Derivatives of amides of amino acids, method of production, the fungicidal composition for agricultural and horticultural

 

(57) Abstract:

Derived amide amino acids of the formula I,

< / BR>
in which the radicals take the values specified in paragraph 1 of the formula of the invention exhibit broad spectrum antifungal activity, particularly against downy mildew of cucumbers, against downy mildew of grapes and late blight of tomato. 4 C. and 7 C.p. f-crystals, 20 PL.

The technical field to which the invention relates.

The present invention relates to the derivatives of amides of amino acids, as well as fungicide for agriculture and horticulture containing such compounds as active ingredients. The present invention also relates to a method of obtaining derivatives of amides of amino acids.

The premise of the invention

Derivatives of amides of amino acids are disclosed as intermediates for medicines patent applications in Japan, first publication Sho NN 56-8352 and Sho 62-89696. However, these documents do not disclose the usefulness of derivatives of amides of amino acids. Although patent applications in Japan, the primary publication NN Hei - 3-5451, Hei 3-153657, Hei - 4-230652, Hei 4-230653, Hei 4-283554, Hei 4-308507 and Hei 4-338372, revealed that some amides amineko amino acids, of the present invention.

Description of the invention

The inventors have synthesized various derivatives of amides of amino acids and conducted extensive research related to the effect of these compounds on physiological activity of fungi. The result found that compounds corresponding to the present invention exhibit broad spectrum antifungal activity, particularly against downy mildew of cucumbers, downy mildew of grapes and late blight of tomato.

In accordance with a distinctive feature of the present invention features derived amide amino acids represented by the formula (I)

< / BR>
in which R1represents a lower alkyl group (optionally having at least one identical or different substituents selected from the group consisting of a halogen atom, alkoxygroup and ceanography), lower alkenylphenol group, lower alkylamino group, cycloalkyl group (optionally containing at least one identical or different substituents selected from the group consisting of a methyl group and halogen atom), cycloalkylcarbonyl group, cycloalkenyl group, alke is different substituents, selected from the group consisting of methyl group, ceanography and nitro group), phenyl group (optionally having at least one identical or different substituents selected from the group consisting of halogen atoms; lower alkyl groups which may be substituted by identical or different halogen atoms; lower alkoxygroup, which can be substituted by identical or different halogen atoms; ceanography and nitro), or a heterocyclic group;

R2represents ethyl group, n-sawn group, isopropyl group, isobutylene group, sec-boutelou group, tert-boutelou group, alkenylphenol group, cycloalkenyl group, phenyl group (optionally containing at least one Deputy from among halogen atoms);

R3represents a hydrogen atom or a lower alkyl group;

R4represents a hydrogen atom, a lower alkyl group, or cyano;

R5, R6and R7independently represent hydrogen atoms or lower alkyl groups;

R8represents a hydrogen atom, a lower alkyl group, aracelio group, phenyl group, alkoxycarbonyl the ohms sulfur;

Z3represents an oxygen atom, a sulfur atom, a group N-R10(where R10represents a hydrogen atom, methyl group, methylcarbamyl group, phenylcarbonylamino group, methoxycarbonyl group or methoxymethyl group), sulfinyl group, sulfonyloxy group, group COO, group CONR11(where R11represents a hydrogen atom or a lower alkyl group),

Q represents a phenyl group (optionally containing at least one identical or different substituents selected from the group consisting of a halogen atom; a lower alkyl group which may be substituted by at least one of halogen atoms; lower alkoxygroup, which can be substituted by identical or different halogen atoms; ceanography; nitro; lower alkoxycarbonyl group; methylsulfinyl group; methylthiourea, which may be substituted by a halogen atom; dimethylaminopropyl; phenylsulfonyl; acyl group and a phenyl group), alkalinising group, a heterocyclic group (optionally containing a Deputy, selected from the group consisting of halogen atom, alkyl group, triptorelin group and nitrogen is, optionally containing a Deputy selected from the group consisting of a halogen atom and nitro group;

m is an integer from 0 to 2,

n is 0 or 1,

and fungicide for agriculture or horticulture, containing such a derivative as an active ingredient.

The terms used in the present invention, the means listed below. Used herein, the term "alkyl group" means a linear or branched alkyl group containing from 1 to 6 carbon atoms, including, but not limited to these groups, methyl group, ethyl group, n-sawn group, isopropyl group, n-boutelou group, isobutylene group, sec-boutelou group, tert-boutelou group, n-pentelow group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 2,2-dimethylpropylene group, 1,1-dimethylpropyl group, 1-ethylpropyl group, n-hexoloy group or a similar group.

Used herein, the term "halogen atom" means a fluorine atom, chlorine atom, bromine atom or iodine atom.

Used herein, the term "lower Alchemilla group" means a linear or branched alkenylphenol group containing from 2 to 6 atoms manilow group, 1-butenyloxy group, 2-butenyloxy group, 3-butenyloxy group, 1-methyl-1-propenyloxy group, 2-methylpropenyl group, 1-ethylvinyl group or a similar group.

Used the term "lower Alchemilla group" means a linear or branched alkylamino group containing from 2 to 6 carbon atoms and includes, for example, etinilnoy group, propenyloxy group, butenyloxy group, 1-methyl-2-propenyloxy group or similar.

Used herein, the term "cycloalkyl group" means cycloalkyl group containing from 3 to 8 carbon atoms and includes, but is not limited to these groups, cyclopropyl group, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group, cycloheptyl group or similar.

Used herein, the term "cycloalkenyl group" means cycloalkenyl group containing from 4 to 8 carbon atoms and includes, for example, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group or a similar group.

Used herein, the term "kalkilya group" means aracelio group containing 7 to 8 carbon atoms and includes, but is not ogranicavajuci the term "acceleratedly group" means alkalinising group, containing from 2 to 6 carbon atoms and includes, for example, oxiranyl group, oxetanyl group, tetrahydrofuranyl group, tetrahydropyranyl group or a similar group.

Preferred compounds of the present invention are compounds represented by the formula I, in which R1is a linear or branched alkyl group, soteriades from 2 to 6 carbon atoms; linear or branched alkenylphenol group containing 3 carbon atoms; cycloalkyl group containing 5 to 6 carbon atoms, or phenyl group, optionally containing a Deputy; R2represents ethyl group, n-sawn group, isopropyl group, or second-boutelou group; R3represents a hydrogen atom or methyl group; R4represents a hydrogen atom or methyl group; R5represents a hydrogen atom or methyl group; R6represents a hydrogen atom or a methyl group; Q represents a phenyl group, optionally containing a Deputy; m is an integer of 0 or 1; n is 0; Z1, Z2or Z3are oxygen atoms or sulfur atoms; and the amino acid to avsette in the form of stereoisomers, due to the presence of two or more chiral centers. The present invention relates to all such stereoisomers, including the diastereomers, enantiomers and mixtures thereof, which can be separated by appropriate means.

Forth in tables 1 through 12 provides a list of compounds of formula I in accordance with the invention. However, it should be understood that the invention is not limited to these compounds. Rooms compounds, which are given in tables 1 through 12 will be referenced in the subsequent description.

In tables 1 to 12 connections NN 108, 433, 456, 459, 460, 461, 462, 464, 467, 470, 471, 472 and 475 are particles of amino acids from D,L-configuration; the connection 109 has an amino acid residue with a D-configuration; connection NN 233, 234, 235, 236, 237, 238, 425, 426, 427 have the remnants of (2S)-butyric acid; other, not listed above compounds are amino acid residues L-configuration. Connection NN 33, 345 and 346; connection NN 107, 116 and 117; connection NN 135, 395 and 396; connection NN 228, 414, and 415; connection NN 452, 453 and 454 are mixtures of diastereoisomers and also are separate diastereomers. In addition, the compounds NN 26 and 27, the connection NN 45, 356; connection NN 335 and 336; connection NN 397 and 401 and the connection NN 409 and 410 represent the 8 is a mixture of four isomers and connection 433 N is a mixture of two isomers. Connection NN 483 - 501, 504, 505, 510 - 518, 521 and 522 represent L-Val-DL-Ala; connection NN 502, 503, 508, 509, 519 and 525 are L-Val-D-Ala; connection 520 N is L-Val-Ala; connection NN 506 and 523 are L-Ile-D-Ala; connection 526 N is L-Val-Gly and compounds 507 NN and 524 are (2S)-Butylin-D-Ala.

The tables in the present description, the expression "C3H7-i", "C4H9-t", "C4H9-s" and "C4H9-i" is used to denote the isopropyl group, tert-boutelou group, sec-boutelou group and isobutylene group, respectively.

Relevant to the present invention, compounds represented by formula I, can be obtained, for example, in the following ways:

The method of obtaining A

(Reaction scheme 1)

< / BR>
Here R1, R2, R3, R4, R5, R6, R7, R8, Z1, Z2, Z3, Q, m and n have the foregoing significance.

Corresponding to the invention of compounds represented by formula I, can be obtained by the reaction of amino acid derivatives, represented by formula IX, or derivatives of amino acids, in which the activated carboxyl group with an amine represented by f and as the amino acid derivative with an activated carboxyl group, represented by formula IX may be, for example, galodamadruga acids, such as acid chlorides, and anhydrides of the acids formed by two molecules of amino acid derivatives, represented by formula IX, mixed anhydrides formed derivatives of amino acids of formula IX and the other acid or O-alkalicarbonate acid, and activated esters such as p-nitrophenyloctyl ether, 2-tetrahydropyranyloxy ether, 2-pyridyloxy ether, etc., Such derivatives of amino acids with activated carboxyl groups can be obtained in the usual way (see, for example, Methods der Organischen Chemie, Vol. 15, N 2, from p. 2; Georg Thieme Verlag Stuttgart: 1974; Chemische Berichte, Vol. 38, p. 605 (1905); Journal of the American Chemical Society, Vol. 74, p. 676 (1952); and Journal of the American Chem. Soc., Vol 86, p. 1839 (1964)).

In addition, the above reaction can be carried out using a condensing agent such as N,N'-dicyclohexylcarbodiimide, carbonyldiimidazole, 2-chloro-1,3-dimethylimidazolidine or similar.

The above reaction can be carried out in a standard solvent, this solvent may be any solvent which does not interfere with the reaction, for example a hydrocarbon, such as pentane, hexane, heptane, cyclohexane, petroleum ether, ligroin, arakhleisky carbon, chlorobenzene, dichlorobenzene and so on; a simple ether, such as diethyl ether, diisopropyl ether, dimethyl ether of ethylene glycol, tetrahydrofuran, dioxane and so forth; ketone such as acetone, methyl ethyl ketone, methylisobutylketone, methyl isobutyl ketone and so on; esters such as methyl acetate, ethyl acetate and so on; a nitrile such as acetonitrile, propionitrile, benzonitrile and etc.; aprotic polar solvent such as dimethylsulfoxide, dimethylformamide, sulfolane and so on; and a mixed solvent, a combination of solvents from the number mentioned above.

In reactions of this type can be used for the basis of any type. We can mention, for example, hydroxides of alkali metals such as sodium hydroxide, potassium hydroxide, etc.; hydroxides of alkaline earth metals such as calcium hydroxide, etc.; carbonates of alkali metals such as sodium carbonate, potassium carbonate, etc.; bicarbonates of alkali metals such as sodium bicarbonate, potassium bicarbonate, etc; organic bases such as triethylamine, trimethylamine, dimethylaniline, pyridine, N-methylmorpholine, N-methylpiperidine, 1,5-diazabicyclo[4.3.0] non-5-ene (DBN), 1,8-diazabicyclo[5.4.0] undec-7-ene (DBV), etc.; and preferred is the RA can be mentioned 4-dimethylaminopyridine, 1-hydroxybenzotriazole, dimethylformamide, etc., This reaction can be carried out at temperatures from -75oC to 100oC, preferably from -60oC to 40oC. the reaction Time is preferably from 1 to 20 hours.

In addition, compounds represented by formula IX, as the initial substance can be synthesized, in General, standard methods (see, for example, Methods der Organischen Chemie vol. 15, N 2, p 2; Georg Thieme Verlag Stuttgart: 1974; Chemistry of the Amino Acids, vol. 2 p. 891; John Wiley and Sons., N. Y. (1964); and Juornal of the American Chemical Society, vol. 79, p. 4686 (1957)). Also can be considered different methods of producing compounds X, such as the methods proposed in the patent application of Japan, the primary publication N Sho 63-146876, Tetrahedron Letters, p. 21, 1973, and in the patent application of Japan, the primary publication N Hei5-271206.

The method of obtaining B

(Reaction scheme 2)

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Here R1, R2, R3, R4, R5, R6, R7, R8, Z1, Z2, Z3, Q, m and n have the meanings specified above and Y represents a halogen atom, 4,6-dimethylpyrimidine, the group R1OC(O)O - or a group-ON=C(CN)Ph (where Ph means phenyl group).

Compounds of the present invention represented by formula I, can be ), such as hydrochloride, etc., or with a salt of the amine and organic acid as toilet, etc. in the presence of a base, if required.

The reaction can be carried out in a conventional solvent; the solvent may be any solvent which does not disturb the reaction, for example a hydrocarbon, so as pentane, hexane, heptane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene and so on; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride, chlorobenzene, dichlorobenzene and so on; a simple ether, such as diethyl ether, diisopropyl ether, dimethyl ether of ethylene glycol, tetrahydrofuran, dioxane and so forth; ketone such as acetone, methyl ethyl ketone, methylisobutylketone, methyl isobutyl ketone and so on; esters such as methyl acetate, ethyl acetate and so on; a nitrile such as acetonitrile, propionitrile, benzonitrile and etc.; aprotic polar solvent such as dimethylsulfoxide, dimethylformamide, sulfolane etc., water and a mixed solvent, a combination of solvents selected from among those mentioned above.

For reactions of this type can be used osnovaniaya etc.; hydroxides of alkaline earth metals such as calcium hydroxide, etc.; carbonates of alkali metals such as sodium carbonate, potassium carbonate, etc.; bicarbonates of alkali metals such as sodium bicarbonate, potassium bicarbonate, etc; organic bases such as triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, pyridine, N-methylpiperidine, 1,5-diazabicyclo 4,3,0 non-5-ene (DBN) and 1,8-diazabicyclo 5,4,0 undec-7-ene (DBU), etc.; and preferred are tertiary amines, such as triethylamine, pyridine, N-methylpiperidine, etc. Mentioned reaction is carried out at a temperature of from -20oC to 100oC, preferably from 0oC to 40oC. the reaction Time is preferably from 30 minutes to 20 hours.

The compounds of formula XII as the original substances are novel compounds and can be obtained, for example, by treatment of the carbamates of compounds I, synthesized according to the method of obtaining A conventional method of removing the protective group for protecting the amino group in the amino acid, such as catalytic reduction or by treatment with acids such as liquid hydrofluoric acid, sulfonic acid, hydrochloric acid, Brestovitsa derivatives of amides of amino acids, which are novel intermediate compounds for the compounds of the present invention, represented by formulas X and XII.

Reference example 1

Synthesis of 2-(4-cianfrocca)-1-methylethylamine (intermediate compound No. 1)

To a solution containing 66.5 g of 4-cyanoprokaryota dissolved in 1500 ml of methanol, add 293 g of ammonium acetate and 16.7 g of cyanoborohydride sodium and the resulting mixture is stirred for 30 hours at room temperature. The reaction mixture was then concentrated under reduced pressure and acidified with concentrated hydrochloric acid. Then it added 500 ml of diethyl ether and 300 ml of water. After this, the resulting aqueous layer was alkalinized with 5% aqueous sodium hydroxide solution, the solution is extracted with 1000 ml of diethyl ether and the ether layer washed with water. The organic layer is then dried over anhydrous sodium sulfate and then diethyl ether is removed under reduced pressure. The resulting residue is distilled under reduced pressure and gain of 13.0 g of the desired product (19%). Boiling point 132oC when 0,26 mm RT.article.

Reference example 2

Synthesis of 2-(4-chloro-2-methylphenoxy)-1-methylethylamine (intermediate compound N 2)

the ammonium and 9.8 g of cyanoborohydride sodium and the resulting mixture is stirred for 20 hours at room temperature. Then the reaction mixture was concentrated under reduced pressure and to the residue add 180 ml of concentrated hydrochloric acid and 100 ml of water. The whole mixture is stirred for 1 hour and then extracted with 300 ml of diethyl ether. The aqueous layer was alkalinized using 5% aqueous solution of sodium hydroxide, and then extracted with 500 ml of ethyl acetate. The organic layer is washed with water, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. From the obtained oily product are removed fraction with a low boiling point and receive a 25 g (yield 81%) of the desired product. The refractive index 1,5360.

Reference example 3

Synthesis of 2-(4-chlorophenoxy)-1-methylpropylamine (intermediate compound No. 3)

To a solution containing 21 g of 3-(4-chlorophenoxy)-2-butanone dissolved in 500 ml of methanol, added 82 g of ammonium acetate and 6.7 g of cyanoborohydride sodium and the reaction mixture is stirred for 20 hours at room temperature. The reaction mixture was then concentrated under reduced pressure and to the residue add 180 ml of concentrated hydrochloric acid and 100 ml of water. The entire mixture is extracted with 300 ml of diethyl ether. The obtained aqueous layer was alkalinized using 5% aqueous solution of denim magnesium sulfate and then concentrated under reduced pressure. From the obtained oily product are removed fraction with a low boiling point and obtain 18 g (yield 86%) of the desired product. The refractive index 1,5360.

Reference example 4

Synthesis of 1-methyl-2-(2-methylphenoxy) ethylamine (intermediate compound No. 4)

A solution containing 36 g 0-methyl ether 2-(2-methylphenoxy)acetonitrile dissolved in 150 ml of dimethoxyethane, is added dropwise to a suspension containing 13 g of sodium borohydride in 500 ml of dimethoxyethane at room temperature. The mixture is then stirred for 15 minutes at room temperature and to the mixture at room temperature, is added dropwise a solution containing 66 g of the complex of trevormoran with diethyl ether, dissolved in 100 ml of dimethoxyethane. The reaction mixture is stirred for 30 minutes at room temperature and then refluxed for 3 hours. The resulting mixture is left to cool naturally to room temperature and then acidified using 10% hydrochloric acid. Dimethoxyethane layer concentrated and combined with the aqueous layer. The mixture is alkalinized using sodium carbonate, and then extracted with dichloromethane, then washed with water. Organizationat under reduced pressure and obtain 6.4 g (yield 21%) of the desired product. Boiling point 65oC at 0.08 mm RT.article.

Reference example 5

Synthesis of 2-(4-cianfrocca)-1-methylethylamine (intermediate compound No. 1)

Under stirring at 0oC to the mixture to 29.8 g of 60% sodium hydride and 300 ml of N, N-dimethylformamide is added dropwise to 50.0 g of 2-amino-1-propanol. After stirring the reaction mixture for 30 minutes at 0oC thereto is added dropwise a solution containing 121,2 g of 4-bromobenzonitrile dissolved in N, N-dimethylformamide. The resulting mixture is stirred for 20 hours at room temperature. After completion of the reaction the resulting mixture was poured into water and extracted with ethyl acetate. The organic layer is washed with water and then dried over anhydrous magnesium sulfate. The ethyl acetate is removed under reduced pressure. The residue is distilled under reduced pressure and get to 48.0 g of the desired product (yield 41%). Boiling point 132oC when 0,26 mm RT.article.

Reference example 6

Synthesis of (-)-2-(4-cianfrocca)-1-methylethylamine (intermediate compound No. 5)

Under stirring, at a temperature of from 5oC to 10oC, to a mixture of 14.0 g of 60% sodium hydride and 200 ml of N,N-dimethylformamide is added dropwise to 25.0 g of R (-)-2-amino-1-propanol. Pic is of benzonitrile, dissolved in N,N-dimethylformamide. The reaction mixture is stirred for 20 hours at room temperature. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer is washed with water and then dried over anhydrous magnesium sulfate. The ethyl acetate is removed under reduced pressure. The residue is distilled under reduced pressure and get 33,0 g of the desired product (yield 56%). Boiling point 60 - 66oC at 0.08 mm RT.art., []2D0- 15,7o(C 1,0 CH3OH).

Reference example 7

Synthesis of 1-methyl-2-(2-pyrimidinone) ethylamine (intermediate compound No. 6)

Under stirring, at room temperature, to a mixture of 1.3 g of 60% sodium hydride and 30 ml of N,N-dimethylformamide is added dropwise 2.0 g of 2-amino-1-propanol. After stirring the reaction mixture for 30 minutes and thereto is added dropwise a solution containing 3.7 g of 2-chloropyrimidine dissolved in N,N-dimethylformamide. The reaction mixture is stirred for 2 hours at 100oC. After completion of the reaction, the reaction mixture is cooled. Solids filtered off. The solvent of the filtrate is removed under reduced pressure. The residue is purified column chromatography on forces is R>
Synthesis of 1-methyl-2-(4-pyridyloxy)ethylamine (intermediate compound No. 7)

With stirring, 5oC - 10oC, to a mixture of 4.0 g of 60% sodium hydride and 50 ml of N,N-dimethylformamide added dropwise 6.2 g of 2-amino-1-propanol. After stirring the reaction mixture for 30 minutes to it in small portions add 12.5 g of the hydrochloride of 4-chloropyridine. The mixture is stirred for 20 hours at room temperature. After completion of the reaction, the solids filtered off. The solvent of the filtrate is removed under reduced pressure. The residue is purified column chromatography on silica gel and obtain 3.8 g of the desired product (30% yield). The refractive index 1,5469.

Specific examples of the intermediate compounds X, obtained according to the methods of reference examples 1 to 8 shown in table. 13.

Reference example 9

Synthesis of hydrochloride of N1[-2-(4-cianfrocca)-1-methylethyl] -L - valinamide (intermediate compound N 23)

In a solution containing 3.7 g of N2-tert-butoxycarbonyl - N1[-2-(4-cianfrocca)-1-methylethyl] -L-valinamide dissolved in 100 ml of methylene chloride for 1 hour at room temperature, introducing gaseous hydrogen chloride. After completion of the reaction methylthio the hold and get 3.1 g of the desired product (yield 100%). So pl. 59-63oC.

Reference example 10

Synthesis of N1[-2-(4-cianfrocca)-1-methylethyl]-L - isolationand (intermediate compound N 24)

In a solution containing 15.0 g of N2-tert-butoxycarbonyl - N1[-2-(4-cianfrocca)-1-methylethyl] -L-isolationand dissolved in 300 ml of methylene chloride for 1 hour at room temperature, introducing gaseous hydrogen chloride. After completion of the reaction, the methylene chloride is removed under reduced pressure and the thus obtained crude crystalline substance. To the crude crystalline substance, add 200 ml of saturated aqueous sodium bicarbonate solution and 200 ml of methylene chloride, the mixture is stirred for 30 minutes and extracted with methylene chloride. The organic layer is washed with water and dried over anhydrous sodium sulfate. The methylene chloride is removed under reduced pressure. The resulting crude product is washed with acetone and obtain 10.0 g of the desired product (yield 90%). So pl. 64-67oC.

Specific examples of the intermediate compounds XII, obtained according to the methods of reference examples 9 and 10, are given in table. 14.

Preferred embodiments of the invention

Methods for obtaining compounds of this is ASS="ptx2">

Example of synthesis 1

Synthesis of N2-tert-butoxycarbonyl-N1-[1-methyl-2- (4-nitrophenoxy)-ethyl]-L-valinamide (compound No. 16)

To a solution containing 1.1 g of N-tert-butoxycarbonyl-L-valine dissolved in 40 ml of methylene chloride, at -20oC add 0.5 g of N-methylpiperidine. After stirring the mixture for 10 minutes at the same temperature there was added 0.7 g of isobutylphthalate already at -40oC. To this mixture at -60oC add 1 g of 1-methyl-2-(4-nitrophenoxy)ethylamine and then the reaction mixture is left to warm up naturally to room temperature while continuing the stirring, and stirred for 15 hours at room temperature. Then to the reaction mixture, water is added. After the dichloromethane layer is successively washed with 5% aqueous sodium bicarbonate solution and water, the organic layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The remainder, which represents a crude crystalline substance, clear column chromatography on silica gel and thus receive the 0.7 g of the desired product as a yellow powder (yield 55%).

Example of synthesis 2

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] - the N1-[2-(4-cianfrocca)-1-methylethyl] -L-valinamide dissolved in 50 ml of methylene chloride at -15oC add 0.6 g N-methylmorpholine and then 0.4 g of isopropylcarbamate. The mixture is left to warm up naturally to room temperature and then stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing dichloromethane layer with water, this organic layer is dried over anhydrous magnesium sulfate, and then the methylene chloride is removed under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the grade of 0.23 g of the desired product as colourless grains (yield 13%).

Example of synthesis 3

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- phenoxycarbonyl-L-valinamide (compound N 107)

To a solution containing 3 g of N-phenoxycarbonyl-L-valine dissolved in 50 ml of methylene chloride, at -20oC add 1.3 g of N-methylmorpholine. After stirring the mixture for 10 minutes at the same temperature, -40oC to the mixture of 2.2 g of 2-(4-cianfrocca)-1-methylethylamine, the reaction mixture while stirring and allowed to warm up naturally to room temperature and for 20 hours paramesh edutella washed with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue which is the crude crystalline substance, clear column chromatography on silica gel and thus receive the 1.1 g of the desired product as a white powder (yield 22%).

Example of synthesis 4

Synthesis of N2-tert-butoxycarbonyl-N1[-2-(4 - cianfrocca)-1-methylethyl]-L-isolationand (compound No. 228)

To a solution containing 3 g of N-tert-butoxycarbonyl-L-isoleucine, dissolved in 60 ml of methylene chloride, at -20oC add 1.3 g of N-methylpiperidine. After stirring the mixture for 10 minutes at the same temperature at -40oC, add 1.8 g of isobutylacetate and stirred the mixture for 1 hour at -20oC. To this mixture at -60oC add 2.3 g of 2-(4-cianfrocca)-1-methylethylamine and then the mixture is left to warm up naturally to room temperature while continuing the stirring and at room temperature the mixture is stirred for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, the organic layer is dried neomaterial on silica gel, thus receiving 0.6 g of the desired product as a white powder (yield 12%).

Example of synthesis of 5

Synthesis of N2-tert-butoxycarbonyl-N1-(2-phenylthiomethyl)-L - valinamide (compound N 551)

To a solution containing 2.1 g of N-tert-butoxycarbonyl-L-valine dissolved in 40 ml of methylene chloride, at -20oC add 1 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added 1.3 g of isobutylacetate and the mixture is stirred for 1 hour at -20oC. To this mixture at -60oC add 1.5 g of 2-phenylethylamine and then the reaction mixture was left to reach naturally to room temperature while continuing the stirring, and stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, the organic layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 0.4 g of the desired product as a yellow-cream grains (yield 12%).

Example of synthesis 6

Synthesis of N2tert is containing 1 g of N-tert-butoxycarbonyl-L - valine, dissolved in 40 ml of methylene chloride, at -20oC add 0.5 g of N-methylpiperidine. After stirring the mixture for 15 minutes at this temperature, there was added 0.7 g of isobutylacetate and the mixture is stirred for 1 hour at -20oC. To this mixture at -60oC add 1 g of 1-methyl-2-(4-nitrophenoxy)Propylamine and then the reaction mixture with stirring, allowed to warm up naturally to room temperature and stirred for 20 hours at room temperature. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water in this layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The remainder, which is an oily substance, and purified column chromatography on silica gel, thus obtaining 1.1 g of the desired product as a viscous yellow liquid (yield 56%).

Example of synthesis of 7

Synthesis of N2-tert-butoxycarbonyl-N1[-2-(3,5 - dimethoxyphenoxy)-1-methylethyl]-L-valinamide (compound No. 22)

To a solution containing 1.0 g of N-tert-butoxycarbonyl-L-valine dissolved in 100 ml of methylene chloride, at -20oC we use the -40oC 0.7 g of isobutylacetate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC add 1 g of 2-(3,5-cianfrocca)-1-methylamine and the reaction mixture was then allowed to warm up naturally to room temperature while continuing the stirring, and the mixture is stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and metalachlor removed under reduced pressure. The remainder, which represents a crude crystalline substance, clear column chromatography on silica gel, thus obtaining 1.3 g of the desired product as a white powder (yield 64%).

Example of synthesis 8

Synthesis of N2-tert-butoxycarbonyl-N1-[1-methyl-2-(2,4,6 - trichlorophenoxy)ethyl]-L-valinamide (compound No. 25)

To a solution containing 3.8 g of N-tert-butoxycarbonyl-L-valine dissolved in 80 ml methylacrylamide, at -20oC add 1.5 g of N-methylpiperidine. After stirring the mixture for 15 minutes at this temperature, there was added 2.4 g of isobutylacetate and CME is noxi)ethylamine and the reaction mixture was then allowed to warm up naturally to room temperature, while continuing the stirring, and stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue is purified column chromatography on silica gel, thus obtaining 4.6 g of the desired product as colorless needle crystals (yield 58%).

Example 9 synthesis

Synthesis of N2-isopropoxycarbonyl-N1-[1-methyl-2- (4-nitrophenoxy)ethyl]-L-valinamide (compound No. 45)

To a solution containing 2.5 g of N-isopropoxycarbonyl-L-valine dissolved in 100 ml of methylene chloride, at -20oC add 1.2 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added 1.7 g of isobutylacetate and the mixture is stirred for 1 hour at -20oC. To this mixture at -60oC add 2.2 g of 2-(4-nitrophenoxy)-1-methylethylamine, the reaction mixture was then allowed to warm with stirring and naturally to room temperature and the mixture is stirred at room temperature for 20 hours. C is a solution of sodium bicarbonate and water in this layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue is purified column chromatography on silica gel, thus obtaining 0.3 g of the desired product as a yellow glassy substance (yield 6%).

1NMR: (CDCl3, ) of 1.16 and 1.33 (6H, m), USD 1.43 - of 1.36 (9H, m), of 2.56 (1H, m) to 4.01 (2H, m), 4,00 - 5,33 (3H, m), 6,17 (1H, d), 6.87 in (2H, d), of 8.06 (2H, d).

Example 10 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- cyclohexyloxycarbonyl-L-valinamide (compound N 97)

To a solution containing 2.0 g of N-cyclohexyloxycarbonyl-L-valine dissolved in 150 ml of methylene chloride, at -20oC add 0.8 g of N-methylpiperidine. After stirring the mixture for 1 minute at this temperature, there was added 1.1 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC add 1.5 g of 2-(4-cianfrocca)-1-methylethylamine and the reaction mixture is left to warm up, continuing the stirring naturally to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and the methylene chloride is Asom 0.5 g of the desired product as a pale brown powder (yield 16%).

Example 11 synthesis

Synthesis of N1-[1-methyl-2-(4-triptoreline)ethyl]-N2- phenoxycarbonyl-L-valinamide (compound N 114)

To a solution containing 4.0 g of N-phenoxycarbonyl-L-valine dissolved in 80 ml of methylene chloride, at -20oC add 1.6 g N-methylpiperidine. After stirring the mixture for 16 minutes at this temperature, there was added 2.2 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC add 3.5 g of 1-methyl-2-(4-triptoreline)ethylamine, the reaction mixture was then allowed to warm up naturally with stirring to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water in this layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 2.8 g of the desired product as white crystals (yield 40%).

Example 12 synthesis

Synthesis of N1-[1-methyl-2-(4-triftormetilfosfinov)ethyl] - N2-phenoxycarbonyl-L-is of milenaria, at -20oC add 1.7 g of N-methylpiperidine. After stirring the mixture for 15 minutes at this temperature, there was added 2.3 g of isobutylacetate and stirred for 1 hour at -20oC.

To this mixture at -60oC add 4.0 g of 1-methyl-2-(4 - triptoreline)ethylamine, then the reaction mixture is left to warm up naturally, while continuing the stirring, to room temperature and stirred the mixture at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water in this layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue is purified column chromatography on silica gel and obtain 3.4 g of the desired product as white crystals (yield 45%).

Example of synthesis 13

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- phenoxycarbonyl-L-valinamide (compound No. 116 and 117)

To a solution containing of 4.2 g of N-phenoxycarbonyl-L-valine dissolved in 100 ml of methylene chloride, at -20oC add 1.8 g N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature and -60oC added 3.1 g of 2-(4-cianfrocca)-1-methylethylamine, the reaction mixture while stirring and allowed to warm up naturally to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing chloride layer with 5% aqueous sodium bicarbonate solution and water in this layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue is purified column chromatography on silica gel, thus obtaining 1.0 g of a white powder. Part of the obtained white powder - 0.6 g - purified using liquid chromatography high pressure (hereinafter referred to as "HPLC") (VMC-063-15, hexane:ethyl acetate = 55:45) to select the two factions. The first fraction with a short retention time is 0.3 g of white powder (yield 7%) with a melting point of from 145 to 147oC, and the second fraction with a long retention time is 0.3 g of white powder (yield 7%) with T. pl. from 166 to 170oC.

Example 14 synthesis

Synthesis of N2-[2-(4-cianfrocca)-1-methylethyl] -N2- (3-methoxyphenethyl)-L-valinamide (compound N 166)

To a solution containing 1.5 g of the hydrochloride of N1-Ethylmorpholine. Then to the mixture at -20oC add 0.9 g of 3-methoxyphenylacetate, the reaction mixture is left to warm up naturally with stirring to room temperature and stirred the mixture at room temperature for 2 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue is purified column chromatography on silica gel, thus obtaining 0.25 g of the desired product as white plate crystals (yield 12%).

Example 15 synthesis

Synthesis of N2-(2-chlorocarbons)-N1-[2-(4 - cianfrocca)-1-methylethyl]-L-valinamide (compound N 184)

To a solution containing 1.1 g of N-(2-chlorocarbons)-L-valine dissolved in 40 ml of methylene chloride, at -20oC add 0.5 g of N-methylpiperidine. After stirring the mixture for 15 minutes at this temperature, to the mixture at -40oC 0.7 g of isobutylacetate and the mixture is stirred for 1 hour at -20oC. To this mixture at -60oC add 0.9 g of 2-(4-cianfrocca)-1-methylethylamine, the reaction mixture was then left under stirring hot e is Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The remainder, which is an oily substance, and purified column chromatography on silica gel, thereby obtaining 1.0 g of the desired product as colourless grains (yield 52%).

Example 16 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- (4-methylbenzyloxycarbonyl)-L-valinamide (compound N 195)

To a solution containing 1.5 g of N-(4-methylbenzyloxycarbonyl)-L-valine dissolved in 100 ml of methylene chloride, at -20oC add 0.6 g N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, to the mixture of 0.8 g of isobutylacetate and the mixture is stirred for 1 hour at -20oC. To this mixture at -60oC add 1.0 g of 2-(4-cianfrocca)-1-methylethylamine, the reaction mixture is left to be heated, with stirring, naturally to room temperature and stirred the mixture at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing denim magnesium sulfate and removing the methylene chloride under reduced pressure. The remainder, which represents a crude crystalline substance, clear column chromatography on silica gel and thus obtain 0.6 g of the desired product in the form of a white powder (yield 28%).

Example 17 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- phenoxythiocarbonyl-L-valinamide (compound N 208)

To a suspension containing 1.1 g of N1-[2-(4-cianfrocca)1-methylethyl]-L-valinamide, suspended in 40 ml of methylene chloride at -15oC add 0.4 g N-methylmorpholine. Then added to the mixture at -15oC 0.7 g of penishealthinformation, the reaction mixture is left to warm up naturally to room temperature while continuing the stirring, and the mixture is stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue is purified column chromatography on silica gel, thus obtaining 1.2 g of the desired product as a yellow sticky substance (yield 75%).

1H NMR: (CDCl3, ) of 1.05 (6H, m) of 1.35 (3H, m), is 2.30 (1H, m) 4,00 (2H, m), of 4.44 (1H, m), of 4.54 (1H, m), 6,16, and 6.25 (1H, d), 7, is ltio)-thiocarbonyl-L-valinamide (compound N 211)

To a suspension containing 1.04 g of N1-[2-(4-cianfrocca)-1-methylethyl]-L-valinamide, suspended in 40 ml of methylene chloride at -15oC add 0.5 g of N-methylmorpholine. Then added to the mixture at -15oC 0.9 g phenylisothiocyanate, the reaction mixture is left to warm up naturally to room temperature while continuing the stirring, and the mixture is stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The residue is purified column chromatography on silicagel, thereby obtaining 1.4 g of the desired product as a yellow sticky substance (yield 66%).

1H NMR: (CDCl3, ) 0,83 (6H, m), 1,32 (3H, m) to 2.13 (1H, m), of 3.96 (2H, m), 4,35 (1H, m), to 4.73 (1H, D. D.), 6,04, 6,13 (1H, d), of 6.96, 6,98 (2H, d), 7,15, 7,22 (1H, d), EUR 7.57 (7H, m).

Example 19 synthesis

Synthesis of N1-(1-methyl-2-phenylthiomethyl)-N2-phenoxycarbonyl- -L-valinamide (compound N 212)

To a suspension containing 3.0 g of the hydrochloride of N1-(1-methyl-2-phenylthiomethyl)-L-valinamide suspended in 80 ml of methylene chloride at -15oC add 1.3 g of N-methylmorpholine the m by under stirring to room temperature and stirred the mixture at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The residue is purified column chromatography on silicagel, thus obtaining 2.3 g of the desired product as white crystals (yield 54%).

Example 20 synthesis

Synthesis of N1-[2-(4-chloroanilino)-1-methylethyl] -isopropoxycarbonyl- -L-valinamide (compound N 221)

To a solution containing 3.8 g of N-isopropoxycarbonyl-L-valine dissolved in 80 ml of methylene chloride, at -20oC added to 1.9 g of N-methylpiperidine. After stirring the mixture for 15 minutes at this temperature, there was added 2.6 g of isobutylacetate, and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC add 3.5 g of 2-(4-chloroanilino)-1-methylethylamine, the mixture is left to warm up naturally with stirring to room temperature and then the mixture is stirred at room temperature for 20 hours. Then the reaction mixture was added water. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over without what graphy on silica gel, thus receiving of 3.3 g of the desired product as white crystals (yield 47%).

Example 21 synthesis

Synthesis of 2-tert-butoxycarbonylamino-N-[2-(4-chlorophenoxy)-1 - methylethyl]-(2S)-butyramide (compound 233)

To a solution containing 4.1 g of (2S)-2-tert-butoxycarbonylamino acid, dissolved in 60 ml of methylene chloride, at -20oC add 2.0 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added at -40oC 2.7 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC add 3.7 g of 2-(4-chlorophenoxy)-1-methylethylamine, then the reaction mixture is left to warm up naturally with stirring to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous sodium sulfate and remove the methylene chloride under reduced pressure. The resulting crude crystalline substance purified column chromatography on silica gel and thus receive the 5.6 g of the desired product in amino-N-[2-(4-cianfrocca)-1 - methylethyl] -(2S)-butyramide (compound N 235)

To a solution containing 1.0 g of (2S)-2-tert-butoxycarbonylamino acid dissolved in 40 ml of methylene chloride, at -20oC add 0.5 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added at -20oC 0.7 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC add 0.9 g (2-(4-cianfrocca)-1-methylethylamine, the reaction mixture is left to warm up naturally with stirring to room temperature and stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel, thus obtaining 1.0 g of the desired product in the form of a sticky substance (yield 54%).

1NMR: (CDCl3, ) to 0.94 (3H, t), 1,20 - 1,50 (12H, m), 1.69 in (2H, m), 3,83 - 4,56 (4H, m), and 5.30 (1H, d), 6,60 (1H, m), of 6.90 (2H, d), to 7.50 (2H, d).

Example 23 synthesis

Synthesis of N1-[2-(4-chlorobenzoyloxy)-1-methylethyl] -N2- isopropoxycarbonyl-L-VL of metilenhloride, at -20oC add 0.5 g of N-methylpiperidine. After stirring the mixture for 15 minutes at this temperature, there was added at -40oC 0.7 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC add 1 g of 2-(4-chlorobenzoyloxy)-1-methylethylamine, then the reaction mixture is left under stirring to warm naturally to room temperature and the mixture is stirred at room temperature for 20 hours. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The obtained oily residue is purified column chromatography on silica gel, thus obtaining 0.9 g of the desired product as colorless plate crystals (yield 48%).

Example 24 synthesis

Synthesis of N2-tert-butoxycarbonyl-N1-[1-methyl-2- (4-methylthiophene)ethyl] -L-valinamide (compound N 327)

To a solution containing 7.5 g of N-tert-butoxycarbonyl-L-valine dissolved in 100 ml of methylene chloride, at -20oC added 3.4 g of N-methylpiperidine. After stirring the mixture forC for 1 hour. To this mixture at -60oC added 6.8 g of 1-methyl-2-(4-methylthiophene)ethylamino, then the reaction mixture is left to warm up naturally with stirring to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous sodium sulfate and remove the methylene chloride under reduced pressure. The obtained oily residue is purified column chromatography on silica gel and thus obtain 6.2 g of the desired product as colorless prismatic crystals (yield 46%).

Example 25 synthesis

Synthesis of N2-tert-butoxycarbonyl-N1-[1-methyl-2-(4 - methylsulfinylphenyl)ethyl]-L-valinamide (compound 328 N)

To a solution containing 3.0 g of N2-tert-butoxycarbonyl-N1-[1-methyl-2-(4-methylthiophene) ethyl] -L-valinamide dissolved in 60 ml of methylene chloride, at 0oC add 1.5 g of m-chloroperbenzoic acid. After stirring the mixture for 5 hours at room temperature the reaction mixture is filtered. The filtrate serial what LifeCam sodium and remove the methylene chloride under reduced pressure. The obtained oily residue is purified column chromatography on silica gel and thus receive the 1.7 g of the desired product as colorless crystals (yield 56%).

Example 26 synthesis

Synthesis of N2-tert-butoxycarbonyl-N1-[1-methyl-2- (4-methylsulfinylphenyl)ethyl]-L-valinamide (compound No. 329)

To a solution containing 2.0 g of N2-tert-butoxycarbonyl-N1-[1-methyl-2-(4-methylthiophene) ethyl] -L-valinamide dissolved in 50 ml of methylene chloride, at 0oC add 2.1 g m-chloroperbenzoic acid. After stirring the mixture for 8 hours at the boiling temperature of a refrigerator, the reaction mixture was cooled naturally to room temperature and filtered. The filtrate is successively washed with saturated aqueous potassium carbonate and water, the organic layer is dried over anhydrous sodium sulfate and remove the methylene chloride under reduced pressure. The resulting residue is purified column chromatography on silica gel and receive 1.3 g of the desired product as colorless prismatic crystals (yield 60%).

Example 27 synthesis

Synthesis of N1-[2-(4-chlorophenylsulfonyl)-1-methylethyl]- N2-isopropoxycarbonyl-L-valinamide (link-link is-L-valinamide, dissolved in 50 ml of methylene chloride, at 0oC add 1.3 g of m-chloroperbenzoic acid. After stirring the mixture for 5 hours at room temperature the reaction mixture is filtered. The filtrate is successively washed with saturated aqueous potassium carbonate and water, the organic layer is dried over anhydrous sodium sulfate and remove the methylene chloride under reduced pressure. The resulting residue is purified column chromatography on silica gel and thus receive the 1.8 g of the desired product as colorless prismatic crystals (yield 69%).

Example 28 synthesis

Synthesis of N1-[2-(4-perpenicular)-1-methylethyl]- N2-isopropoxycarbonyl-L-valinamide (compound N 355)

To a solution containing 2.2 g of N1-[2-(4-forfinally)-1 - methylethyl]-N2-isopropoxycarbonyl-L-valinamide dissolved in 50 ml of methylene chloride, at 0oC add 3.4 g m-chloroperbenzoic acid. After stirring the mixture for 8 hours boiling under reflux, the reaction mixture is allowed to cool to room temperature and then filtered. The filtrate is successively washed with saturated aqueous potassium carbonate and water, the organic layer is dried nadorozny chromatography on silica gel and thus receive the 2.0 g of the desired product as white crystals (yield 83%).

Example 29 synthesis

Synthesis of N2-isopropoxycarbonyl-N1-[1-methyl-2- (2-methylphenylthio)ethyl]-L-valinamide (compound N 367)

To a solution containing 3.9 g of N-isopropoxycarbonyl-L-valine dissolved in 80 ml of methylene chloride, at -20oC added to 1.9 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, to the mixture of 2.6 g of isobutylacetate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC add 3.5 g of 1-methyl-2-(2-methylphenylthio)ethylamine, then the reaction mixture is left to be heated, with stirring, naturally to room temperature and stirred the mixture at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous sodium sulfate and remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 3.6 g of the desired product as white crystals (yield 51%).

Example 30 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- (3-tetrahydrofur is noproxy)-1-methylethyl] -L-valinamide, suspended in 100 ml of methylene chloride, at -20oC add 1.0 g of N-methylmorpholine and then 0.7 g of 3-tetrahydrofurfurylamine. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 2 hours. Then to the reaction mixture, water is added. After washing dichloromethane layer with water, this organic layer is dried over anhydrous magnesium sulfate and then removed under reduced pressure. The residue is purified column chromatography on silica gel and thus obtain 1.1 g of the desired product as a white powder (yield 61%).

Example 31 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- (3-methylcyclohexanecarboxylic-L-valinamide (compound 379 N)

To a suspension containing 1.0 g of N1-[2-(4-cianfrocca)-1-methylethyl]-L-valinamide, suspended in 50 ml of methylene chloride at -15oC add 0.4 g N-methylmorpholine and then 0.8 g of 3-tetrahydrofurfurylamine. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer water this organicheskoi column chromatography on silica gel and thus receive the 1.2 g of the desired product as white crystals (yield 80%).

Example 32 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- propylenecarbonate-L-valinamide (compound 381 N)

To a suspension containing 0.5 g of N1-[2-(4-cianfrocca)- 1-methylethyl]-L-valinamide, suspended in 30 ml of methylene chloride at -15oC add 0.2 g N-methylmorpholine and then 0.2 g of propargylamine. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus obtain 0.5 g of the desired product as a white powder (yield 78%).

Example 33 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- (2-methoxy-1-methylethyl)oxycarbonyl-L-valinamide (compound No. 383)

To a suspension containing 1.5 g of N1-[2-(4-cianfrocca)- 1-methylethyl]-L-valinamide, suspended in 150 ml of methylene chloride, at -20oC add 1.0 g of N-methylmorpholine and then 0.7 g of 2-methoxy-1-methylethylacetate. A mixture of OST is an increase of 2 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and obtain 0.87 g of the desired product as white plate crystals (yield 20%).

Example 34 synthesis

Synthesis of N1-[2-(4-fluoro-N-methylaniline)-1-methylethyl]-N2- phenoxycarbonyl-L-valinamide (compound N 391)

To a solution containing 3.9 g of N-phenoxycarbonyl-L-valine dissolved in 80 ml of methylene chloride, at -20oC add 1.6 g N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, to the mixture of 2.2 g of isobutylacetate and stirred at -20oC for 1 hour. To this mixture at -60oC add 3.0 g of 2-(4-fluoro-N-methylaniline)-1-methylethylamine, the mixture is left to warm with stirring under natural conditions to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic SL is Nochnoi by chromatography on silica gel, thereby obtaining 1.2 g of the desired product as white crystals (yield 19%).

Example 35 synthesis

Synthesis of N2-(4-chlorophenoxyacetic)-N1-[2-(4 - cianfrocca)-1-methylethyl] -L-valinamide (connection NN 395 and 396)

To a solution containing 4.7 g of N-(4-chlorophenoxyacetic)-L-valine dissolved in 250 ml of methylene chloride, at -20oC add 1.7 g of N-methylpiperidine. After stirring for 10 minutes at this temperature, to the mixture of 2.3 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC add 3.0 g of 2-(4-cianfrocca)-1-methylethylamine, then the reaction mixture is left to be heated, with stirring, naturally to room temperature, and at room temperature is stirred for 15 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removed under reduced pressure. The resulting crude crystalline substance purified column chromatography on silica gel and thus obtain 0.4 g of the desired product as a white powder. Powder additionally cleaned HPLC (VMC-063-15, hexane : ethyl acetate = 55:45) and there are two factions. One faction is bladaya long retention time, is 0.17 g of a white powder with so pl. 174-179oC (yield 2%).

Example 36 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl]-N2-2 - nitrophenoxyacetic-L-valinamide (compound No. 400)

To a suspension containing 3.4 g of N1-[2-(4-cianfrocca)-1 - methylethyl]-L-valinamide, suspended in 100 ml of methylene chloride, at -20oC add 1.3 g of N-methylmorpholine and then 2.5 g of 2-nitrophenylphosphate. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 2 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 1.0 g of the desired product in the form of lamellar crystals (yield 18%).

Example 37 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl]-N2- (4-pertenecieron-L-valinamide (compound N 401)

To a solution containing 3,0 N-(4-pertenecieron)-L-valine dissolved in 80 ml of methylene chloride, add 1.2 g of N-methylpiperidine at -20oC. After p is eshivot the mixture at -20oC for 1 hour. To this mixture at -60oC add 2.3 g of (-)-2-(4-cianfrocca)-1-methylethylamine, the mixture was then allowed to warm up naturally and with stirring to room temperature and stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The resulting crude crystalline substance purified column chromatography on silica gel, thus obtaining 1.1 g of the desired product as a white crystalline substance (yield 23%).

Example 38 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2-2- (3,4-dimethylthiocarbamyl)-L-valinamide (compound N 403)

To a suspension containing 1.5 g of N1-[2-(4-cianfrocca)-1 - methylethyl]-L-valinamide, suspended in 50 ml of methylene chloride at -15oC add 0.6 g N-methylmorpholine and then 1.2 g of 3,4-dimethylphenylcarbamate. The mixture is left to warm to room temperature naturally and stirred at room temperature for 1 the definition layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 1.7 g of the desired product as white crystals (yield 74%).

Example 39 synthesis

Synthesis of N2-tert-butyloxycarbonyl-N1-[2-(2-pyridyloxy)-1 - methylethyl]-L-valinamide (compound N 409)

To a solution containing 4.3 g of N-tert-butoxycarbonyl)-L-valine dissolved in 80 ml of methylene chloride, at -20oC add 2.0 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature thereto at -40oC added 2.7 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC added to 3.3 g of 2-(2-pyridyloxy)-1-methylethylamine, then the reaction mixture is left to warm up naturally and with stirring to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous sodium sulfate and removed under reduced pressure. The resulting crude crystalline substance purified column chromatography on silica gel and the floor of the BR> Synthesis of N1-[2-(5-chloro-2-pyridyloxy)-1-methylethyl)- N2-isopropoxycarbonyl-L-valinamide (compound N 412)

To a suspension containing 1.4 g of the hydrochloride of N1-[2-(5 - chloro-2-pyridyloxy)-1-methylethyl]-L-valinamide, suspended in 50 ml of methylene chloride at -15oC add 0.8 g of N-methylmorpholine and then 0.5 g of isopropylcarbamate. The mixture is left to warm to room temperature naturally and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and obtain 0.6 g of the desired product as colourless grains (yield 38%).

Example 41 synthesis

Synthesis of N1-[2-(5-chloro-2-pyridyloxy)-1-methylethyl] - N2-phenoxycarbonyl)-L-valinamide (compound 413 N)

To a suspension containing 1.4 g of the hydrochloride of N1-[2-(5-chloro-2-pyridyloxy)-1-methylethyl] -L-valinamide, suspended in 50 ml of methylene chloride at -15oC add 0.8 g of N-methylmorpholine and then 0.7 g of phenylcarbamate. The mixture is left to warm to Kok reaction mixture are added water. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus obtain 0.6 g of the desired product as colourless grains (yield 34%).

Example 42 synthesis

Synthesis of N1-[2-(4-fluoro-N-methylaniline)-1-methylethyl]-N2- phenoxycarbonyl-L-isolationand (compound N 422)

To a solution containing 4.8 g of N-phenoxycarbonyl-L-isoleucine, dissolved in 80 ml of methylene chloride, at -20oC added to 1.9 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added 2.6 g of isobutylacetate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC add 3.5 g of 2-(4-fluoro-N-methylaniline)-1-methylethylamine and then the reaction mixture is allowed to warm with stirring and naturally to room temperature and stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer successively with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over bezobolochnoe chromatography on silica gel and thus receive the 1.1 g of the desired product as white crystals (yield 13%).

Example 43 synthesis

Synthesis of N2(ethylthio)carbonyl-N1-[1-methyl-2-(4-nitrophenoxy)-ethyl]- L-valinamide (compound 432 N)

To a suspension containing 0.9 g of N1-1-methyl-2-(4-nitrophenoxide]- L-valinamide, suspended in 50 ml of methylene chloride at -15oC add 0.3 g of N-methylmorpholine and then 0.4 g of ethylchloride. The mixture is left to warm to room temperature naturally and stirred the mixture at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 1.0 g of the desired product as a yellow grains (yield 79%).

Example 44 synthesis

Synthesis of N2-tert-butyloxycarbonyl-N1-[2-(4-cianfrocca-1 - methylethyl] - L-leucinamide (compound N 455)

To a solution containing 3.4 g of N-tert-butoxycarbonyl-L-leucine dissolved in 60 ml of methylene chloride, at -20oC add 1.5 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature is added to the mixture at -40o

1NMR: (CDCl3, ) to 0.92 (6H, m), 1,28, of 1.32 (3H, d), 1,39, was 1.43 (9H, s), 1,46, of 1.65 (2H, m), of 1.65 (2H, m), of 1.65 (1H, m), 3,98 (2H, m) 4,06 (1H, m), 4,35 (1H, m), 4,91 (1H, sh), 6,46 (1H, sh), 6,97 (2H, d), EUR 7.57 (2H, D. D.).

Example 45 synthesis

Synthesis of N-tert-butyloxycarbonyl-N1-[2-(4-cianfrocca-1 - methylethyl]-L-tert-leucinamide (compound N 457)

To a solution containing 4 g of N-tert-butoxycarbonyl-L-leucine dissolved in 50 ml of methylene chloride, at -20oC add 1.7 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, to the mixture at -40oC add 2.4 g of isobutylacetate and the mixture is stirred at -20o

Example 46 synthesis

Synthesis of amide 2-tert-butoxycarbonylamino-3-methyl-N- [2-(4-cianfrocca)-1-methylethyl]-3-butenova acid (compound N 460)

To a solution containing 1.1 g of 2-tert-butoxycarbonylamino-3-methyl-3-butenova acid dissolved in 40 ml of methylene chloride, at -20oC add 0.5 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added at -40oC 0.7 g of isobutylacetate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC type of 1.9 g of 2-(4-cianfrocca)-1-methylethylamine, then the reaction mixture is allowed to warm with stirring and naturally to room temperature and stirred the mixture at room temperature for 20 hours. SeaStorm sodium bicarbonate and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The resulting crude crystalline substance purified column chromatography on silica gel and thus receive the 0.3 g of the desired product as a colorless gummy substance (yield 32%).

Example 47 synthesis

Synthesis of amide N-2-(4-cianfrocca)-1-methylethyl-2 - isopropylidenedicyclohexanol acid (compound N 462)

To a suspension containing 1.2 g of amide 2-amino-N-[2-(4-cianfrocca)-1-methylethyl] cyclopentyloxy acid, suspended in 40 ml of methylene chloride at -15oC add 0.4 g N-methylmorpholine and then 0.5 g of isopropylcarbamate. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel, thus obtaining 1.4 g of the desired product as colorless plate crystals (yield 90%).

Example 48 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- phenoxycarbonyl-L-nonvalidated (connection N is about 40 ml of methylene chloride, at -15oC add 0.5 g of N-methylmorpholine and then 0.8 g of phenylcarbamate. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate, and then the methylene chloride is removed under reduced pressure. The residue is purified column chromatography on silica gel and thus obtain 1.4 g of the desired product as colorless plate crystals (yield 57%).

Example 49 synthesis

Synthesis of N1-[2-(4-cianfrocca)-1-methylethyl] -N2- phenoxycarbonyl-L-leucinamide (compound No. 466)

To a suspension containing 1.5 g of N1-[2-(4-cianfrocca)- 1-methylethyl]-L-leucinamide, suspended in 40 ml of methylene chloride at -15oC add 0.5 g of N-methylmorpholine and then 0.8 g of phenylcarbamate. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate is hardly and thus receive the 1.5 g of the desired product as a colorless powder (yield 73%).

Example of synthesis 50

Synthesis of amide 2-(4-chlorophenethylamine)-N-[2- (4-cianfrocca)-1-methylethyl]cyclopentyloxy acid (compound N 471)

To a suspension containing 1.2 g of amide 2-amino-N-[2- (4-cianfrocca)-1-methylethyl] cyclopentyloxy acid, suspended in 40 ml of methylene chloride at -15oC add 0.4 g N-methylmorpholine and then 0.8 g of 4-khlorfenilalanina. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus obtain 0.6 g of the desired product as colourless grains (yield 80%).

Example 51 synthesis

Synthesis of N2-benzyloxycarbonyl-N1-[2- (4-cianfrocca)-1-methylethyl]-(4-chlorophenyl)glycinamide (compound N 475)

To a suspension containing 1.3 g of N1-[2-(4-cianfrocca)- 1-methylethyl]-(4-chlorphenyl)glycinamide, suspended in 40 ml of methylene chloride at -15oC add 0.4 g N-methylmorpholine, and then to 0.6 the Ute at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel, thereby obtaining 1.2 g of the desired product as colourless grains (yield 70%).

Example 52 synthesis

Synthesis of N2-(1-cyano-1-methylethanolamine)-N1- [2-(4-cianfrocca)-1-methylethyl]-L-valinamide (compound N 476)

To a suspension containing 0.7 g of the hydrochloride of N1-[2- (4-cianfrocca)-1-methylethyl]-L-valinamide, suspended in 50 ml of methylene chloride, at -20oC add 0.5 g of N-methylmorpholine and then 0.4 g of 1-cyano-1-methylethylacetate. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 0.6 g of the desired product as colourless grains (wieneke)-1-methylethyl]-L-valinamide (compound N 477)

To a suspension containing 1.0 g of the hydrochloride of N1-[2- (4-cianfrocca)-1-methylethyl]-L-valinamide, suspended in 50 ml of methylene chloride, at -20oC add 0.4 g N-methylmorpholine and then 0.9 g of 2-chlorocyclohexanone. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 1.1 g of the desired product as white colorless crystals (yield 71%).

Example 54 synthesis

Synthesis of N2-tert-butyloxycarbonyl)-N1- [2-(3-chloro-5-trifluoromethyl-2-pyridyloxy)-1-methylethyl]-L-valinamide (compound N 479)

To a solution containing 5.6 g of N-tert-butoxycarbonyl-L-valine dissolved in 100 ml of methylene chloride, at -20oC add 2.0 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, to the mixture -40oC added 2.7 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour.nnuu the mixture is left to warm with stirring and naturally to room temperature and stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous sodium sulfate and remove the methylene chloride under reduced pressure. The resulting crude crystalline substance purified column chromatography on silica gel and thus receive the 7.0 g of the desired product as colourless grains (yield 77%).

Example 55 synthesis

Synthesis of N1-[1-(5-chloro-6-ethyl-4-pyrimidinone)-2-propyl] -N2-isopropoxycarbonyl-L-valinamide (compound N 481).

To a solution containing 0.7 g of N-isopropoxycarbonyl-L-valine dissolved in 50 ml of methylene chloride, at -20oC added 0.34 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, to the mixture of 0.47 g of isobutylacetate and then stirred the mixture at -20oC for 1 hour. To this mixture at -60oC added 0.74 g of 1-(5-chloro-6-ethyl-4-pyrimidinone)-2-Propylamine, the reaction mixture is allowed to warm with stirring and naturally to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction SATA sodium and water this layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The resulting crude crystalline substance purified column chromatography on silica gel and thus receive the 0.6 g of the desired product as white prismatic crystals (yield 43%).

Example 56 synthesis

Synthesis of N-tert-butoxycarbonyl-L-poured-(4-chloro-phenyl)-N-methyl - DL-alaninemia (compound 490 N).

To a solution containing 2.0 g of N-tert-butoxycarbonyl-L-valine dissolved in 40 ml of methylene chloride, at -20oC add 0.9 g N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added 1.3 g of isobutylacetate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC add 2.0 g of N-(4-chlorophenyl)-N1-methyl-DL - alaninemia, the reaction mixture is allowed to warm with stirring and naturally to room temperature and stirred the mixture at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The resulting crude crystalline substance cleanse kalateh crystals (yield 87%).

Example 57 synthesis

Synthesis of N-isopropoxycarbonyl-L-isoleucine-N-(4-cyanophenyl)-D - alaninemia (compound 506 N)

To a solution containing 0,57 g N-isopropoxycarbonyl-L-isoleucine, dissolved in 60 ml of methylene chloride, at -20oC added 0.26 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added 0.36 g of isobutylacetate and the mixture is stirred at -20oC for 1 hour. To this mixture at -60oC add 0.5 g of N1-(4-cyanophenyl)-D-alaninemia, then the reaction mixture is allowed to warm with stirring and naturally to room temperature and stirred the mixture at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous sodium sulfate and remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus receive the 0.5 g of the desired product as a white powder (yield 49%).

Example 58 synthesis

Synthesis of N-cyclohexyloxycarbonyl-L-poured-N-(4-cyanophenyl)-D-alaninemia (compound 509 N)
Lienhard, at -20oC add 0.6 g N-methylmorpholine and then 0.6 g of cyclopentylpropionate. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus obtain 0.6 g of the desired product as white crystals (yield 49).

Example 59 synthesis

Synthesis of N-phenoxycarbonyl-L-poured-N-(4-chlorbenzyl)-DL-alaninemia (compound N 516)

To a suspension containing 0.95 g of the hydrochloride of L-poured-N-(4 - chlorbenzyl-DL-alaninemia, suspended with 50 ml of methylene chloride at -15oC added 0.55 g of N-methylmorpholine and then 0,43 g phenylcarbamate. The mixture is left to warm up naturally to room temperature and stirred at room temperature for 15 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer of water, this organic layer is dried over anhydrous magnesium sulfate and then remove methylene chloride at Pongo product as a white powder (yield 75%).

Example 60 synthesis

Synthesis of phenyl ether N-phenoxycarbonyl-L-poured-DL-alanine (compound N 522)

To a solution containing 0,57 g N-phenoxycarbonyl-L-valine dissolved in 40 ml of methylene chloride, at -20oC added 0.24 g of N-methyleneimine. After stirring the mixture for 10 minutes at this temperature, there was added 0.33 g of isobutylacetate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC add 0.5 g of phenyl ether, DL-alanine, and then the reaction mixture is allowed to warm with stirring and naturally to room temperature and the mixture is stirred at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel and thus obtain 0.2 g of the desired product as a white powder (yield 20%).

Example 61 synthesis

Synthesis of N1-(4-cyanophenyl)-N2- (2 phenoxycarbonylamino)- (2S)-butyryl-D-alaninemia (compound N 524)

TO A -20oC add 0.45 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added 0,61 g isobutylphthalate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC type of 0.85 g of N-(4-cyanophenyl)-D-alaninemia, then the reaction mixture is allowed to warm with stirring and naturally to room temperature and stirred the mixture at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The resulting crude crystalline substance purified column chromatography on silica gel and thus obtain 0.8 g of the desired product as a white powder (yield 45%).

Example 62 synthesis

Synthesis of N-isopropoxycarbonyl-L-poured-N-(4-cyanophenyl)glycinamide (compound N 526)

To a solution containing 0.6 g of N-isopropoxycarbonyl-L-valine dissolved in 40 ml of methylene chloride, at -20oC add 0.3 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this pace the art at -60oC add 0.5 g of N-(4-cyanophenyl)glycinamide, then the reaction mixture is allowed to warm with stirring and naturally to room temperature and stirred the mixture at room temperature for 20 hours. Then to the reaction mixture, water is added. After sequential washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure.

The residue is purified column chromatography on silica gel and thus obtain 0.5 g of the desired product as a colorless powder (yield 49%).

Example 63 synthesis

Synthesis of N2-tert-butoxycarbonyl-N1-(1,2-dimethyl-2 - phenoxyethyl)-L-valinamide (compound 602 N)

To a solution containing 1.3 g of N-tert-butoxycarbonyl-L-valine dissolved in 40 ml of methylene chloride, at -20oC add 0.6 g N-methylpiperidine. After stirring the mixture for 15 minutes at this temperature, there was added 0.8 g of isobutylacetate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC add 1 g of N1-(1,2-dimethyl-2 - phenoxyethyl)-L-valinamide, then the reaction mixture osteomeatal temperature for 20 hours. Then to the reaction mixture, water is added. After washing methylenchloride layer successively with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous magnesium sulfate and removing the methylene chloride under reduced pressure. The obtained oily substance is purified column chromatography on silica gel and thus receive the 1.3 g of the desired product as a white sticky substance (yield 57%).

1H NMR(CDCl3) ) from 0.8 to 1.02 (6H, m), 1.18 to 1,45 (15H, m), 2,10 (1H, m), 3,65 is 4.45 (3H, m), is 5.18 (1H, m), 6,38 (1H, m), 6,72 - to 7.35 (6H, m).

Example 64 synthesis

Synthesis of N2-tert-butoxycarbonyl-N1-[2-(4 - cianfrocca)-1,2-dimethylethyl] -L-valinamide (compound N 607).

To a solution containing 1.1 g of N-tert-butoxycarbonyl-L-valine dissolved in 60 ml of methylene chloride, at -20oC add 0.5 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, there was added 0.7 g of isobutylacetate and stirred the mixture at -20oC for 1 hour. To this mixture at -60oC add 1.0 g of 2-(4-cianfrocca)-1,2-dimethylethylamine, then the reaction mixture is allowed to warm with stirring and naturally to room temperature and peremeshivaemogo washing methylenchloride layer with 5% aqueous sodium bicarbonate solution and water, this organic layer is dried over anhydrous sodium sulfate and remove the methylene chloride under reduced pressure. The residue is purified column chromatography on silica gel, thereby obtaining 1.2 g of the desired product as a colorless glassy substance (yield 61%).

1H-NMR (CDCl3, ) 0,79-of 1.03 (6H, m), 1,15 - 1,46 (15H, m) 2,03 (1H, m), 3,63 - 4,72 (3H, m), is 5.06 (1H, m), 6,30 (1H, m), 6,83 - of 7.60 (4H, m).

Example 65 synthesis

Synthesis of N1-[2-(4-cianfrocca)propyl] -N2- phenoxycarbonyl-L-valinamide (compound N 750).

To a suspension containing 0.25 g of the hydrochloride of N1-[2-(4-cianfrocca)propyl]-L-valinamide, suspended in 20 ml of methylene chloride, at -20oC added 0.16 g of N-methylpiperidine. After stirring the mixture for 10 minutes at this temperature, thereto are added dropwise 0,13 g phenylcarbamate, the mixture was then allowed to warm with stirring and naturally to room temperature and stirred the mixture at room temperature for 3 hours. After removal of the methylene chloride under reduced pressure the residue is purified column chromatography on silica gel and thus obtain 0.2 g of the desired product as a white sticky substance (yield 63%).

1H-NMR: (CDCl3, ) and 1.00 (6H, m) of 1.23 (3H, d) by 2.13 (1H, m), and 3.31 (1H, m) 4,00 (2H, m), of 4.49 (1H, m), to 5.93 (1H, d), of 6.52 (1H, m), 6,80 - 7,56 (9H, m).

NGF the second composition, containing as active ingredient a derivative of amide amino acids represented by formula I. In the case when the connection corresponding to the present invention are used as fungicides for agriculture or horticulture, connections, acting as active ingredients, can be entered in the appropriate language, depending on the purpose. The active ingredient is usually diluted with an inert liquid or solid carrier and, if necessary, add surfactants or other similar substances. The mixture is then prepared by known methods as, for example, fine powder, wettable powder, emulsifiable concentrate, granules, etc.

Suitable examples of carriers used in the formulations are solid carriers such as talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, slaked lime, silica sand, ammonium sulfate, urea, etc.; and liquid media, such as isopropylene alcohol, xylene, cyclohexanone, methylnaphthalene, etc., Examples of surfactants and dispersing substances include salts dinaftiletilena acid, sulfonic ethers of alcohols, alkylenediamines, simple polyoxyethylene clucalc carboxymethyl-cellulose, etc., Such drugs can be applied directly or after diluting them to a suitable concentration.

Fungicides for agriculture or horticulture of the present invention can be used for various purposes, for example, for seed treatment, spray the leaves and stems, in water or irrigation and soil. The amount of the active ingredient is chosen according to needs. When the formulation is in the form of powder or granules, preferably the content of the active ingredient from 0.1 wt.% up to 20 wt.%. For emulsifiable concentrate or wettable powder is adequate amount of the active ingredient from 5 wt.% up to 80 wt.%.

Consumption of fungicide for agriculture or horticulture corresponding to the present invention, in use, may vary depending on the type of active compound, the type of pest or disease you are fighting, the location of the pest or disease, the extent of the damage, environmental conditions, form of medication, which is used, etc. When a fungicide for agriculture or horticulture, corresponding to the present invention, is used directly in Vedanta in the range of from 0.1 to 5 kg per 10 ar preferably in the range from 1 g to 1 kg per 10 ar. In addition, when the fungicide of the present invention is in liquid form such as emulsifiable concentrate or wetting the powder, an appropriate amount of the active ingredient for use it is recommended to choose in the range from 0.1 ppm to 10,000 ppm, preferably in the range from 10 ppm to 3000 ppm.

Compounds corresponding to the present invention, as described above formulations may be useful in the fight against plant diseases caused by fungi Oomycetes, A. scomycetes, Deuteromycetes and Basidiomycetes or other pathogenic fungi. These include, but are not limited to, Pseudoperonospora, such as downy mildew of cucumber (Pseudoperonospora cubensis), Phytophthora, late blight of tomato (Phytophthora infestans and Plasmopara, such as downy mildew of grapes.

Fungicides for agriculture or horticulture, corresponding to the present invention can be used alone or in combination with other fungicides, insecticides, herbicides, modifiers plant growth, fertilizers, etc.

Further examples of formulations are typical formulation, in which all "%" means "weight%".

Example formulations 1
< / and 93% of clay and grind into fine powder.

Example formulation 2

Wettable powder

Mix until smooth 50% of the compound N 16, 45% of diatomaceous earth, 2% dinaftiletilena sodium and 3% of sodium lignosulphonate and stirred wettable powder.

Example formulation 3

Emulsifiable concentrate

Mix until smooth 30% of compound No. 19, 20% of cyclohexanone, 11% alkylsilanes ester of polyoxyethylene, 4% of Las calcium and 35% of methylnaphthalene and thus receive the emulsifiable concentrate.

Example formulations 4

Granules

Mix and grind 5% of the compound N 101, 2% laurylsulphate sodium, 5% sodium lignosulphonate, 2% carbometalation and 86% of clay. To the milled mixture is added 20% water. The resulting mixture is stirred and molded into pellets from 14 to 32 mesh mesh by extrusion granulator and then dried, obtaining the desired granules.

Fungicides for agriculture or horticulture, corresponding to the present invention, reveal a high ability to fight the growth or spread of downy mildew of cucumber (Pseudoperonospora cubensis), late blight of tomato (Phytophthora infestans) and downy mildew wines for agriculture and horticulture, relevant to the present invention, not only find the ability to prevent infection by the fungus, but also find the ability to eliminate pathogenic fungus after it has invaded the host plant. Moreover, fungicides for agriculture or horticulture of the present invention differ in that they are not harmful chemicals and find such excellent properties as a systemic effect, the residual activity and stability after a rainstorm.

The effect of the compounds of the present invention, further illustrated by the following test examples. Connection to compare X and the connection for the comparison of Y used in the test examples are compounds, which are disclosed as intermediates for pharmaceuticals in a patent application in Japan, the primary publication N Sho 62-89696. These compounds are used in the comparison are after they are entered in the same wording, which entered the compound of the present invention, which are tested.

Connection for comparison, X - N2-tert-butoxycarbonyl-N1-(2-phenoxyethyl)-D-alaninate

Connection to compare Y - N2

Seeds of cucumber (variety Sagami hanjiro) were seeded at number 10 seeds in each square polyvinylchloride (PVC) pot, the size of each side of which 9 see the Seeds left to germinate in a greenhouse for 7 days prior to the stage cotyledons. Wettable powder prepared as described in example formulation 2, dilute with water to the concentration of the active ingredient 500 ppm (part per million) and the resulting aqueous preparation is used at the rate of 10 ml per pot of seedlings of cucumbers in stage cotyledons. After drying in air plants inoculant spore suspension downy mildew of cucumbers and Pseudoperonospora cubensis using spraying, and then placed in a moist chamber for 24 hours at 22oC, and then placed in the greenhouse. On the seventh day after inoculation to assess the degree of damage in accordance with the standards of the estimates are given in table. 15 to set the warning effect of the compounds of the present invention. The test results are given in table 16.

Test example 2

Check processing activities during infection of downy mildew of cucumber (Pseudoperonospora cubensis)

Seeds of cucumber (variety "Sagami hanjiro" sown in the amount of 10 seeds per square polyvinylchloride (PV is anti inoculant spore suspension of the fungus downy mildew of cucumber (Pseudoperonospora cubensis) and then placed in a moist chamber for 24 hours at 22oC. Wettable powder prepared as described in example formulation 2, dilute with water to the concentration of the active ingredient 500 ppm and the resulting aqueous drug treated cucumber seedlings after they have dried in air after treatment in a humid chamber, at a rate of 10 ml per pot of seedlings of cucumbers. Then the seedlings are placed in the greenhouse. On the seventh day after inoculation determine the degree of damage in accordance with the standards of the estimates presented in table. 15 to set the operation processing of the compounds disclosed in this invention. The test results are given in table 17.

Test example 3

Verification steps for the prevention of infection by late blight of tomato (Phytophtora infestans).

In porcelain pots (diameter 12 cm) planted seedlings of tomato (variety "Ponterosa) - one in each pot and grow them in the greenhouse. Wettable powder prepared as described in example formulation 2, dilute with water to the concentration of the active ingredient 500 ppm and apply the resulting aqueous preparation at the rate of 20 ml per pot of tomato seedlings at the stage of the 6-th or 7-th sheet. After drying in air plants inoculant suspension fourth day after inoculation to determine the index of coverage (index incidence) on the size of the damaged surface, as shown in table 18.

The degree of damage calculated in accordance with equation (1), and the index of coverage and the ability to prevent the disease (intensity suppression) is calculated in accordance with equation (2). The results are given in table 19.

< / BR>
Test example 4

Verification steps for the prevention of infection of downy mildew of grapes (Plasmapara viticola).

Rooted cuttings of grapes (variety "Kyoho"), each grown from cuttings and pruned, planted in porcelain pots (diameter 13 cm) and kept in the greenhouse. Wettable powder prepared as described in example formulation 2, dilute with water to the concentration of the active ingredient 500 and the resulting aqueous preparation is then applied at the rate of 20 ml per pot on grape seedlings at the stage of the 4-th or 5-th sheet. After drying in air plants inoculant suspension of zoosporangium inside host fungus downy mildew of grapes (Plasmapara viticola) and then placed in a moist chamber for 24 hours at 22oC. On the seventh day stay in the greenhouse after inoculation plants are again placed in the moist chamber for 24 hours at 22oC to grow conidiospore. On each sheet check the scope, on the face 18. The degree of damage calculated in accordance with equation (1), and the index of coverage and the ability to prevent the disease (the intensity of the action during the fight) is calculated in accordance with equation (2). The results of the tests are presented in table 20.

1. Derivatives of amides of amino acids of the formula I

< / BR>
in which R1is a (C1- C6)alkyl group, optionally containing at least one identical or different substituents selected from the group consisting of a halogen atom (C1- C6)alkoxygroup and cyanopropyl; lower alkenylphenol group, lower alkylamino group, (C3- C8)cycloalkyl group, optionally containing a Deputy selected from the group comprising methyl, or halogen atom; and (C3- C8)cycloalkyl(C1- C6)alkyl group; aracelio group, optionally containing a Deputy from the group consisting of methyl group, nitro; phenyl group, optionally containing at least one identical or different substituents selected from the group consisting of halogen atoms, (C1- C6)alkyl group which may be substituted by halogen atoms; and (Cteracycline group, selected from tetrahydropyran and tetrahydrofuran;

R2represents ethyl group, n-sawn group, isopropyl group, isobutylene group, sec-boutelou group, tert-boutelou group, lower alkenylphenol group, (C3- C8)cycloalkyl group, phenyl group, optionally containing at least one Deputy from among halogen atoms;

R3represents a hydrogen atom, or (C1- C6)alkyl group;

R4represents a hydrogen atom, (C1- C6)alkyl group, or cyano;

R5, R6independently represent a hydrogen atom or (C1- C6)alkyl group; R7, R8represent a hydrogen atom;

Z1- atom of O or S;

Z2represents an oxygen atom or a sulfur atom;

Z3represents an oxygen atom, a sulfur atom; a group N - R10where R10represents a hydrogen atom, methyl group, methylcarbamyl group, phenylcarbonylamino group, or sulfonyloxy group, sulfonyloxy group, group COO, group CONR11where R11represents a hydrogen atom or a lower alkyl group;

Q pryh substituents, selected from the group consisting of a halogen atom; and (C1- C6)alkyl group which may be substituted with three fluorine atoms; and (C1- C6)alkoxygroup, which can be substituted by identical or different halogen atoms; ceanography; nitro; and (C1- C6)alkoxycarbonyl group; methylsulfonyl group; methylsulfinyl group; methylthiourea; or Q represents a heterocyclic group selected from pyridyl, optionally containing at least one Deputy, selected from the group consisting of: halogen atom, triptorelin group; or Q represents pyramidalnou group, optionally containing at least one Deputy, selected from the group consisting of a halogen atom and (C1- C3)alkyl;

m is an integer from 0 to 2;

n is 0 or 1.

Derivatives of amides of amino acids under item 1, of formula II

< / BR>
in which R1represents (a) lower (C1- C6)alkyl group, optionally containing at least one identical or different substituents selected from the group consisting of a halogen atom and (C1- C6)alkoxygroup; (b) lower alkane is containing a methyl group; (e) Uralkaliy group, optionally containing a Deputy from the group consisting of a methyl group and nitro group; (f) phenyl group, optionally containing at least one identical or different substituents selected from the group consisting of a halogen atom, a methyl group, metoxygroup, ceanography, triptorelin group, cryptometer and nitro; or (g) a heterocyclic group selected from tetrahydropyran and tetrahydrofuran;

R3represents a hydrogen atom or (C1- C6)alkyl group;

R4represents a hydrogen atom, (C1- C6)alkyl group, or cyano;

R5, R6independently represent a hydrogen atom or (C1- C6)alkyl group;

R7, R8represent a hydrogen atom;

R9represents a hydrogen atom, methyl group or ethyl group;

Z1and Z2independently represent oxygen atoms or sulfur;

Z3represents an oxygen atom or a sulfur atom; a group N-R10where R10represents a hydrogen atom, methyl group, methylcarbamyl group, phenylcarbonylamino gruno containing at least one identical or different substituents, selected from the group consisting of a halogen atom; and (C1- C6)alkyl group which may be substituted with three fluorine atoms; and (C1- C6)alkoxygroup, which may be substituted by at least one halogen atom; ceanography; nitro; and (C1- C6)alkoxycarbonyl group; methylsulfinyl group; methylsulfonyl group; methylthiourea; or Q represents a heterocyclic pyridyloxy group, optionally containing at least one Deputy, selected from the same or different halogen atoms or CF3; or Q represents pyramidalnou group, optionally containing at least one different or identical substituents from the group consisting of a halogen atom and (C1- C3)alkyl;

m is an integer from 0 to 2;

n is 0 or 1.

3. Derivatives of amides of amino acids under item 1, of the formula III

in which R1is a (C1- C6)alkyl group, optionally containing at least one identical or different substituents selected from the group comprising a halogen atom and (C1- C6)alkoxygroup; and (C2- C6)alkenylphenol group; (the methyl group; (C7- C8)Uralkaliy group, optionally substituted methyl group; or phenyl group, optionally containing at least one identical or different substituents selected from the group comprising halogen atom, methyl group, methoxy group, triptorelin group, cryptometer and the nitro-group;

R4represents a hydrogen atom, (C1- C3)alkyl group, or cyano;

R6represents a hydrogen atom or (C1- C3)alkyl group;

R9represents a hydrogen atom, methyl group or ethyl group;

Z1and Z2independently represent oxygen atoms or sulfur;

Z3represents an oxygen atom, a sulfur atom, a group N - R10where R10represents a hydrogen atom, methyl group, methylcarbamyl group or phenylcarbonylamino group; or represents sulfonyloxy group or sulfonyloxy group;

Q represents a phenyl group, optionally containing at least one identical or different substituents selected from the group comprising halogen atom; and (C1- C3)alkyl, which may be zamochnye halogen atoms; a cyano; a nitro-group; methylsulfonyl group; methylsulfinyl group; matitiahu; or Q is a pyrimidine-2-ilen group, pyridine-2-ilen group, pyridine-4-ilen group or 4-chloro-pyridine-2-ilen group, 5-chloropyridin-2-yl, 5-triptorelin-2-yl, 3-chloro-5-triptorelin-2-yl, 5-chloro-6-ethylpyrimidine-4-yl;

m represents 0 or 2;

n is equal to 0 and 1.

4. Derivatives of amides of amino acids under item 1, of the formula IV

< / BR>
in which R1represents an ISO-propyl group, tertbutylphenol group, cyclopentyloxy group or phenyl group, optionally having at least one identical or different substituents selected from the group consisting of a halogen atom, a methyl group, metoxygroup and nitro;

X represents a halogen atom, a cyano or a nitro-group.

5. Derivatives of amides of amino acids under item 1, of the formula V

< / BR>
in which R1represents an ISO-propyl group, tertbutylphenol group, cyclopentyloxy group, tsiklogeksilnogo group which may be substituted methyl group, or phenyl group, optionally having at least one identical or different substituents, the choice is timecategory and nitro;

X represents a halogen atom, a cyano or a nitro-group.

6. Derivatives of amides of amino acids under item 1, of the formula VI

< / BR>
in which R1represents an ISO-propyl group, tertbutylphenol group, cyclopentyloxy group or phenyl group, optionally having at least one identical or different substituents selected from the group consisting of a halogen atom, a methyl group, metoxygroup and nitro;

X represents a halogen atom, a cyano or a nitro-group.

7. Derivatives of amides of amino acids under item 1, of the formula VII

< / BR>
in which R1is a (C1- C6)alkyl group, optionally containing at least one Deputy - cyano, (C3- C8)cycloalkyl group, optionally containing at least one Deputy is a halogen atom, (C4- C8)cycloalkyl (C1- C3)alkyl group, benzyl group, phenyl group, optionally having at least one particular Deputy selected from the group consisting of a halogen atom and dipterocarp;

R2is a n-sawn group, isopropyl group, Isobe is phenyl group, optionally having at least one Deputy is a halogen atom;

Q represents a phenyl group, optionally containing at least one Deputy - cyano, pyridyloxy group, optionally containing at least one identical or different substituents selected from halogen atoms.

8. Derivatives of amides of amino acids under item 1, of the formula VIII

< / BR>
in which R1is a (C1- C3)alkyl group, (C3- C8)cycloalkyl group or phenyl group, optionally having at least one Deputy from among halogen atoms;

R2represents an ethyl group, isopropyl group or a sec-boutelou group;

R4represents a hydrogen atom or (C1- C3)alkyl group;

Z3is a group COO, group CONR12where R12represents a hydrogen atom or (C1- C3)alkyl group;

Q represents a phenyl group, optionally having at least one identical or different substituents selected from the group consisting of a halogen atom, (C1- C3)alkyl groups, (C1is in the amino acids of the formula I

< / BR>
where R1= (C1- C6)alkyl, optionally substituted by a halogen atom, cycloalkyl (C5- C6); phenyl group, optionally having at least one identical or different substituents selected from the group comprising halogen atom, (C1- C6)alkoxygroup and the nitro-group, benzyl group, optionally substituted stands;

R2is ethyl, isopropyl, n-propyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, alkenyl, phenyl, optionally substituted by a halogen atom;

Z1is an oxygen atom or a sulfur atom;

Z2is an oxygen atom;

R3is hydrogen, lower alkyl;

R4is hydrogen, lower alkyl, cyano;

R5, R6is a hydrogen atom, lower alkyl;

R7, R8is hydrogen;

m = 0, 1, 2;

n = 0, 1;

Z3represents an oxygen atom, a sulfur atom, a group N - R10where R10represents a hydrogen atom or methyl group, group COO, group CONR11where R11represents a hydrogen atom or methyl group;

Q represents a phenyl group, optionally having at least one identical or different substituents selected from the group on>alkoxygroup, which may be substituted by a fluorine atom; a cyano; a nitro-group; matitiahu and (C1- C6)alkoxycarbonyl; Uralkaliy (benzyl) group which may be substituted by halogen atom; or Q is pyridyloxy group, optionally having at least one identical or different substituents selected from the group comprising a halogen atom and triptorelin group; pyramidalnou group optionally substituted by a halogen atom or (C1- C3)alkyl, characterized in that it includes a step of interaction between the compounds of formula IX

< / BR>
values of R1, R2, Z1described above, with the compound of the formula X

< / BR>
values of R3, R4, R5, R6, R7, R8, Z3, Q, n and m above.

10. The method of obtaining derivatives of amides of amino acids of the formula I

< / BR>
where R1is a (C1- C6)alkyl, optionally having as a substituent a methoxy group or a cyano; lower alkenyl; and (C5- C6)cycloalkyl, optionally having as a substituent methyl group or a halogen atom; and (C3- C8)cycloalkyl (C1- C6)alkyl; the data from the group includes halogen atom; and (C1- C6)alkyl which may be substituted by a fluorine atom; a lower alkoxygroup, which may be substituted by a fluorine atom and a nitro-group; aracelio group optionally having as a substituent a nitro-group; tetrahydrofuran; tetrahydropyran;

R2represents ethyl, isopropyl, n-propyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl; phenyl group optionally having as a substituent a halogen atom;

R3is a hydrogen atom, (C1- C6)alkyl;

R4is a hydrogen atom, (C1- C6)alkyl;

R5, R6is a hydrogen atom;

R7, R8is a hydrogen atom;

Z1is an oxygen atom or a sulfur atom;

Z2is an oxygen atom or a sulfur atom;

Z3is an oxygen atom, a sulfur atom, a CONH group;

m = 0, 1;

n = 0, 1;

Q represents phenyl, optionally having at least one identical or different substituents selected from the group comprising halogen atom, a cyano, a nitro-group; aralkyl (benzyl), optionally substituted by halogen atom; a pyridyl which may be substituted by a halogen atom, wherein interact connection form>OS(O)O - or a group-ON=C(CN)Ph, where Ph means phenyl group, and Z1, Z2and R1above, with a compound of formula XII

< / BR>
values of R2R3, R4, R5, R6, R7, R8, Z3, m and n above.

11. Fungicidal composition for agricultural or horticultural comprising an effective amount of the active ingredient - derived amino acids, and special additive, characterized in that as the derived amino acid contains a compound of the formula 1 on p. 1.

 

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