Amido - or urea - derivatives, or their pharmaceutical salts and the composition having inhibitory activity against acyl-coa:cholesterol acyltransferase

 

(57) Abstract:

The proposed compounds of formula (I):

< / BR>
where R1means alkyl group; or a group of formula (II), (III), (IV) or (Y):

< / BR>
and where R2, R3, R4and R5are hydrogen or various organicheskoi groups; and their pharmaceutically acceptable salts; as well as methods for their preparation and their use in the treatment and prevention of hypercholesteremia and atherosclerosis. 3 S. and 29 C.p. f-crystals, 32 ill., 12 table.

The invention relates to a series of new amido, urea compounds with antihypercholesterolemic activity, which therefore can be used in the treatment and prevention of hypercholesteremia, atherosclerosis and related diseases. The invention also encompasses methods and compositions using such compounds, and methods for their preparation.

It is believed that among the reasons for ischemic heart failure (which may be the result of angina, myocardial infarction and the like) atherosclerosis is the most important. It is believed that the surface of the cells under the endodermal cell layer of blood vessels accumulate cholesterol esters, and this is the main reason atrocities cholesterol on the cell surface and inhibit the formation and development of atherosclerosis, caused by accumulation of cholesterol esters.

In addition, it was found that there is a link between atherosclerosis and hypercholesterolemia. The cholesterol contained in food is absorbed in the form of free cholesterol in the cells lining the intestinal tract. Then he tarifitsiruetsya using AST and enters the bloodstream. Therefore, the ACAT inhibitor prevents the increase in the concentration of cholesterol in the blood by inhibiting the absorption of dietary cholesterol in the blood.

For this reason, the compounds according to the present invention, which has the ability to inhibit the activity of AST, are useful in the treatment and prevention of atherosclerosis.

Compounds of the present invention have (9H-xanthene-9-yl)methyl group, 6,11-dihydrobenzo[b, e] azepin-11-strong group, (1-phenylcyclohexyl)methyl group, n-alkoxyphenyl group or alkyl group attached to the amide or urea group. The compound containing (9H-xanthene-9-yl)methyl group, described in the publication WO 93/06096 and EP 337375. Compounds containing 6,11-dihydrobenzo[b, e] azepin-11-strong group, described in the publication EP 497201. Compounds containing (1-phenylcyclohexyl)methyl group, described in the publication EP 293880. Soy is the SCP, described in the publication EP 283742. Connection diphenylacetone described in WO 92/03413. Other somewhat similar compounds described in the publication EP 439059 and 477778.

It was found that the compounds of the present invention, and especially those which contain (9H-xanthene-9-yl)methyl group, possess much better ACAT inhibitory activity than the previously known compounds mentioned above and/or have much better oral absorption ability.

Thus, an object of the present invention is a series of new amido, urea derivatives, mainly present invention relates to such compounds with useful antihypercholesterolemic activity.

The present invention relates to compounds of formula (I)

< / BR>
where

R1means an alkyl group having from 1 to 20 carbon atoms, or a group of formula (II), (III), (IV) or (V)

< / BR>
where

R5means an alkyl group having from 1 to 15 carbon atoms;

m means an integer from 1 to 4;

any aromatic ring in said group represented by R1is unsubstituted;

R2means a hydrogen atom or alkyl group having from 1 to 10 atonomous from 1 to 10 carbon atoms,

allylthiourea having from 1 to 10 carbon atoms,

alkylsulfonyl group having from 1 to 10 carbon atoms,

alkylsulfonyl group having from 1 to 10 carbon atoms, alkoxyalkyl group, in which CNS part has from 1 to 6 carbon atoms and the alkyl part has from 1 to 4 carbon atoms;

R4means a group of the formula (VI), (VII), (VIII), (IX), (X) or (XI)

< / BR>
where

A1means a single bond or alkilinity group having from 1 to 4 carbon atoms;

A2means a single bond or alkilinity group having from 1 to 6 carbon atoms;

A3, A3a, A4and A5independently selected from the group consisting of single bond and alkylenes group having from 1 to 10 carbon atoms which may be saturated or may include a carbon-carbon double bond, provided that the total number of carbon atoms in A3, A4and A5and in A3a, A4and A5does not exceed 10;

R6means an alkyl group having from 1 to 6 carbon atoms, cycloalkyl group having 3 to 9 carbon atoms in one or more aliphatic carbocyclic rings, these rings are unsubstituted or have Il the other and benzimidazole groups may be unsubstituted or substituted with at least one C1-C4is an alkyl group,

R7means a hydrogen atom, a benzyl group, phosphonopropyl or a group of the formula (XII)

< / BR>
where

X1is 0 or 1;

Z2is 0, 1 or 2;

X is an oxygen or sulfur atom or sulfinil, sulfonium or a phenylene group, provided that when Z2is 2, at least one X is phenylenebis group;

Z3is 9 or an integer from 1 to 4;

R8is carboxypropyl, phenyl group, a group of the formula

-NR9R10,

where

R9and R10are independently selected from the group consisting of a hydrogen atom or alkyl group having from 1 to 4 carbon atoms;

or heterocyclic group having from 5 to 6 atoms in the ring, of which 1 or 2 are heteroatoms selected from the group containing oxygen atom or nitrogen, specified heterocyclic group is unsubstituted or substituted at a carbon atom, an oxygen atom or alkyl group having from 1 to 4 carbon atoms;

These groups of the formula (CH2)z1 and (CH2)z2 are unsubstituted or substituted at the carbon atoms of alkyl groups having from 1 1 is 0 or 1;

n2is 0 or 1;

M denotes oxygen, sulfur atom, sulfinyl group or sulfonyloxy group.

Provided that when R4means specified group of the formula (VII), (IX), (X) or (XI), R1does not mean the specified alkyl group, and when n2is 1, A4does not mean a single bond, and when n1is 0, R3is ethyl and R4is 2-acetyl, R1does not mean a methyl group;

or their pharmaceutically acceptable salts.

The invention relates also to compositions for the treatment or prevention of hypercholesterolemia or atherosclerosis, which contains an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt in a mixture with a pharmaceutically acceptable carrier or diluent.

The invention also relates to a method of treatment or prevention of hypercholesterolemia or atherosclerosis in a mammal, in particular humans, which include the purpose specified mammal an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt.

The method of obtaining these compounds and salts are also forms part of the structure, where R1means alkyl group, this may be pravarasena or branched alkyl group having from 1 to 20 carbon atoms, and examples include methyl groups, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, heptyl, 1-etylhexyl, 2-etylhexyl, 3-etylhexyl, 4-etylhexyl, 5-methylhexan, 1-propinball, 4,4-dimethylpentyl, octyl, 1-methylheptan, 2-mitigar, 3-methylheptan, 4-mitigar, 5-methylheptan, 6-methylheptan, 2-propylpentyl, 2-ethylhexyl, 5,5-diethylhexyl, nonyl, 3-metrotel, 4-metrotel, 5-metrotel, 6-metrotel, 1-propyloxy, 2-atergatis, 2,2-dimethylheptyl, decyl, 1-methylnon, 3-methylnon, 8-methylnon, 3-etilosti, 1,1-dimethyloctyl, 2,2-dimethyloctyl, undecyl, 4,8-dimethylene, dodecyl, tridecyl, 1,1-dimethyluracil, tetradecyl, 2,2-dimethylthiazol, pentadecyl, 3,7,11-trimethyldodeca, hexadecyl, 4,8,12-trimethylacetyl, 1-methylpentanol, 14-methylpentadiene, 13,13-dimethylacetal, heptadecyl, 15-methylhexadecanoic, octadecyl, 1-methylheptadecyl, Needell,laroda, especially from 4 to 20 carbon atoms, more preferably those which have from 10 to 16 carbon atoms, and more preferably those which have from 11 to 14 carbon atoms, in particular, the group undecyl, 1,1-dimethylphenol and 2,2-dimethyluracil.

When R1means a group of formula (II), (III), (IV) or (V)

< / BR>
any aromatic ring may be unsubstituted or they may be substituted by one or more substituents , for example:

alkyl group having from 1 to 4 carbon atoms, such as methyl group, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, of which methyl group, ethyl, propyl and isopropyl are preferred;

CNS group having from 1 to 4 carbon atoms, such as methoxy group, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, of which the methoxy group and ethoxy are preferred; and

the halogen atoms such as fluorine atoms, chlorine, bromine and iodine, of which fluorine atoms, chlorine and bromine are preferred.

In the case of groups of the formula (II), preferred substituents are alkyl and CNS group having 1 or 2 carbon atoms and halogen atoms, especially Mitilini the e of these substituents, particularly preferred and more preferred substituents may be at any substitutable carbon atom (9H-xanthene 9-yl)methyl group represented by the formula (II), but preferably presented on a 2 - or 3-atom of carbon. There is also no particular restriction on the number of substituents, the exceptions being the number of substitutable positions and the possibility of steric hindrance, however, when the group is substituted, preferred are 1 to 3 substituents, one Deputy is preferred. However unsubstituted group is more preferred.

In the case of groups of the formula (III) is preferred substituents are alkyl and CNS group having 1 or 2 carbon atoms and halogen atoms, especially methyl and metaxylene groups and chlorine atoms and bromine. Any of these substituents, particularly preferred substituents may be at any alternate carbon atom 6,11-dihydrobenzo[b, e]azepin-11-strong group represented by the formula (III), but is preferably presented on the 2-carbon atoms. There is also no particular restriction on the number of substituents, except being the number of substitutable positions and the possibility of steric hindrance, however, Kogalym. However unsubstituted group is more preferred.

In the case of groups of the formula (IV) are preferred substituents are alkyl and CNS group having 1 or 2 carbon atoms and halogen atoms, especially methyl and metaxylene groups and chlorine atoms and bromine, more preferably a methoxy group and chlorine atoms and bromine. Any of these substituents, particularly preferred and more preferred substituents may be at any substitutable carbon atom of the benzene ring, represented by formula (IV), but is preferably presented on 2-, 3 - or 4-carbon atoms. There is also no particular restriction on the number of substituents, except being the number of substitutable positions and the possibility of steric hindrance, however, when the group is substituted, preferred are 1 to 3 substituents, and one Deputy is preferred. However unsubstituted group is more preferred. In the group of the formula (IV) is preferably 2 or 3.

In the case of groups of the formula (V) are preferred substituents are alkyl and CNS group having 1 or 2 carbon atoms and halogen atoms, but preferably the group has no more substituents on may be a straight or branched alkyl group, having from 1 to 15 carbon atoms, and examples include methyl groups, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, 2-Metamucil, neopentyl, 1-ethylpropyl, hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-biotinbiotin, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, heptyl, 1-etylhexyl, 2-etylhexyl, 4-etylhexyl, 5-methylhexan, 1-propinball, 4,4-dimethylpentyl, octyl, 1-methylheptan, 2-mitigar, 3-methylheptan, 4-methylheptan, 5-methylheptan, 6-methylheptan, 1-propylpentyl, 2-atikaki, 5,5-diethylhexyl, nonyl, 3-metrotel, 4-metrotel, 5-metalaxyl, 6-metrotel, 1-propyloxy, 2-atergatis, 6,6-dimethylheptyl, decyl, 1-methylnon, 3-methylnon, 8-methylnon, 3-etilosti, 3,7-dimethyloctyl, 7,7-dimethyloctyl, undecyl, 4,8-dimethylene, dodecyl, tridecyl, tetradecyl, pentadecyl and 3,7,11-trimethyldodeca. Among them we preferred such groups, which have from 3 to 20 carbon atoms, particularly 4 to 15 carbon atoms, more preferably those which have from 9 to 12 carbon atoms.

From all values of R1preferred such compounds, where R1means a group of the formula (I):

When R2and R32those which have from 4 to 8, more preferably from 5 to 8 carbon atoms, and from this group a more preferred group with a straight chain. Alternative R2is preferably a hydrogen atom. Preferred groups for R3are those which have from 1 to 8, more preferably from 1 to 8, more preferably from 1 to 6, carbon atoms, which can be groppetti, 1,1-dimethylpentyl and 1,1-diethylhexyl, more preferably group, isopropyl and tert-butyl.

When R3means alkoxygroup, it can be pravarasena or branched alkyl group having from 1 to 10 carbon atoms, and examples include methoxy group, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentane, 2-methylbutoxy, neopentylene, 1 ethylpropoxy, 1,1-DIMETHYLPROPANE, hexyloxy, 4-methylpentylamino, 3 methylpentane, 2-methylpentane, 1 methylpentylamine, 3,3-Dimethylbutane, 2,2-Dimethylbutane, 1,1-Dimethylbutane, 1,2-Dimethylbutane, 1,3-Dimethylbutane, 2,3-Dimethylbutane, 2-ethylbutane, heptyloxy, 1 methylhexanoic, 2-methylhexane, 3-methylhexane, 4-methylhexane, 5-methylhexane, 1 propylboronic, 1,1-dimethylpentyl, octyloxy, 1 methylheptane, 2-methylheptane, 3 methylendioxy, 4-methylheptane, 5-methylheptane, 6-methylheptane, 1 propylpentyl, 2-ethylhexyloxy, 1,1-dimethylheptyl, nonyloxy, 1 methylacrylate, 2-methyloctane, 3 methylacrylate, 6-methylacrylate, 1 propylhexedrine, 1 atergatis, 1,1-dimethylheptyl, decyloxy, 1 methylaniline, 3 methylnonane, 8-methylnonane, 3 ethylacrylate of these groups, particularly preferred are isopropoxy and tert-butoxy group.

When R3means alkylthio group, it may pravarasena or branched, alkylthio group having from 1 to 10 carbon atoms, and examples include the methylthio group, ethylthio, propylthio, isopropylthio, butylthio, isobutyric, sec-butylthio, tert-butylthio, pentylthio, isopentyl, 2-methylbutyl, neopentyl, 1 ethylpropyl, 1,1-dimethylpropyl, hexylthio, 4-methylphenylthio, 3 methylphenylthio, 2-methylphenylthio, 1 methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, Gentilly, 1 methylhexane, 2-methylhexane, 3 methylhexane, 4-methylhexane, 5-methylhexane, 1 propylbetaine, 1,1-dimethylpentyl, octyltin, 1 methylheptane, 2-methylheptane, 3 methylheptane, 5-methylheptane, 6-methylheptane, 1 propylpentyl, 2-ethylhexyl, 1,1-diethylhexyl, nonillion, 1 Metrocity, 2-Metrocity, 3 Metrocity, 6-Metrocity, 1 propylhexedrine, 1 elilgibilty, 1,1-dimethylheptyl, decillia, 1 maternality, 3 maternality, 8-maternality, 3 atrocity, 1,1-dimethyloctyl and 7.7-dimethyloctyl from which such preferred that from 1 to 4 carbon atoms. Of these groups, particularly preferred is ing group, this can be pravarasena or branched alkylsulfonyl group having from 1 to 10 carbon atoms, and examples include group methylsulfinyl, propylsulfonyl, isopropylphenyl, butylsulfonyl, isobutylphenyl, second-butylsulfonyl, tert-butylsulfonyl, pentasulfide, isopentylamine, 2-methylbutylamine, neopentylglycol, 1-ethylpropylamine, 1,1-dimethylpropylene, hexylaniline, 4-methylphenylsulfonyl, 3-methylphenylsulfonyl, 2-methylphenylsulfonyl, 1-methylphenylsulfonyl, 3,3-dimethylbutylamino, 2,2-dimethylbutylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,3-dimethylbutylamino, 2-ethylbutylamine, heptylaniline, 1-methylcellulose, 2-methylhexanamine, 3-methylcellulose, 4-methylcellulose, 5-methylcellulose, 1-propylethylene, 1,1-dimethylpentylamine, octylsilane, 1-methylheptacosane, 2-methylheptanoic, 3-methylheptacosane, metalgearsolid, 5-methylheptacosane, 6-methylheptanoic, 1-propylaniline, 2-ethylhexanoyl, 1,1-dimethylhexylamine, noninsulin, 1-methylacrolein, 2-methylacrolein, 3-methylanthranilic, 6 is inil, 1-metallomesogens, 3-metallomesogens, 8-metallomesogens, 3-atractylenolide, 1,1-dimethylsulfide and 7.7-dimethylsulfide, of which preferred those who have one to four carbon atoms. Of these groups, particularly preferred group methylsulfinyl, isopropylphenyl and tert-butylsulfonyl.

When R3means alkylsulfonyl group, it may be pravarasena or branched alkylsulfonyl group having from 1 to 10 carbon atoms, and examples include methylsulphonyl group, ethylsulfonyl, propylsulfonyl, isopropylphenyl, butylsulfonyl, isobutylphenyl, second-butylsulfonyl, tert-butylsulfonyl, peterculter, isopentylamine, 2-methylbutylamine, neopentylene, 1-ethylpropylamine, 1,1-dimethylpropylene, hexylsilane, 4-methylpropanesulfonic, 3-methylphenylsulfonyl, 2-methylphenylsulfonyl, 1-methylphenylsulfonyl, 3,3-dimethylbutylamino, 2,2-dimethylbutylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,3-dimethylbutylamino, 2-ethylbutylamine, septinsular, 1-methylcellulose, 2-methylcellulose, 3-methylcellulose, 4 MSIL, 1-methylheptanoic, 2-methylheptanoic, 3-methylheptanoic, 4-methylheptanoic, 5-methylheptanoic, 6-methylheptanoic, 1-problematically, 2-ethylhexylamine, 1,1-dimethylbenzenesulfonyl, 1-methylacrolein, 2-methylacrolein, 3-methyloctanoic, 6-methyloctanoic, 1-propylbenzenesulfonyl, 1-ethylheptylamino, 1,1-dimethylvaleronitrile, decimalpoint, 1-methylnonanoic, 3-methylnonanoic, 8-methylnonanoic, 3-ethylacrolein, 1,1-dimethylsulfone and 7.7-dimethylsulfone, of which we prefer, which have from 1 to 4 carbon atoms. Of these groups, particularly preferred group methylsulphonyl, isopropylphenyl and tert-butylsulfonyl.

When R3means phenylthio, phenylsulfinyl or phenylsulfonyl group, phenyl group can be unsubstituted or can be substituted by one or more substituents selected from the group consisting of the substituents defined and shown in the examples below. There is also no particular restriction on the number of substituents, except being the number of substitutable positions and the possibility of steric hindrance, however, when the group is substituted, predpochtitel the substituted groups include groups of phenylthio, 4 methylphenylthio, 2-methylphenylthio, 3 methylphenylthio, 4-propylphenyl, 2-methoxyphenyl, 3 methoxyphenylazo, 4-ethoxyphenyl, 3 forfinally, 4-chlorophenylthio, 3 pampanito, phenylsulfonyl, 4-methylphenylsulfonyl, 2-methylphenylsulfonyl, 3-ethylvanillin, 4-propylresorcinol, 2-methoxyphenylacetyl, 3-methoxybenzenesulfonyl, 4-ethoxyphenylacetic, 3-perpenicular, 4-chlorophenylsulfonyl, 3-brompheniramine, phenylsulfonyl, 4-methylphenylsulfonyl, 2-methylphenylsulfonyl, 3-ethylvanillin, 4-propylpentanoic, 2-methoxyphenylacetyl, 3-methoxybenzenesulfonyl, 4-ethoxyphenylacetic, 3-perpenicular, 4-chlorophenylsulfonyl and 3-brompheniramine, preferably group phenylthio, 4-methylphenylthio, 2-methylphenylthio, 4-chlorophenylthio, phenylsulfonyl, 4-methylphenylsulfonyl, 2-methylphenylsulfonyl and 4-chlorophenylsulfonyl.

When R3means alkoxyalkyl group, they contain alkoxy group having from 1 to 6, preferably from 1 to 4, carbon atoms, which may be a Deputy from alkyl groups having from 1 to 4 carbon atoms. Examples of such groups include alkoxy groups having from 1 to 6 carbon atoms, including groups that may be represented by R3, the s R1. Specific examples of such alkoxyalkyl groups include methoxymethyl, ethoxymethyl, isopropoxide, tert-butoxymethyl, 1-methoxyethyl, 2-methoxyethyl, 1-ethoxyethyl, 2-ethoxyethyl, 1-isopropoxide, 2-isopropoxyethanol, 1-tert-butoxyethyl, 2-tert-butoxyethyl, 1-methoxypropyl, 2-methoxypropyl, 3-methoxypropyl, 1-ethoxypropanol, 2-ethoxypropan, 3-ethoxypropan, 1-isopropoxyphenyl, 2-isopropoxyphenyl, 3-isopropoxyphenyl, 4-isopropoxyphenyl, 1-tert-butoxymethyl, 2-tert-butoxyethyl, 3-tert-butoxymethyl, 4-tert-butoxymethyl and 1,1-dimethyl-2-methoxyethyl. Of those, more preferred groups are those in which the alkoxy group having from 1 to 4 carbon atoms are substituents at the methyl group, preferably a group methoxymethyl, ethoxymethyl, isopropoxy and tert-butoxymethyl, and more preferred groups are groups methoxymethyl and isopropoxyphenyl.

R4means a group of the formula (VI), (VII), (VIII), (IX), (X) or (XI):

< / BR>
In the case of the groups of formulas (VI) and (VIII), where A1means alkylenes group having from 1 to 4 carbon atoms, this may be pravarasena or branched chain group, preferably having from 1 to 4 carbon atoms. Two "free" jobs can b meets 2 or more carbon atoms, different carbon atoms. Remotemachine group are preferred. Examples of such groups include methylene group, ethylene, propylene, 1-ethylethylene, trimethylene and tetramethylene, of which groups are methylene, ethylene and propylene are preferable. Alternative A1may represent a single bond, however, preferred are such compounds where A1is alkylenes group, preferably a methylene group.

In the case of the groups of formulas (VI) and (VIII) A2means a single bond or alkilinity group having from 1 to 6 carbon atoms. This can be pravarasena or branched chain group, preferably having from 2 to 4 carbon atoms. Two "free" opportunities may be on the same carbon atom or from different carbon atoms. Remotemachine group are preferred. Examples of such groups include ethylene group, trimethylene, 1-mutilation, tetramethylene, 1-metallisation, 2-metallisation, 3-metallisation, 1-methylpropyl, 1,1-dimethylethylene, pentamethylene, 1-methyltyramine, 2-methyltyramine, 3-methyltyramine, 4-methyltyramine, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylphenylene, 2.2-dimethyltrimethylene, 3,3-dimethyltrimethylene and 4,4-dimethyltrimethylene. Of these preferred groups are ethylene, trimethylene, 1-mutilation and tetramethylene. In compounds in which n2is 1, it is preferable that A2was not a single bond and alkilinity group other than methylene.

Also in the case of formulas (VI) and (VIII) imidazolidine and benzimidazolyl groups can be unsubstituted or substituted by at least one Deputy, selected from the group consisting of the substituents defined above. Examples of such substituents include:

alkyl group having 1 to 4 carbon atoms, such as defined; confirmed by the examples above for the substituents, preferably methyl group and ethyl, and

phenyl groups which are unsubstituted or substituted by at least one Deputy, selected from the group consisting of the above substituents (which may be as defined and confirmed by the examples above), groups such as phenyl, 2-chlorophenyl, 4-chlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl and 2-were, more preferably phenyl group and 2-chlorophenyl.

However unsubstituted group imidazolyl and benzimidazolyl and they substituted group , A3a, A4and A5can each mean alkylenes group having from 1 to 10 carbon atoms, which may have at least one double bond. When a group contains 2 or more double bonds, the group presented A3, A3a, A4and A5may be the same or different from each other. Examples of such groups include saturated alkylene group having from 1 to 10 carbon atoms such as methylene group, ethylene, trimethylene, 1-mutilation, tetramethylene, 1-mediatisation, 2-metallisation, 3-metallisation, 1-methylpropyl, 1,1-dimethylethylene, pentamethylene, 1-methyltyramine, 2-methyltyramine, 3-methyltyramine, 4-methyltyramine, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylpentylamino, 2-methylpentylamino, 3-methylpentylamino, 4-methylpentylamino, 5-methylpentanediol, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, 4,4-dimethyltrimethylene, hexamethylene, 1-methylhexanamine, 2-methylhexanamine, 5-methylhexanamine, 3-acilitation, octamethylene, 2-methylheptadecyl, 5-methylheptadecyl, 2-ethylhexylamine, 2-ethyl-3-methylpentylamino, 3-ethyl-2-methylpentanediol, nonmotile, 2-mediametrie, 2-methyleneimine, 8-methyleneimine, 5-etrochemical, 3-ethyl-2-methylheptadecyl and 3.3-diarylheptanoids; and remotemachine or branched alkylene group having from 2 to 10 carbon atoms, such as 2-propylene, 1-methyl-2-propylene, 2-methyl-2-propylene, 2-ethyl-2-propylene, 2-butylene, 1-methyl-2-butylene, 2-methyl-2-butylene, 1-ethyl-2-butylene, 2-papanyan, 1-methyl-2-penttinen, 2-methyl-2-penttinen, 3-penttinen, 1-methyl-3-penttinen, 2-methyl-3-pentikinen, 1-methyl-4-penttinen, 2-methyl-2-penttinen, 2-hexarelin, 3-hexarelin, 4-hexarelin, 5-hexarelin, heptenyl, hoktanyan, Nonlin and the mission. The alternative any one or more of these groups may signify a single bond.

A3and A3aeach preferably denote a single bond or alkylene group having from 1 to 7 carbon atoms, more preferably from 1 to 4 carbon atoms and most preferably alkylenes group having from 1 to 7, more preferably from 1 to 4 carbon atoms, while A4represents a single bond or alkilinity group having from 1 to 7 carbon atoms. In addition, the most preferred single bond or a methylene or ethylene group.

A5preferably means staresina alkyl group, having from 1 to 4 carbon atoms, and examples include a methylene group, METROTILE, ethylene, trimethylene, 1-mutilation, tetramethylene, 1-metallisation, 2-metallisation, 3-metallisation, 1-methylpropyl, 1,1-dimethylethylene, pentamethylene, 1-methyltyramine, 2-methyltetrazole, 3-methyltyramine, 4-methyltyramine, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylpentylamino, 2-methylpentylamino, 3-methylpentylamino, 4-methylpentylamino, 5-methylpentanediol, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene 4,4-dimethyltrimethylene, of which the preferred groups are methylene, ethylene and propylene.

In those cases, when a group of the formula (VII), (IX), (X) or (XI) includes two or more groups represented by A3, A3a, A4and5the total number of carbon atoms contained in these groups should not exceed 10.

Also in the case of the groups of formulae (VII), (IX), (X) and (XI), where R6means alkyl group, which may be remotemachine or branched group having from 1 to 4 carbon atoms, and examples include methyl groups, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, and tert-butyl, of which predpochtitel the ring carbon atoms and one or more preferably one or two or more, preferably one, hydrocarbon ring, and examples include group cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cycloneii, norinyl and norbornyl, preferably group cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl and more preferably cyclopentyl and cyclohexyl. These cycloalkyl groups can be unsubstituted or they may have in his ring at least one Deputy, selected from the group consisting of Deputy defined and shown in the examples above. Examples of such substituted groups include groups cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 4-ethylcyclohexyl, 4-propylcyclohexyl, 4-tert-butylcyclohexyl, 4-methoxycyclohexyl, 4-Toxicological, 4-Toxicological and bornyl.

When R6means aryl group, this has from 6 to 10 carbon atoms, more preferably from 6 to 10 carbon atoms, in one or more, preferably one or two, and more preferably in one carbocyclic ring, and examples of the unsubstituted groups include phenyl group, 1-naphthyl and 2-naphthyl, preferably phenyl group. Such groups may be unsubstituted or they can and otverzhdennye in the examples above. Examples of such substituents include phenyl group, 2-were, 2-methoxyphenyl, 2-chlorophenyl and 3-chlorophenyl.

By definition, R7, R9and R10can be hydrogen atoms or alkyl groups having from 1 to 4 carbon atoms. In the case of alkyl groups that can be remotemachine or branched alkyl group, and examples include methyl groups, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl. Of them such preferred alkyl groups have from 1 to 2 carbon atoms, and most preferred methyl group. Alternative preferably, R9and R10each mean a hydrogen atom. With the combination of R9and R10in the group-NR9R10preferably, R9and R10both meant a hydrogen atom or a methyl group.

Heterocyclic group, which may be represented by R8can have from 5 to 6 ring atoms, of which from 1 to 2 are heteroatoms selected from the group consisting of nitrogen atoms and oxygen. Examples of such groups include furyl group, pyranyl, tetrahydrofuryl, tetrahydropyranyl, pyrrolyl, imidazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyrrolidinyl, imidazolidine are groups of morpholino, imidazolyl and DIOXOLANYL. Such groups can be unsubstituted or can be substituted at a carbon atom by an oxygen atom or alkyl group having from 1 to 4 carbon atoms. Examples of alkyl substituents described above. Of the substituted groups are particularly preferred optional alkyl substituted 2-oxo-1,3-dioxolan-4-yl group, and most preferred 5-methyl-2-oxo-1,3-dioxolan-4-yl.

Examples of groups which may be represented by R7include a hydrogen atom and groups carbamoyl, benzyl, benzoyl and phosphono [-PO(OH)2]and groups of the formulas (XIII) - (XXXV), which is shown in Fig. 1 and 2.

n1is preferably 0.

All of the groups represented by R1preferred (9H-xanthene-9-yl)methyl, 6, 11-dihydrobenzo[b,e]azepin-11-yl, 4-disiloxanyl and (1-phenylcyclohexyl)methyl group.

All of the groups denoted by R4preferred having the formula (VIa), (VIIa) and (IXa)

,

in which R6is cyclopentyloxy group, tsiklogeksilnogo group, cycloheptyl group, phenyl group, 2-methylthieno group, 2-chloraniline group or 4-chloraniline group;

R7'is 3-carboxypropyl group, 2-carboxen represent alkylenes group, having from 2 to 4 carbon atoms;

A3'represents a single bond or alkilinity group having from 1 to 3 carbon atoms, which can be braked double bond (in particular methylene or ethylene group);

A4'represents a single bond or alkilinity group having from 1 to 5 carbon atoms, which can be braked double bond;

Of all R7preferred 3-carboxypropyl, 2-carboxybenzoyl and 3-aminoacetyl group.

Of all groups included in substituents , preferred are methyl and methoxy groups, and fluorine atoms, chlorine and bromine.

Of all groups included in substituents, preferred are the groups methyl, ethyl, propyl and phenyl.

R2preferably means hydrogen atom or a group of hexyl or heptyl.

R3preferably means a group of methyl, ethyl, isopropyl, tert-butyl, methoxymethyl, isopropoxide, tert-butylthio, isopropylthio, methylthio or phenylthio.

R4can be in any position of the benzene ring, forming a part of the compounds of formula (I). However, particularly preferably those that would be in the ortho-position of the SCP and in the para-position with respect to R3.

Preferred classes of compounds of the present invention are;

(A) such compounds of formula (I) and their salts, as defined above, in which R1means a group of formula (II) and (IV)

,

(in which the aromatic rings are unsubstituted or substituted by at least one Deputy, selected from the group consisting of the substituents defined above, and m is definitely above) and n1is 0, and the preferred

(B) such compounds of formula (I) and their salts, as defined above, in which R1means a group of the formula (I) and the aromatic rings are unsubstituted.

Preferred classes of compounds of formula (I) and their salts, as defined above, in which:

(C) R3means an alkyl group having from 1 to 10 carbon atoms, alkylthio group having from 1 to 10 carbon atoms, or CNS group having from 1 to 10 carbon atoms, more preferably.

(D) R3means an alkyl group having from 1 to 6 carbon atoms, alkylthio group having from 1 to 6 carbon atoms, or CNS group having from 1 to 6 carbon atoms.

Preferred classes of compounds of formula (I) and Sol is toroi M represents an oxygen atom, more preferably

(F) in the case when n2is 1, R4means a group of the formula (VI), in which the total number of carbon atoms in A1and A2is from 2 to 4, or

(F') when n2is 0, R4means a group of the formula (VI), in which the total number of carbon atoms in A1and A2is from 1 to 3, or

(G) R4means a group of the formula (VII), in which the total number of carbon atoms in A3, A4and A5is from 1 to 6, and R6means an alkyl group having from 1 to 6 carbon atoms, or cycloalkyl group having from 1 to 6 carbon atoms, more preferably.

(H) R4defined in (G) above and R7means a hydrogen atom or a group of the formula (XVI), (XXIV), (XXV) or (XXX), even more preferably.

(I) R4defined in (H) above and R6means unsubstituted group, or

(J) R4means a group of formula (X), in which the total number of carbon atoms in A3, A4and A5is from 1 to 6, and R6means an alkyl group having from 1 to 6 carbon atoms, or cycloalkyl group having from 3 to 7 carbon atoms, more preferably.

(K) R4defined in (J) above and R7Osano in (K) above and R6means unsubstituted tsiklogeksilnogo group.

Especially preferred are such compounds of formula (I) and its salts mentioned above, in which any combination of definitions (A) - (J) are also used. For example, preferred those in which RIthe same as in (A) or (B), and R3the same as in (A) or (B), and R3the same as in (C) or (D), especially (A) + (C) or (B) + (D) and more preferably (B) + (D) + (E) and, more particularly (B) + (D) + (E) + [(F-or (F) or (G) or (J)]. Even more preferred are (B) +(D) + (E) + [(F) or (F')] and (B) + (D) + (E) + (H) and (B) + (D) + (E) + (K). Of them, particularly preferred are (B) + (D) + (E) + [(F) or (F')] or (B) + (D) + (E) + (J) and (B) + (D) + (E) + (L).

In the most preferred compounds of this invention RImeans (9H-xanthene-9-yl)methyl group; nIis 0; R3means methylthio group, isopropylthio, isopropyl or tert-butyl; R4means a group of formula (VIa), (VIIa) or (IXa) or (IXa) in which R6'means cyclopentyloxy group, tsiklogeksilnogo group, cycloheptyl group, phenyl group, 2-methylphenyl group, 2-chloraniline group or 4-chloraniline group; R7'mean 3-carboxypropyl group, 2-carboxy-benzoyloxy group the SCP, having from 2 to 4 carbon atoms; A3'represents a single bond or alkilinity group having from 1 to 3 carbon atoms, which can be braked double bond (in particular, methylene or ethylene group); A4'represents a single bond or alkilinity group having from 1 to 5 carbon atoms, which can be braked double bond.

The place of attachment of R4to baselinea in the compound of formula (I) is in ortho-position to the amino group in the meta position with respect to R3or in the meta-position to the amino group in the para-position with respect to R3.

When the compound of the present invention contains a basic group in its molecule, for example an amino group or imidazolidinyl group, it may form an additive salt of the acid. Examples of such salt add acid: salts with mineral acids, especially halogen acids such as hydrofluoric acid, Hydrobromic acid, uudistoodetena acid or hydrochloric acid), nitric acid, carbonic acid, sulfuric acid or phosphoric acid; salts with low alkylsulfonate acids such as methanolate, such as benzolsulfonat acid or n-toluensulfonate acid; salts with organic carboxylic acids such as acetic acid, fumaric acid, grape acid, oxalic acid, maleic acid, malonic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid or citric acid; and salts with amino acids such as glutamic acid or aspartic acid.

Specific examples of the compounds of the present invention are given in the following formulas from (I-I) to (I-5), in which the group of substituents defined in the relevant formulas table. 1-5, such as a table.1 relates to formula (I-I), PL. 2 relates to formula (1-2), and so on up to the table. 5, which refers to the formula (1-5). In formulas, numbers matching peripheral positions, shown in Fig. 3-6. In table. 1-5 use the following abbreviation:

Bimd - Benzimidazole

Bu - Butyl

cBu - Cyclobutyl

iBu is Isobutyl

tBu is Tert-butyl

Bz - Benzyl

Et - Ethyl

Hp - Heptyl

cHp - Cycloheptyl

Hx - Hexyl

cHx - Cyclohexyl

Imd - Imidazolyl

Me - Methyl

cOc - Cyclooctyl

Ph - Phenyl

Pn - Pentyl J - Undecyl

K - 2.2-Dimethylthiazol

Of the compounds listed in table.1-5, the preferred are the compounds given in table. 6.

The most preferred compounds are compounds N:

I - I. N-[Tret-Butyl-5-(cyclohexyl-3-hydroxyphenyl)-phenyl]-2- (9H-xanthene-9-yl)ndimethylacetamide;

1-25. N - [2-tert-Butyl-5-(4-cyclohexyl-3-hydroxybutyl)-phenyl]-2- (9H-xanthene-9-yl)ndimethylacetamide;

1 - 49. N-[2-tert-Butyl-5-(6-cyclohexyl-3-hydroxyhexyl)-phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide;

1 - 73. N-[2-tert-Butyl-5-(7-cyclohexyl-3-hydroxymethyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide;

1 - 131. N-[2-tert-Butyl-5-(3-cyclohexyl-3-hydroxypropyl)- phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide;

1 - 179. N-[2-tert-Butyl-5-(2-cyclohexyl-1-hydroxyethyl)- phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide;

1 - 684. N-[2-tert-Butyl-5-(6-cyclopentyl-1-hydroxyethyl)- phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide;

1 - 1102. I-(2-(4-tert-Butyl-3-[2-(9H-xanthene-9-yl)-acetamido] phenyl)ethyl)-2-cyclohexylethyl sodium succinate;

1 - 1111. I-(2-(4-tert-Butyl-3-[2-(9H-xanthene-9-yl)-acetamido] phenyl)ethyl)-3-cyclohexylprop sodium succinate;

1-1129. Sodium I-(2-(4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl)ethyl) -5-cyclohexylmethyl succinate;

1-1474. N-{ 2-[3-(I-Imidazolyl)propoxy]methyl-6-methylthiophenyl} -29-yl)ndimethylacetamide;

1-1480. N-{ 2-[3-(I-Imidazolyl)propoxy] methyl-6-tert-butylphenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide hydrochloride;

1-1552. Sodium salt of 1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl) -2-cyclohexyl ethyl of carboxymethylcysteine;

1-1565. N-(2-tert-Butyl-5-{ 3-[2-(1-imidazolyl)acetoxy] -4-cyclohexylmethyl}phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide hydrochloride;

1-1567. Sodium salt of N-(2-tert-butyl-5-{3- [2-(carboxymethoxy)acetoxy] -4-cyclohexylmethyl} phenyl) -2-(9H-xanthene-9-yl)ndimethylacetamide;

1-1933. Sodium salt of N-(2-tert-butyl-5-{7-cyclohexyl-3-[2(carboxymethoxy)acetoxy] heptyl}phenyl)-2-(encantan-9-yl)ndimethylacetamide;

1-1977. N-[2-tert-Butyl-5-[4-cyclohexyl-2-(hydroxymethyl) butyl]phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide;

1-2389. N-{ 2-tert-Butyl-5-[4-(2-cyclohexylmethoxy)-3-hydroxymethyl]phenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide;

1-2390. N-[2-tert-Butyl-5-(5-cyclohexyloxy-3-hydroxyphenyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide;

1-2713. N-[2-tert-Butyl-5-{ 4-(2-cyclohexylmethoxy)-3-[2-(1- imidazolyl)acetoxy]butyl}phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide hydrochloride;

1-2768. Sodium salt of N-(2-tert-butyl-5-{3-[2-carboxymethoxy)acetoxy] -4-cyclohexylmethyl} phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide;

1-2920. N-{ 2-tert-Butyl-5-[(2-ethyl-1-imidazolyl)methyl] phenyl} -2-(9H-xanthene-9-yl)aceti obtained in various ways, for example, as shown in the following reaction schemes I-XXVI; see Fig.7-32.

In the above formulas:

R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, A1, A2, A3, A4, A5and m are defined above;

R11means an alkyl group having from 1 to 6 carbon atoms (preferably a methyl or ethyl group);

R12means alkylsulfonyl or arylsulfonyl group in which the aryl group defined above, and the alkyl group has from 1 to 6 carbon atoms (preferably methanesulfonyl or n-toluensulfonyl group);

A3bmeans alkylenes group having from 1 to 8 carbon atoms (provided that the number of carbon atoms in a carbon chain of less than A3one carbon atom);

R4ahas the same values as specified for R4(provided that it may not necessarily be protecting group);

R4bmeans alkylenes group having from 1 to 10 carbon atoms which may be saturated or may include a carbon-carbon double bond (provided that the number of carbon atoms in a carbon chain of less than A4;

X2means a halogen atom (preferably bromine or iodine), alkylsulfonate group having from 1 to 6 carbon atoms (preferably, methanesulfonate group) or arylsulfonate the group in which the aryl part is as defined above;

W1means hydroxyamino group (preferably trialkylsilyl group, in particular tert-butyldimethylsilyloxy group), methoxymethyl group, acyl group, aracelio group (particularly benzyl group) or tetrahydropyranyloxy group;

W2means hydroxyimino group (preferably trialkylsilyl group, in particular tert-butyldimethylsilyloxy group), aracelio group (particularly benzyl or trityloxy group), acyl group (particularly acetyl group) or tetrahydropyranyloxy group;

W3means hydroxyamino group (preferably trialkylsilyl group, in particular tert-butyldimethylsilyloxy group; alkoxyalkyl group, in particular methoxymethyl group; or tetrahydropyranyloxy group, most preferably tert-butyldimethylsilyloxy group);

Xsmeans a group of the formula

[R13S(O)p]C[R14S(O)q]

the Dom carbon or aryl group as defined above, or R13and R14taken together, mean alkylenes group having from 1 to 5 carbon atoms; and p and q are the same or different and each is 0,1 or 2), preferably one of the following groups of the formula(101), (102), (103), (104) or (105)

,

R6ameans(M)n2-A5-R6in which M, n2, A5and R6defined above;

R15means imidazolidinyl or benzimidazolyl group, substituted by at least one Deputy, selected from the group consisting of the Deputy mentioned above;

s denotes 0 or an integer from 1 to 7;

v denotes an integer from 1 to 10.

Reaction scheme 1

Stage 1: Condensation

In this stage, the compound of formula (4) is produced by interaction of the compounds of formula (2) with the compound of the formula (3) in an inert solvent. When X1means a hydroxy-group, the reaction is carried out in the presence of a condensing agent and a base; and when X1means a halogen atom, it is conducted in the presence of a base.

When X1means a hydroxyl group (stage 1A), the reaction is normally and preferably carried out in the presence of a suitable solvent. N is esteem on the reaction and that it can dissolve the starting material at least to some extent. Examples of preferred solvents include: aromatic hydrocarbons, such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane, chlorobenzene or dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl, butyl acetate or diethylmalonate; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; ketones, such as acetone or methyl ethyl ketone; nitro compounds such as nitroethane or nitrobenzene; NITRILES, such as acetonitrile or isobutyronitrile; amides, such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide; and sulfoxidov, such as dimethylsulfoxide or sulfolane; more preferred aromatic hydrocarbon (particularly benzene), halogenated hydrocarbons (particularly methylene chloride) or an ether (particularly tetrahydrofuran).

There is also no particular restriction on the nature of the used condensing agent, and examples of suitable agents include di(lower alkyl)azodicarboxylate-triphenylphosphine, such as diethylazodicarboxylate-triphenylphosphine; N-(lower alkyl)-5 is such as N, N'-dicyclohexylcarbodiimide (DCC); 2-halo-1-(lower alkyl)pyridine halides, such as 2-chloro-1-methylpyridinium iodides; directorrelated, such as diphenylphosphoryl (DPPA); phosphorylchloride, such as diethylphosphate; imidazole derivatives such as N,N'-carbonyldiimidazole (CDI); and derivatives, carbodiimide, such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAPC); preferably N,N'-dicyclohexylcarbodiimide, 2-chloro-1-methylpyridinium iodide and the diethyl phosphorylchloride.

There is also no particular restriction on the nature of the used grounds, provided that there are no negative impacts on the molecules of the reagents, and examples include organic bases such as triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N, N-dimethylamino)pyridine, 4-pyrrolidinone, N, N-dimethylaniline, N,N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo[4,3,0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane (DABCO) and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU). Which one is preferable ethylamine, diisopropylethylamine or pyridine.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature is C the om, convenient to conduct the reaction at a temperature of from 0 to 150oC, more preferably from 25 to 120oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 48 h, more preferably from 1 to 24 hours, will usually suffice.

After completion of the reaction, the desired compound of formula (1) can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. The desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods,but preferably is carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of preferred solvents include aromatic hydrocarbons such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane, chlorobenzene or dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl, butyl acetate or diethylmalonate; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; ketones, such as acetone or methyl ethyl ketone; amides, such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide. Of these preferred aromatic hydrocarbons (particularly benzene), halogenated hydrocarbons (particularly methylene chloride).

There is also no particular restriction on the nature of the used grounds, provided that it does not adversely affect the molecules of the reagents, and examples include organic bases such as triethylamine, tributylamine, Diisopropylamine] non-5-ene, 1,4-diazabicyclo[2, 2, 2]octane(DABCO) and 1,8-diazabicyclo[5, 4, 0] undec-7-ene (DBU). Of them preferred pyridine or N,N-dimethylaniline.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. However, and generally convenient to conduct the reaction at a temperature of from -78 to 50oC, more preferably from 40 to 25oC. the Time required for implementation, may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 5 minutes to 24 hours, more preferably from 10 minutes to 24 hours, will usually suffice.

After completion of the reaction, the desired compound of formula (1) can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and immiscible with wadeskog phase, containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. The desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stages 2: removing the protective group

At this stage, the compound of formula (1a) is produced by interaction of the formula (4) by removing the protective group agent in an inert solvent to remove the group represented by W1.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material at least to some extent. Examples of suitable solvents include; aromatic hydrocarbons such as benzene, toluene or xylene; halogenoalkane hydrocarbons such as methyl chloride, chloroform, dichloroethane; ethers, such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane; alcohols, such as methanol or ethanol; and NITRILES, such as AC is (particularly tetrahydrofuran) and alcohols (particularly methanol).

When used protective group is a silyl group such as tert-butyldimethylsilyl group, they can be removed using an inorganic acid such as hydrochloric acid or reagent capable of forming ion fluoride, such as tetrabutylammonium fluoride. The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature from room temperature up to 70oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

When used protective group is methoxymethyl group, it can be removed with the use of inorganic acids such as hydrochloric acid, in an organic solvent, such as dioxane, methanol or those who tion on the image. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature from room temperature up to 70oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

When used protective group is tetrahydropyranyloxy group, it may be removed using an inorganic acid such as hydrochloric acid, or organic acids, such as n-toluensulfonate. The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. However, and generally convenient to conduct the reaction at a temperature from room temperature up to 50oC. the Time required for the reaction may also widely sonatala. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

When used protective group is an acyl group such as acetyl group, they can be removed using an alkali metal alkoxide such as sodium methoxide or potassium methoxide or hydroxide of an alkali metal such as sodium hydroxide or potassium hydroxide. The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature from room temperature up to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

After completion of the reaction, the desired compound can be isolated from Renai mixture; filtration of insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. The desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stages 3: Etherification

At this stage, the compound of formula (1b) have the interaction of the compounds of formula (1a) with an acid anhydride, monoufia, in particular benzyl-, Ter-butyl or benzhydrylamine ether, or monoether, in particular benzyl, tert-butyl or benzhydrylamine ether, monohalogenated carboxylic acid in an inert solvent. When using an anhydride of dicarboxylic acid, the reaction is usually carried out in the presence of a base; when using monoether dicarboxylic or carboxylic acid, the reaction is usually carried out in the presence of a condensing agent and a base; and, when used monoether Housego agent or cause; and, when used monoether monohalogenated dicarboxylic acid, the reaction is normally and preferably carried out in the presence of a base.

When using the acid anhydride (stage 3a), the reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of preferred solvents include: aromatic hydrocarbons, such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane, chlorobenzene or dichlorobenzene; esters such as ethyl acetate, propyl, butyl acetate or diethylmalonate; ethers, such as tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; ketones, such as acetone or methyl ethyl ketone; NITRILES, such as acetonitrile or isobutyronitrile; and pyridine or its substituted derivatives, such as pyridine or 2,6-lutidine. Of these preferred aromatic hydrocarbons, in particular toluene or xylene) and pyridine or substituted pros provided there are no negative impacts on the molecules of the reagents, and examples include organic bases such as triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(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 (DABCO) or 1,8-diazabicyclo [5, 4, 0]undec-EN (DBU), preferably triethylamine or pyridine.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 50 to 150oC, preferably from 70 to 120oC. the Time required for the reaction may also vary widely, depending on many factors, the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 72 hours, preferably from 1 to 30 hours, will usually suffice.

After completion of the reaction, the desired compound can be the separation of the ow of the mixture, filtering to remove insoluble material, if there is one; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound can be, if necessary, and then purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely columnar chromatography.

When you use monoether dicarboxylic or carboxylic acid (stage 3b), the reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of preferred solvents include: aromatic carbohydrates, such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane, chlorobenzene or dichlorobenzene; esters such as ethyl acetate, propyl, bout icol dimethyl ether; ketones, such as acetone or methyl ethyl ketone; and NITRILES, such as acetonitrile or isobutyronitrile. Of these preferred aromatic hydrocarbons (particularly benzene), ethers (in particular tetrahydrofuran) and halogenated hydrocarbons (particularly methylene chloride).

There is also no particular restriction on the nature of the used condensing agent, and examples of suitable agents include di(lower alkyl)azodicarboxylate-triphenylphosphine, such as diethylazodicarboxylate-triphenylphosphine; N-(lower alkyl)-5-arylisocyanate-3'-sulfonates, such as N-ethyl-5-phenylisoxazole-3'-sulfonate; N,N'-dicyclohexylcarbodiimide, such as N,N'-dicyclohexylcarbodiimide; 2-halogen-1-(lower alkyl) pyridine halides, such as 2-chloro-1-methylpyridinium iodides; directorrelated, such as diphenylphosphoryl (DPPA); imidazole derivatives such as N,N'-carbonyldiimidazole (CDI); and carbodiimide, such as 1-ETL-3-(3-dimethylaminopropyl)carbodiimide (EADAPC). Of them, preferred are N,N'-dicyclohexylcarbodiimide, 2-chloro-1-methylpyridinium iodide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.

There is also no particular restriction on the nature of the used grounds, provided that no otrain, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N, N-dimethylamino)pyridine, N,N-limecellen, N,N-diethylaniline, 1,5-diazabicyclo[4,3,0]non-5-ene,1,4 diazobicyclo[2,2,2]octane (DABCO) or 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU). Of them preferred triethylamine or N-aminobutiramida N-ethylaniline.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -60oC to 120oC, preferably from 0 to 70oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents in the preferred conditions described above, the period of time from 10 min to 48 h, preferably from 1 to 24 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture; filtering storytale, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound can be, if necessary, and then purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely chromatography.

Dibenzylidene thus obtained monobenzyl ether can be carried out by catalytic regeneration using a catalyst such as palladium on coal or palladium black, in stock hydrogen or formic acid to obtain compounds of carboxylic acids.

Removing the protective group of the thus obtained monotributo ether can be carried out using an acid catalyst such as hydrogen chloride/dioxane, to obtain the compounds of carboxylic acids.

Removing the protective group of the thus obtained monobenzyl ether can be carried out using an acid catalyst, such as triperoxonane acid/anisole to obtain the I 3c), the reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform or dichloroethane; esters such as ethyl acetate, butyl acetate or diethylmalonate; ethers, such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; ketones, such as acetone or methyl ethyl ketone; and NITRILES, such as acetonitrile or isobutyronitrile. Of these preferred aromatic hydrocarbons (particularly benzene) or halogenated hydrocarbons (particularly methylene chloride).

There is also no particular restriction on the nature of the used grounds, provided that there are no negative impacts on the vapor molecules, t any, which can be used in conventional reactions may likewise be used here. Examples include organic CCA)pyridine, N,N-dimethylalanine, N,N-diethylamin, 1,5-diazabicyclo[4,3,0] non-5-ene, 1,4-diazabicyclo[2,2,2]octane (DABCO)or 1,8-diazabicyclo[5,4,0] undec-7-ene (DBU). Of them preferred triethylamine or pyridine.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at temperatures from -40 to 100oC, preferably from 0 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 48 h, preferably from 1 to 24 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water iodoy; separation of the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound can be, if necessary, and then purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Dibenzylidene thus obtained monobenzyl ether can be carried out by catalytic regeneration using a catalyst such as palladium on charcoal, in a stream of hydrogen in a compound of carboxylic acid.

Removing the protective group of the thus obtained mono-tert-butyl ether can be carried out using an acid catalyst such as hydrogen chloride/dioxane, to obtain the compounds of carboxylic acids.

Removing the protective group of the thus obtained monobenzyl ether can be carried out using an acid catalyst, such as triperoxonane acid/anisole to obtain compounds of carboxylic acids.

When3means a group of the formula-C(=O)-CHR88-NR9R10the same method as that described in method stage 3b. When R7means a group of the formula-C(=O)-CHR8-NR9R10(where R9and R10means a hydrogen atom), the desired compound of formula (Ib) can be obtained by the coupling of compounds of formula (Ia) with the compound of the formula: HO-C(= O)-CHR8-NR10-COOB and the same method as that described in method stage 3b, and with the subsequent removal of the tert-butoxycarbonyl group using acid such as hydrochloric acid.

When R7means a group of formula-P(=O)(OH)2the desired compound of formula (Ib) can be obtained by the coupling of compounds of formula (Ia) with the compound of the formula: CIP(=O)(OCH2Ph)2the same method as that described in method stage 3c with subsequent removal of the benzyl group by catalytic regeneration.

Stage 4: the Oxidation

In this stage, the compound of formula (Ic) can be obtained by the coupling of compounds of formula (Ia) with an oxidizing agent.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and that it can which are: aromatic hydrocarbons, such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform or dichloroethane; esters such as ethyl formate or ethyl acetate; ethers, such as tetrahydrofuran, dimethoxyethane or dioxane; ketones, such as acetone, methyl ethyl ketone or methyl isobutyl ketone; and NITRILES, such as acetonitrile or isobutyronitrile. Of them preferred halogenated hydrocarbons (particularly methylene chloride).

There is also no particular restriction on the nature of the used oxidizing agent, and any agent of such a kind used in conventional reactions may be similarly applied here. Examples of preferred oxidizing agents include inorganic metal oxides, including oxides of manganese, such as potassium permanganate; compounds, chromic acids, such as chromic acid-sulfuric acid complex anhydride chromic acid-pyridine or pyridine chlorproma; and cerium compounds, such as ammonium cerium nitrate (CAN); and reagents that can be used when dimethylsulfoxide oxidation (such as dimethylsulfoxide and dicyclohexylcarbodiimide, oxalyl chloride, acetic anhydride, phosphorus pentoxide or a complex of pyridine-serially can be performed in a wide temperature range, and the exact temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -78 to 50oC, more preferably from -60 to 25oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 24 h, more preferably from 1 to 12 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous is t then be purified by such conventional methods, as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 5: Condensation

In this stage, the compound of formula (1c) can be obtained by the coupling of compounds of formula (2) with the compound of the formula (5) in an inert solvent. Included in this stage the reaction is essentially the same as in stage 1 of reaction scheme 1 and can be carried out using the same reagents and under the same reaction conditions.

Stage 6: Recovery

In this stage, the compound of formula (1A) can be obtained by the coupling of compounds of formula (1C) in the reducing agent.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic carbohydrates, such as benzene, toluene or xylene; ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; and alcohols, such as methanol or ethanol. From them predbannikami on the nature of the used recovery agent, and any reduction agent such kind used in conventional reactions may be similarly applied here. Examples of suitable remedial agents include detribalized and diisobutylaluminium.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -78 to 50oC, more preferably from -60 to 25oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 5 min to 24 h, more preferably from 10 min to 12 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture; filtrowa solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Reaction scheme II

Stage 7: Alkylation

In this stage, the compound of formula (8) can be obtained by alkylation of compounds of formula XsH2with the compound of the formula (7).

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has a negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, toluene or xylene; ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; nitro compounds such as nitroethane; NITRILES, such is triamide; and sulfoxidov, such as dimethylsulfoxide or sulfolane. Of them preferred amides (particularly dimethylformamide) and sulfoxidov (in particular dimethyl sulfoxide).

There is also no particular restriction on the nature of the used grounds, provided that there are no negative impacts on the molecules of the reactants and any that can be used in conventional reactions may likewise be used here. Examples of suitable bases include hydrides of alkali metals such as lithium hydride, sodium hydride or potassium hydride; alkoxides of alkali metals such as sodium methoxide, ethoxide sodium tert-piperonyl potassium or lithium methoxide; and organic base metals, such as utility or diisopropylamide lithium. Of them preferred hydrides, alkali metal (in particular sodium hydride) or an organic base metals (in particular utility or diisopropylamide lithium).

Suitable compounds of formula XsH2include sulfur-containing compounds as 1,3-dition, (methylthio) methyl n-tomasulo and (methylthio)methyl methylsulfoxide.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critia solvent and used the original reaction product. In General, however, convenient to conduct the reaction at a temperature of from -20 to 100oC, more preferably from 0 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 24 h, more preferably from 1 to 12 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and nesmeshivaemykh with water, an organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound, drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or different is this stage, the compound of formula (10) can be obtained by alkylation of compounds of formula (8) with the compound of the formula (9).

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, toluene or xylene; ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphoramide; and sulfoxidov, such as dimethylsulfoxide or sulfolane. Of them preferred ethers (particularly tetrahydrofuran or dimethoxyethane).

There is also no particular restriction on the nature of the used grounds, provided that there are no negative impacts on the molecules of the reactants and any that can be used in conventional reactions may likewise be used here. Examples of suitable bases include hydrides of alkali metals such as lithium hydride, sodium hydride or potassium hydride; alkoxides of alkali metals such as sodium methoxide, ethoxide sodium tert-piperonyl or potassium methoxide flaxes hydrides, alkali metal (in particular sodium hydride) or an organic base metals (in particular utility).

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -78 to 100oC, more preferably from -60 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 24 h, more preferably from 30 minutes to 6 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired spolocenke thus the desired connection, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

When the desired connection is unstable, you can use

Stage 9: Desulfuromonas

In this stage, the compound of formula (11) can be obtained by solvolysis of the compounds of formula (10) in the presence of an acid catalyst, mercury salts or salts of silver.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material; at least to some extent. Examples of suitable solvents include: ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; alcohols, such as methanol or ethanol; ketones, such as acetone or methyl ethyl ketone; and water. Of them preferred alcohols (particularly methanol) or ethers (particularly tetrahydrofuran).

There is also no particular restriction on the nature of the used acid catalyst, and any acid is. the reamers of suitable acid catalysts include inorganic acids such as hydrochloric acid, Hydrobromic acid, sulfuric acid, perchloric acid or phosphoric acid; organic acids, such as methanesulfonate, n-toluensulfonate, triperoxonane acid three triftormetilfullerenov acid. Which one is preferable concentrated hydrochloric acid.

When the compounds of the formula XsH2use of 1,3-dition, the solvolysis can be carried out in the presence of mercury chloride or silver nitrate.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 25 to 150oC, more preferably from 50 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in a preferred SS="ptx2">

After completion of the reaction do the connection can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Step 10: Restore keto group

In this stage, the compound of formula (6) can be obtained by the coupling of compounds of formula (11) with a regenerating agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 6 of the reaction scheme 1, and can be carried out using the same reagents and under the same reaction conditions.

Stage 10A: In the texts of the formula (11) regenerating agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 12 of reaction scheme III can be carried out using the same reagents and under the same reaction conditions.

Reaction scheme III

Steel II: Introduction of protective groups

In this stage, the compound of formula (12) can be obtained by the coupling of compounds of formula (6) with a protective agent.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: halogenoalkane hydrocarbons, such as methylene chloride, chloroform or dichloroethane; ethers, such as tetrahydrofuran, dioxane or dimethoxyethane; and amides, such as formamide, dimethylformamide or dimethylacetamide. Of them preferred halogenated hydrocarbons (particularly methylene chloride) and amides (in particular dimethylforamide).

There is also no particular restriction on the nature of the used protective groups, and any protective group commonly used in OAuth tert-butyldimethylsilyl chloride, dihydropyran or methoxymethane.

For example, the protection with the use of the above groups may be implemented as described in "Protective Croups in Organic synthesis, Second Edition, T. W. Green &P. G. M. Wut; John Wiley and Sons, Inc., New York (1991).

The reaction can be performed in a wide interval of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend on such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -20 to 100oC, more preferably from 0 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 48 h, more preferably from 30 minutes to 24 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture; filtering Neretva, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Step 12: the Recovery of the nitro group

This stage includes obtaining the compounds of formula (3) restoration of the compounds of formula (12) regenerating agent.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: alcohols, such as methanol or ethanol and water. Of them preferred alcohols.

There is also no particular restriction on the nature of the used recovery agent, and any reduction agent such adenovirally agents include zinc/acetic acid, iron/hydrochloric acid, or tin/hydrochloric acid, preferably zinc/acetic acid.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention, the preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. Mainly, however, convenient to conduct the reaction at a temperature of from -20 to 150oC, more preferably from 0 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above for the period of time from 10 minutes to 24 hours, more preferably from 20 minutes to 12 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent such as these is the scale of the extract over a drying agent, such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Reaction scheme IV

Stage 13: the Education of oxocarboxylate

In this stage, the compound of formula (14) can be obtained by exposure to the compounds of formula (13) with carbodiimides and then with potassium salt of monoether malonic acid (preferably R11means a methyl or ethyl group) in the presence of epirate of minibrain.

Activated the connection of the corresponding compounds of formula (13) can be obtained by a method known in the art, for example, similarly to the method described in Synthesis 478 (1978).

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromafloria, chloroform or dichloroethane; ethers, such as tetrahydrofuran, dioxane or dimethoxyethane; NITRILES, such as acetonitrile or isobutyronitrile; amides, such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphoramide; and sulfoxidov, such as dimethylsulfoxide or sulfolane. Which one is preferable diethyl ether, tetrahydrofuran or NITRILES, such as acetonitrile.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend on the same factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature from 0 to 60oC. When the decarboxylation proceeds slowly, the reaction temperature allow to rise until the interval from 20 to 50oC for promotion of the reaction. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions outlined above, a period of time of about 12 hours is usually dotage to be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 14: Alkylation

In this stage, the compound of formula (16) can be obtained by the coupling of compounds of formula (14) with the compound of the formula (15) in the presence of a base.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solution of the odes, such as dichloromethane; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane or dimethoxyethane; alcohols such as methanol, ethanol or tert-butanol; nitro compounds such as nitroethane; amides, such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphoramide; and sulfoxidov, such as dimethylsulfoxide or sulfolane. Of them preferred ethers (particularly tetrahydrofuran), amides (particularly dimethylformamide) or alcohols.

There is also no particular restriction on the nature of the used grounds, provided that there are no negative impacts on the molecules of the reactants and any that can be used in conventional reactions may likewise be used here. Examples of suitable bases include: inorganic bases, including hydrides of alkali metals such as lithium hydride, sodium hydride or potassium hydride; or alkoxides of alkali metals such as sodium methoxide, ethoxide sodium tert-piperonyl potassium or lithium methoxide; more preferred alkoxides of alkali metal (in particular sodium methoxide, ethoxide or sodium tert-piperonyl potassium).

The reaction can be performed in a wide temperature range, t depend on such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -30 to 100oC, more preferably from 0 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 h, more preferably from 1 to 10 hours will normally suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified from such ordinary the night chromatography.

Stage 15: the Decarboxylation

In this stage, the compound of formula (11) can be obtained by subjecting the compound of formula (16) to hydrolysis in the presence of base, followed by decarboxylation.

These reactions usually and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of preferred solvents include: ethers, such as tetrahydrofuran, dioxane or dimethoxyethane; alcohols such as methanol, ethanol or tert-butanol; and mixtures of alcohols and water. Of them preferred alcohols or mixture of alcohol and water.

There is also no particular restriction on the nature of the used grounds, provided that there are no negative impacts on the molecules of the reactants and any that can be used in conventional reactions may likewise be used here. Examples of suitable bases include carbonates of alkali metals such as sodium carbonate, potassium carbonate or lithium carbonate; hydroxides of alkali metals or hydroxides of deliciosamente the equipment hydroxide potassium.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 0 to 150oC, more preferably from 25oC to 100oC.

The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 min to 24 h, preferably from 1 to 10 hours will normally suffice.

After completion of the hydrolysis, the pH of the reaction mixture is brought to a pH of about 5 by the addition of an acid such as concentrated hydrochloric acid or dilute sulfuric acid, to effect decarboxylation.

The decarboxylation reaction can be carried out in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature is C the om, convenient to conduct the reaction at a temperature of from 50 to 150oC, more preferably from 70 to 120oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 min to 24 h, preferably from 1 to 4 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or different chromatograhy

In this stage, the compound of formula (18) can be obtained by exposure to the compounds of formula (2) with the compound of the formula (17) in an inert solvent. Included in this stage the reaction is essentially the same as in the stage I reaction scheme 1, and can be carried out using the same reagents and under the same reaction conditions.

Stage 17: removing the protective group

At this stage, the compound of formula (19) can be obtained by the coupling of compounds of formula (18) by removing the protective group agent.

The method chosen for removing the protective group, will vary depending on the nature of the protective groups, however, such methods are well known and removing the protection can be carried out in the usual way.

When the protective group is tert-butyldimethylsilyl, it can be removed by removing the protecting agent.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of preferred solvents including methanol or ethanol.

There is also no particular restriction on the nature of the used removing the protecting agent, and removing any protecting agents commonly used in conventional reactions may likewise be used here. Examples of suitable removing the protecting agents include hydrochloric acid or tetrabutylammonium, preferably hydrochloric acid.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -20 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 48 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization Riego with water, an organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired connection if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 17: Maintain the leaving group

At this stage, the compound of formula (20), (93) and (95) can be obtained by the coupling of compounds of formula (19), (23) or (30) with a compound containing alkylsulfonyl or arylsulfonyl group (preferably methanesulfonyl or n-toluensulfonyl group) in the presence of a base.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of preferred solvents include: aromatic hydrocarbons, such as benzene; halogenerators, dioxane or dimethoxyethane.

There is also no particular restriction on the nature of the used removing the protecting agent, and removing any protecting agents commonly used in conventional reactions may likewise be used here. Examples of suitable removing the protecting agents include hydrochloric acid or tetrabutylammonium, preferably hydrochloric acid. Preferred halogenated hydrocarbons (particularly methylene chloride or dichloroethane).

There is also no particular restriction on the nature of the used grounds, and any bases that can be used in conventional reactions may likewise be used here. Examples of suitable bases include organic bases, such as triethylamine, Diisopropylamine, isopropylacrylamide, N-methylmorpholine, pyridine, 4-(N,N-dimethylamino)pyridine, N,N-dimethylaniline or N, N-diethylaniline, of which the preferred triethylamine or Diisopropylamine.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent and used the original product a from 0 to 25oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 5 min to 10 h, more preferably from 10 minutes to 3 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired compound, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 19: the Introduction imidazolyl is of formula (20), (93), (95) or (40) with imidazole or benzimidazole.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; NITRILES, such as acetonitrile or isobutyronitrile; amides, such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphoramide; and sulfoxidov, such as dimethylsulfoxide or sulfolane. Of them preferred amides (particularly dimethylformamide) or sulfoxidov (in particular dimethyl sulfoxide).

The reaction can sometimes be accelerated by conducting it in the presence of sodium iodide or potassium iodide.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. However, the OS is required for the reaction, can also vary widely depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours, more preferably from 2 to 12 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method comprises: adding water to the reaction mixture and the water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Reaction scheme VI

Stage 20: Condensation

In this stage, the compound of formula (22) can be obtained by the coupling of compounds of formula (2) with the connection is Westley using the same reagents and under the same reaction conditions.

Stage 21: removing the protective group

At this stage, the compound of formula (23) can be obtained by the coupling of compounds of formula (22) by removing the protective group agent.

When hydroxyamino group is tert-butyldimethylsilyl group, it can be removed by treatment with inorganic acid, such as hydrochloric acid, or a compound capable of forming anion fluoride, such as tetrabutylammonium fluoride.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has a negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: alcohols, such as methanol; and ethers, such as tetrahydrofuran or dioxane.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to carry out reaction at the same time is their factors, namely, the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 18 hours is usually sufficient.

When hydroxyamino the aliphatic group is acetyl group, it can be removed by treatment with a base.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include; water; organic solvents, including alcohols such as methanol, ethanol or propanol; ethers, such as tetrahydrofuran or dioxane; or a mixture of water and one or more of these organic solvents.

There is also no particular restriction on the nature of the used grounds, and any base commonly used in conventional reactions may likewise be used here, except for those groups, compounds which do not have the steps for removing the protective group. Primaryemail, such as sodium carbonate, potassium carbonate or lithium carbonate; hydroxides of alkali metals such as sodium hydroxide, potassium hydroxide or lithium hydroxide; and ammonia, which can be in various forms, such as aqueous ammonia or concentrated ammonia in methanol.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used in the initial reaction product. In General, however, convenient to conduct the reaction at a temperature of from 0 to 150oC to prevent adverse reactions. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 10 hours will normally suffice.

When hydroxyamino group is alkoxymethyl, tetrahydropyranyl, tetrahydropyranyl, tetrahydrofuranyl, tetrahydrofuranyl or substituted ethyl group, she can usually be removed there are No special restrictions on the nature of the solvent used, provided he has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: alcohols, such as methanol or ethanol; ethers, such as tetrahydrofuran or dioxane; and mixtures of water and one or more of these organic solvents.

There is also no particular restriction on the nature of the used acidic agent, and any acid commonly used in conventional reactions may likewise be used here. Examples of suitable acids include acids of Bronsted, including inorganic acids such as hydrochloric acid or sulfuric acid; organic acids such as acetic acid or n-toluensulfonate; and strong acid ion exchange resin such as Dowex (trade mark) 50W.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 0 to 50oC. the Time required for the reaction, new and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 minutes to 18 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 22: Oxidation

In this stage, the compound of formula (24) can be obtained by the coupling of compounds of formula (23) with an oxidizing agent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no special limitation that it can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform or dichloroethane; esters such as ethyl formate, ethyl acetate or diethylmalonate; ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; ketones, such as acetone or methyl ethyl ketone; and NITRILES, such as acetonitrile or isobutyronitrile. Of them preferred halogenated hydrocarbons (particularly methylene chloride) or ethers (particularly tetrahydrofuran).

There is also no particular restriction on the nature of the used oxidizing agent, and any oxidizing agent used in conventional reactions may be similarly applied here. Examples of preferred oxidizing agents include% manganese oxides, such as potassium permanganate; chromium oxides, such as complex anhydride chromic acid-pyridine; and reagents that can be used when dimethylsulfoxide oxidation (such as complexes of dimethyl sulfoxide and dicyclohexylcarbodiimide, oxalicacid, acetic anhydride, phosphorous pentoxide or a pyridine-sulfur and which is critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature from 60 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 2 to 16 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional the Naya chromatography.

Reaction scheme VII

Stage 23% Condensation

In this stage, the compound of formula (26) can be obtained by the coupling of compounds of formula (25) with the compound of the formula (2) in an inert solvent. Included in this stage the reaction is essentially the same as in stage 1 of reaction scheme 1, and can be carried out using the same reagents and under the same reaction conditions.

Stage 24: Substitution (X _ Aco)

At this stage, the compound of formula (27) can be obtained by the coupling of compounds of formula (26) with a salt of acetic acid in the presence of sodium iodide.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as tetrahydrofuran, dioxan or dimethoxyethane; alcohols, such as tert-butanol; ketones, such as acetone or methyl ethyl ketone; nitro compounds such as nitromethane; amides, such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide; sulfox pactically amides (particularly dimethylformamide) or sulfoxidov (in particular dimethyl sulfoxide).

Suitable for use in this reaction acetates include alkali metal salts of acetic acid such as sodium acetate or potassium acetate.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. Mainly, however, convenient to conduct the reaction at a temperature of from 0 to 150oC, more preferably from 25 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 h, more preferably from 2 to 6 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and immiscible with viescas phase, containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 25: removing the protective group

At this stage, the compound of formula (28) can be obtained by the coupling of compounds of formula (27) with dealerused agent.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane: alcohols, such as methanol or ethanol; and water. Of them preferred alcohols (particularly methanol) or a mixture of water and one or more alcohols (particularly methylene chloride).

There is also no particular restriction on the nature of the used deaem the same manner used here. Examples of suitable dealerused agents include inorganic bases, including carbonates of alkali metals such as sodium carbonate, potassium carbonate or lithium carbonate; bicarbonates of alkali metals such as sodium bicarbonate, potassium bicarbonate or hydrocarbonate lithium; hydroxides of alkaline metals such as sodium hydroxide, potassium hydroxide or lithium hydroxide; hydroxides of alkaline earth metals such as barium hydroxide; or alkoxides of alkali metals such as sodium methoxide, ethoxide sodium tert-piperonyl potassium or lithium methoxide. Of them preferred hydroxides of alkali metal (in particular sodium hydroxide or potassium hydroxide).

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 0 to 100oC, more preferably from 25 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and pryh conditions, as described above, the period of time from 10 min to 24 h, more preferably from 30 minutes to 12 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 26: Oxidation

In this stage, the compound of formula (24A) can be obtained by the coupling of compounds of formula (28) with an oxidizing agent. Included in this stage the reaction is essentially the same as in stage 22 of the reaction scheme VI can be carried out using the same reagents is their formula (29) can be obtained vzaimodeistvie the compounds of formula (24) with a reagent of the Wittig-Horner (Witting-Hjrner), such as diethoxyphosphoryl in the presence of a base.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene: ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; amides, such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphoramide; and sulfoxidov, such as dimethylsulfoxide or hexamethylphosphorotriamide; and sulfoxidov, such as dimethylsulfoxide or sulfolane; more preferred ethers (particularly tetrahydrofuran) or an amide (particularly dimethylformamide).

There is also no particular restriction on the nature of the used grounds, and any base commonly used in conventional reactions may likewise be used here. Examples of suitable bases include compounds that are used in stage 7.

The reaction can be performed in a wide interval pace is and will depend on such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -20 to 100oC, more preferably from 0 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time t 10 min to 48 h, more preferably from 1 to 24 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound, drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified such obychaemaja chromatography.

The double bond formed in the product may be, if desired, a catalytic restored in a stream of hydrogen.

Response recovery usually and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include% esters, such as ethyl acetate; ethers, such as tetrahydrofuran, dioxane or dimethoxyethane; and alcohols, such as methanol or ethanol; more preferred alcohols, such as methanol or ethanol; ethers, such as tetrahydrofuran or dioxane; fatty acids, such as acetic acid, or mixtures of one or more organic solvent and water.

There is also no particular restriction on the nature of the used catalyst, and any catalyst commonly used in well-known reactions, can be similarly used here. Examples of suitable acid catalysts include palladium on coal or Raney Nickel.

The reaction can be performed in a wide temperature range, tavist on factors such as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of -10 to 50oC, more preferably from 0 to 25oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 24 h, more preferably from 30 minutes to 6 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes% filtration of the catalyst and distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 28% Recovery

In this stage, the compound of formula (30) can be obtained by the coupling of compounds of formula (29) with a reducing agent. The reaction is normally and preferably carried the ri condition, he has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane: alcohols, such as methanol or ethanol. Of them preferred ethers (particularly tetrahydrofuran) or an alcohol (particularly methanol).

There is also no particular restriction on the nature of the used recovery agent, and any reduction agent such kind used in conventional reactions may be similarly applied here. Examples of suitable remedial agents include detribalized and diisobutylaluminium.

The reaction can be performed in a wide temperature range, and turned the temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -20oC to 100oC, more preferably from 0 to 80oC. the Time required for the reaction may also vary widely in savikko provided the reaction is carried out in the preferred conditions described above, the period of time from 10 minutes to 24 hours, more preferably from 1 to 10 hours will normally suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 29: Oxidation

In this stage, the compound of formula (31) can be obtained by the coupling of compounds of formula (30) with an oxidizing agent.

The reaction is normally and preferably carried out in the presence of a solvent. There is the influence on the reaction and that it can dissolve the starting material, at least to some extent. Examples of suitable solvents include: halogenated hydrocarbons, such as methylenchlorid or chloroform; and ethers, such as tetrahydrofuran, dimethoxyethane or dioxane. Of them preferred halogenated hydrocarbons (particularly methylene chloride).

There is also no particular restriction on the nature of the used oxidizing agent, and any agent of such a kind used in conventional reactions may be similarly applied here. Examples of suitable oxidizing agents include compounds of chromium, such as complex anhydride chromic acid-pyridine or pyridine-chlorimet; and reagents that can be used when dimethylsulfoxide oxidation ( such as the complex of dimethyl sulfoxide and dicyclohexylcarbodiimide, oxalyl chloride, acetic anhydride, phosphorus pentoxide or a complex of a pyridine-sulfuric anhydride). Of them preferred pyridineboronic or dimethylsulfoxide/oxalicacid).

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of rature from -78 to 40oC, more preferably from -60 to 25oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 minutes to 6 hours, more preferably from 1 to 3 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene; and ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention, the Preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -78 to 50oC, more preferably from -60 to 25oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 24 h, more preferably Nero isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product may then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 31: Etherification

In this stage, the compound of formula (If) can be obtained by esterification of compounds of formula (Ie) in an inert solvent. Included in this stage the reaction is essentially the same as in stage 3 of reaction scheme 1, and can be implemented using the same de reagents and under the same reaction conditions.

Stage 32: Oxidation

In this stage, the compound of formula (Ig) can be obtained by the coupling of compounds of formula (Ie) with an oxidizing agent in an inert solvent. Included in this article is eat the same reagents and under the same reaction conditions.

The reaction scheme X

Stage 33: Alkylation

In this stage, the compound of formula (Ih) can be obtained by the coupling of compounds of formula (24) with the desired reactor Grignard reagent in an inert solvent. Included in this stage the reaction is essentially the same as in stage 30 of the reaction scheme IX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 34: Etherification

In this stage, the compound of formula (Ii) can be obtained by esterification of compounds of formula (Ih) in an inert solvent. Included in this stage the reaction is essentially the same as in stage 3 of reaction scheme 1, and can be carried out using the same reagents and under the same reaction conditions.

Stage 35: Oxidation

In this stage, the compound of formula (Ij) can be obtained by the coupling of compounds of formula (Ih) with an oxidizing agent in an inert solvent. Included in this stage the reaction is essentially the same as in stage 22 of reaction scheme VI can be carried out using the same reagents and under the same reaction conditions.

The reaction scheme XI

Stage 36:

In this stage, the compound of formula (Ik) can be obtained vzaimode the Ktsia usually and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, toluene or xylene; ethers, such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphoramide; and sulfoxidov, such as dimethylsulfoxide or sulfolane. Of them preferred ethers (particularly tetrahydrofuran) or an amide (particularly dimethylformamide).

There is also no particular restriction on the nature of the used grounds, and any base commonly used in conventional reactions may likewise be used here. Examples of suitable bases include bases that are used in stage 7.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent and the use of/SUP>C, more preferably from 0 to 70oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 24 h, more preferably from 30 minutes to 12 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

the type.

Response recovery usually and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as ethyl acetate; ethers, such as tetrahydrofuran, dioxane or dimethoxyethane; alcohols, such as methanol or ethanol; and fatty acids such as acetic acid; water, more preferred alcohols, such as methanol or ethanol, ethers, such as tetrahydrofuran or dioxane, fatty acids, such as acetic acid, or a mixture of one or more organic solvent and water.

There is also no particular restriction on the nature of the used catalyst, and any catalyst commonly used in well-known reactions, can be similarly used here. Examples of suitable acid catalysts include palladium on charcoal, platinum and Raney Nickel.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. Predpochtitelnye the reaction product. However, in General, comfortable carrying out the reaction at a temperature of -10 to 50oC, more preferably from 0 to 25oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 20 min to 24 h, more preferably from 30 minutes to 6 hours, will usually suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method comprises: filtering the catalyst and distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 37: Restoration

In this stage, the compound of formula (Im) can be obtained by reduction of compounds of formula (Ik) regenerating agent in an inert solvent. Included in this stage the reaction is essentially the same as in stage 6 of the reaction scheme 1, and M38: Etherification

In this stage, the compound of formula (In) can be obtained by esterification of compounds of formula (Im) in an inert solvent. Included in this stage the reaction is essentially the same as in stage 3 of reaction scheme 1, and can be carried out using the same reagents and under the same reaction conditions.

The reaction scheme XII

Stage 39: Sozialarbeit (carboxylic acid)

In this stage, the compound of formula (33) can be obtained by the coupling of compounds of formula (32) with diphenylphosphorylacetate in the presence of a base.

The reaction is normally and preferably carried out in the presence of a solvent, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, toluene Il acids; halogenated hydrocarbons such as methylene chloride or dichloroethane; ethers, such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; NITRILES, such as acetonitrile or isobutyronitrile; and amides, such as formamide, dimethylformamide, dimethylacetamide or hexamer is (particularly tetrahydrofuran).

There is also no particular restriction on the nature of the used grounds, and any base commonly used in conventional reactions may likewise be used here. Examples of suitable bases include bases, such as triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N, N-dimethylamino)pyridine, N,N-dimethylaniline or N,N-diethylaniline. Of them preferred triethylamine or diisopropylethylamine.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend on factors such_ as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 50 to 150oC, more preferably from 70 to 120oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 min to 24 h, more preferably from 1 to 12 hours, will usually suffice.

After the head is that it can be used in subsequent reactions without purification.

Stage 40: Attach

in this stage, the compound of formula (34), in which R2means a hydrogen atom, can be obtained by the coupling of compounds of formula (33) with the specified connection formula(3), (5), (17), or (21).

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride or dichloroethane; and ethers, such as tetrahydrofuran, dioxane or dimethoxyethane. Of these preferred aromatic hydrocarbons (particularly benzene or toluene). 2 Reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 0 to 150o

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent. Thus obtained the desired product, if necessary, can then be purified by such conventional techniques as recrystallization, pereosazhdeniya or various chromatographic methods, namely column chromatography.

Stage 41: Sozialarbeit (Amin)

In this stage, the compound of formula (36) can be obtained by the coupling of compounds of formula (35) with foroudastan in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: halogenated hydrocarbons, such as methylene chloride, chloroform or dichloroethane; and ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane or diethylene glycol. Of them preferred methylene chloride.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -40 to 50oC., more preferably -20 to 0oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 24 h, more predpochtiteljno used in subsequent reactions without purification due to the instability of the connection.

Stage 42: Attach

In this stage, the compound of formula (34) can be obtained by the coupling of compounds of formula (36) with the amine of the formula: R1R2NH in an inert solvent. Included in this stage the reaction is essentially the same as in stage 40, the reaction scheme XII, and can be carried out using the same reagents and under the same reaction conditions.

Stage 43: removing the protective group

In this stage, the compound of formula (1p) can be obtained by the coupling of compounds of formula (34) by removing the protecting agent in an inert solvent. Included in this stage the reaction is essentially the same as in stage 2 of the reaction scheme 1, and can be implemented using the same reagent and under the same reaction conditions. If desired, the secondary hydroxyl group of compounds of formula (34) can be modified according to the method described in stage 3.

Methods of obtaining these starting compounds of the formulas(15), (17), (21) and (25) are explained next.

The reaction scheme XIII

Stage 44: Restoration

In this stage, the compound of formula (38) can be obtained by the coupling of compounds of formula (37) with a reducing agent.

There is also a special agripolicy in ordinary reactions, can be similarly applied here. Examples of suitable remedial agents include DIBORANE, such as DIBORANE or a complex DIBORANE-dimethyl sulfide.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include ethers, such as tetrahydrofuran, dioxane or 1,2-dimethoxyethane.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 20 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in a preferred conditions, the description is a group of formula (37) is subjected to interaction with chloroformiate, such as ethylchloride, getting a mixed anhydride, and then the product can be recovered by sodium borohydride.

The solvent used in the synthesis of the mixed anhydride, preferably an ether, such as 1,2-dimethoxyethane or tetrahydrofuran.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -20 to 30oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 minutes to 6 hours is usually sufficient.

After completion of the reaction, the anhydride can be isolated from the reaction mixture of various well-known methods, for example by filtration of the reaction mixture at Celite (trade mark). The filtrate is then added to the mixture of water and tetrag the Oia can be performed in a wide temperature range, and the exact temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 0 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 minutes to 3 hours is usually sufficient.

Stage 45: Introduction of the leaving group

At this stage, the compound of formula (15) can be obtained by the coupling of compounds of formula (38) with alkylsulfonamides in an inert solvent in the presence of a base. Included in this stage the reaction is essentially the same as in stage 13 of the reaction scheme V, and can be carried out using the same reagents and under the same reaction conditions.

The sulfonates obtained in this stage, if desired, is subjected to the interaction with sodium iodide or potassium iodide with getting iodide.

A suitable solvent is in a wide temperature range, and the exact temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 0 to 80oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 8 hours is usually sufficient.

The reaction scheme XIV

Stage 46: Introduction of the leaving group

At this stage, the compound of formula (40) can be obtained by the coupling of compounds of formula (39) alkylsulfonyl or arylsulfonamides in an inert solvent. Included in this stage the reaction is essentially the same as in stage 45 of reaction scheme XIII, and can be carried out using the same reagents and under the same reaction conditions. This stage is used to obtain compounds in which m1is other than a single bond.

Further, the sulfonates obtained in this stage, Engl="ptx2">

Stage 46(a): Obtaining alcohol compounds

At this stage, the compound of formula (41) can be obtained by the coupling of compounds of formula (39) with the desired diol compound (HO-A2-OH) or halogenoacetyl compound of the formula hal-A2-OH) in the presence of a base. This stage is used to obtain compounds in which m1is a single bond.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as tetrahydrofuran or 1,2-dimethoxyethane; and amides, such as dimethylformamide or dimethylacetamide.

There is also no particular restriction on the nature of the used grounds, and any base commonly used in conventional reactions may likewise be used here. Examples of suitable bases include carbonates of alkali metals such as potassium carbonate.

The reaction can be performed in a wide temperature range, and the exact teat factors such as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 20 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 2 to 12 hours will normally suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture; the Stripping of the solvent; adding water and a water-immiscible organic solvent, such as diethyl ether; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent.

Stage 47: Obtaining alcohol compounds

At this stage, with a compound of formula (41) can be obtained by the coupling of compounds of formula (40) with the desired diol compound in the presence of base">

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as tetrahydrofuran or 1,2-dimethoxyethane; and amides, such as dimethylformamide or dimethylacetamide.

There is also no particular restriction on the nature of the used grounds, and any base commonly used in conventional reactions may likewise be used here. Examples of suitable bases include carbonates of alkali metals such as sodium hydride or potassium hydride.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at temperatures from -20 to 60oC. the Time required for the reaction may also vary widely, depending on many factual carried out in a preferred conditions, as described above, the period of time from 1 to 24 hours will normally suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent.

Stage 48: the Introduction of protective groups

At this stage, the compound of formula (42) can be obtained by the coupling of compounds of formula (41) with a protecting agent in an inert solvent. Included in this stage the reaction is essentially the same as in stage 11 of reaction scheme III can be carried out using the same reagents (except methoxymethane) and in the same reaction conditions.

Stage 49: Restoring nitro

In this stage, the compound of formula (17) can be obtained by reduction of compounds of formula (42) regenerating agent in an inert dissolve the Lena using the same reagents and under the same reaction conditions.

The reaction scheme XIV

Stage 50: Restoration

In this stage, the compound of formula (44) can be obtained by reduction of compounds of formula (43) regenerating agent in an inert solvent. Included in this stage the reaction is essentially the same as in stage 44 of reaction scheme III can be carried out using the same reagents and under the same reaction conditions.

Stage 51: the Introduction of protective groups

At this stage, the compound of formula (45) can be obtained by the coupling of compounds of formula (414) with a protecting agent in an inert solvent. Included in this stage the reaction is essentially the same as in stage 11 of reaction scheme III can be carried out using the same reagents (except methoxymethane) and in the same reaction conditions.

Stage 52: the Introduction of a nitro group

In this stage, the compound of formula (21) can be obtained by reduction of compounds of formula (45) with a regenerating agent in an inert solvent. Included in this stage the reaction is essentially the same as in stage 12 of reaction scheme III can be carried out using the same reagents and under the same reaction conditions.

The reaction of the compounds of formula (46) with dimethylsulfoxide in the presence of N-chlorosuccinimide.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include halogenated hydrocarbons such as methylene chloride or chloroform.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at temperatures from -20 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. N the population halogenated hydrocarbon solvent, such as methylene chloride; washing the organic phase with saturated aqueous sodium hydrogen carbonate solution; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent.

Stage 54: Oxidation

In this stage, the compound of formula (48) can be obtained by the coupling of compounds of formula (47) with an oxidizing agent.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: halogenated hydrocarbons, such as methylene chloride or chloroform; alcohols, such as methanol or ethanol.

There is also no particular restriction on the nature of the used oxidizing agent, and any agent of such a kind used in conventional reactions may be similarly applied here. Examples of preferred oxidizing agents include m-chloroperbenzoic acid.

The reaction can be done by the sustained fashion, the reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at temperatures from -20 to 60oC (preferably at room temperature). The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method comprises: filtering the insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with saturated aqueous sodium hydrogen carbonate solution, and then separating the organic phase containing the desired compound; drying the extract over a drying agent such as benzoic magnesium sulfate, and stripped of solvent.

Stage 55: Halogenoalkane

In this stage the compound of formula (25) can be obtained by the interaction sevii solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include halogenated hydrocarbons such as methylene chloride, chloroform or 1,2-dichloroethane.

Used by halogenation, for example, may be hydrogen chloride or hydrogen bromide.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at temperatures from -20 to 60oC. the Time required for the reaction at temperatures from -20 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

example, the desired compound can be selected by collecting the precipitate by filtration.

The source material of the formula (2) used in the present invention, can be obtained by synthesis gelegenheid from commercially available carboxylic acids or of carbonic acid, which can be obtained well-known in a special way. In particular the connection with (N-xanthene-9-yl)methyl group, can be obtained similarly to the method described in the patent application of Japan Hei 4-243357. 6,11-Dihydrobenzo[b,e]azepin-11-carboxylic acid is known from EP 0497201 (1992). An alternative source of compounds used in the present invention, can be obtained as follows.

The reaction scheme XVII

Stage 56:

In this stage, the compound of formula (50) can be obtained by the coupling of compounds of formula (49) with oxalylamino to obtain the carboxylic acid and then by the interaction of the product with diazomethane.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, the edge is called

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at temperatures from -20 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods. For example, one suitable method includes: full neutralization of the reaction mixture, filtering to remove insoluble material, if any; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; what aimogasta the compounds of formula (50) with an alcohol in the presence of metal, such as silver benzoate.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include alcohols, such as methanol or ethanol.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 40 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 3 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by conventional methods.constituent material, if there is one; adding water and a water-immiscible organic solvent, such as ethyl acetate; washing the organic phase with water; separating the organic phase containing the desired compound; drying the extract over a drying agent such as anhydrous magnesium sulfate; and the distillation of the solvent.

Stage 58:

At this stage, the compound of formula (2A) can be obtained by hydrolysis of the formula (51) in an inert solvent. Included in this stage the reaction is essentially the same as in stage 25 reaction scheme VII,and may be carried out using the same reagents and in the same reaction conditions.

The reaction scheme XVIII

Stage 59: Restoring sociallyengaged

This stage includes obtaining alcohol compounds of the interaction of the compounds of formula (49) with a reducing agent.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: PR is topical dimethyl ether (particularly tetrahydrofuran).

There is also no particular restriction on the nature of the used restoration agent and any reduction agent such kind used in conventional reactions may be similarly applied here. Examples of suitable remedial agents include sociallyengaged.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature from 0 to 70oC, more preferably from 40 to 70oC. the Time required for the reaction may also vary widely, depending on many factors the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 15 minutes to 2 hours is usually sufficient.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture is cooled in an ice bath; add water and n is, for example diethyl ether; filtered off the insoluble material, if any; the filtrate is washed with water, aqueous sodium hydrogen carbonate solution and aqueous solution of sodium chloride in the order mentioned, and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product can, if desired, then clear such conventional techniques as recrystallization or the various chromatography methods, namely column chromatography.

Stage 60: Introduction of the leaving group

This stage includes obtaining alkyl - or arylsulfonate compounds by reacting an alcohol compound obtained as described in stage 59, the reagent used to introduce alkyl - or arylsulfonyl groups (preferably methanesulfonyl group) in the presence of a base in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 18 of the reaction scheme V, and can be carried out using the same reagents and reaction conditions.

Stage 61: Iodination

This stage includes obtaining compound (52) the interaction of alkyl - or arylsulfonate connection, sex is between the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ketones, such as acetone, methyl ethyl ketone or methyl isobutyl ketone (especially methyl isobutyl ketone).

There are no such restrictions on the nature of the used jodorowski agent, and any Jodorowsky agent commonly used in well-known reactions, can be similarly used here. Examples of suitable Jodorowsky agents include sodium iodide.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 30 to 150oC, more preferably from 60 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. One h more preferably from 5 to 20 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of such technique is as follows : the reaction mixture is freed from solvent by distillation; the residue is mixed with water; the aqueous mixture is extracted with water-immiscible solvent, for example benzene, diethyl ether, ethyl acetate or the like; and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product, if desired, is purified further well-known methods such as recrystallization or the various chromatography methods, namely column chromatography.

Stage 62: Synthesis of the precursor aldehyde

Stage includes obtaining alkylated predecessor alkylated aldehyde interaction of the compounds of formula (52) and the compound of the formula X3H2in the presence of a base in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 7 of the reaction scheme 11, and can be carried out using the same reagents and under the same reaction conditions.

aldehyde, obtained as described in stage (57) 62, in the presence of heavy metal.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include a mixture of water with a nitrile, such as acetonitrile, or an alcohol, such as methanol or ethanol.

Used a combination of heavy metal can be, for example, mercury chloride or silver nitrate.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 50 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out after completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture is cooled in an ice bath; add water-immiscible solvent, for example benzene, ethyl ether, ethyl acetate or the like; insoluble material is filtered off; the filtrate is washed with water, aqueous sodium acetate solution, an aqueous solution of ammonium chloride and an aqueous solution of sodium chloride in the order mentioned, and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product can, if desired, then clear such conventional techniques as recrystallization or the various chromatography methods, namely column chromatography.

Stage 64: Oxidation (to obtain a carboxyl group)

This stage includes obtaining compound (2A) by the interaction of the compounds of formula (53) with an oxidizing agent.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvent is slideling agent, and any agent of such a kind used in conventional reactions may be similarly applied here. Examples of suitable oxidizing agents include sodium chloride.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 0 to 50oC, more preferably at room temperature. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 min to 5 h, more preferably from 1 to 3 hours is usually sufficient.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture is extracted with water-immiscible solvent, for example methylene chloride; the extract is washed with water; and product can, if it is desired then to clear such conventional techniques as recrystallization or the various chromatography methods, namely column chromatography.

The reaction scheme XIX

Stage 65: Reaction Wittig

This stage includes obtaining the compounds of formula (54) the interaction of the compounds of formula (Ig) with ethoxymethylenemalononitrile in the presence of a base. +The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether (particularly tetrahydrofuran).

There is also no particular restriction on the nature of the used grounds, and any base commonly used in well-known reactions, can be similarly used here. An example of a suitable base includes utility.

The reaction can be performed in a wide internalerror will depend on such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 10 to 40oC and when the Foundation is applied utility, more preferably at a temperature of from 0 to 5oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 5 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture was poured into an aqueous solution of ammonium chloride; the aqueous mixture is extracted with water-immiscible solvent, for example diethyl ether, ethyl acetate and the like; and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product can, if desired, then be cleaned by conventional means, such as recrystallization or the various chromatography methods, namely column chromatography.

One hundred is rmula (54) acid.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether (particularly tetrahydrofuran).

There is also no particular restriction on the nature of the acid used, and any acid commonly used in well-known reactions, can be similarly used here. An example of a suitable acid includes hydrochloric acid.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. However, in General, is conveniently carrying out the reaction is from 10 to 100oC, more preferably at a temperature of from 30 to 80oC. the Time required for the reaction may also widely sonatala. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture is poured into water, the aqueous mixture is extracted with water-immiscible solvent, for example benzene, diethyl ether, ethyl acetate or the like; and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product can be used in further reactions without purification or can, if desired, be purified by conventional means, such as recrystallization or the various chromatography methods, namely column chromatography.

Stage 67: Restoration

This stage includes obtaining the compounds of formula (56) the interaction of the compounds of formula (55) with a reducing agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 10 of the reaction scheme 11, and can be carried out using the same reagents and under the same reaction conditions.

The reaction is the influence of the compounds of formula (23) with a halogenation agent.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: halogenated hydrocarbons, such as methylene chloride and chloroform (particularly methylene chloride).

used halogenation agents can be, for example, a combination of triphenylphosphine and tetrabromophenol.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 10 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 h, in order to be isolated from the reaction mixture by conventional methods, for example, the reaction mixture was washed with water and then the solvent is distilled off from the organic phase, leaving the desired product as a residue. Thus obtained product, if desired, can then be purified by conventional means, such as recrystallization or the various chromatography techniques, namely column chromatography.

Stage 69: Education postoyalogo connection

This stage includes obtaining the compounds of formula (58) the interaction of the compounds of formula (57) with triphenylphosphine.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include hydrocarbons, such as benzene, toluene or xylene (particularly toluene).

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent and used the original product La reaction, can also vary widely depending on many factors, namely, the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 5 to 24 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. As such a method is the following: the reaction temperature was raised to room temperature; the remainder is collected by filtration and washed with toluene or hexane and then dried. Thus obtained product, if desired, can then be purified by conventional means, such as recrystallization.

This stage also included in obtaining the compounds of formula (84) of the compounds of formula (15A). (Reaction scheme XXI)/

Stage 70: Reaction of Grignard

This stage includes obtaining the compounds of formula (61) by a Grignard reaction between the compound of formula (59) and (60).

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and clay include ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether (particularly diethyl ether).

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature from 0 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 minutes to 2 hours is usually sufficient.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of such a method is the following: an aqueous solution of ammonium chloride is added to the reaction mixture; the aqueous mixture is extracted with water-immiscible solvent, for example benzene, diethyl ether, ethyl acetate or the like; and then the solvent is distilled may then be purified by conventional means, such as recrystallization or the various chromatography methods, namely column chromatography.

Stage 71: Oxidation Swarna (Swern)

This stage includes obtaining the compounds of formula (62) the interaction of the compounds of formula (61) with an oxidizing agent.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane (particularly methylene chloride).

Used oxidizing agent may be, for example, a combination of oxalicacid and dimethyl sulfoxide.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from -100 to -50omperature reaction and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 min to 1 hour is usually sufficient. After that the reaction mixture is cooled to -78oC and then add a base (preferably triethylamine), after which the temperature allow to rise to ambient over a period of from 10 to 30 minutes

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture was poured into water; the aqueous mixture is extracted with water-immiscible solvent, for example benzene, diethyl ether, ethyl acetate or the like; the extract was washed with diluted hydrochloric acid and water in that order; and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product may normally be used in further reactions without purification or can, if desired, can then be purified by conventional means, such as recrystallization or the various chromatography methods, namely column chromatography.

Stage 72? The reaction of the Wittig

This stage includes obtaining the compounds of formula (63) through regadio reaction is essentially the same, as in stage 65 reaction scheme XIX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 73: Dibenzylamine and recovery of the double bond

This stage includes obtaining the compounds of formula (64) the recovery of the compounds of formula (63) with a regenerating agent.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, Isobutanol or tert-butanol (especially ethanol); and ethers, such as diethyl or tetrahydrofuran.

There is also no particular restriction on the nature of the used reducing agent, and any base commonly used in well-known reactions, can be similarly used here. An example of a suitable reducing agent include hydrogen in the presence of palladium catalyst.

The reaction can be performed in the reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 10 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 10 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods, for example, the catalyst is filtered off and then the solvent is distilled off from the filtrate, leaving the desired product as a residue. Thus obtained product can, if desired, then be cleaned by conventional means, such as recrystallization or the various chromatography methods, namely column chromatography.

The reaction scheme XXI

Stage 74: Protection of hydroxyl groups

This stage includes obtaining the compounds of formula (65) the interaction of the compounds of formula (61) with the reagent, a hydroxyl protecting group.

The reaction is normally and preferably carried out in the presence of dissolve inim effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include dimethylformamide.

Examples of suitable protective groups include methoxymethyl and tert-butyldimethylsilyloxy group. Reaction conditions will depend on the nature of the introduced protective group, for example:

(I) Introduction methoxymethyl group

The desired compound can be obtained by the coupling of compounds of formula (61) methoxymethane in the presence of an organic tertiary amine such as triethylamine in a suitable solvent, for example dimethylformamide.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 50 to 100oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions outlined above, a period BP is actionnow mixture by conventional methods. An example of such technique is as follows: the reaction mixture is freed from solvent by distillation; the residue is added ice-cold water; the aqueous mixture is extracted with water-immiscible solvent, for example benzene, diethyl ether, ethyl acetate or the like; the extract was washed with diluted hydrochloric acid and water in that order; and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product, if you prefer, you can clear the next well-known methods such as recrystallization or the various chromatography methods, namely column chromatography.

(II) the Introduction of tert-butyldimethylsilyloxy group

The desired compound can be obtained by the coupling of compounds of formula (61) with tert-butyldimethylsilyloxy in the presence of an organic tertiary amine, such as triethylamine (if necessary, with additional presence of 4-(N,N-dimethylamino)pyridine in a suitable solvent, for example dimethylformamide.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction of the party. In General, however, convenient to conduct the reaction at a temperature of from 10 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 minutes to 5 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of such technique is as follows: the reaction mixture is freed from solvent by distillation; the residue is added ice-cold water; the aqueous mixture is extracted with water-immiscible solvent, such as benzene, diethyl ether, ethyl acetate or the like; the extract was washed with diluted hydrochloric acid and water in that order; and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product, if you prefer, you can clear the next well-known methods such as recrystallization or the various chromatography methods, namely column chromatography.

Stage 75: Dibenzylamine

ETM agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 73 reaction scheme XX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 76: Oxidation Swarna (Swern)

This stage includes obtaining the compounds of formula (67) the interaction of the compounds of formula (66) with an oxidizing agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 71 of the reaction scheme XX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 77: the Wittig Reaction

This stage includes obtaining the compounds of formula (68) by Wittig reaction with compounds of the formulas (67) and (84) in the presence of a base in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 65 reaction scheme XIX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 78a and 78b: Restoration

This stage includes obtaining compounds of formulas (69) and (85) the interaction of the compounds of formula (68) in the reducing agent in an inert solvent.

Included in this stadig same reagents and under the same reaction conditions, except that the reaction stage 78a preferably carried out in diethyl ether at room temperature over a period of time from 30 min to 1 h, and on stage 78b preferably carried out in ethanol at room temperature for a period from 5 to 10 PM

The reaction scheme XXII

Stage 79: Restoration

This stage includes obtaining compounds of formula (71) the interaction of the compounds of formula (70) with a reducing agent.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: halogenated hydrocarbons, such as methylene chloride, chloroform: tetrachlorophenol, dichloroethane. chlorobenzene and dichlorobenzene (particularly methylene chloride).

There is also no particular restriction on the nature of the used recovery agent, and any reduction agent commonly used in well-known reactions, can be similarly used here. An example of a suitable Westerwelle temperature, and the exact temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 10 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 minutes to 5 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of such technique is as follows: the reaction mixture was quenched by addition of methanol under ice cooling; the reaction mixture was added diluted hydrochloric acid to dilute the undissolved material; the mixture is extracted with water-immiscible solvent, such as benzene, diethyl ether, ethyl acetate or the like; and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product, if desirable, can C the Oba, namely column chromatography.

Stage 80: Oxidation Swarna (Swern)

This stage includes obtaining aldehyde compounds by reacting the compounds of formula (71) with an oxidizing agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 71 of the reaction scheme XX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 81: Reaction Wittig

This stage includes obtaining the compounds of formula (72) by the interaction of the aldehyde compound obtained as described in stage 80, with a Wittig reagent, using triphenylphosphine in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 65 reaction scheme XIX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 82: Education diol group

This stage includes obtaining diol compounds by the interaction of the compounds of formula (72) with a reagent for the formation of a diol group.

The reaction is normally and preferably carried out in the presence of a suitable solvent. There are no special restrictions on who can dissolve the starting material, at least to some extent. An example of a suitable solvent includes a mixture of acetonitrile and water.

An example of a suitable oxidizing agent, which can be used is osmium tetroxide (which can be used in combination with morpholine-N-oxide as an oxidizing agent).

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 0 to 100oC, more preferably from 10 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 5 to 12 h, more preferably from 1 to 24 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this technique are the two what realem, such as benzene, diethyl ether, ethyl acetate or the like; then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product, if you want, you can then clear the well-known methods such as recrystallization or the various chromatography methods, namely column chromatography.

Stage 83: Education benzylidene group

This stage includes obtaining the compounds of formula (73) by the interaction of the diol compound obtained as described in stage 82, with benzyliden dimethylacetal in the presence of an acid catalyst.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include halogenated hydrocarbons such as methylene chloride, chloroform, tetrachlorophenol or dichloroethane (particularly methylene chloride).

There is also no particular restriction on the nature of the used acid catalyst, and any acid ka is the mayor of a suitable acid catalyst is n-toluensulfonate acid.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 10 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 5 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of such technique is the following: to the reaction mixture is added aqueous sodium hydrogen carbonate solution; the aqueous mixture is extracted with water-immiscible solvent, such as benzene, diethyl ether, ethyl acetate or the like; the extract is washed with water, and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product can be used in the following is talisay or various chromatographic methods, namely column chromatography.

Stage 84: Restoration

This stage includes obtaining compounds of the formulas (74) and (75) the interaction of the compounds of formula (73) with a reducing agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 79 of the reaction scheme XXII, and can be carried out using the same reagents and under the same reaction conditions.

The reaction scheme XXIII

Stage 85: Oxidation Swarna (Swern)

This stage includes obtaining the compounds of formula (76) by reacting the compounds of formula (74) with an oxidizing agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 71 of the reaction scheme XX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 86: Reaction Wittig

This stage includes obtaining the compounds of formula (77) by Wittig reaction using compounds of the formulas (76) and (58) (see reaction scheme XX), in the presence of a base in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 65 reaction scheme XIX, and can be carried out with the use of the stage and includes obtaining the compounds of formula (78) by reacting the compounds of formula (75) with an oxidizing agent in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 71 of the reaction scheme XX, and can be carried out using the same reagents and under the same reaction conditions.

Stage 88: Reaction Wittig

This stage includes obtaining the compounds of formula (79) by Wittig reaction using compounds of formula (78) and (58), in the presence of a base in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 65 reaction scheme XIX, and can be carried out using the same reagents and under the same reaction conditions.

The desired compound according to the invention can be obtained recovery dibenzylammonium and restoration of the double bond of the compounds of formula (77) and (79), using the same methods as described in stage 73.

The reaction scheme XXIV

Stage 85: Epoxidation

This stage includes obtaining the compounds of formula (80) by reacting the compounds of formula (31) with trimethylsulfoxonium in the presence of a base.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it is not the region of the second degree. Examples of suitable solvents include: ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether (particularly tetrahydrofuran); and sulfoxidov, such as dimethylsulfoxide.

There is also no particular restriction on the nature of the used grounds, and any base commonly used in well-known reactions, can be similarly used here. An example of suitable bases include sodium hydride.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 20 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 30 minutes to 5 hours will normally suffice.

After the blowing: the reaction mixture is diluted with water-immiscible solvent, such as benzene, diethyl ether, ethyl acetate or the like; the organic phase is washed with water; and then the solvent is distilled off from the extract, leaving the desired product as a residue. Thus obtained product can, if necessary, then clean up such conventional techniques as recrystallization or the various chromatography methods, namely column chromatography.

Stage 90: the Splitting of the epoxy group

This stage includes obtaining compounds of formulas (82) and (83) by reacting the compounds of formula (80) with the compound of the formula (81) in the presence of Lewis acid.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and that it can dissolve the starting material, at least to some extent. Examples of suitable solvents include halogenated hydrocarbons such as methylene chloride, chloroform, tetrachlorophenol or dichloroethane (particularly methylene chloride).

There is also no particular restriction on the nature of the used acid Lewis, and any Lewis acid, typically ispolzovati Lewis includes athirat of boron TRIFLUORIDE.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from 10 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 5 minutes to 15 hours is usually sufficient.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture is freed from solvent by distillation; the concentrate was poured into water; the aqueous mixture is extracted with water-immiscible solvent, such as benzene, diethyl ether, ethyl acetate or the like; and then the solvent is distilled off from the extract, leaving the products of formulas (82) and (83) as a residue. The products can, if desired, to clear the next well-known methods, t is CLASS="ptx2">

If necessary, the hydroxyl group of compounds of formulas (82) and (83) can be allerban and each of these obtained acylated compounds can be separated by chromatography, followed by deacetylation with obtaining compound (82) or (83) in the individual.

Stage 90: Grignard Reactions

This stage includes obtaining the compounds of formula (61) the interaction of the compounds of formula (61A) with a Grignard reagent (R6A4bMgBr) in the presence of copper iodide, which provides an alternative method of obtaining the compound (61), used as starting product in the reaction scheme XXI.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether (particularly tetrahydrofuran).

The reaction can be performed in a wide temperature range, t depend on such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from-to -50oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 5 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture is cooled in an ice bath; add an aqueous solution of ammonium chloride, and then stirred the mixture; the mixture is then extracted with a water-immiscible solvent, such as diethyl; ether; the extract was washed with aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride in that order; and then the solvent is distilled off from the extract, leaving the desired product as a residue. The product, if desired, can then be purified by conventional means, such as recrystallization or the various chromatography methods, namely the column chromatography the group is tert-butyldimethylsilyl group, it may be removed by treatment with a compound capable of forming anion fluoride, such as tetrabutylammonium fluoride or hydrochloric acid.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include ethers, such as tetrahydrofuran, or alcohols, such as methanol.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature from 0 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 10 until it can be removed by treatment with acid.

There is also no particular restriction on the nature of the acid used, and any acid commonly used in conventional reactions may be similarly applied here. Examples of suitable acids include acids of Bronsted, including halogen acids such as hydrochloric acid or Hydrobromic acid, and organic acids such as acetic acid or n-toluensulfonate; and strong acid ion exchange resin such as Dowex (trade mark) 50W.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least some degree. Examples of suitable solvents include alcohols, such as methanol or ethanol; ethers, such as tetrahydrofuran or dioxane; and mixtures of one or more solvents with water.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of Rasta from 0 to 50oC. 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 used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 19 minutes to 18 hours is usually sufficient.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture was poured into water; the aqueous mixture is extracted with water-immiscible solvent, such as benzene, diethyl ether, ethyl acetate or the like; and then the solvent is distilled off from the extract, leaving the desired product as a residue. The product can usually be used in further reactions without purification or can, if desired, be purified by conventional means, such as recrystallization or the various chromatography methods, namely column chromatography.

Stage 93: Reaction inversion of Mitsunobu (Mitsunobu)

This stage includes obtaining the compounds of formula (87) the interaction of the compounds of formula (86) with benzoic acid in the presence of triphenylphosphine and diethyl of azodicarboxylate.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. Preferably, the reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. However, in General, handy conversion reaction at a temperature from 0 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture was poured into water; water quality, etc.; diluted aqueous solution is washed with aqueous sodium hydrogen carbonate solution, and then the solvent is distilled off from the extract, leaving the desired product as a residue, the Product, if desired, can then be purified by conventional means, such as recrystallization or the various chromatography methods, namely column chromatography.

In the next stage, the compound of formula (88) can be obtained from compounds of formula (87) in the same manner as described in stage 12 (reaction scheme III), with subsequent processing, as described in stage I (reaction scheme I).

Stage 94:

This stage includes obtaining the compounds of formula (89) the interaction of the compounds of formula (88) with a base.

There is also no particular restriction on the nature of the used grounds, and any base commonly used in well-known reactions, can be similarly used here. Examples of suitable bases include alkoxides of alkali metals such as sodium methoxide, ethoxide sodium tert-piperonyl potassium or lithium methoxide, preferably ethoxide sodium.

The reaction is normally and preferably carried out in the presence of a solvent. There is no special limitation that it can dissolve the starting material, at least to some extent. Examples of suitable solvents include alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, Isobutanol, tert-butanol or isoamyl alcohol.

The reaction can be performed in a wide range of temperatures and the precise temperature is not critical to the invention. The preferred reaction temperature will depend upon such factors as the nature of the solvent used and original product of the reaction. In General, however, convenient to conduct the reaction at a temperature of from room temperature to the boiling point of the used solvent. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions described above, the period of time from 1 to 24 hours will normally suffice.

After completion of the reaction product can be isolated from the reaction mixture by conventional methods. An example of this method follows: the reaction mixture was poured into water and then neutralized; the mixture is extracted with water-immiscible solvent, such as benzene, diethyl ether, this is TKA. The product, if desired, can then be purified by conventional means, such as recrystallization or the various chromatography methods, namely column chromatography.

Stage 95: Introduction of the leaving group

This stage includes obtaining the compounds of formula (90) the interaction of the compounds of formula (41) with alkylsulfonamides predpochtitelno methanesulfonamido) in the presence of a base.

Included in this stage the reaction is essentially the same as in stage 18 of the reaction scheme Y, and can be carried out using the same reagents and under the same reaction conditions.

Stage 96: Introduction imidazolidine group

This stage includes obtaining the compounds of formula (91) the interaction of the compounds of formula (90) with imidazole in an inert solvent.

Included in this stage the reaction is essentially the same as in stage 19 of the reaction scheme Y, and can be carried out using the same reagents and the same reaction conditions.

Stage 97: Restoring nitro

This stage includes obtaining the compounds of formula (92) the interaction of the compounds of formula (91) with a reducing agent in an inert solvent.

settled on using the same reagents and under the same reaction conditions.

Stage 98: Condensation

This stage includes obtaining the compounds of formula (1d) the interaction of the compounds of formula (92) with the compound of the formula (2) (reaction scheme I) in an inert solvent.

Included in this stage the reaction is essentially the same as in the stage I reaction scheme I, and can be carried out using the same reagents and under the same reaction conditions.

Such compounds that contain the group represented by the formula, R7in accordance with the present invention can be obtained using compounds derived regenerative dibenzylammonium and restoration of the double bond of compounds of formula (77) and (79) or with compounds of the formula(56), (64). (82), (83) and (89), which can be obtained from the stages described above, in the same manner as described in stage 3.

When R7includes oxycarbonyl group, the reaction can be carried out as follows.

Add a solution of trichloromethylcarbonate in tetrahydrofuran under ice cooling to tertrahydrofuran ring solution containing pyridine, and the resulting mixture was stirred at room temperature for a suitable period of time, for example 1 ) in tetrahydrofuran and the mixture is again stirred, for example, 1 o'clock, the Tetrahydrofuran is removed by distillation and the residue is dissolved in methylene chloride. Then add a solution of the desired alcohol in methylene chloride. To the thus obtained mixture is added 4-(N,N-dimethylamino)pyridine and the resulting mixture was stirred at room temperature, for example, 1 h

After completion of the reaction, the reaction mixture can be diluted with water-immiscible solvent, such as benzene, diethyl ether, ethyl acetate or the like. The diluted mixture was then washed with water and saturated aqueous sodium chloride in this order, and the solvent is distilled off from the organic phase to obtain the product. The product, if desired, can then be purified chromatography or recrystallization.

Connection, where the carboxyl group represented by R7is the salt of an alkali metal, can be obtained as follows.

To a solution of carboxylic acid derivative type base in a solvent. The amount of base is preferably from 0.9 to 1 mol per mol of carboxylic acid derivative. There is also no particular restriction on the nature of the used grounds, and any base commonly used in the try: bicarbonate of alkali metals, such as sodium bicarbonate, potassium bicarbonate or bicarbonate of lithium; carbonates of alkali metals such as sodium carbonate, potassium carbonate or lithium carbonate; hydroxides of alkali metals such as sodium hydroxide, potassium hydroxide or lithium hydroxide; alkoxides of alkali metals, such as methods of sodium, ethoxide sodium tert-piperonyl potassium or lithium methoxide. If necessary, the resulting mixture was dissolved to obtain a solution (using ultrasound, if necessary), after which the solvent is distilled off to obtain the desired salt of an alkali metal.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; alcohols such as methanol, ethanol or isopropanol; esters such as ethyl acetate or methyl acetate; halogenated hydrocarbons such as methylene chloride or chloroform; water; and a mixture of water and one Il the th alcohol). When using water mixture solvent, lyophilization, as such or after distillation of the organic solvent gives the desired salt of an alkali metal.

Salt of inorganic acid such as hydrochloric acid, or organic acids, such as maleic acid, the compounds of the present invention having amino group or a heterocyclic group containing a basic nitrogen atom, such as imidazole group can be obtained as follows.

This compound is dissolved in a suitable solvent and then adding 1 to 10 equivalents of the desired acid. The resulting residue is collected by filtration to obtain the desired salt. If no sediment, the solvent is distilled to obtain the desired salt. If the resulting salt forms a glassy material, salt again dissolved in water or in a mixture of water and a water-soluble organic solvent, such as dioxane, dimethoxyethane, methanol or isopropyl alcohol, and the solution is then lyophilized as such or after distillation of the water-soluble organic solvent. Therefore, the purified compound can be obtained as a salt in the form or powder, or foam. The product may be, if neobhodimosti. There are no special restrictions on the nature of the solvent used, provided that it has no negative effect on the reaction and can dissolve the starting material, at least to some extent. Examples of suitable solvents include: ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; alcohols such as methanol, ethanol or isopropanol; esters such as ethyl acetate or methyl acetate; halogenated hydrocarbons such as methylene chloride or chloroform.

Compounds of the present invention have excellent inhibitory activity against acyl-CoA: cholesterol acyltransferase, well absorbed after oral administration and is less toxic than previously known compounds. They are therefore useful in the treatment and prevention of atherosclerosis.

The activity of the compounds of the present invention is illustrated in the following tests.

- Lipoprotein very low density ( - VLDL)

The blood get [using anticoagulatory ethylenediaminetetraacetic acid (5 mm)] from Japanese white rabbits fed 2% by weight cholesterol diet for 2 weeks. - VLDL (d<1,006 g/ml) was isolated from a submarine is s phosphate buffer (pH 7,4), containing 150 mm sodium chloride at 4oC.

Getting macrophages of mice (MT)

Peritoneal cells from unstimulated female DDY mice (body weight 20 - 30 g), harvestroad in phosphate buffer solution (PBS) as described Adelson and Koch [Edelson, PJ. and Cohn, ZA., 1976, IN VITRO Methods in Cell-Medi ated and Tumor Ymmunity, eds, Bloon, BR and David, JR., (Academic, New York), 333 - 340]. Fluid from mice collected and cells are separated by centrifugation at 400 xg for 10 min at 4oC and washed once with PBS. Cells are again suspended in modified by Dulbecco medium Eagle (DMEM) containing 10% (vol) newborn calf serum (FCS), penicillin (100 units/ml) and streptomycin (100 l/ml ) at a final concentration of 3106cells / ml. Aliquots (1 ml) suspensions of these cells dispersed in plastic Petri dishes (3510 mm) and then incubated in the incubator CO2(5% CO2/95% air) at 37oC for 2 hours Each Cup washed twice in PBS without serum to remove Eclipsys cells. Cells are washed twice in 2 ml PBS and used in the experiment.

Inhibition of ACAT IN MT

Inhibition of ACAT in MT is determined according to the method described by Brown et al. [Brown, MS. , Goldstein JL., Krieger, M., Ho, YK. and Anderson RGW. (1979) J. Cell Biol., 82, 597 - 613]. Perebazirovano cholesterol is called dottrace: 0.2 mm oleate and 0.6 mg/ml albumin), and the test compound dissolved in ethanol in a monolayer Matt, the preparation is incubated at 37oC for 3 h in the incubator CO2. Cells are washed three times with PBS, and the cell liquid is extracted with 1 ml hexane/isopropanol (3:2 by volume). The extract liquid is evaporated in a stream of nitrogen. [14C] cholesterol oleate shared by thin-layer chromatography on silica gel using 85: 15: 1 by volume mixture of hexane, diethyl ether and acetic acid as separating solvents. The ACAT activity in MT is determined by measurement of the radioactivity and the rate of inhibition (%) calculated by the comparison of the activity that the compounds at these concentrations. The results are shown in the following table. 7.

The connection is A previously known compound having the formula (A):

< / BR>
It is described in WO 93/06096.

Compounds of the present invention can be assigned to any known method known to the previously known compounds having the same type of activity. For example, they can be assigned orally acceptable in the form of tablets, capsules, granules, powders or syrups. These pharmaceutical compositions can be obtained by conventional methods by adding under the EU ETS), lubricating agents and stabilizers. The dosage may vary depending on the patient's condition and age; however, a daily dose of from 1 to 500 mg per kg body weight, preferably from 1 to 100 mg per kg of body weight, can, basically, be an adult in a single dose or in divided doses.

The present invention is further illustrated by the following non-limiting examples. In these examples, the numbers of the compounds correspond to the numbers table. 1 - 5. Getting some of the original materials used in these examples are illustrated by the subsequent preparations. Some pharmaceutical preparations comprising compounds of the present invention, shown in the next subsequent compositions.

Example 1. N-{ 2-[3-(1-Imidazolyl)propoxy]methyl-6-methyl-thiophenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide

(compound No. 1 - 1475)

I (i) N-{2-[3-(1-Mesilate)propoxy]methyl-6-methylthiophenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide

212 mg (0.48 mol) of N-[2-(3-hydroxypropoxy)methyl-6-methylthiophenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 4) are suspended in 15 ml of methylene chloride. The suspension is cooled in an ice bath and then added 102 mg (0.89 mmol) of methanesulfonamide and then 94 mg (0.90 mmol) trimesium additional 1 h At the end of this time the reaction is stopped by the addition of water. The mixture is then diluted with methylene chloride, then the organic layer is washed with diluted aqueous hydrochloric acid solution and then with water. The solvent is then removed by distillation under reduced pressure to obtain 251 mg (quantitative yield) specified in the connection header in the form of crystals. These crystals are used in the next stage without purification.

I(ii) N-{2-[3-(1-Imidazolyl)propoxy]methyl-6-methylthiophenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide

151 mg of crude crystals of N-{2-[3-(mesilate)propoxy]methyl-6-methylthiophenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide [obtained as described in stage (i) above] suspensorium in 3 ml of dimethylformamide. To the suspension is added 162 mg (2,39 mmol) of imidazole and the mixture is stirred for 5.5 h at 90oC. after this time the reaction allow to return to room temperature, then diluted with ethyl acetate and washed several times with water. The solvent is then removed by distillation under reduced pressure and the resulting residue is subjected to column chromatography through 15 g of silica gel. Faction, erwerbende mixtures of methylene chloride and methanol ranging from 100:2 to 100:7 by volume collected. Paracrystalline in the form of crystals, melting at 176,5 - 177oC.

Infrared absorption spectrum (KBR),maxcm-1: 3267, 1649, 1515, 1481, 1260, 757.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: of 1.88 (2H, quintet, J = 6.5 Hz); of 2.28 (3H, singlet); 2,73 (2H, doublet, J = 6.5 Hz); 3,17 (2H, triplet, J = 6.5 Hz); 3,93 (2H, triplet, J = 6.5 Hz); 4,10 (2H, singlet); the 4.65 (1H, triplet, J = 6.5 Hz); 6,7 - in 7.7 (14H, multiplet).

Example 2. N-{2-[3-(1-Imidazolyl)propoxy]methyl-6-methylthiazolyl}-2-(9H-xanthene-9-yl) ndimethylacetamide hydrochloride (compound No. 1 - 1474)

100 mg N-{2-[3-(1-imidazolyl)propoxy]methyl-6-methylthiophenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 1) dissolved in a mixture of methanol methylene chloride. To the solution is added an excess of concentrated hydrochloric acid, and then the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in methanol and add diethyl ether to obtain 85 ml specified in the title compound as crystals, melting at 175 - 184oC.

Infrared absorption spectrum (KBR),maxcm-1: 3405, 3269, 1649, 1516, 1482, 1261, 758.

Elemental analysis:

Designed for:

C29H29N3O3SHCl1/2H2O:

Calculated:% C 6390%, H 5,73; N 7,71; Cl 6,50.

the n-9-yl) ndimethylacetamide (compound N 1 - 1477)

Following the method similar to that described in example 1, but using N-[5-(3-hydroxypropoxy)methyl-2-methylthiophenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 4) as the original product, in an appropriate amount that is used in this example, get mentioned in the title compound as an oily substance.

Infrared absorption spectrum (KBR),maxcm-1: 2923, 1679, 1574, 1480, 1254, 757.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: 1,88 - 2,4 (2H, multiplet); is 2.05 (3H, singlet); a 2.75 (2H, doublet, J = 6.5 Hz); 3.43 points (2H, triplet, J = 6.5 Hz); 3.9 to a 4.3 (2H, multiplet); of 4.45 (2H, singlet); 4,70 (1H, triplet, J = 6.5 Hz); of 6.8 to 7.6 (12H, multiplet); 8,0 - 8,2 (1H, broadened singlet); 8,3 - 8,5 (1H, broadened singlet).

Example 4. N-{5-[3-(1-Imidazolyl)propoxy]methyl-2-methylthiophenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide hydrochloride (compound No. 1 - 1476)

Following the method similar to that described in example 2, but using N-{5-[3-(1-imidazolyl)propoxy] methyl-2-methylthiophenyl} -2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 3) as starting product, get mentioned in the title compound as crystals, melting at 85 - 86oC (after paracrystalline is UP>-1: 3036, 1660, 1526, 1479, 1458, 1258, 760.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: of 2.1 to 2.35 (2H, broadened singlet); of 2.21 (3H, singlet); 2,80 (2H, doublet, J = 7 Hz); 3,49 (2H, broadened singlet); 4,3 - 4,6 (2H, broadened singlet); 4,47 (2H, singlet); 4,69 (1H, triplet, J = 7 Hz); of 6.9 to 7.4 (12H, multiplet); 8,11 (1H, singlet); of 8.27 (1H, singlet); 9,0 is 9.15 (1H, broadened singlet).

Example 5. N-[2-Ethyl-6-(1-hydroxypropyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1434).

9.6 mg (0.18 mol) of sodium methoxide are added to a methanol solution containing 37 mg (to 0.060 mmol) of N-(2-ethyl-6-{1-[2-(9H - xanthene-9-yl)acetoxy] propyl} phenyl-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 55). The mixture was then stirred for 4 h at 60oC. after this time the reaction solution was diluted with diethyl ether. To the reaction mixture, water is added, and specified in the header connection partitioned between an organic solvent and water. The organic layer is then separated and washed with water 3 times. The solvent is removed by distillation under reduced pressure, and the obtained residue is subjected to column chromatography through 5 g of silica gel. Elution with a mixture of methylene chloride and ethyl acetate ranging from 10:1 to 5: volume of leads is cristallization from a mixture of diethyl ether and hexane.

Infrared absorption spectrum (KBR),maxcm-1: 1655, 1635, 1520, 1482, 1460, 1260, 756.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,78 (3H, triplet, J = 7 Hz), of 1.06 (3H, triplet, J = 7.5 Hz); 1,55 - 1,8 (2H, multiplet); 2,33 (2H, Quartet, J = 7 Hz), and 2.79 (2H, doublet, J = 7 Hz), 4,34 (1H, triplet, J = 7 Hz), 4.72 in (2H, triplet, J = 7 Hz), 6,95 is 7.5 (11H, multiplet).

Example 6. N-[2-(hydroxy-3-phenyl-1-propenyl)-6-methoxymethyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1443

10 ml tetrahydropyranol suspension containing 152 mg (0,392 mol) of N-(2-formyl-6-ethoxymethyleneamino)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 53), 199 mg (0,432 mmol) finallettergrade bromide and 48 mg (0,471 mmol) of triethylamine, and heated for 6 h at boiling under reflux. At the end of this time the mixture was allowed to reach room temperature. Add 4 ml of methanol and then gradually add to the mixture 155 mg (4,10 mmol) of sodium borohydride, which is then stirred for 1 h the Reaction solution was diluted with ethyl acetate and washed for some time by the water. The solvent is removed by distillation under reduced pressure. The residue is subjected to column chromatography through 20 g of silica gel. Elution with 4:1 by volume of the growth, melting at 204,5 - 206,5oC (after recrystallization from methanol).

Infrared absorption spectrum (KBR),maxcm-1: 3258, 1652, 1482, 1457, 1263, 752.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 2,72 (2H, doublet, J = 7 Hz); 3,10 (3H, singlet); of 3.94 (2H, singlet); 4,70 (1H, triplet, J = 7 Hz); of 5.34 (1H, doublet, J = 7 Hz); 6,32 (1H, doublet of doublets, J = 16 & 7 Hz); 6,53 (1H, doublet, J = 16 Hz); 7,1 - 7,6 (16H, multiplet).

Example 7. N-[2-(3-Hydroxy-3-phenylpropyl)-6-methoxymethyl-phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1444) 35 mg, 10% weight of palladium on coal added to 15 ml of tertrahydrofuran ring solution containing 111 mg (0,226 mmol) N-[2(3-hydroxy-3-phenyl-1-propenyl)-6-methoxymethyl]-2-(9H-xanthene - 9-yl)ndimethylacetamide (received as described in example 6), and the mixture is vigorously stirred for 15 h in a stream of hydrogen. The reaction solution is then filtered using filter Zeolite (trade mark), and the catalyst washed with tetrahydrofuran. The filtrate and wash water are combined and the solvent removed from the combined solution by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 15 g of silica gel. Elution with 4:1 by volume mixture of methylene chloride and ethyl acetate leads to cristallization from methanol and hexane).

Infrared absorption spectrum (KBR),maxcm-1: 3370, 3280, 1652, 1515, 1480, 1457, 1260, 757.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: a 1.7 - 2.1 (2H, multiplet); 2,2 - 2,6 (2H, multiplet); 2,53 (2H, doublet, J = 7 Hz); of 3.07 (3H, singlet); 3.96 points (2H, singlet); 4,2 - 4,6 (1H, multiplet); 4,59 (1H, triplet, J = 7 Hz); 6,9 - 7,7 (16H, multiplet).

Example 8. N-[2-Ethyl-6-(3-oxo-6-phenylhexa)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (8A) (compound N 1-1445); and N-[2-Ethyl-6-(3-hydroxy-6-phenylhexa)phenyl]-2-(9H-xanthene - 9-yl) ndimethylacetamide (8b) (compound N 1-1446)

93 mg of 10% by weight palladium on coal added to 5 ml of a methanol solution containing 154 mg of N-[2-ethyl-6-(3-oxo - 6-phenyl-1-hexenyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 68), and the mixture is vigorously stirred for 3 h in a stream of hydrogen. At the end of this time the reaction solution is then filtered using filter Celite (trade mark), and the catalyst was washed several times with ethyl acetate. The filtrate and wash water are combined and the solvent removed from the combined solution by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 10 g of silica gel. Elution with 2:1 by volume mixture of diethyl ether and hexane leads to 87 mix)phenyl-2-(9H-xanthene - 9-yl)ndimethylacetamide:

Melting at 113 - 114oC (after recrystallization from a mixture of methylene chloride and diethyl ether).

Infrared absorption spectrum (KBR),maxcm-1: 3246, 1709, 1653, 1528, 1480, 1459, 1262, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,09 (3H, triplet, J = 7.5 Hz); of 1.78 (2H, Quartet, J = 7 Hz); and 2.26 (2H, triplet, J = 7.5 Hz); 2,38 is 2.55 (6H, multiplet); 2,62 (2H, triplet, J = 6 Hz); 2,84 (2H, doublet, J = 7 Hz); to 4.73 (1H, triplet, J = 7 Hz); 6,94 - 7,43 (16H, multiplet).

(8b) N-[2-Ethyl-6-(3-hydroxy-6-phenylhexa)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide:

Melting at 131 - 132oC (after recrystallization from a mixture of diethyl ether and hexane).

Infrared absorption spectrum (KBR),maxcm-1: 3274, 1648, 1522, 1480, 1459, 1260, 754.

Spectrum of nuclear magnetic resonance (CDCl3, 237 MHz), ppm: 1,09 (3H, triplet, J = 7.5 Hz); 1,31 - to 1.79 (6H, multiplet); 2,18 - 2,47 (4H, multiplet); of 2.56 (2H, triplet, J = 7.5 Hz); a 2.71 (1H, doublet of doublets, J = & 14,5 Hz); was 2.76 (1H, doublet of doublets, J = 7 & 14,5 Hz); 3,18 - 3,30 (1H, multiplet); 4,70 (1H, triplet, J = 7 Hz); 6,97 - 7,42 (16H, multiplet).

Example 9. N-{2-tert-Butyl-5-[5-(4-forfei)-3-hydroxy-1 - pentyl]phenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1319)

Following the method similar to that described in example 6 is on the product, get listed in the title compound as an oily substance. The original product is obtained according to the method described in example 68, but using 4-fluoro-1-(4-diethoxyphosphoryl-3-oxobutyl)benzene and N-(Tret-butyl-5-formylphenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 15).

Infrared absorption spectrum (KBR),maxcm-1: 3450, 1673, 1600, 1573, 1508, 1477, 1456.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,17 (9H, singlet); 1.85 to a 2.0 (2H, multiplet); 2,4 - 2,5 (1/3H, multiplet); 2,65 - 2,8 (2H, multiplet); 2,72 (5/3H, doublet, J = Hz); 4,2 is 4.35 (1H, multiplet); of 4.77 (1H, triplet, J - 7 Hz); from 6.22 (1H, doublet of doublets, J = 7 & 16 Hz); 6,53 (1H, doublet, J = 16 Hz); 6,9 - 7,6 (15H, multiplet).

Example 10. N-{2-tert-Butyl-5-[5-(4-forfinal)-3 - hydroxyphenyl)phenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1318)

Following the method similar to that described in example 7, but subjecting N-{2-tert-butyl-5-[5-(forfinal)-3-hidroxi-1-pentenyl] phenyl} -2- (9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 9) catalytic recovery specified in the title compound obtained as foamy substance.

Infrared absorption spectrum (KBR),maxcm-1: 3450, 1677, 1600, 1575, 1509, 1479, 1456.

Example 11. N-[2-Ethyl-6-(3-hydroxy-1-phenylpropyl)phenyl-2-(N-xanthene-9-yl)ndimethylacetamide (compound N 1-1440)

Following the method similar to that described in example 8, but using N-[2-ethyl-6-(3-oxo-3-phenyl-1-propenyl)phenyl-2-(N-xanthene-9-yl) ndimethylacetamide as the original product, in an appropriate amount that is used in this example, get mentioned in the title compound as crystals, melting at 192-193oC (after recrystallization from a mixture of ethyl acetate and hexane). The original product is obtained according to the method described in example 6, but using N-(2-ethyl-6-formylphenyl)-2-(N-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 29).

Infrared absorption spectrum (KBr),maxcm-1: 3242, 1657, 1522, 1480, 1459, 1254, 760.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,09 (1H, triplet, J=7.5 Hz), 1,82-of 1.93 (2H, multiplet), 2,23-2,48 (4H, multiplet), 2,68 (2H, doublet, J= 7 Hz), 4,36 (1H, triplet, J=6 Hz), 4,69 (1H, triplet, J=7 Hz), of 6.96-7,44 (16H, multiplet).

Example 12. N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl]-2-(N-xanthene-9-yl) ndimethylacetamide (compound 1-25 N).

of 0.18 ml I M Rath to -78oC. 2 ml of tertrahydrofuran ring of a solution containing 50 mg (0.12 mmol) of N-[2-tert-butyl-5-(3-oxopropyl)-phenyl] -2-(N-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 19), then add dropwise to this solution over a period of 5 minutes the Mixture was then stirred for 40 min at this temperature, after which the temperature allow to return gradually to 0oC. the Reaction is then stopped by the addition of saturated aqueous solution of ammonium chloride. Add diethyl ether, giving you the opportunity to headline the connection is to be distributed between the organic solvent and water. The organic layer is separated and washed with water, after which the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 10 g of silica gel. Elution 100:15 by volume mixture of methylene chloride and ethyl acetate leads to 41 mg (pin 67%) indicated in the title compound as crystals, melting at 145-146oC (after recrystallization from a mixture of methylene chloride and diethyl ether).

Infrared absorption spectrum (KBr), cm-1: 3343, 3244, 1654, 1529, 1478, 1458, 1252, 760, 749.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm from 0.76 to 1.87 (15H, multip the>

Example 13. N-[2-tert-Butyl-5-(4-cyclohexyl-3-oxobutyl)phenyl]-2(9H-xanthene-9 - yl)-ndimethylacetamide (compound N 1-1263)

1 ml methylenchloride solution containing 16 mg (0.13 mmol) of oxalicacid cooled to -78oC. 1.5 ml methylenchloride solution containing 20 mg (0.25 mmol) of dimethyl sulfoxide, then add to this solution. The resulting mixture was then stirred for 5 min, after which 1 ml methylenchloride solution containing 56 mg (0.11 mmol) N-[2-tert-butyl-5(4-cyclohexyl-3-hydroxybutyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 12), then add dropwise to this solution over a period of 5 min at the same temperature. The mixture was then stirred for 15 min and added dropwise 1 ml methylenchloride solution containing 64 mg (0.64 mmol) of triethylamine. The mixture is stirred for 10 min, and then the reaction mixture was allowed to return to room temperature. The reaction is then diluted with diethyl ether and washed with dilute aqueous hydrochloric acid and then with water. The solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 10 g of silica gel. Elution 100: 8 by volume of methylene chloride in ethyl acetate leads to 51 mg (yield 91%) specified in the business of ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3233, 1711, 1637, 1529, 1481, 1456, 1261, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,80-1,91 (11H, multiplet); 1,15 (N, singlet); to 2.29 (2H, doublet, J=6.5 Hz); 2,36-2,90 (6N, multiplet); 4,74 (1H, triplet, J=7 Hz); 6,91 was 7.45 (11N, multiplet).

Example 14. N-[2-tert-Butyl-5-(2-cyclohexyl-1-hydroxyethyl)phenyl] -2(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-179)

8 ml of tertrahydrofuran ring of a solution containing 100 mg (0.25 mmol) of N-(2-tert-butyl-5-formyl)-2-(9H-xanthene-9-yl)-ndimethylacetamide (obtained as described in preparation 15) cooled in an ice bath. Then to the solution is added dropwise to 0.38 ml (0.38 mmol) of 1 M solution of cyclohexylmaleimide in diethyl ether. The resulting mixture was then stirred for 20 min at this temperature, then diluted with diethyl ether and washed with dilute aqueous hydrochloric acid and then with water. The solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 20 g of silica gel. The elution mixture of methylene chloride and ethyl acetate, which varies from 7:1 to 2:1 by volume, leads to the production of 95 mg (yield 76%) indicated in the title compound in the form of a foamy product.

Infer the spas resonance (CDCl3, 270 MHz), ppm: 0,80-1,95 (13H, multiplet); of 1.18 (9H, singlet); 2,32-2,54 (0.5 H, multiplet); 2,70 (1,5 H, doublet, J= 7 Hz); to 4.41-4,54 (0,25 H, multiplet); 4,67 of 4.83 (0,75 H, multiplet); at 4.75 (1H, triplet, J=7 Hz); 7,01-7,49 (11H, multiplet).

Example 15. N-[2-Ethyl-6-(1-hydroxy-2-phenylpropyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1441)

Following the method similar to that described in example 14, but using N-(2-ethyl-6-formylphenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 29) and cyclohexylethylamine as initial products in the appropriate ratio used in this example, get mentioned in the title compound as crystals, melting at 128-129oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3240, 1648, 1524, 1480, 1459, 1260, 754.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: of 1.03 (3H, triplet, J= 7.5 Hz); 1,81 is 1.96 (1H, multiplet); 2,07-of 2.23 (1H, multiplet); 2,28 (2H, Quartet, J=7.5 Hz); of 2.54 (2H, triplet, J=7.5 Hz); 2,56 (1H, doublet of doublets, J=7 and 15 Hz); 2,62 (1H, doublet of doublets, J=7 and 15 Hz); was 4.42 (1H, triplet, J=7 Hz); of 4.67 (1H, triplet, J=7 Hz); 7,01-7,42 (16H, multiplet).

Example 16. N-[2-tert-Butyl-5-(6-phenyl-1-hydroxyhexyl)polyzoa 5-phenylpentane iodide and N-(2-tert-butyl-5-formylphenyl -2(9H-xanthene-9-yl)ndimethylacetamide (received as described in preparation 15) as initial products in the appropriate ratio used in this example, receive specified in the header of the connection in the foam form.

Infrared absorption spectrum (KBr), maxcm-1: 3395, 3280, 1653, 1522, 1480, 1459, 1256, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,17 (9H, multiplet); 1,25-of 1.85 (8H, multiplet); 2,42 (0,4 H, doublet, J=7 Hz); 2,61 (2H, triplet, J=8 Hz); 2,69 (1,6 H, doublet, J=7 Hz); 4.26 deaths-4,34 (0,2 H, multiplet); 4.63 to (0,8 H, triplet, J=6.5 Hz); to 4.73 (1H, triplet, J=7 Hz); 6,97 was 7.45 (16H, multiplet).

Example 17. N-[2-tert-Butyl-5-(4-cyclohexyl-1-hydroxybutyl)phenyl}-2-)(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-227)

Following the method similar to that described in example 14, but using 3-cyclohexylpropionate and N-(2-tert-butyl-5-formylphenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 15) as the original products, in the appropriate ratio used in this example, receive specified in the header of the connection in the foam form.

Infrared absorption spectrum (KBr),maxcm-1: 3395, 3280, 1655, 1522, 1480, 1459, 1256, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,80-0,94 (2H, multiplet); 1 is tiplet); to 4.73 (1H, triplet, J= 7 Hz); 6,97-7,94 (11H, multiplet).

Example 18. N-[2-tert-Butyl-5-(6-cyclohexyl-1-hydroxyhexyl)phenyl]-2-(cantan-9-yl) ndimethylacetamide (compound N 1-275)

Following the method similar to that described in example 14 but using 5-cyclohexylmaleimide and N-(2-tert-butyl-5-formylphenyl)-2-(9H-xanthyl (obtained as described in preparation 15) as initial products in the appropriate ratio used in this example, receive specified in the header of the connection in the foam form.

Infrared absorption spectrum (KBR),maxcm-1: 3395, 3290, 1653, 1522, 1480, 1459, 1256, 756.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0.77-a of 0.94 (2H, multiplet); 1,06-1,80 (19H, multiplet); of 1.17 (9H, singlet); 2,43 (0,4 H, doublet, J = 7 Hz); 2,70 (1,6 H, doublet, J = 7 Hz); 4,28-4,35 (0,2 H, multiplet); 4.63 to- (0,8 H, triplet, J = 6.5 Hz); 4,74 (1H, triplet, J = 7 Hz); of 6.96-7,46 (11H, multiplet).

Example 19. N-[2-tert-Butyl-5-(oxo-6-phenylhexa)phenyl]-2-(9H-canteen-9-yl) ndimethylacetamide (compound N 1-1325)

Following the method similar to that described in example 13, but using N-[2-tert-butyl-5-(6-phenyl-1-hydroxyhexyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 16) as the original product, in an appropriate amount,20oC (after recrystallization from a mixture of hexane and ethyl acetate).

Infrared absorption spectrum (KBR),maxcm-1: 3240, 1686, 1646, 1524, 1482, 1459, 1258, 758.

Spectrum of nuclear magnetic resonance (CDCl3, Mg), ppm: 1,19 (9H, singlet); to 1.45 (2H, quintet, J=7.5 Hz); to 1.70 (2H, quintet, J = 7.5 Hz); of 1.78 (2H, quintet, J= 8 Hz), 2.40 a-2,45 (0,2 H, multiplet); 2,60-2,80 (0,2 H, multiplet); to 2.65 (2H, triplet, J = 7,7 Hz); 2,74 (1,8 H, doublet, J=Hz); 2,94 (1,8= 7 Hz); 4,74 (1H, triplet, J = 7 Hz); 7,05-7,43 (14,1 H, multiplet); 7,72 (1H,doublet of doublets, J = 2&8 Hz); 8,05 (0,9 H, doublet, J = 2 Hz).

Example 20 N-[2-tert-Butyl-5-(6-cyclohexyl-1-oxohexyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-1262)

Following the method similar to that described in example 13, but using N-[2-tert-butyl-5-(6-cyclohexyl-1-hydroxyhexyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 18) as a starting product in the appropriate amount used in this example, receive specified in the procurement compound as crystals, melting at to 133.5-134oC (after recrystallization from a mixture of hexane and diisopropyl ether).

Infrared absorption spectrum (KBR),maxcm-1: 3235, 1986, 1644, 1524, 1482, 1459, 1258, 758.

Spectrum of nuclear magnetic rez is 5-2,75 (0,2 H, multiplet); 2,74 (1,8 H, doublet, J 7 Hz); 2,93 (1,8 H, triplet, J = 7 Hz); at 4.75 (1H, triplet, J = 7 Hz); 7,07-7,43 (9, 1H, multiplet); 7,73 (1H, doublet of doublets, J = 2&8 Hz); 8,06 (0,9 H, singlet).

Example 21. N-[2-tert-Butyl-5-(6-cyclohexyl-5-oxohexyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-1268)

of 0.66 ml (the 7.65 mmol) oxalicacid and 30 mg of N,N-dimethylformamide added to 10 ml methylenchloride suspension containing 368 mg (1.53 mmol) of 2-(9H-xanthene-9-yl)-acetic acid. The suspension is stirred in an ice bath for 30 min and then at room temperature for 1 h after which time the solvent and excess reagents are removed by distillation under reduced pressure. The residue is again dissolved in 10 ml of methylene chloride, and the resulting solution was put in an ice bath. Then to the solution was added 2 ml of methylene chloride solution containing 2-tert-butyl-5-(6-cyclohexyl-5-oxohexyl)aniline and 0.56 ml of pyridine, and the mixture is stirred for 10 minutes, the Reaction solution is then diluted with diethyl ether, washed with diluted aqueous sodium hydroxide solution and dilute aqueous hydrochloric acid and then with water, in that order. The solvent is then removed by distillation under reduced pressure. The resulting residue is subjected to column chrom mg (yield 86%) specified in the procurement connections in the form of crystals, melting at 126-127oC (after recrystallization from a mixture of diisopropyl ether and hexane) foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 1709, 1663, 1518, 1478, 1459, 1256, 762.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,81-1,02 (2H, multiplet); 1,05-1,93 (13H, multiplet); of 1.18 (9H, singlet); of 2.27 (2H, doublet, J = 7 Hz); 2,28 is 2.75 (6H, multiplet); 4,74 (1H, triplet, J = 7 Hz); 6,88 was 7.45 (11H, multiplet).

Example 22. N-[2-tert-Butyl-5-(6-hexyl-5-hydroxyhexyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-587)

37 ml (0,99 mmol) borgert sodium added to 10 ml of a methanol suspension containing 544 mg (0,986 mmol) N-[2-tert-butyl-5-(6-hexyl-oxohexyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 21), in an ice bath. The ice bath is then removed and the reaction mixture stirred for 1 h at room temperature. After this time the reaction solution was diluted with diethyl ether, washed with saturated aqueous ammonium chloride and then with water several times. The solvent is then removed by distillation under reduced pressure to obtain 523 mg (yield 97%) indicated in the title compound in the form of a foamy product.

Infrared is anansa (CDCl3, 270 MHz), ppm: 0,77-1,85 (19H, multiplet); to 1.16 (9H, singlet); 2,23-2,37 (0.5 H, multiplet); 2,45 (0.5 H, doublet, J = 7 Hz); 2,60 (1,5 H, triplet, J = 7 Hz); 2,70 (1,5 H, doublet, J = 7 Hz); 3,63-with 3.79 (1H, multiplet); 4,74 (1H, triplet, J = 7 Hz); 6.89 was 7.45 (11H, multiplet).

Example 23. N-[2-tert-butyl-5-(4-cyclohexyl-2-oxobutyl)phenyl]-2-(9H-xanthene - 9-yl)ndimethylacetamide (compound N 1-1265)

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(4-cyclohexyl-2-oxobutyl)aniline as starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 143-135oC (after recrystallization from a mixture of acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3379, 2922, 1701, 1663, 1480, 1458, 1258, 761.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,7-1,0 (2H, multiplet); 1,0-1,3 (3H, multiplet); to 1.16 (9H, singlet); 1,3-1,7 (8H, multiplet); 2,2-of 2.75 (4H, multiplet); 3,39 (2/5H, singlet); 3,66 (8/5H, singlet); to 4.73 (1H, triplet, J = 7 Hz); 6,9 was 7.45 (11H, multiplet).

Example 24. N-[2-tert-Butyl-5-(4-cyclohexyl-2-hydroxybutyl)phenyl]-2-(9H-xanthene-9-yl-ndimethylacetamide (compound N 1-373)

Following the method similar to that described in example 22, but using N-[2-tert-butyl-5-(4-th product in the appropriate number, used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3430, 1678, 1600, 1575, 1480, 1457.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,8-1,0 (2H, multiplet); 1,0-1,8 (13H, multiplet); to 1.70 (9H, singlet); 2,3-2,9 (4H, multiplet); 3,7-of 3.85 (1H, multiplet); 4,74 (1H, triplet, J = 7 Hz); the 6.9 to 7.5 (11H, multiplet).

Example 25. N-[2-tert-Butyl-5-(5-cyclohexyl-3-oxobutyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1264)

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(5-cyclohexyl-3-oxobutyl)aniline (obtained by the method similar to that described in preparation 7) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3460, 1708, 1678, 1480, 1458.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: 0,7-1,0 (2H, multiplet); 1,1-1,8(IIH, multiplet); to 1.15 (9H, singlet), 2,3-2,9 (8H, multiplet); 4,74 (IH, triplet, J =7 Hz); 6,9-7,5 (IIH, multiplet).

Example 26. N-[2-tert-Butyl-5-(5-cyclohexyl-3-hydroxyben is using N-[2-tert-Butyl-5-(5-cyclohexyl-3-oxobutyl)phenyl] - -2-(9H-xanthene-9-yl)ndimethylacetamide(obtained as described in example 23) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 148-149oC (after recrystallization from a mixture of acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3371, 2921, 2849, 1658, 1518, 1480, 1458, 1259, 761.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: 0,7-1,0 (2H, multiplet); 1,0-1,85 (15H, multiplet); to 1.16 (9H, singlet); 2,3-2,9 (4H, multiplet); 3,4-3,7(IH, multiplet); 4,74 (IH, triplet, J=Hz); and 6.9-7.5 (a IIH, multiplet).

Example 27. N-[2-tert-Butyl-5-(5-cyclohexyl-4-oxobutyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide(compound N 1-1269)

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(5-cyclohexyl-4-oxobutyl)phenyl aniline as starting product, in an appropriate amount used in this example, receive specified in the procurement compound as crystals, melting at 193-194,5oC (after recrystallization from a mixture of methylene chloride and diethyl ether). The original product is obtained according to the method similar to that described in preparation 7, but using 2-tert-butyl-5-"ptx2">

Infrared absorption spectrum (KBr),maxcm-1: 3233, 1703, 1640, 1536, 1480, 1459, 1258, 756.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: 0,8-1,0(2H, multiplet); 1,05-1,4 (3H, multiplet); of 1.17 (9H, singlet); 1,6-2,0 (8H, multiplet); 2,2-of 2.75 (8H, multiplet); 4,74 (IH, triplet, J = Hz); 6,9-7,45 (IIH, multiplet).

Example 28. N-[2-tert-Butyl-5-(5-cyclohexyl-4-hydroxyphenyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-495)

Following the method similar to that described in example 22, but using N-[2-tert-butyl-5-(5-cyclohexyl-4-oxobutyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 27) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 157-158oC (after recrystallization from a mixture of diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3238, 1639, 1531, 1482, 1459, 1257, 756.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: 0,75-1,05 (2H, multiplet); 1,1-1,9 (15H, multiplet); to 1.16 (9H, singlet); 2,25-2,4 (1/2H, multiplet); 2,45 (I/2H, broadened doublets, J = 8 Hz); 2,61 (3/2H, triplet, J = 7 Hz); 2,70 (3/2H, doublet, J =7 Hz); the 3.65-3.75 to (IH, broadened singlet); 4,75 (IH, triplet, J =7 l)ndimethylacetamide (compound N 1-1266)

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(5-cyclohexyl-2-oxobutyl)aniline as starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 146-147oC (after recrystallization from a mixture of diisopropyl ether and hexane). The original product is obtained according to the method similar to that described in preparation 7, but using 2-tert-butyl-5-(5-cyclohexyl-2-oxobutyl)-1-nitrobenzene (obtained by the method similar to that described in preparation 9).

Infrared absorption spectrum (KBr),maxcm-1: 3386, 1711, 1663, 1519, 1480, 1458, 1259, 764.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: 0.77-a of 0.94 (2H, multiplet); 1,08 of 1.28 (6H, multiplet); to 1.16 (9H, singlet); 1,50-2,72 (7H, multiplet); 2,28-2,40 (0,4 H, multiplet); of 2.45 (2H, triplet, J = 7 Hz); 2,70 (I,6H, doublet, J =7 Hz); 3,38 (0,4 H, singlet); 3,65 (I,6H, singlet); to 4.73 (IH, triplet, J = 7 Hz); 6,94-7,40 (IIH, multiplet).

Example 30. N-[2-tert-Butyl-5-(5-cyclohexyl-2-hydroxyphenyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-397)

Following the method similar to that described in example 22, but using N-[2-tert-butyl-5-(5-cyclohexyl-2-oxobutyl)phenyl]-2-(kolichestvo, used in this example, get mentioned in the title compound as crystals, melting at 109-111oC (after recrystallization from diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3246, 1643, 1527, 1482, 1458, 1259, 760.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: to 0.80 to 0.97 (2H, multiplet); 1,12-1,77 (15H, multiplet); 1,17 (9H, multiplet); 2,35-2,55 (0,8 H, multiplet); 2,60 (0,8 H, doublet of doublets, J = 9 &14 Hz); 2,70 (1,6 H, doublet, J = 7 Hz); 2,80 (IH, doublet of doublets, J = 4 &14 Hz); 3,55-a 3.87 (IH, multiplet); 4,74 (IH, triplet, J = 7 Hz); 6,97-7,41 (IIH, multiplet).

Example 31. N-[2-tert-Butyl-5-(6-cyclohexyl-2-oxohexyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1267)

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(6-cyclohexyl-2-oxohexyl)aniline as starting product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product. The original product is obtained according to the method similar to that described in preparation 7, but using 2-tert-butyl-5-(6-cyclohexyl-2-oxohexyl) -1-nitrobenzene (obtained by the method similar to that described in preparation 9).

aqueous magnetic resonance (CDCI3, 270 MHz), ppm: 0,75-0,90 (2H, multiplet); 1,10-1,30 (8H, multiplet); of 1.17 (9H, singlet); 1,50-2,70 (7H, multiplet); 2,31 -2,42 (0,4 H, multiplet); 2,47 (2H, triplet, J = 7 Hz); 2,70 (1,6 H, doublet, J = 7 Hz), 3,38 (0,4 H, singlet), 3,65 (1,6 H, singlet); to 4.73 (IH, triplet, J = 7 Hz); 6,94-7,40 (IIH, multiplet).

Example 32 N-[2-tert-Butyl-5-(6-cyclohexyl-2-hydroxyhexyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-421)

Following the method similar to that described in example 22, but using N-[2-tert-butyl-5-(6-cyclohexyl-2-oxohexyl)phenyl] -2-(9-xanthene-9-yl) ndimethylacetamide (obtained as described in example 31) as the original product, in an appropriate amount used in this example, receive specified in the header of the connection in view of the foam product.

Infrared absorption spectrum (KBr),maxcm-1: 3380, 3275, 1656, 1522, 1480, 1459, 1256, 758.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: from 0.8 to 0.94 (2H, multiplet); 1,12-1,75 (17H, multiplet); of 1.17 (9H, singlet); 2,33-2,55 (0,8, multiplet); 2,60(0,8 H, doublet of doublets, J = 9 &14 Hz); 2,70 (1,6 H, doublet, J = 7 Hz); 2,80 (0,8 H, doublet of doublets, J = 3 & 14 Hz); 3,52-3,88 (IH, multiplet); 4,74 (IH, triplet, J = 7 Hz); 6,97-7,41 (IIH, multiplet).

Example 33. N-[2-tert-Butyl-5-(4-cycloheptyl-2-oxobutyl)phenyl]-4-decyloxybenzoic (connection # 4-util-5-(4-cyclohexyl-2-oxobutyl)aniline as starting products in the appropriate ratio, used in this example, get mentioned in the title compound as crystals, melting at 98-99oC (after recrystallization from a mixture of ethyl acetate and hexane). 2-tert-Butyl-5-(4-cycloheptyl-3-oxobutyl)aniline used as starting product, receive according to the method similar to that described in preparation 7, but using 2-tert-butyl-5-(4-cycloheptyl-3-oxobutyl)-1-nitrobenzene (obtained by the method similar to that described in preparation 6).

Infrared absorption spectrum (KBr),maxcm-1: 3314, 1715, 1640, 1502, 1251, 766.

Spectrum of nuclear magnetic resonance (CLCl3, 270 MHz): 0,88 (3H, triplet, J = 7 Hz; of 1.05 to 1.7 (26H, multiplet); USD 1.43 (9H, singlet); 1,75 - 1,9 (2H, multiplet); 1,9 - 2,1 (1H, multiplet); 2,31 (2H, doublet, J = 7 Hz); 2,7 - 2,8 (2H, multiplet); 2,8 - 2,9 (2H, multiplet); a 4.03 (2H, triplet, J = 7 Hz); 6,95 -7,05 (3H, multiplet); to 7.32 (1H, doublet, J=8gts); 7,60 (1H, singlet); for 7.78 (1H, singlet); a 7.85 (2H, doublet, J = 8 Hz).

Example 34. N-[2-tert-Butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -4 - decyloxybenzoic (compound N 4-17)

Following the method similar to that described in example 22, but using N-[2-tert-butyl-5-(4-cycloheptyl-3-oxobutyl) phenyl] -4-decyloxybenzoic (obtained as described in example 31) as the source is s in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3480, 1664, 1607, 1503, 1468.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz): 0,88 (3H, triplet, J=HZ); 1,05 - 1,9 (33H,multiplet);USD 1.43 (9H, singlet); 2,6-2,9(9H, multiplet): 3,65 to 3.8 (1H, multiplet); was 4.02 (2H, triplet, J= 7 Hz); 6,98 (2H, doublet, J= 8gts); 7,02 (1H, doublet, J=8gts); 7,33 (1H, doublet, J=8gts); to 7.61 (1H, singlet); for 7.78 (1H, singlet); a 7.85 (2H, doublet, J=8 Hz).

Example 35 N-[2-tert-Butyl-5-(3-phenyl-3-oxopropyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (Compound N 1-1326)

of 0.58 ml (4.20 mmol) of triethylamine and 0.31 ml (2.10 mmol) of diethylphosphoramidite added to 20 ml of benzene suspension containing 505 mg (2.10 mmol) of 2-(9H-xanthene-9-yl)acetic acid and the mixture is then stirred for 1 h, after this time the reaction suspension add 5 ml of benzene solution containing 587 mg (2,09 mmol) 2-tert-butyl-5-(3-phenyl-3-oxopropyl)aniline (obtained by the method similar to that described in preparation 7), and then 10 mg of 4-pyrrolidinedione, and the resulting mixture heated under reflux for 4.5 hours, the Reaction mixture was then diluted with diethylacetal, washed with diluted aqueous hydrochloric acid solution, water and then saturated aqueous sodium carbonate and nasyshennaya and the resulting residue is subjected to column chromatography on silica gel. Elution with 4:1 by volume mixture of methylene chloride and cyclohexane gives 934 mg (yield 86%) indicated in the title compound as crystals, melting at 116-118oC (after recrystallization from diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3216, 1686, 1640, 1481, 1457, 1254.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,17 (27/4 H, singlet); 1,22 (9/4H, singlet); 2,46 (9/4H, doublet, J = 7 Hz); 2,65 -2,85 (1H, multiplet); 2.71 to (3/2H, doublet, J=Hz); 3.04 from (3/2H, triplet, J=7 Hz); 3,05-3,02 (1/2H, multiplet); 3,32 (3/2H, triplet, J=Hz); 4,74 (1H, triplet, J= 7 Hz); 6,7-6,7 (14H, multiplet); 7,99 (2H, doublet, J=Hz).

Example 36. N-[2-tert-Butyl-5-(3-hydroxy-3-phenylpropyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (Compound N 1-1300)

Following the method similar to that described in example 22, but using N-[2-tert-butyl-5-(3-phenyl-3-ecoprofile)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 35) as the original product, in an appropriate amount used in this example, get the specified header in the form of crystals, melting at 136-137oC (after recrystallization from diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3267, 1658, 1525, 1479, 1255.

the years); 4,5-4,8 (2H, multiplet); the 6.9 to 7.5 (16H, multiplet).

Example a N-[2-tert-Butyl-5-(3-oxo-4-phenylbutyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (Compound N 1-1327)

Following the method similar to that described in example 37, but using 2-tert-butyl-5-(3-oxo-4-phenylbutyl) aniline ( obtained by the method similar to that described in preparation 7) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 122-123oC (after recrystallization from diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3224, 1716, 1640, 1456, 1257.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,15 (27/4H, singlet): of 1.18 (9H, singlet); 2,41 (1/2H, doublet, J=7 Hz); 2,5-2,6 (1/2H, multiplet); 2,69 (3-2H, doublet, J=HZ): 2,7-2,9 (3/2H, multiplet); 3,67 (1/2H, singlet); 3,71 (3/2H, singlet); 4,74 (1H, triplet, J=7 Hz); 6,85 to 7.4 (16H, multiplet); 1,8-2,8 (6H, multiplet): 4,5-4,8 (2H, multiplet); the 6.9 to 7.5 (16H, multiplet).

Example 38. N-[2-tert-Butyl-5-(3-hydroxy-4-phenylbutyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide

(Compound N 1-1301)

Following the method similar to that described in example 22, but using the compound obtained in example 37, receive specified in the , cm-1: 3403, 3278, 1655, 1458, 14116, 1256.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,16 (27/4H, singlet); 1,20 (9/4H, singlet); 1,75-2,0 (2H, multiplet); 2,3-2,95 (6H, multiplet); 3,7-4,0 (1H, multiplet); 4,74 (1H, triplet, J=7 Hz); 6,9-7,45 (16H,multiplet).

example 39. N-[2-tert-Butyl-5-(4-cycloheptyl-3-hydroxybutyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (Compound N 1-949)

Following the method similar to that described hereinafter in example 40, but using N-[2-tert-butyl-5-(4-cycloheptyl-3-tert-butyldimethylsilyloxy) phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation II) as starting product in the appropriate number, using this example, you receive specified in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3400, 1668, 1596, 1475, 1458.

Range nuclear resonance (CDCl3, 270 MHz), ppm: 1,0-1,8 (17H,multiplet); to 1.16 (9H, singlet); 2,3-2,9 (4H, multiplet); 3,6-3,8 (1H,multiplet); 4,74 (1H, triplet, J=7 Hz); and 7.5 (11H, multiplet).

Example 40. N-[2-tert-Butyl-5-(3-cyclohexyl-2 - hydroxypropyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-349)

1.5 ml 2 H aqueous hydrochloric acid is added to 15 ml of tertrahydrofuran ring xanthen-9-yl) ndimethylacetamide ( received as described in preparation II), and the mixture is stirred for 2.5 h at 50oC. the Reaction mixture was allowed to return to room temperature. The addition of a mixture of ethyl acetate and water allows specified in the header of the connection is to be distributed between the organic solvent and water. The organic layer is separated and washed with saturated aqueous sodium bicarbonate and then saturated aqueous sodium chloride. The solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 50 g of silica gel. Elution with a mixture of ethyl acetate and hexane, varying from 1:2 to 2:3 by volume, leads to the production of 650 mg (yield 98%) indicated in the title compound as crystals, melting at 177-178oC (after recrystallization from isopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3393, 3223, 1641, 1537, 1482, 1457, U 760.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,82 of-1.04 (2H, multiplet); 1,12-1,87 (11H, multiplet); 1,17 (9H, multiplet); 2,35-2,50 (0,08 H, multiplet); 2.57 m (0,8 H, doublet of doublets, J=8 & GC); 2,70 (1,6 H, doublet, J=7 Hz); 2,79 (0,8 H, doublet of doublets, =4 J & 8 Hz); 3,67 -3,99 (1H, multiplet); 4,74 91H, J=7 Hz); 6,97-7,41 (1H, mult is inania N 1-26)

Following the method similar to that described in example 40, but using N-[5-(4-cyclohexyl-3-tert-butyldimethylsilyloxy)-2 - isopropylphenyl-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation II) as starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 144-145oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3282, 2919, 1644, 1528, 1481, 1260, 757.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), pp m: 0,8-1,9 (15H, multiplet); of 1.05 (6H, doublet, J=7 Hz); 2,5-2,9 (5H, multiplet), 3,65-of 3.85 (1H, multiplet); 4,69 (1H, triplet, J=7 Hz); 7,0-7,5 (11H, multiplet).

Example 42. N-[2-tert-Butyl-5-(3-cyclohexyl-3-hydroxypropyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (Compound 1-131 N)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(3-cyclohexyl-3-tert-butyldimethylsilyloxy)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation II) as starting product, in an appropriate amount used in this example, get the criminal code is (KBr),maxcm-1: 3400, 3270, 1653, 1522, 1480, 1457, 1256, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm b: 0,9001,89 (13H, multiplet); to 1.16 (9H, singlet); 2,30-2,87(4H, multiplet); 3,28 is-3.45 (1H, multiplet); 4,74 (1H, triplet, J=7 Hz); 6,95-7,42 (11H, multiplet).

Example 43. N-[2-tert-Butyl-5-(6-cyclohexyl-3-hydroxyhexyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (Compound N 1-49)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(6-cyclohexyl-3-tert-butyldimethylsilyloxy) phenyl-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation II) as starting product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product

Infrared absorption spectrum (KBr),maxcm-1: 3390, 3280, 1655, 1522, 1480, 1459, 1256, 758.

Spectrum of nuclear magnetic resonance (CDCL3, 270 MHz), ppm: to 0.80-0.95 (2H, multiplet); 1,10-1,82 (17H, multiplet); to 1.16 (9H, singlet); 2,30-2,82 (4H, multiplet); 3,50 at 3.69 (1H, multiplet); 4,74 (1H, triplet, J=7 Hz); 6,95-7-41 (11H, multiplet).

Example 44. N-[2-tert-Butyl-5-(7-cyclohexyl-3-hydroxymethyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (Compound N 1-73)

Following the manner similar to the op is-xanthene-9-yl)ndimethylacetamide (obtained by the method, similar to that described in preparation II) as starting product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3390, 3270, 1653, 1522, 1480, 1459, 1256, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0.77-a of 0.93 (2H, multiplet); 1,10-1,81 (19H, multiplet); to 1.16 (9H, singlet); 2,30-2.83 (4H, multiplet; 3,47-369 (1H, multiplet); 4,74 (1H, triplet, J= 7 Hz); 6,95-7,42 (11H, multiplet).

Example 45. N-[2-tert-Butyl-5-(6-cyclohexyl-4-nitroxyethyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (Compound N 1-519)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(6-cyclohexyl-4-tert-butyldimethylsilyloxy - phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation II) as starting product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3450, 1659 (broad0, 1600, 1575, 1478, 1453.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,7-1,0 (2,9-to 7.5 (11H, multiplet). N-[2[tert-Butyl 5-(5-cyclohexyl-5-hydroxyphenyl)phenyl]- 2-(9H-xanthene-9-yl)ndimethylacetamide (Compound N 1-577)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(5-cyclohexyl-5-tert-butyldimethylsilyloxy) phenyl] -2-(nkanted-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation II) as starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 147-148oC (after recrystallization from a mixture of methylene chloride and diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3336, 1657, 1519, 1480, 1458, 1260, 761.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,93-1,86 (17H, multiplet); to 1.16 (9H, singlet); of 2.27 to 2.35 (0,4 H, multiplet); 2,45 (0,4 H, doublet, J=7 Hz); 2,60 (1,6 H, triplet, J=7 Hz); 2,70 (1,6 H, doublet, J= 7 Hz); 3,32-to 3.41 (1H, multiplet); 4,74 (1H, triplet, J=7 Hz); 6,93-7,41 (11H, multiplet).

Example 47. N-[2-tert-Butyl-5-(4-cyclopentyl-3-hydroxybutyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (Compound N 1-747)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(4-cyclopentyl-3-tert-butyldimethylsilyloxy) phenyl] -2-(9 is oduct in an appropriate amount, used in this example, get mentioned in the title compound as crystals, melting at 142-143oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 2951, 1654, 1529, 1478, 1253, 760.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,0-1,3 (2H, multiplet); to 1.16 (9H, singlet(; 1,3-2,0 (11H, multiplet); 2,2-2,9 (4H, multiplet); 3.5 to 3.8 (1H, multiplet); 4,74 (1H, triplet, J=7 Hz); the 6.9 to 7.5 (11H, multiplet).

Example 48. N-[2-tert-Butyl-5-(6-cyclopentyl-5-hydroxyhexyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-839)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(6-cyclopentyl-5-tert-butyldimethylsilyloxy) phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation II) as starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 132-133oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 2949, 1649, 1523, 1479, 1458, 1258, 760.

Spectrum of nuclear magnetic resonator, ubly, J=7 Hz); 2,60 (8/5H, triplet, J=8 Hz); 2,69 (8/5H, doublet, J=7 Hz); up 3.6-3.7 (1H, multiplet); 4,74 (1H, triplet, J=7 Hz); the 6.9 to 7.5 (11H, multiplet).

Example 4. N-[2-tert-Butylthio-6-(3-hydroxy-3-phenylpropyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide

(compound N 1-1442)

Following the method similar to that described in example 40, but using N-[2-tert-butylthio-6-(3-tert-butyldimethylsilyloxy-3-phenylpropyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 11) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 145-147oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 2959, 1662, 1481, 1456, 1259, 762.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,13 (9H, singlet); 1,99 (2H, Quartet, J=7 Hz); 2,60 (2H, triplet, J=8 Hz); a 2.75 (2H, doublet, J= 7 Hz); 4,51 (1H, triplet, J=6 Hz); 4,70 (1H, triplet, J=7 Hz); 7,0-7,5 (16H, multiplet).

Example 50. N-[2-Methyl-6-(3-hydroxy-3-phenylpropyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1438)

Following the method similar to that described in example 40, but using N-[2-methyl-6-(3-tert-butylimide the manufacture 11) as starting product, in the corresponding amount used in this example, get mentioned in the title compound as crystals, melting at 193-194oC (after recrystallization from a mixture of methylene chloride, methanol and hexane).

Infrared absorption spectrum (KBr), maxcm-1: 3235, 1648, 1523, 1479, 1458, 754.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: 1,5-2,8 (6H, multiplet); is 2.05 (3H, singlet); 4,2-4,5 (1H, multiplet); and 4.68 (1H, triplet, J=7 Hz); 6,9-7,56 (11H, multiplet),

Example 51. N-[2-Methyl-6-(3-oxo-3-phenylpropyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide connection N 1-1437)

Following the method similar to that described in example 13, but using N-[2-methyl-6-(3-hydroxy-3-phenylpropyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 50) as the original product, in an appropriate amount used in this example, get mentioned in the title compound, melting at 175-176oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3280, 1684, 1653, 1480, 1457, 1259, 762.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: 2,10 (3H, singlet); 2,62 (2H, triplet, J=7 Hz), 2,85 (2H, doublet, J=7 Hz), 3,23 (2H, triplet, is troxerutin)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1435)

Following the method similar to that described in example 40, but using N-[2-methyl-6-(3-tert-butyldimethylsiloxy)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 11) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 167-168oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3244, 1653, 1530, 1481, 1457, 1260, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: of 1.05 (3H, doublet, J= 7 Hz); 1,4-1,9 (2H, multiplet); to 2.06 (3H, singlet); 2,32 (2H, triplet, J=7 Hz); 2,70 (2H, doublet, J=7 Hz); 3.1 to 3.6V (1H, multiplet); and 4.68 (1H, triplet, J=7 Hz); 6,8-7,9 (11H, multiplet).

Example 53. N-[2-Methyl-6-(3-oxobutyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1436)

Following the method similar to that described in example 13, but using N-[2-methyl-6-(3-hydroxybutyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method described in example 52) as the source of the product in the appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 167-168maxcm-1: 3281, 1711, 1648, 1480, 1260, 754.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: 1,95 (3H, singlet); 2,03 (3H, singlet); 2,1-2,9 (4H, multiplet); a 2.75 (2H, doublet, J= 7 Hz); and 4.68 (1H, triplet, J=7 Hz); 6.75 in-7,5 (11N, multiplet); of 8.0 to 8.3 (1H, broadened singlet).

Example 54. N-[4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]-phenyl]-6-phenylhexa hydrosylate (compound N 1-1337)

1 ml of pyridine solution containing 276 mg (0,504 mmol) N-[2-tert-butyl-5-(6-phenyl-1-hydroxyhexyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 16), 58 mg (of 0.58 mmol) of succinic anhydride and 64 mg (0.52 mmol) of 4-(N,N-dimethylamino)-pyridine, stirred for 1 h at 100oC. after this time the reaction solution is diluted with ethyl acetate, washed with 2 N. aqueous hydrochloric acid, once with water twice and saturated aqueous sodium chloride. The solvent is then removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography on silica gel. Elution 9:1 by volume mixture of methylene chloride and methanol leads to 294 mg (yield 90%) specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (liquid film), maxcm-14H, multiplet); to 1.16 (9H, singlet); 1,53-to 1.98 (4H, multiplet); 2,38 is 2.80 (8H, multiplet); 4,74 (1H, triplet, J=7 Hz); 5,67 (1H, triplet, J=7 Hz);? 7.04 baby mortality-7,51 (16H, multiplet).

Example 55. N-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]-phenyl}-6-phenylhexa hydrosylate (compound N 1-1336)

4 ml of a methanol solution containing 165 mg (0,255 mmol) 1-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}-6-phenylhexa of hydrosylate (obtained as described in example 54), cooled in an ice bath and then added dropwise 0.1 N. aqueous sodium hydroxide solution. The reaction solution was condensed by evaporation under reduced pressure, keeping the temperature below 15oC. To the residue is added 20 ml of toluene and then add enough ethanol to until the solution becomes homogeneous. The solvent is then distilled off under reduced pressure. In order to remove residual water to the residue is added toluene and the mixture is again evaporated. This procedure is repeated several times and obtain 170 mg (quantitative yield) specified in the connection header in the form of a foamy product.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,03 and 1.80 (8H, multiplet); of 1.06 (9H, multiplet); 2,10-2,59 (7,2 H, multiplet); 2,80-2,98 (0,8 H, multiplet); br4.61 (0,8 H, trip the example 56. 1(2-{ 4-tert-Butyl-3-[2-9H-xanthene-9-yl)acetamido] -phenyl} ethyl)-2-cyclohexyl hydrosylate (compound N 1-1109)

4 ml of a methanol solution containing 74 mg (0.14 mmol) of N-[2-tert-butyl-5-(4-cyclopentyl-3-hydroxybutyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 12), 15 mg (0.15 mmol) of succinic anhydride, 18 mg (0.15 mmol) of 4-(N,N-dimethylamino)pyridine and 112 mg (1,41 mmol) of pyridine, stirred for 9 h at 125oC. after this time the reaction mixture was allowed again to reach room temperature. The reaction mixture was then diluted with diethyl ether and washed with dilute aqueous hydrochloric acid and then with water. The solvent is then removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 20 g of silica gel. Elution using the method of gradient elution with mixtures of methylene chloride and methanol ranging from 100: 5 to 10: 1, leads to obtain 73 mg (yield 84%) indicated in the title compound in the form of a foamy product.

Infrared absorption spectrum (CHCl3),maxcm-1: 1722, 1671, 1479, 1458, 1250.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0.75 to 2.00 in (15 NM, multiplet); 1.14 in (N, death 57. 1-(2-{4-tert-Butyl-3-[2-[(9H-xanthene-9-yl)acetamido]-phenyl} ethyl)- 2-cyclohexyl sodium succinate (compound N 1-1102)

Following the method similar to that described in example 55, but using 1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl}ethyl)- 2-cyclohexylethyl hydrosylate (obtained as described in example 56) as the source of the product in the appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr), maxcm-1: 1720, 1655, 1578, 1524, 1480, 1459, 1414, 1255, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,68-1,86 (15H, multiplet); of 1.09 (9H, singlet); 2,14-2,74 (8H, multiplet); 4,70 (1H, triplet, J= 7 Hz); 4,73-of 5.05 (1H, multiplet); 6,79-the 7.43 (11H, multiplet).

Example 58 1-(2-{ 4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido] -phenyl} ethyl)-3 - cyclohexylprop hydrosylate (compound N 1-1118)

Following the method similar to that described in example 56, but using N-[2-tert-butyl-5-(5-cyclohexyl-3-hydroxyphenyl)-phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 26) as the original product, in an appropriate amount used in this example, receive specified in the header coedine
: 1728, 1672, 1479, 1457, 1418.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,7-1,0 (2H, multiplet); 1.0 to 2.0 (15H, multiplet); to 1.15 (9H, singlet); 2,3-2,8 (8H, multiplet); to 4.73 (1H, triplet, J=7 Hz); 4,9-5,0 (1H, multiplet); the 6.9 to 7.5 (11H, multiplet),

Example 59. 1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]-phenyl} ethyl)- 3-cyclohexylprop sodium succinate (compound N 1-1111)

Following the method similar to that described in example 55, but using 1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)- 3-cyclohexylprop hydrosylate (obtained as described in example 58) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (CHCl3),maxcm-1: 3100-3500 (broad), 1716, 1672, 1573, 1455, 1412.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: of 0.65 to 0.9 (2H, multiplet); 0,9-1,85 (15H, multiplet); 1,10 (9H, singlet); a 2.0 to 2.75 (8H, multiplet); 4,69 (1H, triplet, J=7 Hz); 4,8-4,9 (1H, multiplet); of 6.9 to 7.4 (11H, multiplet).

Example 60. 1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]-phenyl} ethyl)- 3-cyclopentylmethyl hydrosylate (compound N 1-1183)

Following the method similar to that described in pri, as described in preparation 47) as the source of the product in the appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (CHCl3), maxcm-1: 1725, 1671, 1478, 1456, 1417.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,9-1,2 (2H, multiplet); 1.14 in (9H, singlet); 1,3-2,0 (11H, multiplet); of 2.0-3.8 (8H, multiplet); 4.72 in (1H, triplet, J=7 Hz); 5,0-of 5.15 (1H, multiplet); the 6.9 to 7.5 (11H, multiplet).

Example 61. 1-(2-{ 4-tert-Butyl-3-[-(9H-xanthene-9-yl)acetamido]-phenyl} ethyl)- 3-cyclopentylmethyl sodium succinate (compound N 1-1176)

Following the method similar to that described in example 55, but using 1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl}ethyl)- 2-cyclopentylmethyl hydrosylate (obtained as described in example 60) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (CHCl3),maxcm-1: 3100-3500 (broad), 1711, 1672, 1576, 1478, 1454.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: from 0.9 to 1.15 (2H, multiplet); of 1.09 (9H, singlet); is 1.3-1.8 (11H, multi 5-[3-(1-Imidazolyl)propoxy] -2-methylthiophenyl}-2-(9H-xanthene - 9-yl)ndimethylacetamide (compound N 1-1479)

Following the method similar to that described in example 1, but using N-[5-(3-hydroxypropoxy)-2-methylthiophenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 54) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 127-129oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3297, 1658, 1576, 1480, 1456, 1257, 756.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: 1,95 (3H, singlet); 2.0 to 2.5 (2H, multiplet); a 2.75 (2H, doublet, J=7 Hz); 3,95 (2H, triplet, J= 5 Hz); 4,18 (2H, triplet, J=6 Hz); 4,70 (1H, triplet, J=7 Hz); 6,51 (0,6 H, doublet, J= 2 Hz); 5,65 (0,4 H, doublet, J=2 Hz); of 7.6 to 7.9 (11H, multiplet); 8,0 an 8.4 (2H, multiplet).

Example 63. N-{ 5-(3-(1-Imidazolyl)propoxy] -2-methylthiophenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide hydrochloride (compound N 1-1478)

Following the method similar to that described in example 2, but using N-{5-[3-(1-imidazolyl)propoxy] -2-methylthiophenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 62) as the original product, in an appropriate amount used in this example, receive specified in the header soedineniya).

Infrared absorption spectrum (KBr),maxcm-1: 3262, 2921, 1658, 1574, 1482, 1259, 751.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: to 1.98 (3H, singlet); 2,3-2,6 (2H, broadened singlet); a 2.75 (2H, doublet, J=7 Hz); 4,0-4,2 (2H, broadened singlet); 4,5-4,8 (3H, multiplet); 6,55 (1H, broadened singlet); 7,0-7,5 (11H, multiplet); 8,11 (1H, broadened singlet); by 8.22 (1H, broadened singlet); a 9.60 (1H, broadened singlet).

Example 64. N-[2-tert-Butyl-5-(5-cycloheptyl-3-oxobutyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-1271)

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(5-cycloheptyl-3-oxobutyl)aniline (obtained as described in preparation 6) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 136-137oC (after recrystallization from a mixture of methylene chloride, diethyl ether and Hasana).

Infrared absorption spectrum (KBr),maxcm-1: 1701, 1665, 1520, 1480, 1458, 1300.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,06-1,73 (15H, multiplet); to 1.16 (9H, singlet); 2,38-2,59 (8H, multiplet); 4,74 (1H, triplet, Y = 7 Hz); 6,91-7,44 (11H, multiplet).

Example sposobu, similar to that described in example 22, but using N-[2-tert-butyl-5-(5-cycloheptyl-3-oxobutyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 64) as the original product, in an appropriate amount used in this example, get the specified header in the form of crystals, melting at 136-137oC (after recrystallization from a mixture of methylene chloride, diethyl ether and Hasana).

Infrared absorption spectrum (KBr),maxcm-1: 3380, 1659, 1518, 1480, 1459, 1260, 760.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,09-1, 86 (19H, multiplet); to 1.16 (9H, singlet); 2,30-to 2.85 (4H, multiplet); 3.46 in-to 3.67 (1H, multiplet); 4,74 (1H, triplet, Y = 7 Hz); 6,95-7,42 (11H, multiplet).

Example 66. 1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido] -phenyl} ethyl)-2-cycloheptylmethyl hydrosylate connection N 1-1221)

Following the method similar to that described in example 56, but using N-[2-tert-butyl-5-(4-cycloheptyl-3-hydroxybutyl)phenyl] -2-(9H-xanthene- -9-yl)ndimethylacetamide (obtained as described in example 39) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorp the ANSA (CDCl3, 270 MHz), ppm: 1,05-2,0 (17H, multiplet); 1.14 in (9H, singlet); about 2.2-2.8 (8H, multiplet); to 4.73 (1H, triplet Y = 7 Hz); 4,9-5,2 (1H, multiplet); the 6.9 to 7.5 (11H, multiplet).

Example 67. 1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]- phenyl} ethyl)-2-cycloheptylmethyl sodium succinate (compound N 1-1220)

Following the method similar to that described in example 55, but using 1-(2-{ 4-tertbutyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl}ethyl-2 - cycloheptylmethyl hydrosylate (obtained as described in example 66) as the original product, in an appropriate amount used in this example, get the title compound in the form of a foamy product.

Infrared absorption spectrum (CHCl3,maxcm-1: 3100-3500 (broad), 1711, 1674, 1652, 1576, 1480, 1457.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,0-1,9 (17H, multiplet); of 1.09 (9H, singlet); 2,2-2,7 (8H, multiplet); 4,70 (1H, triplet, J = 7 Hz); 4,70-5,0 (1H, multiplet); 6,8-7,5 (11H, multiplet).

Example 68. N-[2-Ethyl-6-(3-oxo-6-phenyl-1-hexenyl)phenyl]- -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1447)

49 mg (1.13 mmol) of sodium hydride (as a 55% by weight suspension in mineral oil) is washed twice, each time with hexane, and suspended in 6 ml of dimethylformamide. To the suspension was added 2 mladeni ice. The reaction mixture is then immediately returned to room temperature, then stirred for 30 minutes To the reaction mixture is added 300 mg (0,808 mmol) of N-(2-ethyl-6-formyl)-2-(9H-xanthene-9-yl)acetamide", she again cooling with ice. The mixture was then stirred for 1 h at the temperature of ice-cooling and then 3 h at room temperature. After this time the reaction solution was poured into ice water and extracted with diethyl ether. The organic extract is washed with water. The solvent is removed by distillation under reduced pressure, and the obtained residue is recrystallized from a mixture of methylene chloride and diethyl ether to obtain 220 mg (yield 53%) indicated in the title compound as crystals, melting at 168-170oC.

Infrared absorption spectrum (KBr),maxcm-1: 3287, 1651, 1518, 1480, 1459, 1260.

Spectrum of nuclear magnetic resonance. (CDCl3, 270 MHz), ppm: 0,92 (1/2H, triplet, J = 7 Hz); 1,02 (5/2H, triplet, J = 7 Hz); to 1.98 (2H, quintet, J = 7 Hz); 2,15 (1/3H, doublet, J = 7 Hz); of 2.23 (2H, Quartet, J = 7 Hz); of 2.56 (2H, triplet, J = 7 Hz); and 2.26 (2H, triplet, J = 7 Hz); 2,77 (5/3H, doublet, J = 7 Hz); 4,70 (1H, triplet, J = 7 Hz); 6,5-6,7 (2H, multiplet); the 6.9 to 7.5 (16H, multiplet).

Example 69. 3-[4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]- -phenyl]1-cyclohexyl-tert-butyl-5-(3-cycloheptyl-3-hydroxypropyl)-phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (received as described in example 42) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxb cm-1: 2930, 1732, 1713, 1481, 1458, 1254, 761.

Example 70. Sodium-3-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]-phenyl}-1- -cyclohexylprop succinate (compound N 1-1093)

Following the method similar to that described in example 55, but using 3-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}-1- -cyclohexylprop hydrosylate (obtained as described in example 69) as the source of the product in the appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2929, 1726, 1657, 1578, 1481, 1457, 1255, 759.

Example 71. 1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]- -phenyl} ethyl)-5-cyclohexylmethyl hydrosylate (compound N 1-1136)

Should the method similar to that described in example 56, but using N-[2-tert-butyl-5-(7-cyclohexyl-3-hydroxyacyl)-phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 44) as a source about the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 1733, 1713, 1481, 1458, 1253, 760.

Example 72. Sodium 1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl) - acetamido] phenyl}ethyl-5-cyclohexylmethyl succinate (compound N 1-1129)

Following the method similar to that described in example 70, but using 1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-5- -cyclohexylmethyl hydrosylate (obtained as described in example 71) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 1726, 1656, 1578, 1524, 1481, 1458, 1415, 1364, 1300, 1255, 759.

Example 73. 1-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]- -phenyl}-2-cyclohexylethyl hydrosylate (compound N 1-1022)

Following the method similar to that described in example 56, but using N-[2-tert-butyl-5-(2-cyclohexyl-1-hydroxyethyl)phenyl] -(9H-xanthene- -yl)ndimethylacetamide (obtained as described in example 14) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectra is acetamido]-phenyl}-2- -cyclohexylethyl succinate (compound N 1-1023)

Following the method similar to that described in example 70, but using 1-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl}- -2-cyclohexylethyl hydrosylate (obtained as described in example 73) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 1728, 1658, 1578, 1481, 1458, 1256, 758.

Example 75. 1-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]- -phenyl}-3-cyclohexylprop hydrosylate (compound N 1-2865)

Following the method similar to that described in example 56, but using N-[2-tert-butyl-5-(3-cyclohexyl-1-hydroxypropyl)phenyl] -2-(9H-xanthene- -9-yl)ndimethylacetamide (obtained as described in example 99) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr), maxcm-1: 2923, 1736, 1714, 1481, 11458, 1255, 759.

Example 76. Sodium 1-{4-tert-butyl-3-(9H-xanthene-9-yl)-acetamido] phenyl} -3-chicagocraig succinate (compound N 1-1026)

Following the method similar to that described in example 70, but Vapiano in example 75) as the original product, in the corresponding amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 1728, 1658, 1578, 1481, 1458, 1255, 758.

Example 77. 1-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}-6- -cyclohexyloxy hydrosylate (compound N 1-1053)

Following the method similar to that described in example 56, but using N-[2-tert-butyl-5-(6-cyclohexyl-1-hydroxyhexyl)phenyl] -2-(9H-xanthene- -9-yl)ndimethylacetamide (obtained as described in example 18) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 2852, 1736, 1713, 1652, 1480, 1458, 1245, 1165, 759.

Example 78. Sodium 1-{4-tert-butyl-3-[2-(9H-xanthene-4-yl)acetamido]-phenyl}- -6-cyclohexyloxy succinate (compound N 1-1046)

Following the method similar to that described in example 70, but using 1-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}-6- -cyclohexyloxy hydrosylate (obtained as described in example 77) as the original product, in an appropriate amount used in this is th absorption spectrum (KBr),maxcm-1: 2923, 2852, 1728, 1656, 1567, 1480, 1458, 1416, 1255, 757.

Example 79. (R)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl} ethyl)- -2-cyclohexylethyl hydrosylate (connected N 1-1109)

A solution of 337 mg (0,471 mmol) (R)-1-(2-{4-tert-butyl-3-[2-(9H - xanthene-9-yl)acetamido] phenyl} ethyl)-2-cyclohexylethyl benzyl of hydrosylate (obtained as described in preparation 25) in 10 ml of ethyl acetate vigorously stirred in a stream of hydrogen in the presence of 173 mg of 10% by weight palladium on coal. The reaction mixture was then filtered and the catalyst washed with ethyl acetate. The filtrate and wash water are combined and the solvent is removed by distillation under reduced pressure. The residue is purified column chromatography through 15 g of silica gel using a 1: 19 by volume mixture of methanol and methylene chloride as eluent, to obtain specified in the connection header in the form of a foamy product.

[]2D2= -5.3o(C = 1.16 CHCl3).

Example 80. Sodium (R)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene- -9-yl)-acetamido]phenyl}ethyl)-2-cyclohexylethyl succinate (compound N 1-1102)

Following the method similar to that described in example 70, but using (R)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl}ethyl)- -2-cyclohexylethyl hydrosylate (the m in this example, get listed in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 1721, 1655, 1576, 1526, 1482, 1459, 1416, 1256, 760.

[]2D6= = -6.1o(C=1.05, methanol).

Example 81. (S)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl} ethyl)- -2-cyclohexylethyl hydrosylate (compound N 1-1109)

Following the method similar to that described in example 54, but using (S)-N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2- -(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 102) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

[]2D3= +4.9o(C = 1.14, CHCl3).

Example 82. Sodium (S)-1-(2-{4-tert butyl-3-[2-(9H-xanthene-9-yl) - acetamido]phenyl}ethyl)-2-cyclohexylethyl succinate (compound N 1-1102)

Following the method similar to that described in example 70, but using (S)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido)phenyl} ethyl)- -2-cyclohexylethyl hydrosylate (obtained as described in example 81) as the original product, in an appropriate amount used in this example, the first spectrum (KBr),maxcm-1: 1721, 1655, 1578, 1482, 1459, 1416, 1256, 760.

= +5.4o(C = 1.10, methanol).

Example 83. 1-(2-{ 4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-4-cyclohexylmethyl hydrosylate (compound N 1-1127)

Following the method similar to that described in example 56, but using N-[2-tert-butyl-5-(6-cyclohexyl-3-hydroxyhexyl)phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 43) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 1733, 1713, 1481, 1458, 1254, 760.

Example 84. Sodium 1-(2-ethyl-{4-tert-butyl-3-[2-(9H-xanthene-9- -yl)-acetamido]phenyl}ethyl)-4-cyclohexylmethyl succinate (compound N 1-1120)

Following the method similar to that described in example 70, but using 1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-4- -cyclohexylmethyl hydrosylate (obtained as described in example 83) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr) is}-1-(cyclohexylmethyl)cut hydrosylate (compound N-1-2441)

Following the method similar to that described in example 56, but using N-[2-tert-butyl-5-(4-cyclohexyloxy-3-hydroxybutyl)phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 215) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2922, 1736, 1481, 1458, 1254, 761.

Example 86. Sodium 3-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl} -1- -[(cyclohexyloxy)methyl]propyl succinate (compound N 1-2657)

Following the method similar to that described in example 70, but using 3-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}-1 - (cyclohexylmethyl)cut hydroxyzine (obtained as described in example 85) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr), maxcm-1: 2932, 1728, 1656, 1578, 1481, 1458, 12256, 760.

Example 87. (S)-1-(2-{4-tert-Butyl-3-[2-(9H-counton-9-yl)acetamido]phenyl}ethyl)- 3-cyclohexylprop hydrosylate (compound B1-1118)

Following the way, under-9-yl)ndimethylacetamide received, as described in example 114) as the source of the product in the appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared adsorption spectrum (KBr),maxcm-1: 2923, 2851, 1733. 1713, 1652, 1480, 1458, 1414, 1253, 760.

Example 88. Sodium (S)-1-(2-{ 4-tert-butyl-3-x2-(9H-consented-9-yl)acetamido]phenyl}ethyl)-3 - cyclohexylprop succinate (compound N 1-1111)

Following the method similar to that described in example 70, using (S)-1-(2-{ 4-tert-hotel-3-[3-(9H-xanthene-9-yl)acetamido] phenyl} ethyl-3 - cyclohexylprop hydrosylate (obtained as described in example 87) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 2851, 1726, 1656, 1577, 1480, 1458, 1414, 1254, 759. []2D2= - 6.79o(C=3.80 CHCl3).

Example 89.(R)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]-phenyl} ethyl)-3 - cyclohexylprop hydrosylate (compound N 1-1118)

Following the method similar to that described in example 56, but using (R)-N_ [2-tert-butyl-5-(5-cyclohexyl-3-hydroxyphenyl)penousal number, used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 2851, 1733, 1713, 1652, 1480, 1458, 1414, 1253, 760.

Example 90. Sodium (R)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)-acetamido]phenyl}ethyl)-3-cyclo exipres succinate (compound N 1-1111)

Following the method similar to that described in example 70, but using (R)-1-(2-{ 4-tert-butyl-3-[2(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-3-cyclohexylprop hydrosylate (obtained as described in example 89) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 2851, 1726, 1656, 1577, 1480, 1458, 1414, 1254, 759.

Example 91. 1-(2-{3-Isopropyl-2-[2-(9H-xanthene-9-yl)acetamido]-phenyl}ethyl)-4-cyclo paxilbuy hydrosylate (compound N 1-2866)

Following the method similar to that described in preparation 25, but using N-[2-isopropyl-6-(6-cyclohexyl-3-hydroxyhexyl) phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 125) as the original product, in an appropriate amount used is special, similar to that described in example 79, obtaining specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (KBr,maxcm-1: 2924, 2851, 1718, 1655, 1578, 1479, 1458, 1406, 1255.

Example 92. Sodium 1-(2-{ 3-isopropyl-2-[2-(9H-xanthene-9-yl)acetamido] phenyl}ethyl)-4-cyclohexylmethyl succinate (compound N 1-2867)

Following the method similar to that described in example 70, but using 1-(2-{ 3-isopropyl-2-[2-(9H-xanthene-9-yl)acetamido] phenyl}ethyl) -4-cyclohexylmethyl hydrosylate (obtained as described in example 91) as the source of the product in the appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2851, 1732, 1655, 1578, 1479, 1458, 1255.

Example 93. 2-(2-{ 4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-3-cyclohexylprop hydrosylate (compound N 1-2349)

Following the method similar to that described in preparation 25, but using N-[2-tert-butyl-5-[4-cyclohexyl-3-(hydroxymethyl)butyl] phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 207) as the original product, in an appropriate amount, ipoltm, similar to that described in example 79, obtaining specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2851, 1732, 1655, 1649, 1639, 1524. 1479, 1458, 1255.

Example 94. Sodium 2-(2-{tit-Butyl-3-[2-(9H - xanthene-9-yl)acetamido] phenyl}ethyl)-3-cyclohexylprop succinate (compound N 1-2367)

Following the method similar to that described in example 70, using 2-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl) -3-cyclohexylprop hydrosylate (obtained as described in example 93) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2922, 2851, 1724, 1655, 158, 1479, 1458, 1414, 1255.

Example 95. N-[2-tert-Butyl-5-(7-cycloheptyl-5-oxoethyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-2868)

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(7-cycloheptyl-5-oxoethyl)aniline (obtained by the method similar to that described in preparation 7) as the source of the product in the appropriate amount used in this example, get the Tr (KBr),maxcm-1: 2922, 2855, 1711. 1657, 1520, 1479, 1458, 1414, 1363, 1255.

Example 96. N-[2-tert-Butyl-5-(7-cycloheptyl-5-hydroxyethyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1013)

Following the method similar to that described in example 22. but using N-[2-tert-butyl-5-(7-cycloheptyl-5-oxoethyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 95) as starting product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1:2924, 2855, 1655, 1576, 1524, 1479, 1458, 1414, 1363, 1300, 1255.

Example 97. N-[2-tert-Butyl-5-(3-cycloheptyl-3-oxopropyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2869)

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(3-cycloheptyl-3-oxopropyl)aniline (obtained by the method similar to that described in preparation 7) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 155-156o(after recrystallization from a mixture of methylene chloride and hexane).

infrared absorption spectrum (hydroxypropyl)phenyl] -2 -(9H-xanthene-9-yl)ndimethylacetamide (Connection N1-943)

Following the method similar to that described in example 22, but using N-[2-tert-butyl-5-(3-cycloheptyl-3-oxopropyl)phenyl]-2 -(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 97) as starting product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr)maxcm-1: 3400, 3272, 2922, 2855, 1655, 1577, 1522, 1480, 1458, 1255, 759.

Example 99. N-[2-tert-Butyl-5-(3-cycloheptyl-1-hydroxypropyl)phenyl] -2 -(9H-xanthene-9-yl)ndimethylacetamide (Connection N1-203)

Following the method similar to that described in example 14, but using 2-cyclohexylethylamine iodide as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr)maxcm-1: 3390, 3284, 2923, 1656, 1577, 1520, 1481, 1481, 1458, 1256, 758.

Example 100. (R)-N-[2-tert-Butyl-5-(4-cycloheptyl-3-hydroxybutyl)phenyl] -2 -(9H-xanthene-9-yl)ndimethylacetamide (Connection N1-25)

Following the method similar to that described in example 40, but using (R)-N-{ 2-tert-butyl-5-[4-cyclohexyl-3-(tert-butyldimethylsilyloxy)butyl]phenyl}-2-(9H-CSEM number, used in this example, get mentioned in the title compound as crystals, melting at 140-141oC (after recrystallization from isopropyl ether).

Infrared absorption spectrum (KBr)maxcm-1: 3340, 3230, 165, 1532, 1478, 1459, 1254, 760. []2D2= -1,5o. (C=1.03, CHCl3).

Example 101. (S)-N-[2-tert-Butyl-5-(4-cyclohexyl-3-benzoyloxymethyl)-phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1547)

Following the method similar to that described in example 21, but using (S)-[Tret-Butyl-5-(4-cyclohexyl-3-benzoyloxymethyl)aniline (obtained as described in preparation 24) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as a glassy product.

Infrared absorption spectrum (film), amaxcm-1: 3280, 1715, 1655, 1520, 1480, 1457, 1275, 1258, 1115, 909. []2D3= = +8.4o(C=1.18, CHCl3).

Example 102. (S)-N-[2-tert-Butyl-5-(4-cyclohexyl-3-hydroxybutyl)-phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound 1-25 N)

13.3 ml of 0.58 M ethanol solution ethoxide sodium added to 1,62 g (2.57 mmol) of (S)-N-[2-tert-butyl-5-(4-cyclohexyl-3-benzoyloxymethyl)phenyl] -2-(9H-creature for 8 hours, after which it is heated under reflux for 2 hours, after this time the solvent is removed by distillation under reduced pressure and the resulting residue is mixed and then extracted with ethyl acetate. The extract is washed with water and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous magnesium sulfate and the solvent is removed by distillation under reduced pressure. The residue is purified column chromatography through 150 g of silica gel using 2:8 by volume mixture of acetonitrile and benzene as eluent. The concentrated eluate is recrystallized from diisopropyl ether and get to 1.14 g (yield 85%) indicated in the title compound, melting at 141-142oC.

Infrared absorption spectrum (KBr)maxcm-1: 3350, 3240, 1655, 1532, 1478, 1459, 1254, 760. []2D3= + 2.0o(C=1.09, CHCl3).

Example 103. N-[(9H-Xanthene-9-yl)methyl] -N'-[2-tert-butyl-5-(4-cyclohexyl-3-hydroboil)phenyl]urea (compound N 1-39)

Following the method similar to that described in example 40, but using N-[(9H-Xanthene-9-yl)methyl] -N'-[2-tert-butyl-5-(4-cyclohexyl-3-hydroboil)phenyl] urea (obtained as described in preparation 20) as the source is s in the form of crystals, melting at 156-157oC (after recrystallization from a mixture of methylene chloride and hexane).

Infrared absorption spectrum (KBr)maxcm-1: 3343, 2923, 2851, 1641, 1558, 1481, 1458, 1297, 1256, 1188, 756.

Example 104. N-[2-tert-Butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl]-2,2-diethyldodecanamide (compound N 5-19)

Following the method similar to that described in example 40, but using N-[2-tert-Butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2,2-diethyldodecanamide (obtained as described in preparation 46) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

infrared absorption spectrum (KBr)maxcm-1: 3395, 3304, 2923, 1651, 1509, 1479, 1448, 1363, 823.

Example 105. N-[2-tert-Butyl-5-(5-cyclohexyl-1-hydroxyphenyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-251)

Following the method similar to that described in example 14, but using 4-cyclohexylaniline bromide as starting product in the appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 121-122oC (after recrystallization from a mixture of UP>: 2922, 28521, 1655, 1643, 1578, 1527, 1481, 1458, 1410, 1257

Example 106. N-[2-tert-Butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl]-6,11-dihydrodiols[b,e]oxepin-11-carboxamide (compound N 2-19)

Following the method similar to that described in example 40, but using N-[2-tert-Butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl]-6,11-dihydrodiols[b,e] oxepin-11-carboxamide (obtained as described in preparation 47) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr)maxcm-1: 3407, 3278, 2922, 2872, 2851, 1655, 1519, 1497, 1448, 699.

Example 107. N-[2-tert-Butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl-2-(1-phenylcyclohexyl)ndimethylacetamide (compound N 3-13)

Following the method similar to that described in example 40, but using N-[2-tert-Butyl-5-[4-cyclohexyl-3-(tert-butyl-dimethylsiloxy) butyl] phenyl]-2-(1-phenylcyclohexyl)ndimethylacetamide (obtained as described in preparation 48) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr)maxcmthe ski - butyl]phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2870)

Following the method similar to that described in example 14, but using cyclohexylethylamine bromide and N-[2-(1,1-dimethyl-2-methoxyethyl)-6-3-(oksipropil)phenyl] -2-(9H - xanthene-9-yl)-ndimethylacetamide (obtained as described in preparation 26) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (film), amaxcm-1: 3260, 1667, 1509, 1480, 1459, 1254, 1096, 963, 758.

Example 109. (S)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]-phenyl}ethyl)-2 - cyclohexylethyl dihydrophosphate (compound N 1-2871)

Following the method similar to that described in example 79, but using (S)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)-2 - cyclohexylethyl)dibenzyl dihydrophosphate (obtained as described in preparation 49) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as a glassy product.

Infrared absorption spectrum (film), amaxcm-1: 3260, 1659, 1526, 1480, 1459, 1254, 1188, 1096, 988, 758.

Example 110. Sodium (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-2 - cyclohe)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-2 - cyclohexylethyl dihydrophosphate poluchenii, as described in example 109) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 1717, 1651, 1576, 1480, 1459, 1404, 1256, 1134, 1077, 909, 760.

Example 111. (S)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)-2 - cyclohexylethyl hydroptila (compound N 1-2872)

Following the method similar to that described in example 54, but using (S)-N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl[-2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 102) and phthalic anhydride as starting products in the appropriate ratio used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (film), amaxcm-1: 1717, 1651, 1576, 1480, 1459, 1404, 1256, 1134, 1077, 909, 760.

Example 112. Sodium (S)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)-2 - cyclohexylethyl phthalate (compound N 1-1104)

Following the method similar to that described in example 70, but using (S)-1-(2-{4-tert-butyl-3-[-2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)-2 - cyclohexylethyl (obtained as openlucht specified in the title compound in the form of a foamy product.

Infrared absorption spectrum (film), a maxcm-1: 3260, 1705, 1653, 1574, 1480, 1459, 1397, 1258, 1079, 909, 758.

Example 113. (S)-N-[2-tert-Butyl-5-(5-cyclohexyl-3-benzoyloxymethyl)-phenyl]-2- (9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1857)

Following the method similar to that described in example 21, but using (S)-2-tert-butyl-5-(5-cyclohexyl-3-benzoyloxymethyl)aniline as starting product in the appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr), maxcm-1: 3260, 2923, 2851, 1717, 1653, 1519, 1481, 1457, 1275, 1257, 1115, 759, 712.

[]2D3= +1.89o(C = 0.95, CHCl3).

Example 114. (S)-N-[2-tert-Butyl-5-(5-cyclohexyl-3-hydroxyphenyl)-phenyl]-2- (9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1)

Following the method similar to that described in example 102 but using (S)-N-[2-tert-butyl-5-(5-cyclohexyl-3-benzyloxyphenyl)phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 113) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 136-137oC (after perakis>1
: 3377, 2921, 1660, 1516, 1481, 1458, 1423, 1412, 1260, 756.

[]2D5= +0.55o(C=1,09, CHCL3).

Example 115. (R)-N-[2-tert-butyl-5-(5-cyclohexyl-3-hydroxyphenyl)-phenyl]-2- (9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1)

Following the method similar to that described in example 40, but using (R)-N-{ 2-tert-butyl-5-[5-cyclohexyl-3-(tert - butyldimethylsilyloxy)pentyl] phenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method described in preparation 11) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 136-137oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3377, 2921, 2849, 1660, 1516, 1481, 1458, 1423, 1412, 1260, 756.

[]2D5= -0.75o(C=1.07 CHCl3).

Example 116. (S)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]-phenyl}ethyl)-2 - cyclohexylethyl (compound N 1-2873)

Following the method similar to that described in example 79, but using (S)-[1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-ID)acetamido] phenyl} ethyl)-2 - cyclohexylethyl] the benzyl malonate (obtained as described in example 27) as the source of the product in the various product.

Infrared absorption spectrum (KBr),maxcm-1: 3260, 1729, 1632, 1480, 1459, 1302, 1254, 1156, 910, 760.

Example 117. Sodium (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)- acetamido]phenyl}ethyl)-2-cyclohexylethyl malonate (compound N 1-1101)

Following the method similar to that described in example 70, but using (S)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-2 - cyclohexylethyl gidromolot (obtained as described in example 116) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (film), amaxcm-1: 3250, 1717, 1653, 1605, 1480, 1459, 1300, 1256, 1256, 1156, 909, 758.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,70-0,90 (2H, multiplet); 1,13-of 1.80 (13H, multiplet); a 1.08 (9H, singlet); and 2.26-to 2.67 (4H, multiplet); 3,03 (0,2 H, doublet, J=16 Hz); 3,20 (0,2 H, doublet, J= 16 Hz); 3,23 (1,6 H, singlet); 4,70 (1H, triplet, J=7 Hz); 4.80 to 4,84 (0,2 H, multiplet); 4,92-5,00 (0,8 H, multiplet); 6,82 (11H, multiplet).

Example 118. N-[(1-Phenylcyclohexyl)methyl] -N'-[2-tert-butyl-5-(4 - cyclohexyl-3-hydroxybutyl)phenyl]urea (compound N 3-19)

Following the method similar to that described in example 40, but using N-[2-(1-fenell is, as described in preparation 22) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3344, 2922, 2852, 1641, 1558, 1448, 1418, 1364, 1253, 1073, 763, 701.

Example 119. Glycine (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)- 2-cyclohexylethyl ester hydrochloride (compound No. 1 - 1105)

of 0.21 ml of 4 n solution of hydrogen chloride in dioxane is added to 374 ml (0,547 mmol) 11-tert-butoxycarbonylamino (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)- 2-cyclohexylethylamine ether and the resulting mixture is stirred over night. The reaction mixture was then diluted with diethyl ether, and then add saturated aqueous solution of sodium bicarbonate. The mixture is stirred and the organic layer was separated and then washed with water; the solvent is then removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 15 g of silica gel using the method of stepwise elution, with a mixture of ethyl acetate and methanol varying from 100:0 to 100:3 by volume, which gives 277 mg of the free base, sootvetstvujushej is the Xan added to the free base and from the mixture to remove the solvent by distillation under reduced pressure, obtaining specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2853, 1747, 1655, 1576, 1522, 1481, 1458, 1365, 1254.

Example 120. N, N-Dimethylglycine (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)- 2-cyclohexylethyl ester (compound N 1-2874)

Following the method similar to that described in preparation 25, but using (S)-N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 102) and N, N-dimethylglycinamide as the original product, in an appropriate amount used in cooking, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2853, 1736, 1655, 1578, 1522, 1479, 1458, 1255, 1194.

Example 121. N,N-Dimethylglycine (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)- 2-cyclohexylethyl ester hydrochloride (compound No. 1 - 1106)

Following the method similar to that described in example 119, but using N,N-dimethylglycine (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)- 2-cyclohexylethyl ester (obtained as described in example 120), and 4 N. the solution is this preparation, get listed in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2853, 1743, 1655, 1576, 1522, 1481, 1458, 1414, 1363, 1255.

Example 122. (S)-1-(2-{4-tert-Butyl 3-{2-(9H-xanthene-9-yl)acetamido]-phenyl}ethyl)- 2-cyclohexylethyl hydrogelators (compound N 1-2875)

Following the method similar to that described in preparation 56, but using (S)-N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 102) and glutaric anhydride as starting materials, in the appropriate ratio used in this preparation, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2853, 1730, 1709, 1655, 1649, 1641, 1578, 1524, 1479, 1458, 1254.

Example 123. Sodium (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)-acetamido]phenyl}ethyl)- 2-cyclohexylethyl glutarate (compound N 1-1103)

Following the method similar to that described in example 70, but using (S)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)- 2-cyclohexylethyl hydroglycolic (obtained as described in example 122) as the original product, in an appropriate quantity is 2">

Infrared absorption spectrum (KBr),maxcm-1: 29224, 2853, 1720, 1655, 1576, 152226, 1479, 1458, 1410, 1302, 1254.

Example 124. N-[2-Isopropyl-6-(6-cyclohexyl-3-oxo-2-hexenyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2976)

The suspension containing 239 g (0,620 mmol) of N-(2-isopropyl-6-formylphenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 29), 347 mg (0,682 mmol) (5-cyclohexyl-2-oxobutyl)triphenylphosphonium bromide and 66 mg (0,652 mmol) of triethylamine in 10 ml of tetrahydrofuran is heated under reflux for 4 hours, after this time the reaction mixture is cooled to room temperature and then diluted with diethyl ether; the diluted mixture was then washed with diluted hydrochloric acid. The organic phase is separated and washed with water until neutral, then dried and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 25 g of silica gel using 4:1:1 by volume mixture of hexane, methylene chloride and ethyl acetate as eluent, to obtain 223 mg (yield 67%) indicated in the title compound as crystals, melting at 190 - 1191oC (after recrystallization from a mixture of methylene chloride and hexar CLASS="ptx2">

Example 125. N-[2-Isopropyl-6-(6-cyclohexyl-3-hydroxyhexyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1387)

Following the method similar to that described in example 8, but using N-2-isopropyl-6-(6-cyclohexyl-3-oxo-2-hexenyl)phenyl - 2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 124) as the original product, in an appropriate amount used in this example, the original product catalytically hydronaut, after which ketogroup reduced to a hydroxyl group in the same way as described in example 9, obtaining specified in the title compound as crystals, melting at 142 - 143oC (after recrystallization from a mixture of diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 29224, 22851, 1655, 1634, 1578, 1518, 1479, 1458, 1300, 1255.

Examples 126 - 152.

Repeat the method described in example 35 or 21, except that as the source of the product using the appropriate aniline derivative, in an appropriate amount used in this example, to obtain the compounds defined in the following table 8. The number of connections (N Conn.), listed in the table. 8, are the rooms used for the join table.CTR - Infrared absorption spectrum

MI - methylene chloride

iPr2O - Diisopropyl ether

Hxa - Hexane

AcOE - ethyl Acetate

AT - Acetone

Other abbreviations are defined here in relation to the table. 1 - 5.

In the column "so square", when the product is not crystalline, its physical form, such as "butter".

Examples 159 - 161. Repeat the method described in example 14, except that as the original product using N-(2-isopropyl-6-formylphenyl)-2-(9H-xanthene-9-yl)acetamide", she in an appropriate amount similar to that used in that example, to obtain the compounds shown in table. 10.

Examples 162 - 188. Repeat the method described in example 22, except that as the original product using the compound obtained in the corresponding example 126 - 152 in an appropriate amount similar to that used in that example, to obtain the compounds shown in the following table 11, the recovery ketogroup.

1) a certain method of Noyola

2) caused by polymorphism

Example 189. (S)-N-[2-tert-Butyl-5-(6-cyclohexyl-3-hydroxyhexyl)-phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-49)

Following the SPO is XI-hexyl] phenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide as the original product, in the corresponding amount used in this example, get mentioned in the title compound as crystals, melting at 125-127oC (after recrystallization from diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 1658, 1518, 1480, 1458, 1256, 763, 756.

[]2D5= +1.9o(C = 1.0, CHCl3).

Example 190. (R)-N-[2-tert-Butyl-5-(6-cyclohexyl-3-hydroxyhexyl)-phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-49)

190 (I) (R)-N-[2-tert-Butyl-5-(6-cyclohexyl-3-benzyloxyethyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide.

Following the method similar to that described in preparation 24 (II), but using (S)-N-[2-tert-butyl-5-(6-cyclohexyl-3-hydroxyphenyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 189) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

190 (II) (R)-N-[2-tert-Butyl-5-(6-cyclohexyl-3 hydroxyhexyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide

5 ml of I n sodium hydroxide solution are added to a solution of 460 mg (0.70 mmol) of (R)-N-[2-tert-butyl-5-(6-cyclohexyl-3-benzyloxyethyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (Paul is the time of the reaction mixture to remove the solvent by distillation under reduced pressure, dilute then diethyl ether, and the residue is first diluted with ethyl acetate and then acidified with 2 N. aqueous hydrochloric acid. The organic phase delay and then washed with aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride, in that order. The mixture is dried over anhydrous sodium sulfate and the solvent then removed by distillation under reduced pressure. The resulting residue is purified by recrystallization from diisopropyl ether to obtain 180 mg (yield 47%) indicated in the title compound as crystals, melting at 128-129oC.

Infrared absorption spectrum (KBr), maxcm-1: 1658, 1515, 1480, 1458, 1255, 758.

[]2D5= -1.2o(C=1.0, CHCl3).

Example 191. (S)-N-[2-tert-Butyl-5-(7-cyclohexyl-3-hydroxyacyl)-phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-73)

A mixture of 1.20 g (a 1.96 mmol) of (S)-N-{ 2-tert-butyl-5-[7-cyclohexyl-3- (methoxyethoxy)heptyl]phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 43) in 12 ml of 4 n solution of hydrogen chloride in dioxane is stirred for 30 minutes and then the solvent is removed by distillation under reduced pressure, the pH of the solution set to 7 by addition of an aqueous solution T saturated aqueous sodium chloride. The washed extracts are dried and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 4: 1 by volume mixture of hexane and ethyl acetate as eluent, to obtain 0.9 g specified in the connection header in the form of oil. The oil is triturated in hexane and the resulting crystalline product is collected from the receipt of 0.83 g (yield 75%) specified in the header of the product in the form of crystals.

Infrared absorption spectrum (KBr),maxcm-1: 1656, 1524, 1479, 158, 1255, 759.

[]2D5= + 0.97o(C=1.03, CHCl3).

Example 192. (R)-N-[2-tert-Butyl-5-(7-cyclohexyl-3-hydroxyacyl)-phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-73).

Following the method similar to that described in example 190 (I), but using (S)-N-[2-tert-butyl-5-(7-cyclohexyl-3 hydroxyethyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 191) as the original product, in an appropriate amount used in this example, receive (R)-benzoylpropionate the original product. It hydrolyzing method similar to that described in example 190 (II) obtaining specified in the title compound as crystals, melting PR is SUB> cm-1: 1656, 1524, 1479, 1458, 1255, 759.

[]2D5= +0/97o(C=1.03, CHCl3).

Example 193. N-{2-[3-(2-Ethyl-1-imidazolyl)propyl]oxymethyl-6-methyl-thiophenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2906)

Following the method similar to that described in example 1, but using 2-ethylimidazole as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 159-160oC (after recrystallization from a mixture of hexane and methylene chloride).

Infrared absorption spectrum (KBr),maxcm-1: 3266, 1676, 1649, 1600, 1576, 1518, 1493, 1481, 1457, 1433, 1366, 1258.

Example 194. N-{2-[3-(1-Imidazolyl)propyl]oxymethyl-6-methylsulphonyl-methyl} -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1989) and N-{2-[3-(1-imidazolyl)propyl]oxymethyl-6-methylsulfinyl-fetal} -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1990)

224 mg (0.71 mmol) of m-chlorbenzoyl acid (55% purity) is added dropwise within 3 minutes to a solution of 200 mg (0.40 mmol) N-{2-[3-(1-imidazolyl)propoxy]methyl-6-methylthiophenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 1) in 15 ml of methylene chloride, and the resulting mixture is stirred for 2.5 hours after this time p is i.i.d. solution was washed with saturated aqueous sodium bicarbonate and water, in this procedure. The organic phase is dried and the solvent is removed by distillation under reduced pressure. The residue is purified column chromatography through 12 g of silica gel using the method of gradient elution with mixtures of methylene chloride and methanol in ratios from 100:1 to 100:6 by volume as the eluent, and obtain 114 g (yield 54%) of the less polar sulfonylurea derivative (compound N 1-1989) and 87 g (yield 42%) of the more polar sulfanilimide derivative (compound N 1-1990), respectively, both in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1:

(connection N 1-1989) 3249, 1679, 1600, 1577, 1507, 1480, 1458, 1309, 1255, 1127, 961, 760.

(connection N 1-1990) 3222, 3165, 3108, 1680, 1600, 1576, 1509, 1480, 1457, 1256, 1110, 1096, 1080, 1052, 1034.

Example 195 N-{2-[3-(1-Imidazolyl)propyl]oxymethyl-6-isopropylphenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2907)

Following the method similar to that described in example 1, but using N-[2-isopropyl-6-[(3-hydroxypropyl)oxymethyl] phenyl]-2 -(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 31) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 131 the red absorption spectrum (KBr),maxcm-1: 2960, 1670, 1480, 1460, 1250, 1080.

Example 196. N-{2-[3-(1-Imidazolyl)propyl]oxymethyl-6-isopropylphenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide hydrochloride (compound N 1-1481)

of 0.39 ml of 4 n solution of hydrogen chloride in dioxane are added to a solution of 192 mg (0,39 mmol) N-{2-[3-(1-imidazolyl)propyl]oxymethyl-6-isopropylphenyl}-2-(9H-xanthene-9-yl)-ndimethylacetamide (obtained as described in example 195) in 2 ml of methylene chloride, and the resulting mixture to remove the solvent by distillation under reduced pressure. The resulting residue is dissolved in a small amount of dioxane and, after addition of water, the resulting mixture lyophilized to obtain 206 mg specified in the connection header in the form of powder.

Infrared absorption spectrum (CHCl3),maxcm-1: 2960, 1670, 1480, 1460, 1250, 1090.

Example 197. N-{ 2-Isopropyl-6-[3-(1-imidazolyl)propyl] phenyl]-2 -(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2028)

Following the method similar to that described in example 1, but using N-[2-isopropyl-6-(3-hydroxypropyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 30) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of crystals, ASS="ptx2">

Infrared absorption spectrum (KBr),maxcm-1: 3272, 2963, 1645, 1525, 1480, 1457, 1257, 757.

Example 198. N-(2-Isopropyl-6-[3-(1-imidazolyl)propyl]phenyl}-2-(9H - xanthene-9-yl)ndimethylacetamide hydrochloride (compound N 1-2027)

Following the method similar to that described in example 196, but using N-(2-isopropyl-6-[3-(1-imidazolyl)propyl] phenyl} -2-(9H-xanthene - 9-yl)ndimethylacetamide (obtained as described in example 197) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (CHCl3),maxcm-1: 2960, 1660, 1570, 1480, 1458, 1250.

Example 199. N-(2-Isopropyl-6-[2-(1-imidazolyl)ethyl]oxymethylphenyl}-2-(OH-xanthene-9-yl) ndimethylacetamide (compound N 1-2908).

Following the method similar to that described in example 1, but using N-[2-isopropyl-6-(2-hydroxyethyl)oxymethylphenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in preparation 32) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (CHCl3),maxcm-1: And hydrochloride (compound N 1-1484)

Following the method similar to that described in example 196, but using N-(2-isopropyl-6-[2-(1-imidazolyl)ethyl]coimetidine}-2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 199) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorbing spectrum (CHCl3),maxcm-1: 2960, 1670, 1480, 1458, 1250, 1120, 1090.

Example 201. N-[2-Isopropyl-6-(1-imidazolidinyl)phenyl]-2-(9H-rcfynty-9-ylacetamide (compound N 1-2024)

A suspension of 500 g (1,23 mmol) of N-(2-isopropyl-6-chloromethylene)- 2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 28 (iv)), 847 mg (12.3 mmol) of imidazole and 277 mg (1.9 mmol) of sodium iodide in 10 ml of N, N-dimethylformamide was stirred at 90oC for 2 h, and then the temperature is reduced to room temperature. The resulting mixture was diluted with ethyl acetate. The diluted mixture was washed several times with water and once with saturated aqueous sodium chloride. The organic phase is dried over anhydrous sodium sulfate and then the solvent is removed by distillation under reduced pressure. The resulting residue is triturated in a mixture of diethyl ether and hexane, and obtained the crystals, melting at 193-195" (after recrystallization from a mixture of methanol, diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 2961, 1671, 1508, 1475, 1458, 1250, 1236, 758.

Example 202. N-[2-Isopropyl-6-(1-imidazolidinyl)phenyl] -2-(9H-xanthene - 9-yl)ndimethylacetamide hydrochloride (compound N 1-2023)

Following the method similar to that described in example 196, but using N-(2-isopropyl-6-(1-imidazolidinyl)phenyl]-2-(encantan-9-yl) ndimethylacetamide (obtained as described in example 201) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (CHCl3),maxcm-1: 2960, 1670, 1480, 1458, 1250, 1120, 1090.

Example 203. N-[2-Isopropyl-6-(1-benzimidazolyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2001)

Following the method similar to that described in example 201, but using the benzimidazole as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 244-245oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrarail-6-(1-benzimidazolyl)phenyl]2-(9h-xanthene-9-yl)ndimethylacetamide hydrochloride (compound N 1-2002)

Following the method similar to that described in example 196, but using N-[2-isopropyl-6-(1-benzimidazolyl)phenyl] -2-(9H-xanthene - 9-yl)ndimethylacetamide (obtained as described in example 203) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (CHCl3),maxcm-1: 2960, 1670, 1576, 1510, 1480, 1458, 1250.

Example 205. N-(2-Methyl-6-[3-(1-imidazolyl)propyl]oxymethylphenyl}- -2-(9H-xanthene-9-yl)ndimethylacetamide hydrochloride (compound N 1-2909)

Following the method similar to that described in example 35, but using 2-methyl-6-{ [3-(1-imidazolyl)propyl] oxymethyl} aniline (obtained as described in preparation 45) as the original product, in an appropriate amount used in this example, carry out the acylation with getting amide derivative of the original compound that is converted into indicated in the title hydrochloride as crystals, melting at 109-110oC (after recrystallization from a mixture of ethanol and diethyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 1652, 1632, 1576, 1520, 1481, 1481, 1458, 1258, 1086, 763.

Example 206. N-[2-Isopropyl-6-(4-cyclohe the WMD in preparation 19, oxidize N-[2-isopropyl-6-(3-hydroxypropyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 30) to obtain N-[2-isopropyl-6-(3-oxopropyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide, which then interacts with the Grignard reagent is similar to the method described in example 14, to obtain specified in the connection header in the form of crystals, melting at 148oC (after recrystallization from a mixture of diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3262, 2923, 1648, 1523, 1481, 1457, 1259, 757.

Example 207. N-(2-Tert-Butyl-5-[4-cyclohexyl-3-(hydroxymethyl)butyl] phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1984)

Following the method similar to that described in example 22,restore N-[2-tert-butyl-5-(4-cyclohexyl-3-formylmethyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 33) to obtain the specified title compound as crystals, melting at 130-131oC (after recrystallization from a mixture of diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 2922, 2851, 1736, 1655, 1603, 1578, 1524, 1479, 1458, 1416, 1363, 1255.

Example 208. N9[2-tert-Butyl-5-(5-cyclohexyl-1-benzoyloxymethyl-1 - pentenyl)acetamido] phenyl]methyltriphenylphosphonium bromide (obtained, as described in preparation 34) in 15 ml of tetrahydrofuran is subjected to ice-cooling, and added dropwise over 3 min 2.10 ml (2, 10 mmol) tertrahydrofuran ring solution of sodium hexamethyldisilazide. After 35 min to the mixture add a solution of 511 mg (1,86 mmol) 2-benzyloxy-5-cyclohexyl-2-pentanone (obtained as described in preparation 35) in 5 ml of tetrahydrofuran. The resulting mixture was stirred for 10 minutes under ice cooling, 35 min at room temperature and finally at 50oC for 4.5 hours, after this time the temperature of the reaction mixture is reduced to room temperature and then add saturated aqueous solution of ammonium chloride to stop the reaction. The reaction mixture was then diluted with ethyl acetate, and the diluted mixture was washed with water and saturated aqueous sodium chloride in this order. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 100 g of silica gel using 1:4 by volume mixture of ethyl acetate and hexane as eluent, to obtain 781 mg (yield 65%) indicated in the title compound in the form of a foamy product.

Example 209. N-(2-tert-Butyl-5-[5-cyclohexyl-2-(hydroxymethyl)- pentyl] phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1979)

A solution of 1.54 g (2,30 mmol) N-[2-tert-butyl-5-(5-cyclohexyl - 2-benzoyloxymethyl-1 pentyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 208) in 15 ml of ethanol vigorously stirred in a stream of hydrogen in the presence of 1.54 g of 10% by weight palladium on coal at room temperature for 260 min and then at 40oC for 2 hours, after this time the reaction mixture is filtered and the filtrate concentrated by distillation under reduced pressure. The concentrate is column chromatography through 75 g of silica gel using 2:3 by volume mixture of ethyl acetate and hexane as eluent. The fractions containing the desired compound with a small amount of impurities are combined and concentrated under reduced pressure. Concentrate again purified column chromatography under the same conditions as described above to obtain 1.19 g (yield 90%) specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (film), amaxcm-1: 3260, 1651, 1518, 1480, 1457, 1364, 1256, 1096, 1071, 754.

Example 210. N-[2-tert-Butyl-5-(7-cyclohexyl-2-benzoyloxymethyl-1-heptenyl)phenyl]-2 - is 1-benzyloxy-7-cyclohexyl-2-heptanon as the original product, in the corresponding amount used in this example, get mentioned in the title compound as crystals, melting at 110oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3222, 2925, 2853, 1641, 1536, 1481, 1457, 1258, 964, 759, 753.

Example 211. N-(2-tert-Butyl-5-[7-cyclohexyl-2-(hydroxymethyl)heptyl] phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1982)

Following the method similar to that described in example 209, but using N-[2-tert-butyl-5-(7-cyclohexyl-2-benzoyloxymethyl-1-heptenyl)phenyl] - 2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 210) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3396, 3269, 29243, 2851, 1655, 1523, 1481, 1458, 1256, 758.

Example 212. N-[2-tert-Butyl-5-(4-cyclohexyl-2-benzoyloxymethyl-1-butenyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1954)

Following the method similar to that described in example 208, but using 1-benzyloxy-4-cyclohexyl-2-butanone as the original product, in an appropriate amount, COI the sorption spectrum (liquid film), maxcm-1: 2922, 2851, 1643, 1576, 1514, 1479, 1456, 1410, 1365, 1255.

Example 213. N-[2-tert-Butyl-5-[4-cyclohexyl-2-(hydroxymethyl)butyl] phenyl]2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1977)

Following the method similar to that described in example 209, but using N-[2-tert-butyl-5-(4-cyclohexyl-2-benzoyloxymethyl-1-butenyl) phenyl]2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 212) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2922, 2851, 1655, 1578, 1560, 1524, 1479, 1458, 1419, 1363, 1255.

Example 214. N-{2-tert-Butyl-5-[4-cyclohexyloxy-2 - (hydroxymethyl)butyl] phenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2186)

Should the method similar to that described in example 208, but using 1-benzyloxy-4-cyclohexyloxy-2-butanone (obtained as described in preparation 37), it is subjected to the Wittig reaction. The resulting product then reacts in the manner similar to that described in example 209, which gives specified in the title compound in the form of a foamy product.

Infrared absorption spectrum (film), amaxcm-1: 3260, 1653, the antennas-9-yl)ndimethylacetamide (connected N 1-2387)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(4-cyclohexyloxy-3-tert - butyldimethylsilyloxy)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method described in preparation 11) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr), maxcm-1: 3270, 2932, 1655, 1522, 1481, 1458, 1256, 1118, 1096, 760.

Example 216. N-[2-tert-butyl-5-(5-cyclohexyloxy-3-benzyloxy-1- -pentenyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (connected N 1-1945)

Following the method similar to that described in example 208, but using 1-benzyloxy-4-cyclohexanedimethanol (obtained as described in example 38) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (film), amaxcm-1: 1655, 1520, 1480, 1459, 1364, 1256, 1096, 758.

Example 217. N-[2-tert-Butyl-5-(5-cyclohexyloxy-3- -hydroxyphenethyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2390)

Following the method similar to that described in paid (received as described in example 216) obtaining specified in the connection header in the form of a foamy product.

Infrared adsorption spectrum (film), amaxcm-1: 3250, 1655, 1522, 1480, 1459, 1354, 1256, 1190, 1094, 758.

Example 218. N-[2-tert-Butyl-5-(4-cyclohexylmethoxy-3- -hydroxybutyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2388)

and

N-{ 2-tert-butyl-5-[3-cyclohexylmethoxy-3 - (hydroxymethyl)propyne] phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2189(

(I) 4 l epirate of boron TRIFLUORIDE are added to a solution of 73 mg (0,165 mmol) N-[2-tert-butyl-5-2-(oxiran-2-yl)ethyl] -2-(9H-xanthene- -9-yl)ndimethylacetamide (obtained as described in preparation 39) and 41 mg (0,359 mol) of cyclohexylmethanol in 2 ml of methylene chloride and the resulting mixture is stirred for 280 minutes after this time it was concentrated by distillation under reduced pressure. Thus obtained colorless oil as residue dissolved in 2 ml of ethyl acetate, 0.2 ml of pyridine and 0.1 ml of acetic anhydride are added to a solution, and the mixture was left for 45 minutes, the Reaction mixture was then diluted with ethyl acetate, and the diluted mixture was washed with 2 N. aqueous hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate and saturated in varicel removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 10 g of silica gel using 1:3 by volume mixture of ethyl acetate and hexane as eluent, yielding 62 mg (yield 63%) of a mixture of acetyl derivatives containing the compound N 1-2188 and connection N 1-2189 as a resinous product.

(II) 15 mg (0.28 mmol) of sodium methoxide are added to a solution of 72 mg (0.12 mmol) of the mixture of products obtained as described in stage (I) above in 2 ml of methanol and the resulting mixture was stirred at 50oC for 70 minutes, after this time the reaction mixture is concentrated by distillation under reduced pressure, and the concentrate is diluted by distillation at lower pressure, and the concentrate is diluted with ethyl acetate. The diluted mixture was washed with saturated aqueous ammonium chloride and saturated aqueous sodium chloride, in that order. Limited phase is dried over anhydrous magnesium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 40 g of silica gel using 2:3 by volume mixture of ethyl acetate and hexane as eluent, giving a mixture containing less polar compound which is the compound N 1-2388, and the more polar compound, above, to obtain 44 mg (yield 66%) of compound N 1-2388 and 20 mg (30% yield) of compound N 1-2189, both in the form of a resinous product.

Infrared absorption spectrum (liquid film),maxcm-1:

(connection N 1-2388) 3390, 3270, 1653, 1522, 1480, 1458, 1256, 1121, 909, 758;

(connection N 1-2389) 3400, 3270, 1653, 1522, 1480, 1458, 1256, 1117, 909, 758.

Example 219. N-{2-tert-Butyl-5-[4-(2-cyclohexylmethoxy)-3 - hydroxybutyl]phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2389)

Following the method similar to that described in example 218, but using 2-cyclohexylethane as the original product, in an appropriate amount used in this example, get mentioned in the title compound as a glassy product.

Infrared absorption spectrum (film), amaxcm-1: 3270, 1655, 1522, 1480, 1459, 1256, 1094, 758.

Example 220. -(S)-1-(2-{4-tert-Butene-3-[2-(9H-xanthene-9-yl) acetamido] phenyl}ethyl)-2-cyclohexylethyl L-aspartate hydrochloride (compound N 1-1548)

Following the method similar to that described in preparation 25, but using dichlorophenylamino salt-tert-butoxycarbonyl-L-aspartate and (S)-N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 102) as shotwells specified in the header of the connection, 3 ml of 4 n solution of hydrogen chloride in dioxane is added to 292 mg (0,366 mmol) of free base and the resulting mixture left at room temperature for 20 hours after which time the solvent is removed by distillation under reduced pressure, and obtain 198 mg specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (film), amaxcm-1: 3240, 1746, 1651, 1618, 1482, 1459, 1254, 909, 760.

Example 221. N-Lysine-(S)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)- 2-cyclohexylethylamine ether dihydrochloride (compound N 1-1549)

Following the method similar to that described in preparation 25, but using dicyclohexylamine salt of N,N'-di-tert-butoxycarbonyl-L-lysine and (S)-N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 102) as the original products, in the appropriate ratio used in this example, the gain derived ether derivative of L-lysine. Subjected to removal of the protective group by the method described in example 220, obtaining specified in the connection header in the form penoobraznogo product.

Infrared absorption spectrum (film), amaxcm-1
Following the method similar to that described in preparation 25, but using N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 12) and benzyl N-benzyloxycarbonyl-L-glutamate, get a glutamate derivative. 293 mg (of 0.333 mmol) glutamate derivative dissolved in 10 ml of methanol and then added to 0.88 ml of a solution obtained by diluting 4 n solution of hydrogen chloride in dioxane ten times relative to the initial volume. The resulting mixture was vigorously stirred in a hydrogen atmosphere and in the presence of 60 mg of 10% by weight palladium on coal for 1 h after which time the catalyst is filtered off and washed with methanol. The filtrate and wash water are combined in the solvent is removed by distillation under reduced pressure to obtain 220 mg specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (film), amaxcm-1: 3230, 1732, 1651, 1520, 1480, 1458, 1418, 1256, 758.

Example 223. -1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl} ethyl)-2 - cyclohexylethyl carboxymethylchitin (compound N 1-1551)

A solution of 200 mg of N-[4-tert-butyl-5-(4-cyclohexyl-3-{9-[(benzyloxycarbonyl)methylthio] azelaic from 0.44 ml of formic acid and the resulting mixture was vigorously stirred under heating at 50oC for 3 h in the presence of 200 mg of palladium mobiles. After this time the reaction mixture is allowed to cool to room temperature. The reaction mixture was then filtered using filter Celite (trade mark) and the catalyst washed with matanya. The filtrate and wash water are combined and the solvent is removed by distillation under reduced pressure.

The resulting residue is purified column chromatography through 10 g of silica gel using the method of gradient elution with a mixture of methylene chloride and methanol varying from 100:5 to 100:15 by volume as the eluent, to obtain 121 mg (yield 69%) indicated in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 1726, 1602, 1577, 1481, 1458, 1416, 1256, 760.

Example 224. Sodium salt of 1-(2-{4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-2 - cyclohexylethyl of carboxymethylcysteine (compound N 1-1552)

Following the method similar to that described in example 70, but using-1-(2-{ 4-tert-butyl-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-2 - cyclogeranyl carboxymethylchitin (obtained as described in example 223) as the original product, in an appropriate amount used is maxcm-1: 2923, 1722, 1641, 1602, 1481, 1457, 1393, 1292, 1257, 760.

Example 225. -1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-2-cyclohexylethyl karboksimetilsellulozdan (compound N 1-1553)

Following the method similar to that described in example 223, but using N-[2-tert-butyl-5-(4-cyclohexyl-3-{2-[(benzyloxycarbonyl)methylsulphonyl] acetoxy}butyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 41), get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2925, 1733, 1633, 1480, 1458, 1398, 1320, 1255, 760.

Example 226. Sodium salt of 1-(2-{4-tert-butyl-3-[2-9H-xanthene-9-yl)acetamido] phenyl} ethyl)-2-cyclohexylethyl of karboksimetilsellulozdan (compound N 1-1554)

Following the method similar to that described in example 70, but using-1-(2-{ 4-tert-butyl-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl-2-cyclohexylethyl karboksimetilsellulozdan (obtained as described in example 225) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-l)-2-cyclohexylethyl karboksimetilcellyuloze (compound N 1-1555)

Following the method similar to that described in example 223, but using N-[2-tert-butyl-5-(4-cyclohexyl-3-{ 2-[(benzyloxycarbonyl) methylsulphonyl]acetoxy} butyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 41), get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 1729, 1605, 1481, 1458, 1414, 1385, 1298, 1256, 1034, 760.

Example 228. Sodium salt of 1-(2-{4-tert-butyl-3-[2-(9H-kanren-9-yl)acetamido] phenyl} ethyl) -2-cyclohexylethyl of karboksimetilcellyuloze (compound N 1-1556)

Following the method similar to that described in example 70, but using - 1-(2-{ 4-tert-butyl-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl) -2-cyclohexylethyl karboksimetilcellyuloze (obtained as described in example 225) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2852, 1727, 1640, 1615, 1481, 1458, 1384, 1295, 1257, 1033, 760.

Example 229. -1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl} ethyl) -2-cyclohexylethyl 4-(morpholinomethyl)benzoate (compound N 1-1557)

SIL)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (received as described in example 12) and 4-morpholinobutyrophenone acid as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 123-125oC (after recrystallization from diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 1713, 1650, 1480, 1457, 1274, 1258, 1116, 1097, 869, 758.

Example 230. N-[2-tert-Butyl-5-(3-carboxybenzeneboronic-4 - cyclohexylmethyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1558)

Following the method similar to that described in example 79 N-{2-tert-butyl-5-[3-(benzyloxycarbonyl)methoxycarbonylamino-4-cyclohexyl - butyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 42), dibenzyline obtaining specified in the title compound as crystals, melting at 143-145oC (after recrystallization from a mixture of ethyl acetate and hexane)

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2852, 1745, 1629, 1481, 1458, 1366, 1255, 1118, 1097, 760.

Example 231. Sodium salt of N-[2-tert-butyl-5-(3 - carboxybenzeneboronic-4-cyclohexylmethyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-1559)

Following the manner similar to the-2-(9H-xanthene-9-yl)ndimethylacetamide (received as described in example 230) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of a powder.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2852, 1742, 1626, 1577, 1518, 1481, 1458, 1423, 1257, 760.

Example 232. N-[2-tert-Butyl-5-[3-(4-carboxyphenoxy)carbonyloxy-4-cyclohexylmethyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1560)

Following the method similar to that described in preparation 42, but using 4-(benzyloxycarbonyl)METHYLPHENOL and N-[2-tert-butyl-5-(4 - cyclohexyl-3-hydroxybutyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 12) as starting materials, in the appropriate ratio used in this example, receive carbonate derivative. It dibenzyline manner similar to that described in example 79, obtaining specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2853, 1757, 1710, 1509, 1481, 1458, 1255, 1218, 1193.

Example 233. Example 233. Sodium salt of N-[2-tert-butyl-5-[3-(4 - carboxyphenoxy)carbonyloxy-4-cyclohexylmethyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1561)

After the XI-4-cyclohexylmethyl) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (received as described in example 230) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2852, 1756, 1657, 1600, 1577, 1509, 1481, 1458, 1256, 1217, 1198.

Example 234. N-[2-tert-butyl-5-[3-(1-carboxymethoxy)carbonyloxy-4 - cyclohexylmethyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1562)

Following the method similar to that described in preparation 42, but using benzyl L-lactate and N-[2-tert-butyl-5-(4-cyclohexyl-3 - hydroxybutyl)phenyl] -2-(9H-Kasten-9-yl)ndimethylacetamide (obtained as described in example 12) as starting materials, in the appropriate ratio used in this example, receive carbonate derivative. It dibenzyline manner similar to that described in example 79, obtaining specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 1744, 1480, 1458, 1259, 761.

Example 235. Sodium salt of N-[2-opt-butyl-5-[3-(1 - carboxy)carbonyloxy-4-cyclohexylmethyl)phenyl] -2-(9H-xanthene - 9-yl)ndimethylacetamide (compound No. 1 -1563)

Following the method similar to that described in example 70, but using N - as described in example 234) as the original product, in the corresponding amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 3270, 1728, 1614, 1577, 1522, 1481, 1458, 1415, 1366, 1259.

Example 236 N-{2-tert-Butyl-5-[3-(5-methyl-2-oxo,3-dioxolan-4-yl)- methoxycarbonylamino-4-cyclohexylmethyl] phenyl} -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1564)

Following the method similar to that described in preparation 42, but using (5-methyl-2-oxo-1.3-dioxolan-4-yl)methyl alcohol and N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl]-2- (9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 12 as the original products, in the appropriate ratio used in this example, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 1822, 1745, 1657, 1480, 1458, 1257, 1226, 788, 761.

Example 237. N-(Tret-Butyl-5-{ 3-[2-(1-imidazolyl)acetoxy] -4 - cyclohexylmethyl} phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide hydrochloride (compound N 1-1565)

(i) N-(2-tert-Butyl-5-{3-[2-(1-imidazolyl)acetoxy]-4 - cyclohexylmethyl} phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide

Suspension, sotiriadou mg (0.80 mmol) of N-[2-tert-butyl-5- (cyclohexyl-is silbermedaille, 142 l (of 1.76 mmol) of pyridine, 20 mg (0.16 mmol) of 4-(N,N-dimethylamino)pyridine and 156 mg (0.96 mmol) of the hydrochloride of 2-(1-imidazolyl) acetic acid in 10 ml of methylene chloride, stirred for 3 days. Upon expiration of this time, insoluble products is filtered off and the filtrate is washed with water and saturated aqueous sodium chloride, in that order, then dried over anhydrous sodium sulfate. The solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 75 g of silica gel using 1:4 by volume mixture of ethyl acetate and hexane as eluent, obtaining 507 mg (quantitative yield) specified in the title compounds as colorless foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2926, 2853, 1748, 1655, 1510, 1480, 1458, 1256, 1080, 758, 731.

(ii) N-(2-tert-Butyl-5-{ 3-[2-(1-imidazolyl)acetoxy]-4 - cyclohexylmethyl} phenyl)-2-(9H-xanthene-9-yl)-ndimethylacetamide [obtained as described in stage (i) above] in 3 ml of diethyl ether and the resulting crystals are collected by filtration and washed with diethyl ether. The crystal clear liquid chromatography high resolution through ODS (120 30 mm 250 mm) using a 3: 1 by volume mixture of acetone what rucenim 170 mg (yield 85%) indicated in the title compound as colourless crystals, melting at 125 - 133oC.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2853, 1746, 1655, 1576, 1522, 1482, 1459, 1258, 1230, 758.

Examples 238 - 243. Repeat the method described in preparation 25, except that as the source of the product using the appropriate compound obtained in the respective examples 213, 209, or 211 in an appropriate amount similar to that used in that example, to obtain the corresponding derivative of benzyl ether, which is then dibenzyline manner similar to that described in example 79, to obtain the compounds according to examples 238, 240 and 242. Connection examples 238, 240 and 242 are then converted into their sodium salt according to the method similar to that described in example 70 (examples 239, 241 and 243). Details are listed in the following table. 12. Abbreviation previously explained above.

Example 244. N-(2-tert-Butyl-5-{3-[2-(carboxymethoxy)acetoxy]-4 - cyclohexylmethyl}phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1566)

Following the method similar to that described in preparation 25, but using benzyl N-[2-(tert-butyl-5-(clogical-3 - hydroxybutyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 12) and 2-(benzyloxycarbonyloxy)acetic kesisoglou benzyl ether. It then dibenzyline manner similar to that described in example 79, obtaining specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 1744, 1652, 1480, 1458, 1253, 1217, 1142, 760.

Example 245. Sodium salt of N-(Tret-butyl-5-{3-[2- (carboxymethoxy)acetoxy] -4-(cyclohexylmethyl} phenyl-2- (9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1556)

Following the method similar to that described in example 70, but using N-(2-tert-butyl-5-{ 3-[2-(carboxymethoxy)acetoxy] -4 - cyclohexylmethyl}phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 244) as the original product, in an appropriate amount used in cooking, get mentioned in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 3249, 1741, 1642, 1615, 1577, 1523, 1481, 1458, 1421, 1365, 1338, 1300, 1255, 1137.

Example 246. (S)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)-2 - cyclohexylmethyl hydrosylate (compound N 1-1127)

Following the method similar to that described in preparation 25, but using (S)-N-[2-tert-butyl-5-(6-cyclohexyl-3 - hydroxyhexyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 189) as a researcher is ensilage ether, It then dibenzyline manner similar to that described in example 79, obtaining specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 1732, 1713, 1656, 1480, 1458, 1253, 1167, 760.

Example 247. Sodium salt of (S)-1-(2-{4-tert-butyl-3-[2- (9H-xanthene-9-yl)acetamido]phenyl}ethyl)-4-cyclohexylmethyl succinate (compound N 1-1120)

Following the method similar to that described in example 70, but using (S-1-(2-{ Tret-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl}ethyl)-4 - cyclohexylethyl hydrosylate (obtained as described in example 246) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 3270, 1726, 1656, 1578, 1524, 1481, 1458, 1415, 1365, 1301, 1256.

Example 248. (R)-1-(2-{ 4-tert-Butyl-3-[2-(9H-xanthene-9 - yl)acetamido] phenyl}ethyl)-4-cyclohexylmethyl hydrosylate (compound N 1-1127)

Following the method similar to that described in preparation 79, but using (R)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl}ethyl)- 4-cyclohexylmethyl benzylsuccinic poluchenii as described in preparation 25), dibenzyline with receiving the th spectrum (KBr),maxcm-1: 1733, 1713, 1655, 1480, 1458, 1253, 1166, 760.

Example 249. Sodium salt of (R)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene - 9-yl)acetamido]phenyl}ethyl)-4-cyclohexylmethyl succinate (compound N 1-1120)

Following the method similar to that described in example 70, but using (R)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)- 4-cyclohexylmethyl hydrosylate (obtained as described in example 248) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 3270, 1728, 1656, 1577, 1523, 1481, 1416, 1365, 1301, 1255.

Example 250. (S)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9 - yl)acetamido]phenyl}ethyl)-5-cyclohexylmethyl hydrosylate (compound N 1-1136)

Following the method similar to that described in preparation 25, but using (S)-N-[2-tert-butyl-5-(7-cyclohexyl-3-hydroxymethyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 191) as the original product, in an appropriate ratio used in this example, receive a derivative of benzyl ether. It then dibenzyline manner similar to that described in example 79, obtaining specified in the header connection is rainy absorption spectrum (KBr),maxcm-1: 1732, 1713, 1610, 1480, 1458, 1252, 1166, 760.

Example 251. Sodium salt of (S)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene - 9-yl)acetamido]phenyl}ethyl)-5-cyclohexylmethyl succinate (compound N 1-1129)

Following the method similar to that described in example 70, but using (S)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl}ethyl)-5 - cyclohexylmethyl hydrosylate (obtained as described in example 250) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 3274, 1726, 1656, 1578, 1523, 1481, 1458, 1416, 1365, 1300, 1256.

Example 252. (R)-1-(2-{4-tert-Butyl-3-[2-(9H-xanthene-9 - yl)acetamido]phenyl}ethyl-5-cyclohexylmethyl hydrosylate (compound N 1-1136)

Following the method similar to that described in preparation 25, but using (R)-N-[2-tert-butyl-5-(7-cyclohexyl-3-hydroxymethyl)phenyl]-2- (9H-Kelantan-9-yl)ndimethylacetamide (obtained as described in example 192) as the original product, in an appropriate ratio used in this example, receive a derivative of benzyl ether. It then dibenzyline manner similar to that described in example 79, obtaining specified in the header of Infrakrasnye absorption spectrum (KBr),maxcm-1: 1732, 1712, 1627, 1480, 1457, 1251, 1221, 1165, 752.

Example 253. Sodium salt of (R)-1-(2-{4-tert-butyl-3-[2-(9H-xanthene - 9-yl)acetamido]phenyl}ethyl)-5-cyclohexylmethyl succinate (compound N 1-1129)

Following the method similar to that described in example 70, but using (R)-1-(2-{ 4-tert-butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} ethyl)-5 - cyclohexylmethyl hydrosylate (obtained as described in example 252) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 3273, 1727, 1656, 1578, 1523, 1481, 1458, 1416, 1365, 1300, 1255.

Example 254. N-{2-tert-Butyl-5-[3-(4-(carboxymethylation)-4 - cyclohexylmethyl]phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1568)

Following the method similar to that described in example 79 N-(2-tert-butyl-5- { 3-[(4-benzyloxycarbonylamino)benzoyloxy-4-cyclohexylmethyl] phenyl}-2- (9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 44) dibenzyline obtaining specified in the connection header in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2853, 1713, 1639, 1612, 1578, 1522, 1458, 1418, 1365, 1275, 1255, 1180, 1117.

Example 255. Sodium salt of N-{2-tert-butyl-5-[3-(4- (carboxylmethylcellulose)-4-cyclohexylmethyl] phenyl} -2-(9H-xanthene - 9-yl)ndimethylacetamide (compound N 1-1569)

Following the method similar to that described in preparation 42, N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 12) communicates with diphenylmethyl-4-hydroxybenzoate with getting carbonate derivative. ,24 mg of the thus obtained derivative was dissolved in 5 ml of methylene chloride and added dropwise to the obtained solution of 1 ml of anisole and 5 ml triperoxonane acid. Thus obtained mixture is allowed to stand for 1 h after which the solvent is removed under reduced pressure. The resulting residue is crystallized by rubbing in a mixture of hexane and diisopropyl ether. The crystals are collected by filtration and then recrystallized from diisopropyl ether to obtain 403 mg (yield 80%) indicated in the title compound, melting at 139-141oC.

Infrared absorption spectrum (KBr),maxcm-1: 1759, 1715, 1694, 1641, 1605, 1577, 1508, 1481, 1458, 1422, 1366, 12(the compound N 1-1572)

64 l (0.54 mmol) trichloroacetimidate added to a solution of 272 mg (0.52 mmol) of N-[2-tert-butyl-5-(4-cyclohexyl-3 - hydroxybutyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 12) in 6 ml of benzene, and the resulting mixture is stirred for 10 minutes At the end of this time add a methanol solution of calcium carbonate with stirring. The reaction mixture is mixed with water and the organic phase is separated and dried. The solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 50 g of silica gel using 15: 85 by volume mixture of ethyl acetate and methylene chloride as eluent, yielding 135 mg (yield 46%) indicated in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3389, 2924, 1715, 1575, 1480, 1458, 1333, 1256, 760, 733.

Example 259. N-[2-tert-Butyl-5-(3-hydroxydiphenyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2910)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(3-tert-butylcyclohexylamine)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 11) as the original product, in appropriate product.

Infrared absorption spectrum (KBr),maxcm-1: 2953, 2926, 2855, 1655, 1578, 1524, 1479, 1458, 1414, 1363, 1300, 1255.

Example 260. N-[2-tert-Butyl-5-(4-cyclohexyl-3-hydroboil)phenyl]- 2,2-dimethylpropanamide (compound N 5-118)

Following the method similar to that described in example 40, but using N-[2-tert-butyl-5-(3-tert-butyldimethylsilyloxy-4-cyclohexyl)phenyl] - 2,2-dimethylpropanamide (obtained by the method similar to that described in preparation 11) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of foam.

Infrared absorption spectrum (KBr),maxcm-1: 2957, 2922, 2853, 1655, 1508, 1481, 1448, 1416, 1363, 1200, 1165.

Example 261. N-(2-tert-Butyl-5-{ 4-cyclohexyl-3-[(4 - carboxyphenyl)carbonyloxy] butyl} phenyl)--2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1573)

Following the method similar to that described in example 79, but using N-(2-tert-butyl-5-{ 4-cyclohexyl-3-[(4 - benzyloxycarbonylamino)carbonyloxy] butyl} phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 25) as the original product, in an appropriate amount used in this example, receive specified in the header is connected to the 1256, 1118, 760.

Example 262. Sodium salt of N-(2-tert-butyl-5-{4-cyclohexyl-3-[(4-carboxyphenyl)carbonyloxy]butyl}phenyl) -2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1574)

Following the method similar to that described in example 70, but using N-(2-tert-butyl-5-[4-cyclohexyl-3-[(4-carboxyphenyl)carbonyloxy] butyl} phenyl)- 2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 261) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 2923, 1715, 1481, 1397, 1273, 1259, 1117, 760, 742.

Example 263. N-(2-tert-Butyl-5-{7-cyclohexyl-3-[2-(carboxymethoxy) acetoxy]heptyl}phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1932)

Following the method similar to that described in example 79, but using N-(2-tert-butyl-5-{ 7-cyclohexyl-3-[2-(benzyloxycarbonyloxy)acetoxy] heptyl} phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 25) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxexil-3-[2-(carboxymethoxy)acetoxy] heptyl} phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1933)

Following the method similar to that described in example 70, but using N-(2-tert-butyl-5-{ 7-cyclohexyl-3-[2-(carboxymethoxy)acetoxy] heptyl} phenyl)- 2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 263) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 1740, 1651, 1611, 1518, 1256, 1140, 876, 759.

Example 265. N-{ 2-[3-(1-Imidazolyl)propoxymethyl]-6-methoxyphenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-2077)

Following the method similar to that described in example 35, but using 2-[3-(1-imidazolyl)propoxymethyl]-6-methoxyaniline (obtained in the manner similar to that described in preparation 45) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 155-156oC (after recrystallization from ethyl acetate).

Infrared absorption spectrum (KBr),maxcm-1: 1676, 1553, 1479, 1471, 1462, 1367, 1261, 1246, 1081, 760.

Example 266. N-{2-[3-(1-Imidazolyl)propoxymethyl]-6-methoxy-phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide hydrochloride (compound N 1-2076)

SL(9H-xanthene-9-yl) ndimethylacetamide (received as described in example 265) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Infrared absorption spectrum (KBr),maxcm-1: 3397, 3274, 1652, 1527, 1483, 1458, 1286, 1260, 1080, 761.

Example 267. N-(2-tert-Butyl-5-{3-cyclohexyl-3-[2-(carboxymethoxy)acetoxy] propyl} phenyl)- 2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1848)

Following the method similar to that described in example 79, but using N-(2-tert-butyl-5-{ 3-cyclohexyl-3-[2-(benzyloxycarbonyloxy)acetoxy] propyl} phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained by the method similar to that described in preparation 25) as the original product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 128-129oC (after recrystallization from diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3292, 1750, 1656, 1481, 1458, 1255, 1215, 1139, 760.

Example 268. Sodium salt of N-(2-tert-butyl-5-{ 3-cyclohexyl-3-[2-(carboxymethoxy)acetoxy] propyl} phenyl)- 2-(9H-xanthene-9-yl)ndimethylacetamide (compound N 1-1849)

Following the method similar to that described in example MFA (received as described in example 267) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of foam.

Infrared absorption spectrum (KBr),maxcm-1: 3419, 3278, 1741, 1651, 1614, 1481, 1458, 1421, 1256, 1222, 1138, 760.

Example 269. N-[2-tert-Butyl-5-(1-imidazolidinyl)phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (compound N 1-2922)

Following the method similar to that described in preparation 21(I), but using N-(2-tert-butyl-5-hydroxymethylene)-2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in preparation 14) as the original product, in an appropriate amount used in this example, receive methanesulfonyl derived. It is converted into indicated in the title compound as crystals, melting at 222-223oC (after recrystallization from a mixture of methanol, methylene chloride and hexane), following the method similar to that described in example 1(II).

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), pppm: to 1.16 (9H, singlet); 2,70 (2H, doublet, J=7 Hz); 4,69-4,80 (1H, multiplet); 5,09 (2H, singlet); 6,79-EUR 7.57 (15H, multiplet).

Example 270. N-[2-tert-Butyl-5-(1-imidazolidinyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide hydrochloride (compound N 1-2919]-2-(9H-xanthene-9-yl)ndimethylacetamide (received as described in example 269) as the original product, in an appropriate amount used in this example, receive specified in the title compound in the form of powder.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: to 1.16 (9H, singlet); a 2.75 (2H, doublet, J=7 Hz); 4,68-to 4.73 (1H, multiplet); to 5.35 (2H, singlet); 7,01-7,46 (13H, multiplet); a 7.62 (1H, broadened singlet); 9,01 (1H, broadened singlet).

Example 271. N-{ 2-tert-Butyl-5-[(2-ethyl-1-imidazolyl)methyl]phenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide (compound N 1-2921)

Following the method similar to that described in example 269, but using 2-ethylimidazole instead of imidazole in an appropriate amount, get mentioned in the title compound as an amorphous solid product.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: to 1.16 (9H, singlet); to 1.21 to 1.37 (3H, multiplet); 2,52-a 2.71 (4H, multiplet); 4,70-4,80 (1H, multiplet); to 5.03 (2H, singlet); 6,72-7,43 (14H, multiplet).

Example 272. N-{ 2-tert-Butyl-5-[(2-ethyl-1-imidazolyl)methyl]phenyl}-2-(9H-xanthene-9-yl) ndimethylacetamide hydrochloride (compound N 1-2920)

Following the method similar to that described in example 196, but using N-[2-tert-butyl-5-(2-ethyl-1-imidazolidinyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in example 271) Sagalova compound in powder form.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,15 (9H, singlet); to 1.48 (1H, triplet, J=7.5 Hz); a 2.75 (2H, doublet, J=7 Hz); 3,07-and 3.16 (2H, multiplet); 4,70 (1H, triplet, J=7 Hz); 5,16 (2H, singlet); for 6.81 (1H, doublet, J=7.5 Hz 6,93-7,42 (12H, multiplet); b (1H, broadened singlet).

Preparation 1

2-[(3-Hydroxypropoxy)methyl]-6-methylthio-1-nitrobenzene

I(I) 2-Methyloxime-6-methylthio-1-nitrobenzene

76 ml (0,66 mmol of methylchloride and then 69 mg (of 0.68 mmol) of triethylamine is added to 5 ml methylenchloride solution containing 1-- mg (0.50 mmol) of 2-hydroxymethyl-6-methylthio-1-nitrobenzene in an ice bath. The mixture is stirred at the temperature of the ice bath for 75 minutes On otoczenie this time to the reaction mixture, water is added and the mixture extracted with ethyl acetate. The organic extract is separated by 2 H, aqueous hydrochloric acid and then with water. The solvent is removed by distillation under reduced pressure to obtain specified in the connection header. This product is used in the next stage without purification.

I(II) 2-[(3-Hydroxypropoxy)]-6-methylthio-1-nitrobenzene

33 mg (from 0.76 mmol) of sodium hydride (as a 55% by weight suspension in mineral oil) is washed twice with hexane and then to the suspension was added 1 ml of dimethylformamide. The floor of the Ute for 30 min at this temperature and then for 30 min at room temperature. To the resulting solution was 1 ml dimethylformamide solution containing all 2-methyloxime-6-methylthio-1-nitrobenzene, obtained as described in stage (i) under ice cooling, and the mixture is stirred for 2 h at the temperature of ice-cooling and then for 1.5 h at room temperature. After this time the reaction solution was added water and the mixture extracted with ethyl acetate. The organic extract is washed several times with water and then the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 10 g of silica gel using mixtures of methylene chloride and ethyl acetate in a ratio varying from 10:1 to 8:1 by volume as the eluent to obtain 95 mg (yield 74%) indicated in the title compound as an oily product.

Infrared absorption spectrum (CDCl3),maxcm-1: 3530, 1590, 1525, 1357.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: to 1.83 (2H, quintet, J=6 Hz); the 2.46 (3H, singlet); 3,61 (2H, triplet, J=6 Hz); of 3.73 (2H, triplet, J=6 Hz); of 4.57 (2H, singlet); 7,25 and 7.6 (3H, multiplet).

Preparation of 2

2-[(3-tert-Butyldimethylsilyloxy)methyl]-6 methylthio-1-nitrobenzene

927 mg (x 6.15 mmol) of tert-butyldimethylsilyl solution, contains 1,044 g (4,06 mmol) 2-[(3-hydroxypropoxy)methyl] -6-methylthio-1-nitrobenzene (obtained as described in preparation 1). The mixture is stirred over night at room temperature. After this time the reaction solution is diluted with methylene chloride and washed with dilute aqueous hydrochloric acid and then with water. Then the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 40 g of silica gel. Elution with mixtures of methylene chloride and hexane in a ratio varying from 1:1.5 to 1:1 by volume, leads to the production of 1.26 g (yield 83%) indicated in the title compound as an oily product.

Infrared absorption spectrum (CHCl),maxcm-1: 1590, 1527, 1358.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: 0,04 (6H, singlet); to 0.88 (9H, singlet); of 1.78 (2H, quintet, J=6 Hz); the 2.46 (3H, singlet); of 3.53 (2H, triplet, J= 6 Hz); 3,68 (2H, triplet, J=6 Hz); of 4.54 (2H, singlet); of 7.25 and 7.5 (3H, multiplet).

Preparation of 3.

N-{ 2-[(3-tert-Butyldimethylsilyloxy)methyl] -6-methyl-thiophenyl} - 2-(9H-xanthene-9-yl)ndimethylacetamide

(i) 2-[(3-tert-Butyldimethylsilyloxy)methyl]-6 - methylthioinosine

of 3.53 mg (54 mmol) of zinc and 0.5 ml of vinegar is propoxy)methyl] - 6-methylthio-1-nitrobenzene (obtained as described in preparation 2) in an ice bath. The mixture was then stirred for 50 min, then diluted with ethyl acetate. The mixture was then filtered using filter Zeolite (trade mark).

The insoluble residue is washed with ethyl acetate. The filtrate and wash water are combined to concentrate by evaporation under reduced pressure to approximately 5 ml and again diluted with ethyl acetate; then add saturated aqueous solution of sodium bicarbonate. The desired connection is partitioned between an organic solvent and a solution of bicarbonate. The organic layer containing the precipitate and the aqueous layer was filtered, re-use the filter Zeolite, and the insoluble product is washed with ethyl acetate. The organic layers are combined and washed with water. The solvent is then removed by distillation under reduced pressure to obtain 1.10 g (yield 96%) indicated in the title compound as an oily product.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: 0,04 (6H, singlet); to 0.88 (9H, singlet), 1,89 (2H, quintet, J=6 Hz); 2,31 (3H, singlet); 3,51 (2H, triplet, J= 6 Hz); 3,68 (2H, triplet, J=6 Hz); 4,48 (2H, singlet) and 4.9 (2H, broadened singlet); 6,60 (1H, triplet, J=7.5 Hz); 6,98 (1H, doublet of doublets, J=7,5 b 1.5 iphenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in example 21, the weight of 2-[3(3-tert-butyldimethylsilyloxy)methyl]-6-methylthioinosine, obtained as described in stage (I) above, acelerou, getting mentioned in the title compound as crystals, melting at 185,5-186oC (after recrystallization from a mixture of methylene chloride and methanol) to yield 77%.

Infrared absorption spectrum (KBr),maxcm-1: 3263, 1648, 1517, 1260, 1097.

Spectrum of nuclear magnetic resonance (CDCl3, 60 MHz), ppm: 0,01 (6H, singlet); from 0.84 (9H, singlet); to 1.67 (2H, quintet, J=6 Hz); of 2.30 (3H, singlet); 2,85 (2H, doublet, J=7 Hz); or 3.28 (2H, triplet, J=6 Hz); 3,63 (2H, triplet, J=6 Hz); 4.09 to (2H, singlet); 4,72 (1H, triplet, J=7 Hz); the 6.9 to 7.5 (11H, multiplet).

Preparation 4.

N-[2-[(3-Hydroxypropoxy)methyl] -6-methylthiophenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in example 40, N-{2-[(3-tert-butyldimethylsilyloxy)methyl] -6-methylthiophenyl} -2- (9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 3) is subjected to removal of the silyl protective group to obtain specified in the title compound as crystals, melting at 207-208oC (after recrystallization from acetone) with a quantitative yield.

Infr is on resonance (CDCl3, 270 MHz), ppm: 1,71 (2H, quintet, J=5.5 Hz); to 1.86 (1H, triplet, J=5.5 Hz); is 2.37 (3H, singlet); 2,80 (2H, doublet, J=7 Hz); of 3.32 (2H, triplet, J=5.5 Hz); of 3.69 (2H, Quartet, J=5.5 Hz); 4.09 to (2H, singlet); to 4.73 (1H, triplet, J=7 Hz); 7,0-7,5 (11H, multiplet).

Preparation 5.

Ethyl-5-cycloheptyl-3-oxovalerate

343 mg (2,12 mmol) carbonyldiimidazole added to 4 ml acetonitrile solution containing 300 mg (1,76 mmol) 3-cycloheptylamine acid. The mixture is then stirred for 1 h at 40oC to obtain the active ester.

Separately 273 mg (b mmol) of the complex magnesium bromide in diethyl ether is added to 4 ml tetrahydropyranol suspension containing 360 mg 92,12 mmol) etincelante, in an ice bath. The mixture is then stirred for 1 h at the temperature of the ice bath and then 1 h at room temperature. After this time acetonitrile solution containing an active ester, which is obtained as described above, is added dropwise at room temperature over a period of time for more than 5 min to the resulting suspension, which contains a magnesium salt of mono-ester of malonic acid. When the dropwise addition is completed the mixture is then stirred 1 h at 60oC. the Reaction solution is further diluted with diethyl ether and washed with the aqueous solution of sodium chloride, in this procedure. Then the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 20 g of silica gel. Laurerobie single methylene chloride leads to the production of 376 mg (yield 87%) indicated in the title compound as an oily product.

Infrared absorption spectrum (net),maxcm-1: 1733, 1710, 1305, 1230, 1030.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,06-1,73 (15H, multiplet); of 1.26 (3H, triplet, J=7 Hz); of 2.54 (2H, triplet, J=7.5 Hz); 3,44 (2H, singlet); 4,20 (2H, Quartet, J=7 Hz).

Preparation of 6.

2-tert-Butyl-5-(5-cycloheptyl-3-oxobutyl)-1-nitrobenzene 454 mg (4,06 mmol) of tert-butoxide potassium added to 10 ml of tertrahydrofuran ring solution containing 1,00 g (4,16 mmol) ethyl-5-cycloheptyl-3-oxovalerate (obtained as described in preparation 5). The mixture is then stirred for 10 min to obtain the corresponding potassium salt. 1.1 g (3,47 mmol) 2-tert-butyl-5-iodomethyl-1 - nitrobenzene (obtained as described in preparation 51) is added to the mixture while cooling in an ice bath, and the mixture is stirred for 2 h at the temperature of the ice bath. The reaction solution was diluted with diethyl ether and washed with water. Solvent orstore sodium hydroxide and the mixture is heated for 4 hours at boiling under reflux. The reaction mixture was cooled in an ice bath, add a sufficient amount of aqueous hydrochloric acid to achieve the values of the mixture pH 5.0, and then the mixture is heated under reflux for 2 h while boiling under reflux. After this time the reaction solution was diluted with diethyl ether and washed with water. The solvent is removed by distillation under reduced pressure and the resulting residue is subjected to column chromatography over 70 g of silica gel. Elution with 2:1 by volume mixture of methylene chloride and hexane leads to 850 kg (yield 68%) indicated in the title compound as an oily product.

Infrared absorption spectrum (net),maxcm-1: 1703, 1525, 1362.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,06 is 1.23 (2H, multiplet); 1,25-1,71 (13H, multiplet); to 1.38 (9H, singlet);2,39 (2H, triplet, J= 7.5 Hz); 2,73 (2H, triplet, J=Hz); is 2.88 (2H, triplet, J= Hz); for 7.12(1H,doublet, J=2 Hz); 7,26 (1H, doublet of doublets, J= 2 and 8 Hz); 7,44 (1H, doublet, J=8 Hz).

Preparation of 7

2-tert-Butyl-5-(5-cycloheptyl-3-oxobutyl)aniline

is 3.08 mg (47,1 mmol) of powdered zinc and then of 0.32 ml of acetic acid is added to 16 ml of a methanol solution containing 847 mg (2.36 mmol) of 2-tert-butyl-5 the ATEM stirred for 1 h After this time add the addition of 0.32 ml of acetic acid and the mixture is additionally stirred for 1 h, the Reaction mixture was then filtered using filter Celite. The insoluble residue is washed with ethyl acetate. The filtrate and wash water are combined to concentrate to 10 ml by evaporation under reduced pressure and diluted with ethyl acetate to distribute the desired connection between the organic solvent and water. To remove insoluble material, the solvent is filtered using the filter Celite, and the insoluble product is washed again with ethyl acetate. The organic layers are combined and washed with saturated aqueous sodium bicarbonate and then with water. The solvent is then removed by distillation under reduced pressure to obtain 789 mg (quantitative yield) specified in the title compound as an oily product.

Infrared absorption spectrum (net),maxcm-1: 3490, 3375, 1702, 1618, 1419.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,05-1,22 (2H, multiplet); 1,23-1,71 (13H, multiplet); of 1.39 (9H, singlet); 2,39 (2H, triplet, J=7.5 Hz); 2,65-of 2.81 (4H, multiplet); 3,65-a 3.83 (2H, broadened singlet); 6,47 (1H, doublet, J=2 Hz); of 1.05 to 1.22 (2H, multiplet); 6,55 (1H, doublet is an 990 mg (22.7 mmol) of sodium hydride (as a 55% by weight suspension in mineral oil) is washed twice with hexane and suspended in 40 ml of dimethylformamide. To this suspension is added 4,35 mg (20,1 mmol) methylthiomethyl-n-tamilselvan and after 5 min add 3.1 kg(22,2 mmol) cyclohexylethylamine. Mixture was allowed to reach room temperature, then stirred for 5 hours

After this time add the diluted aqueous solution of ammonium chloride to stop the reaction. The reaction mixture was extracted with diethyl ether and the extract washed with saturated aqueous sodium chloride. The solvent is then removed by distillation under reduced pressure. The resulting residue is subjected to crank chromatography through 100 g of silica gel. Elution with 1:3 by volume mixture of ethyl acetate and hexane results to 5.57 g (yield 89%)specified in the procurement compound as crystals, melting at 65-66oC (after recrystallization from a mixture of diisopropyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 1595, 1445, 1300, 1146, 1084, 961, 816, 760.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,74 is 1.34 (5H, multiplet); of 1.46 (1H, doublet of doublets. J=3 and 132 and 13 Hz); 1,50-of 1.74 (6H, multiplet); of 1.92 (1H, doublet of doublets, J=3 and 9 and 9 and 13 Hz); of 2.23 (3H, singlet); the 2.46 (3H, singlet); of 3.75 (1H, doublet of doublets, J=3 and 12 Hz); to 7.35 (2H, doublet, J=8 R>
9(I) 2-tert-Butyl-5-[3-cyclohexyl-2-(4-were - sulfonyl-2-methylthiouracil]-1-nitrobenzene

of 3.45 ml (5,52 mmol) of 1.6 M hexane solution of utility added dropwise over a period of time for more than 5 min to 10 ml of tertrahydrofuran ring solution containing 1.73 g (5,52 mmol) 1-[2-(4-were)sulfonyl-2-mettiti]hexane (obtained as described in preparation 8), maintaining a temperature of 78oC. After 15 min added dropwise 12 ml dimethylformamide solution containing 1.68 g (5,26 mmol) 5-iodomethyl-2-tert-butyl-1-nitrobenzene (obtained as described in preparation 51). The reaction mixture was allowed to reach room temperature, then stirred for 80 minutes, after this time add the diluted aqueous solution of ammonium chloride to stop the reaction. Add water and diethyl ether and the product is partitioned between an organic solvent and water. The organic layer is separated and washed with saturated aqueous sodium chloride. The solvent is then removed by distillation under reduced pressure to obtain specified in the connection header. As this connection is unstable, it is used in the next stage without purification.

9(i) 2-tert-Butyl-5-(3-cyclohex the-1-nitrobenzene, obtained as described in stage (i) above, dissolved in 50 ml of methanol, Add 5 ml of concentrated aqueous hydrochloric acid and the resulting solution was heated 2 hours at the boil under reflux. After this time the solvent is removed under reduced pressure. The resulting residue is dissolved in diethyl ether and the solvent is washed with water, saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride, in that order. The solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 150 g of silica gel. Elution of 1:5 by volume mixture of ethyl acetate and hexane leads to obtain 1.20 g (yield 73%) indicated in the title compound as an oily product.

Infrared absorption spectrum (liquid film), maxcm-1: 1717, 1532, 1449, 1370, 814.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz). ppm: 0,83-0,98 (2H, multiplet); 1,04 of 1.46 (3H, multiplet); of 1.39 (9H, singlet); 1,59-of 1.73 (5H, multiplet); 1,76-of 1.92 (1H, multiplet); 2,35 (2H, doublet, J=7 Hz); to 3.67 (2H, singlet); 7,14 (1H, doublet, J=2 Hz); 7,26 (1H, doublet of doublets, J= 2 and 8gts); 7,50 (1H, doublet, J=8 Hz).

Preparation 10

5-(3-Cyclohexyl-2-tert-butyldibenzo

Following the method similar to that described in example 22, but using 1.70 g (are 5.36 mmol) 2-tert-butyl-5-(3-cyclohexyl-2-oxopropyl) -1-nitrobenzene (obtained as described in preparation 9), get 1,74 g specified in the title compound as an oily product. The product is used in the next stage without purification.

Infrared absorption spectrum (liquid film)maxcm-1: 3560, 3410, 1532, 1449, 1368, 812.

Spectrum of nuclear magnetic resonance (CDCL3, 270 MHz), ppm: 0,80 was 1.04 (2H, multiplet); 1,07-of 1.55 (6H, multiplet); of 1.39 (9H, singlet); 1.61 of the of-1.83 (5H, multiplet); of 2.64 (1H, doublet of doublets, J=8 and 14 Hz); 2,78 (1H, doublet of doublets, J= 4 and 14 Hz); 3,89-4,00 (1H, multiplet); to 7.18 (1H, doublet, J= 2 Hz); 7,30 (1H, doublet of doublets, J= 2 and 8 Hz); 7,47 (1H, doublet, J=8 Hz).

10(i) 5-(3-Cyclohexyl-2-tert-butyldimethylsilyloxy)- 2-tert-1-nitrobenzene

973 mg (6,46 mmol) tert-butyldimethylsilyloxy, of 0.90 ml (6,46 mmol) of triethylamine and 67 mg (0.55 mmol) of 4-(N,N-dimethylamino) pyridine are added to 10 ml dimethylformamide solution containing of 1.74 g of 5-(3-cyclohexyl-2-hydroxypropyl)-2-tert-butyl-1-nitrobenzene [obtained as described in stage (i) above] . The mixture was then stirred for 1.5 h at room temperature and then for 2.5 hours at 40oC. after the organic layer was washed with dilute aqueous hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride. Then the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 75 g of silica gel. Elution with 1: 9 by volume mixture of diethyl ether and hexane results in 2,22 g (yield 96% over 2 stages) specified in the title compound as an oily product.

Infrared absorption spectrum (liquid film),maxcm-1: 1534, 1368, 1254, 1067, 835.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: -0,26 (3H, singlet); to-0.05 (3H, singlet); to 0.78 to 0.97 (2H, multiplet); 0,81 (9H, singlet); 1,10-1,40 (6H, multiplet); to 1.38 (9H, singlet); of 1.62 and 1.75 (5H, multiplet); 2,60 (1H, doublet of doublets, J = 7 and 13 Hz); 2,78 (1H, doublet of doublets, J = 5 and 13 Hz); 3,85-of 3.94 (1H, multiplet); for 7.12 (1H, doublet, J = 2 Hz). of 7.23 (1H, doublet of doublets, J = 2 and 8 Hz); 7,42 (1H, doublet, J = 8 Hz).

Preparation II

N-[2-tert-Butyl-5-(3-cyclohexyl-2-tert-butyldimethylsilyloxy) phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide

11 (I) 2-tert-Butyl-5-(3-cyclohexyl-2-tert-butyldimethylsilyloxy-propyl)aniline

Following the method similar to that described in example 7, but using 1.70 g (are 5.36 mmol) 5-(3-cyclohexyl-2-tert-butultimately the th product the appropriate amount used in cooking, get mentioned in the title compound as an oily product.

11 (II) N-[2-tert-Butyl-5-(3-cyclohexyl-2-tert-butyldimethylsilyloxy)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide.

Following the method of acylation, such as described in example 21, but using 2-tert-butyl-5-(3-cyclohexyl-2-tert-butyldimethylsilyloxy)aniline [obtained as described in stage (I) above] as a starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 148-150oC (after recrystallization from a mixture of diisopropyl ether and hexane). Output in both quantitative stages.

Infrared absorption spectrum (KBr),maxcm-1: 3232, 1641, 1533, 1482, 1256, 759.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: -0,37 (0,6 H, singlet); -0,20 (2,4 (H, singlet); -0,10 (0,6 H, singer); -0,02 (2,4 (H, singlet); of 0.75 to 0.97 (2H, multiplet); 0,78 (1,8 H, singlet); 0,82 (7,2 H, singlet); of 1.06 to 1.47 (6H, multiplet); to 1.16 (9H, singlet); 1.60-to 1.77 in (5H, multiplet); 2,37 was 2.76 (4H, multiplet); 3,68 was 2.76 (0,2 H, multiplet); 3,92 (0,8 H, quintet, J = 6 Hz); at 4.75 (1H, triplet, J = 7 Hz); 6.90 to-7,41 (11H, multiplet).

PR is rasego 3.12 g (28.8 mol) ethylchloride, added dropwise within 10 min to 60 ml of tertrahydrofuran ring solution containing 6.0 g (26.9 mmol) of 4-tert-butyl-3-nitrobenzoic acid and 3.12 g (30,9 mmol) of triethylamine in an ice bath. The reaction solution is stirred for 45 min at this temperature, and then filtered using filter Celite. The insoluble residue is washed with tetrahydrofuran, and the filtrate and washing water combine. The combined solution is added dropwise to a mixed solution consisting of 40 ml of tetrahydrofuran and 40 ml of water containing 3,76 g (9,95 mmol) sodium borohydride, for 25 min in an ice bath. The reaction mixture is then stirred for 2 hours at the temperature of the ice bath, then concentrated by evaporation under reduced pressure. As much as possible remove the tetrahydrofuran under reduced pressure and the residue partitioned between diethyl ether and water. The product is extracted from the aqueous layer with diethyl ether. The organic layers are combined and washed twice with water and then once with a saturated aqueous solution of sodium chloride. The solvent is then removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 100 g of silica gel. Elution with mixtures of ethyl acetate and hexane in the ratio, the IDA oily product.

Range nuclear resonance (CDCl3, 270 MHz), ppm: of 1.40 (9H, singlet); 4,69 (2H, doublet, J = 5 Hz). 7,33 (1H, singlet); 7,41 (1H, doublet, J = 9.5 Hz). 7,53 (1H, doublet, J = 9.5 Hz).

Preparation of 13

2-tert-Butyl-5-(2-tert-butyldimethylsilyloxy)-1-nitrobenzene

4,15 mg (27.5 mmol) of tert-butyldimethylsilyloxy, of 3.85 ml (27.6 mmol) of triethylamine and 815 mg (0,503 mmol) of 4-(N, N-dimethylamino)pyridine are added to 50 ml methylenechloride solution containing of 5.24 g (25,0 mmol) 2-tert-butyl-5-hydroxymethyl-1-nitrobenzene (obtained as described in preparation 12) in an ice bath. The reaction mixture is allowed to return to room temperature, then stirred for 40 minutes, after this time the reaction solution of 1: 1 by volume elute hexane and diethyl ether and washed with water, diluted hydrochloric acid, again with water, saturated aqueous sodium hydrogen carbonate, in that order. Then the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 100 g of silica gel. Elution with 1:1 mixture of methylene chloride and hexane results of 8.04 g (yield 99%) specified in the title compound as an oily product.

Range nuclear minitablet).

Preparation 14

N-(2-tert-Butyl-5-hydroxymethylene)-2-(9H-xanthene-9-yl)ndimethylacetamide

14 (I) 2-tert-Butyl-5-(2-tert-butyldimethylsilyloxy)aniline

Following the method similar to that described in example 7, but using 2-tert-butyl-5-(2-tert-butyldimethylsilyloxy)-1-nitrobenzene (obtained as described in preparation 13) as the original product, in an appropriate amount used in cooking, get mentioned in the title compound as an oily product with a quantitative yield.

14 (II) N-[2-tert-Butyl-5-(2-tert-butyldimethylsilyloxy)phenyl]-2- (9H-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in example 21, but using 2-tert-butyl-5-(2-tert-butyldimethylsilyloxy)aniline [obtained as described in stage (I) above] as a starting product, specified in the title compound in the form of crystals with a yield of 84%.

14 (III) N-(2-tert-Butyl-5-hydroxymethylene)-2-(9H-xanthene-9-yl)ndimethylacetamide.

Following the method similar to that described in example 40, but using N-[2-tert-butyldimethylsilyloxy)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide [obtained as described in stage (II) above] as a starting product in the appropriate quantity and 137-138oC (after recrystallization from a mixture of ethyl acetate and hexane) with a quantitative yield.

Infrared absorption spectrum (KBr),maxcm-1: 1664, 1541, 1478, 1460, 1250.

Range nuclear resonance (CDCl3, 270 MHz), ppm: 1,17 (9H, singlet); 2,41 (2/5H, broadened doublet, J = 7 Hz); 2.71 to (8/5H, doublet, J = 7 Hz); 4,35 is 4.45 (2/5H, singlet); to 4.73 (1H, triplet, J = 7 Hz); 7,05-of 7.55 (11H, multiplet).

Preparation 15

N-(2-tert-Butyl-5-formylphenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide

1.24 g (is 3.08 mmol) of N-(2-tert-butyl-5-hydroxymethylene)-2 -(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 14) are added to 12 ml methylenchloride suspension containing 1.06 g (4,92 mmol) pyridylamine. The mixture was then stirred for about 1.75 hours after this time the reaction suspension was diluted with diethyl ether, filtered through a column using 50 ml of absorbent Florisil (trade mark), and elute 1: 1 by volume mixture of methylene chloride and diethyl ether. Then the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 50 g of silica gel. Elution with 1:9 by volume mixture of diethyl ether and methylene chloride results specified in the header of coedine leads to 442 mg specified in the connection header in the form of crystals, melting at 172,5-174oC (after recrystallization from a mixture of ethyl acetate and hexane). The mother liquor is concentrated and subjected to column chromatography through 100 g of silica gel. Elwira 4: 6 by volume mixture of ethyl acetate and hexane results in 643 mg specified in the connection header. The total yield of 88%.

Infrared absorption spectrum (KBr),maxcm-1: 1702, 1642, 1482, 1459, 1260, 760.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: to 1.21 (6H, singlet); to 2.74 (2H, doublet, J = 7 Hz); at 4.75 (1H, triplet, J = 7 Hz); 7,07-to 7.15 (4H, multiplet); 7,21-7,29 (2H, multiplet); 7,39 (2H, doublet of doublets, J = 2 and 8 Hz); 7,49 (1H, doublet, J = 8 Hz); 7,66 (1H, doublet of doublets, J = 2 and 8 Hz); 0,08 (1H, broadened singlet); 9,98 (1H, singlet).

Preparation 16

N-[2-tert-Butyl-5-(2-ethoxycarbonylethyl)phenyl] -2 -(9H-xanthene-9-yl)ndimethylacetamide

153 mg (3,51 mmol) of sodium hydride (as a 55% by weight suspension in mineral oil) is washed twice with hexane; then add 5 ml of dimethylformamide. The suspension is cooled in an ice bath and then added 1 ml dimethylformamide solution containing 673 mg (3.00 mmol) of 2-diethoxyphosphoryl. When the foaming has ended, the reaction mixture is stirred for further 40 min at room temperature the IO)-2-(9H-Xanten-9-yl)ndimethylacetamide. The mixture is stirred for 20 minutes at the temperature of the ice bath and 10 min at room temperature. After this time the reaction mixture was diluted with diethyl ether, and poured ice-cold water and extracted with diethyl ether. The organic extract is washed with water. The solvent is removed by distillation under reduced pressure. The obtained residue is recrystallized from a mixture of methylene chloride, diethyl ether and hexane to obtain 804 mg specified in the title compound as crystals, melting at 180-181oC. the mother liquor is concentrated and recrystallized from the same solvent mixture with additional 263 mg specified in the connection header. Just get 1,067 g (yield 90%) specified in the connection header.

Infrared absorption spectrum (KBr),maxcm-1: 3235, 1711, 1645, 1523, 1480, 1458, 1257, 116, 756.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: of 1.18 (9H, singlet); 136 (3H, triplet, J = 7 Hz); 2,33-2,46 (0,4 H, multiplet); 2,72 (0,4 H, doublet, J = 7 Hz); 4,28 (2H, Quartet, J = 7 Hz); 4,74 (1H, triplet, J = 7 Hz); 6.42 per (1H, doublet, J = 16 Hz); 7.03 is was 7.45 (10H, multiplet); 7,63 (1H, doublet, J = 16 Hz); of 7.70 (1H, singlet).

Preparation 17

N-[2-tert-Butyl-5-(2-ethoxycarbonylethyl)phenyl] -2-(9H-CC is using N-[2-tert-Butyl-5-(2-ethoxycarbonylethyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (received as described in preparation 16) as the original product, in an appropriate amount used in this example, is obtained in a yield of 95% is indicated in the title compound as crystals, melting at 160,5-11,5oC (after recrystallization from a mixture of methylene chloride and diethyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3223, 1736, 1640, 1539, 1481, 1261, 1192, 760.

Range nuclear resonance (CDCl3, 270 MHz), ppm: to 1.16 (9H, singlet); of 1.26 (3H, triplet, J = 7 Hz); 2,35-2,50 (1H, multiplet); 2,58-2,75 (3,5 H, multiplet); 2,86-2,98 (1,5 H, multiplet); to 4.16 (2H, Quartet, J = 7 Hz); 4,74 (1H, triplet, J = 7 Hz); 6,91 was 7.45 (11H, multiplet).

Preparation 18

N-[2-tert-Butyl-5-(3-hydroxypropyl)phenyl]-2-(9H - xanthene-9-yl)ndimethylacetamide

5,96 ml (5,96 mmol) 1 M gexanova solution diisobutylaluminium-hydride is added dropwise during 10 min to 14 ml of tertrahydrofuran ring solution containing 702 mg (1,49 mmol) N-[2-tert-butyl-5- (ethoxycarbonylethyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 17), pre-cooled to -78oC. the Mixture is stirred for 75 min at this temperature and then 45 min at room temperature. After this time the reaction solution was poured in the mixture is raybaut water, and then the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 30 g of silica gel. Elution with 5:4 by volume mixture of methylene chloride and ethyl acetate leads to 427 mg (yield 67%) indicated in the title compound as crystals, melting at 185-186oC (after recrystallization from a mixture of methylene chloride and diethyl ether).

Infrared absorption spectrum (KBr), maxcm-1: 3417, 3212, 1659, 1530, 1481, 1457, 1254, 765, 757.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: to 1.16 (9H, singlet); 1,67-to 1.98 (2H, multiplet); 2,33 of $ 2.53 (1H, multiplet); 2,61 was 2.76 (3H, multiplet); 3,53 of 3.75 (2H, multiplet); 4,74 (1H, triplet, J=7 Hz); 6,92-7,46 (11H, multiplet).

Preparation 19

N-[2-tert-Butyl-5-(3-oxopropyl)phenyl]-2-(9H-kazanan-9-yl) ndimethylacetamide

2 ml methylenchloride solution containing 155 mg (1,98 mmol) of dimethyl sulfoxide, is added dropwise within 5 min to 2 ml methylenchloride solution containing 126 mg (0,99 mmol) oxalicacid, which is pre-cooled to -78oC. the Mixture was then stirred for 5 min at this temperature, then add 15 ml methylenchloride solution containing 354 mg (0,825 mmol) N-[2-tert-butyl-5-(3-hydroxyp is at this temperature. To the reaction mixture 501 mg (of 4.95 mmol) of triethylamine, and the mixture is stirred for 5 min at the same temperature. Then the reaction mixture is allowed to return to room temperature, then diluted with diethyl ether and washed with diluted hydrochloric acid and then with water. The solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 20 g of silica gel. Elution 100:5 by volume mixture of methylene chloride and ethyl acetate leads to 310 kg (yield 88%) indicated in the title compound as crystals, melting at 176-177oC (after recrystallization from a mixture of methylene chloride and diethyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3230, 1729, 1641, 1534, 1481, 1458, 1260, 759.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: to 1.16 (9H, singlet); 2,36-of 3.00 (6H, multiplet); 4,74 91H, triplet, J= 7 Hz); 6,92-7,45 11H, multiplet); 9,84 (1H, singlet).

Preparation 20

N-[(9H-Xanthene-9-yl)methyl] =N'-(2-tert-butyl-5-[4-cyclohexyl-3- (tert-butyldimethylsilyloxy)butyl]phenyl}urea

A solution of 240 mg (1.0 mmol) of 2-(9H-xanthene-9-yl)acetic acid, 275 mg (1.00 mmol) diphenylphosphinite and 139 l (1.00 mmol) of triethylamine in 3 ml of benzene is) 2-tert-butyl-5-[4-cyclohexyl-3-(tert-butyldimethylsilyloxy)butyl] aniline in 0.5 ml of benzene. The resulting mixture was heated under reflux for 3 hours, after this time the reaction mixture was diluted with ethyl acetate, and the diluted mixture is washed with diluted aqueous hydrochloric acid solution, water, then saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 25 g of silica gel using 95: 5 by volume mixture of methylene chloride and ethyl acetate as eluent to obtain 414 mg (yield 65%) of the specified header in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3341, 2953, 2926, 2854, 1637, 1561, 1481, 1458, 1256, 1075, 835, 755.

Preparation 21

(2-Vinylcyclopentane) acetic acid

21 (i) (1-Phenyltropane) methanol

A solution of 1.15 g (6,04 mmol) (1-phenyltropane) carboxylic acid in 10 ml of tetrahydrofuran is added dropwise over 20 min to a suspension of 344 mg (9,06 mmol) sociallyengaged in 20 ml of tetrahydrofuran under ice-cooling, and the mixture was stirred for 30 min at 60oC. the second solution of sodium hydroxide and 1 ml of water, in this sequence, and the resulting mixture was diluted with diethyl ether. The resulting white gel-like product is filtered and the filter washed with water, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography through 50 g of silica gel using methylene chloride as eluent to obtain 1.06 g (yield 99%) specified in the procurement connection in the form of colorless crystals.

Infrared absorption spectrum (KBr),maxcm-1: 3310, 2952, 2929, 2873, 1496, 1446, 1059, 1032, 766, 699, 567,

21 (II) (1-Phenylcyclohexyl)methylmethanesulfonate

659 mg (6,07 mmol) methanesulfonanilide and then 838 l (6,01 mmol) of triethylamine added under cooling in an ice bath to a solution of 1.00 g (5,67 mmol) (1-phenyltropane)methanol) obtained as described in stage (I) above] in 18 ml of methylene chloride, and the mixture was stirred for 1 h, after this time the reaction mixture was diluted with diethyl ether, and the diluted mixture was washed with 2 N. aqueous hydrochloric acid, water, rich in the economic phase is dried over anhydrous sodium sulfate and the solvent is distilled off to obtain 1.44 g (yield quantitative) specified in the procurement connection in the form of colorless crystals.

Infrared absorption spectrum (KBr), maxcm-1: 2959, 2943, 2874, 1337, 1180, 1166, 975, 960, 853, 845, 770, 750, 702, 526, 505.

21 (III) (1-Phenylcyclohexyl)methyliodide

to 5.00 g (33.3 mmol) of sodium iodide are added to a solution of 1.00 g (3.93 mmol) (1-phenylcyclohexyl)methylmethanesulfonate [obtained as described in stage (II) above] in 10 ml of isobutyl ketone, and the mixture was heated under reflux with stirring for 18 hours after which time the solvent is removed by evaporation under reduced pressure and the resulting residue partitioned between diethyl ether and water. The organic phase is washed with water, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 50 g of silica gel using 1:1 by volume mixture of methylene chloride and hexane as eluent to obtain 504 mg (yield 45%) specified in the procurement connections in the form of butter.

Infrared absorption spectrum (liquid film), maxcm-1: 2956, 2872, 1496, 1446, 1210, 1188, 760, 699, 546.

UP>o
C to a solution of 126 mg (1,05) 1,3-dithiane in a mixture of 1.5 ml of tetrahydrofuran and 720 l hexamethylphosphorotriamide under stirring, and the mixture was stirred for 10 min while cooling in a bath of ice and salt. After this time a solution of 200 mg (0,699 mmol) (1-phenylcyclohexyl)methyl iodide [obtained as described in stage (III) above] is added dropwise to the mixture at -78oC. the resulting mixture was then stirred for 20 minutes under cooling in an ice bath salt. To stop the reaction mixture is added saturated aqueous solution of ammonium chloride, then extracted with diethyl ether. The extract was washed with saturated aqueous sodium chloride. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 15 g of silica gel using 3:2 by volume mixture of hexane and methylene chloride as eluent to obtain 100 mg (yield 51%) indicated in the title compounds as colorless foamy product.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,57 - 2,10 (12h, multiplet); 2,61 - to 2.85 (4H, multiplet); to 3.58 (1H, triplet, J= 5,9 Hz); 7.18 in-7,37 (5H, multiplet).

21 (V) 2-ylamine added to a suspension of 90 mg (0,323 mmol) 2-(1-phenyltropane)methyl-1,3-dithiane [received, as described in stage (IV) above] in a mixture of 4 ml of acetonitrile and 0.6 ml of water, and the mixture was stirred for 3 h at 90oC. after this time the reaction mixture is cooled and diluted with ethyl acetate. Insoluble material is filtered using a filter Celite (trade mark). The filtrate is then washed with IM aqueous solution of sodium acetate, saturated aqueous ammonium chloride and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 5 g of silica gel using methylene chloride as eluent, to obtain 58,4 mg (yield 96%) specified in the connection header in de colorless foamy product.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,76 of 1.99 (8H, multiplet); 2,64 92H, doublet, J = 3?3 Hz); 7,1807,34 (5H, multiplet); 9,43 (1H, triplet, J = 3.3 Hz).

21 (VI) 2-(1-Phenylcyclohexyl)acetic acid

1 ml of an aqueous solution of 39 mg (0,402 mmol) of sulfamic acid and then 1 ml of an aqueous solution of 37.6 mg (0,416 mmol) of sodium chloride is added dropwise to a solution for 58.4 mg (0,310 mmol) 2-(1-fanikizo and the resulting mixture was stirred for 1 h at room temperature, then extracted with methylene chloride. The extract is washed with water and then dried over anhydrous sodium sulfate. The solvent is removed by distillation under reduced pressure to obtain colorless crystals. Their is recrystallized from a mixture of ethyl acetate and hexane to obtain 57 mg (yield 90%) specified in the connection header in the form of lamellar crystals.

Infrared absorption spectrum (KBr),maxcm-1: 2967, 2945, 2869, 1706, 1426, 1400, 1204, 1195, 911, 773, 698.

Preparation 22

N-[(1-Phenylcyclohexyl)methyl] -N'-[2-tert-butyl-5- (3-tert-butyl-dimethylsiloxy-4-cyclohexylmethyl)phenyl]urea

Following the method similar to that described in preparation 20, but using 2-(1-phenylcyclohexyl)acetic acid (obtained, as described in preparation 21) as the original product, in an appropriate amount used in cooking, get mentioned in the title compound in the form of a foamy product.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,59 (6H, singlet); to 0.92 (9H, singlet); 1,17-1,93 (23 H, multiplet); of 1.27 (9H, singlet); 2,39-2,62 (2H, multiplet); and 3.31(3H, doublet, J = 5 Hz);3,80 - 3,82 (1H, multiplet); 5.74 (1H, singlet); 6,84 - 7,28 (8H, multiplet).

Made the

23(I) (S)-2-Cyclohexyl-1-(benzoyloxymethyl)ethyl alcohol

The solution of the Grignard reagent derived from 9,79 g (60,0 mmol) cyclohexylamine and of 1.46 g (60,0 mmol) of magnesium in 85 ml of tetrahydrofuran, is added dropwise over 10 min to a suspension of 1.90 g (9,98 mmol) of copper iodide in 50 ml of tetrahydrofuran at -75oC. the Mixture is left for 10 min, and then added dropwise a solution of (S)-benzyloxypyrrolidine, []D= 4,82o(C = 1, toluene) in 20 ml of tetrahydrofuran for 15 minutes the mixture is stirred for 3 hours at the same temperature and then 30 minutes at 0oC. after the reaction stopped by the addition of saturated aqueous solution of ammonium chloride. The reaction mixture is then mixed with 20 ml of concentrated aqueous ammonia, and then extracted with diethyl ether. The extract was washed with saturated aqueous ammonium chloride, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 250 g of silica gel using 1:4 by volume mixture of ethyl acetate and methylthymol oil.

Infrared absorption spectrum (liquid film),maxcm-1: 3460, 1451, 1364, 1102, 1048, 1028, 737, 699.

[]2D5= -0,84o(C = 1.78, CHCl3).

23 (II) (S)-[3-Benzyloxy-2-(tert-butyldimethylsilyloxy) cyclohexane

Following the method similar to that described in preparation 10 (II), but using (S)-2-cyclohexyl-1-(benzoyloxymethyl)ethanol [obtained as described in stage (I) above] as a starting product, in an appropriate amount used in cooking, get mentioned in the title compound in the form of an oil in quantitative yield.

Infrared absorption h (liquid film),maxcm-1: 1451, 1362, 1252, 1125, 1028, 970, 835, 776.

[]2D5= 17.4o(C = 1.22, CHCl3).

23 (iii) (S)-2-tert-Butyldimethylsilyloxy-3-cyclohexylpropionic alcohol

A solution of 3.46 g (of 9.55 mmol) of (S)-[3-benzyloxy-2-(tert-butyldimethylsilyloxy)cyclohexane [obtained as described in stage (II) above] in 50 ml of ethanol is stirred for 320 minutes in a stream of hydrogen in the presence of 580 mg of 10% by weight palladium on coal. After this time the reaction mixture is filtered and the catalyst washed with ethanol. The filtrate and PR column chromatography through 180 g of silica gel, using 1:4 by volume mixture of ethyl acetate and hexane as eluent, obtaining of 2.54 g (yield 98%) specified in the header of the alcohol derivative in the form of a colorless oil.

Infrared absorption spectrum (liquid film),max3400, 1449, 1254, 1080, 969, 837, 776.

[]2D5= + 3.6o(C = 1.02, CHCl3).

23 (IV) (S)-2-tert-Butyldimethylsilyloxy-3-cyclohexylpropionate 1.5 ml (21.1 mmol) of dimethyl sulfoxide is added dropwise over 2 min to a solution of 1.0 ml (11.5 mmol) of oxalicacid in 20 ml of methylene chloride at -78oC. the Mixture is allowed to stand for 10 minutes, then added dropwise over 5 minutes a solution of 2.54 g (to 9.32 mmol) of (S)-2-tert-butyldimethylsilyloxy-3-cyclohexylpropionic alcohol [obtained as described in stage (III) above] in 12 ml of methylene chloride. The resulting mixture was stirred for 20 minutes at the same temperature, then added to 6.5 ml (with 46.6 mmol) of triethylamine. The mixture is allowed to stand for 7 minutes, and the cooling bath removed. After another 10 minutes the reaction is stopped by adding an aqueous solution of ammonium chloride. The reaction mixture was extracted with diethyl ether. The extract is washed twice with water and once with saturated aqueous sodium chloride. The organic phase vysushila the output quantity) specified in the header of the aldehyde compound as a colourless oil.

Infrared absorption spectrum (liquid film),maxcm-1: 1738, 1472, 1449, 1256, 1115, 1007, 940, 839, 778.

23 (V) (S)-2-tert-Butyl-5-(3-tert-butyldimethylsilyloxy-4-cyclohexyl-1-butenyl)-1-nitrobenzene

8.6 ml (8.6 mmol) of 1M tertrahydrofuran ring solution hexamethyldisilazide sodium added during 20 minutes to a suspension 5,04 g (8,67 mmol) (4-tert-butyl-3-nitrophenyl)methyltriphenylphosphonium iodide (obtained as described in preparation 52) in 80 ml of tetrahydrofuran at -78oC, and the mixture is allowed to stand for 1 h Then all at once add a solution of 2.33 G (8,61 mmol) of (S)-2-tert-butyldimethylsilyloxy-3-cyclohexylpropionate [obtained as described in stage (IV) above] in 7 ml of tetrahydrofuran, and the mixture was stirred for 1 h at the same temperature. The cooling bath is removed and the mixture is stirred for further 4 hours the Reaction is stopped by adding a saturated aqueous solution of ammonium chloride, after which the reaction mixture is extracted with 1:3 by volume mixture of ethyl acetate and hexane. The extract is washed with water and saturated aqueous solutions of sodium chloride, in that order, then dried over anhydrous magnesium sulfate. The solvent is removed by distillation under reduced pressure and the resulting residue is purified column is uent, obtaining fractions containing small amounts of impurities. These fractions are again purified column chromatography through 150 g of silica gel using 1:4 by volume of methylene chloride and hexane as the eluent, to obtain the 2,78 g (yield 72%) specified in the header olefin derived in the form of a colorless oil.

Infrared absorption spectrum (liquid film),maxcm-1: 1534, 1368, 1254, 1096, 1073, 1003, 970, 938, 837,776.

23 (vi) (R)-2-tert-Butyl-5-(3-tert-butyldimethylsilyloxy-4-cyclohexylmethyl)-1 - nitrobenzene

A solution of 2.75 g (6,17 mmol) of (S)-2-tert-butyl-5-(3-tert - butyldimethylsilyloxy-4-cyclohexyl-1-butenyl)-1-nitrobenzene [obtained as described in stage (v) above] in 30 ml of diethyl ether vigorously stirred for 20 minutes at 0oC in a stream of hydrogen in the presence of 303 mg of 10% by weight palladium on coal. The reaction mixture is then treated by the method similar to that described in stage (III) above, to obtain 2.65 g (yield 96%) specified in the header nitrobenzene derived in the form of a colorless oil.

Infrared absorption spectrum (liquid film),maxcm-1: 1532, 1472, 1449, 1368, 1254, 1077, 1024, 1005, 978, 835, 774.

[]2D2= - 4,4o(C = 1,46, CHCl3)/

23 is ledua method, similar to that described in preparation 3, but (R)-2-tert-butyl-5-(3-tert-butyldimethylsilyloxy-4-cyclohexylmethyl) -1-nitrobenzene [obtained as described in stage (VI) above] is converted into aniline derivative. It acelerou manner similar to that described in example 21, with the receipt specified in the connection header with the release of 94% in the form of crystals, melting at 173 - of 174.5oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr)maxcm-1: 3460, 1640, 1538, 1482, 1459, 1256, 1079, 835, 758.

[]2D5= -5.9o(C = 1.14, CHCl3).

Preparation 24

(S)-2-tert-Butyl-5-(benzoyloxy-4-cyclohexylmethyl)aniline

24 (I) (R)-2-tert-Butyl-5-(3-hydroxy-4-cyclohexylmethyl)-1-nitrobenzene

Following the method similar to that described in example 40, but ipolisa (R)-2-tert-butyl-5-(3-tert-butyldimethylsilyloxy-4-cyclohexylmethyl) -1-nitrobenzene [obtained as described in preparation 23 (VI) ] as the original product, in appropriate proportions, similar to that used in example 40, receive specified in the header of the alcohol derived from 98% yield as a colourless oil.

Infrared absorption spectrum (liquid film),max
The solution 734 ml (4,21 mmol) of diethylazodicarboxylate in 5 ml of tetrahydrofuran is added dropwise during 5 minutes to a solution of 1.16 g (3,48 mmol) of (R)-2-tert-butyl-5-(3-hydroxy-4-cyclohexylmethyl)-1 - nitrobenzene [obtained as described in stage (I) above], 1.10 g (4,21 mmol) of triphenylphosphine and 512 mg (4,19 mmol) of benzoic acid in 12 ml of tetrahydrofuran while cooling with ice. The temperature of the reaction mixture is allowed to rise gradually to room, after which the resulting mixture was stirred for 12 hours, after this time the reaction mixture was diluted with ethyl acetate. The diluted mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous magnesium sulfate and then the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 150 g of silica gel using 1:9 by volume mixture of diethyl ether and hexane as eluent to obtain 1.19 g (yield 78%) specified in the header of the benzyl derivative in the form of butter.

Infrared absorption spectrum (liquid film),maxcm-1: 1715, 1532, 1451, 1368, 1273, 1113, 1069, 1026, 712.

[]2D2

Preparation 25

(R)-1-(2-{ 4-tert-Butyl 3-(N-xanthene-9-yl)acetamido]-phenyl} ethyl)-2-cyclohexylethyl benzylsuccinic

Suspension 249 mg (0,474 mmol) of (R)-N-[2-tert-butyl-5-(4 - cyclohexyl-3-hydroxybutyl)phenyl]-2-(N-xanthene-9-yl)ndimethylacetamide (obtained as described in example 100), 218 mg (1.05 mmol) of benzylhydroxylamine, 76 mg (of 0.62 mmol) of 4-(N,N-dimethylamino)pyridine and 256 mg (1,34 mmol) of the hydrochloride of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide in 5 ml of tetrahydrofuran is stirred for 17 h at room temperature. After this time the reaction mixture was diluted with ethyl acetate, and the diluted mixture was washed with 2 N. aqueous hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous magnesium sulfate and satedalen. The resulting residue is purified column chromatography through 20 g of silica gel using 1:9 by volume mixture of ethyl acetate and hexane as eluent to obtain 352 mg (quantitative yield) specified in the procurement connection in the form of a glassy product.

Infrared absorption spectrum (film), amaxcm-1: 1734, 1659, 1480, 1459, 1416, 1256, 1215, 1158, 870, 758.

Preparation 26

N-[2-1,1-Dimethyl-2-methoxy)ethyl-6-(3-oxopropyl)phenyl] -2-(N - xanthene-9-yl)ndimethylacetamide

26(I) N-[2-(1,1-Dimethyl-2-methoxy)ethyl-6-[3-(tert-butyl - dimethylsiloxy)propyl]phenyl]-2-(N-xanthene-9-yl)-ndimethylacetamide.

Following the method similar to that described in example 21, using 2-(1,1-dimethyl-2-methoxy)ethyl-6-[3-(tert-butyldimethylsilyloxy) propyl]aniline as starting product, in an appropriate amount used in this example, get mentioned in the title amide derivative as colorless crystals.

Infrared absorption spectrum (KBr),maxcm-1: 3249, 1649, 1526, 1480, 1459, 1258, 1102, 8837, 754.

26(II)N-[2-(1,1-Dimethyl-2-methoxy)ethyl-6-(3-oxopropyl)phenyl) -2-(N-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in example 40, N-[2-(1,1-dimethyl-2-methoxy)ethyl-6-[3-(tert-buildiers illinoi protective group, then it oxidizes manner similar to that described in preparation 19, obtaining specified in the title compound as crystals, melting at 112-113,5oC.

Infrared absorption spectrum (KBr),maxcm-1: 3225, 1725, 1648, 1534, 1482, 1459, 1262, 1107, 756.

Preparation 27

(S_-1-(2-{ 4-tert-Butyl-3-[2-(N-xanthene-9-yl)acetamido]phenyl}ethyl - 2-cyclohexylethyl benzylsuccinic

Following the method described in preparation 25, but using (S)-N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl 2-(N-xanthene-9-yl)ndimethylacetamide (obtained as described in example 102) and benzylidenemalonate as the original products, in the appropriate ratio used in this preparation specified in the title compound obtained as foamy product.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,78-1,02 (2H, multiplet); 1,10-1,90 (13H, multiplet); 1.16 to (N, singlet); 2,40-a 2.71 (4H, multiplet); to 3.38 (2H, singlet); 4,74 (1H, triplet, J=7 Hz); of 5.05-5,16 (1H, multiplet); 5,19 (2H, singlet); 6.90 to-7,40 (m, multiplet).

Preparation 28

N-(2-Isopropyl-6-hydroxymethylene)-2-(N-Santen-9-yl) ndimethylacetamide

Method AND

28(I) 2-Isopropyl-methylthiopyrimidin

15,51 g (116 mmol) of N-succinum 200 ml of methylene chloride while maintaining the internal temperature between 10 and 20oC. After 15 min 11,73 g (116 mmol) of triethylamine is added to the mixture at reflux for 9 hours after this time the solvent is removed by distillation under reduced pressure. The resulting residue is mixed with diethyl ether and appeared insoluble products filtered. The filtrate is concentrated by evaporation under reduced pressure, and the concentrate purified column chromatography through 300 g of silica gel, use the method of gradient elution with mixtures of hexane and methylene chloride varying from 4: 1 to 0:1 as eluent to obtain 10,45 g (yield 65%) specified in the header sulfide derivative in the form of butter.

Infrared absorption spectrum (liquid film),maxcm-1: 3447, 3354, 1623, 1460, 1447, 1280, 1268, 1242, 1049, 747.

28(II) 2-Isopropyl-6-methylsulfonylmethane

12.9 g (52,3 mmol) m-chlorbenzoyl acid (70% purity) is added dropwise within 15 min to a suspension of 10.21 g (52,3 mmol) of 2-isopropyl-6-methylthiopyrimidine [obtained as described in stage (I) above] and 5,31 (50 mmol) of sodium carbonate in 200 ml of methylene chloride under cooling with ice. The reaction mixture was stirred 1.5 h at the same temperature, after which it was diluted with diethyl ether, and razvalistoj, in this procedure. Then the solvent is removed by distillation under reduced pressure, and the obtained residue is recrystallized from a mixture of diethyl ether and diisopropyl ether to obtain 7,74 g specified in the title compounds as the first batch of product. The mother liquor is concentrated by evaporation under reduced pressure, and the concentrate is again recrystallized in the same solvent mixture to obtain additional 0.75 mg specified in the header of the S-oxide derivative. Specified in the title compound melts at 91-91,5oC (after recrystallization from a mixture of methylene chloride and diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3465, 3367, 1644. 1461, 1437, 1417, 1018, 948, 752.

28 (III) 2-Isopropyl-6-CHLOROTHALONIL hydrochloride

Gaseous hydrogen chloride is administered for 35 min in a solution 7,74 g 2-isopropyl-6-methylsulfonylmethane [obtained as described in stage (II) above] in 80 ml of 1,2-dichloroethane, heated to 50oC, through the venting tube. The reaction mixture is then cooled to room temperature and add 50 mg of hexane. The precipitated crystals are collected by filtration and washed with hexane to obtain 7.78 g (o) - Rev. yl)-2-(N - xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in example 21, but using 1.0 g (4,17 mmol) of 2-(N-xanthene-9-yl)acetic acid, to obtain the acid chloride. All this acid chloride was dissolved in 30 ml of methylene chloride and then add 917 mg (4,17 mmol) of 2-isopropyl-6-CHLOROTHALONIL hydrochloride [received CAC described in stage (III) above], and the resulting mixture is cooled to -78oC. a Solution of 1.18 mg (9,17 mmol) N-aminobutiramida-N-ethylamine in 5 ml of methylene chloride is then added dropwise to this mixture. The temperature of the mixture is allowed to rise gradually to 0oC for 2 h, then add a solution of 0.30 g (2.32 mmol) of N-aminobutiramida-N-ethylamine in 1 ml of methylene chloride. The mixture was then stirred for 20 min at the same temperature. After this time the reaction mixture is diluted with methylene chloride and the diluted mixture was washed with 2 N. aqueous hydrochloric acid, once with saturated aqueous sodium hydrogen carbonate solution and then once with a saturated aqueous solution of sodium chloride. The organic phase is concentrated by evaporation under reduced pressure to a volume of about 10 ml and the concentrate is diluted with 10 ml of diethyl ether. The precipitated crystals are collected to obtain 0.73 g specified in the title compounds as the first batch of product. MA ether for planting and 0.46 g of the second batch of product. The concentrate obtained from the mother liquor of the second party product, purified column chromatography through 15 g, using 50:1 by volume mixture of methylene chloride and ethyl acetate as eluent, to obtain additional 0,19 g specified in the connection header in the form of crystals. The total yield of 1.38 g (yield 82%). Specified in the title compound melts at 199,5-202oC (after recrystallization from ethyl acetate and diethyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3218, 1656, 1598, 1576, 1530, 1482, 1456, 1409, 1359, 1262.

28(V) N-(2-Isopropyl-6-acetoxymethyl)-2-(N-xanthene - 9-yl)ndimethylacetamide

Suspension 189 mg (0,467 mmol) of N-(2-isopropyl-6-chloromethylene) -2-(N-xanthene-9-yl)ndimethylacetamide [obtained as described in stage (IV) above], 153 mg (186 mmol) of sodium acetate and 105 mg (0.70 mmol) of sodium iodide in 2 ml of N,N-dimethylformamide is stirred for 3 h at 50oC. the Reaction mixture was diluted with ethyl acetate, and the diluted mixture was washed several times with water. The organic phase is dried over anhydrous magnesium sulfate and then the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 7 g of silica gel, using a gradient method of allaround 63%) specified in the header of the acetyl derivative in the form of crystals, melting at 159-160oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3249, 1746, 1647, 1600, 1577, 1525, 1480, 1458, 1261, 1217.

28(VI) N-(2-Isopropyl-6-hydroxymethylene)-2-(N - xanthene-9-yl)ndimethylacetamide

A solution of 79 mg (1,98 mmol) of sodium hydroxide in 1 ml of water are added to a solution of 567 mg (1,32 mmol) of N-(2-isopropyl-6-acetoxymethyl)-2-(9H-xanthene-9-yl)ndimethylacetamide [obtained as described in stage (v) above in 15 ml of methanol, and the mixture was stirred for 1 h at room temperature. After this time the reaction mixture is distributed between ethyl acetate and water. The organic phase is washed with saturated aqueous sodium chloride and the solvent is removed by distillation under reduced pressure to obtain 511 mg (quantitative yield) specified in the procurement compound, melting at 155-156oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3248, 1660, 1646, 1528, 1480, 1457, 1255, 1045.

Method B

28(vii) N-(2-Isopropyl-6-hydroxymethylene)-2-(9H-xanthene-9-yl) ndimethylacetamide

4,24 g (25 mmol) of silver nitrite are added to a solution 10,14 g (25,0 mmol) of N-(2-soon, 100 ml of tetrahydrofuran and 200 ml of water at 60oC. after this time the reaction mixture is concentrated by evaporation under reduced pressure and the concentrate is diluted with ethyl acetate. The diluted mixture was washed with water and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous magnesium sulfate and then the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through silica gel, using 3:1 by volume mixture of methylene chloride and ethyl acetate as eluent to obtain 6,41 g (yield 66%) indicated in the title compound in the form of crystals.

Preparation 29

N-(2-Isopropyl-6-formylphenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide

How A

Should the method similar to that described in preparation 19, but using N-(2-isopropyl-6-hydroxymethylene)-2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in preparation 28) as starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 201-202oC (after recrystallization from a mixture of methylene chloride, diethyl ether and hexane).

Infr Method B

300 mg (4.0 mmol) of trimethylamine N-oxide are added under ice cooling to a solution of 406 mg (1.0 mmol) of N-(2-isopropyl-6-chloromethylene)-2-(9H-xanthene-9-yl)ndimethylacetamide [obtained as described in stage (IV) above] in a mixture of 6 ml of dimethyl sulfoxide and 2 ml of methylene chloride. After completion of addition, the temperature give to gradually reach room temperature and the resulting mixture was stirred for 15 h at room temperature. After this time the reaction mixture was diluted with ethyl acetate, and the diluted mixture was washed with water and saturated aqueous sodium chloride. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through silica gel, using methylene chloride as eluent to obtain 173 g (yield 45%) specified in the connection header in the form of crystals.

Preparation 30

N-[2-Isopropyl-6-(3-hydroxypropyl)phenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide

30(I) N-[2-Isopropyl-6-(2-ethoxycarbonylethyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in preparation 16, but using N-(2-isopropyl-6-formylphenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in photocathode the title compound as crystals, melting at 217-218oC (after recrystallization from a mixture of ethyl acetate and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3275, 2969, 1709, 1666, 1638, 1517, 1480, 1460, 1313, 1253, 1178, 761.

30(II) N-[2-Isopropyl-6-(3-hydroxy-1-propylene)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide

68 l epirate of boron TRIFLUORIDE added at -78oC to a solution of 228 mg (0.5 mmol) N-[2-isopropyl-6-(2-ethoxycarbonylethyl) phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide [obtained as described in stage (I) above] in 6 ml of methylene chloride. The resulting mixture was stirred for 30 minutes, then for 5 min added dropwise 2.0 ml, 1.0 M solution diisobutylaluminium. The temperature of the mixture is allowed to rise to room and then to the reaction mixture add 10 ml of 10% wt./the amount of aqueous solution of grape acid to stop the reaction. The reaction mixture is then diluted with methylene chloride. The diluted mixture was washed with saturated aqueous sodium bicarbonate and then saturated aqueous sodium chloride. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is triturated in a mixture of diethyl ether and hexane to cause crystal is one, melting at 225-227oC (after recrystallization from a mixture of acetonitrile and diisopropyl ether).

Infrared absorption spectrum (KBr),maxcm-1: 3285, 2962, 1653, 1480, 1458, 1256, 756.

230(III) N-[2-isopropyl-6-(3-hydroxypropyl)phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in example 8, but using N-[2-isopropyl-6-(3-hydroxy-1-propenyl)phenyl] -2-(9H-xanthene-9-yl) ndimethylacetamide [obtained as described in stage (II) above] as a starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 218-219oC (after recrystallization from a mixture of diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 3405, 3236, 2963, 1652, 1518, 1482, 1458, 1260, 758.

Preparation 31

N-{ 2-Isopropyl-6-[(3-hydroxypropyl)oxymethyl]phenyl}-2- (9H-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in preparation 1, using N-(2-isopropyl-6-hydroxymethylene)-2-(9H-xanthene-9-yl) ndimethylacetamide (obtained as described in preparation 28) as starting product, in an appropriate amount used in cooking, get the decree and diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1:

Preparation 32

N-[2-Isopropyl-6-(2-hydroxyethyl)oxymethylphenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in preparation 1 (II), but using N-(2-isopropyl-6-chloromethylene)-2-(9H-xanthene-9-yl)ndimethylacetamide [obtained as described in preparation 28 (IV)] and ethylene glycol as starting materials, in the appropriate ratio used in this preparation, get mentioned in the title compound, melting at 153-154oC (after recrystallization from a mixture of diethyl ether and hexane) to yield 52%.

Infrared absorption spectrum (KBr),maxcm-1: 3384, 3255, 2962, 2869, 1650, 1522, 1478, 1457, 1258, 1116, 752.

Preparation 33

N_ [2-tert-Butyl-5-(4-cyclohexyl-3-formylmethyl)phenyl] -2- (9H-xanthene-9-yl)ndimethylacetamide

33(i) N-[2-tert-Butyl-5-(4-cyclohexyl-3-(methoxybenzylidene) butyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide

1,51 ml (2,42 mmol) of 1.6 M hexane solution of utility added dropwise over 3 min to a suspension 828 mg (2,42 mmol) ethoxymethylenemalononitrile in 10 ml of tetrahydrofuran while cooling with ice. The resulting mixture was then stirred for 30 min at the same temperature, and then to the scientists, as described in example 13). The temperature of the mixture is allowed to rise to room temperature and then the reaction mixture was stirred an additional 1 h To stop the reaction, to the reaction mixture is added saturated aqueous solution of ammonium chloride, then extracted with diethyl ether. The extract is washed twice with water and once with saturated aqueous sodium chloride. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 25 g of silica gel using the method of gradient elution with mixtures of methylene chloride and ethyl acetate, varying from 100:3 to 100:5 by volume as the eluent. United eluate concentrated by evaporation under reduced pressure, and the concentrate is recrystallized from a mixture of diethyl ether and hexane to obtain 278 g (yield 62%) specified in the header of the vinyl ester derived in the form of crystals, melting at 117-118oC.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2847, 1670, 1639, 1578, 1541, 1529, 1481, 1458, 1257, 1213.

33 (i) N-[2-tert-Butyl-5-(4-cyclohexyl-3-(methoxybenzylidene) butyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide

2 ml of 2 N. aqueous hydrochloric who-(9H-xanthene-9-yl)ndimethylacetamide [received, as described in stage (I) above] in 8 ml of tetrahydrofuran, and the mixture was stirred for 4 h at 50oC. after this time the reaction mixture is allowed to cool to room temperature, then diluted with diethyl ether. The diluted mixture was washed with water until neutral environment and then saturated aqueous sodium chloride. The organic phase is then dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 15 g of silica gel using the method of gradient elution with mixtures of methylene chloride and ethyl acetate, the changing relations from 100:3 to 100:5 by volume as the eluent. United eluate concentrated by evaporation under reduced pressure, and the concentrate is recrystallized from a mixture of diethyl ether and hexane to obtain 227 g (yield 83%) indicated in the title compound, melting at 121-122oC.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2851, 1726, 1655, 1639, 1576, 1527, 1479, 1458, 1419, 1363, 1298, 1257.

Preparation 34

{ A-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido] phenyl} methylmethcathinone bromide

34 (I) N-[2-tert-Butyl-5-bromomethylphenyl the pet-butyl-5-hydroxymethylene)-2- (9H-xanthene-9-yl)ndimethylacetamide (received as described in preparation 14) and 2,04 g (to 7.77 mmol) of triphenylphosphine in 20 ml of methylene chloride, and the mixture was stirred for 4 h at room temperature. After this time the reaction mixture is placed in a column containing 100 g of silica gel, and column elute 1: 9 by volume mixture of diethyl ether and methylene chloride. Eluate are combined and concentrated by evaporation under reduced pressure to get 2,52 g (yield 85%) specified in the header of bromide in the form of crystals, melting at 229-231oC (after recrystallization from ethyl acetate).

Infrared absorption spectrum (KBr),maxcm-1: 3216, 1640, 1535, 1487, 1457, 1414, 1366, 1262, 1236, 763.

34 (II) { 4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl} methylmethcathinone bromide

The solution 2,52 g (5,42 mmol) N-[2-tert-butyl-5-bromomethylphenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide [obtained as described in stage (I) above] and 1.58 g (of 6.02 mmol) of triphenylphosphine in 25 ml of toluene is heated under reflux for 5 h with vigorous stirring. After this time, allow to cool to room temperature and the resulting precipitate is collected by filtration and spray. The precipitate was washed with toluene and hexane and dried over anhydrous sodium sulfate with receipt is sny absorption spectrum (KBr),maxcm-1: 3420, 1669, 1482, 1459, 1439, 1256, 1111, 834, 753, 691.

Preparation 35

1-Benzyloxy-5-cyclohexyl-2-pentanon

35 (I) 4-Cyclohexyl-1-(benzoyloxymethyl)butanol

A solution of 1.01 g (of 6.73 mmol) of 2-benzyloxyacetaldehyde in 6 ml of diethyl ether is added dropwise over 3 min to 14 ml (8.6 mmol) of 0.6 M solution in diethyl ether 3-cyclohexylpropionic bromide under ice-cooling, and the mixture was stirred for 30 min at the same temperature and then for 10 min at room temperature. To stop the reaction, to the reaction mixture is added saturated aqueous solution of ammonium chloride. The reaction mixture was then diluted with diethyl ether, and the diluted mixture was washed with water and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous magnesium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 150 g of silica gel using 1:3 by volume mixture of ethyl acetate and hexane as eluent, to obtain 1.27 g (yield 68%) specified in the header of the alcohol derivative in the form of butter.

Infrared absorption spectrum (liquid film),maxcm-1: 3470, 3031, 1497, 1451, Nomo in preparation 19, but ispolzuya 4-cyclohexyl-1-(benzoyloxymethyl)butanol [obtained as described in stage (I) above] as a starting product, in an appropriate amount used in cooking, get mentioned in the title compound in the form of butter.

Infrared absorption spectrum (liquid film),maxcm-1: 3032, 1721, 1497, 1451, 1260, 1210, 1102, 1028, 737, 699.

Preparation 36

3 Cyclohexyloxy-1-(benzoyloxymethyl)propyl alcohol

and

4 cyclohexyloxy-2-benzyloxyethanol alcohol

36 (i) 4-Cyclohexylpropionic alcohol

of 14.0 ml (14.0 mmol) of 1 M hexane solution diisobutylaluminium hydride is added dropwise within 5 min to a solution of 1.01 g (647 mmol) of 1,5-dioxaspiro[5,5] undecane in 5 ml of methylene chloride, and the mixture was stirred for 1 h at room temperature. After this time the reaction mixture is cooled with ice and added dropwise within 5 min and 20 ml of methanol to stop the reaction. The mixture is stirred for 20 min at room temperature and then add 2 N. aqueous solution of hydrochloric acid to dissolve the precipitate. The mixture is then extracted with diethyl ether. The extract is washed with water, saturated aqueous sodium hydrogen carbonate and neymann the Oia and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 25 g of silica gel using 3:1 by volume mixture of diethyl ether and hexane as eluent, to obtain 774 mg (yield 76%) specified in the header of the alcohol derivative in the form of butter.

Infrared absorption spectrum (liquid film),maxcm-1; 3390, 1451, 1366, 1258, 1092, 984, 967, 930, 889.

36 (II) 1-Cyclohexyloxycarbonyl

Following the method similar to that described in preparation 19, but using 3-cyclohexylpropionic alcohol (obtained as described in stage (I) above) as the original product, in an appropriate amount used in this example, get mentioned in the title compound in the form of butter.

Infrared absorption spectrum (liquid film),maxcm-1: 2728, 1727, 1451, 1364, 1258, 1212, 1100, 1025, 984,889.

36 (III) 4-Cyclohexyloxy-1-butene

3,3 ml of 1.6 M hexane solution of utility added dropwise over 4 min to a suspension of 1.88 mg (5,26 mmol) methyltriphenylphosphonium bromide in 19 ml of tetrahydrofuran at -20oC. the Reaction mixture is left for 25 min, then added dropwise over 3 min to a solution of 747 mg (of 4.75 mmol) 3-cyclohexanedione (obtained as described in stage 1 the setting reaction to the reaction mixture is added saturated aqueous solution of ammonium chloride, then extracted with diethyl ether. The extract is washed with water and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous magnesium sulfate and then the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 25 g of silica gel using 1:1 by volume mixture of methylene chloride and hexane as the eluent, to obtain 462 mg ( yield 63) specified in the header olefin derived in the form of butter.

Infrared absorption spectrum (liquid film) maxcm-1: 3079, 1642, 1451, 1364, 1258, 1107, 992, 957, 913.

36 (IV) 4-Cyclohexyloxy-2-hydroxybutanoic alcohol 1.9 ml (0.15 mmol) 2% weight/volume solution of osmium tetroxide added to a solution of 462 mg (3.00 mmol) of 4-cyclohexyloxy-1-butene [obtained as described in stage (III) above] and 702 mg (of 5.99 mmol) N-methylmorpholine-N-oxide in a mixture of 20 ml of acetonitrile and 5 ml of water, and the resulting mixture was stirred for 12 h at room temperature. To stop the reaction mixture is added an aqueous solution of sodium sulfite, and then extracted with utilitatem. The extract is washed with water, 2 N. aqueous hydrochloric acid, saturated aqueous sodium hydrogen carbonate and nashatm magnesium and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 15 g of silica gel, using ethyl acetate as eluent, to obtain 443 mg (yield 78%) specified in the header of the derived diol in the form of butter.

Infrared absorption spectrum (liquid film),maxcm-1: 3990, 1451, 1366, 1258, 1092, 994, 951, 872, 791.

36 (v) 2-Phenyl-4-(2-cyclohexylethyl)-1,3-dioxolane

43 mg (1,23 mmol) n-toluensulfonate acid monohydrate added under ice cooling to a solution of 473 mg (2.51 mmol) of 4-cyclohexyloxy-2-hydroxybutyrate alcohol [obtained as described in stage (IV) above] and 1.14 ml (7.56 mmol) of dimethylacetal benzaldehyde in 10 ml of methylene chloride, and the mixture was stirred for 2.5 h at room temperature. To stop the reaction, to the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, then extracted with diethyl ether. The extract was washed with saturated aqueous sodium chloride. The organic phase is dried over anhydrous magnesium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 50 g of silica gel using 1:9 by volume mixture of diethyl and methyl chloride as the eluent, to receive the absorption spectrum (liquid film),maxcm-1: 1453, 1403, 1366, 1219, 1096, 1026, 914, 758, 699.

36 (VI) 3-Cyclohexyloxy-1-(benzoyloxymethyl)propyl alcohol and 4-cyclohexyloxy-2-benzyloxyethanol alcohol.

a 4.5 ml (4.5 mmol) of 1 M hexane solution diisobutylaluminium hydride is added dropwise within 5 min to a solution of 560 mg (2.03 mmol) of 2-phenyl-4-(2-cyclohexylethyl)-1,3-dioxolane [obtained as described in stage (V)above) in 5 ml of methylene chloride, and the mixture was stirred for 50 minutes To stop the reaction, to the reaction mixture add 0.8 ml of methanol, and the precipitate is dissolved by adding 2 N. aqueous hydrochloric acid, then extracted with diethyl ether. The extract is washed with water, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. The organic phase is dried over anhydrous magnesium sulfate and the solvent is removed by distillation under reduced pressure. The obtained residue cleans column chromatography through 60 g of silica gel using 1:4 by volume mixture of ethyl acetate and methylene chloride as eluent, obtaining 409 mg (yield 72%) of the less polar alcohol, 3-cyclohexyloxy-1-(benzoyloxymethyl)propyl alcohol and 133 mg (yield 24%) of the more polar secondary alcohol, 4-cyclog the config spectrum (liquid film),maxcm-1:

3 Cyclohexyloxy-1 (benzoyloxymethyl)propyl alcohol 3450, 1453, 1364, 1206, 1100, 1026, 737, 699.

4 Cyclohexyloxy-2-benzyloxyethanol alcohol 3440, 1453, 1208, 1092, 1938, 737, 699.

Preparation 37

1-Benzyloxy-4-cyclohexyloxy-2-butanone

Following the method similar to that described in preparation 19, but using 3-cyclohexyloxy-1-(benzoyloxymethyl)propyl alcohol (obtained as described in preparation 36) as the original product, in an appropriate amount used in cooking, get mentioned in the title compound in the form of butter.

Infrared absorption spectrum (liquid film, maxcm-1: 3032, 1725, 1453, 1366, 1258, 1209, 1195, 1026, 739, 698.

2-Benzyloxy-4-cyclohexanedimethanol

Following the method similar to that described in preparation 19, but using 4-cyclohexyloxy-2-benzyloxyethanol alcohol (obtained as described in preparation 36) as the original product, in an appropriate amount used in cooking, get the title compound in the form of butter.

Infrared absorption spectrum (liquid film),maxcm-1: 3032, 1734, 1453, 1366, 1209, 1104, 1026, 951, 739, 699.

The cooking is reed sodium (in the form of a 55% by weight dispersion in mineral oil, pre-washed helsana) in 10 ml of dimethylsulfoxide is stirred for 30 minutes, then add 2.66 g (12.1 mmol) trimethylsulfoxonium iodide. The resulting mixture was stirred for 1 h at 40oC and then added dropwise over 5 min a solution 4,50 g (10.5 mmol) of N-[2-tert-butyl-5-(3-oxopropyl)phenyl] -2-(9N-xanthene-9-ml)ndimethylacetamide (obtained as described in preparation 19) in 25 ml of tetrahydrofuran. The reaction mixture was then stirred for 1 h, after which the reaction mixture is then stirred for 1 h, after which the reaction mixture is then stirred for 1 h, after which the reaction mixture is cooled to room temperature and then diluted with ethyl acetate. The diluted mixture was washed several times with water and once with saturated aqueous sodium chloride. The organic phase is dried over anhydrous magnesium sulfate and then the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 250 g of silica gel using 9:1 by volume mixture of methylene chloride and ethyl acetate as eluent to obtain 3.00 g (yield 65%) indicated in the title compound as crystals, melting at 156-157oC (after recrystallization from ethyl acetate and hexane)

Infrared BR>
N-(2-tert-Butyl-5-{ 4-cyclohexyl-3-[2-(benzyloxycarbonylamino) acetoxy]butyl}phenyl-2-(9N-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in preparation 25, but using N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2-(9N - xanthene-9-yl)ndimethylacetamide (obtained as described in example 12) and 2-(benzyloxycarbonylamino)acetic acid as starting materials, in the appropriate ratio used in this preparation, receive specified in the header of the United in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 3275, 2923, 1733, 1660, 1481, 1457, 1256, 1153, 1119, 760.

Preparation 41

N-(2-tert-Butyl-5-{4-cyclohexyl-3- [2-(benzyloxycarbonylamino)acetoxy] butyl}phenyl) - 2-(9H-xanthene-9-yl)ndimethylacetamide

and

N-(2-tert-Butyl-5-{4-ciclohexyl-3- [2-(benzyloxycarbonylamino)acetoxy] butyl}phenyl) - 2-(9H-xanthene-9-yl)ndimethylacetamide

Following the method similar to that described in example 194, but using N-(2-tert-butyl-5-{ 4-cynthesis-3- [2-(benzyloxycarbonylamino)acetoxy]butyl} phenyl) -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in preparation 40) as the original product, in an appropriate number, using regreny absorption spectrum (KBr),maxcm-1:

N-(2-tert-butyl-5-{ 4-cyclohexyl-3- [2-benzyloxycarbonylamino)acetoxy] butyl] phenyl) -2-(9H-xanthene-9-yl)ndimethylacetamide 3274, 2924, 1738, 1660, 1481, 1458, 1340, 1294, 1256, 1117, 760;

N-(2-tert-butyl-5-{4-cyclohexyl-3- [2-(benzyloxycarbonylamino)acetoxy] butyl}phenyl)-2-(9H-xanthene-9-yl)ndimethylacetamide 3271, 2923, 1732, 1660, 1481, 1457, 1257, 1118, 1058, 759.

Preparation 42

N-{ 2-tert-Butyl-5-[3-(benzyloxycarbonylamino) -4-cyclohexylmethyl]phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide

A solution of 55 l (0.46 mmol) of trichloromethyl of chloroformate in 1 ml of tetrahydrofuran is added dropwise a solution of 74 l (of 0.91 mmol) of pyridine in 1 ml of tetrahydrofuran with ice cooling and then the temperature gradually give to reach room. The mixture is stirred for 1 h at room temperature, and then again cooled and added dropwise to 400 mg (from 0.76 mmol) of N-[2-tert-butyl-5- (4-cyclohexyl-3-hydroxybutyl)phenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 12) in 3 ml of tetrahydrofuran. The mixture is stirred for 1 h at the same temperature and then the solvent is removed by distillation under reduced pressure to get the foam product in the form of sediment. The residue is dissolved in 1 ml of methylene chloride and added dropwise a solution of 151 mg (of 0.91 mmol who drop ice. The mixture is stirred at room temperature for 1 h and then the reaction mixture is diluted with methylene chloride, after which it is washed with water and saturated aqueous sodium chloride, in that order. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through 75 g of silica gel using 1: 9 by volume mixture of methylene chloride and ethyl acetate as eluent, obtaining 522 g (yield 96%) specified specified in the title compounds as colorless foamy product.

Infrared absorption spectrum (KBr), maxcm-1: 3274, 2924, 2853, 1750, 1655, 1480, 1458, 1422, 1256, 1194, 758.

Preparation 43

N-{ 2-tert-Butyl-5-[7-cyclohexyl-3-(methoxyethoxy) heptyl] phenyl}-2-(9H-xanthene 9-yl)ndimethylacetamide

43 (I) (S)-[6-Benzyloxy-5-(methoxyethoxy)hexyl] cyclohexane of 25.6 ml (184 mmol) of triethylamine and then with 9.3 ml (122 mmol) of methoxymethane added to a solution of 10 g (34.4 mmol) of (S) -(I-benzyloxyethyl-5-cyclohexyl)pentalofos alcohol [obtained similarly to the method described in preparation 23 (I), but using cyclohexylamine bromide] in 200 ml of N, N-dimethylformamide, and the resulting mixture paramesh the second pressure and the concentrate is mixed with ice water, then extracted three times with ethyl acetate. The combined extracts washed with saturated aqueous sodium chloride. The organic phase is dried over anhydrous sodium sulfate and the solvent is distilled off under reduced pressure. The resulting residue is purified column chromatography through silica gel using 9:1 by volume mixture mehsana and ethyl acetate as eluent, to obtain 10.2 g (yield 89%) specified in the header ethoxymethylene derived in the form of butter.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: 0,73-1,80 (19H, multiplet); 3,39 (3H, singlet); 3,51 (2H, doublet, J = 5Hz), 3,69-3,85 (IH, multiplet); 4,56 (2H, singlet); and 4.68(IH, doublet, J=7 Hz); 4,79 (IH, doublet, J = 7 Hz); 7.23 percent-7,42 (5H, multiplet).

43 (II) (S)-6-Cyclohexyl-2-(methoxyethoxy)hexyl alcohol

Following the method similar to that described in preparation 23 (III), but using (S)-[6-benzyloxy-5-(methoxyethoxy)hexyl] cyclohexane [obtained as described in stage (I) above] as a starting product, in an appropriate amount used in cooking, get mentioned in the title compound in the form of butter.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: 0.75 to 1.8 m (19H, multiplet); 2,9-3,2 (IH, usernotes-5-(3-methoxyethoxy-7-cyclohexyl-1 - heptenyl)-1-nitrobenzene

(S)-6-Cyclohexyl-2-(methoxyethoxy)hexyl alcohol [obtained as described in stage (II) above] are oxidized by the method similar to that described in preparation 23 (IV) to give the aldehyde derivative. It is subjected to a Wittig reaction by a method similar to that described in preparation 23(V), obtaining specified in the header olefin derived in the form of butter.

43 (IV) (S)-2-tert-Butyl-5-(3-methoxyethoxy-7 - cyclohexylmethyl)aniline.

A solution of 2.2 g (5,27 mmol) of (S)-2-trebuil-5-(3-methoxyethoxy-7-cyclohexyl-1-heptenyl) -1-nitrobenzene [obtained as described in stage (III) above] in 40 ml of ethanol vigorously stirred in a stream of hydrogen for 6 h in the presence of 1.5 g of 10% by weight palladium on coal. The catalyst was then filtered off and washed with ethanol. The filtrate and wash water are combined and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography through silica gel using 9:1 by volume mixture of hexane and ethyl acetate as eluent, obtaining of 1.16 g (yield 57% specified in the header of a derivative of aniline in the form of butter.

Spectrum of nuclear magnetic resonance (CDCI3, 270 MHz), ppm: 0,75-1,9 (21H, multiplet); of 1.40 (9H, signet); 2,43-2,70 21H, mu 8 Hz).

43 (V) (S)-N-(2-tert-Butyl-5-[7-ciclohexyl-3-(methoxyethoxy) heptyl] phenyl}-2-(9H-xanthene 9-yl)ndimethylacetamide

Following the method similar to that described in example 35, but using (S)-2-tert-butyl-5-(3-methoxyethoxy-7-cyclohexylmethyl)aniline [obtained as described in stage (IV) above] as a starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 71-73oC (after recrystallization from hexane). Infrared absorption spectrum (KBr)maxcm-1: 3221, 1639, 1577, 1535, 1482, 1456, 1263, 1255, 1034. Spectrum of nuclear magnetic resonance (CDCL3, 270 MHz), ppm: 0.75 to 1,90 (21H, multiplet); 2,25-8,80 (4H, multiplet); 3.42 points (3H, singlet); 3.45 points-3,70 (IH, multiplet); 4,60-4,82 (3H, multiplet); 6.90 to-7,46 (IIH, multiplet).

Preparation 44

N-{2-tert-Butyl-5-[3-(4-benzyloxycarbonylamino) -4-cyclohexylmethyl]phenyl}-2-(9H-xanthene-9-yl)ndimethylacetamide

44 (I) 4-Hydroxymethylbilane acid

A solution of 9.00 g (39,3 mmol) n-bromomethylphenyl acid, 3,14 g (78,6 mmol) of sodium hydroxide and of 3.54 g (43.2 mmol) of sodium acetate in 40 ml of water is stirred for 4 hours at a temperature of 100oC. after this time it is cooled to room temperature saturated aqueous sodium chloride. The organic phase is dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The precipitate is recrystallized from a mixture of ethyl acetate and methylene chloride with the receipt of 3.60 g (yield 55%) indicated in the title compound, melting at 136-137oC.

Infrared absorption spectrum (KBr),maxcm-1: 3304, 1703, 1520, 1421, 1408, 1360, 1288, 1234, 1200, 1188, 1009.

44 (II) Benzyl 4-hydroxymethylimidazole 2,52 g (of 23.8 mmol) of sodium carbonate and 8,13 g (47,6 mmol) benzylbromide added to a solution of 3.95 g (23,8 mmol) 4-hydroxymethylcellulose acid [obtained as described in stage (I) above] in 40 ml of N, N-dimethylformamide, and the mixture is stirred for 3.5 hours At the end of this time the reaction mixture was diluted with diethyl ether, and the diluted mixture was washed with water and then saturated aqueous sodium chloride. The organic phase is dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The precipitate purified column chromatography through 200 g of silica gel using a gradient method of elimination, with a mixture of methylene chloride and ethyl acetate, varying from 100: 5 to 100:3 by volume, which gives to 5.03 g (Vya film),maxcm-1: 2941, 2876, 1734, 1516, 1499, 1456, 1423, 1377, 1336, 1259, 1221, 1149.

44 (III) Benzyl 4-formylphenylboronic

Following the method similar to that described in preparation 19, but using benzyl 4-hydroxymethylimidazole [obtained as described in stage (II) above] as a starting product, in an appropriate amount used in this example, get mentioned in the title compound as crystals, melting at 54-55oC (after recrystallization from a mixture of diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 1726, 1689, 1607, 1578, 1458, 1425, 1383, 1338, 1225, 1192, 1169.

44 (IV) Benzyl 4-carboxyphenylazo

Following the method similar to that described in preparation 21 (vi), but using benzyl 4-formylpyrazole [obtained as described in stage (III) above] as a starting product, in an appropriate amount used in cooking, get mentioned in the title compound as crystals, melting at 123-124oC (after recrystallization from a mixture of methylene chloride and ethyl acetate).

Infrared absorption spectrum (KBr),maxsee-1: 1718, 1703, 1685, 1610, 1450, 1429, 1323, 1292, 1271, 1182, 1151.

44 (V) N-(2-tert-Butyl-5-[3-(4-benzile the WMD described in preparation 25, but using benzyl 4-carboxyphenylazo [obtained as described in stage (VI) above] and N-[2-tert-butyl-5-(4-cyclohexyl-3 - hydroxybutyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide (obtained as described in example 12) as starting materials, in the appropriate ratio used in this preparation, get mentioned in the title compound in the form of a foamy product.

Infrared absorption spectrum (KBr),maxcm-1: 2924, 2851, 1736, 1715, 1686, 1655, 1612, 1578, 1522, 1479, 1458, 1273, 1257.

Preparation 45

2-Methyl-6-{[3-(1-imidazolyl)propyl]oxymethyl}aniline

45 (I) 2-Methyl-6-methyloxime-2-nitrobenzene

Following the method similar to that described in preparation I (I), but using 2-methyl-6-hydroxymethyl-1-nitrobenzene as the starting product, in an appropriate amount used in this preparation, receive specified in the header methanesulfonyl derived in the form of crystals, floating at 48-50oC.

45 (II) 2-Methyl-6-[(3-hydroxypropyl)oxymethyl]-1-nitrobenzene

Following the method similar to that described in preparation I (II), but using 2-methyl-6-methyloxime-1-nitrobenzene [obtained as described in stage (i) above] as a starting product in sootvetstvuyu.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: of 1.84 (2H, quintet, J=6 Hz); 2,35 (3H, SIGINT); 3,62 (2H, triplet, J=6 Hz); of 3.75 (2H, broad singlet); 4,56 (2H, singlet); 7,2-the 7.43 (3H, multiplet),

45 (III) 2-Methyl-6-[(3-methyloxirane)oxymethyl]-1 - nitrobenzene

Following the method similar to that described in example 1 (I), but using 2-methyl-6-[(3-hydroxypropyl)oxymethyl]-1-nitrobenzene [obtained as described in stage (II) above] as a starting product, in an appropriate amount used in this example, receive specified in the header methanesulfonyl derived in the form of butter.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: a 2.01 (2H, quintet, J= 6 Hz); 2,35 (3H, singlet); 3,03 (3H, singlet); of 3.56 (2H, triplet, J=6 Hz); 4,32 (2H, triplet, J=6 Hz); 4,56 (2H, singlet); 7,20-7,42 (3H, multiplet).

45 (IV) 2-Methyl-6-{[3-(1-imidazolyl)propyl]oxymethyl]-1 - nitrobenzene

Following the method similar to that described in example I (II), but using 2-methyl-6-[(3-methyloxirane)oxymethyl] -1-nitrobenzene [obtained as described in stage (III) above] as a starting product, in an appropriate amount used in this example, receive specified in the header of imidazolyl derived in the form of butter.

Range nuclear magnitno is of 4.54 (2H, singlet); 6,91 (1H, singlet); 7,05 (1H, singlet); 7,2-7,42 (3H, multiplet); of 7.48 (1H, singlet).

45 (V) methyl-6-{[3-(1-imidazolyl)propyl]oxymethyl}aniline

Following the method similar to that described in preparation 43 (IV), but using 2-methyl-6-{ [3-(1-imidazolyl)propyl] oxymethyl} -1-nitrobenzene [obtained as described in stage (IV) above] as a starting product, in an appropriate amount used in this preparation, receive specified in the header of the aniline derivative in the form of butter.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: a 2.01 (2H, quintet, J=6 Hz); 2,19 (3H, singlet); to 3.38 (2H, triplet, J=6 Hz); Android 4.04 (2H, broadened singlet); to 4.52 (2H, singlet); of 6.65 (1H, triplet, J=7 Hz); 6,85 (1H, singlet); 6,93 (1H, doublet, J=7 Hz);? 7.04 baby mortality (1H, singlet); 7,06 (1H, doublet, J=7 Hz); 7,40 (1H, singlet).

Preparation 46

N-{ 2-tert-Butyl-5-[4-cyclohexyl-3-(tert-butyldimethylsilyloxy) butyl} -2,2-diethyldodecanamide

Following the method similar to that described in example 21, but using 2,2-diethyldodecanamide acid and 2-tert-butyl-5-[4-cyclohexyl-3- (tert-butyldimethylsilyloxy)butyl] aniline [obtained as described in preparation II (I) above] as a starting product, in an appropriate ratio used in this example, receive Uksa (CDCl3, 270 MHz), ppm: 0,05 (6H singlet); or 0.83 (9H, singlet); 0,85-to 0.96 (6H, multiplet); 1,11-1,35 (30H, multiplet); of 1.40 (9H, singlet); 1,58-of 1.78 (6H, multiplet); 2,53-to 2.67 (2H, multiplet); of 3.80 (1H, nhbgktn, J=5 Hz); 6,94 (1H, doublet, J=8 Hz); 7,29 )1H, doublet, J=8 Hz); 7,38 (1H, singlet); 7,56 (1H, singlet).

Preparation 47

N-{2-tert-Butyl-5-[4-cyclohexyl-3-(tert-butyldimethylsiloxy) butyl]phenyl}-6, 11-dihydrobenzo-[b, e]oxyphenyl-11-carboxamide

Following the method similar to that described in example 21, but using 6, 11-dihydrobenzo[b, e] oxepin-11-carboxylic acid and 2-tert-butyl--5-[4-cyclohexyl-3-(tert-butyldimethylsilyloxy)butyl] aniline [obtained as described in preparation II (I) above] as a starting product, in an appropriate ratio used in this example, get mentioned in the title compound as colorless crystals.

Infrared absorption spectrum (KBr),maxcm-1: 3276, 2925, 1648, 1520, 1447, 1256, 1075, 835, 774, 759.

Preparation 48

N-{ 2-tert-Butyl-5-[4-cyclohexyl-3-(tert-butyldimethylsilyloxy) butyl] phenyl}--2-(phenyl-cyclopentyl)ndimethylacetamide

Following the method similar to that described in example 21, but using 2-(1-phenylcyclohexyl)acetic acid and 2-tert-butyl-5- [4-cyclohexyl-3-(tert-butyldimethylsilyloxy)butyl] anichini, used in the form of a foamy product.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 0,06 (6H, singlet); 0,85-to 0.96 (6H, multiplet); of 0.91 (9H, singlet); of 1.07 (9H, singlet); 1.18 to 1.41 for (12H, multiplet); 1,57-2,19 (5H, multiplet); 2,55-2,60 (2H, multiplet); 2,70 (1H, singlet); 3,02 (NB singlet); of 3.78 (1H, triplet, J=6 Hz); 6,33 (1H, singlet); 6,88 was 7.45 (8H, multiplet).

Preparation 49

(S)-1-(2-{ 4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl} ethyl)-2-cyclohexylethyl dibenzyl phosphate

0,86 ml (1,72 mmol) 2 M tertrahydrofuran ring solution tributyltinchloride added over 2 min to a solution of 420 mg (0,799 mmol) of (S)-N-[22-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl] -2-(9H-xanthene-9-yl) acetamide (obtained as described in example 102) in 5 ml of tetrahydrofuran, and the resulting mixture is stirred for another 10 minutes Then add a solution of 556 mg (1,87 mmol) dibenzylpiperazine in 2 ml of tetrahydrofuran, then the mixture is stirred for 1 h To stop the reaction, to the reaction mixture is added saturated aqueous solution of ammonium chloride and then diluted with water. The diluted mixture is extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride. The organic phase is dried over anhydrous magnesium sulfate, and the solvent leakages, using a 1: 9 by volume mixture of ethyl acetate and methylene chloride as eluent getting 505 mg (yield 80%) specified in the connection header in the form of a resinous product.

Infrared absorption spectrum (film), amaxcm-1: 3255, 1655, 1522, 1480, 1459, 1256, 999, 758, 696.

Preparation 50

(K)-2-(2{4-tert-Butyl-3-[2-(9H-xanthene-9-yl)acetamido]phenyl} ethyl)-2-cyclohexylmethyl benzyl succinate

0.09 mg of Diethylazodicarboxylate added under cooling in an ice bath to a solution of 260 mg (0.47 mmol) of (S)-N-[2-tert-butyl-5-(6-cyclohexyl-3-hydroxyhexyl)phenyl] -2-(9H - xanthene-9-yl)ndimethylacetamide (obtained as described in example 189), 117 mg (0,56 mmol) of benzyl hydrosylate and 148 mg (0,56 mmol) of triphenylphosphine in 5 ml of tetrahydrofuran, and the mixture was stirred for 1 h at room temperature. After this time the reaction mixture was stirred with saturated aqueous sodium bicarbonate, then extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate. The solvent is removed by distillation under reduced pressure, and the obtained residue is purified column chromatography through silica gel, using a method proluction fractions, containing small amounts of impurities. Chromatography is repeated in the same conditions and obtain 258 mg (yield 74%) indicated in the title compound in the form of a foamy product.

[]D= + 5.05o(C=1.11, CHCl3)/

Preparation 51

2-tert-Bugil-5-(iodomethyl)-1-nitrobenzene

51(i) 2-tert-Butyl-5-(methanesulfonylaminoethyl)-1-nitrobenzene

Following the method similar to that described in preparation 21 (ii), but using 2-tert-butyl-5-hydroxymethyl-1-nitrobenzene (obtained as described in preparation 12) as the original product, in an appropriate amount used in this preparation, receive specified in the procurement methysulfonylmethane.

51 (ii) 2-tert-Butyl-5-(iodomethyl)-1-nitrobenzene of 1.65 g (11 mol) of sodium iodide are added to a solution of 2.00 g (of 6.96 mmol) 2-tert-butyl-5-(methanesulfonylaminoethyl)-1-nitrobenzene [obtained as described in stage (i) above] in 40 ml of acetone, and the mixture was stirred at 50oC for 20 minutes, after this time the reaction mixture is cooled to room temperature and filtered. The residue is washed with ethyl acetate and the combined filtrate and washing liquid are concentrated by evaporation under reduced pressure. Concentrate rastvoryayas solution of sodium chloride, in this sequence. The organic phase is dried over anhydrous sodium sulfate and the solvent is removed by distillation under reduced pressure to get to 2.18 g (yield 98%) indicated in the title compound as crystals, melting at 98-99oC (after recrystallization from a mixture of methylene chloride, diethyl ether and hexane).

Infrared absorption spectrum (KBr),maxcm-1: 1530, 1370, 1250, 1169, 1061, 886, 839, t 807, 627.

Spectrum of nuclear magnetic resonance (CDCl3, 270 MHz), ppm: 1,39 (H, singlet); 4,39 (2H, singlet); to 7.32 (1H, doublet, J=2 Hz); 7,44 (1H, doublet of doublets, J= 2&8 Hz); of 7.48 (1H, doublet, J=8 Hz).

Preparation 52

(4-tert-Butyl-3-nitrophenyl)methyltriphenylphosphonium iodide

Following the method similar to that described in preparation 34 (II), but using 2-tert-butyl-5-(iodomethyl)-1-nitrobenzene (obtained as described in preparation 51) as the original product, in an appropriate amount used in cooking, get mentioned in the title compound in the form of a powder. The product is used in the next stage without additional purification.

Preparation 53

N-[2-Methoxymethyl-6-formylphenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide

53 (i) N-[2-Methoxymethyl-6-(Geopolis 2-methoxymethyl-6-(tert-butyldimethylsilyloxy)-1-nitrobenzene as the starting product, the appropriate amount used in cooking, get mentioned in the title amide derivative in the form of crystals, melting at 194-194,5oC (after recrystallization from a mixture of methyl chloride and ethyl acetate).

Infrared absorption spectrum (KBr),maxcm-1: 3256, 1647, 1596, 1577, 1523, 1484, 1457, 1362, 1301, 1263, 1098, 1066, 752.

53(II) N-[2-Methoxymethyl-6-formylphenyl]-2-(9H-xanthene-9-yl)ndimethylacetamide.

Following the method similar to that described in preparation 19, but using N-[2-methoxymethyl-6-(hydroxymethyl)phenyl] -2-(9H-xanthene-9-yl)ndimethylacetamide [obtained as described in stage (I) above] as a starting product in the appropriate amount used in cooking, get mentioned in the title compound as crystals, melting at 202,5-203oC (after recrystallization from a mixture of methylene chloride and acetone).

Infrared absorption spectrum (KBr),maxcm-1: 3270, 1698, 1645, 1592, 1578, 1518, 1482, 1456, 1254, 1250, 1112, 755.

Preparation 54

N-[5-(3-hydroxypropoxy)-2-methylthiophenyl]-2-(9H-xanthene-9-yl) ndimethylacetamide

After the procedure similar to that described in preparation 14, but using 5-(3-tert-butyldimethylsilyloxy)hydroxy-2-methylthio-the data preparation, the target compound obtained as crystals with a melting point of 136-137oC (after recrystallization from a mixture of ethyl acetate, diethyl ether and hexane).

Spectrum infrared absorption (KBr),max: 3297, 1657, 1600, 1574, 1530, 1481, 1457, 1299, 1260, 1237, 1189.

Preparation 55

N-(2-ethyl-6-{ 1-[2-(9H-xanthene-9-yl)acetoxy]propyl}phenyl)-2 (9H-xanthene-9-yl)ndimethylacetamide

After the procedure similar to that described in example 21, but using 2.2 equivalents of 2-(9H-xanthene-yl)acetylchloride and 1 equivalent of 2-ethyl-6-(1-hydroxypropyl)-aniline, get the target compound in the form of Prepodobnogo material.

Spectrum infrared absorption (KBr),max: 2968, 2932, 2876, 1726, 1657, 1601, 1576, 1479, 1458, 1363, 1342, 1255.

Medicinal part 1

The drug is in the form of hard capsules.

100 mg one of the following active compounds: 150 mg of lactose, 50 mg of cellulose and 6 mg of magnesium stearate, placed in a hard gelatin capsule conventional separate type, and the capsules are washed and then dried. The active compounds are obtained as described in examples 2, 4, 12, 26, 57 and 59.

Medicinal part 2

The drug is in the form of soft capsules

Prepare a mixture of one of the compounds, recip is shining the pump to obtain soft capsules, each of which contains 100 mg of active ingredient. The capsules are washed and dried. Other capsules are prepared using the oil of cotton seeds instead of soybeans. If desirable, can also be used with other edible oils.

Medicinal part 3

drug pill

100 g of the active compound, 0.2 mg of colloidal silicon dioxide, 5 mg of magnesium stearate, 275 mg of high quality crystalline cellulose, 11 mg of starch and 98,8 mg of lactose are mixed and then formed into tablets by conventional methods. The active compounds are obtained as described in examples 2, 4, 12, 26, 57 and 59. When desirable, carry out the coating of tablets.

1. Amido - or carbamazapine formula I

< / BR>
where R1means an alkyl group having from 1 to 20 carbon atoms, or a group of formula II, III, IV or V

< / BR>
where R5means an alkyl group having from 1 to 15 carbon atoms; m denotes an integer from 1 to 4; and any aromatic ring in the specified group, raspredelenie R1is unsubstituted;

R2means a hydrogen atom or alkyl group having from 1 to 10 carbon atoms;

R3means

alkyl group, Youssou from 1 to 10 carbon atoms,

alkylsulfonyl group having from 1 to 10 carbon atoms,

alkylsulfonyl group having from 1 to 10 carbon atoms, or

alkoxyalkyl group, in which CNS part has from 1 to 6 carbon atoms and the alkyl part has from 1 to 4 carbon atoms;

R4means a group of the formula VI, VII, VIII, IX, X or XI

< / BR>
where A1means a single bond or alkilinity group having from 1 to 4 carbon atoms;

A2means dangerou communication or alkilinity group having from 1 to 6 carbon atoms;

A3, A3aand A5independently selected from the group consisting of single bond and alkylene group having from 1 to 10 carbon atoms which may be saturated or may include carbon-carbon double bond, provided that the total number of carbon atoms in A3, A4and A5and in A3a, A4and A5does not exceed 10;

R6means an alkyl group having from 1 to 6 carbon atoms, cycloalkyl group having 3 to 9 carbon atoms in one or more aliphatic carbocyclic rings, these rings are unsubstituted or phenyl group, substituted by at least one atom is displaced by at least one1- C4is an alkyl group;

R7means a hydrogen atom, a benzyl group, phosphonopropyl or a group of formula XII

< / BR>
where z1is 0 or 1;

z2is 0, 1 or 2;

X is an oxygen or sulfur atom, or sulfinil, sulfonium or phenylenebis group, provided that when Z2is 2, at least one X is phenylenebis group;

Z3is 0 or an integer from 1 to 4; and

R8is carboxypropyl, phenyl group, a group of the formula

-NR9R10,

where R9and R10is independently selected from the group consisting of a hydrogen atom or alkyl group having from 1 to 4 carbon atoms,

or heterocyclic group having from 5 to 6 atoms in the ring, of which 1 or 2 are heteroatoms selected from the group containing oxygen atom or nitrogen, specified heterocyclic group is unsubstituted or substituted at a carbon atom by an oxygen atom or alkyl group having from 1 to 4 carbon atoms; and

the groups of the formulas are unsubstituted or substituted at the carbon atom alkyl group having from 1 to 4 carbon atoms, or a group 0 or 1;

n2is 0 or 1;

M denotes an oxygen atom or sulfonyloxy group, provided that when R4means specified group of formula VII, IX, X or XI, R1does not mean the specified alkyl group, and when n2is 1, A4does not mean a single bond, and when n1is 0, R3is ethyl and R4is 2-acetyl, R1does not mean a methyl group,

or their pharmaceutically acceptable salts.

2. The compound of formula I and its salts under item 1, in which R1means a group of formula II or IV

< / BR>
and n10.

3. The compound of formula I or its salts under item 1, where R1means a group of formula II, as described in paragraph 1 and the aromatic rings are unsubstituted.

4. The compound of formula I and its salts under item 1, where R3means an alkyl group having from 1 to 10 carbon atoms, allylthiourea having from 1 to 10 carbon atoms, or CNS group having from 1 to 10 carbon atoms.

5. The compound of formula I and its salts under item 1, where R3means an alkyl group having from 1 to 6 carbon atoms or CNS group having from 1 to 6 carbon atoms.

6. The compound of formula I and its SS="ptx2">

7. The compound of formula I and its salts under item 1, where in the case when n2is 1, R4means a group of formula VI, as described in paragraph 1, in which the total number of carbon atoms in A1and A2is from 2 to 4.

8. The compound of formula I and its salts under item 1, where, in the case when n20, R4means a group of formula VI, as described in paragraph 1, in which the total number of carbon atoms in A1and A2is from 1 to 3.

9. The compound of formula I and its salts under item 1, where R4means a group of the formula VII, as described in paragraph 1, in which the total cisler of carbon atoms in A3, A4and A5is from 1 to 6, R6means an alkyl group having from 1 to 6 carbon atoms or cycloalkyl group having from 3 to 7 carbon atoms.

10. The compound of formula I and its salts under item 1, where R4means a group of the formula VII, as described in paragraph 1, in which the total number of carbon atoms in A3, A4and A5is from 1 to 6, and R7means a hydrogen atom or a group of the formula XVI, XXIV, XXV or XXX:

< / BR>
11. The compound of formula I and its salts under item 1, where R4means a group of the formula VII, as described in paragraph 1, in which the total number of carbon atoms in A3, A4and A5is the Oli on p. 1, where R4means a group of formula X, as defined in paragraph 1, in which the total number of carbon atoms in A3, A4and A5is from 1 to 6, and R6oznachaet alkyl group having from 1 to 6 carbon atoms or cycloalkyl group having from 3 to 7 carbon atoms.

13. The compound of formula I and its salts under item 1, which means a group of formula X, as defined in paragraph 1, in which the total number of carbon atoms in A3, A4and A5is from 1 to 6, and R7means a hydrogen atom or a group of the formula XXX, as indicated in paragraph 10.

14. The compound of formula I and its salts under item 1, where R4means a group of formula X, as defined in paragraph 1, in which the total number of carbon atoms in A3, A4and A5is from 1 to 6, and R6means unsubstituted tsiklogeksilnogo group.

15. The compound of formula I and its salts under item 1, where R1means a group of the formula III or IV

< / BR>
n10 and R3means alkiline group having from 1 to 10 carbon atoms, allylthiourea having from 1 to 10 carbon atoms, or CNS group having from 1 to 10 carbon atoms.

16. The compound of formula I and its salts under item 1, where R1means a group of formula II or IV

< / BR>
n

17. The compound of formula I and its salts under item 1, where R1means a group of formula II, as described in paragraph 1 and the aromatic rings are unsubstituted, and R3means an alkyl group having from 1 to 10 carbon atoms, allylthiourea having from 1 to 10 carbon atoms or CNS group having from 1 to 10 carbon atoms.

18. The compound of formula II and salts thereof under item 1, where R1means a group of formula II, as described in paragraph 1 and the aromatic ring Vlada unsubstituted, and R3means an alkyl group having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms or CNS group having from 1 to 6 carbon atoms.

19. Connection fomula I and its salts under item 1, where

R1means a group of formula II, and the aromatic rings are unsubstituted;

R3means an alkyl group having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms, or CNS group having from 1 to 6 carbon atoms, and

R4means a group of formula IV, VII, or X, as indicated in paragraph 1, in which M stands for an oxygen atom.

20. The compound of formula I and its salts under item 1, where

R1snpu, having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms, or CNS group having from 1 to 6 carbon atoms;

R4means a group of the formula VI, VII or X, as indicated in paragraph 1, in which M stands for an oxygen atom; and

in the case when n2is 1, R4means a group of formula VI, as described in paragraph 1, in which the total number of carbon atoms in A1and2is from 2 to 4.

21. The compound of formula I and its salts under item 1, where:

R1means a group of formula II, and the aromatic rings are unsubstituted;

R3means an alkyl group having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms, or CNS group having from 1 to 6 carbon atoms;

R1means a group of the formula VI, VII or X, as Kazanov p. 1, in which M stands for an oxygen atom; and

in the case when r20, R4means a group of formula VI, as described in paragraph 1, in which the total number of carbon atoms in A1and2is from 1 to 3.

22. The compound of formula I and its salts under item 1, where

R1means a group of formula II, and the aromatic rings are unsubstituted;

R3means alkyl grupului from 1 to 6 carbon atoms; and

R4means a group of the formula VII, as described in paragraph 1, in which the total number of carbon atoms in A3AND4and5is from 1 to 6,

R6means an alkyl group having from 1 to 6 carbon atoms or cycloalkyl group having from 3 to 7 carbon atoms.

23. The compound of formula I and its salts under item 1, where

R1means gurpo formula II, and the aromatic rings are unsubstituted;

R3means an alkyl group having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms, or CNS group having from 1 to 6 carbon atoms; and

R4means a group of formula X, as defined in paragraph 1, in which the total number of carbon atoms in A3AND4and5is from 1 to 6, and

R6means an alkyl group having from 1 to 6 carbon atoms, or cycloamino group having from 3 to 7 carbon atoms.

24. The compound of formula I and its salts under item 1, where

R1means a group of formula II, and the aromatic rings are unsubstituted;

R3means an alkyl group having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms, or CNS group with the carbon AND3AND4and5is from 1 to 6

R7means a hydrogen atom or a group of the formula XVI, XXIV, XXV or XXX;

< / BR>
25. The compound of formula I and its salts under item 1, where:

R1means a group of formula II, and the aromatic rings are unsubstituted;

R3means an alkyl group having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms, or CNS group having from 1 to 6 carbon atoms;

R4means a group of formula X, as defined in paragraph 1, in which the total number of carbon atoms in A3AND4and5is from 1 to 6, and

R7means a hydrogen atom or a group of the formula XVI, XXIV, XXV or XXX as specified in paragraph 24.

26. The compound of formula I and its salts under item 1, where

R1means a group of formula II, and the aromatic rings are unsubstituted;

R3means an alkyl group having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms, or CNS group having from 1 to 6 carbon atoms;

R4means a group of the formula VII, as described in paragraph 1, in which the total number of carbon atoms in A3AND4and5is from 1 to 6, and

R6means unsubstituted in formula II, and the aromatic rings are unsubstituted;

R3means an alkyl group having from 1 to 6 carbon atoms, allylthiourea having from 1 to 6 carbon atoms, or CNS group having from 1 to 6 carbon atoms;

R4means a group of formula X, as defined in paragraph 1, in which the total number of carbon atoms in A3AND4and5is from 1 to 6, and

R6means unsubstituted tsiklogeksilnogo group.

28. The compound of formula I and its salts under item 1, where

R1means (N-xanthene-9-yl) methyl gurpo;

n10;

R3means methylthio group, isopropylthio-, isopropyl or tert-butyl;

R4means a group of the formula VIa, VIIa or IXa

< / BR>
in which R6means cyclopentyloxy group, tsiklogeksilnogo group, cycloheptyl group, phenyl group, 2-chloraniline group or 4-chloraniline group;

R7' means 3-carboxypropyl group, 2-carboxybenzoyl group or aminoacetyl group;

AND1' means methylene group;

AND2' oncet alkylenes group having from 2 to 4 carbon atoms;

AND3' means single bond or alkilinity a group that has group);

AND4' means single bond or alkilinity group having from 1 to 5 carbon atoms which may be interrupted by a double bond;

the place of attachment of R4to the benzene ring of the compounds of formula I is in the ortho-position to the amino group and the meta-position with respect to R3or in the meta-position to the amino group and the para-position with respect to R3.

29. The compound of formula I on p. 1, selected from the group consisting of:

N-[2-tert-butyl-5-(5-cyclohexyl-3-hydroxyphenyl)phenyl] -2-(N-xanthene-9-yl)ndimethylacetamide;

N-[2-tert-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl] -2-(N-xanthene-9-yl)ndimethylacetamide;

N-[2-tert-butyl-5-(6-cyclohexyl-3-hydroxyhexyl)phenyl] -2-(N-xanthene-9-yl)ndimethylacetamide;

N-[2-tert-butyl-5-(7-cyclohexyl-3-hydroxymethyl)phenyl] -2-(N-xanthene-9-yl)ndimethylacetamide;

N-[2-tert-butyl-5-(3-cyclohexyl-3-hydroxypropyl) phenyl] -2-(N-xanthene-9-yl)ndimethylacetamide;

N-[2-tert-butyl-5-(2-cyclohexyl-1-hydroxyethyl) phenyl]-2-(N-xanthene-9-yl)ndimethylacetamide;

N-[2-tert-butyl-5-(6-cyclopentyl-1-hydroxyethyl) phenyl]-2-(N-xanthene-9-yl)ndimethylacetamide;

1-(2-{ 4-tert-butyl-3-[2-(N-xanthene-9-yl)acetamido] phenyl} ethyl)-2-cyclohexylethyl sodium succinate;

1-(2-{ 4-tert-butyl-3-[2-(3H-xanthene-9-yl)amino]phenyl}ethyl-5-cyclohexylmethyl succinate;

N-{ 2-[3-(1-imidazolyl)propoxy] methyl-6-methylthiophenyl}-2-(N-xanthene-9-yl)ndimethylacetamide hydrochloride;

N-{ 2-[3-(1-imidazolyl)propoxy]methyl-6 methylthiophenyl}-2-(N-xanthene-9-yl)ndimethylacetamide;

N-{ 2-[3-(1-imidazolyl)propoxy] methyl-6-tert-butylphenyl} -2-(N-xanthene-9-yl)ndimethylacetamide hydrochloride;

sodium salt of 1-(2-{ 4-tert-butyl-3-[2-(N-xanthene-9-yl) acetamido] phenyl} ethyl)-2-cyclohexyl ethyl of carboxymethylcysteine;

N-[2-tert-butyl-5-{ 3-[2-(1-imidazolyl) acetoxy] -4-cyclohexylmethyl} phenyl]-2-(N-xanthene-9-yl)ndimethylacetamide hydrochloride;

sodium salt of N-(2-tert-butyl-5-{ 3-[2-carboxymethoxy) acetoxy]-4-cyclohexylmethyl} phenyl)-2-(N-xanthene-9-yl)ndimethylacetamide;

sodium salt of N-2(2-tert-butyl-5-{7-cyclohexyl-3-[2-(carboxymethoxy)acetoxy]heptyl} phenyl)-2-(N-xanthene-9-yl)ndimethylacetamide;

N-[2-tert-butyl-5-[4-cyclohexyl-2-(hydroxymethyl) butyl]phenyl]-2-(N-xanthene-9-yl)ndimethylacetamide;

N-[2-tert-butyl-5-{ 4-(2-cyclohexylmethoxy)-3-hydroxybutyl] phenyl] -2-(N-xanthene-9-yl) ndimethylacetamide;

N-[2-tert-butyl-5-(5-cyclohexyloxy-3-hydroxyphenyl) phenyl]-2-(N-xanthene-9-yl) ndimethylacetamide;

N-(2-tert-butyl-5-{4-(2-cyclohexylmethoxy)-3-[2-(1-imidazolyl] acetoxy] butyl}phenyl)-2-(N-xanthene-9-yl) ndimethylacetamide hydrochloride;

sodium salt of N-(2-tert-butyl-5-{3-[2-(carboxymethoxy) aceil] phenyl}-2-(N-xanthene-9-yl)ndimethylacetamide;

and its pharmaceutically acceptable salts.

30. The composition having inhibitory activity against acyl-CoA : cholesterol acyltransferase, including an active ingredient and a pharmaceutically acceptable carrier or diluent, wherein the active ingredient it contains an effective amount of amido - or urea-derivative of the formula I according to any one of paragraphs.1 - 29, or its pharmaceutically acceptable salt.

31. Amido - or urea-derivative of the formula I according to any one of paragraphs.1 - 29, or its pharmaceutically acceptable salt having inhibitory activity against acyl-CoA : cholesterol.

 

Same patents:

The invention relates to compounds of the formula

(I)

where R1represents hydrogen, lower alkyl, lower alkenyl, lower quinil, aryl lower alkyl, cycloalkyl lower alkyl, lower alkoxy lower alkyl, hydroxy lower alkyl, amino lower alkyl, mono - or di-lower alkyl, amino lower alkyl, formyl, lower alkylsulphonyl, amino lower alkylsulphonyl, lower alkoxycarbonyl, mono - or di-aryl-substituted lower alkyl, arylcarbamoyl lower alkyl, aryloxy lower alkyl, or lower alkylene

< / BR>
X represents O or S;

W represents hydrogen, halogen, hydroxy, lower alkoxy, aryl lower alkoxy, nitro, trifluoromethyl or

< / BR>
where R3represents hydrogen, lower alkyl or aryl lower alkyl, and R4represents lower alkyl or aryl lower alkyl; or alternatively the groupas a whole represents the

< / BR>
R5is hydrogen, lower alkyl, aryl or aryl lower alkyl; and

Z predepression

The invention relates to new chemical substances, which have valuable pharmacological properties, more particularly to a nitrogen-containing heterocyclic compounds of General formula I

< / BR>
where X is oxygen or sulfur;

Y is carbon or nitrogen;

Z is carbon or nitrogen, and Y and Z are not simultaneously mean nitrogen;

R1and R2independent from each other and denote hydrogen, alkyl with 1 to 6 carbon atoms, halogen, trifluoromethyl, nitrile, alkoxy with 1 to 6 carbon atoms, a group of CO2R7where R7means hydrogen or alkyl with 1 to 6 carbon atoms, group-C(O)NR8R9where R8and R9not dependent from each other and denote hydrogen, alkyl with 1 to 3 carbon atoms, methoxy or together with the nitrogen form a morpholine, pyrrolidine or piperidine-NR10R11where R10and R11denote hydrogen or alkyl with 1 to 6 carbon atoms, group-C(O)R12where R12means alkyl with 1 to 6 carbon atoms, group-SO2R12where R12has the specified value, -NHC(O)R12where R12has the specified value, -NHSO2R12where R12has a specified value, and-SO2NR13R14where R13and R142R12where R12has the specified value, -NHC(O)R12where R12has the specified value, -NHSO2R12where R12has the specified value, -SO2NR13R14where R13and R14have a specified value, a nitrogroup, 1-piperidinyl, 2-, 3 - or 4-pyridine, morpholine, thiomorpholine, pyrrolidine, imidazole, unsubstituted or substituted at the nitrogen by alkyl with 1 to 4 carbon atoms, 2-thiazole, 2-methyl-4-thiazole, dialkylamino with 1 to 4 carbon atoms in each alkyl group, or alkilany ether with 1 to 4 carbon atoms;

R4an ester of formula-CO2R16where R16means alkyl with 1 to 4 carbon atoms, the amide of formula C(O)NR17R18where R17and R18independent from each other and denote hydrogen, alkyl with 1 to 2 carbon atoms, methoxy or together with the nitrogen form a morpholine, piperidine or pyrrolidine, phenyl, unsubstituted or substituted by residues from the group comprising halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, 3-methyl-1,2,4-oxadiazol-5-yl, 2 - or 3-thienyl, 2-, 3 - or 4-pyridyl, 4-pyrazolylborate 4 stands, the ketone of the formula C(O)R19'where R19means alkyl with 1 to 3 carbon atoms, phenyl or 1-Mei-2-yl, a simple ester of the formula-CH2OR20where R20means alkyl with 1 to 3 carbon atoms, thioether formula-CH2SR20where R20has the specified value, the group CH2SO2CH3amines of the formula-CH2N(R20)2where R20has the specified value, the remainder of the formula-CH2NHC(O)R21where R21means methyl, amino or methylamino - group-CH2NHSO2Me2where Me denotes methyl carbamate of the formula CH2OC(O)NHCH3;

R5and R6independent from each other and denote hydrogen or methyl;

n is 0,1 or 2,

Provided that the substituents are not simultaneously have the following meanings: Y and Z is carbon, R1or R2hydrogen, halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, cyano, nitro, trifluoromethyl, R3unsubstituted phenyl and R4group-C(O)OR16'where R16'means hydrogen, alkyl, alkenyl or quinil, group-C(O)N(R18')(R19'), where R18'and R19'denote hydrogen, alkyl with 1 to 6 carbon atoms, phenyl, alkoxy or together with the nitrogen form pyrrolidine, piperidine or morpholine, cyanotic, unsubstituted phenyl and 4-imidazole,

in the form of a racemate or an individual enantiomers and their salts, are inhibitors of leukotriene biosynthesis

The invention relates to a series of new piperidyl - occaisonally and khinuklidinilbenzilata derivatives that can be used in the treatment and prevention of various disorders, especially senile dementia / including disease of Alzheimer/

The invention relates to new derivatives of 3(2H)-pyridazinone and to their pharmaceutically acceptable salts, possessing inhibitory activity against the aggregation of platelets, cardiotonic activity, vasodilating activity, anti-SRS-A activity, to processes for their preparation and to pharmaceutical compositions containing them as active ingredient

The invention relates to new derivatives substituted benzoylbenzene-, biphenyl - 2-oxazolidinone acid, which has inhibitory activity against lipoxygenase, phospholipase A2and which are leukotriene antagonists; derivatives, which are suitable for use as anti-inflammatory, antiallergic agents, but also as protectors

The invention relates to new derivatives of 3(2H)-pyridazinone and to their pharmaceutically acceptable salts, possessing inhibitory activity against the aggregation of platelets, cardiotonic activity, vasodilating activity, anti-SRS-A activity, to processes for their preparation and to pharmaceutical compositions containing them as active ingredient

The invention relates to a compound of General formula (I)

,

where R1- C1-C6alkyl; R2and R3- C1-C6alkyl; R4= R5= R7= a hydrogen atom; R6is a hydrogen atom or halogen, C1-C6alkyl, C1-C6alkoxy - or nitro-group; R8is a hydrogen atom or allyl; X = ClO4have a high spectral characteristics, high photochemical stability, stable in polar and non-polar solvents and can be used as fluorescent dyes for various textile and notextile materials in the production of ink, pencils, cosmetic preparations, signal colors, synthons for the production of fluorescent dyes as active medium in liquid lasers with different methods of excitation, etc
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