponding acid (II, II', II""). Acid II", II'", II"" can be subjected to interaction with the corresponding amine IIIa with obtaining amides II", II'", II"". The reaction can be carried out either by using the acid chloride in the presence of a base (pyridine or triethylamine) in an inert solvent or preferably directly using activator (for example, dicyclohexylcarbodiimide, carbonyldiimidazole or hexaphosphate benzotriazol-1-yloxytris(dimethylamino)phosphonium (THIEF) in an inert solvent and optionally in the presence of a base (tertiary amine) according to the method of the see scheme 1).

Intermediate products of the XVIII, XIX and XX, where R6' denotes alkyl, can also be directly subjected to the interaction with the amine IIIa in a solvent with a high boiling point or without him at temperatures of 70-S according to the method described in WO 94/29267.

Stage e: carboxylic acid Derivative HHP having a leaving group X1, is subjected to a reaction mix according to the method of Suzuki with arylboronic acid or its ester XXIII obtaining biphenylenes derived XXI (Synth. Comm. 11, 513 (1981); Acta Chem. Scand. 47, 221; Chem. Rev. 95, 2457; Heterocycles 34, 1395) in the presence of a base (carbonate of an alkali metal, fluoride of an alkali metal (e.g., CsF), tertiary amine (ethyldiethanolamine or ligand Buchwald (2'-dicyclohexylphosphino-2-yl)dimethylamine) and palladium catalyst (for example, a PdP(Ph)4Pd(OAc)2, (PPh)3PdCl2) in an inert solvent (benzene, toluene, acetonitrile, dioxane, water, aliphatic alcohols) at 0-150C.

Stage A: the resulting carboxylic acid derivative XXI subjected to amidation according to the method described for stage A (see scheme 1). By direct amidation of compound XXII receive end products Ia-f.

The who and bactericidal properties. They can be used in the agricultural sector or related fields as a means of prevention or treatment for combating phytopathogenic microorganisms. The compounds of formula I according to the invention are characterized in that they are at low consumption rates have not only a high bactericidal, primarily fungicidal activity, but also by the fact that they are very well tolerated by plants.

With the invention it has been unexpectedly found that the compounds of formula I have a very valuable from a practical point of view spectrum biocidal activity against phytopathogenic microorganisms, especially fungi. They have a very valuable therapeutic and prophylactic properties and can be used to protect many species of agricultural plants. Using compounds of formula I can inhibit or destroy pathogenic microorganisms that are found on different species of cultivated plants or on parts of such plants (fruits, flowers, leaves, stems, tubers, roots), while protection of these microorganisms, such as pathogenic fungi, also applies to those parts of the plants, which are formed in the later period.

New the m genera of the class of imperfect fungi (Fungi deuteromycota) (for example, Cercospora), Basidiomycetes (for example, Puccinia) and Ascomycetes (for example, Erysiphe and Venturia) and primarily against Oomycetes (for example, Plasmopara, Peronospora., Pythium and Phytophthora). Thus, the present invention represents a valuable contribution to the development of compositions intended to combat phytopathogenic fungi. The compounds of formula I can also be used as treaters for protecting seeds (fruit, tubers, grains) and cuttings of plants from fungal infections and against phytopathogenic fungi which occur in the soil.

The invention relates also to compositions containing as active ingredient the compounds of formula I, primarily to compositions for plant protection, and to their use in the agricultural sector or related fields.

In addition, the invention includes a method of preparing such compositions, according to which the active substance is mixed to a homogeneous state with one or more compounds or groups of compounds presented in this description. The invention also includes a method of processing plants, characterized in that it used the new compounds of formula I or new compositions.

Subject to protection under nastojashem, oats, rice, maize, sorghum and related crops); beet (sugar beet and fodder beet); pome fruit, stone fruit and berries (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil crops (rape, mustard, poppy, olive, sunflower, coconut, castor, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus crops (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, peppers); Laurel crops (avocado, cinnamon tree, camphor tree), and plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamental plants.

The compounds of formula I, generally used in the form of compositions and can be used for processing the cultivated area or plant to be treated, simultaneously or sequentially with other active substances. These other ingredients may constitute fertilizers, micronutrient donors or other preparations that influence n tidy, the nematicides, molluscicides or a mixture of several of these preparations, if necessary together with other carriers, surfactants or other facilitating the application of adjuvants, which are usually used for the manufacture of preparative forms.

The compounds of formula I can be mixed with other fungicides, resulting in unexpectedly can be obtained a synergistic effect.

Particularly preferred components of such mixtures are azoles such as azaconazole, bitertanol, propiconazol, difenoconazol, diniconazole, tsyprokonazolu, epoxiconazol, Fluconazol, flusilazol, flutriafol, hexaconazole, imazalil, kabekona, ipconazole, tebuconazole, tetraconazole, fenbuconazole, metconazole, myclobutanil, perforated, penconazole, bromuconazole, pirivenas, prochloraz, triadimefon, triadimenol, triflumizole or triticonazole; pyrimidinylidene, such as ancymidol, fenarimol or nuarimol; 2-aminopyrimidine, such as bupirimate, dimethirimol or ethirimol; morpholines such as dodemont, fenpropidin, fenpropimorph, spiroxamine or tridemorph; anilinopyrimidines, such as cyprodinil, Pyrimethanil or mepanipyrim; pyrrole, such as phenoxazine; the benzimidazole, such as benomyl, carbendazim, dibakar, fuberidazole or thiabendazole; dicarboximide, such as chlozolinate, diplozoon, iprodion, mickleton, procymidon or vinclozolin; carboxamide, such as carboxin, fanforum, flutolanil, mepronil, oxycarboxin or leflunamide; guanidine, such as guazatine, Dodin or iminoctadine; strobilurin, such as AZOXYSTROBIN, kresoxim-methyl, metamyosyn, SSF-129, methyl-2-[(2-trifluoromethyl)pyrid-6-intoximeter]-3-ethoxyacrylate or O-methyloxime 2-[-{[(-methyl-3-trifloromethyl)imino]oxy}-ortho-tolyl]Glyoxylic acid (Trifloxystrobin); dithiocarbamate, such as ferbam, MANCOZEB, MANEB, metiram, propineb, thiram, zineb or Tsira; N-holomediterranean, such as captafol, Kaltan, dichlofluanid, pluromed, folpet or tolyfluanid; copper compounds such as Bordeaux liquid, copper hydroxide, copper oxychloride, copper sulphate, copper oxide, marcopper or oxen copper; nitroaniline derivatives, such as dynacal or nitrates-isopropyl; organophosphorus derivatives, such as edifenphos, iprobenfos, isoprothiolane, forgiven, pyrazophos or tolios-methyl, and other compounds from different classes, such as acibenzolar-S-methyl, anilazine, Metamorph, dithianon, etridiazole, famoxadone, fenamidone, fentin, verison, fluazinam, glucolipid, fenhexamid, foretelling, hymexazol, kasugamycin, metasurfaces, pencycuron, phtalic, polyoxin, provenzal, propamocarb, pyroxylin, jenoxifen, hintzen, sulfur, triazoxide, tricyclazole, triforine, validamycin, (S)-5-methyl-2-methylthio-5-phenyl-3-phenylamino-3,5-dihydroimidazole-4-one (RPA 407213), 3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide (RH-7281), N-allyl-4,5-dimethyl-2-trimethylsilylmethyl-3-carboxamide (MON 65500), 4-chloro-4-cyano-N,N-dimethyl-5-para-tolylimidazo-1-sulfonamide (IKF-916), N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorphenoxy)propionamide (AC 382042), iprovalicarb (SZX 722).

Suitable carriers and surfactants can be solid or liquid and they are substances commonly used for the manufacture of preparative forms, for example natural or regenerated mineral substances, solvents, dispersing agents, wetting agents, adhesives, thickeners, binders or fertilizers. Such carriers and additives are described, for example, in WO 95/30651.

The preferred method of applying the compounds of formula I or agrochemical composition comprising at least idnorma consumption depend on the degree of risk of contamination addressed by the pathogen. The compounds of formula I can also be applied to seeds (coating) either by impregnating the seeds with a liquid composition containing the active substance, or by application of the coating of the dry composition.

The compounds of formula I are used in unmodified form or preferably together with the adjuvants normally used for the manufacture of preparative forms prepared by known method to obtain, for example, mulgirigala concentrates covering pastes, ready-to-use solutions for spraying or dilutable solutions, diluted emulsions, wettable powders, soluble powders, Farrukh Dustov, granules or by encapsulation, for example in polymeric substances. Processing methods, such as spraying, spraying in the form of a mist, dusting, scattering, coating or irrigation, is chosen depending on the type of composition, and in accordance with the objectives and specific conditions.

The preferred consumption rates typically range from 1 g to 2 kg of active ingredient (doctor). per hectare (ha), preferably from 10 g to 1 kg D. C./ha, most preferably from 25 to 750 g D. C./ha When used for seed norms-rasii, preparations or mixtures containing the compound(I) (current(s) substance(s)) of the formula I and optionally a solid or liquid adjuvant, get a known method, for example by mixing until smooth and/or grinding the active substances with extenders, for example with solvents, solid carriers and, if necessary, surface active substances (detergents).

Surfactants commonly used in the field of preparation preparative forms are known to the person skilled in the art or can be found in the relevant technical literature.

Agricultural compositions usually contain from 0.1 to 99 wt.%, preferably from 0.1 to 95 wt.%, the compounds of formula I, from about 99.9 to 1 wt.%, preferably from about 99.9 to 5 wt.% solid or liquid adjuvant and 0 to 25 wt.%, preferably from 0.1 to 25 wt.%, surface-active substances.

While concentrated compositions are more preferred as marketed products, direct consumer typically uses dilute compositions.

The composition can also contain other ingredients such as stabilizers, p. the other active ingredients for achieving specific actions.

The following examples serve to illustrate the invention, but they in no way limit its scope. Temperatures are given in degrees Celsius. Ph denotes phenyl.

Examples of the processes of obtaining

Example E1: 2-(3,4-Dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]ndimethylacetamide

To a mixture containing (3,4-dichlorophenyl)hydroxilase acid (3 g), hydrochloride 4-(2-amino-ethyl)-2-methoxyphenol (2.7 g) and ethyldiethanolamine (7 ml) in dimethylformamide (60 ml) is added in one portion hexaphosphate benzotriazol-1-yloxytris(dimethylamino)phosphonium (6 g). The mixture is stirred at room temperature for 3 hours Then add water (400 ml). The mixture is extracted with ethyl acetate (2400 ml) and washed with brine (2200 ml). The organic layers collected, dried over MgSO4and evaporated. The result is 2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]ndimethylacetamide, which is cleaned by rapid chromatography on columns on silica gel (ethyl acetate/hexane, 2:1) to give the product as oil.

A mixture containing 2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]ndimethylacetamide, propylbromide (0.5 ml) and potassium carbonate (1.5 g) in dimethyl sulfoxide, pereault with ethyl acetate (2 x 200 ml) and washed with brine (100 ml). The organic layers collected, dried over MgSO4and evaporated. The result is 2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]ndimethylacetamide, which is cleaned by rapid chromatography on columns on silica gel (ethyl acetate/hexane, 2:1) to give the product as oil.

Working according to the process described in example E1, obtain the compounds listed in table E1, E1.

Example E2: 2-(3,4-Dichlorophenyl)-2-methoxyimino-[2-(3-methoxy-4-prop-2-injectively)ethyl]ndimethylacetamide

To a solution containing 1.30 grams (3,20 mmole) of 2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate 7.0 ml of ethanol, add the value of 0.52 ml of pyridine (of 0.64 mmole) and 0.33 g (3,98 mmole) of the hydrochloride of O-methylhydroxylamine. The solution is maintained at 80C for 4 hours After evaporation of the solvent the residue is subjected to rapid chromatography, obtaining 2-(3,4-dichlorophenyl)-2-methoxyimino-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]ndimethylacetamide in the form of a solid white (tPL107-S)

Example E3: 2-(3,4-Dichlorophenyl)-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]-2-oxoacetate

To a solution containing 0.8 ml of oxalicacid (9.0 mmol) in 8 ml of methylene chloride, add-S in techenterprise 2.6 g (6.0 mmol) of 2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]ndimethylacetamide in 30 ml of CH2Cl2. After incubation for 10 min at-65S added dropwise within 15 min a solution containing 3.2 ml (24,0 mmole) of triethylamine in 8 ml of CH2Cl2. After incubation for 15 min at the same temperature, the mixture is subjected to hydrolysis using 6,0 ml of water and allow it to warm to room temperature. The solution is washed with solutions of KHSO4(20%), Panso3(saturated) and NaCl (saturated). After evaporation the residue is subjected to rapid chromatography (ethyl acetate/hexane, 25/75) to give 2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]-2-oxoacetate.

1H-NMR (300 MHz. Dl3): to 1.15 (t, 3 H, CH2CH3), 2,22 (m, 2 H, CH2CH3), 2,87 (t, 2 H, CH2CH2), to 3.64 (t, 2 H, CH2CH2), 3,88 (s, 3 H, och3), 4,72 (m, 2 H, och2), 6,77 (m, 2 H, CH arene.), of 6.99 (d, 1 H, CH arene.), 7,16 (t, 1 H, NH), EUR 7.57 (d, 8.22 m), and 8,49 (m. 3 H, CH arene.).

Example E4: 2-(4'-Chlorobiphenyl-4-yl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate

A mixture containing 652 mg of 2-(4'-chlorobiphenyl-4-yl)-2-octoxynol acid, 1.5 g of ethyldiethanolamine and 1.25 g of hexaflurophosphate benzotriazol-1-yloxytris(dimethylamino)phosphonium (THIEF), 15 ml of dimethylformamide, and stirred overnight while cooling to 0C. Then barivat and purified using GHUR (Lichrosphere Si-60/ethylacetate), getting the desired 2-(4'-chlorobiphenyl-4-yl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate, tPL122-124C.

Working according to processes described in the examples, E2, E3 and E4, get connections, perechislennye in table E2.

Example E5: 2-(3,4-Dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]ndimethylacetamide

3.4 g (13.0 mmol) of N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]formamide and 4.3 ml (32 mmole) of triethylamine are dissolved in 13 ml of CH2CL2. Add 5C 1.4 g (4.7 mmole) of bis(trichloromethyl)carbonate (triphosgene) in 9 ml of CH2CL2. The mixture is stirred for 4 h at 5 ° C and then cooled to-S. Add a solution containing 1,43 ml (13,0 mmole) TiCl4in 20 ml of CH2CL2and the mixture is stirred for 2 hours at-40C. Added dropwise 2.5 g (12.9 mmole) of 3,4-dichlorobenzaldehyde in 7 ml of CH2CL2and the mixture is stirred for 17 h at room temperature. The mixture is subjected to hydrolysis with 7 ml of 5 N. HCl, mix for 30 min at room temperature and washed with water. After evaporation the residue is subjected to rapid chromatography (ethyl acetate/hexane, 6:4) to give 2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]ndimethylacetamide.

1N-51 (m, 2 H, CH2CH2), 3,69 (d. 2 H; HE), 3,83 (s, 3 H, och3), 4,74 (m, 2 H, och2), 4,96 (d, 1 H, SNON), 6,27 (t, 1 H, NH), to 6.58 (m, 1 H), of 6.68 (m, 1 H), 6.92 (d. 1 H), 7,19 (d, 1 H), 7,42 (d, 1 H) and 7,49 (m, 1 H, CH arene.).

Example E6: 2-(4'-Triptoreline-4-yl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]ndimethylacetamide

a) 4-(4-Trifluoromethyl)acetophenone

The suspension containing 3,44 g of 4-bromoacetophenone, 4.94 g of 4-tripteronotus acid, 7,88 g of cesium fluoride, 80 mg of palladium acetate and (2'-dicyclohexylphosphino-2-yl)dimethylamine (Buchwald ligand)), in 100 ml of dioxane is heated in a nitrogen atmosphere. After completion of the reaction, the suspension is filtered through a filter type Hyflo, the filtrate evaporated and purified by filtration through silica gel (hexane/ethyl acetate, 7:3) to give 4-(4'-triptoreline)acetophenone in the form of a solid yellowish, tPL114-S.

b) 2-(4'-Triptorelin-4-yl)-2-Okrokana acid

Mixture of 3.96 g of 4-(4'-triptoreline)of acetophenone and 3.9 g of selenium dioxide in 21 ml of pyridine, maintained at 105C. After completion of the reaction, the reaction mixture was evaporated, dissolved in diethyl ether, alkalinized using diluted with 1 n sodium hydroxide and washed with diethyl ether. The aqueous layer is m sodium. After evaporation receive 2-(4'-triptorelin-4-yl)-2-octoxynol acid, tPLC (decomp.).

a) 2-(4'-Triptoreline-4-yl)-2-hydroxyestra acid

The solution containing 1.47 g of 2-(4'-triptoreline-4-yl)-2-octoxynol acid in 20 ml of tetrahydrofuran, is subjected to hydrogenation at room temperature in the presence of 160 mg of platinum oxide(IV) under reduced pressure until, until the absorption of hydrogen. The reaction mixture is filtered and evaporated, obtaining 2-(4'-triptoreline-4-yl)-2-hydroxilase acid, tPL185-C.

g) To a solution containing 662 mg of the hydrochloride of N-(2-(3-methoxy-4-prop-2-injectively)ethylamine in 35 ml of N,N-dimethylformamide and 1.5 ml of N-ethyldiethanolamine, successively added 740 mg of 2-(4'-triptoreline-4-yl)-2-hydroxyoctanoic acid and 1.25 g of hexaflurophosphate benzotriazol-1-yloxytris(dimethylamino)phosphonium. The yellowish solution is stirred over night at 20 ° C, diluted with ethyl acetate, washed with water and with brine and dried over sodium sulfate. The filtrate is evaporated and the resulting residue purified via chromatography (silica gel; hexane/ethyl acetate) to give the desired 2-(4'-triptoreline-4-yl)-2-hydroxy-N-[2-(3-methoxy-4-ol the E5 and E6, obtain the compounds listed in table E3.

Example E7: N-[2-(3-Methoxy-4-Penta-2-injectively)ethyl]formamide

41 ml of 30% aqueous solution of sodium methylate in methanol are added to a solution containing 31.5 g (180 mmol) of N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]formamide in 880 ml of methanol. Type of 48.1 g (184 mmole) Penta-2-innovage ester toluene-4-sulfonic acid and the mixture was kept at the temperature of reflux distilled for 4 hours After evaporation the residue is dissolved in ethyl acetate and washed with water. After evaporation the residue is subjected to rapid chromatography and after crystallization in a simple ether obtain N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]formamide.

1H-NMR (300 MHz, CDCl3): 1.14 (t, 3 H, CH2CH3), 2,22 (m, 2 H, CH2CH3), of 2.81 (t, 2 H, CH2CH2), of 3.48 and 3.57 (2 q (17:83), 2 H, CH2CH2), 3,88 (s, 3 H, och3), 4,70 (m, 2 H, och2), 5,58 (b, 1 H, NH), 6.73 x (m, 2 H, arene.), 6,98 (m, 1 H, arene.), to 8.14 (s, 1 H, Cho).

Example E8: 2-(4-Bromophenyl)-2-methyloxirane-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]ndimethylacetamide

To a solution containing 2-(4-bromophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]ndimethylacetamide (0.7 g, 1.6 mmole) in 30 ml of methylene chloride, add pyridine (0.3 g, 3.8 mmol the room temperature and the solvent is removed under vacuum and the residue evaporated three times with toluene. The resulting residue is subjected to chromatography on silica gel (simple ether/hexane, 60:40) to give 2-(4-bromophenyl)-2-methyloxirane-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]ndimethylacetamide.

1H-NMR (300 MHz, Dl3): 2,31 (t, 1H, ), 2,59 (m, 2H, CH2CH2), to 3.35 (m, 2H, CH2CH2), 3,62 (s, 3H, och3), 3,70 (s, 3H, och3), of 4.54 (s, 2H, ), to 5.85 (s, 1H CHC=O), 6,13 (t, 1H, NH), 6,47 (m, 2H, CH arene.), of 6.73 (d, 1H, CH arene.), 7,03 (d, 2H, CH arene.), 7,28 (d, 2H, CH arene.).

Working analogously to the process described in example E8 receive the compounds listed in table E4.

Example e: 2-(1,1-Dimethylethylenediamine)-N-{2-[3-methoxy-4-(4-chlorpheniram-2-ynyloxy)phenyl]ethyl}-3-methylbutyrate

To a mixture containing BOC-L-valine (4.7g), hydrochloride 4-(2-amino-ethyl)-2-methoxyphenol (4.5 g) and ethyldiethanolamine (6.5 g) in dimethylformamide (90 ml), is added in a single portion of hexaflurophosphate benzotriazol-1-yloxytris(dimethylamino)phosphonium (9.8 g). The mixture is stirred at room temperature for 4 hours Then add water (400 ml). The mixture is extracted with ethyl acetate (2400 ml) and washed with brine (2200 ml). The organic layers collected, dried (MgS4) and evaporated.

The result is 2-(1,1-dimethylethylenediamine)-N-[2-(4 on silica gel (ethyl acetate/hexane, 2:3) to give the product as oil.

To a mixture containing 3-(4-chlorophenyl)prop-2-in-1-ol (3.3 grams) and toluene-4-sulphonylchloride (3.7 g) in diethyl ether (100 ml), previously cooled to-15C, add small portions over 10 min powdered potassium hydroxide (2.8 g). The reaction mixture is stirred at 0C for 90 minutes then add water (200 ml), the mixture is extracted with diethyl ether (2100 ml) and washed with brine (50 ml). The organic layers collected, dried (Na2SO4) and evaporated. The result is 3-(4-chlorophenyl)prop-2-injuly ester toluene-4-sulfonic acid.

A mixture containing 2-(1,1-dimethylethylenediamine)-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-3-methylbutyrate (4.0 g), 3-(4-chlorophenyl)prop-2-injuly ester toluene-4-sulfonic acid (5.3g) and 1 M solution of sodium methoxide in methanol (18 ml) in methanol (100 ml), heated to a temperature of reflux distilled for 3 hours Then the solvent is removed by distillation. Add water (300 ml). The mixture is extracted with ethyl acetate (2200 ml) and washed with brine (100 ml). The organic layers collected, dried (MgSO4) and evaporated. The result is 2-(1,1-dimethylethylenediamine)-N-{2-[3-methoxy-4-(4-chlorpheniram-2-ynyloxy)phenyl]ethyl}-3 is an, 1:1) and recrystallization (ethyl acetate/hexane), tPL141-S.

Working analogously to the process described in example I receive the compounds listed in table E5.

Example E10: N-[2-(3,4-Dihydroxyphenyl)ethyl]formamide

Formic acid (198 ml, 5,26 mole) is added dropwise to 372 ml (3,95 mole) of acetic anhydride at 0C. The mixture is stirred for 2 h at 55C and then cooled to 0C. At this temperature, add 500 ml of tetrahydrofuran, and then 50 g (of 0.26 mole) of the hydrochloride of 3-hydroxytyramine. The resulting white suspension is stirred for 18 h at 75S, causing it turns into a yellow solution. The reaction mixture is evaporated and the residue is subjected to rapid chromatography, obtaining N-[2-(3,4-dihydroxyphenyl)ethyl]formamide.

1H-NMR (300 MHz, CDCl3): of 2.72 (t, 2H, CH2CH2), to 3.49 (t, 2H, CH2CH2), 6,67-7,20 (m, 3H, CH arene.), of 8.04 (s, 1H, CHO).

Example E11: N-[2-(3,4-Biprop-2-injectively)ethyl]formamide

120 ml of 30% aqueous solution of sodium methylate in methanol are added to a solution containing 52 g (to 0.29 mol) of N-[2-(3,4-dihydroxyphenyl)ethyl]formamide in 670 ml of methanol. Add 73 g (of 0.62 mol) of propargylamine and the mixture is maintained at a tempera is magnesium sulfate. The solvent is removed in vacuo and the residue purified using the rapid chromatography, obtaining N-[2-(3,4-biprop-2-injectively)ethyl]formamide.

1H-NMR (300 MHz, CDCl3): of 2.54 (m, 2H, CLO), 2,82 (t, 2H, CH2CH2), of 3.57 (t, 2H, CH2CH2), 4,78 (m, 4H, CH2SS), for 6.81 (d, 1H, CH arene.), make 6.90 (s, 1H, CH arene.), ? 7.04 baby mortality (d, 1H, CH, arene.), 8,19 (s, 1H, CHO).

Example E12: 2-(4-Chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-prop-2-iniatiated

a) 5-(4-Chlorophenyl)-2,2-dimethyl-5-prop-2-inyl-(1,3)-dioxolane-4-one

3,3 ml utility (a 1.6 molar solution in hexane) is added under stirring in nitrogen atmosphere at-S to the solution containing 0.8 ml of Diisopropylamine in 20 ml of tetrahydrofuran. After stirring for 30 min at this temperature, add 1.13 g of 5-(4-chlorophenyl)-2,2-dimethyl-(1,3)-dioxolane-4-it is in 5 ml of tetrahydrofuran and continue stirring for 1.5 hours then the reaction mixture is treated with a solution containing 0,57 ml propylbromide in 3 ml of tetrahydrofuran. The stirring at approximately 60C continue throughout the night. Then the reaction stopped by adding 1 N. Hcl (pH 6) and a mixture of ice/water, the mixture extracted with diethyl ether. The extracts are dried over sodium sulfate is directly used for the next stage.

b) 2-(4-Chlorophenyl)-2-hydroxyben-4-INOVA acid

The solution containing 530 mg of 5-(4-chlorophenyl)-2,2-dimethyl-5-prop-2-inyl-1-(1,3)-dioxolane-4-it in 10 ml of tetrahydrofuran and 5 ml of methanol, treated with 2 ml of 1 N. NaOH and incubated at 60C for 1 h then the solution is cooled, diluted with water and washed with simple ether. Then an aqueous solution acidified with 1 N. Hcl and extracted with ethyl acetate. The extracts are dried over sodium sulfate and evaporated, obtaining 2-(4-chlorophenyl)-2-hydroxyben-4-inoubou acid in the form of a thick brownish oil, which is used in the next stage.

C) a Suspension containing 1.2 g of the hydrochloride of 2-(3-methoxy-4-prop-2-injectively)ethylamine in 50 ml of dichloromethane, treated 1,53 ml of N-ethyldiethanolamine. To the resulting solution added dropwise to 50 mg of 4-dimethylaminopyridine and 1.2 g of 2-(4-chlorophenyl-2-hydroxyben-4-inophloia (freshly prepared from the acid obtained above and oxalicacid in dichloromethane) in 15 ml dichloromethane. The reaction mixture was stirred over night at 20 ° C and then the reaction stopped, merging into a mixture of ice/water. The reaction mixture is extracted with dichloromethane, the extracts dried over sodium sulfate, filtered and evaporated. After GHUR-GC iphenyl)ethyl]-2-prop-2-iniatiated in the form of a viscous oil.

1H-NMR (CDCl3; frequent./million): of 7.48 (d, 2H); 7,30 (d, 2H); 6,99 to 6.75 (m, 1H, + NH); 6,75-6,56 (m, 2H); 4.72 in (m, 2H); 3,83 (s, 1H); of 3.80 (s, 3H); of 3.48 (m, 2H); 3,05 (AB-q, 2H); to 2.75 (t, 2H); 2,52 (m, 1H); is 2.05 (m, 2H).

This product is 2-(4-chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-prop-2-iniatiated is obtained by keeping 5-(4-chlorophenyl)-2,2-dimethyl-5-prop-2-inyl-(1,3)-dioxolane-4-it with 1.2 EQ. hydrochloride of 2-(3-methoxy-4-but-2-injectively)ethylamine and 1,2 EQ. DBU (1,8-diazabicyclo(5.4.0)undec-7-ene) at 150C.

Example E13: 2-(4-Chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]propionamide

a) Ethyl ester of 2-(4-chlorophenyl)-2-hydroxypropionic acid

To a solution containing 11.5 g atilirovanie in 20 ml of diethyl ether, with stirring, is added slowly with cooling (0C) freshly prepared Grignard solution (obtained from 23,9 g of 4-chlorodibenzo and 3 g of magnesium turnings). To prevent the formation of a viscous suspension is added a small amount of tetrahydrofuran. After stirring for 2 h at room temperature the reaction is stopped by dumping the solution into a mixture of ice and 2 N. sulfuric acid. After extraction with diethyl ether, followed by washing with brine, drying over sodium sulfate arvanil)-2-hydroxypropionic acid in the form of a yellowish oil.

1H-NMR (CDCl3; frequent./million): 7,52 (2, 2H); 7,31 (d, 2H); 4,22 (q); 3,82 (s, 1H); or 1.77 (s, 3H);of 1.29 (t,3H).

b) 2-(4-Chlorophenyl)-2-hydroxypropionic acid

The solution containing 5,72 g of ethyl ester of 2-(4-chlorophenyl)-2-hydroxypropionic acid in 170 ml of tetrahydrofuran, is subjected to hydrolysis at 0C with a solution containing 30,5 ml of 1 n lithium hydroxide in 19 ml of water. After completion of the reaction, the reaction mixture was diluted with water, washed with diethyl ether, acidified with 1 N. Hcl and extracted with ethyl acetate. The extracts are washed with brine, dried over sodium sulfate and evaporated, obtaining 2-(4-chlorophenyl)-2-hydroxypropionic acid.

1H-NMR (CDCl3; frequent./million): to 7.61 (2H, d); to 7.32 (2H. d); 4,0-6,5 (broad OH); 10,7 (broad, COOH).

To the solution containing 906 mg of the hydrochloride of 2-(3-methoxy-4-but-2-injectively)ethylamine and 2.75 ml of N-ethyldiethanolamine, with stirring consistently add 752 mg of 2-(4-chlorophenyl)-2-hydroxypropionic acid and 1,875 g of hexaflurophosphate benzotriazol-1-yloxytris(dimethylamino)phosphonium. The resulting clear solution is stirred overnight and extracted with ethyl acetate. The extracts are washed several times with water, dried over sodium sulfate, filtered and UPA-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]propionamide.

1H-NMR (CDCl3; frequent./million): 7,42 (d, 2H); 7,28 (d, 2H); 6.90 to (d, 1H); 6,66 (s, 1H); 6,55 (dd, 1H), 6,47 (m, broad, 1H); 4,71 (d, 2H); 3,81 (s, 3H); of 3.48 (q, 2H); 3.24 in (s, 1H); of 2.72 (t, 2H); 2,52 (m, 1H).

Example E14: 2-(3',4'-Chlorobiphenyl-4-yl)-2-Okrokana acid

A mixture containing 2.2 g of 4-bromophenylacetate acid, 3,4-dichlorophenylamino acid and 440 mg of 5% palladium on coal 2.5 ml of 2-propanol and 30 ml of water, stirred for overnight at 65S. Then the reaction mixture is allowed to cool to 40C and treated with 30 ml of a mixture containing 2-propanol, water and 2 N. NaOH (70:15:1), filtered through Hyflo and washed 4 times with 70 ml of the above mixture. The filtrate is acidified with 2 N. sulfuric acid, distilled 2-propanol and the remaining mixture is allowed to settle at 0C. After filtering, gain 2-(3',4'-chlorobiphenyl-4-yl)-2-octoxynol acid in the form of solids, tPL168-169,5 C.

Working analogously to the processes described above in the examples, get the compounds listed in tables 1-48. Ph denotes phenyl.

Table 1: Compounds represented by formula I. 1

where the combination of the groups R5, R6, R7, R8and R10in each case corresponds to the combination shown in one of the rows of table A.

Table 2: Compounds present is each variant corresponds to a row of table A.

Table 3: Compounds represented by formula I. 3

where the combination of the groups R5, R6, R7, R8and R10in each case corresponds to a row of table A.

Table 4: Compounds represented by formula I. 4

where the combination of the groups R5, R6, R7, R8and R10in each case corresponds to a row of table A.

Table 5: Compounds represented by formula I. 5

where the combination of the groups R5, R6, R7, R8and R10in each case corresponds to a row of table A.

Table 6: Compounds represented by formula I. 6

where the combination of the groups R5, R6, R7, R8and R10in each case corresponds to a row of table A.

Table 7: Compounds represented by formula I. 7

where the combination of the groups R5, R6, R7, R8and R10in each case corresponds to a row of table A.

Table 8: Compounds represented by the formula 1.8

where the combination of the groups R5R6, R7, r8and R10in each case corresponds to one of very near to the5R6, R7, R8and R10in each case corresponds to a row of table B.

Table 10: Compounds represented by formula I. 10

where the combination of the groups R5R6, R7, R8and R10in each case corresponds to a row of table B.

Table 11: Compounds represented by formula I. 11

where the combination of the groups R5R6, R7, R8and R10in each case corresponds to a row of table B.

Table 12: Compounds represented by formula I. 12

where the combination of the groups R5R6, R7, R8and R10in each case corresponds to a row of table B.

Table 13: Compounds represented by formula I. 13

where the combination of the groups R5R6, R7, R8and R10in each case corresponds to a row of table B.

Table 14: Compounds represented by formula I. 14

where the combination of the groups R5R6, R7, R8and R10in each case corresponds to a row of table B.

Table 15: Compounds represented by formula I. 15

g is one of the table rows Century

Table 16: Compounds represented by formula I. 16

where the combination of the groups R5R6, R7, R8, R10and R12in each case corresponds to a row of table C.

Table 17: Compounds represented by formula I. 17

where the combination of the groups R5R6, R7, R8, R10and R12corresponds in each case to one of rows of the table Century.

Table 18: Compounds represented by formula I. 18

where the combination of the groups R5R6, R7, R8, R10and R12corresponds in each case to one of rows of the table Century.

Table 19: Compounds represented by formula I. 19

where the combination of the groups R5R6, R7, R8, R10and R12corresponds in each case to one of rows of the table Century.

Table 20: Compounds represented by formula I. 20

where the combination of the groups R5R6, R7, R8, R10and R12corresponds in each case to one of rows of the table Century.

Table 21: Compounds represented by formula I. 21

where the combination of the groups R5R6, R7, R8, Rdostavlennya formula I. 22

where the combination of the groups R5R6, R7, R8, R13, R14and R15corresponds in each case to one of rows of the table,

Table 23: Compounds represented by formula I. 23

where the combination of the groups R5R6, R7, R8, R13, R14and R15corresponds in each case to one of rows of the table,

Table 24: Compounds represented by formula I. 24

where the combination of the groups R5R6, R7, R8, R13, R14and R15corresponds in each case to one of rows of the table,

Table 25: Compounds represented by formula I. 25

where the combination of the groups R5R6, R7, R8, R13, R14and R15corresponds in each case to one of rows of the table,

Table 26: Compounds represented by formula I. 26

where the combination of the groups R5R6, R7, R8, R13, R14and R15corresponds in each case to one of rows of the table,

Table 27: Compounds represented by formula I. 27

where the combination of the groups R5R6, R7, R8, R13, R14 is raised by the formula I. 28

where the combination of the groups R5R6, R7, R8, R13, R14and R15corresponds in each case to one of rows of the table,

Table 29: Compounds represented by formula I. 29

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 30: Compounds represented by formula I. 30

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 31: Compounds represented by formula I. 31

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 32: Compounds represented by formula I. 32

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 33: Compounds represented by formula I. 33

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 34: Compounds represented by formula I. 34

where the qi that is

Table 35: Compounds represented by formula I. 35

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 36: Compounds represented by formula I. 36

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 37: Compounds represented by formula I. 37

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 38: Compounds represented by formula I. 38

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 39: Compounds represented by formula I. 39

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 40: Compounds represented by formula I. 40

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 41: Connections, predstave in each case to one of rows of the table that is

Table 42: Compounds represented by formula I. 42

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 43: Compounds represented by formula I. 43

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 44: Compounds represented by formula I. 44

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 45: Compounds represented by formula I. 45

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 46: Compounds represented by formula I. 46

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 47: Compounds represented by formula I. 47

where the combination of the groups R1, R2, R3and R4corresponds in each case to one of rows of the table that is

Table 48: Connections, predstave in each case to one of rows of the table that is

The composition can be prepared analogously to the method described, for example, in WO 95/30651.

Biological examples

D-1: Activity against Plasmopara viticola on cultural grapes

a) Residual protective action

The shank of cultural grapes at the stage of 4-5 leaves sprayed with the mixture for spraying (0.02% of active substance) prepared from the composition of the tested compounds in the form of a wettable powder. After 24 hours the treated plants are infected by a suspension of sporangia of the fungus. Defeat the fungus is evaluated after incubation for 6 days at 95-100% relative humidity and at 20 ° C.

b) Residual therapeutic effect

The shank of cultural grapes at the stage of 4-5 leaves infected by a suspension of sporangia of the fungus. After incubation for 24 h in a special chamber at a relative humidity of 95-100% at 20 ° C and infected plants are dried and sprayed with a mixture for spraying (0.02% of active substance) prepared from the composition of the tested compounds in the form of wetting of the powder. After drying obtained by spray coating the treated plants are placed again in the moistening chamber. Defeat the fungus assessed 6 days after infection.

D-2: Activity against Phytophthora on tomato plants

a) Residual protective action

After culturing for 3 weeks, tomato plants are sprayed with the mixture for spraying (0.02% of active substance) prepared from the composition of the tested compounds in the form of a wettable powder. After 48 hours the treated plants are infected by a suspension of sporangia of the fungus. Defeat the fungus evaluated after incubation of the infected plants for 5 days at 90-100% relative humidity and at 20 ° C.

b) System action

After culturing for 3 weeks, tomato plants watered mixture for spraying (0.02% of active substance relative to the volume of soil) prepared from the composition of the tested compounds in the form of a wettable powder. Take precautions to ensure that the mixture for spraying did not get on above-ground parts of plants. After 96 h, the treated plants are infected by a suspension of sporangia of the fungus. The defeat of the areas rich in mushrooms is.

The compounds listed in tables 1-47, have a long action in respect of the destruction of the fungus. This experience of connection E1.01, E1.02, E1.05, E1.06, E1.08, E1.13, E1.21, E1.30, E1.40, E1.42, E1.46, E1.48, E1.49, E1.50, E1.53, E1.55, E1.56, E1.57, Ea1.01, Ea1.02, E2.01, E2.02, E2.06, E2.07, E2.08, E2.14, E2.19, E2.26, E3.01, E3.02, E3.03, E4.01 and 1.86 completely inhibit the defeat of the mushroom.

D-3: Activity against Phytophthora on potato plants

a) Residual protective action

2-3-week-old potato plants (cultivar Bintje) sprinkle the mixture for spraying (0.02% of active substance) prepared from the composition of the tested compounds in the form of a wettable powder. After 48 hours the treated plants are infected by a suspension of sporangia of the fungus. Defeat the fungus evaluated after incubation of the infected plants for 4 days at 90-100% relative humidity and at 20 ° C.

b) System action

2-3-week-old potato plants (cultivar Bintje) pour mixture for spraying (0.02% of active substance relative to the volume of soil) prepared from the composition of the tested compounds in the form of a wettable powder. Take precautions to ensure that the mixture for spraying did not get on above-ground parts of plants. After 48 h Agen plants for 4 days at 90-100% relative humidity and at a temperature of 20C. The compounds listed in tables 1-47 have efficacy against lesions of the mushroom.

This experience of connection E1.01, E1.02, E1.06, E1.08, E1.13, E1.30, E1.40, E1.41, E1.42, E1.49, E1.53, E1.55, E1.56, E2.06, E2.07, E2.19, E3.01 and E3.02 completely inhibit the defeat of the mushroom.

1. Derived simple propargilovyh ether of General formula I

including their optical isomers and mixtures of such isomers,

where r1denotes hydrogen, C1-C6alkyl WITH3-C6cycloalkyl or aryl, optionally substituted by 1-3 halogen atoms,

R2and R3each independently of one another denote hydrogen or C1-C6alkyl,

R4stands WITH1-C6alkyl or C3-C6quinil,

R5, R6, R7and r8each UB>10denotes aryl, optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl,1-C4haloalkoxy,1-C4alkoxyl1-C4alkyl, C1-C6alkylthio,3-C6alkyloxy, nitro and C1-C6alkoxycarbonyl, or optionally substituted heteroaryl represents an aromatic ring system containing as the heteroatom is at least one oxygen atom or sulfur

r11denotes hydrogen, C1-C6alkyl or C3-C6quinil,

R12denotes hydrogen or C1-C6alkyl,

Z represents hydrogen ,-CO-R16or-CO-COOR16and

R16stands WITH1-C6alkyl, -CH2-CO - C1-C6alkyl or phenyl.

2. Connection on p. 1, where R11denotes hydrogen or C1-C6alkyl, Z represents hydrogen or-CO-R16, R16denotes hydrogen or C1-C6alkyl.

3. Connection under item 1 or 2, where R1denotes hydrogen, C1-C6alkyl or phenyl, optionally substituted by 1-3 halogen atoms, R<6alkyl, R10denotes phenyl, optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl,2-C4alkyloxy and nitro, or furyl or thienyl, optionally substituted C1-C4the alkyl, Z represents hydrogen or-CO-R16, R16stands WITH1-C6alkyl.

4. Connection under item 1 or 2, where R1denotes hydrogen, C1-C6alkyl or phenyl, optionally substituted with halogen, R2, R3, R5, R6, R7and R8denote hydrogen, R4stands WITH1-C6alkyl, R10denotes phenyl, naphthyl, 1,3-biphenyl or 1,4-biphenyl, each optionally substituted by 1-3 substituents selected from the group comprising FROM1-C4alkyl, C1-C4haloalkyl,1-C4alkoxy, C1-C4haloalkoxy,1-C4alkylthio, halogen, nitro and C1-C6alkoxycarbonyl, R11denotes hydrogen or C3-C4quinil, Z denotes hydrogen or-CO-R16, R16stands WITH1-C6alkyl.

5. The compound of formula I on p. 1, selected from the group including

2-(4-forfinal)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-bromophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-methoxyphenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-were)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(2-naphthyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]-2-oxoacetate,

2-(4-chlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(4-bromophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(4-were)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(3,4-acid)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-oxoacetate,

2-(1-methylethanolamine)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-3-methylbutyrate,

2-(1,1-dimethylethylenediamine)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-3-methylbutyrate,

2-(1,1-dimethylethylenediamine)-N the C-4-(4-forgeryproof-2-ynyloxy)phenyl]ethyl}-3-methylbutyrate,

2-(1,1-dimethylethylenediamine)-N-{2-[3-methoxy-4-(4-chlorpheniram-2-ynyloxy)phenyl]ethyl}-3-methylbutyrate,

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide,

2-(4-chlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide,

2-(4-were)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide,

2-(4-bromophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide.

6. The compound of formula I on p. 1, selected from the group including

2-(4-chlorophenyl)-2-hydroxy-N-[(R)2-(3-methoxy-4-prop-2-injectively)propyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-N-[(S) - 2-(3-methoxy-4-prop-2-injectively)propyl]acetamide", she

2-(4-chloro-2-nitrophenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-ethylphenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-triptoreline)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-were)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]acetamide", she

2-(4-bromophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-(4-bromophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-(4-were)-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-(3,4-dichlorophenyl)-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-naphthyl-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-(4-triptoreline)-2-hydroxy-N-[2-(3-methoxy-4-Gex-2-injectively)ethyl]acetamide", she

2-(4-biphenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-bromophenyl)-2-methyloxirane-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(4-chlorophenyl)-2-hydroxy-2-(prop-2-inyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]acetamide", she

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-Penta-2-injectively)ethyl]-2-oxoacetate,

2-(4-chlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)ethyl]-2-methoxybenzamide,

2-(4-were)-N-[2-(3-methoxy-4-prop-2-injectively)-ethyl]-2-methoxybenzamide,

2-(3,4-dichlorophenyl)-N-[2-(3-methoxy-4-prop-2-injectively)-ethyl]-2-methoxybenzamide.

 

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< / BR>
where X represents-O-, -NH-, -CH2-, -CH=, -SNON - or-CO-; R1-R4independently from each other denote hydrogen, a hydroxy-group, (lower) alkylsulfonyl or acetaminoph; R5-R8independently from each other denote hydrogen, a hydroxy-group, (lower)alkyl, halogen, (lower)alkoxygroup, trifluoromethyl or cryptometrics; a and b may denote a double bond, provided that when a represents a double bond, b is unable to designate a double bond; n = 0-2; m = 1-3; p = 0 or 1, and their pharmaceutically acceptable additive salts

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