Fungicidal derivatives of oxetane and their salts

 

(57) Abstract:

Usage: in agriculture as a fungicide. The inventive product-octane derivatives f-ly I, where R1-R9have appropriate values, and their salts. These compounds are highly effective antifungal agents, no harm to plants, to which they are applied. Connection structure of f-crystals I 27 C. p. F.-ly.

The invention relates to a series of new oxetanone derivatives, the molecular structure of which is characterized by the presence of four-membered rings containing an oxygen atom (i.e., oceanologia rings), and which have agricultural and pharmaceutical antifungal or fungicidal activity. This invention is also a method of obtaining these compounds, and methods and compositions containing them, for the protection of animals, including humans, and plants from fungi.

Although already known for many different types of triazole derivatives having agricultural antifungal or fungicidal activity, almost all of them do not have oceanologia fragment, which is a characteristic feature of the compounds of the proposed image is methyl)oxetan-4-it is as intermediates in the process of receiving antifungal agents (which are not derived from oxetane), but these intermediate compounds structurally different from the compounds of the present invention, and it was found that by themselves they do not have any antifungal activity.

In addition, in the European patent N 318214 describes the use of a limited number of 2-(triazolylmethyl)-oxetanone derivatives as antifungal agents, although this preceding description relates mainly relevant tetrahydrofuranyl compounds and 2-(triazolylmethyl)-oxetanone derivatives, specifically disclosed therein are different from the compounds of the present invention the nature of the substituent in 4-position oceanologia rings.

Currently, we found a number of new triazole compounds having oxetanyl skeleton, which differ structurally triazole derivatives and which have excellent pharmaceutical and agricultural antifungal or fungicidal activity.

The aim of the invention is the provision of new substances of some new derivatives of oxetane.

Following the aim of the invention is the provision of a method of producing these compounds.

for use as a pharmaceutical, or agricultural antifungal or fungicidal agents, and providing methods of using these compounds and compositions for pharmaceutical and agricultural purposes.

New derivatives of oxetane of the invention can be represented by the formula

HCR8R (I) in which R1and R2independently selected from the group consisting of hydrogen atoms and alkyl groups having from 1 to 6 carbon atoms, or R1and R2together with the carbon atom to which they are attached, form cycloalkyl group having from 3 to 6 carbon atoms; R3and R4independently selected from the group consisting of hydrogen atoms, alkyl groups having from 1 to 6 carbon atoms, and phenyl groups, or R3and R4together with the carbon atom to which they are attached, form cycloalkyl group having from 3 to 6 carbon atoms; or R1and R3and the carbon atoms to which they are attached, together form cycloalkyl group having 5 or 6 ring atoms and condensed with oxetanone ring; R2selected from the group consisting of hydrogen atoms and alkyl groups having from 1 to 6 carbon atoms; and R4selected from the group consisting of the strong group, substituted groups R5, R6and R7where R5, R6and R7independently selected from the group consisting of hydrogen atoms, halogen atoms, alkyl groups having from 1 to 6 carbon atoms, alkoxygroup having from 1 to 6 carbon atoms, halogenated alkyl groups having from 1 to 6 carbon atoms and the halogenated alkoxygroup having from 1 to 6 carbon atoms; and R8and R9independently selected from the group consisting of hydrogen atoms and alkyl groups having from 1 to 4 carbon atoms; and their salts.

The invention is also a pharmaceutical composition for prevention or treatment of fungal infections, which includes funguide or fungistaticeski effective amount of an antifungal agent, in which the antifungal agent is selected from the group consisting of compounds of the formula I and their pharmaceutically acceptable salts, as defined above.

Further, the invention provides a method of prevention or treatment of fungal infections, which includes the use or purpose fungicide or fungistaticeski effective amount of an antifungal agent to an animal, e.g. a mammal, which may be people, and in which FR is defined above.

The invention also provides an agricultural composition for protecting plants and substances for the production of plants from fungi, which includes fungicide or fungistaticeski effective amount of the compounds of formula I or its salts as defined above, in a mixture with an agricultural carrier or diluent.

The invention is also a method of protecting plants and substances for the production of plants from fungi, which involves applying to said plant or substances for their reproduction, or to the place of distribution, fungicide or fungistaticeski effective amount of the compounds of formula I or salts thereof, as defined here above.

The invention also introduces several new methods of producing compounds of the present invention, which are described in more detail below.

In the compounds of the invention in which R1, R2, R3, R4, R5, R6or R7represents an alkyl group, this group may be an alkyl group with straight or branched chain, having from 1 to 6 carbon atoms. Examples of such groups include methyl, ethyl, propyl, isopropyl, butyl, who terpencil, 3-methylpentyl, 2-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dime - terbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl and 2,3-dimethylbutyl group, of which these preferred alkyl groups containing from 1 to 4 carbon atoms.

In those cases where R1and R2or R3and R4together with the carbon atom to which they are attached, form cycloalkyl group having from 3 to 6 carbon atoms, is formed Spirodela ring system with oxetanone ring. Such cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl and tsiklogeksilnogo group, of which cyclopentolate and tsiklogeksilnogo group are preferred, and most preferred is tsiklogeksilnogo group. Preferably only one of R1and R2or R3and R4form such spinosissima, and more preferably such pair is R3and R4.

When R1and R3together with the carbon atoms to which they are attached, form cycloalkyl group, the latter is cyclopentolate or tsiklogeksilnogo group condensed with oxetanone ring, and preferably tsiklogeksilnogo group. Astelin Inoi group.

Of the groups and atoms which may be represented by the symbols R1, R2, R3and R4we particularly prefer that they were the same or different, and each one represented a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms. More preferably one of R1and R2must represent a hydrogen atom, and the other alkyl group containing from 1 to 4 carbon atoms, and one of R3and R4must represent a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, and the other should represent an alkyl group containing from 1 to 4 carbon atoms. Even more preferably, one of R1and R2represents a hydrogen atom and the other is a methyl or ethyl group, and one of R3and R4represents a hydrogen atom or a methyl group and the other represents a methyl group. Most preferably R1and R4both represent methyl group, and R2and R3both represent a hydrogen atom; or R1represents ethyl group, R4represents a methyl group and R2and R3both represent hydrogen atoms; or R1and R2both represent hydrogen atoms and R2represents a hydrogen atom.

Ar represents a phenyl group having from 1 to 5 substituents, represented by the symbols R5, R6and R7i.e. it can be substituted or unsubstituted phenyl group, which has 1, 2 or 3 substituent. When there are two or three of these substituents, they may be the same or different.

When R5, R6or R7represents a halogen atom, they can be an atom of fluorine, chlorine, bromine or iodine, preferably a fluorine atom or a chlorine atom.

When R5, R6or R7represents an alkyl group, it may be the group defined above.

When R5, R6or R7represents an alkoxy group, it may be alkoxygroup straight or branched chain, having from 1 to 6 carbon atoms. Examples of such groups include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentylamine, tert-pentyloxy, neopentylene, hexyloxy, isohexane, 2-methylbutoxy, 4-methylpentylamino, 3 methylpentane, 2-methylpentane, 3,3-Dimethylbutane, 2,2-Dimethylbutane, 1,1-Dimethylbutane, 1,1-Dimethylbutane, 1,3 is glared.

When R5, R6or R7represents a halogenated alkyl group, this has from 1 to 6 carbon atoms and can be alkyl group with straight or branched chain having one or more, preferably from 1 to 5 (or less if there is less capable of substitution positions), more preferably from 1 to 3, halogen substituents. Examples include any of the alkyl groups, examples of which are outlined above, but more preferably a group having from 1 to 4, and most preferably 1 or 2 carbon atoms, in which one or more hydrogen atoms substituted by halogen atom (e.g. fluorine atom, chlorine, bromine or iodine). Specific examples include trifluoromethyl, trichloromethyl, deformity, dichloromethyl, dibromomethyl, vermeil, chloromethyl, methyl bromide, iodomethyl, 2,2,2-trichloroethyl, 2,2,2-triptorelin, 2-bromacil, 2-chloroethyl, 2-foradil and 2,2-dibromoethyl groups, of which we prefer trifluoromethyl, trichloromethyl, deformity, 2-bromacil, 2-chloroethyl and 2-florachilena group, especially triptorelin group.

When R5, R6or R7represents a halogenated alkoxygroup, it has from 1 to 6 carbon atoms and may be alkoxygroup straight and is on the substituted provisions), more preferably from 1 to 3 halogen substituents. Examples include any of alkoxygroup, examples of which are given above, in which one or more hydrogen atoms replaced by halogen atoms (e.g. fluorine atom, chlorine, bromine or iodine). Specific examples include triptoreline trichlormethane, deformedarse, dichloromethoxy, dibromethane, formatosi, chloromethoxy, bromoethoxy, admetox, bromodifluoromethane, chloroformate, 2,2,2-trichlormethane, 2,2,2-triptoreline, 2-bromoethoxy, 2-chloroethoxy, 2-floratone and 2,2-dibromethane groups, of which we prefer triptoreline group.

When the phenyl group Ar is the only Deputy, it preferably is 2-(ortho) or 4-(para-position, more preferably 4-position. When there are two such Deputy, they are preferably in the 2,4 - or 2,6-positions, more preferably 2,4-positions. When there are three such Deputy, they preferably are in the 2,4,5-or 2,4,6-positions, more preferably in the 2,4,6-positions. We prefer to have one and two Deputy.

Of the groups and atoms which may be represented by the symbols R5, R6and R7we especially predpochitaesh alkyl groups, having from 1 to 4 carbon atoms, more preferably from the group consisting of hydrogen atoms and halogen atoms, in these cases, they are preferably hydrogen atoms, chlorine, fluorine or bromine. In one preferred class of such compounds one of R5, R6and R7represents a hydrogen atom, and the other two are the same or different and each represents a halogen atom or a halogenated alkyl group having from 1 to 4 carbon atoms; more preferably one of R5, R6and R7represents a hydrogen atom, and the other two are the same or different, and each represents a halogen atom; even more preferably, one of R5, R6and R7represents a hydrogen atom, and the other two are the same or different and each represents a chlorine atom, fluorine or bromine.

Preferred groups represented by the symbol Ar, are on-chloraniline, p-chloraniline, p-Fortunella, p-bratinella, 2,4-differenly, 2,6-differenly, 2,4-dichloraniline, 2-chloro-4-Fortunella, 4-chloro-2-Fortunella, 6-chloro-2-Fortunella, 4-triftormetilfullerenov and 4-triphtalocyaninine group, of which p-PI is I's most preferred.

When R8or R9represents an alkyl group, this may be an alkyl group with straight or branched chain, having from 1 to 4 carbon atoms. Examples of such groups include methyl, ethyl, sawn, ISO-propyl, boutelou, isobutylene, second-boutelou and tert-boutelou groups, of which we prefer alkyl group containing 1 or 2 carbon atoms. More preferably one of R8and R9represents a hydrogen atom and the other represents a hydrogen atom or alkyl group having from 1 to 4 carbon atoms, and more preferably both of R8and R9represent hydrogen atoms.

Compounds of the invention include a few basic nitrogen atoms and can, therefore, form an acid additive salt. There is no particular restriction on the nature of these salts, provided that when they are intended for therapeutic use, they are pharmaceutically acceptable, and when they are intended for agricultural use, they are acceptable in agriculture. When they are intended for naturalistisch or non-agricultural applications, n is and this restriction is not necessary. Examples of such acid additive salts include: salts with mineral acids, especially halomonadaceae acid (such as hydrochloric, hydrofluoric, Hydrobromic acid or itestosterone acid), or another mineral acid (such as sulfuric acid, nitric, perchloric acid or phosphoric acid); salts with organic carboxylic acid, such as oxalic, maleic, succinic acid or citric acid; and salts of sulfonic acids, for example, with alkanesulphonic or ganodermanontriol acid, such as methanesulfonate, triftoratsetata or econsultation, or arylsulfonic acid, such as baselslt - or p-toluensulfonate. Preferred nitrates and oxalates.

Compounds of the invention necessarily contain several asymmetric carbon atoms in their molecules, each of which may exist in the R-configuration or t-configuration, and thus can form stereoisomers. Although they are presented here only the molecular formula, the invention includes both the individual separated isomers and mixtures, including racemates. When applied techniques stereospecific C is', the individual isomers may be obtained using standard techniques cleavage.

The stereochemistry at the 4-position oceanologia rings, apparently, has no effect on the activity of the compounds of the invention. However, the stereochemistry at the 3-position seems to be is important. When the connection has two deputies, one in the 3-position and one at the 4-position oceanologia rings, for example, 3,4-dimethyloxetane connection, the preferred configuration is (2R, 3S) configuration or diastereomers (2S, 3R) configuration, or a racemate (1:1 mixture of two diastereomers, which can be presented as or (2R*, 3S*) or (2S*, 3R*), more preferably (2R, 3S, 4R) configuration or diastereomers (2S, 3R, 4S) configuration, or a racemate of two diastereomers, which may be represented, or (2R*, 3S*, 4R*) or (2S*, 3R*, 4S*).

Examples of specific compounds of the invention are given in formulas I-1, I-2 and I-3, in which the substituents have the meanings given in the corresponding table. 1-3, respectively, i.e., PL.1 relates to formula I-1, PL. 2 to the formula I-2 and table.3 to the formula I-3.

HCH (I-1)

HCH (I-2)

HCH (I-3)

Of the compounds illustrated above connection 1-7, 1-21, 1-114, 1-118, 1-145, 1-146, 1-246, 1-277, 1-137, 1-355, 1-383, 1-393, 1-409, 1-447, 1-4�Vlada preferred.

The most preferred compounds are compounds 1-7, 2-(2,4-di-forfinal)-3,4-dimethyl-2-[(1-1,2,4-triazole-1-yl)methyl] oxetane, especially(2*, 3*, 4*)-2-(2,4-differenl)-3,4-dimethyl-2- [(1H-1,2,4-triazole-1-yl) methyl]oxetan isomer;

1-383, 2-(4-chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetane, especially(2*, 3*, 4*)-2-(4-chlorophenyl)-3,4-dimethyl-2-[(1-1,2,4-triazole-1-yl)methyl]oxetan ISO - measures;

1-483, 4-ethyl-2-(4-forfinal)-3-methyl-2-[(1-1,2,4-triazole-1-yl)methyl] oxetane, especially(2*, 3*, 4*)-4-ethyl-2-(4-forfinal)-3-methyl-2-[(1-1,2,4-triazole-1-yl)me - til] oxetan isomer;

1-486, 2-(4-forfinal)-3,4-dimethyl-2-[(1-1,2,4-triazole-1-yl)methyl]oxetane, especially(2*, 3*, 4*)-2-(4-forfinal)-3,4-dimethyl-2-[(1-1,2,4-triazole-1-yl)methyl]oxetan ISO - measures.

Also are the preferred salts, especially nitrates and oxalates, the above compounds.

Compounds of the invention can be prepared by various methods, some of them are well-known in the technical field of the preparation of compounds of this type. For example, in a General sense, the compounds can be prepared by any of the following methods a, b, C and D, which are new methods in and of themselves form part of the invention.

S p o C o b A.

In this process soedineniya, defined above; R10represents a hydrogen atom or hydroxyamides group; and Y represents a nucleophilic tsepliaeva group or atom, is treated with a base to cause cyclization to obtain the compound of formula I, which may, if desired, be subjected to the reaction of formation of salt.

S p o C o b C.

An alternative method of preparing compounds of the invention involves reacting the compounds of formula

Y-CR8R (III) in which R1, R2, R3, R4, R8, R9, Ar and Y have the above meanings, with a compound of the formula

(IV) i.e., 1-1,2,4-triazole in the presence of a base to obtain the compounds of formula I, which may, if desired, be then subjected to the formation of salt.

S p o C o b C.

Another method of preparing compounds of the invention involves reacting the compounds of formula

(V) in which R8, R9and Ar have the abovementioned meanings, with a compound of the formula

CC (VI) in which R1, R2, R3and R4have the above meanings, or with its functional equivalent, to obtain compounds of formula (I), which may, if desired, then be on the ring corresponding epoxysilane formula

(VII) in which R3, R4, R8, R9and Ar have the abovementioned meaning, and then, if desired, the resulting compound is subjected to the formation of salt.

Hereinafter described in more detail data response.

S p o C o b A.

In the method a compound of formula II cyclized by treatment with base.

In the compound of formula II hydroxyamide group represented by the symbol R10can be any of the groups commonly used in reactions of this type, and because it does not remain in the final product, its nature is not essential, and it can be selected from a wide range of such protecting groups are known only on the basis of its functionality in the reaction.

Examples of such groups include:

aliphatic acyl group, preferably: alcoholnye group having from 1 to 25 carbon atoms, more preferably from 1 to 20 carbon atoms, and most preferably from 1 to 6 carbon atoms such as formyl, acetyl, propionyl, butyryl, isobutyryl, pivaloyl, valeryl, isovaleryl, hexanoyl, heptanoyl, octanoyl, lauroyl, myristoyl, tridecanol, palmifolia and caarolina group); halodurans the AK chlorocichla, dichloroacetylene, trichloroethylene and trifluoracetyl group); lower alkoxyalkanols group, in which alkoxides preferably has from 1 to 3 carbon atoms, and alcoolica part has from 2 to 6 carbon atoms and is preferably acetyl group (such as methoxyacetyl group); and unsaturated analogs of such groups, especially alkanoyloxy or alkanoyloxy group having from 3 to 6 carbon atoms (such as calolina, metakaoline, Propylamine, crotonoideae, isotretinoina and ()-2-methyl-2-butenolide group);

aromatic acyl groups, preferably arylcarbamoyl groups in which the aryl part has from 6 to 14, more preferably from 6 to 10 and most preferably 6 or 10 ring carbon atoms and is a carbocyclic group which is not substituted or is from 1 to 5, preferably from 1 to 3 substituents, preferably: unsubstituted groups (such as benzoline, -napolina and-napolina group); halogenated arylcarbamoyl group (such as 2-bromobenzoyl and 4-chlorbenzoyl groups); lower alkyl substituted arylcarbamoyl group, in which alkyl or each alkyl substituent preferably placed arylcarbamoyl group, in which alkoxy or each alkoxylation preferably has from 1 to 4 carbon atoms (such as 4-ansorena group); nitrosamino arylcarbamoyl group (such as 4-nitrobenzoyl or 2-nitrobenzoyl groups); lower alkoxycarbonylmethyl arylcarbamoyl group, in which alkoxycarbonyl or each alkoxycarbonyl Deputy preferably has from 2 to 5 carbon atoms [such as 2-(methoxycarbonyl)-benzoline group] and aryl-substituted arylcarbamoyl groups in which the aryl Deputy is the same as above, except that, if it is replaced by the additional aryl group, then the aryl group is itself substituted by an aryl group (such as 4-phenylbenzophenone group);

tizanidine silyl group, in which all three or two or one of the substituents are alkyl groups having from 1 to 4 carbon atoms, and none, one or two Deputy represent aryl groups, as defined above, but preferably phenyl or substituted phenyl groups, preferably three (lower alkyl) silyl groups such as trimethylsilyl, triethylsilyl, isopropylethylene, tert-butyldimethylsilyl, IU the group, in which one or two alkyl groups, substituted aryl groups (such as phenylmethylene, diphenylmethylene, diphenyl-tert-Boticelli, diphenylethylene and phenyldimethylsilane group);

alkoxyalkyl groups in which the alkoxy and alkyl parts each have from 1 to 4 carbon atoms, especially alkoxymethyl groups, and such groups which have at least one, preferably from 1 to 5, more preferably from 1 to 3 and most preferably 1, substituents, preferably lower alkoxymethyl groups and other alkoxyalkyl group (such as methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxyphenyl, butoxymethyl, and tert-butoxymethyl groups); lower alcoholization lower alkoxymethyl groups (such as a 2-methoxyethoxymethyl group); halogenated low alkoxymethyl groups such as 2,2,2-trichloroethylene and bis(2-chloroethoxy)methyl group] and lower alkoxy-substituted ethyl groups (such as 1-amoxicilina and 1-isopropoxyaniline group);

other substituted ethyl group, preferably: halogenated ethyl group such as 2,2,2-trichlorethylene group); and allseeingeye] kalkilya group, preferably alkyl groups having from 1 to 4, more preferably from 1 to 3 and most preferably 1 to 2 carbon atoms, which are substituted by 1-3 aryl groups, as defined and illustrated above, which may be unsubstituted (such as benzyl, -naphthylmethyl-naphthylmethyl, diphenylmethyl, triphenylmethyl-naphthylmethyl and 9-intellilink group) or substituted in the aryl part of the lower alkyl group, lower alkoxygroup, a nitro-group, a halogen atom, a cyano or alkylenedioxy group having from 1 to 3 carbon atoms, in which the alkyl or alkoxy group may be as defined and illustrated above, and alkylenedioxy represents preferably methylenedioxy (such as 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenylalanine, 2-nitrobenzyl, 4-nitrobenzyl, 4-Chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, 4-cyanobenzaldehyde, bis-(2-nitrophenyl)methyl and piperella group), alkoxycarbonyl group, especially such groups, which have from 2 to 7, more preferably from 2 to 5 carbon atoms and which may be unsubstituted (such as methoxycarbonyl, atoxic the military silyl group, for example, three(lower alkylsilane)group (such as 2,2,2-trichlorocyanuric and 2-trimethylsilylethynyl group);

altneratively groups in which Alchemilla part has from 2 to 6, preferably from 2 to 4 carbon atoms (such as vinyloxycarbonyl and allyloxycarbonyl group), and aracelikarsaalyna groups in which kalkilya part is the same as described and illustrated above, and in which the aryl ring, if it is substituted, preferably has one or two lower alkoxy or microsatellites (such as benzyloxycarbonyl, 4-methoxybenzenesulfonyl, 3,4-dimethoxybenzonitrile group). Of these we prefer kalkilya and three(lower alkyl)silyl group, most preferably benzyl and trimethylsilyl group. Examples of nucleophilic delete groups and atoms which may be represented by the symbol Y include halogen atoms such as chlorine, bromine and iodine;

lower alkanesulfonyl group, whose alkyl part has from 1 to 6, preferably from 1 to 4 carbon atoms (such as methanesulfonate, econsultancy group);

halogenated lower alkanesulfonyl in which and the ne atom of halogen and can be perhalocarbon (such as trichlorocarbanilide, pentafluoroethanesulfonyl group); and

arylsulfonate groups in which the aryl part is the same as described and illustrated above (such as benzosulfimide and p-toluensulfonate group).

Of these, we prefer the lower alkanolammonium and halogen atoms, and more preferably methysulfonylmethane and a chlorine atom.

The reaction in this method involves the cyclization of the compounds of formula II by treatment with base, preferably more than one equivalent of base, and typically and preferably in a solvent, for ring closure.

When R10represents hydroxyamino group which can be removed in the presence of basic conditions, the reaction at this stage can be carried out using a starting material of formula II with such hydroxyamino group. Otherwise, you must use a connection that is free from such groups, in this case, depending on how you received the compound of formula II, may be necessary to first remove hydroxyamino group.

The reaction is normally and preferably carried out in the presence of a solution of the tion and provided that it dissolves the starting material at least to some extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons, including aliphatic and aromatic halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichlorethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylethylenediamine ether; alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, Isobutanol, tert-butanol, isoamyl alcohol, diethylenglycol, glycerin, octanol, cyclohexanol, and etilenglikolevye ether (for example, sold under the trade name "Methylcellosolve");

nitro compounds such as nitroethane and nitrobenzene; NITRILES such as acetonitrile and isobutyronitrile; amides, such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide and 1,3-dimethyl-2-imidazolidinone; and sulfoxidov, such as dimethyl sulfoxide and sulfolane.

Similarly, there is no particular restriction on the nature of the base, to ispolzolzovalsja here. Examples of preferred bases include inorganic bases such as alkali metal carbonates (e.g. sodium carbonate or potassium carbonate); the acid carbonates of alkali metals (for example, acidic sodium carbonate or potassium bicarbonate); hydrides of alkali metals (e.g. lithium hydride, sodium hydride or potassium hydride), alkali metal hydroxide (e.g. sodium hydroxide, potassium hydroxide or barium hydroxide); cyanides of alkali metals (e.g. sodium cyanide or potassium cyanide); an alcoholate of alkali metals (e.g. sodium methylate, sodium ethylate or tert-butyl potassium); azides of alkali metals (e.g. lithium azide or sodium azide); and mercaptide alkali metals (for example, methylmercaptan sodium or ethylmercaptan sodium). Other preferred bases include: organic bases, especially tertiary amines, such as triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 2-(N,N-dimethylamino)pyridine, N, N-dimethylaniline, N,N-diethylaniline, 1.5-diazabicyclo(4.3.0)non-5-ene, 1,4-diazabicyclo(2.2.2)- octane(DASO) and 1,8-diazabicyclo(5.4.0)- undec-7-ene; and organic base metals, such as utility and lithium diisopropylamide.

In order to promote is monia, such as the chloride benzyltriethylammonium or tetrabutylammonium chloride, or crown ethers such as dibenzo-18-crown-6.

The reaction occurs in a wide temperature range, and choose exactly the reaction temperature is not critical for the invention. Mostly we find convenient to conduct the reaction at a temperature in the range from -78aboutC to the boiling point of the employed solvent, preferably from -20 to 100aboutC. the Time required for the reaction may likewise vary widely, depending on many factors, namely the reaction temperature and the nature of the reagent or solvent used. However, in most cases, the period of time from 10 minutes to 24 hours is usually sufficient.

After completion of the reaction, the desired product can be isolated from the reaction mixture by standard methods. An example of such a process includes receiving: add is not miscible with water and organic solvent to the reaction mixture; washing the organic phase with water, drying the washed organic phase; and, finally, the distillation of the organic solvent to obtain the desired product. If necessary, the resulting compound may dalnesrochnye techniques chromatography namely chromatography on a column or preparative thin layer chromatography.

S p o C o b C.

In this way the compound of formula I is produced by the interaction of the compounds of formula III, 1-1,2,4-triazole in the presence of a base.

The reaction is a substitution reaction of the same kind as the reaction in method A, and can be carried out using the same reagents and reaction conditions. Preferably the reaction is additionally osushestvlya in the presence of inorganic salts, especially alkali metal halide such as sodium iodide or lithium bromide.

S p o C o b C.

In this way, the compound of formula I is produced by the interaction of the compounds of formula V with ethyleneamines compound of formula VI, preferably using a photochemical reaction, and typically and preferably in the presence of a solvent.

The reaction is preferably carried out by irradiation of the reaction mixture with light, the wavelength of which depends on the nature of the olefin of the formula VI and a ketone of the formula V, but is preferably from 280 to 350 nm. It is preferable to fix the light having a wavelength less than 280 nm, for example, by Iveta this wavelength, for example, benzene or mixtures thereof. In addition, there are no special restrictions regarding the nature of the employed solvent, provided that it has no adverse effect on the reaction or participating in the reaction reagents. Examples of suitable solvents include: hydrocarbons, especially aromatic hydrocarbons, such as benzene, toluene or xylene; alcohols such as methanol, ethanol or isopropanol; NITRILES, such as acetonitrile or benzonitrile; ethers, such as diethyl ether or tetrahydrofuran, and the lower aliphatic and cycloaliphatic hydrocarbons, such as pentane, hexane or cyclohexane. You can use one of these solvents or a mixture of any two or more solvents.

The reaction can be carried out in a wide temperature range, and the particular reaction temperature is not critical for the invention. Mostly we find convenient to conduct the reaction at temperatures from -20 to +80aboutS, more preferably from 10 to 40aboutC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, provided that the reaction is carried out in a preferred conditions, ouassini rings in this way can be achieved by reacting the compounds of formula VII with a reagent of the type known to extend the ring of compounds of this type, for example Corley reagent, such as metered dimethylsulfoxide; or a halide trimethylsulfoxonium, such as chloride trimethylsulfoxonium or iodide trimethylsulfoxonium; or using transfer reactions nucleophilic methylene, for example, in the presence of sodium-dimethyl-N-(para-toluensulfonyl)sulfoximine (J. Am.Chem.Soc. 1973, S. 4287 and forth). Reagent ring extensions usually used in amounts of CO2 equivalent or more per equivalent of the compound of formula VII, more preferably from 2 to 3 equivalents. The reaction is preferably conducted in the presence of a base, preferably a basic compound of an alkali metal, such as alkali metal hydride such as sodium hydride; alkali metal hydroxide such as sodium hydroxide or potassium hydroxide; or alcoholate of an alkali metal, such as tert-butyl potassium.

There is no special restrictions regarding the nature of the employed solvent, provided that it has no adverse effect on the reaction or on the involved reagents. Examples of suitable solvents include sulfoxidov, such as dimethyl sulfoxide, ethers such as tetrahydrofuran.

The reaction can be carried out in a wide infodir convenient to conduct the reaction at temperatures from -20 to +130aboutS, more preferably from 0aboutC to the ambient temperature.

In any of the ways described above, when synthesized a racemate, it can optically be separated using any of the known methods, for example, through education crystalline salt with an optically active acid, such as 1-camphorsulfonic acid, and then select one of the active compounds of the racemate.

After completing any of the reactions described above, the desired compound can be isolated from the reaction mixture by standard methods. An example of this technique involves adding to the reaction mixture is not miscible with water, an organic solvent, washing the organic phase with water, drying the washed organic phase, and, finally, the distillation of the organic solvent to obtain the desired product. If necessary, the resulting compound can be further purified using conventional techniques of purification such as recrystallization, the resultant deposition rates, or the various chromatography techniques, namely chromatography on a column or preparative thin-layer chromatography.

Obtaining raw materials.

aetsa compound of the formula IIA, can be obtained, as shown in the following reaction scheme:

Reaction scheme A:

< / BR>
< / BR>
< / BR>
< / BR>
In the above formula R1, R2, R3, R4, R8, R9, R10, Y and Ar have the meanings defined above; and R10is hydroxyamides group, which can be any of hydroxyamides groups defined and described in the examples above in relation to R10.

In stage a1this reaction scheme ketone compound of formula VIII is subjected to interaction with ethyleneamines connection Grignard reagent of the formula

C (XIII) in which R1, R3and R4have the meanings defined above, and X represents MgZ, where Z is a halogen atom, e.g. chlorine, fluorine, bromine or iodine), giving the compound of formula IX.

This reaction is normally and preferably carried out in the presence of a solvent. There is no special limitation on the nature of the solvent, provided that it has no adverse effect on the reaction and that it can dissolve the starting material at least to some extent. Examples of preferred solvents include ethers, such as diethyl ether d The reaction can be carried out in a wide temperature range, and the particular reaction temperature is not critical for the invention. Basically, we find convenient to conduct the reaction at temperature from -20 to +30aboutC. the Time required for the reaction may also vary widely, depending on many factors, namely temperautre reaction and the nature of the reagents and solvent used. However, provided that the reaction is carried out in the preferred conditions outlined above, a period of from 30 minutes to 3 hours is usually sufficient.

In some cases, the reaction is more preferably can be carried out in the presence of a Lewis acid such as zinc chloride, tin chloride, titanium chloride, apirat boron TRIFLUORIDE or chlorine diethylaluminium.

The source material used in this stage may biete easily obtained according to the method described in Japanese patent provisional publication N Sho 63-46075 or Japanese Patent Publication N Sho 63-5390.

In stage a2the reaction scheme of the hydroxy-group in the compound of formula IX is protected by a suitable protecting group. There are no special restrictions regarding the nature of the input protecting group, provided that it protects the hydroxy-group and prevents its participation iteni to be used here, and the details of such groups and the methods used for their introduction can be found in Green et al, "Proter tive Groups in Orgavic Synthesis, chief 2, publ. Wiley-Interscience (1981).

Examples of such protecting groups are given above, and the method chosen for including such a protecting group is, of course, depend on the nature of the input group and is well known. They can be found in the work of Protective Groups in Organic Synthesis, by which the link above.

In stage a3, a carbonyl compound of the formula XI obtained by oxidative cleavage of the vinyl compounds of the formula X obtained as described in stage a2.

This reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions regarding the nature of the employed solvent, provided that it has no adverse effect on the reaction and can dissolve the starting material at least to some extent. Examples of preferred solvents include halogenated hydrocarbons, especially halogenated, alifaticheskii hydrocarbons, such as methylene chloride or chloroform, esters such as ethyl acetate or propyl; ketones, such as acetone; or ethers, such is the nature of the reagent, used for oxidation, provided that it can oxidation to cleave the double bond, giving a carbonyl group, and there can be used any oxidizing agent known for reactions of this type. The reaction may preferably be carried out by passing ozone through a solvent (such as galoidirovaniya plodored or ester) with a suitable temperature, for example when temperautre from -78aboutWith up to room temperature, and then by processing the product sulfides such as dimethyl sulfide. Alternatively, the reaction can be carried out with a suitable temperature, for example, from 0 to 50aboutWith, using from 2 to 4 equivalents of alkali-metal salts metaperiodic acid, such as metaperiodate sodium in a suitable solvent, a mixture of water and ether or ketone, in the presence of catalytic amounts of osmium oxide, such as tetrakis OS. The time required for the reaction may vary widely depending mainly on the reaction temperature and the nature of the source material and the solvent, and the reaction usually ends within a period of from 3 to 10 PM

On stage AND4the alcohol of formula XII Pius Grignard.

This reduction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction and that it can dissolve at least to some extent the source material. Examples of preferred solvents include ethers, such as tetrahydrofuran, dioxane or dimethoxyethane; and alcohols, such as methanol, ethanol or propanol.

Recovery can be carried out in accordance with conventional methods and preferably by using conventional reducing agents such as metal hydrides, preferably, borhydride alkali metal (e.g. sodium borohydride).

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not critical to this invention. Usually we consider convenient to carry out the reaction at a temperature of from -30aboutWith up to room temperature. The time required for the reaction may also vary widely, depending on many factors, namely, depending on the reaction temperature and the nature of the reagents and Rast is enough is a reaction period of from 5 minutes to 3 o'clock

Reaction using a Grignard reagent may be, for example, by using a Grignard reagent of formula R12-X, in which R12represents an alkyl group having from 1 to 4 carbon atoms (e.g. methyl, ethyl, sawn, ISO-propyl, boutelou, isobutylene, second-boutelou or tert-boutelou group), and X represents MgZ, where Z represents a halogen atom. This reaction is usually predpochtitelno is carried out in a solvent and can be carried out in accordance with standard procedure.

There are no special restrictions on the nature of the employed solvent, provided that it has no adverse effect on the reaction or involved in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol-dimethyl ether.

The reaction may proceed in a wide range of temperatures, and the precise temperautre reaction is not critical for the invention. Usually we consider convenient to conduct the reaction at temperatures from -20 to +30aboutC. Remacle and the nature of the reagents. However, provided that the reaction is carried out under the above preferred conditions are usually sufficient period of from 30 minutes to 3 hours

On stage AND5the compound of formula IIa is obtained by the conversion of free alcoholic hydroxy-group of compounds of formula XII in nucleophilic remove the group Y. This reaction is normally and preferably carried out in a solvent, in the presence or absence of a base. At the same time, if necessary, hydroxyamides group R10also can be deleted.

The nature of the reaction, of course, depends on the nature of the nucleophilic delete groups that you want to enter.

For example, in the case of haloiding, the reaction may be carried out by exposure to the interaction of the compounds of formula XII with the usual palodiruyut agent type, well known for the reaction of haloiding this species. Examples of preferred Ganoderma agents include thionylchloride, such as thionyl chloride, thienylboronic or tionalized; sulphonylchloride, such as sulphonylchloride or sulfanilamide; trihalogen phosphorus, such as phosphorus trichloride, or trichromacy phosphorus; pentachloride phosphorus, such as p is CIS phosphorus or bromacil phosphorus. One of them we preferred oxychloride phosphorus and thionylchloride.

If sulfanilamide reaction can be carried out by administering the compounds of formula XII in the reaction with the compound of the formula R11SO2-O-SO2R11(where R11represents a lower alkyl group, preferably having from 1 to 4 carbon atoms (such as methyl or ethyl group), a halogenated lower alkyl group, preferably having from 1 to 4 carbon atoms (such as triptorelin or panafcortelone group) or aryl group (such as benzene - or p-colorgroup) or with the compound of the formula R11SO2-Y (where R11and Y have the meanings defined above, and Y is preferably halogen, e.g. chlorine atom).

This reaction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction and it is at least to some extent, can dissolve the starting material. Examples of preferred solvents include aromatic hydrocarbons such as benzene, toluene or xylene; halogenated; the false esters, such as ethyl acetate or propyl; ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane and amides, especially amides of fatty acids, such as dimethylformamide, dimethylacetamide or hexamethylphosphoric triamide.

Similarly there are no particular limitations as to the nature of used grounds, provided that it can be used as a base in conventional reactions of this type. Examples of preferred bases include inorganic bases, especially basic compounds of alkali metal, such as hydrides of alkali metals (e.g. lithium hydride, sodium hydride or potassium hydride); organic bases, especially tertiary amines, such as triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N, N-dimethylamino)pyridine, N, N-dimethylaniline, 1,5-diazabicyclo(4.3.0) non-5-ene, 1,4-diazabicyclo(2.2.2)octane, 1,8-diazabicyclo(5.4.0)undec-7-ene (DWI) and the organic base in the form of metal compounds, especially alkali metals, such as utility or sitedisability.

The reaction can be carried out in a wide temperature range, and accurate temperautre reaction is not essential for the invention. Usually the>TheWith up to room temperature. The time required for the reaction may also vary widely, depending on many factors, namely the reaction temperature and the nature of the reagents and solvents. However, if the reaction is carried out in the preferred conditions described above, is usually sufficient period of from 5 minutes to 10 o'clock

If desired hydroxyamides group can be removed or at this point in time, or immediately prior stage AND5to obtain the compounds of formula IIa in which R10represents a hydrogen atom.

Although the reaction conditions for the implementation unprotect hydroxyamino group change depending on the nature of the protecting group, the reaction can be carried out in accordance with methods well known in the art, for example, the following.

As hydroxyamino group is silyl group, it can usually be removed by treatment of compounds compound that can form the anion of fluorine, such as tetrabutylammonium. This reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions with regard to the character used dlsode substance at least to some extent. Preferred solvents include ethers, such as tetrahydrofuran or dioxane.

The reaction may proceed in a wide temperature range, but the precise reaction temperature is not essential for the invention. Usually we find it convenient to carry out the reaction at about room temperature. The time required for the reaction may also vary widely, depending on many factors, namely the reaction temperature and the nature of the reagents. However, provided that the reaction is carried out in the preferred conditions described above, is usually sufficient period of from 10 to 18 o'clock

As hydroxyamide group applies aracelikarsaalyna group or kalkilya group, it usually can be removed by contacting a secure connection with the regenerating agent. For example, the reaction may be carried out by introducing a secure connection in the reaction of catalytic reduction at room temperature using such a catalyst as palladium on charcoal, platinum on Raney Nickel, preferably in the presence of a solvent. There are no special restrictions with regard to the nature of ispolzuemogo least to some degree to dissolve the starting material. Examples of preferred solvents include alcohols, such as methanol or ethanol; ethers, such as tetrahydrofuran or dioxane; and fatty acids such as acetic acid; or a mixture of one or more of these organic solvents and water.

The reaction can occur in a wide temperature range, but the precise reaction temperature is not critical for the invention. Usually we consider convenient to carry out the reaction at a temperature of from 0aboutWith up to room temperature. The time required for the reaction may also vary widely, depending on many factors, namely the reaction temperature and the nature of the reagents. However, provided that the reaction is carried out in the preferred conditions described above, is usually sufficient period of from 5 minutes to 12 o'clock

Alternative kalkilya and aracelikarsaalyna protective group can be removed by processing a secure connection metal lithium or sodium in liquid ammonia or alcohol, such as methanol or ethanol, at temperatures from -78 to -20aboutC.

Alternative kalkilya or aracelikarsaalyna group can be removed through reaction of the protected compound with combined is normally and preferably carried out in the presence of a solvent. There are no special restrictions related to the nature of the solvent used for the reaction, provided that it has no adverse effect on the reaction and at least to some extent, can dissolve the starting material. Examples of preferred solvents include NITRILES, such as acetonitrile, and halogenated hydrocarbons, especially halogenated aliphatic hydrocarbons, such as methylene chloride or chloroform, and mixtures of any two or more of them.

The reaction can take place in a wide temperature range, but the precise reaction temperature is not critical for the invention. Usually we find it convenient to carry out the reaction at a temperature of from 0 to 50aboutC.

In this process, when the substrate, the compound of formula XII, contains one or more sulfur atoms, the preferred reagent is a combination of aluminum chloride and iodine sodium.

When hydroxyamino group is an aliphatic acyl group, aromatic acyl group or alkoxycarbonyl group, it may be removed by treatment of the protected compound in the presence of a solvent. There are no special restrictions with regard to the use of a junction. Examples of preferred bases include metal alcoholate, such as sodium carbonate or potassium carbonate, alkali metal hydroxide, such as sodium hydroxide or potassium hydroxide, or a mixture of concentrated aqueous ammonia and methanol. In regard to the nature of the solvent there are no particular restrictions, and the usual solvent normally used for conventional reactions of hydrolysis, can be used here equally. Examples of preferred solvents include water, organic solvents, such as alcohols (e.g. methanol, ethanol or propanol) and ethers (e.g. tetrahydrofuran or dioxane), or a mixture of any two or more of these solvents, especially mixtures of water and one or more organic solvents.

The reaction may proceed in a wide temperature range, but the precise reaction temperature is not critical for the invention. Usually, in order to suppress side reactions, we find it convenient to carry out the reaction at a temperature of from 0 to 150aboutC. the Time required for the reaction may also vary widely, depending on many factors, namely the reaction temperature and the nature of the reagents, the solution is described above, usually it is sufficient a period of 1 to 10 hours

When hydroxyamino group is alkoxymethyl group or a substituted ethyl group, it usually can be removed by processing secure connections acid, preferably in the presence of a solvent. Suitable acids used are preferably hydrochloric acid, a mixture of acetic and sulfuric acids, p-toluensulfonate; alternative can also be used strongly acidic cation exchange resin, such as Dowex (trademark) 50. There are no special restrictions regarding the nature of the solvent, provided that it does not exert adverse influence on the reaction and can dissolve the starting material, at least to some extent. Preferred solvents are alcohols, such as methanol or ethanol, ethers, such as tetrahydrofuran or dioxane, mixtures of any two or more of them, and mixtures of any one or more of them and the water.

The reaction can occur in a wide temperature range, but the precise reaction temperature is not critical for the invention. Usually we consider convenient to carry out the reaction at a temperature of from 0 to 50aboutC. the Time required is eacli and the nature of the reagents and acids. However, with the proviso that the reaction is carried out in the preferred conditions described above, is usually sufficient period of from 10 minutes to 18 hours

When hydroxyamide group is altneratively group, it can usually be removed by processing a secure connection base in the reaction conditions, the same conditions that apply when hydroxyamino group is an aliphatic acyl group, aromatic acyl group or alkoxycarbonyl group.

Further, when hydroxyamino group is allyloxycarbonyl group, the reaction of removing the protection can be carried out simply using a combination of palladium and triphenylphosphine or tetracarbonyl Nickel, which has the advantage that it reduces to limit adverse reactions.

After completion of each of the reactions described above, the desired compounds can be emitted from the reaction mixture according to conventional methods. One example of such methods involves adding is not miscible with water and organic solvent to the reaction mixture, washing the organic base with water, drying the washed organic phase, and the distillation of organic race be purified using well-known methods, for example, using recrystallization, the resultant deposition rates, or the various chromatography techniques, namely preparative thin-layer chromatography or chromatography on a column.

An alternative method of obtaining the compounds of formula IIa is illustrated by the following schematic reaction:

The reaction scheme IN

Triz-CR8R= CH2< / BR>
Triz-CR8RH2Triz-CR8ROH

Stage B3 _ (IIa)

In the above formulas, R1, R3, R4, R8, R9, R12and Ar have the meanings defined above, and Triz means 1-1,2,4-triazole-1-ilen group which has the formula

< / BR>
Alternatively, the compound of formula XII in which R12represents a hydrogen atom, in other words, the compound of formula XIIc, can be obtained from compounds of formula XV, see reaction scheme A, as shown in the following reaction scheme:

The reaction scheme WITH

Trz-CR8R= O

In the above reaction scheme, R1, R3, R4, R8, R9, Ar and Triz have the meanings given above.

The compound of formula VIII, which is a starting material in reaction scheme a, and thus in the reaction schemes above, can be obtained, as shown in roar> and Ar have the meanings defined above.

The compound of formula III in which R8and R9both represent hydrogen atoms, which is a compound of formula IIIA, used as starting material in the method, can be obtained, as shown in the following reaction scheme F:

Reaction scheme F

< / BR>
HO Y

In the above reaction scheme, R1, R2, R3, R4, R and Ar have the meanings defined above.

In stage F1 above reaction scheme derived paxilbuy acid of formula XX is subjected to a photochemical reaction with the compound of the formula VI

(VI) in which R1, R2, R3and R4have the meanings given above.

The compound of formula III in which R8and R9can represent either hydrogen atoms or carbon atoms having from 1 to 4 carbon atoms, and Y represents a chlorine atom, can be obtained as shown in reaction scheme G:

The reaction scheme G

Cl

This reaction can be carried out using conventional techniques, for example, as described by the authors T. Sato, and K. Tamura in the journal Tetrahedron Letters, 25 so, S. 1821-1824, 1984. The compound of formula XIX, which is a starting material, can be photoroll R10represents a hydrogen atom, and R2methyl group, i.e. the compound of formula XIIe, can also be obtained, as shown in the reaction scheme N.

The reaction scheme N

Triz= CH2TrizCR8ROH

In the above formulas, R1, R3, R4, R8, R9, Ar and Triz have the meanings given above.

Upon completion of each of the above reactions, the desired compound can be released from the reaction mixture by conventional means. An example of such method involves adding to the reaction mixture is not miscible with water, an organic solvent, washing the organic phase with water, drying the washed organic phase, and the distillation of the organic solvent to obtain the desired product. If necessary, the resulting compound can be further purified using conventional purification techniques, for example by recrystallization, the resultant deposition rates or the various chromatography techniques, namely chromatography on a column or preparative thin-layer chromatography.

Compounds of the invention have a variety of valuable biological activity, as shown by the following experiments, which makes them useful in the quality of the clusters of the present invention is illustrated by the following examples, while gaining some of the starting compounds used in these examples is illustrated by the following preparative examples.

P R I m e R 1. (2R*,3S*,4R*)-2-(2,4-Di-forfinal)-3,4-dimethyl-2-[(1H-1,2,4-tri - azole-1-yl)methyl]oxetane, as well as its oxalate and nitrate.

309 mg of an aqueous solution of methylmercaptan sodium, having a concentration of about 15% was added to a solution of 389 mg (2R*,3S*,4S*)-2-(2,4-differenl)[-4-(methane - sulfonyloxy)-3-methyl-1H- (1H-1,2,4-triazole-1-yl)-2-pentanol] obtained in accordance with preparative example 2(C) of 4,5-epoxysilane having low polarity of the stereoisomers obtained in accordance with preparative example 2(a), representing one of the isomers of oxetane in position WITH4/ in 10 ml of methanol. The resulting mixture was stirred over night at room temperature and then poured into a mixture of ice water, after which extraction was performed with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, then the solvent was removed by distillation under reduced pressure. The resulting oily residue (256 mg) was subjected to column chromatography through silica gel, using as is in the form of butter.

Mass spectrum (m/z): 279 (M+), 246, 231, 224, 213, 197, 182, 167, 149, 141, 127, 113, 101, 83.

NMR-spectrum (Dl3), h/million or 0.83 (3H, doublet of doublets, J 7.2 Hz); of 1.18 (3H, doublet, J 7 Hz); 3,18 (1H, quintet, J 7 Hz); 4,50 (1H, doublet, J of 14.5 Hz); 4,58 (1H, quintet, J 7 Hz); 4,94 (1H, doublet, J of 14.5 Hz); 6.8 or 6.9 (2H, multiplet); to 7.4 and 7.5 (1H, multiplet); 7,87 (1H, singlet); 8,24 (1H, singlet).

IR spectrum (liquid film),max. cm-1: 3100, 1610, 1600.

33 mg oksolinovoj acid was added to a solution of 100 mg of oxetane, synthesized as described above, dissolved in ethyl acetate, after which the purpose of the deposition of crystals was added hexane. The obtained crystals having a melting point 145-150aboutWith that collected by filtration to obtain 92 mg of the oxalate of the target compounds.

NMR-spectrum (hexadeuterated dimethyl sulfoxide), h/million of 0.74 (3H, doublet of doublets, J 7 Hz and 2 Hz); of 1.10 (3H, doublet, J 7 Hz); 2,7-4,5 (2H, broad singlet); 3,18 (1H, quintet, J 7 Hz); of 4.57 (1H, doublet, J of 14.5 Hz); of 4.66 (1H, quintet, J 7 Hz); is 4.93 (1H, doublet, J of 14.5 Hz); 7,05 (16, doublet of triplets, J of 8.5 Hz, 2.5 Hz); 7,2-7,4 (2H, multiplet); 8,80 (1H, singlet); to 8.40 (1H, singlet).

IR-spectrum (Nujol-trade name),max. cm-1: 3500, 3130, 28800-2300, 1740, 1610, 1600.

1 ml of nitric acid (platnost is e, in methylene chloride. The precipitated crystals were collected by filtration to obtain 115 mg of nitrate target compound, so pl. 160-177aboutC.

NMR-spectrum (hexadeuterated dimethylsulfoxid), h/million of 0.75 (3H, doublet of doublets, J 7 and 2 Hz); 1,1 (3H, doublet, J 7 Hz); 3,19 (1H, quintet, J 7 Hz); 4,59 (1H, doublet, J of 14.5 Hz); 4,70 (1H, quintet, J 7 Hz); is 4.93 (1H, doublet, J of 14.5 Hz); 7,05 (1H, doublet of triplets, J 8.5 and 3 Hz); 7,2-7,3 (1H, multiplet); 7,89 (1H, singlet); 8,53 (1H, singlet).

P R I m m e R 2. (2R*,3S*,4S*)-2-(2,4-Differenl)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan.

This substance is a stereoisomer of the compound of example 1 in position WITH4.

Following a methodology similar to that described in example 1, but using 221 mg of (2R*, 3S*,4R*)-2-(2,4-differenl)-4-(methane - sulfonyloxy)-3-methyl - 1-(1H-1,2,4-triazole-1-yl)-2-pentanol (stereoisomer of starting compound of example 1 in position WITH4obtained by processing stereoisomer of preparative example 2(a) as described in preparative examples 2(b) and 2(C)), obtained 43 mg of target compound in the form of butter.

Mass spectrum (M/Z): 280 (M++ 1), 279, 270, 256, 234, 224, 197, 179, 165, 151, 142, 127, 113, 101, 82.

NMR-spectrum (l3), h/million: 0,86 (3H, doublet of doublets, J 7 Hz and 2.5 Hz); a 1.11 (3H, doublet is); of 7.5 to 7.7 (1H, multiplet); to 7.93 (1H, singlet), of 8.28 (1H, singlet).

IR spectrum (liquid film),maxcm-1: 1610, 1600. By recrystallization of the oil from ethyl acetate was given a clean sample with a melting point 105-107aboutC.

P R I m e R 3. (2R*,3R*,4R*)-2-(2,4-Di-forfinal)-3,4-dimethyl-2-[(1H-1,2,4-tri - azole - 1-yl)methyl]oxetan.

This substance is a stereoisomer of the compound of example 1 in position WITH3.

Following a methodology similar to that described in example 1, but using 255 mg of (2R*, 3R*,4S*)-2-(2,4-differenl)-4-(IU - consultonline)-3-methyl - 1-(1H-1,2,4-triazole-1-yl)-2-pentanol (which was obtained by metilirovaniem as described in preparative example 2(C) main stereoisomeric component of the product obtained in accordance with preparative example 4, and represents a single isomer at position C4), received 135 mg of the target compound, having a melting point 100-110aboutC.

Mass spectrum (m/z): 279 (M+), 235, 224, 215, 197, 182, 166, 153, 141, 133, 127, 113, 101, 83.

NMR-spectrum (l3), h/million: of 1.37 (3H, doublet, J 6 Hz); of 1.39 (3H, doublet, J 7 Hz); 2,80 (1H, quintet, J 7 Hz); 4,63 (1H, quintet, J 7 Hz); of 4.67 (1H, doublet, J 14 Hz); 4,94 (1H, doublet, J 14 Hz); 6,6-6,8 (2H, multiplet); 7,0-7,2 (1H, mule is P R I m e R 4. (2R*,3S*,4R*)-2-(2-chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetan.

11 mg of 60% (wt.) dispersion of sodium hydride in mineral oil was added to a solution of 51 mg of (2R*,3S*,4S*)-2-(2-chlorophenyl)-4-(methanesulfonate)-3-methyl-1- (1H-1,2,4-triazole-1-yl)-2-pentanol (which was synthesized according to the method similar to that described in preparative example 2(b) and 2(C), which is derived from 4,5-epoxysilane with low polarity of the stereoisomers at position4obtained by the procedure similar to that described in preparative example 2(a) in 2 ml of dimethylformamide; the mixture is then stirred for 2 h at 60aboutC. after this time the mixture was poured into a mixture of ice water and was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The resulting oily residue was purified by the method of preparative thin-layer chromatography on silica gel using as developing solvent a mixture of hexane with ethyl acetate in a volume ratio of 1:2, to obtain 10 mg of the target compound in the form of butter.

Mass spectrum (m/z): 280 (M++ 2), 278 (M+), 259, 242, 222, 197, 195, 141, 139, 129, 111, 101, 89, 75.

NMR-80 (1H, doublet, J of 14.5 Hz); 5,19 (1H, doublet, J of 14.5 Hz); 7,2-7,6 (4H, multiplet); to 7.84 (1H, singlet); to 8.12 (1H, singlet).

P R I m e R 5. (2R*,3S*,4S*)-2-(2-chlorophenyl)-3,4-dimethyl)-1-[(1H-1,2,4-triazole-1 - yl)methyl]oxetan.

This compound is a stereoisomer of the compound of example 4 in position E4.

Following a methodology similar to that described in example 4, but using 50,7 mg of (2R*, 3S*, 4R*)-2-(2-chlorophenyl)-4-(methanol - phenyloxy)-3-methyl-1- (1H-1,2,4-triazole-1-yl)-2-pentanol (which was synthesized according to the method similar to that described in preparative examples 2(b) and 2(C) and which is a derivative of 4,5-epoxysilane high polarity of the stereoisomers at position4obtained by the procedure similar to that described in preparative example 2(a)) received 10 mg of target compound in the form of butter.

Mass spectrum (m/z): 280 (M++ 2), 278 (M+), 266, 253, 242, 222, 195, 141, 139, 129, 125, 111, 101, 89.

NMR-spectrum (l3), h/million of 0.99 (3H, doublet, J 7 Hz); of 1.12 (3H, doublet, J 7 Hz); 2,80 (1H, quintet, J 7 Hz); 4,19 (1H, quintet, J 7 Hz); of 4.66 (1H, doublet, J of 14.5 Hz); of 5.17 (1H, doublet, J of 14.5 Hz); of 7.2 to 7.7 (4H, multiplet); of 7.90 (1H, singlet); to 8.20 (1H, singlet).

P R I m e R 6. (2R*,3S*,4R*)-2-(2-chloro-4-forfinal)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan.

Kenlake)-3 - methyl-1-(1H-1,2,4-triazole-1-yl)-2-pentanol (which was synthesized by the method similar to the method described in preparative example 2, and which is a derivative of 4,5-epoxysilane with low polarity of the stereoisomers at position4obtained by the procedure similar to that described in preparative example 2(a)), received 86 mg of target compound in the form of butter.

Mass spectrum (m/z): 297 (M++ 2), 295 (M+), 280, 278, 260, 251, 240, 216, 215, 214, 213, 182, 160, 159, 158, 157, 147, 129, 123, 107, 94, 82.

NMR-spectrum (l3), h/million: of 0.94 (3H, doublet, J 7 Hz); 1.18 to (36, doublet, J 7 Hz); 3,18 (1H, quintet, J 7 Hz); to 4.62 (1H, quintet, J 7 Hz); 4,80 (1H, doublet, J of 14.5 Hz); 5,14 (1H, doublet, J of 14.5 Hz); the 6.9 to 7.0 (1H, multiplet); for 7.12 (1H, doublet of doublets, J 8.5 and 2.5 Hz); 7,50 (1H, doublet of doublets, J 8.5 Hz and 6.0 Hz); 7,83 (1H, singlet); 8,17 (1H, singlet).

P R I m e R 7. (2R*,3S*,4S*)-2-(2-Chloro-4-forfinal)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan.

This compound is a stereoisomer of the compound of example 6 in position WITH4.

Following a methodology similar to that described in example 4, but using 32 mg (2R*, 3S*, 4R*)-2-(2-chloro-4-forfinal)-4-(IU - consultonline)-3 - methyl-1-(1H-1,2,4-triazole-1-yl)-2-pentanol (which was synthesized in a manner analogous to the procedure described in preparative example 2(b) and 2(C) and which is a derivative of 4,5-epoxyamine the Oh in preparative example 2(a), received 14 mg of target compound in the form of butter.

Mass spectrum (m/z): 296 (M+): 279, 260, 213, 211, 204, 182, 171, 159, 157, 143, 129, 123, 107, 94, 82.

NMR-spectrum (l3), h/million: 0,98 (3H, doublet, J 7 Hz); to 1.15 (3H, doublet, J 7 Hz); and 2.79 (1H, quintet, J 7 Hz); 4,18 (1H, quintet, J 7 Hz); of 4.67 (1H, doublet, J of 14.5 Hz); 5,10 (1H, doublet, J of 14.5 Hz); 6,9-7,1 (1H, multiplet); 7,17 (1H, doublet of doublets, J 8.5 Hz and 2.5 Hz); to 7.68 (1H, doublet of doublets, J 8.5 and 6.5 Hz); of 7.90 (1H, singlet); by 8.22 (1H, singlet).

P R I m e R 8. (2R*,3R*)-2-(2-Chloro-4-forfinal)-3,4-dimethyl-2-[(1H-1,2,4-triazole - 1-yl)methyl]oxetan.

This substance is a stereoisomer of the compound of example 6 in position WITH3.

Following a methodology similar to that described in example 4, but using 139 mg of (2R*, 3R*)-2-(2-chloro-4-forfinal)-4-(methane-sulfonyloxy)-3-methyl - 1-(1H-1,2,4-triazole-1-yl)-2-pentanol (which was obtained by metilirovaniem main stereoisomeric component, isomeric WITH4synthesized by a method similar to that described in preparative example 4), received 91 mg of target compound in the form of crystals with a melting point 145-147aboutC.

Mass spectrum (m/z): 297 (M++ 2), 295, 260, 240, 213, 211, 198, 178, 159, 158, 149, 129, 123, 109, 98, 83.

NMR-spectrum (l3), h/1,32 million (doublet, J 7 Hz); doublets, J 8.5 and 2.5 Hz); 7,20 (1H, doublet of doublets, J 8.5 and 6 Hz); 6,69 (1H, singlet); 7,94 (1H, singlet).

P R I m e R 9. (2R*,3S*,4S*)-2-(4-Chloro-2-forfinal)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan.

Following a methodology similar to that described in example 4, but using 260 mg of (2R*, 3S*, 4R*)-2-(2-fluoro-4-chlorophenyl)-4-(IU - consultonline)-3 - methyl-1-(1H-1,2,4-triazole-1-yl)-2-pentanol (which was synthesized according to the method similar to that described in preparative examples 2(b) and 2(C) and which is a derivative of 4,5-epoxysilane with increased polarity of the stereoisomers at position4obtained by the method similar to that described in preparative example 2(a), received 150 mg of target compound in the form of butter.

Mass spectrum (m/z): 297 (M++ 2), 295 (M+), 280, 250, 240, 215, 214, 206, 179, 159, 158, 143, 129, 123, 109, 99, 82, 94.

NMR-spectrum (l3), h/0,84 million (3H, doublet of doublets, J 7 and 2.5 Hz); of 1.10 (3H, doublet, J 7 Hz); is 2.74 (1H, quintet, J 7 Hz); is 4.21 (1H, quintet, J 7 Hz); however, 4.40 (1H, doublet, J of 14.5 Hz); 4,80 (1H, doublet, J of 14.5 Hz); 7,14 (1H, doublet of doublets, J 10.5 and 2.0 Hz); 7,20 (1H, doublet of doublets, J 8 and 2.0 Hz); 7,56 (1H, triplet, J 8 Hz); to $ 7.91 (1H, singlet); by 8.22 (1H, singlet).

IR spectrum (liquid film),maxcm-1: 3120, 1610, 1570.

P R I m e R 10. (2R*,3S*,4R*)-2-(2-fluoro-4-chlorophenyl)-3,4-dimethane4.

Following a methodology similar to that described in example 4, but using 390 mg of (2R*, 3S*, 4S*)-2-(2-fluoro-4-chlorophenyl)-4-(methanesulfonate)-3 - methyl-1-(1H-1,2,4-triazole-1-yl)-2-pentanol (which was synthesized in the manner similar to that described in preparative examples 2(b) and 2(C) and which is a derivative of 4,5-epoxysilane with reduced polarity of the stereoisomers at position4obtained in the manner similar to that described in preparative example 2(a)), was obtained 220 mg of target compound in the form of butter.

Mass spectrum (m/z): 297 (M++ 2), 295 (M+), 247, 240, 215, 214, 182, 159, 158, 157, 147, 129, 122, 107, 94, 82.

NMR-spectrum (l3), h/million or 0.83 (3H, doublet of doublets, J 7 and 2 Hz); of 1.17 (3H, doublet, J 7 Hz); 3,19 (1H, quintet, J 7 Hz); 4,49 (1H, doublet, J of 14.5 Hz); of 4.57 (1H, quintet, J 7 Hz); the 4.90 (1H, doublet, J of 14.5 Hz); to 7.0, and 7.1 (1H, multiplet); to 7.15 (1H, doublet of doublets, J 8.5 and 2.0 Hz); 7,46 (1H, triplet, J 8.5 Hz); 7,86 (1H, singlet); 8,21 (1H, singlet).

IR spectrum (liquid film),maxcm-1: 3110, 1610, 1570.

P R I m e R 11. (2R*,3S*,4R*)-2-(2,6-di-forfinal)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan.

Following a methodology similar to that described in example 4, but using 120 mg of (2R*, 3S*, 4S*)-2-(2,6-differenl)-4-(methane-sulfonyloxy)-3-methyl - 1-(1H-1,2,4-t(b) and 2(C) and which is a derivative of 4,5-epoxysilane with low polarity stereo - isomers in position WITH4obtained in the manner similar to that described in preparative example 2(a)), obtained 63 mg of target compound in the form of butter.

Mass spectrum (m/z): 297 (M+), 224, 197, 179, 166, 151, 141, 127, 113, 101, 82.

NMR-spectrum (l3), h/million of 1.00 (3H, doublet of triplets, J 7 and 1 Hz); of 1.24 (3H, doublet, J 7 Hz), 3,20 (1H, quintet, J 7 Hz); of 4.57 (1H, quintet, J 7 Hz); 4,60 (doublet, J of 14.5 Hz); 4.92 in (1H, doublet, J of 14.5 Hz); 6,86 (2H, triplet, J 9 Hz); 7,2-7,3 (1H, multiplet); 7,87 (1H, singlet); 8,31 (1H, singlet).

P R I m e R 12. (2R*,3S*,4S*)-2-(2,6-di-forfinal)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan.

This compound is a stereoisomer of the compound of example 11 in position WITH4.

Following a methodology similar to that described in example 4, but using 121 mg (2R*, 3S*,4R*)-2-(2,6-differenl)-4-(methane - sulfonyloxy)-3-methyl - 1-(1H-1,2,4-triazole-1-yl)-2-pentanol (which was synthesized in the manner similar to that described in preparative examples 2(b) and 2(C) and which is a derivative of 4,5-epoxysilane with increased polarity of the stereoisomers at position4obtained in the manner similar to that described in preparative example 2(a)), received 54 mg of target compound in the form of butter.

Mass spectrum (m/z): 279 (M+), 261, 235, 224, 206, bet, J 7 Hz); 2,82 (1H, quintet, J 7 Hz); of 4.38 (1H, quintet, J 7 Hz); 4,55 (1H, doublet, J of 14.5 Hz); a 4.83 (1H, doublet, J of 14.5 Hz); 6,8-7,0 (2H, multiplet); 7,2-7,4 (1H, multiplet); a 7.92 (1H, singlet); with 8.33 (1H, singlet).

P R I m e p 13. (2R*,3S*)-2-(2,4-differenl)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)me - til]oxetan.

Following a methodology similar to that described in example 1, but using 100 mg (2R*, 3S*)-2-(2,4-differenl)-4-(methanesulfonate)-3-methyl-1- (1H-1,2,4-triazole-1-yl)-2-butanol (which was synthesized by a method similar to that described in preparative example 7), received 54 mg of target compound in the form of butter.

Mass spectrum (m/z): 265 (M+), 247, 232, 224, 184, 165, 153, 141, 133, 127, 113, 101, 94, 82.

NMR-spectrum (l3), h/million of 0.93 (3H, doublet of doublets, J 7 Hz and 2 Hz); 3.15 in (1H, sextet, J 7 Hz); 3,99 (1H, triplet, J 7 Hz); 4,37 (1H, doublet of doublets, J 7 and 6 Hz); 4,48 (1H, doublet, J 7 Hz); the 4.90 (1H, doublet, J of 14.5 Hz); 6,8-7,0 (2H, multiplet); 7,2-7,4 (1H, multiplet); of 7.90 (1H, singlet); 8,30 (1H, singlet).

P R I m e R 14. 2-(2,4-Differenl)-4-methyl-2-[(1H-1,2,4-triazole-1-yl)-methyl]oaks - tan.

Following a methodology similar to that described in example 4, but using 590 mg of 2-(2,4-differenl-4-(methanesulfonate)-4-me - til-(1H-1,2,4 - triazole-1-yl)-2-butanol (which was synthesized from chloride Allemagne similar method on the SP and one of the stereoisomers at position4as the main product in the form of butter.

Mass spectrum (m/z): 265 (M+), 250, 224, 202, 184, 183, 142, 141, 133, 127, 119, 113, 99, 83.

NMR-spectrum (l3), h/million of 1.28 (3H, doublet, J 7 Hz); 2,35 (1H, doublet of quartets, J 8 and 6 Hz); 3,10 (1H, doublet of doublets, J 8 and 7 Hz); 4,34 (1H, doublet, J of 14.5 Hz); 4,3-4,5 (1H, multiplet); 4.72 in (1H, doublet, J of 14.5 Hz); 6.8 or 6.9 (2H, multiplet); to 7.4 and 7.5 (1H, multiplet); of 7.90 (1H, singlet); to 8.20 (1H, singlet).

IR spectrum (liquid film),maxcm-1: 1610, 1600, 1500.

P R I m e R 15. (2R*,3S*)-2-(2,4-Differenl)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)- methyl]oxetan and nitrate.

Following a methodology similar to that described in example 1, but using 72 mg of (2R*, 3S*)-2-(2,4-dichlorophenyl)-4-(methanol - phenyloxy)-3-methyl-1- (1H-1,2,4-triazole-1-yl)-2-butanol (which was synthesized by a method similar to that described in preparative example 7), received 25 mg of target compound in the form of butter.

NMR-spectrum (l3), h /million of 1.05 (3H, doublet, J 7 Hz); 3.15 in (1H, multiplet); 3,90 (1H, doublet of doublets, J 6 and 5.5 Hz); of 4.38 (1H, doublet of doublets, J 7 and 6 Hz); of 4.67 (1H, doublet, J of 14.5 Hz); 5,16 (1H, doublet, J of 14.5 Hz); and 7.1 and 7.6 (3H, multiplet); 7,88 (1H, singlet); to 8.20 (1H, singlet).

IR-spectrum (l3),max. cm-1: 1590, 1275, 1137, 975.

About 0.1 ml of ether Rasi cooling system with ice. The mixture is then processed in traditional ways to obtain 17 mg of nitrate of target compound in the form of crystals with a melting point of 162 to 165 of theaboutC.

P R I m e R 16. (2R*,3S*)-2-(2,4-dichlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetan and nitrates.

0.5 ml of an aqueous solution containing 15 wt./about. methylmercaptan sodium, was added to a solution of 54 mg of the mixture in the ratio 1:1 WITH4stereoisomers nelfinavir (which was obtained from a mixture in the ratio 1:1 WITH4stereoisomers (2R*,3S*)-2-(2,4-dichlorophenyl)-3-methyl-1-(1H-1,2,4-triazole-1 - yl)- 2,4-pentanediol (which was synthesized by a method similar to that described in preparative example 4) in 1 ml of dimethylformamide. Then the resulting mixture was stirred for 2 h at 50-60aboutC and then processed according to the method similar to that described in example 1. The resulting crude product was purified by the method of preparative thin layer chromatography through silica gel, using a mixture (in the ratio 3:1) of ethyl acetate and hexane as a showing agent, to obtain 8 mg of stereoisomer A (low polarity) and 10 mg of stereoisomer (high polarity), both substances were in the form of butter.

Stereoisomer (2R*,3S*,4S*):

NMR spectrum a doublet, J 15 Hz); 5,12 (1H, doublet, J 15 Hz); 7,31 (1H, doublet of doublets, J 9 and 2 Hz); 7,46 (1H, doublet, J 2 Hz); 7,71 (1H, doublet, J 9 Hz); of 7.90 (1H, singlet); to 8.20 (1H, singlet).

Stereoisomer (2R*,3S*,4R*):

NMR-spectrum (l3), h/million of 0.92 (3H, doublet, J 7 Hz); of 1.17 (3H, doublet, J 7 Hz); 3,17 (1H, quintet, J 7 Hz); 4,59 (1H, quintet, J 7 Hz); 4.72 in (1H, doublet, J 15 Hz); further 5.15 (1H, doublet, J 15 Hz); 7,20 (1H, doublet of doublets, J 9 and 1.5 Hz); 7,38 (1H, doublet, J 1.5 Hz); 7,50 (1H, doublet, J 9 Hz); 7,81 (1H, singlet); 8,13 (1H, singlet).

Each of these stereoisomers turned in his nitrate traditional ways, by adding an ethereal solution containing 5% nitric acid to a solution of the corresponding oceanologia connection with the cooling system with ice, to obtain the desired nitrate in the form of crystals.

Nitrate stereoisomer And had a melting temperature of 150-165aboutC.

Nitrate stereoisomer In had a melting point 160-164aboutC.

P R I m e R 17. 2-(2,4-Differenl)-2-[(1H-1,2,4-triazole-1-yl)methyl]-3,3,4 - trimethyloctane.

Following a methodology similar to that described in preparative example 2(a), two stereoisomer 4,5-epoxysilane was synthesized from 2-(2,4-differenl)-3,3-dimethyl-1-(1H-1,2,4-triazole-1-yl)-4 - penten-2-ol. Then stereoisomer low polarising in preparative example 4. Then the resulting material was metilirovanie according to the method described in preparative example 2(C) to obtain 2-(2,4-differenl)-3,3-dimethyl-4-(methane-sulfonyloxy)-1-(1H - 1,2,4-triazole-1-yl)-2-pentanol.

10 mg of sodium hydride was added to a solution of 77 mg of 2-(2,4-differenl-3,3-dimethyl-4-(methanesulfonate)-1-(1H-1,2,4 - triazole-1-yl)-2-pentanol in 1.5 ml of tetrahydrofuran while cooling with ice and stirring, after which was added 1 ml of methanol. After 10 min the reaction mixture was diluted with water and extracted with ethyl acetate. The resulting crude product was purified by the method of column chromatography on silica gel using mixtures of ethyl acetate and hexane in a ratio of 3:2 as eluent. The resulting compound was recrystallized from cyclohexane to obtain 39 mg of the pure sample of the target compound with a melting point 112-113aboutC.

NMR-spectrum (l3), h/0,86 million (3H, singlet); to 1.24 (3H, doublet, J 6 Hz); of 1.36 (3H, singlet); 4,72 (1H, doublet, J 15 Hz); 4,82 (1H, Quartet, J 6 Hz); 5,02 (1H, doublet, J 15 Hz); 6,5-7,4 (3H, multiplet); to 7.61 (1H, singlet); 7,94 (1H, singlet).

P R I m e R 18. 2-(2,4-Differenl)-2-[(1H-1,2,4-triazole-1-yl)-methyl]-3,3,4 - trimethyloctane.

This substance is stereonation example 2(a), two stereoisomer 4,5-epoxysilane was synthesized from 2-(2,4-differenl)-3,3-dimethyl-1-(1H-1,2,4-triazole-1-yl)-4 - penten-2-ol. Then stereoisomer with high polarity was converted into 2-(2,4-differenl)-3,3-dimethyl-1-(1H-1,2,4-tri - azole-1-yl)-2,4 - pentanediol in accordance with the procedure described in preparative example 4. Then this substance was metilirovanie according to the method described in preparative example 2(C) to obtain 2-(2,4-di - forfinal)-3,3-dimethyl-4-(methanesulfonate)-1-(1H - 1,2,4-triazole-1-yl)-2-pentanol.

Following a methodology similar to that described in example 17, but using 4-mesilate, obtained as described above, the received target connection and recrystallized it from a mixture of benzene and hexane to obtain pure sample with a melting point 93-94aboutC.

NMR-spectrum (l3), h/million of 0.93 (3H, doublet, J 2 Hz); of 1.34 (3H, singlet); the 1.44 (3H, doublet, J 6.5 Hz); 4,50 (1H, Quartet, J 6.5 Hz); to 4.81 (2H, singlet); of 6.6 and 7.1 (2H, multiplet); of 7.23 (1H, triplet of doublets, J 9 and 6 Hz); 7,60 (1H, singlet); of 7.96 (1H, singlet).

P R I m e R 19. (2R*,3S*,4R*)-2-(4-tri - formatexception)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan.

Following a methodology similar to that described in example 4, but using 250 mg of (2R*, 3S*,4S*)-2-(4-cryptomaterial described in preparative example 2(b) and 2(C) and which is a derivative of 4,5-epoxysilane with reduced polarity of the stereoisomers at position4obtained by the procedure similar to that described in preparative example 2(a)), obtained 82 mg of target compound in the form of butter.

Mass spectrum (m/z): 328 (M++ 1), 308, 272, 245, 214, 197, 190, 189, 175, 161, 141, 129, 115, 95, 82.

NMR-spectrum (l3), h /million 0,70 (3H, doublet, J 7.5 Hz); of 1.16 (3H, doublet, J 6.5 Hz); 3,18 (1H, quintet, J 7.5 Hz); of 4.35 (1H, doublet, J of 14.5 Hz); 4,39 (1H, doublet of quartets, J 7.5 and 6.5 Hz); 4,70 (1H, doublet, J of 14.5 Hz); 7,2-7,4 (4H, multiplet); to 7.93 (1H, singlet); 8,23 (1H, singlet).

IR spectrum (liquid film),maxcm-1: 1610, 1590, 1500, 1260, 1020.

P R I m e R 20. (2R*,3S*,4R*)-2-(4-Chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole - 1-yl)methyl]oxetan.

Following a methodology similar to that described in example 4, but using 230 mg of (2R*, 3S*, 4S*)-2-(4-chlorophenyl)-4-(methanol - phenyloxy)-3-methyl-1- (1H-1,2,4-triazole-1-yl)-2-pentanol (which was synthesized according to the method similar to that described in preparative example 2(b) and 2(C), which is a derivative of 4,5-epoxysilane with reduced polarity of the stereoisomers at position4obtained by the procedure similar to that described in preparative example 2(a)), received 112 mg of the target compound with a melting point 111-118aboutC.

Mass spectrum (m/z): 278 (M++ 1), 256, 222, 197, 164, 149, 141, 139, 7,25 Hz); to 4.41 (1H, doublet, J of 14.5 Hz); 4,4-4,53 (1H, multiplet); was 4.76 (1H, doublet, J of 14.5 Hz); of 7.25 (2H, doublet, J 8,46 Hz); of 7.36 (2H, doublet, J 8,46 Hz); 7,98 (1H, singlet); 8,42 (1H, singlet).

P R I m e R 21. 2-(4-Chlorophenyl)-3,3-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetan.

160 mg of sodium hydride (60 wt./wt. dispersion in mineral oil) was added to a solution of 750 mg of 2-(4-chlorophenyl)-3,3-dimethyl-4-methanesulfonate-1-(1H-1,2,4 - triazole-1-yl)-2-butanol in 12 ml of dimethylformamide and the resulting mixture was stirred at room temperature for 3 hours By the end of this time the reaction mixture was poured into a mixture of ice water and was extracted with ethyl acetate. The extract was washed with water, aqueous ammonium chloride solution, dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The resulting residue was purified by the method of preparative thin-layer chromatography using mixtures of ethyl acetate with hexane in a volume ratio of 1:4 as the developing solvent, to obtain 170 mg (yield 31%) of target compound, melting point 90-102aboutC.

NMR-spectrum (l3, 60 MHz), am/million of 0.90 (3H, singlet); to 1.38 (3H, singlet), 4,11 (1H, doublet, J 6 Hz); 4,50 (1H, doublet, J 6 Hz); 4,60 (1H, double (M+), 222, 195, 137.

P R I m e R s 22-32. Using a technique similar to that described in example 21 was synthesized following substances:

P R I m e R 22. 2-(2,4-Differenl)-2-[(1H-1,2,4-triazole-1-yl)methyl]-oxetan, in the form of oil, with a yield of 56%

NMR-spectrum (l3), h/2,66 million-2,77 (1H, multiplet), 2,93 totaling 3.04 (1H, multiplet); 4,15-to 4.23 (1H, multiplet); 4,34 (1H, doublet, J of 14.9 Hz); 4,43-to 4.52 (1H, multiplet); to 4.73 (1H, doublet, J of 14.9 Hz); for 6.81-6,93 (2H, multiplet); 7,39-of 7.48 (1H, multiplet); 7,94 (1H, singlet); of 8.27 (1H, singlet).

Mass spectrum (m/z): 251 (M+), 170, 141.

P R I m e R 23. 2-(2,4-Differenl)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oaks - tan, in the form of oil, with a yield of 73%

NMR-spectrum (l3), h/million of 0.93 (3H, doublet of doublets, J 7 and 2 Hz); 3.15 in (1H, sextet, J 7 Hz); 3,99 (1H, triplet, J 7 Hz); 4,37 (1H, doublet of doublets, J 7 and 6 Hz); 4,48 (1H, doublet, J of 14.5 Hz); the 4.90 (1H, doublet, J of 14.5 Hz); 6,8-7,0 (2H, multiplet); 7,2-7,4 (1H, multiplet); of 7.90 (1H, singlet); 8,30 (1H, singlet).

Mass spectrum (m/z): 265 (M+), 247, 232, 224, 184, 183.

P R I m e R 24. 2-(2,4-Differenl)-3-ethyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oaks-tan, in the form of oil, with a yield of 39%

NMR-spectrum (l3), h/million 0,70 (3H, triplet, J 7.5 Hz); 1,03-1,15 (1H, multiplet); 1,46-of 1.56 (1H, multiplet); 2,87 are 2.98 (1H, multiplet); 4,07 (1H, multiplet); 4,34 (1H, multipleinput).

Mass spectrum (m/z): 279 (M+), 224, 197, 141, 127.

P R I m e R 25. 2-(2,4-Differenl)-3,3-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetane, melting point 78aboutWith exit 72%

NMR-spectrum (l3), h/1,04 million (3H, singlet); USD 1.43 (3H, singlet); 4,18 (1H, doublet, J 5.6 Hz); to 4.62 (1H, doublet, J 5.6 Hz); 4,79 (1H, doublet of doublets, J 14.1 and 1,6 Hz); free 5.01 (1H, doublet, J 14.1 Hz); 6,68-6,83 (2H, multiplet); 7,1 (1H, double doublet of doublets, J of 6.5, 6.5 and 2.0 Hz); a 7.62 (1H, singlet); of 7.95 (1H, singlet).

Mass spectrum (m/z): 279 (M+), 261, 226, 197, 179, 167, 149.

P R I m e R 26. 2-(2,4-Differenl)-3-phenyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan received in the form of oil, yield 50%

NMR-spectrum (l3), h/million to 4.28 (1H, triplet, J 7.5 Hz); 4.53-in-to 4.62 (2H, multiplet); 5,00 (2H, doublet, J of 14.9 Hz); 6,37-of 6.45 (1H, multiplet); 6,83-of 6.90 (1H, multiplet); 7,00-to 7.15 (5H, multiplet); 7,47-7,56 (1H, multiplet); 7,98 (1H, singlet); at 8.36 (1H, singlet).

P R I m e R 27. 2-(4-Chlorophenyl)-3-ethyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan received in the form of an oil with a yield of 40%

NMR-spectrum (l3), h/0,63 million (3H, triplet, J and 7.3 Hz); 0,91-1,01 (1H, multiplet); 1.16 to-1,32 (1H, multiplet); 2,84-of 2.93 (1H, multiplet); of 4.05-4.09 to (1H, multiplet); 4,22-4,27 (1H, multiplet); to 4.38 (1H, doublet, J of 14.7 Hz); 4,74 (1H, doublet, J of 14.7 Hz); 7,25-7,39 (4H, multiplet); 7,97 (1H, singlet); 8,32 (1H, singlet).

With, exit 83%

NMR-spectrum (l3), h/million of 0.93 (3H, singlet); of 1.41 (3H, singlet); to 2.29 (3H, singlet); 4,19 (1H, doublet, J 5.6 Hz); 4,56 (1H, doublet, J 5.6 Hz); 4,63 (1H, doublet, J 14.1 Hz); 5,07 (1H, doublet, J 14.1 Hz); 6,99-7,02 (2H, multiplet); 7,07-7,10 (2H, multiplet); of 7.69 (1H, singlet); 7,80 (1H, the singlet).

Mass spectrum (m/z): 257 (M+), 202, 175.

P R I m e R 29. 2-(4-Isopropylphenyl)-3,3-dimethyl-2-[(1H-1,2,4-triazole-1-yl)me - til] oxetan received in the form of oil, yield 67%

NMR-spectrum (l3), h/million of 0.92 (3H, singlet); 1,21 (6N, doublet, J and 7.3 Hz); of 1.41 (3H, singlet); 2,80-2,90 (1H, multiplet); 4,19 (1H, doublet, J 5.6 Hz); 4,55 (1H, doublet, J 5.6 Hz); to 4.62 (1H, doublet, J of 14.3 Hz); 6,97-to 7.15 (4H, multiplet); of 7.69 (1H, singlet); to 7.77 (1H, singlet).

Mass spectrum (m/z): 285 (M+), 230, 203.

P R I m e R 30. 2-(4-Methoxyphenyl)-3,3-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan received in the form of oil, yield 29%

NMR-spectrum (l3), h/million of 0.92 (3H, singlet); of 1.41 (3H, singlet); of 3.77 (3H, singlet); 4,56 (1H, doublet, J 5.8 Hz); 4,59 (1H, doublet, J 5.8 Hz); to 4.62 (1H, doublet, J of 14.3 Hz); of 5.06 (1H, doublet, J of 14.3 Hz); 6,80-to 6.88 (2H, multiplet); of 6.96-7,24 (2H, multiplet); of 7.69 (1H, singlet); 7,81 (1H, the singlet).

Mass spectrum (m/z): 273 (M+), 218, 191.

P R I m e R 31. 3-Ethyl-2-(4-forfinal)-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan with a melting point 43-47about

Mass spectrum (m/z): 262 (M+), 246, 206, 179.

P R I m e R 32. 2-(2,4-Dichlorophenyl)-3,3-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan with a melting point 90-100aboutC was obtained with the yield 60%

NMR-spectrum (l3), h/million of 1.12 (3H, singlet); a 1.50 (3H, singlet); 4,13 (1H, doublet, J 5.8 Hz); to 4.62 (1H, doublet, J 5.8 Hz); 5,02 (1H, doublet, J of 14.3 Hz); at 5.27 (1H, doublet, J of 14.3 Hz); was 7.08 (1H, doublet of doublets, J 1,95 and to 8.45 Hz); 7,17 (1H, doublet, J to 8.45 Hz); to 7.35 (1H, doublet, J of 1.95 Hz); 7,66 (1H, singlet); with 8.05 (1H, singlet).

Mass spectrum (m/z): 315 (M+4)+, 313/(M+2)+/ 311 (M+), 276, 256, 231, 229, 199, 173.

P R I m e R 33. (2R*,3S*,4S*)-2-(2,4-Di-forfinal)-4-ethyl-3-methyl-2-[(1H-1,2,4-tri - azole-1-yl)methyl]oxetan.

960 mg (0.24 mmol) of sodium hydride (60% wt./wt. dispersion in mineral oil) was added under cooling with ice to a solution of 77.9 mg (0.2 mmol) of 2-(2-differenl-4-methanesulfonate-3-methyl-1-(1H-1,2,4-triazole - 1-yl)-2-hexanol 4.9 ml of dimethylformamide. Then the resulting mixture was stirred for 3 h at room temperature. Etta. The extract was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. The residue was purified by the method of preparative thin-layer chromatography using a mixture of hexane with ethyl acetate in a volume ratio of 2:1 as a developing solvent, to obtain 13,0 mg (yield of 22.2%) of target compound in the form of butter.

NMR-spectrum (l3), h/million of 0.82 (3H, triplet, J 7.5 Hz); of 0.87 (3H, doublet of doublets, J 2,42 and 6.9 Hz); 1.18 to of 1.34 (1H, multiplet); 1,36 of 1.50 (1H, multiplet); was 2.76 (1H, quintet, J 6.9 Hz); 3,98 (1H, Quartet, J 6,91 Hz); 4,39 (1H, doublet, J of 14.5 Hz); 4,79 (1H, doublet, J of 14.5 Hz); 6,82-6,97 (2H, multiplet); 7,56-the 7.65 (1H, multiplet); 7,88 (1H, singlet); 8,18 (1H, singlet).

Mass spectrum (m/z): 294/(M+1)+/ 224, 211.

P R I m e R 34-35. Using a technique similar to that described in example 3 was synthesized following compounds.

P R I m e R 34. (2R*,3S*,4S*)-4-ethyl-2-(4-forfinal)-3-methyl-2-[1H-1,2,4-triazole - 1-yl)methyl]oxetan received in the form of an oil with a yield of 7.5%

NMR-spectrum (l3), h/million to 0.73 (3H, doublet, J 7,1 Hz); of 0.82 (3H, triplet, J and 7.6 Hz); 1,11-of 1.44 (2H, multiplet);in 2.68 (1H, quintet, J and 17.1 Hz); 4,01 (1H, Quartet, J 7,1 Hz); the 4.29 (1H, doublet, J of 14.9 Hz); 4,59 (1H, doublet, J of 14.9 Hz); 7/SUP> + 1)+/, 193.

P R I m e R 35. (2R*,3S*,4S*)-2-(4-chlorophenyl)-4-ethyl-3-methyl-2-[(1H-1,2,4-triazole - 1-yl)methyl]oxetan received in the form of an oil with a yield of 8.0%

NMR-spectrum (l3), h /million is 0.69 (3H, doublet, J 7.0 Hz); of 0.79 (3H, triplet, J 7.5 Hz); 1,11-of 1.29 (1H, multiplet); 1,31-of 1.44 (1H, multiplet); 2,69 (1H, quintet, J 7.0 Hz); the 4.29 (1H, doublet, J of 14.9 Hz); 4,59 (1H, doublet, J of 14.9 Hz); 7,31 (2H, doublet, J 8.7 Hz); 7,40 (2H, doublet, J 8.7 Hz); of 7.97 (1H, singlet); compared to 8.26 (1H, singlet).

Mass spectrum (m/z): 292 /(M + 1)+/, 209.

P R I m e R 36. 3-tert-butyl-2-(4-forfinal)-2-[(1,2,4-triazole-1-yl)methyl]oxetan.

2,02 g (20 mmol) of triethylamine and to 2.29 g (20 mmol) chloride methanesulfonyl was added while cooling with ice, to a solution of 1.54 g (5 mmol) of 2-(4-forfinal)-3,5-dimethyl-1-(1H-1,2,4-triazole-1-yl)-2,4 - hexanediol in 75 ml of methylene chloride and the resulting mixture was stirred for 3 h at the same temperature and then at room temperature for 1 h By the end of this time the reaction mixture was stirred in 80 ml of a mixture of ice water and was extracted with 150 methylene chloride. The extract was washed with water and dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. The residue was purified by the method of column chromatography on silica gel (yield of 7.8%) of target compound with a melting point 128aboutC.

NMR-spectrum (l3), h/1,06 million (N, singlet); 2,28 (1H, doublet of doublets, J 12.1 and 14,30 Hz); of 2.64 (1H, doublet of doublets, J 1,21 and 14.3 Hz); 4.92 in (1H, doublet, J of 14.5 Hz); a total of 5.21 (1H, doublet, J of 14.5 Hz); equal to 4.97 (1H, doublet of doublets, J 1,21 and 12.1 Hz); 7,01-7,11 (4H, multiplet); to 7.77 (1H, singlet); 7,80 (1H, singlet).

Mass spectrum (m/z): 289 (M+), 207.

P R I m e R 37. 3-tert-butyl-2-(4-chlorophenyl)-2-[(1H-1,2,4-triazole-1-yl)methyl]oxalate.

Following a methodology similar to that described in example 36, the target compound was obtained in the form of oil, the yield of 3.4%

NMR-spectrum (l3), PM/1 million, 10 (N, singlet); of 2.27 (1H, doublet of doublets, J 11.7 and a 13.9 Hz); 2,62 (1H, broad doublet, J a 13.9 Hz); 4,96 (1H, doublet, J 12,5 Hz); 5,19 (1H, doublet, J 12,5 Hz); 7,16 (2H, doublet, J 8,3 Hz); 7,30 (2H, doublet, J 8,3 Hz); 7,81 (1H, broad singlet); 7,86 (1H, broad singlet).

Mass spectrum (m/z): 305 (M+), 223.

P R I m e R 38. 2-(4-Chlorophenyl)-4-isopropyl-2-[(1H-1,2,4-triazole-1-yl)-methyl] oxetan.

Following a methodology similar to that described in example 36, but using 700 mg (of 2.26 mmol) of 2-(4-chlorophenyl)-5-methyl-1-(1H-1,2,4-triazole-1-yl)-2,4-hexanediol received two stereoisomer in position 4 of the target compounds.

The yield of compound (A) having a lower polarity, amounted to 53.5 mg (8,1% ) and the outlet connection (In)>/P>NMR-spectrum (l3), h /million of 1.06 (3H, doublet, J 6.8 Hz); of 1.07 (3H, doublet, J 6.8 Hz); 1,96 (1H, septet, J 6.8 Hz); and 2.27 (1H, doublet of doublets, J 12.1 and 14.1 Hz); to 2.65 (1H, doublet of doublets, J 1.8 and a 14.1 Hz); 4,99 (1H, doublet, J of 14.5 Hz); 5,16 (1H, doublet, J of 14.5 Hz); 4,99-of 5.06 (1H, multiplet); ? 7.04 baby mortality (2H, doublet, J 8.7 Hz); 7.29 trend (2H, doublet, J 8.7 Hz); of 7.82 (1H, singlet); 7,88 (1H, singlet).

Mass spectrum (m/z): 291 (M+), 209.

Connection (IN):

NMR-spectrum (l3), h/million of 1.00 (3H, doublet, J and 7.3 Hz); 1,02 (doublet, J and 7.3 Hz); 1,88 is 2.00 (1H, multiplet); 2,77 (1H, doublet of doublets, J 3,2 and 14.5 Hz); 2,94 (doublet of doublets, J to 12.1 and 14.5 Hz); of 3.94 (1H, doublet of doublets, J 3,2; at 6.4 and 12.1 Hz); of 4.45 (1H, doublet, J of 14.3 Hz); 4,70 (1H, doublet, J of 14.3 Hz); 7,14 (2H, doublet, J 8.7 Hz); to 7.32 (2H, doublet, J 8.7 Hz); of 7.69 (1H, singlet); a 7.92 (1H, singlet).

Mass spectrum (m/z 291 (M+), 209.

P R I m e R 39. 3,3,4-Trimethyl-2-phenyl-(1H-1,2,4-triazole-1-yl)methyloxirane.

4,0 ml (from 37.6 mmol) of 2-methyl-2-butene was added to a solution of 1.1 g (5,88 mmol) of 2-(1H-1,2,4-triazole-1-yl)acetophenone in 15 ml of a mixture of acetonitrile and benzene in the ratio (vol. ) 2: 1. Then the mixture was irradiated using a mercury lamp, medium pressure power 450 W (Hanovia To. Inc.) within 15 hours after this time the reaction mixture was concentrated by evaporation under reduced pressure and estato is Oseni 1: 1 as eluent, obtaining 409,7 mg (yield 27%) of target compound with a melting point 102aboutC.

NMR-spectrum (l3), h/0,76 million (3H, singlet), of 1.26 (3H, doublet, J 6.4 Hz); of 1.36 (3H, singlet); with 4.64 (1H, doublet, J 14.1 Hz); 4,82 (1H, Quartet, J 5.4 Hz); 5,10 (1H, doublet, J 14.1 Hz); 7,1-7,3 (5H, broad multiplet); the 7.65 (1H, singlet); 7,76 (1H, singlet).

Mass spectrum (m/z): 258 (M + 1)+: 188, 175, 152, 144, 129.

P R I m e R s 40-44. Using a technique similar to that described in example 39 was synthesized following compounds.

P R I m e R 40. 2-(4-Isopropylphenyl)-2-(1H-1,2,4-triazole-1-yl)methyl-3,3,4 - trimethyloctane with a melting point 53-60aboutC was obtained with the yield of 4.4%

NMR-spectrum (l3), h/0,76 million (3H, singlet); 1,20 (6N, doublet, J 6.85 Hz); of 1.26 (3H, doublet, J of 6.45 Hz); of 1.35 (3H, singlet); 2,84 (1H, septet, J 6.85 Hz); to 4.62 (1H, doublet, J 14.1 Hz); to 4.81 (1H, Quartet, J of 6.45 Hz); 5,10 (1H, doublet, J 14.1 Hz); of 6.96 for 7.12 (4H, broad multiplet); of 7.69 (1H, singlet); 7,74 (1H, singlet).

Mass spectrum (m/z): 299 (M+), 230, 217.

P R I m e R 41. 2-(4-Methoxyphenyl)-2-(1H-1,2,4-triazole-1-yl)methyl-3,3,4 - trimethyloctane in the form of oil was obtained with the yield of 2.5%

NMR-spectrum (l3), h/million of 0.75 (3H, singlet); of 1.26 (3H, doublet, J 6,44 Hz); of 1.34 (3H, singlet); 3,76 (3H, singlet); 4,63 (1H, J 14.1 Hz); to 4.81 (1H, Quartet, J 6,44 Hz); the range of (m/z): 287 (M+), 218, 205, 135.

P R I m e R 42. 2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazole-1-yl)methyl-3,3,4 - trimethyloctane with a melting point 85-104aboutC was obtained with the yield of 3.2%

NMR-spectrum (l3), h/million of 0.92 (3H, singlet); to 1.24 (3H, doublet, J of 6.45 Hz); the 1.44 (3H, singlet); to 4.81 (1H, Quartet, J of 6.45 Hz); 5,00 (1H, doublet, J of 14.3 Hz); 5,26 (1H, doublet, J of 14.3 Hz); 7,06 (1H, doublet of doublets, J 2,02 and 8,86 Hz); 7,16 (1H, doublet, J 8,86 Hz); to 7.32 (1H, doublet, J 2,02 Hz); 7,63 (1H, singlet); 7,94 (1H, singlet).

Mass spectrum (m/z): 325 (M+), 312, 243, 175.

P R I m e R 43. 2-(4-Forfinal)-2-(1H-1,2,4-triazole-1-yl)methyl-3,3,4 - trimethyloctane with a melting point 108aboutC was obtained with the yield 15%

NMR-spectrum (l3), h/million of 0.74 (3H, singlet); of 1.26 (3H, doublet, J of 6.45 Hz); of 1.36 (3H, singlet); the 4.65 (1H, doublet, J 14.1 Hz); a 4.83 (1H, Quartet, J of 6.45 Hz); 5,08 (1H, doublet, J 14.1 Hz); 6,92-7,07 (4H, broad multiplet); to 7.67 (1H, singlet); of 7.90 (1H, singlet).

Mass spectrum (m/z): 276 (M+), 206, 147.

P R I m e R 44. 2-(4-Chlorophenyl)-2-(1H-1,2,4-triazole-1-yl)methyl-3,3,4-trimethylol - Satan with a melting point 111-114aboutC was obtained with the yield of 2%

NMR-spectrum (l3), h/million to 0.72 (3H, singlet); to 1.24 (3H, doublet, J of 6.35 Hz); of 1.33 (3H, singlet); to 4.62 (1H, doublet, J of 14.2 Hz); 4,80 (1H, Quartet, J of 6.35 Hz); of 5.06 (1H, doublet, J of 14.2 Hz); 6,8-7,24 (4H, broad multiplet) afterfeel)-3,3-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan.

2-Methylpropan was barbotirovany in 5 ml of benzene at 0aboutWith up to 25% increase in volume of the system. Then to the solution was added 6 ml of acetonitrile and 695,2 mg (3,115 mmol) 2',2'-debtor-2-(1H-1,2,4-triazole-1-yl)Aceto - none and the resulting mixture was irradiated with a mercury-arc lamps, medium pressure power 450 W (Hanovia To. Inc.), 15aboutC for 15 h, after this time the reaction mixture was concentrated and evaporated under reduced pressure and then the residue was subjected to chromatography on a column of silica gel to obtain 450 mg of the mixture of target compound with unreacted starting material. This mixture was dissolved in 5 ml of methanol and the resulting solution was added 200 mg (5,27 mmol) of sodium borohydride, after which the mixture was stirred for 3 h at the same temperature. By the end of this time the reaction mixture was diluted with water and extracted with ethyl acetate. Then the organic layer was dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure to obtain light yellow residue. This residue was subjected to chromatographicaliy on a column of silica gel using as eluent a mixture of hexane with ethyl acetate in a volume ratio of 1: 1, with p the obtained product was in all respects identical to the connection, obtained in example 25.

P R I m e R 46. 2-(4-Forfinal)-3,3-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan.

This example illustrates the synthesis of target compound by the expression.

Following a methodology similar to that described in example 39, but using 2-methylpropan and 4'-fluoro-2-(1H-1,2,4-triazole-1 - yl)acetophenone, with a yield of 2% was obtained target compound with a melting point of 110aboutC.

NMR-spectrum (l3), h/million of 0.92 (3H, singlet); USD 1.43 (3H, singlet); 4,20 (1H, doublet, J 5.6 Hz); 4,58 (1H, doublet, J 5.6 Hz); with 4.64 (1H, doublet, J 14.1 Hz); of 5.06 (1H, doublet, J 14.1 Hz); 6,97 (2H, triplet, J 8,86 Hz); 7,00-to 7.09 (2H, broad multiplet); to 7.68 (1H, singlet); 7,99 (1H, singlet).

Mass spectrum (m/z: 261 (M+), 179, 123.

P R I m e R 47. 8-(2,4-Differenl)-7-oxa-8-(1H-1,2,4-triazole-1-yl)netilmicin - lo (4.2.0)octane.

Following a methodology similar to that described in example 39, but using cyclohexane and 2',4'-debtor-2-(1H-1,2,4-triazole-1-yl)acetophenone, received a mixture of stereoisomers of the target compounds in the position 8 in the ratio of 1:1, in the form of resin with a yield of 31%

NMR-spectrum (l3), h /million of 1.0 to 2.2 (broad multiplet); 2,64 (broad doublet of triplets, J of 4.1 Hz); 3,03 (Quartet, J7,15 Hz); to 4.52 (doublet, J of 14.5 Hz); 4,60 (multiplet); 4,70 (doublet, J of 14.5 Hz); 4,89 (doublet, J); 7,81 (singlet).

P R I m e R 48. 2-(2,4-Differenl-3,3,4,4-tetramethyl-2-[(1H-1,2,4-triazole-1 - yl) methyl]oxetan.

Following a methodology similar to that described in example 39, but using 2,3-dimethyl-2-butene and 2',4'-debtor-2-(1H-1,2,4 - triazole-1-yl)acetophenone, received 85 mg (yield 15%) of target compound with a melting point 100-101aboutC.

NMR-spectrum (l3), h/million of 0.93 (3H, doublet, J 1,61 Hz); of 1.27 (3H, singlet); of 1.42 (3H, singlet); was 1.58 (3H, singlet); 4,48 (1H, doublet of doublets, J 1,61; 14,10 Hz); the 4.90 (1H, doublet, J 14,10 Hz); 6,65-PC 6.82 (2H, multiplet); 7,20 (1H, double doublet of doublets, J 2,01; 9,01 and 9,01 Hz); 7,60 (1H, singlet); to $ 7.91 (1H, the singlet).

Mass spectrum (m/z): 307 (M+), 294, 279, 224, 205, 167, 149, 141.

P R I m e R 49. (2R*,4R*)-2-(4-forfinal)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1-yl)- methyl]oxetan.

Following a methodology similar to that described in example 39, but using CIS-2-butene and 950 mg (of 5.68 mmol) of 4'-fluoro-2-(1H-1,2,4-triazole-1-yl)acetophenone, received 80 mg (yield of 5.3%) of a mixture of stereoisomers of the target compounds in the position 3 in the ratio 1:1, in the form of butter.

NMR-spectrum (l3), h/million 0,69 (doublet, J of 7.25 Hz); 1,16 (doublet, J of 6.45 Hz); 1,37 (doublet, J of 6.45 Hz); 2,79 (quintet, J of 7.25 Hz); 3.15 in (quintet, J of 7.25 Hz); 4,39 (doublet, J 14,50 Hz); 4,50 (multiplet); 4,60 (multiplet); 4,59 (doublet, J 14.1 Hz); 4,7; ,27 (singlet).

Mass spectrum (m/z: 261 (M+), 206, 179, 148, 133, 123.

P R I m e R 50. 2-(4-Were)-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetan.

0,98 g (25.5 mmol) of sodium hydride (60 wt./wt. dispersion in mineral oil) was added to 20 ml of dimethyl sulfoxide, and the resulting mixture was stirred for 1 h at 80aboutC. By the end of this time added 5,62 g (25.5 mmol) iodotope trimethylsulfoxonium cooling system with ice, after which the mixture was allowed to warm to room temperature. Then the mixture was stirred for 30 min and the solution was added 2.2 g (11.6 mmol) of 4'-methyl-2-(1H-1,2,4-triazole-1-yl)acetophenone in 5 ml of dimethyl sulfoxide, and the mixture was stirred for 6 h at 50aboutC. After cooling, the reaction mixture was poured into 20 ml of a mixture of ice water and was extracted with 200 ml of ethyl acetate. Then the extract is washed twice with 100 ml portions of a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure to obtain 2.7 g of oily compound. This oil was subjected to column chromatography on silica gel, mixture of hexane with ethyl acetate in a volume ratio of 1:1 as elwen the (3H, singlet); 2,6-2,7 (1H, multiplet); 2.91 in-2,98 (1H, multiplet); as 4.02-4,10 (1H, multiplet); the 4.29 (1H, doublet, J of 14.7 Hz); to 4.52 (1H, doublet, J of 14.7 Hz); of 4.38-to 4.46 (1H, multiplet); 7,22 (4H, singlet); 7,98 (1H, singlet); by 8.22 (1H, singlet).

Mass spectrum (m/z: 229 (M+), 214, 198, 184, 172, 159, 148, 119.

IR spectrum (liquid film),maxcm1:3140, 2980, 2950, 1505, 1271.

P R I m e R s 51-57. Using a technique similar to that described in example 50, synthesized the following compounds.

P R I m e EP 51. 2-(4-Chlorophenyl)-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetan with a melting point 74-75aboutC was obtained with the yield 61%

NMR-spectrum (l3), h/2,62 million is 2.75 (1H, multiplet); 2.95 and was 3.05 (1H, multiplet); 4,06-to 4.14 (1H, multiplet); 4,30 (1H, doublet, J of 14.5 Hz); 4,39 figure-4.49 (1H, multiplet); a 4.53 (1H, doublet, J of 14.5 Hz); 7,27 (2H, doublet, J 8,46 Hz); 7,38 (2H, doublet, J 8,46 Hz); 7,98 (1H, singlet); 8,24 (1H, singlet).

Mass spectrum (m/z): 249 (M+), 169, 139.

P R I m e R 52. 2-(2,4-Differenl)-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan in the form of oil was obtained with the yield 45%

NMR-spectrum (l3), h/2,66 million-2,77 (1H, multiplet); 2,93 totaling 3.04 (1H, multiplet); 4,15-to 4.23 (1H, multiplet); 4,34 (1H, doublet, J of 14.9 Hz); 4,43-to 4.52 (1H, multiplet); to 4.73 (1H, doublet, J of 14.9 Hz); for 6.81-6,93 (2H, multiplet); 7,39-of 7.48 (1H, multiplet); 7,94 (1H, singlet); of 8.27 (1H, the azole-1-yl)methyl] oxetan in the form of oil was obtained with the yield 87%

NMR-spectrum (l3), h /1,27 million (6N, doublet, J and 7.3 Hz); 2,17-of 2.72 (1H, multiplet); 2,90-a 3.01 (2H, multiplet); as 4.02-4,07 (1H, multiplet); the 4.29 (1H, doublet, J of 14.7 Hz); of 4.38-4,47 (1H, multiplet); to 4.52 (1H, doublet, J of 14.7 Hz); 7,27 (4H, singlet); 7,99 (1H, singlet); of 8.25 (1H, singlet).

Mass spectrum (m/z): 257 (M+), 175, 147.

P R I m e R 54. 2-(4-Triptoreline)-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan in the form of oil was obtained with the yield 42%

NMR-spectrum (l3), h/2,66 million-of 2.72 (1H, multiplet); 3,00-3,11 (1H, multiplet); 4,07-to 4.15 (1H, multiplet); 4,32 (1H, doublet, J of 14.9 Hz); 4,40-4,48 (1H, multiplet); of 4.57 (1H, doublet, J of 14.9 Hz); 7,47 (2H, doublet, J 8.1 Hz); to 7.68 (2H, doublet, J 8.1 Hz); 7,99 (1H, singlet); of 8.27 (1H, singlet).

Mass spectrum (m/z): 283 (M+), 201, 173.

P R I m e R 55. 2-(4-Forfinal)-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetan with a melting point 65-66aboutC was obtained with the yield 55%

NMR-spectrum (l3), h/2,61 million-of 2.81 (1H, multiplet); 2,94 totaling 3.04 (1H, multiplet); 4,06-4,16 (1H, multiplet); 4,30 (1H, doublet, J of 14.7 Hz); 4,40-4,48 (1H, multiplet); a 4.53 (1H, doublet, J of 14.7 Hz); 7,06 for 7.12 (2H, multiplet); 7,27-7,33 (2H, multiplet); 7,99 (1H, singlet); of 8.25 (1H, singlet).

Mass spectrum (m/z: 233 (M+), 151, 123.

P R I m e R 56. 2-(4-Methoxyphenyl)-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetan with a melting point 66-67aboutinglet); Android 4.04-to 4.14 (1H, multiplet); 4,30 (1H, doublet, J of 14.7 Hz); of 4.44-4,47 (1H, multiplet); 4,51 (1H, doublet, J of 14.7 Hz); 6,93 (2H, doublet, J 8,86 Hz); of 7.25 (2H, doublet, J 8,86 Hz); 7,98 (1H, singlet); 8,21 (1H, singlet).

Mass spectrum (m/z): 245 (M+), 163, 135.

P R I m e R 57. 2-(4-Chloromethylene)-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetan in the form of oil was obtained with the yield of 59%

NMR-spectrum (l3), h/2,66 million-2,77 (1H, multiplet); 2,94 totaling 3.04 (1H, multiplet); 4,08-to 4.23 (1H, multiplet); 4,34 (1H, doublet, J of 14.7 Hz); 4,39-4,51 (1H, multiplet); to 4.73 (1H, doublet, J of 14.7 Hz); 7,08-to 7.18 (2H, multiplet); 7,37-the 7.43 (1H, multiplet); 7,94 (1H, singlet); of 8.27 (1H, singlet).

Mass spectrum (m/z): 245 (M+), 163, 135.

P R I m e R 58. 2-(4-Were)-2-[1-(1,2,4-triazole-1-yl)ethyl]oxetan.

Following a methodology similar to that described in example 50, but using 4'-methyl-2-(1H-1,2,4-triazole-1-yl)propiophenone received in the form of oil, a mixture of stereoisomers (with different configuration triazole groups) of target compound in the approximate ratio of 2:1 (output to 49.3%).

NMR-spectrum (l3), h/1,33 million (doublet, J of 7.25 Hz); 2.37 (singlet); 2,44-2,53 (multiplet); 2.70 height is 2.80 (multiplet); 3,98-4,06 (multiplet); 4,37-4,47 (multiplet); 4,74 (Quartet, J of 7.25 Hz); 7,20 (singlet); 7,99 (singlet); a 8.34 (singlet).

Mass spectrum (m/z: 243 (M+), 228, 213, 147, 119.

The resulting product was identical with the compound obtained according to the method of example 52.

P R I m e R 60. 5-oxa-4-phenyl-[(1,2,4-triazole-1-yl)methyl]Spiro(2.3)hexane.

NMR-spectrum (l3), h/million of 0.3-0.9 (4H, multiplet); 4,37 (1H, doublet, J 5,46 Hz); of 4.44 (1H, doublet, J of 14.8 Hz); of 4.54 (1H, doublet, J 5,46 Hz); 4,85 (1H, doublet, J 14,80 Hz); 7,19-7,41 (5H, multiplet); 7,88 (1H, singlet); 8,32 (1H, singlet).

Mass spectrum (m/z: 242 (M+), 188, 172, 159.

P R I m e R 61. (2R*,3S*,4S*)-2-(4-Chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetan.

28 mg (1,003 mmol) of sodium hydride (60% wt./wt. dispersion in mineral oil) was added under ice cooling to a solution of 200 mg (0.59 mmol) of (2R*, 3S*,4S*)-2-(4-chlorophenyl)-3-met was stirred for 1.5 hours After this time the reaction mixture was treated in a manner similar to that described in example 60 with obtaining and 32.3 mg (yield of 19.7%) of target compound in the form of butter.

NMR-spectrum (l3), h/million to 0.73 (3H, doublet, J of 7.25 Hz); of 1.06 (3H, doublet, J 6,04 Hz); 2,66 (1H, quintet, J of 7.25 Hz); 4.26 deaths (1H, multiplet); or 4.31 (1H, doublet, J of 14.9 Hz); 7,30 (2H, doublet, J 8,66 Hz); 7,40 (2H, doublet, J 8,66 Hz); 8,01 (1H, singlet); scored 8.38 (1H, singlet).

Mass spectrum (m/z): 278 (M + 1)+, 222, 195, 139.

P R I m e R s 62-66. Using a technique similar to that described in example 61 was synthesized following compounds.

P R I m e R 62. (2R*,3R*,4S*)-2-(4-Chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyloxirane with a melting point 75-118aboutC was obtained with the yield of 8.0%

NMR-spectrum (l3), h/million of 1.39 (3H, doublet, J 6,04 Hz); of 1.42 (3H, doublet, J 4,88 Hz); 3,14 (1H, quintet, J 7,66 Hz); 4,60 (1H, doublet, J of 14.5 Hz); 4,74 (1H, doublet, J of 14.5 Hz); 4.92 in (1H, quintet, J is 6.54 Hz); 7,10 (2H, doublet, J 8,46 Hz); 7,26 (2H, doublet, J 8,46 Hz); 7,83 (1H, singlet); 8,13 (1H, singlet).

Mass spectrum (m/z): 277 (M+), 222, 195, 139.

P R I m e R 63. (2R*,3R*,4R*)-2-(4-Chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl] oxetan with a melting point 113-121aboutC was obtained with the yield of 70%

NMR-spectrum (l3), h/million of 1.37 (3H, d the years, J of 14.3 Hz); was 7.08 (2H, doublet, J 8,46 Hz); of 7.25 (2H, doublet, J 8,46 Hz); 7,78 (1H, singlet); with 8.05 (1H, singlet).

Mass spectrum (m/z): 278 /(M+ 1)/, 222, 195, 139.

P R I m e R 64. (2R*,3S*,4R*)-2-(4-Bromophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetan in the form of oil was obtained with the yield of 62.3%

NMR-spectrum (l3), h/million 0,70 (3H, doublet, J 7,66 Hz); of 1.16 (3H, doublet, J of 6.45 Hz); and 3.16 (1H, quintet, J 7,66 Hz); of 4.38 (1H, doublet, J of 14.5 Hz); 4,40-of 4.54 (1H, multiplet); 4.72 in (1H, doublet, J of 14.5 Hz); 7,19 (2H, doublet, J 8,66 Hz); 7,52 (2H, doublet, J 8,66 Hz); of 7.95 (1H, singlet); 8,30 (1H, singlet).

Mass spectrum (m/z): 322 /(M + 1)+/, 303, 266, 241, 185.

P R I m e R 65. (2R*,3S*,4R*)-2-(4-tri-formationl)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan received in the form of an oil with a yield of 45%

NMR-spectrum (l3), h /million of 0.71 (3H, doublet, J 7.7 Hz); of 1.17 (3H, doublet, J 6.4 Hz); 3,23 (1H, quintet, J 7.7 Hz); however, 4.40 (1H, doublet, J of 14.5 Hz); 4,42-4,48 (1H, multiplet); at 4.75 (1H, doublet, J of 14.5 Hz); 7,44 (2H, doublet, J 8.1 Hz); the 7.65 (2H, doublet, J 8.1 Hz); of 7.95 (1H, singlet); 8,30 (1H, singlet).

Mass spectrum (m/z): 312 /(M + 1)+/, 229, 173.

P R I m e R 66. (2R*,3R*)-2-(4-chloro-2-formationl)-3,4-dimethyl-2-[(1H-1,2,4 - triazole-1-yl)methyl] oxetan with a melting point 114-116aboutC was obtained with the yield of 93%

NMR-spectrum (l3), h/million 1,30-1,41 (6N, multiplet); 2,72-2,84 (1H, multipl is, the singlet).

Mass spectrum (m/z): 296 /(M + 1)+/, 256, 240, 215, 159.

P R I m e R 67. (2R*,3S*,4R*)-2-(4-Chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetan.

38 mg (0,950 mmol) of sodium hydride (60% wt./wt. dispersion in mineral oil) was added at 0aboutWith the suspension of 107 mg (0.351 mmol) of 2-(4-chlorophenyl)-3,4-dimethyl-2-methanesulfonylaminoethyl, 51,5 mg (0,746 mmol) of 1H-1,2,4-triazole, and 45.6 mg (0,304 mmol) iodine sodium in 10 ml of dimethylimidazolidine and the resulting mixture was stirred at room temperature for 30 min and then at 90aboutC for 12 hours then to the mixture was added aqueous sodium thiosulfate solution and extraction was performed with a mixture of ethyl acetate and hexane in a volume ratio of 1: 1. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The obtained residue was subjected to chromatography on a column of silica gel, was suirable mixture of hexane and ethyl acetate in a volume ratio of 1:1 with the receipt of 76.3 mg (yield 78%) of target compound.

Thus obtained compound was identical with the compound obtained in example 20.

P R I m e R 68. (2R*,3S*,4R*)-2-(4-Chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-the lo 61%) was added to a solution of 300 mg (1,08 mmol) of (2R*,3S*,4R*)-2-(4-chlorophenyl)-3,4-dimethyl - 2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetane (obtained according to the method of example 20) in a mixture of 5 ml of diethyl ether and 1 ml of methanol. The resulting mixture was separated from the solvent by distillation under reduced pressure and the resulting residue was mixed with a mixture of diethyl ether and hexane. Precipitated crystals were collected by filtration with education 351 mg (yield of 95.4%) of target compound with a melting point 129-142aboutC.

Elemental analysis for C14H17lN4O4.

Calculated C 49,35; H 5,03; Cl From The 10.40; N 16,44.

Found, C 49,28; H 5,15; Cl 10,32; N 16,64.

P R I m e R 69. (2R*,3S*,4R*)-2-(4-Chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetan oxalate.

The solution 97,2 ml oksolinovoj acid in ethyl acetate was bury to a solution of 300 mg (1,08 mmol) of (2R*, 3S*,4R*)-2-(4-chlorophenyl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetane (obtained according to example 20) in 5 ml of ethyl acetate and the precipitated crystals were collected by filtration. After drying, received 229 mg (yield 57,7% ) of target compound, with a melting point 135-144aboutC.

IR-spectrum (KBR),max. cm-1: 3424, 3119, 2908, 2516, 1967, 1731, 1610.

NMR-spectrum (hexadeuterated dimethyl sulfoxide), h/million of 0.61 (3H, doublet, J of 7.25 Hz); of 1.09 (3H, doublet, J of 6.45 Hz); 3,18 (1H, quintet, J of 7.65 Hz); 3,37 (wide singlet); 4,51 (1H, triplet, J of 7.25 Hz); 4,60 (1H, doublet, J 14,5 G R I m e R 70. 2-(2,4-Dichlorophenyl)-3,3,4-trimethyl-2-[(1H-1,2,4-triazole-1-yl)me - til] oxetan.

84 mg (2.1 mmol) of sodium hydride (60% wt./wt. suspension in mineral oil) was added to a solution of 400 mg (0.95 mmol) of 2-(2,4-dichlorophenyl)-3,3-dimethyl-4-methylsulfonylamino-1-[(1H-1,2,4 - triazole-1-yl]-2-pentanol in 5 ml of N,N-dimethylformamide, and then the mixture was stirred at 90aboutC for 2 h then the reaction mixture is advocated to cool and then poured into ice water and was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate, then the solvent was removed by distillation under reduced pressure. The residue was washed with hexane to obtain 252,4 mg of the crude product which was then purified by chromatography on a column of silica gel, elwira mixture 1:1 by volume of hexane and ethyl acetate, to obtain the 220,7 mg (71.4% ) of target compound, with a melting point 118-125aboutC. This compound is a stereoisomer, isomer at position C4the compound obtained in example 42.

Mass spectrum (m/z): 328, 325, 290, 256, 243, 173.

Mass spectrum (l3), h/million of 1.06 (3H, singlet); of 1.42 (3H, singlet); for 1.49 (3H, doublet, J 6.3 Hz); 4,36 (1H, quadruplet, J 6.3 Hz); a 4.83 (1H, doublet, J of 14.2 Hz); are 5.36 (1H, doublet, J of 14.2 Hz); 7,tx2">

P R I m e R 71. (2R*,3S*,4R*)-2-(4-Chlorophenyl)-3,4-dimethyl-[(1H-1,2,4-triazole-1-yl)- methyl]oxetan.

25 mg (0.38 mmol) 1-1,2,4-triazole and 25 mg (0,19 mmol) of potassium carbonate were added to a solution of 245 mg (1 mmol) of 2-chloromethyl-2-(4-chlorophenyl)-3,4-dimethyloxetane (mixture 3:1 isomers 4* and 4*) and then the mixture was stirred at 130aboutC for 5 hours then the reaction mixture is advocated to cool and then poured into ice water and was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of ammonium chloride and dried over anhydrous sodium sulfate, then the solvent was removed by distillation under reduced pressure to obtain 260 mg of the residue. Then the residue was purified by chromatography on a column of silica gel with receipt of 56.2 mg (yield 81%) of target compound with a melting point 111-118aboutC.

Mass spectrum (m/z): 278 /(M+ 1)+/, 222, 195, 141.

P R I m e R s 72-75. According to the method of example 4 were obtained the following compounds.

P R I m e R 72. (2R*,3S*,4S*)-2-(2,4-Di-forfinal)-4-isopropyl-3-methyl-2-[(1H-1,2,4 - triazole-1-yl)methyl]oxetan acid oxalate, melting point of 140-145aboutC, 5%

NMR-spectrum (l3), h /million is 0.69 (3H, doublet, J 7 Hz); to 0.88 (3H, doublet of doublets, J 2.5 and 7 Hz); of 0.90 (3H, doublet, J 7 Hz); 1.25 or who); 6,8-7,0 (2H, multiplet); 7,60 (1H, triplet of doublets, J 7 and 9 Hz); 7,87 (1H, singlet); 8,19 (1H, singlet).

P R I m e R 73. (2*, 3*, 4*)-2-(2,4-differenl)-4-isopropyl-3-methyl-2-[(1H - 1,2,4-triazole-1-yl)methyl] oxetan acidic oxalate melting temperature 151-154aboutC, 5%

NMR-spectrum (l3), h/million 0,81 (3H, doublet, J 6.5 Hz); of 1.02 (3H, doublet, J 6.5 Hz); of 1.47 (3H, doublet, J 6.5 Hz); to 2.29 (1H, multiplet); 3,19 (1H, multiplet); to 4.17 (1H, doublet of doublets, J 6.5 and 10.5 Hz); the 4.65 (1H, doublet, J 13 Hz); was 4.42 (1H, doublet, J 13 Hz); 6,7-7,2 (3H, multiplet); 7,52 (1H, singlet); 8,13 (1H, singlet).

P R I m e R 74. (2R*,3R*,4R*)-2-(2,4-Differenl)-4-isopropyl-3-methyl-2-[(1H - 1,2,4-triazole-1-yl)methyl]oxetan in the form of an oil with a yield of 35%

NMR-spectrum (l3), h /million of 0.77 (3H, doublet, J 7 Hz); of 0.93 (3H, doublet, J 7 Hz); of 1.40 (3H, doublet of doublets, J 1 and 7.5 Hz); 1,76 (1H, multiplet); 2,84 (1H, multiplet); 4.09 to (1H, doublet of doublets, J 7 and 8 Hz); of 4.67 (1H, doublet of doublets, J 1.5 and 14 Hz); the 4.90 (1H, doublet, J 14 Hz); 6,6-6,8 (2H, multiplet); 7,07 (1H, triplet of doublets, J 6.5 and 8.5 Hz); 7,66 (1H, singlet); 8,03 (1H, singlet).

P R I m e R 75. (2*,3*,4*)-3,4-dimethyl-2-phenyl-2-[(1H-1,2,4-triazole-1-yl)me - til] oxetan in the form of oil, yield 27%

NMR-spectrum (l3), h /million of 0.61 (3H, doublet, J 7.4 Hz); a 1.08 (3H, doublet, J6,5 Hz); 3,09 (1H, multiplet); to 4.28 (1H, doublet, J of 14.7 Hz); 4,32 (1H, multiplet); of 4.67 (1H, 227, 188, 161.

P R I m e R 76. (2R*,3S*,4R*)-2-(4-forfinal)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1 - yl)methyl]oxetan.

Following a methodology similar to that described in example 71, received 110 mg (yield of 38.3%) of target compound in the form of butter.

Spectrum of nuclear magnetic resonance (l3), mln.

0,70 (3H, doublet, J of 7.65 Hz);

of 1.17 (3H, doublet, J 6,44 Hz);

a 3.15 (1H, quintet, J 7,56 Hz);

to 4.38 (1H, doublet, J 14,51 Hz);

4,39-to 4.52 (1H, multiplet);

to 4.73 (1H, doublet, J 14,51 Hz);

was 7.08 (2H, triplet, J 8,66 Hz);

7,22-to 7.32 (2H, multiplet);

of 7.95 (1H, singlet);

8,30 (1H, singlet).

Mass spectrum (m/z): 262 (M+1)+, 244, 218, 206, 179.

P R e p a R a t I n m s p R I m e R 1. (3S*,4R*)-4-(2,4-Differenl)-3-methyl-5- (1H-1,2,4-triazole-1-yl)- 1,4-pentanediol and (2R*,3S*)-2-(2,4-differenl)-3-methyl-[1- (1H - 1,2,4-triazole-1-yl]-2,4-pentanediol.

2.2 ml (4.4 mmol) of a 2M solution brandimensions complex in tetrahydrofuran was added under conditions of cooling with ice and with stirring to a solution of 200 mg (to 0.72 mmol) of (2R*,3S*)-2-(2,4-differenl)-3-methyl-1-(1H-1,2,4-triazole-1-yl)- 4-penten-2-ol (which was synthesized according to the method described in Japanese Patent provisional publication N Sho 60-36468) in 5 ml of tetrahydrofuran. The mixture was allowed to warm up to the for 20 minutes After that, the mixture was again cooled water with ice, and to the mixture was added 1 ml of 15 wt./the amount of aqueous solution of sodium hydroxide and 1 ml of 30 wt./the amount of aqueous solution of sodium peroxide. Then the reaction mixture was stirred at room temperature for 30 min and then at 50-60aboutC for 2 h, after which the mixture was diluted with ethyl acetate and then washed with a saturated aqueous solution of sodium chloride. After drying, the mixture was freed from solvent by distillation under reduced pressure. The resulting oily residue was subjected to chromatography on a column of silica gel using mixtures of ethyl acetate and hexane in the range from 5:1 to 10:1 by volume as the eluent, to obtain 30 mg of the second specified target compound in the form of oil. NMR spectra showed the connection structure, which is a mixture of 1:1 isomers a and b in C4-position.

Isomer A (main peaks).

NMR-spectrum (l3), h/million to 0.80 (3H, doublet of doublets, J 7 and 3.5 Hz); of 1.18 (3H, doublet, J 6 Hz); the 4.90 (2H, singlet); 5,97 (1H, singlet); 7,79 (1H, singlet); with 8.05 (1H, singlet).

Isomer (major peaks).

NMR-spectrum (l3), h/0,76 million (3H, doublet of doublets, J 7 and 1.5 Hz); of 1.27 (3H, doublet, J 6 Hz); vs. 5.47 (1H, singlet); 7,70 (1 is in ethyl acetate to obtain 139 mg of the first specified target compounds which is recrystallized from a mixture of ethyl acetate and hexane to obtain pure sample, melting point 121 - 122aboutC.

NMR-spectrum (l3), h/0,78 million (3H, doublet of doublets, J 7 and 1 Hz); 1,6-2,0 (2H, multiplet); 2,4 (1H, multiplet); 3,3-4,0 (3H, multiplet); to 4.62 (1H, doublet, J 14 Hz); is 4.93 (1H, doublet of doublets, J 14 and 1 Hz); 5,52 (1H, broad peak); 6,5-7,0 (2H, multiplet); the 7.43 (1H, triplet of doublets, J 9 and 7 Hz); 7,73 (1H, singlet); 7,97 (1H, singlet).

P R e p a R a t I n m s p R I m m e R 2. (2R*,3S*, 4S*)-2-(2,4-Differenl)-4-metasolv-yloxy)-3-methyl - 1-(1H-1,2,4-triazole-1-yl)-2-pentanol.

2(a) (2R*, 3S*,4S*)-2-(2,4-differenl)-4,5-epoxy-3-methyl-1-(1H-1,2,4 - triazole-1-yl)-2-pentanol

1,360 g (to 6.19 mmol) 3-chloroperoxybenzoic acid (purity 80%) was added at 0aboutTo a solution of 960 mg (mmol 3,44) (2*,3*)-2-(2,4-differenl)-3-methyl-1- (1-1,2,4-triazole-1-yl)- 4-penten-2-ol (which was synthesized according to the method described in Japanese Patent provisional application N Sho 60-36468) in 30 ml of methylene chloride. After 5 min after the addition the reaction mixture was stirred and the stirring continued at room temperature overnight. Then the reaction mixture was diluted with ethyl acetate, then washed successively with an aqueous solution of sodium sulfite, water rest is orites by distillation under reduced pressure. The resulting residue was subjected to column chromatography on silica gel using 1:2 by volume mixture of ethyl acetate and hexane as eluent to obtain 320 mg of stereoisomer And the target compounds (having low polarity with a melting temperature of 160-180aboutWith and 206 mg of the target stereoisomer In the desired connection (with increased polarity) in the form of butter.

Stereoisomer (2R*,3S*,4S*):

NMR-spectrum (l3), h /million of 0.82 (3H, doublet, J and 7.3 Hz); 1,74 (1H, quintet, J and 7.3 Hz); of 2.54 (1H, doublet of doublets, J 4.0 and 2.8 Hz); 2,89 (1H, triplet, J 4.4 Hz); 3,3-3,4 (1H, multiplet); the 4.90 (2H, AB-doublet, J of 14.5 Hz); of 5.06 (1H, broad singlet); 6,6-6,8 (2H, multiplet); 7,3-7,5 (1H, multiplet); 7,79 (1H, singlet); 7,80 (1H, singlet).

Stereoisomer A: (2R*,3S*,4R*):

NMR-spectrum (l3), h /million of 0.94 (3H, doublet, J 6.9 Hz); to 1.86 (1H, quintet, J 6.9 Hz); is 2.74 (1H, doublet of doublets, J 4.8 and 2.8 Hz); 2,95 (1H, triplet, J 4.8 Hz); 3,2 and 3.3 (1H, multiplet); 4,80 (2H, AB-doublet, J of 13.7 Hz); 4.92 in (1H, singlet); 7,6-7,8 (2H, multiplet); 7,3-7,5 (1H, multiplet); for 7.78 (1H, singlet); 7,86 (1H, singlet).

2(b) (2R*, 3S*, 4S*)-2-(2,4-differenl)-3-methyl-1-(1H-1,2,4-triazole-1 - yl)-2,4-pentanediol.

84 mg (2,16 mmol) sociallyengaged added under nitrogen atmosphere to a solution of 320 mg (1,08 mmol) of (2R*,3S*,4S*)-2-(2,4-differenl)-0 ml of diethyl ether under conditions of cooling with ice and with stirring. After 10 min the reaction mixture is boiled under reflux and this was continued for 1 h At the end of this time the mixture was cooled and slowly added 2 ml of water; then the mixture was stirred for 10 minutes Undissolved substances of the reaction mixture were removed by filtration through celanova filter and then the residue was washed with ethyl acetate. The combined filtrate and wash water were dried and solvent was removed by distillation under reduced pressure. The resulting oily residue was subjected to chromatography on a column of silica gel using 5:5:1 by volume mixture of ethyl acetate, chloroform and hexane as eluent to obtain 240 mg of the target compound.

NMR-spectrum (l3), h /million to 0.80 (3H, doublet of doublets, J 6.9 and 3.0 Hz); 2,00 (1H, Quartet of doublets, J 6,9 and 1.6 Hz); 3,86 (1H, Quartet of doublets, J 6,9 and 1.6 Hz); to 4.62 (1H, doublet, J 14 Hz); is 4.93 (2H, singlet); 6,7-6,9 (2H, multiplet); 7,50 (1H, triplet of doublets, J 8,9 and 6.5 Hz); of 7.82 (1H, singlet); 8,13 (1H, the singlet).

2(C) (2R*, 3S*, 4S*)-2-(2,4-differenl)-4-methanesulfonate)-3-methyl - 1-(1H-1,2,4-triazole-1-yl)-2-pentanol

140 mg (1,22 mmol) methanesulfonanilide added at 0aboutTo a solution of 213 mg (to 0.72 mmol) of (2R*,3S*,4S*)-2-(2,4-differenl)-3-methyl-1-(1H-1,2,4-triazole-1 - yl)-2,4- (to 0.72 mmol) of (2R*, 3S*, 4S*)-2-(who and and the mixture was stirred for 2.5 hours then the pyridine was removed by distillation under reduced pressure. The resulting residue was mixed with diluted aqueous sodium bicarbonate solution and was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and solvent was removed by evaporation under reduced pressure to obtain 270 mg of the target compound in the form of butter.

NMR-spectrum (l3), h /million of 0.79 (3H, doublet of doublets, J 6.5 and 0.8 Hz); for 1.49 (3H, doublet, J 6.5 Hz); 2,6-2,8 (1H, multiplet); is 3.08 (3H, singlet); 4,85 (2H, AB-doublet, J a 13.9 Hz); 5,3-5,4 (1H, multiplet); 6,6-6,8 (2H, multiplet); 7,2-7,4 (1H, multiplet); 7,76 (1H, singlet); 7,81 (1H, singlet).

P R e p a R a t I n m s p R I m e R 3. (2R*,3R*)-2-(2,4-differenl)-4,5-epoxy-3 - methyl-1-(1H-1,2,4-triazole-1-yl)-2-pentanol.

635 mg (3,13 mmol) 3-chloroperoxybenzoic acid (purity 85%) was added to a solution of 514 mg (of 1.84 mmol) of (2R*,3R*)-2-(2,4-differenl)-3-methyl-1-(1-1,2,4-triazole - 1-yl)- 4-penten-2-ol (which was prepared according to the method described in Japanese Patent provisional publication N Sho 60-36468) in 15 ml of methylene chloride. After 5 min the temperature of the reaction mixture was allowed to rise to room temperature and the mixture was stirred 2 h then the reaction mixture was diluted eternalising aqueous solution of sodium chloride. Then the organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The resulting residue was subjected to chromatography on a column of silica gel using 2:1 by volume mixture of ethyl acetate and hexane as eluent, obtaining 472 mg of the target compound in the form of a solid substance.

The product was identified as a mixture of 3:1 two stereoisomers with respect to the carbon atom in position WITH4.

Recrystallization from a mixture of ethyl acetate and hexane led to the main isomer with a melting point of 106-109aboutC.

NMR-spectrum (l3), h/million of 1.30 (3H, doublet, J 6 Hz); 1,90 (1H, broad quintet); 2,00 (1H, doublet of doublets, J 4 and 3 Hz); 2,35 (1H, triplet, J 4 Hz); 2,85 (1H, multiplet); a 4.53 (1H, doublet, J 14 Hz); 4,89 (1H, doublet of doublets, J 14 and 1.5 Hz) and 4.9 (1H, broad peak); 6,5-7,0 (2H, multiplet); of 7.3 to 7.7 (1H, multiplet); 7,79 (1H, singlet); to $ 7.91 (1H, singlet).

P R e p a R a t I n m s p R I m e R 4. (2R*,3R*, 4S*)-2-(2,4-differenl)-3-methyl-1-(1H-1,2,4-triazole-1 - yl)-2,4-pentanediol.

53 mg (1,40 mmol) socialwise hydride was added under nitrogen atmosphere to a solution of 207 mg (0.70 mmol) of (2R*,3R*)-2-(2,4-differenl)-4,5-epoxy-3-methyl-1-(1H-1,2,4 - triazole-1-yl)-2-pentanol (approximately 3:1 the death of the ice cooling and stirred. After 10 min the reaction mixture was heated and boiled under reflux and this was continued for 1 h then the mixture was cooled and slowly added 1 ml of water, after which the mixture was stirred 10 minutes, the Insoluble substances were removed by filtration through celanova filter, after which the residue was washed with ethyl acetate. The combined filtrate and wash liquid were dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The resulting oily residue was subjected to chromatography on a column of silica gel using 5:5:1 by volume mixture of ethyl acetate, chloroform and hexane as eluent, to obtain 160 mg of the target compound.

This product was identified as a mixture of 3:1 two stereoisomers with respect to the carbon atom in position WITH4.

Recrystallization from a mixture of benzene and hexane led to the main isomer with a melting point 145-146aboutC.

NMR-spectrum (l3), h/million of 1.05 (3H, doublet, J 6.5 Hz); 1,25 (3H, doublet, J 6.5 Hz); 2,20 (1H, Quartet of doublets, J 6.5 and 1 Hz); 3,03 (1H, broad singlet); 3,74 (1H, broad Quartet, J 6.5 Hz); 4,51 (1H, doublet, J 14 Hz); of 4.77 (1H, doublet of doublets, J 14.1 Hz); 5,33 (1H, singlet); 6,5-7,0 (2H, multiple the chlorophenyl)-3-hydroxy-2 - methyl-(1H - 1,2,4 - triazole-1-yl)-butanal and (2S*,3R*)-3-(2,4-dichlorophenyl)-3-hydroxy-2 - methyl-4-(1H-1,2,4 - triazole-1-yl)butanal.

290 mg (1,32 mmol) methylphenidate sodium and 1 mg of tetrakis osmium added to a solution of 139 mg (0.45 mmol) of the mixture 1:1 (2*,3*)-4-(2,4-dichlorophenyl)-3-methyl-1- (1-1,2,4-triazole-1-yl)-4 - penten-2-ol and (2*,3*)-isomer (which was synthesized according to the method described in Japanese patent provisional publication N Sho 60-36468) 2.8 ml volumetric mix 5:2 tetrahydrofuran and water, and the mixture was stirred over night at room temperature. After the reaction mixture was diluted with ethyl acetate and washed with saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The resulting oily residue was subjected to chromatography on a column with 4 g of silica gel using a mixture of 4:5 by volume of ethyl acetate and hexane as eluent to obtain 27 mg (2*,3*)-isomer, 25 mg of the mixture (2*, 3*)-isomer and (2*,3*)-isomer and 31 mg (2*,3*)-isomer in the sequence.

Recrystallization (2*,3*)-isomer of benzene resulted in obtaining a clean sample with a melting point 150-151aboutC.

Recrystallization (2*, 3*)-isomer from a mixture of benzene and ethyl acetate resulted in obtaining a clean sample with a melting point 155-157about NMR-spectrum (l3) h/million of 0.96 (3H, doublet, J 7 Hz); 3,47 (1H, Quartet of doublets, J and 7.3 Hz); with 4.64 (1H, doublet, J 14 Hz); and 5.30 (1H, broad peak); 5,42 (1H, doublet, J 14 Hz); 7,11 (1H, doublet of doublets, J 8.2 Hz); 7,31 (1H, doublet, J 2 Hz); 7,52 (1H, doublet, J 8 Hz), and 7.7 (1H, singlet); the 7.85 (1H, singlet); 9,88 (1H, doublet, J 3 Hz).

(2S*,3R*)-isomer:

NMR-spectrum (l3) h/million of 1.40 (3H, doublet, J 7 Hz); 3,52 (1H, Quartet of doublets, J 7 and 1.5 Hz); 4,50 (1H, doublet, J 14 Hz); 5,42 (1H, doublet, J 14 Hz), and 5.5 (1H, broad peak); 7,11 (1H, doublet of doublets, J 8.2 Hz); to 7.35 (1H, doublet, J 2 Hz); rate of 7.54 (1H, doublet, J 8 Hz); to 7.77 (1H, singlet); 7,86 (1H, singlet); 9,39 (1H, doublet, J 1.5 Hz).

P R e p a R a t I n m s p R I m e R 6. (2S*,3R*)-3-(2,4-dichlorophenyl)-2-methyl-4- (1H-1,2,4-triazole-1-yl)-1,3-butanediol and (2R*,3R*)-3-(2,4-dichlorophenyl)-2-methyl-4- (1H-1,2,4-triazole-1-yl)- 1,3-butanediol.

15 mg of sodium borohydride was added under conditions of cooling with ice and with stirring to a solution of 85 mg of a mixture 1:1 (2*, 3R*)-3-(2,4-dichlorophenyl)-3-hydroxy-2-me - Teal-4-(1-1,2,4- triazole-1-yl)butanal and (2*,3*)-isomer (obtained as described in preparative example 5) in 1.5 ml of methanol. After 10 min the reaction mixture was diluted with ethyl acetate, after which the mixture was washed with a saturated aqueous solution of sodium chloride. The organic layer person to distil removal of the solvent under reduced allowing the use of ethyl acetate as eluent to obtain 31 mg of (2*,3*)-isomer of the target compound.

It recrystallization from a mixture of benzene and hexane resulted in obtaining a clean sample with a melting point 120-122aboutC.

Then the column was suirable with ethyl acetate containing about 7. methanol to obtain 33 mg (2*,3*)-isomer of the target compound.

It recrystallization from a mixture of benzene and hexane resulted in obtaining a clean sample with a melting point 176-177aboutC.

(2*,3*)-isomer:

NMR-spectrum (l3) h /million of 1.39 (3H, doublet, J 7 Hz); 2,85 (1H, multiplet); 3.40 in (1H, singlet); of 3.45 (1H, singlet); 4,50 (1H, doublet, J 14 Hz); 5,31 (1H, doublet, J 14 Hz); 7,05 (1H, doublet of doublets, J 8 and 2 Hz); of 7.25 (1H, doublet, J 2 Hz); 7,52 (1H, doublet, J 8 Hz); 7,66 (1H, singlet); to $ 7.91 (1H, singlet).

(2*,3*)-isomer:

IR-spectrum (Nujol)maxcm-1: 3400, 3140.

NMR-spectrum (l3: C3O) 1:1 by volume) hours/million of 0.77 (3H, doublet, J 7 Hz); 2,9 (1H, multiplet); 3,6-4,3 (2H, multiplet); 4,74 (1H, doublet, J of 14.5 Hz); 5,44 (1H, doublet, J of 14.5 Hz);? 7.04 baby mortality (1H, doublet of doublets, J9,2 Hz); 7,30 (1H, doublet, J 2 Hz); of 7.48 (1H, doublet, J 9 Hz); to 7.67 (1H, singlet); 8,07 (1H, singlet).

P R e p a R a t I n m s p R I m e R 7. (2R*,3S*)-2-(2,4-dichlorophenyl)-4-methanol - phenyloxy)-3-methyl-1-(1H - 1,2,4-triazole-1-yl)-2-butanol.

61 mg (0.61 mmol) of triethylamine and 64 mg (0,56 mmol) methane is ethyl-4-(1-1,2,4-Tria - Zol-1-yl)- 1,3-butanediol in 2 ml of methylene chloride. After 15 min the reaction mixture was mixed with diluted aqueous sodium bicarbonate solution and was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and the solvent was removed by evaporation under reduced pressure, to obtain 92 mg of the crude product.

NMR-spectrum (l3), h/million 0,70 (3H, doublet, J 7 Hz); of 3.07 (3H, singlet); 2,9-3,4 (1H, multiplet); 4,22 (1H, doublet of doublets, J 10 and 5 Hz); 4,59 (1H, doublet, J of 14.5 Hz); 4,71 (1H, doublet of doublets, J 10 and 7 Hz); by 5.18 (1H, broad peak); the 5.51 (1H, doublet, J of 14.5 Hz);? 7.04 baby mortality (1H, doublet of doublets, J 8 and 2 Hz); 7,27 (1H, doublet, J 2 Hz); the 7.43 (1H, doublet, J 8 Hz); 7,73 (1H, singlet); 7,81 (1H, singlet).

P R e p a R a t I n m s p R I m e R 8. (2R*,4R*)-2-(4-Chlorophenyl)-2-taxicab - Nile-3,4-dimethyloxetane.

2-Butene was barbotirovany in 200 ml of benzene at 0aboutWith up until the benzene solution is not increased to 1.25 times its original volume. Then was added to the mixture of 24.3 g (114,09 mmol) ethyl-4-chlorophenylglycine and the resulting mixture was illuminated by the mercury lamp, medium pressure power 450 W (Hahnovea Co. Inc.) 15aboutC for 3 h then the reaction mixture was concentrated by evaporation under reduced pressure and the obtained residue was subjected to chromatography on a column of seligertur boiling 141 - 142aboutWith/2.7 mm RT.article.

NMR-spectrum (l3) h /0,76 million (doublet, J 7,66 Hz); of 1.23 to 1.31 (multiplet); 1,34 (doublet, J 6,04 Hz); 2,83 (quintet, J of 7.25 Hz); 3,55 (quintet, J of 7.25 Hz); 4,16-4,32 (multiplet), 4,56 (quintet, J of 6.45 Hz); 5,06 (quintet, J 7 Hz); 7,267,45 (multiplet).

Mass spectrum (m/z): 268 (M+), 224, 213, 195, 178, 167.

P R e p a R a t I n m s p R I m e R 9. (2R*,3S*, 4R*)-2-(4-Chlorophenyl)-3,4-dimethyl-2-hydro - KTimetracker and (2R*, 3R*, 4R*)-2-(-4-chlorophenyl)-3,4-dimethyl-2-hydro - ximations - tan.

3.2 ml (3.2 mmol) of 1M solution of sociallyengaged in tetrahydrofuran was added dropwise at 0aboutTo a solution of 920 mg (3,42 mmol) of the mixture 1:1 (2*, 3*, 4*)-2-(4-chlorophenyl)-3,4-dimethyl-2-etoxycarbonyl - oxetane and(2*, 3*,4*)-isomer (semi-Chennai, as described in preparative example 8) in 7 ml of tetrahydrofuran, and the resulting mixture was stirred at the same temperature for 30 minutes thereafter, to the reaction mixture were sequentially added to a saturated aqueous solution of ammonium chloride and 1 normal aqueous solution of hydrochloric acid. The crude products obtained by extraction of the reaction mixture with ethyl acetate, was subjected to chromatography on a column of silica gel, elwira a mixture of 5: 1 by volume of hexane and ethyl acetate, to obtain the 223,4 mg of the isomer of the target compound Isomer A:

NMR-spectrum (l3), h/million 0,70 (3H, doublet, J 7,44 Hz); of 1.24 (3H, doublet, J 6,44 Hz); of 3.33 (1H, doublet, J 7,66 Hz); 3,63 (1H, doublet, J 12,08 Hz); a 3.87 (1H, doublet, J 12,08 Hz); 4,96 (1H, doublet of quartets, J 6,44 and 7,66 Hz); of 7.25 (2H, doublet, J 8,46 Hz); to 7.35 (2H, doublet, J 8,46).

Mass spectrum (m/z): 223, 195, 181, 167, 153, 139.

The isomer IN:

NMR-spectrum (l3), h/million of 1.36 (3H, doublet, J 6,04 Hz); of 1.36 (3H, doublet, J of 7.25 Hz); 2,18 (1H, broad doublet of doublets, J of 5.53 and of 7.25 Hz); to 2.65 (1H, quintet, J of 7.25 Hz); 3,71 (1H, doublet of doublets, J of 5.53 and 12,09 Hz); was 4.02 (1H, doublet of doublets, J 7.25 and 12,09 Hz); 4,56 (1H, doublet of quartets, J 6,04 and of 7.25 Hz); from 7.24 (2H, doublet, J 8,46 Hz); 7,33 (2H, doublet, J 8,46 Hz).

Mass spectrum (m/z): 195, 167, 139, 129, 125, 115.

P R e p a R a t I n m s p R I m e R 10. 2-(4-Chlorophenyl)-3,4-dimethyl-2-methanol - philogenetically.

of 0.13 ml (1,68 mmol) methanesulfonyl chloride, and then to 0.24 ml (1,708 mmol) of triethylamine was added at 0aboutTo a solution of 123 mg (0,543 mmol) of 2-(4-chlorophenyl)-3,4-dimethyl-2-hydroxyatomoxetine in 10 ml of methylene chloride, and the resulting mixture was stirred for 4 h while allowing the reaction temperature to rise to room temperature. Then to the mixture was added an aqueous solution of sodium bicarbonate and then extracted with methylene chloride. The extract was dried over anhydrous Tografie on a column of silica gel, elwira a mixture of 10:1 by volume of hexane and ethyl acetate to obtain 107 mg (yield 65%) of target compound.

NMR-spectrum (l3), h/million to 0.72 (3H, doublet, J of 7.25 Hz); to 1.21 (3H, doublet, J6,44 Hz); to 3.02 (3H, singlet); of 3.25 (1H, quintet, J of 7.25 Hz); 4,33 (1H, doublet, J 11,68 Hz); 4,60 (1H, doublet, J 11,68 Hz); 5,04 (1H, doublet of quartets, J 6,44 and of 7.25 Hz); 7,28 (1H, doublet, J 8,86 Hz); 7,37 (2H, doublet, J 8,86 Hz).

P R e p a R a t I n m s p R I m e R 11. (2R*,4R*)-2-chloromethyl-2-(4-chlorophenyl)-3,4-dimethyloxetane.

2-Butene was barbotirovany in 180 ml of benzene at 0aboutWith up until the benzene solution was not increased in the amount of up to 1.25 times its initial value. Then to the solution was added 15 g (79,34 mmol) 4-chlorophenacyl chloride, after which the mixture was illuminated by the mercury lamp, medium pressure power 450 W (Hahnovea Co. Inc.) within 15 hours After the reaction mixture was concentrated by evaporation under reduced pressure. Then her person to distil under reduced pressure to get 15,24 mg (78,4%) of target compound with a boiling point 132-133aboutWith/3.2 mm RT.article Based on the NMR spectra of this compound is a mixture of 1:3 - and-isomers with respect to C3position.

Mass spectrum (m/z): 246 (M+2)+), 244 (M+), 195, 190, 155, 151, 141, 139.

NMR-spectrum (l3,00 Hz); 3,24 (doublet of quartets, J 7,54 and rate of 7.54 Hz); 3,82 (doublet, J are 11.62 Hz); 3,90 (doublet, J are 11.62 Hz); 3,91 (doublet, J are 11.62 Hz); 4,00 (doublet, J are 11.62 Hz); 4,55 (doublet of quartets, 6,40 and 7,00 Hz); of 5.05 (doublet of quartets, J 6,40 and 7,00 Hz); 7.23 percent-7,40 (multiplet).

P R e p a R a t I n m s p R I m e R 12. (2R*,3R*)-2-(4-Chlorophenyl)-3-methyl-2-(trimethyl-silyloxy)-1-(1H - 1,2,4-triazole-1-yl)-4-penten.

2,47 ml (to 19.4 mmol) trimethylsilylpropyne and 1.7 g (a 24.3 mmol) of imidazole was added to a solution of 900 mg (3,24 mmol) of (2R*, 3R*)-3-methyl-2-(4-chlorophenyl)-(1H-1,2,4-tri - azole-1-yl)-2 - pentanol in 20 ml of dimethylformamide, and the mixture is then stirred at 50aboutC for 4 h then the reaction mixture is poured into water and was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate, then the solvent was removed by distillation under reduced pressure to obtain 1.3 g of target compound in the form of crude oil.

NMR-spectrum (l3), h/0,17 million (N, singlet), to 0.88 (3H, doublet, J 6,7 Hz); 2,7-to 2.85 (1H, multiplet); 4,47 (1H, doublet, J of 14.7 Hz); 4,82 (1H, doublet, J of 14.7 Hz); of 5.05 was 5.2 (2H, multiplet), 5,5-5,7 (1H, multiplet); 7,2-7,3 (4H, multiplet), 7,54 (1H, singlet), 7,78 (1H, singlet).

P R e p a R a t I n m s p R I m e p 13. (2R*,3R*)-2-(4-Chlorophenyl)-3-methyl-2-trimetric - siloxy-1-(1H-1,2,4-triazole-1-yl)butanal.

NMR-spectrum (l3) h/0,17 million (96, singlet); of 1.28 (3H, doublet, J 6.9 Hz); 3.04 from (1H, Quartet, J 6.9 Hz); 4,48 (1H, doublet, J 15 Hz); of 4.67 (1H, doublet, J 15 Hz);? 7.04 baby mortality (2H, doublet, J 8.6 Hz); 7,27 (2H, doublet, J 8.6 Hz); at 7.55 (1H, singlet); 7,88 (1H, singlet); 9,325 (1H, doublet, J Of 1.26 Hz).

P R e p a R a t I n m s p R I m e R 14. (2R*,3R*)-2-(4-chlorophenyl)-3-methyl-2-trim - telelinks-1-(1H - 1,2,4-triazole-1-yl)-4-pentanol.

of 0.45 ml (0.38 mmol) diethylaluminium chloride (0,84 molar solution in hexane) was added to a solution of 111,1 mg (mmol 0,316) (2*,3*)-3-methyl-2-(4-chlorophenyl)-2-(trimethylsilyloxy)-1-(1 h /million 0,087 (singlet); 0,284 (singlet); 0,77 (doublet, J 6 Hz); 0,94 (doublet, J 6.5 Hz); 1,08 (doublet, J 6 Hz); 1.28 (in the doublet, J 6.9 Hz); a 2.0-2.1 (multiplet); 3,5-3,65 (multiplet); 4,14 (do the R e p a R a t I n m s p R I m e R 15. (2R*,3R*)-2-(4-chlorophenyl)-3-methyl-1-(1H-1,2, 4-triazole-1-yl)-2,4 - pentanediol.

of 0.35 ml (0.35 mmol) tetrabutylammonium fluoride (in the form of a 1 molar solution in tetrahydrofuran) was added to a solution of 85.4 mg (mmol 0,233) (2*, 3*)-3-methyl-2-(4-chlorophenyl)-2-(trimethylsilyloxy)-1-(1*,3*,4*)-isomer and(2*,3*,4*)-isomer.

NMR-spectrum (l3), h/million 0,81 (doublet, J 7 Hz); 1,01 (doublet, J 7 Hz); 1,12 (doublet, J 7 Hz); 1,25 (doublet, J 7 Hz); 1,99 (Quartet, J 7 Hz); 3,68 (Quartet, J 7 Hz); of 4.44 (AB-doublet, J 15 Hz); 4.75 in (AB-doublet, J 15 Hz); and 7.1 to 7.4 (multiplet); 7,68 (singlet); 7,74 (singlet); 8,00 (singlet).

P R e p a R a t I n m s p R I m e R 16. Ethyl 3-(4-chlorophenyl)-2,2-dimethyl-3-hydroxy-4-(1H-1,2,4-trizol-1-yl) butanoate.

30 ml (30 mmol) of diethylaluminium (in the form of a 1.0 molar solution in hexane) was added to a suspension of 2.0 g (30 mmol) of Zn and 0.14 g (1 mmol) of copper bromide in 30 ml of tetrahydrofuran. Then dropwise to the mixture was added a solution of 1.33 g (6 mmol) of 4-chloro-2-(1-1,2,4-triazole-1-yl)acetophenon and 6.7 g (30 mmol) of ethyl 2-bromoisobutyrate in 30 ml of tetrahydrofuran, after which the mixture was stirred at room temperature for 18 hours thereafter, to the reaction mixture were added water and 1 normal aqueous hydrochloric acid to obtain a precipitate which was then filtered using celanova filter the water with hydrochloric acid, aqueous solution of ammonium chloride and saturated aqueous sodium chloride. Then the solution was dried and concentrated by evaporation under reduced pressure, separating the precipitate, which was purified by chromatography on a column of silica gel, elwira a mixture of 1:4 by volume of hexane and ethyl acetate to obtain 1.89 g (93%) of target compound in the form of butter.

Mass spectrum (m/z: 337 (M+), 292, 252, 222, 139.

NMR-spectrum (l3), h/million to 1.21 (3H, singlet); to 1.21 (3H, triplet, J 7 Hz); of 1.23 (3H, singlet); 4,10 (2H, Quartet, J 7 Hz); 4,63 (1H, doublet, J 14 Hz); 5,13 (1H, doublet, J 14 Hz); lower than the 5.37 (1H, broad singlet); 7,05-7,40 (4H, multiplet); the 7.65 (1H, singlet); a 7.92 (1H, singlet).

P R e p a R a t I n s e p R I m e R s 17-32.

By the method of preparative example 16 were obtained the following compounds.

P R e p a R a t I n m s p R I m e R 17. Octyl 3-(2,4-differenl)-3-hydroxy-4-(1-1,2,4-triazole-1-yl)butanoate, in the form of oil, yield 42%

NMR-spectrum (l3), h /0,5 million-1,70 (15 NM, multiplet); to 2.65 (1H, doublet, J 15 Hz); is 3.21 (1H, doublet, J 15 Hz); 3,95 (2H, triplet, J 6 Hz); 4,36 (1H, doublet, J 13 Hz); and 4.68 (1H, doublet, J 13 Hz); 5,10 (1H, broad singlet); 6,55-7,00 (2H, multiplet); 7,10-7,80 (1H, multiplet); 7,81 (1H, singlet); of 8.15 (1H, singlet).

Mass spectrum (m/z): 395 (M+), 313, 201, 183.

the form of oil, exit 42%

NMR-spectrum (l3), h /million 0,70-1,95 (15 NM, multiplet); or 3.28 (1H, Quartet, J 7 Hz); 4,115 (2H, triplet, 6 Hz); 4,46 (1H, doublet, J 13 Hz); 4,85 (1H, doublet, J 13 Hz); by 5.18 (1H, singlet); 6,50-to 6.95 (2H, multiplet); 7,10-the 7.65 (1H, multiplet); 8,17 (1H, singlet).

Mass spectrum (m/z): 409 (M+), 327, 224, 215, 197.

P R e p a R a t I n m s p R I m e R 19. Ethyl-3-(2,4-differenl)-3-hydroxy-4- (1-1,2,4-triazole-1-yl)butanoate, in the form of oil, yield 62%

NMR-spectrum (l3), h /million of 1.10 (3H, triplet, J 7 Hz); to 2.65 (1H, doublet, J 16 Hz); 3,20 (1H, doublet, J 16 Hz); 3,99 (2H, Quartet, J 7 Hz); 4,39 (1H, doublet, J 14 Hz); and 4.68 (1H, doublet, J 14 Hz); 5.25-inch (1H, broad singlet); 6,50-7,00 (2H, multilpe); 7,15 to 7.75 (1H, multiplet); 7,76 (1H, singlet); to 8.12 (1H, singlet).

Mass spectrum (m/z): 312 (M+), 229, 182, 141.

P R e p a R a t I n m s p R I m e R 20. Ethyl-3-(2,4-differenl)-3-hydroxy-2-me - Teal-4-(1-1,2,4-triazole-1-yl) butanoate, in the form of oil, yield 58%

NMR-spectrum (l3), h /million of 0.90 (3H, doublet, J 7 Hz); of 1.23 (3H, triplet, J 7 Hz); 3,19 (1H, Quartet, J 7 Hz); 4,13 (2H, Quartet, J 7 Hz); to 4.41 (1H, doublet, J 13 Hz); of 4.77 (1H, doublet, J 13 Hz); 5,10 (1H, broad singlet); 6,45-7,00 (2H, multiplet); 7,20-the 7.65 (1H, multiplet); 7,66 (1H, singlet); to 7.95 (1H, singlet).

Mass spectrum (m/z): 325 (M+), 243, 224, 197, 182, 141.

P R e p a R a t I n m s p R I m e R 21. This is 57%

NMR-spectrum (l3), h /0,78 million (3H, triplet, J 7 Hz); of 1.32 (3H, triplet, J 7 Hz); 1,00-2,10 (2H, multiplet); of 3.07 (1H, doublet of doublets, J 4 and 10 Hz); 4,22 (2H, Quartet, J 7 Hz); 4,30 (1H, doublet, J 14 Hz); 4,84 (1H, doublet, J 14 Hz); 5,10 (1H, broad singlet); 6,47-6,92 (2H, multiplet); 7,10-of 7.60 (1H, multiplet); to 7.61 (1H, singlet); a 7.92 (1H, singlet).

Mass spectrum (m/z): 339 (M+), 297, 257, 224, 211, 182, 141.

P R e p a R a t I n m s p R I m e R 22. Ethyl-3-(2,4-differenl)-3-hydroxy-2,2 - dimethyl-4-(1-1,2,4- triazole-1-yl)butanoate, with a melting point 90aboutC, yield 70%

NMR-spectrum (l3), h /million of 1.20 (3H, doublet, J 2.0 Hz); 1,25 (3H, triplet, J and 7.3 Hz); of 1.30 (3H, singlet); to 4.17 (2H, doublet of quartets, J 1,2 and 7.3 Hz); the 4.65 (1H, doublet of doublets, J 1.8 and a 14.1 Hz); are 5.36 (1H, doublet of doublets, J 2,4 and 14.1 Hz); 5,42 (1H, singlet); 6,59-PC 6.82 (2H, multiplet); 7,55-to 7.64 (1H, multiplet); 7,73 (1H, singlet); 8,02 (1H, doublet, J 1.6 Hz).

Mass spectrum (m/z): 339 (M+), 294, 257, 224, 141.

P R e p a R a t I n m s p R I m e R 23. Ethyl-3-(2,4-differenl)-3-hydroxy-2-Fe - Neil-4-(1H-1,2,4-triazole - 1-yl)butanoate in the form of oil, yield 9%

NMR-spectrum (l3), h /million of 1.20 (3H, triplet, J 7 Hz); 4,10 (2H, Quartet, J 7 Hz); of 4.38 (1H, singlet); 4,78 (2H, singlet); 6,00 (1H, multiplet); 6,20-7,30 (3H, multiplet); was 7.08 (5H, broad singlet); of 7.70 (1H, singlet); with 8.05 (1H, singlet).

<3-hydroxy-2-methyl-4-(1-1,2,4-triazole-1-yl)butanoate, with the melting temperature of 75-90aboutWith exit 57%

NMR-spectrum (l3), h /million of 1.03 (3H, triplet, J 7 Hz); of 1.30 (3H, triplet, J 7 Hz); 2,98 (1H, Quartet, J 7 Hz); of 4.16 (2H, Quartet, J 7 Hz); of 4.35 (1H, doublet, J 13 Hz); the 4.65 (1H, doublet, J 13 Hz); 5,00 (1H, broad singlet); 7,00-7,30 (4H, multiplet); of 7.70 (1H, singlet); 7,81 (1H, singlet);

Mass spectrum (m/z): 323 (M+), 276, 241, 222.

P R e p a R a t I n m s p R I m e R 25. Ethyl-3-(4-chlorophenyl)-2-ethyl-3-hydroxy-4-(1-1,2,4-triazole-1-yl) butanoate, in the form of oil, yield 91%

NMR-spectrum (l3) h /million of 0.82 (3H, triplet, J and 7.6 Hz); 1,22-of 1.39 (2H, multiplet); to 1.31 (3H, triplet, J 7,1 Hz); 1,63-1,77 (1H, multiplet); 4,18-the 4.29 (2H, multiplet); 4,39 (1H, doublet, J 14.1 Hz); with 4.64 (1H, doublet, J 14.1 Hz); 7,20-7,28 (4H, multiplet); of 7.75 (1H, singlet); to 7.93 (1H, singlet).

Mass spectrum (m/z: 337 (M+), 255, 222, 139.

P R e p a R a t I n m s p R I m e R 26. Ethyl-3-(4-forfinal)-2-ethyl-3-hydroxy-4-(1-1,2,4-triazole-1-yl)butanoate, in the form of oil, yield 35%

NMR-spectrum (l3) h /million of 0.82 (3H, triplet, J 7.5 Hz); of 1.32 (3H, triplet, J 7,1 Hz); 0,94-to 1.77 (3H, multiplet); 2,80 (1H, Quartet, J 3.6 Hz); 4,16-to 4.33 (2H, multiplet); to 4.41 (1H, doublet, J 14.1 Hz); 4,56 (1H, doublet, J 14.1 Hz); 6.89 in-7,02 (2H, multiplet); 7,22-7,29 (2H, multiplet). to 7.77 (1H, singlet), 8,02 (1H, singlet).

Mass spectrum (m/z): 321 (M+), 303, 276, 239.

P R e Ihad 87%

NMR-spectrum (l3), h/million of 1.20-1.28 (in N, multiplet); 4,07-4,19 (2H, multiplet); 4,71 (1H, doublet, J 14.1 Hz); 5,14 (1H, doublet, J 14.1 Hz); 6.89 in-7,38 (4H, multiplet); of 7.75 (1H, singlet); 8,04 (1H, singlet).

Mass spectrum (m/z): 321 (M+), 276, 239, 206.

P R e p a R a t I n m s p R I m e R 28. Ethyl-2-ethyl-3-hydroxy-(4-were)-4- (1-1,2,4-triazole-1-yl)butanoate, in the form of oil, yield 75%

NMR-spectrum (l3), h/million 0,81 (3H, triplet, J and 7.3 Hz); 0,94-of 1.03 (1H, multiplet); to 1.31 (3H, triplet, J and 7.3 Hz); 1,23-of 1.41 (1H, multiplet); 1,63 is 1.75 (1H, multiplet); 4,19-4,27 (2H, multiplet); 4,39 (1H, doublet, J 14.1 Hz); to 4.62 (1H, doublet, J 14.1 Hz); 7,05-7,63 (4H, multiplet); 7,76 (1H, singlet); 7,83 (1H, singlet).

Mass spectrum (m/z): 317 (M+), 235, 202.

P R e p a R a t I n m s p R I m e R 29. Ethyl-3-hydroxy-2,2-dimethyl-3-(4-methylphe - Neil)-4-(1-1,2,4-triazole-1-yl)butanoate, in the form of oil, yield 82%

NMR-spectrum (l3), h /million of 1.20-1.28 (in N, multiplet); and 2.27 (3H, singlet); 4.09 to 4,19 (2H, multiplet); 4,71 (1H, doublet, J14,1 Hz); 5,12 (1H, doublet, J 14.1 Hz); 7.03 is (2H, doublet, J 8.1 Hz); 7,76 (1H, singlet); 7,99 (1H, singlet).

Mass spectrum (m/z): 318 (M++1), 272, 235, 202.

Preparative example 30. Ethyl-3-hydroxy-3-(4-isopropylphenyl)-2,2-dimethyl-4- (1-1,2,4-triazole-1-yl)butanoate, in the form of oil, yield 85%

NMR-spectrum (l3

Mass spectrum (m/z): 345 (M+), 263, 230.

P R e p a R a t I n m s p R I m e R 31. Ethyl-3-hydroxy-3-(4-methoxyphenyl)-2,2-di - methyl-4- (1-1,2,4- triazole-1-yl)butanoate, in the form of oil, yield 95%

NMR-spectrum (l3), h /million to 1.21-1.26 in (N, multiplet); of 3.75 (3H, singlet); 4,07-is 4.21 (2H, multiplet); 4,70 (1H, doublet, J of 14.5 Hz); 5,10 (1H, doublet, J of 14.5 Hz); 5.08 to to 5.13 (1H, broad singlet); 6.73 x-6,79 (2H, multiplet); 7,25-7,30 (2H, multiplet); 7,74 (1H, singlet); 7,97 (1H, singlet).

Mass spectrum (m/z: 334 (M++1), 251, 218.

P R e p a R a t I n m s p R I m e R 32. Ethyl-2-ethyl-3-hydroxy-3-phenyl-4-(1-1,2,4- triazole-1-yl)butanoate, with a melting point 72-79aboutFrom exit 44%

NMR-spectrum (l3), h/million 0,81 (3H, triplet, J 7.5 Hz); of 1.33 (3H, triplet, J 7,1 Hz); 1.32 to the 1.44 (1H, multiplet); 1,94-2,04 (1H, multiplet); 2,86 (1H, Quartet, J 3.6 Hz); 4,18-4,32 (2H, multilpe); was 4.42 (1H, doublet, H a 14.1 Hz); of 4.66 (1H, doublet, J 14.1 Hz); 7,16-7,33 (5H, multiplet); of 7.75 (1H, singlet); to 7.84 (1H, singlet).

Mass spectrum (m/z): 303 (M+), 258, 221, 188.

P R e p a R a t I n m s p R I m e R 33. 3-(4-Chlorophenyl)-2,2-dimethyl-4-(1H-1,2,4 - triazole-1-yl)-1,3-butanediol.

1.9 grams (50,2 mmol) sodium borohydride was added to a solution of 1.75 g (5) - Rev. ü boiled under reflux for 3 hours After the reaction mixture was allowed to cool and the mixture is then poured into ice water and was extracted with ethyl acetate. The extract was washed with an aqueous solution of ameriglide, dried and concentrated by evaporation under reduced pressure to obtain 1.5 g (98%) of target compound with a melting point 120-135aboutC.

Mass spectrum (m/z): 295 (M+), 222, 139, 83.

NMR-spectrum (l3), h/million of 0.82 (3H, singlet); of 0.90 (3H, singlet); 3,23-3,30 (3H, multiplet); 4,56 (1H, doublet, J of 14.7 Hz); at 5.27 (1H, doublet, J of 14.7 Hz); 5.25-inch (1H, singlet); 7.24 to of 7.48 (4H, multiplet); of 7.70 (1H, singlet); of 8.25 (1H, singlet).

P R e p a R a t I n s e p R I m e R s 34-44. By the method of preparative example 33 were obtained the following compounds.

P R e p a R a t I n m s p R I m e R 34. 3-(2,4-Differenl)-4-(1-1,2,4-triazole-1 - yl)-1,3-BU - Tandil with a melting point 89-102aboutFrom exit 89%

NMR-spectrum (l3), h/million 1,80-2,60 (2H, multiplet); 3,35-3,90 (2H, multiplet); 4,50 (4H, broad singlet); 6,50-to 6.95 (2H, multiplet); 7,15-a 7.85 (1H, multiplet); the 7.65 (1H, singlet); 8,00 (1H, singlet).

Mass spectrum (m/z): 270 (M+), 253, 224, 187, 141.

P R e p a R a t I n m s p R I m e R 35. 3-(2,4-Differenl)-2-methyl-4-(1-1,2,4- triazole-1 - yl)-1,3-butanediol, with a melting point 93-113aboutthe wide singlet); is 3.82 (1H, doublet of doublets, J of 5.2 and 11.3 Hz); of 4.77 (1H, doublet, J 14.1 Hz); 4,96 (1H, doublet of doublets, J 1,6 and 14.1 Hz); and 5.30 (1H, broad singlet); 6,68-6,79 (2H, multiplet); 7,35-7,46 (1H, multiplet); of 7.75 (1H, singlet); a 7.92 (1H, singlet).

P R e p a R a t I n m s p R I m e R 36. 3-(2,4-Differenl)-2-ethyl-4-(1-1,2,4-three - azole-1-yl)-1,3-butanediol, in the form of amorphous powder, yield 94%

NMR-spectrum (l3), h/million or 0.83 (3H, triplet, J 7.5 Hz); 0,90-of 1.53 (3H, multiplet); of 3.96 (1H, doublet of doublets, J 4,4 or 11.7 Hz); 4,11 (1H, doublet of doublets, J 2,0 and 11.7 Hz); 4,78 (1H, doublet, J 14.1 Hz); of 4.95 (1H, doublet of doublets, J 1,2 and 14.1 Hz); 5,20 (1H, broad singlet); 6,88-to 6.80 (2H, multiplet); 7,31-7,40 (1H, multiplet); 7,74 (1H, singlet); of 7.90 (1H, singlet).

P R e p a R a t I n m s p R I m e R 37. 3-(2,4-Differenl)-2,2-dimethyl-4-(1-1,2, 4-triazole - 1-yl)-1,3 - butanediol, melting point 94-104aboutWith exit 92%

NMR-spectrum (l3), h /million of 0.93 (3H, doublet, J 2.0 Hz); of 1.13 (3H, doublet, J 2.0 Hz); 3,49 (1H, doublet, J 11.5 Hz); 3,55 (1H, doublet, J 11.5 Hz); 4,60 (1H, doublet of doublets, J 2,0 and 13.9 Hz); and 5.30 (1H, doublet of doublets, J 2.8 and a 13.9 Hz); of 5.82 (1H, broad singlet); 6,60-6,85 (2H, multiplet); 7,60-EUR 7.57 (1H, singlet); 8,02 (1H, singlet).

Mass spectrum (m/z): 298 (M++1), 224, 182, 141.

P R e p a R a t I n m s p R I m e R 38. 3-(2,4-Differenl)-2-phenyl-4-(1-1,2,4- triazole-1 - yl)-1,3-butanediol, Viet has doublets, J of 4.8 and 7.2 Hz); 6,50-of 7.60 (3H, multiplet); then 7.20 (5H, broad singlet); of 7.70 (1H, singlet); to 7.95 (1H, singlet).

P R e p a R a t I n m s p R I m e R 39. 3-(4-Isopropylphenyl)-2,2-dimethyl-4-(1-1, 2,4-tri - azole-1-yl)-1,3 - butanediol, in the form of oil, yield 98%

NMR-spectrum (l3), h /million 1,10-1,23 (N, multiplet); 2,04-2,90 (1H, multiplet); 3,44 (1H, doublet, J 13,1); OF 3.48 (1H, doublet, J 14.1 Hz); 7,06-7,30 (4H, multiplet); 7,72 (1H, singlet); of 7.96 (1H, singlet).

Mass spectrum (m/z): 304 (M+), 230, 221.

P R e p a R a t I n m s p R I m e R 40. 3-(4-Methoxyphenyl)-2,2-dimethyl-4-(1-1,2, 4-triazole-1-yl)-1,3 - butanediol, in the form of oil, yield 61%

NMR-spectrum (l3) h /million 0,81 (3H, singlet); to 1.21 (3H, singlet); 3,54 (1H, doublet, J 11.5 Hz); 3,66 (1H, doublet, J 11.5 Hz); of 3.78 (3H, singlet); 4,60 (1H, doublet, and 14.3 Hz); to 4.98 (1H, doublet, J of 14.3 Hz); 6,72-PC 6.82 (1H, multiplet); 7,15-7,20 (2H, multiplet); 7,72 (1H, singlet); with 8.05 (1H, singlet).

P R e p a R a t I n m s p R I m e R 41. 2,2-Dimethyl-2-ethyl-3-phenyl-3-(1-1,2,4- triazole-1 - yl)-1,3-butanediol, in the form of oil, yield 24%

NMR-spectrum (l3) h /million from 0.84 (3H, triplet, J 7.5 Hz); 1,22-of 1.40 (2H, multiplet); 1,73-to 1.87 (1H, multiplet); of 3.80 (1H, doublet of doublets, J 4.4 and 5.6 Hz); Android 4.04 (1H, doublet of doublets, J 14.1 Hz); 4,80 (1H, doublet, J 14.1 Hz); 7,19-7,38 (5H, multiplet); 7,98 (1H, singlet); of 8.09 (1H, singlet).

Mass spectrum (m/z: 261 (M+
NMR-spectrum (l3) h /million of 0.85 (3H, triplet, J 7,1 Hz); of 2.08 (1H, doublet of triplets, J 3.3 and 7.0 Hz); 2,30-3,20 (2H, broad peak); to 3.64 (1H, doublet of doublets, J 6,8 and 11.1 Hz); of 3.85 (1H, doublet of doublets, J of 3.3 and 11.1 Hz); 4,56 (1H, doublet, J of 14.2 Hz); 4,79 (1H, doublet, J of 14.2 Hz); 7,21-7,31 (4H, multiplet); to 7.84 (1H, singlet); of 8.09 (1H, singlet).

P R e p a R a t I n m s p R I m e R 43. 3-(4-Chlorophenyl)-2-ethyl-4-(1-1,2,4-triazole - 1-yl)-1,3-butanediol in the form of oil, yield 26%

NMR-spectrum (l3) h /million of 0.82 (3H, triplet, J and 7.6 Hz); 1,23-of 1.39 (2H, multiplet); 1,62-1,74 (1H, multiplet); 4,19-4,30 (2H, multiplet); to 4.41 (1H, doublet, J 14.4 Hz); 7,22-7,28 (4H, multiplet); for 7.78 (1H, singlet); with 8.05 (1H, singlet).

Mass spectrum (m/z): 295 (M+), 222, 213.

P R e p a R a t I n m s p R I m e R 44. 2-Ethyl-3-(4-forfinal)-4-(1-1,2,4-triazole - 1-yl)-1,3 - butanediol, temperautre melting 65-75aboutFrom exit 58%

NMR-spectrum (l3) h /million of 0.85 (3H, triplet, J 7.5 Hz); of 1.30 to 1.37 (2H, multiplet); 1,70-of 1.85 (1H, multiplet); 3,51 at 3.69 (2H, multiplet); of 3.77-a-3.84 (1H, multiplet); as 4.02-4,07 (1H, multiplet); of 4.57 (1H, doublet, J 14.1 Hz); of 4.77 (1H, doublet, J 14.1 Hz); 6,92-of 7.90 (4H, multiplet); 8,04 (1H, singlet); compared to 8.26 (1H, singlet).

Mass spectrum (m/z): 279 (M+), 206, 197.

EXPERIMENT 1. Curative activity against rust rice.

Seanice Fig spores of a fungus and keeping seedlings in moist chamber (relative humidity: 100%) at 20-22aboutC. After 24 h the rice seedlings were sprayed with an aqueous suspension of ipetumodu compounds at a concentration of 10 hours/million in the amount of 30 ml per three pots. The rice seedlings were then kept in a moist chamber for an additional 6 days. As a control, a few plants were exposed to the fungus, but they were not treated with any anti-fungal agent.

The activity index was determined on the basis of the number of defects formed on the upper two leaves of each plant. The results are shown in table. 4. In this and subsequent tables, the compounds of the invention are identified by the number of one of the following examples, which describe their receipt.

The activity index was evaluated based on the extent of disease, which was determined by inspection with the naked eye, and the metric is given by the following symbols (the same applies to the subsequent experiments):

5 the absence of disease

4 the degree of disease was 10% or less degree from untreated plants

3 the extent of the disease 10-30% from the disease untreated plants

2 the extent of the disease 30-50% of the extent of disease untreated plants

1 the degree to zabolevaniy unprocessed plant and almost the same as the degree of the disease untreated plants.

EXPERIMENT 2. Activity prevent scurf of rice plants.

Seedlings of rice (variety Hihonbare) in stage 4-5 leaf was sprayed with an aqueous suspension of the test compounds at a concentration of 100 PM/million (30 ml /3 pot). The seedlings then chroniles for 24 h at room temperature, after which they were inoculable Rhizostinia solani by placing 4-5 seeds of oats, which was pre-cultivated fungus around the base of each seedling. The seedlings were then kept in a moist chamber (relative humidity 100% ) for 5 days at 25-27aboutC. the Rate of activity is given on the basis of the height of the damage formed on the seedlings of rice.

The results are shown in table. 5.

EXPERIMENT 3. Curative activity against Rhizoctonia plant rice.

Seedlings of rice (raznovidnosti Hohanbare) at stage 4-5 page inoculable Rhizostinia solani by placing 4-5 grains of oats, which was pre-cultivated fungus, around the base of each seedling rice, and kept in a moist chamber (relative humidity 100%) at 25-27aboutC. After 24 h the rice seedlings were sprayed with an aqueous suspension of the tested compounds in the concentrate the activity is given on the basis of the height of the damage, formed on the seedlings of rice.

The results are shown in table. 6.

EXPERIMENT 4. Preventive activity against Rhizoctonia plant rice.

Seedlings of rice (variety Hihon bare) at the stage of 3-4 leaves grown in pots were filled with water to a depth of 1 cm and Then in relation to the water in the pots was used the test compound in an amount corresponding to 100 g per 10 acres. After the seedlings were kept in a greenhouse for 7 Nam, they were inoculable Rhizostinia solani by placing 4-5 grains of oats, pre-infected with a fungus, around the base of each seedling. The seedlings were then derivates in a moist chamber (relative humidity 100%) for 5 days at 25-27aboutC. the Rate of activity was provided on the basis of the height of the damage formed on the seedlings of rice.

The results are shown in table. 7.

EXPERIMENT 5. Activity against gibberish of rice plants during the impregnation of seeds.

10 g of rice seeds (variety Tangin bozu) that were previously infected with the fungus Jibberella fuji Huroi by spraying them with a spore suspension of the fungus, was immersed in 20 ml of an aqueous suspension of the test compounds at a concentration of 100 PM/million in 3 days. At the end of this periodaboutC. the Rate of activity was provided on the basis of the number of damaged seedlings.

The results are shown in table. 8.

EXPERIMENT 6. Curative activity against leaf rust of wheat.

Seedlings of wheat (variety Noreen N 61) at the stage 1.5 sheet inoculable fungus Puccinia recondita by spraying spores of fungi on seedlings. The seedlings were kept in a moist chamber (relative humidity 100%) within 24 h at 20-22aboutWith, after which they endured in a greenhouse with a temperature of 15-20aboutC. After 2 days, the seedlings were sprayed with an aqueous suspension of the test compounds at a concentration of 3 hours/million (30 ml/3 pot). The seedlings are then continuously maintained in a greenhouse for 10 days. The activity index was cited on the basis of the affected area of the first sheet at the end of this time.

The results are shown in table. 9.

EXPERIMENT 7. Curative activity against powdery mildew of barley.

Seedlings of barley (variety is Sekizinci) at the stage of the first sheet was intolerable condition erysiphe granunis f.sp. hordei by spraying spores of fungi on seedlings, which are then kept in the greenhouse at 15-20aboutC. After one day, the seedlings were sprayed with an aqueous suspension of isptar within 10 days. The activity index was cited on the basis of the affected area of the first sheet at the end of this period of time.

The results are shown in table. 10.

EXPERIMENT 8. Preventive activity to prevent downy mildew of cucumbers.

Seedlings of cucumber (variety to Sagamihara) at the stage of 3-4 leaves were sprayed with an aqueous suspension of the test compounds at a concentration of 300 hours /million (30 ml/3 pot). The seedlings were then kept for 24 h at room temperature, after which they were inoculable condition Sphaerotheca fuliginaa by spraying seedlings with spores of the fungus. After the seedlings were subjected to uderzhivanie in the greenhouse at 20-30aboutC for 7 days was assessed by the rate of activity on the basis of the affected area of the third and fourth leaves.

The results are shown in table. 11.

EXPERIMENT 9. Preventive activity prevent Apple scab.

Apple seedlings at the stage of 3-4 leaves were sprayed with an aqueous suspension of the test compounds with a concentration of 300 hours/million (30 ml/3 pot). The seedlings were then kept for 24 h at room temperature, after which they were inoculable fungus Venturia inaegualis by spraying the IC 100%) for 3 days at 20-22aboutC, and then transferred to the greenhouse at 20-22aboutWith 10 days. The activity index was cited on the basis of the affected area of the third and fourth leaves at the end of this period of time.

The results are shown in table. 12.

EXPERIMENT 10. Protivogribkova activity.

Fungal disk with a diameter of about 4 mm was inoculable on medium agar (2% by weight of malt extract, 1% glucose, 0.3% Penton and 2% agar) in Petri dish with a diameter of 9 cm, by placing the disk in the center environment. Samples of paper discs were prepared by impregnation of a disk (diameter 8 mm, thickness 0.7 mm) 30 μl of an acetone solution containing 300 hours/million of the test compound, and subjected it dry sterilization. The sample disk was placed in a circle at a distance of approximately 1 cm from the edge of the raised spots of fungus three days after inoculation. The samples are then kept at 25aboutC for 5 days, after which the antifungal activity was determined by visual observation of contamination of samples by the fungus.

Tested fungi were Aspergillus niger; Gliocladium virens and Fusarium moliniforme.

The results are shown in table. 13.

EXPERIMENT 11. Activity predgradie wood.

Pro Tyromyces palustris, previously described in the I/S A-9302.

The results are shown in table. 14.

The compounds of formula (1) and their salts are useful as fungicides and fungistatic agents for agricultural, horticultural and similar uses. For such applications, they can be converted or be formulated in the conventional formulation for such use, and they can be applied to plants, parts of plants, the reproductive parts of plants or to the distribution or to the environment containing such plants, plant parts or parts for their reproduction, as is well known conventional fungicides and other agricultural chemicals.

In particular, it was found that they are highly effective antifungal agents, no harm to plants, to which they are applied.

So, for example, Rhizoctonia, an important disease affecting rice culture, can be prevented when the connection is used in the form of the preparation for spraying or sputtering, or for use in immersion conditions. When connections are used for soil or seeds, they are particularly efficient in progenia fungus Rhizostonia and soil infectious diseases, such as Sclerotinia rot of eggplant or cucumbers, etc. or felt the disease (white leg) of potato.

The amount used in practice, such crops as rice, tomato, potato, cotton, eggplant, cucumbers or beans, are not damaged by the compounds of the present invention.

In addition, these compounds may also be applied to gardens, nepolian lands, forests and similar.

Reflecting the activity of the compounds of the present invention, the invention further provides compositions that contain one or more compounds of the invention together with a carrier and optionally other auxiliary agents, if necessary. These compounds can be formulated in the form of drugs of the type commonly used for agricultural or horticultural use in the form of Farrukh Dustov, rough Farrukh Dustov, micro granules, fine granules, wettable powders, emulsifiable concentrates, aqueous or oil suspensions, and aerosols. Of course there is no need to use a completely pure form of the compound of the invention in the composition, and, of course, the cleaning can be carried out at any stage or may be delayed, and the resulting crude substance kompozitsiah can be natural or synthetic and organic or inorganic substances; they are usually used in order to promote the active ingredient of the processed substrate, and in order to facilitate storage,transportation or handling of the active connection. It can be solid, liquid or gaseous.

Suitable solid carriers include inorganic substances such as clay (examples of which include bentonite, kaolinite, montmorillonite, and attapulgite), talc, mica, agalmatolite, pyrophyllite, pumice, vermiculite, gypsum, calcium carbonate, dolomite, diatomaceous earth, magnesium carbonate, appetit, zeolite, silicic anhydride, synthetic calcium silicate; vegetable organic substances such as seluja nuts (for example, different types of nuts, in shell and other) soybean meal, tobacco powder, powder, walnut shell, wheat flour, wood flour, starch and crystalline cellulose; synthetic or natural high molecular weight polymers, especially resins, such as coumarone resin, petroleum resin, alkyd resin, polyvinyl chloride, polyalkylene glycols, ketone resin, ester resin, xantonova resin, resin Kopala and demurova resin; waxes, such as Carnauba wax and beeswax; or urea.

is, mineral oil, engine oil and petrolatum or white oil; aromatic hydrocarbons such as benzene, toluene, xylene, solvent naphtha, benzene, cumene, methylnaphthalene; halogenated hydrocarbons, especially chlorinated hydrocarbons such as carbon tetrachloride, chloroform, trichloroethylene, monochlorobenzene and o-chlorotoluene; ethers such as dioxane and tetrahydrofuran; ketones, such as acetone, methyl ethyl ketone, Diisobutylene, cyclohexanone, acetophenone and isophorone; esters such as ethyl acetate, amylacetate, etilenglikolya, diethylenglycol, dibutylated and diethylamine; alcohols, such as methanol, ethanol, isopropanol, hexanol, ethylene glycol, diethylene glycol, cyclohexanol, and benzyl alcohol; fireparty, such as ethylene glycol-monotropy ether, ethylene glycol-monopoloy ether, diethylene glycol-monotropy ether and dietilen glycol monobutyl ether; other polar solvents such as dimethylformamide and dimethylsulfoxide; and water.

Suitable gaseous media include air, nitrogen, carbon dioxide and fluorocarbon propellants, such as substance sold under the trademark "Freon", they can be mixed world is different agents and/or polymers to improve the properties of the compositions and in order to facilitate their dispersion, emulsification, distribution, penetration due, or to control the disintegration of improving fluidity or imparting corrosion resistance of the composition, or for the stabilization of the active compounds. Can be any of the common classes of surface-active agents (non-ionic, anionic, cationic or amphoteric), but it is preferable to use nonionic and/or anionic surface-active agents, and can therefore improve the wetting, adhesion and absorption and to achieve the desired effects.

Examples of suitable nonionic surface-active agents include the polymerization adducts of ethylene oxide with higher alcohols, such as lauric alcohol, stearyl alcohol and alerby alcohol; the polymerization adducts of ethylene oxide with ALKYLPHENOLS, such as isooctylphenol or Nonylphenol; the polymerization adducts of ethylene oxide with alkylnaphthalene, such as mutilator or occilator; the polymerization adducts of ethylene oxide with higher fatty acids such as palmitic acid, stearic or oleic acid; the polymerization adducts of ethylene oxide with mono - or dialkylphosphinate acids such as steelfactory Comedy or ethoxylated amides of higher fatty acids, such as stearamide, esters of higher fatty acids and polyhydric alcohols, such as sorbitan, and the polymerization adducts of ethylene oxide with them; esters of higher fatty acids and glycerinated or of ethoxylated glycerinated; glycerides and sharefire fatty acid; the polymerization adducts of ethylene oxide with propylene oxide.

Examples of suitable anionic surface-active agents ulkucu salts of higher fatty acids, i.e. soap, for example, sodium oleate, salts, such as sodium and calcium salts of sulfonic acids and these acids, for example, ligninsulfonate acid and arylsulfonate salts such as isopropylnaphthalene sodium, methylenephosphonate sodium, ligninsulfonate sodium or dodecylbenzenesulfonate sodium, or alkylsulfonate salts, especially diallylmalonate sodium, such as dioctylsulfosuccinate sodium or 2-ethylhexylcarbonate sodium; salt, for example sodium, ammonium and amine salts, sulfates polyoxyethyleneglycol ether or sulfates polyoxyethyleneglycol ester or free acid; or salts of the phosphates polyoxyethylenated kilowog ether or polyoxyethylenesorbitan; alkylsulfate salt, such as the on-active substances include higher aliphatic amines and condensates of ethylene oxide; Quaternary ammonium salt, such as chloride; N-alkylamines; and N-alkylamines.

Examples of amphoteric surfactants include betaines and surfactants amino acid type.

In addition, the compositions of the present invention can be used in combination with compounds with high molecular weight or other agents ready preparative forms, for example: protective colloids such as casein, gelatin, Arabian Kamel, albumin, glue, sodium alginate, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose or polyvinyl alcohol; dispersing agents such as sodium polyphosphate; inorganic dispersing agents such as bentonite or veegum; stabilizers; binding agents; and antifreeze agents. For wider application and economy of labor composition of the invention may, if necessary, be combined with one or more other agricultural chemicals such as fungicides, insecticides, herbicides, plant growth regulators and fertilizers.

The above-mentioned carriers and a variety of auxiliary agents can be used alone or in any need is by determining the concentration of active ingredient in the preparative form.

For example, dusty can coderoute from 0.1 to 25% by weight of active compound, and the remainder is solid media. Wettable powders may contain, for example, from 1 to 90%, preferably from 25 to 80% by weight of the connection, and the rest is solid dispersing and wetting agent, if required, together with a protective colloidal agent, thixotropic agent and defoaming or protivoanemi agent.

Granules can contain from 1 to 35% by weight of active compound, with a large proportion of the remainder is solid media. An active connection is homogeneous mixed with a solid carrier, or glued to the surface or adsorbed on the carrier surface; the diameter of each of the granules is preferably from 0.2 to 1.5 mm

Emulsione concentrates may typically contain, for example, from 5 to 50% by weight of active compound and from 5 to 20% by weight of emulsifying agent, and the remainder is liquid carrier, if required, together with corrosion inhibitor.

Oil preparations may contain from 0.5 to 5% by weight of active compound, and the balance is carrier liquid, such as kerosene.

Aerosols can contain from 0.1 to 5% by weight of active soudant, such as liquefied petroleum gas, a fluorocarbon, or carbon dioxide.

Compositions of the invention can be applied, for example, in relation to a filling or other fields, before or after the appearance of disease in plants, or in relation to plants already infected with harmful fungi; suitable is usually the concentration of active ingredient of from 10 to 500 hours/million especially for application to the leaves and stems of plants and to the soil, by means of what can be achieved with effective suppression of disease.

The composition of the invention can be mixed with another fungicide to achieve a more broad-spectrum fungicide, and, in some cases, it can be expected synergies. Other suitable fungicides include fungicides urethane type, such as 3,3-ethylenebis/tetrahydro-4,6-dimethyl-2H-1,3,5-thiadiazin-2-tion, ethylenebisdithiocarbamate zinc or manganese, bis(dimethylthiocarbamyl)disulfide, propyltrimethylammonium zinc, methyl 1-(butylcarbamoyl)-2-benzimidazolone - Mat, 1,2-bis(3-methoxycarbonyl-2-touraid)benzene and bidirectionality-ethylenebisdithiocarbamate;

funktivity dicarboximides type, such as N-trichloromethylthio-4-cyclohexane, as 5,6-dihydro-2-methyl-1,4-oxazin-3-carboxanilide-4,4-dioxide;

fungicides naftochinona type, such as 2,3-dichloro-1,4-naphthoquinone;

other fungicides, such as 3-hydroxy-5-methylisoxazol, 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole, 2,4-dichloro-6-(o-chlorine - anilino)-1,3,5-triazine, 2,3-dicyano-1,4-dicyandiamide, 8-hinlet copper, polyoxin, validamycin, tetrachloroisophthalonitrile, 2-(1-methylpropyl)-4,6-dinitrophenol, dimethylacrylate, hydroxide triphenylamine, mitomycin, dinitrodiethylenediamine, 5-butyl-2-dimethylamino-6-methylpyrimidin-4-ol, 6-(3,5-dichloro-4-methyl - phenyl)-3-(2H)pyridazinone, 6-(3-bromophenyl)-3-(2H)-pyridazinone, N-(2,6-dimetilfenil)-N-methoxyacetanilide ester and bis(8-guanidinoacetic)amidated.

Compositions of the invention can be mixed with the insecticide.

Suitable insecticides include phosphorus-containing insecticides such as 0,0-diethyl 0-(2-isopropyl-4-methyl-6-pyrimidinyl)phosphorothioate, 0,0-diethyl S-[2-(ethylthio)ethyl] phosphodithioate, 0,0-dimethyl 0-(3-methyl-4-nitrophenyl)thiophosphate, 0,0-dimethyl S-(N-methylcarbamoylmethyl)phosphorodithioate, 0,0-dimethyl S-(N-methyl-N - formylmorpholine)phosphorodithioate, 0,0-dimethyl S-[2-(ethylthio)ethyl] phosphorodithioate, 0,0-dimethyl-1-hydroxy-2,2,2-trichlorethylene, 0,0-fenil phenylphosphonate, 0,0-dimethyl-S-(1,2-dicarboximide)phosphorodithioate, 2-chloro-1- (2,4,5-trichlorophenyl)vinyldimethyl-phosphate, 2-chloro-1-(2,4-dichlorophenyl)vinyldimethyl-phosphate, 0,0-dimethyl-0-p-cyanophenyl-phosphorothioate, 2,2-dichlorobenzenesulfonate, ethylmercurithiosalicylate, 0,0 dime - typofonderie, S-[(6-chloro-2-oxo-3-benzoxazolyl)-methyl] -0,0-dietists-traditioal, 4-methylthiophenyl-dipropylacetate, 2-chloro-1-(2,4-dichlorophenyl)vinyldimethyl, 0,0-diethyl-0-(3-oxo-2 - phenyl-2H-pyridazin-6-yl)phosphorothioate, 0,0-dimethyl S-(1-methyl-2-ethylsulfinyl)ethylphosphonate, 0,0-dimethyl S-phthalimidophosphorous, dimethyl - methylcarbamoylmethyl-typosphere - tioat, 0,0-diethyl S-(N-etoxycarbonyl-N-methylcarbamoylmethyl)phosphorodithioate, 0,0-dimethyl-S-[2-methoxy-1,3,4-thiadiazol-5(4H)-IMT-(4)-methyl] dithiophosphate, 2-methoxy-4H-1,3,2-benzodioxaphosphorin-2 - sulfide, 0,0-diethyl-0-(3,5,6-trichloro-2-piridin)phosphorothioate, 0, S-dimethyl-N-acetylphosphoramidothioate, 0-2,4-dichlorophenyl 0-ethyl-S-propylphosphonate, 0,0-diethyl S-(2-chloro-1-phthalimidomethyl)phosphorodithioate and 0-6-ethoxy-2-ethylpyrimidine-4-yl 0,0-dimethylphosphorodithioate;

insecticides urethane type, such as 1-naphthyl N-methylcarbamate, S-methyl-N-[methylcarbamoyl] thioacetimidate, 2-sec-butyl-phenyl-N-methylcarbamate, 2-isopropoxyphenyl-N-metelka is metolcarb - Mat;

and other insecticides, such as nicotinuric, milbemycin D, 6-methyl-2,3-inoxidizability, S,S-ditioner - Bonet, 2,4-dinitro-6-sec-butylphenylmethyl, 1,1-bis-(p-chlorophenyl)-2,2, 2-trichloroethanol, ethoxybenzoyl, di(p-chlorophenyl)-cyclopropyl-carbinol, isopropyl-4,4'-dichlorobenzil, ethyl 4,4'-dichlorobenzil, ethyl 0-benzoyl(3-chloro-2,6-dimethoxybenzonitrile, isopropyl 4,4'-dibromobenzyl, hydroxide tricyclohexyl, hexacis (- dimethylpentyl)-distance - oxen, 2-(4-tert-butylphenoxy)cyclohexyl-prefinished, 3-methyl-1,5-bis- (2,4-xylyl)-1,3,5-tratamento-1,4-diene, 2,4, 5,4'-tetrachlorodiphenyl, hexachlorocyclopentadiene, acid oxalate 5-dimethylamino-1,2,3-trithiane and engine oil.

However, the nature or character of any such additional insecticide is not critical, i.e. the determining factor. Additionally, if desired, the compounds of the present invention can be mixed with other conventional agricultural or horticultural materials such as acaricides, nematicides, herbicides, plant growth regulators, manure or substances, conditioning the soil, to obtain compositions having a wider range of applications and/or to reduce employment from weather conditions, type of application, time of application, method of application, the nature of the environment, the nature of the disease, the type of plants and a variety of other known factors, but preferably the compound may be used in quantities of from 0.1 to 100 g of the effective ingredient in ar, preferably from 5 to 40, Emulsifiable concentrates, wettable powders, suspension concentrates and similar preferably applied by diluting a specified number, for example, 1-10 l of water for ar, and pellets are usually applied without dilution. If desired, the water used for dilution may be added other additives, such as agents, distribution or spreaders, for example surface-active agents, polyoxyethylene resin acid, ligninsulfonate, salts of abietic acid, dinaftiletilena, paraffin.

Compounds of the present invention can also be used as pharmaceutical agents for the treatment of fungal infections, such as skin, in these cases they are usually assigned to the tonic or local application, or intestinal infectious diseases, in which case they can be oral or parenteral. Believe that they are particularly valuable invention is used for pharmaceutical purposes, it may be administered in the form of any generally accepted pharmaceutical finished formulation, the nature of which, as is known, depends on how the purpose and nature of the condition being treated. Thus, the compounds of the invention can be formulated in the form of conventional dosage forms, usually in a mixture with a pharmaceutical diluent or carrier. For oral purpose of the connection may be converted, for example, in the form of tablets, capsules, granules, powders or syrups. For parenteral purposes they can be formulated in the form of injectable preparations in suitable liquid or in the form of medical candles. For topical purposes they can be formulated in the form of ointments, creams, powders, liquids or aerosols. These pharmaceutical preparations can be produced using conventional means using auxiliary agents commonly known in this field, such as excipients, diluents, dispersing funds, binder, disintegrator, lubricant agents, stabilizers, corrigentov and similar.

Dosage and frequency of administration can vary depending on symptoms, age and body weight of patient, but also on the method of appointment and the compulsory dose of from 100 to 600 mg, which can be applied either as a single dose or divided into several doses.

1. Fungicidal derivatives of oxetane General formula

< / BR>
where R1and R2the same or different, are each hydrogen or C1-C6is an alkyl group, or R1and R2together with the carbon atom to which they are attached, form a3-C6-cycloalkyl group;

R3and R4the same or different, are each hydrogen, C1-C6is an alkyl group or phenyl, or R1, R3and the carbon atoms to which they are attached, together form cycloalkyl group having 5 or 6 ring atoms and condensed with oxetanone ring;

Ar is phenyl, substituted by the radicals R5, R6and R7where R5, R6and R7the same or different, are each hydrogen, halogen, C1-C6is an alkyl group, a C1-C6-alkoxygroup,1-C6-haloalkyl group or1-C6-haloalkoxy;

R8and R9the same or different, are each hydrogen or C1-C4is an alkyl group,

and their salts.

2. Connection on p. 1, wherein R1, R2

3. Connection on p. 1, wherein one of R1and R2is hydrogen and the other WITH1-C4is an alkyl group and one of R1and R4is hydrogen or C1-C4is an alkyl group and the other WITH1-C4is an alkyl group.

4. Connection on p. 1, wherein one of R1and R2is hydrogen and the other methyl or ethyl group and one of R3and R4is hydrogen or a methyl group and the other is methyl group.

5. Connection on p. 1, wherein R1and R4methyl group, and R2and R3the hydrogen.

6. Connection on p. 1, wherein R1ethyl group, R4methyl group, and R2and R3the hydrogen.

7. Connection on p. 1, wherein R1and R2hydrogen, and R3and R4methyl group.

8. Connection on p. 1, wherein R1, R3and R4is a methyl group, and R2the hydrogen.

9. Connection on p. 1, wherein Ar is phenyl group substituted by the groups R5, R6and R7where R5, R6and R7the same or different, are each hydrogen, halogen or1-C4-R5, R6and R7where R5, R6and R7the same or different, each a hydrogen or halogen.

11. Connection on p. 1, wherein R5, R6and R7- same or different, are each hydrogen, chlorine, fluorine or bromine.

12. Connection on p. 1, wherein one of R5, R6and R7is hydrogen and the other is the same or different, are each a halogen or1-C4-halogenated alkyl group.

13. Connection on p. 1, wherein one of R5, R6and R7is hydrogen and the other is the same or different, each halogen.

14. Connection on p. 1, wherein one of R5, R6and R7is hydrogen and the other is the same or different, each fluorine or bromine.

15. Connection on p. 1, wherein Ar is o-chlorophenyl, p-chlorophenyl, p-forfinal, p-bromophenyl, 2,4-differenl, 2,6-differenl, 2,4-dichlorophenyl, 2-chloro-4-forfinal, 4-chloro-2-forfinal, 6-chloro-2-forfinal, 4-triptoreline or 4-triphtalocyaninine group.

16. Connection on p. 1, wherein Ar is p-chlorophenyl, p-forfinal, 2,4-differenl, 2,4-dichlorophenyl, 2-chloro-4-forfinal or 4-chloro-2-Fortunella group.

1-C4alkyl group.

18. Connection on p. 1, wherein R8and R9the hydrogen.

19. Connection on p. 1, wherein R1, R2, R3and R4- same or different, are each hydrogen or C1-C4is an alkyl group, Ar is phenyl group, substituted R5, R6and R7where R5, R6and R7- same or different, are each hydrogen, halogen or1-C4-halogenated alkyl group and one of R8and R9hydrogen and the other is hydrogen or C1-C4is an alkyl group.

20. Connection on p. 1, wherein one of R1and R2is hydrogen and the other WITH1-C4is an alkyl group, one of R3and R4hydrogen or C1-C4is an alkyl group and the other WITH1-C4is an alkyl group, Ar is a phenyl group substituted by the substituents R5, R6and R7where R5, R6and R7the same or different, are each hydrogen, halogen, or C1-C4-halogenated alkyl group and one of R8and R9hydrogen and the other is hydrogen or C1-C4is an alkyl group.

21. Connection on p. 1, otlichayas/SUB> is hydrogen or a methyl group and the other is methyl group, Ar is a phenyl group substituted by the substituents R5, R6and R7where R5, R6and R7- same or different, each a hydrogen or halogen and R8and R9- hydrogen.

22. Connection on p. 1, wherein R1and R4a methyl group and R2and P3hydrogen, Ar o-chloraniline, p-chloraniline, p-Fortunella, p-bratinella, 2,4-differenly, 2,6-differenly, 2,4-dichloraniline, 2-chloro-4-Fortunella, 4-chloro-2-Fortunella, 6-chloro-2-Fortunella, 4-triftormetilfullerenov or 4-triphtalocyaninine group and R8and R9the hydrogen.

23. Connection on p. 1, wherein R1and R4methyl group, and R2and R3hydrogen, Ar-p-chloraniline, p-Fortunella, p-bratinella, 2,4-differenly, 2,4-dichloraniline, 2-chloro-4-Fortunella or 4-chloro-2-Fortunella group, and R8and R9- hydrogen.

24. Connection on p. 1, wherein R1ethyl group, R2and R3hydrogen, R4methyl group, Ar p-chloraniline, p-Fortunella, p-bratinella, 2,4-differenly, 2,4-dichloraniline, 2-chloro-4-forfamilies fact, what R1and R2hydrogen, R3and R4a methyl group, Ar p-chloraniline, 2,4-differenly, 2,4-dichloraniline, 2-chloro-4-Fortunella or 4-chloro-2-Fortunella group, and R8and R9the hydrogen.

26. Connection on p. 1, wherein R1, R3and R4is a methyl group, R2hydrogen, Ar p-chloraniline, p-Fortunella, p-bratinella, 2,4-differenly, 2,4-dichloraniline, 2-chloro-4-Fortunella or 4-chloro-2-Fortunella group, and R8and R9- hydrogen.

27. Connection on p. 1, characterized in that it is a 2-(2,4-differenl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetane, 2-(4-chlorophenyl)-4-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetane, 2-(4-forfinal)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1-yl methyl] oxetan, 4-ethyl-2-(4-forfinal)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetane, 4-ethyl-2-(4-forfinal)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oxetan or its salt.

28. Connection on p. 1, characterized in that it is a (2R*, 3S*, 4R*) -2-(2,4-differenl)-3,4-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl] oxetane, (2R*, 3S*, 4R*) -2-(4-chlorophenyl-3,4-dimethyl-2-[(1H-1,2,4-triazole-1-yl)methyl)oxetan, (2R*, 3S*, 4R*) -2-(4-forfinal)-3-triazole-1-yl)methyl] oxetan or its pharmaceutically acceptable salt.

 

Same patents:

The invention relates to water-soluble derivatives of Taxol with antitumor activity, and more particularly to a sulfonated derivative of 2'-acryloyloxy, a derivative of 2'-sulfoalkylation-0-allcollege Taxol 2'-ethylene-glycol-0-allcollege Taxol

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The invention relates to derivatives of Taxol, which have better solubility compared with Taxol and show good anticancer activity

The invention relates to chemical compositions for protecting plants, particularly to fungicidal compositions based on the derived 1-phenyl-2-(1,2,4-triazole-1-yl)-propene

The invention relates to the chemistry of heterocyclic compounds, namely, to a method for producing 4-amino-1,2,4-triazole, which can be used as intermediate for the production of dyes, drugs, corrosion inhibitors, additives for plastics, etc

The invention relates to a method for producing derivatives of triazole, exhibiting antifungal activity, namely the method of production of 2-aryl-3-(3-haloperidol-4-yl or 5-galerimizin-4-yl)-1-(1H-1,2,4-triazole-1-yl)alkyl-2-Aulnay derivatives, applicable to combat fungal infections of animals and humans

The invention relates to the chemistry of heterocyclic compounds, and in particular to an improved method for producing a 1-vinyl-1,2,4-triazole, which is used as a monomer for the synthesis of water-soluble and swollen polymers having valuable technical and biological properties

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FIELD: agriculture.

SUBSTANCE: invention relates to agriculture. Presowing treatment of wheat seeds and oat seeds is carried out with an aqueous solution of dimethyl (2,2-dichlorocyclopropylmethyl) phosphate with a concentration of active ingredient 0.001% at a dose of 1 l per 1 kg of seeds.

EFFECT: invention enables to increase vigor and seed germination.

1 tbl, 1 ex

FIELD: agriculture.

SUBSTANCE: invention relates to agriculture. Bis (2,2-dichlorcyclopropylmethyl) phosphite C8H11Cl4O3P is used as a stimulant for presowing treatment of cereal crops seeds.

EFFECT: invention enables to speed up the ripening of cereal crops.

1 tbl, 1 ex

FIELD: agriculture.

SUBSTANCE: invention relates to agriculture. Presowing treatment of seeds is carried out with an aqueous solution of tris (2,2-dichlorcyclopropylmethyl) phosphate with a concentration of active ingredient 0.001% at a dose of 1 liter per 1 kg of seeds.

EFFECT: invention enables to increase viability and germination of cereal crops seeds.

1 tbl, 1 ex

FIELD: agriculture.

SUBSTANCE: invention relates to agriculture. Dimethyl (2,2- dichlorcyclopropylmethyl) phosphate of formula C6H11CI2O4P is used as a stimulating agent for presowing treatment of cereal crops seeds.

EFFECT: invention enables to increase the viability and germination of cereal crops.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to agriculture. Tris-(2,2-dichlorocyclopropylmethyl)phosphate of formula C12H15Cl6O4P is used as a stimulant for presowing treatment of grain crop seeds.

EFFECT: invention accelerates ripening of grain crops.

1 tbl

FIELD: agriculture.

SUBSTANCE: invention relates to agriculture, and is intended to increase the germinating energy, germinating ability and acceleration of beginning of crop ripening. Presowing treatment of seeds is carried out with an aqueous solution of 0.01% (2,2 dichlorocyclopropylmethyl) dimethylborate C6H11Cl2O3B of the formula (I) at the rate of 1 litre of the solution per 1 kg of seeds.

EFFECT: invention accelerates the beginning of crop ripening, and expands the range of the means of this purpose.

1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to agriculture and is meant for increasing germination power and capacity of seeds and speed up the beginning of ripening of crops. Presowing treatment of the seeds is carried out with 0.01% aqueous solution of bis(2,2-dichlorocyclopropylmethyl)methyl borate C9H13Cl2O3B of formula (I) in amount of 1 l solution per 1 kg seeds.

EFFECT: invention speeds up the beginning of ripening of crops and widens the range of agents for this purpose.

1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a molecule of formula one, where R1 is H, F, Cl, Br or I; R2 is H, F, Cl, Br or I; R3 is H, F, Cl, Br or I; R4 is H, F, Cl, Br or I; R5 is H, F, Cl, Br or I; R6 is a (C1-C8)halogenalkyl; R7 is H; R8 is H; R9 is H; R10 is F, Cl, Br, I, (C1-C8)alkyl or halogen(C1-C8)alkyl; R11 is C(=O)N(R14)((C1-C8)alkylC(=O)R15); R12 is H; R13 is H; R14 is H; R15 is N(R16)(R17) or (C1-C8)alkyl-C(=O)N(R16)(R17); R16 is H; R17 is halogen(C1-C8)alkyl; X1 is CR12; X2 is CR13; X3 is CR9. Formula one

EFFECT: obtaining novel compounds which can be used against pests.

9 cl, 3 tbl, 129 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: 5-aryl-1H-1,2,4-triazole derivatives of general formula I

, pharmaceutically acceptable salts thereof or pharmaceutical composition containing the same are described. In formula R1 is C1-C6-alkyl, C1-C6-haloalkyl or phenyl; R2 is C3-C8-cycloalkyl; phenyl optionally substituted with one or more substituents selected from C1-C4-alkyl; halogen, hydroxyl, C1-C4-alkoxy, nitro, di-(C1-C4)-alkylamino, C1-C4-alkylsulphonyl, C1-C4- alkylsulphonylamino, and methylenedioxy; phenyl-(C1-C4)-alkyl, wherein phenyl is substituted with C1-C4-alkoxy; or pyridil. New compounds are effective and selective cyclooxygenase-2 (COX-2) inhibitors and useful in treatment of inflammations.

EFFECT: new compounds for inflammation treatment.

10 cl, 36 ex, 1 tbl

FIELD: synthesis of lubricant oil additives.

SUBSTANCE: method for production of O-(n-butyl)-O-3,4,5-trithiatricyclo-dez-8-yl-methyl)-dithiophosphoric acid 1-(N,N-dimethylaminomethyl)-1,2,4-triazole salt of general formula

is disclosed. 1-(N,N-dimethylaminomethyl)-1,2,4-triazole is brought into reaction with equimolar amount of O-(n-butyl)-O-3,4,5-trithiatricyclo-dez-8-yl-methyl)-dithiophosphoric acid in toluene medium at 80-100°C for 2-4 h.

EFFECT: ash-free antiscoring lubricant oil additive operating under high pressure.

2 tbl, 1 ex

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