Inhibitors for producing/secretion of β-amyloid protein

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention describes compound of the general formula (3): wherein R15 represents a heterocyclic group chosen from 3-7-membered saturated or 4,7-membered unsaturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom, or 7-14-membered polycyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R16 represents a cycloalkyl group comprising 3-7 carbon atoms, monocyclic aromatic hydrocarbon group comprising 6-14 carbon atoms, or heterocyclic group chosen from 3-7-membered saturated or 4-7-membered unsaturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R17 represents a monocyclic aromatic hydrocarbon group comprising 6-14 carbon atoms or heterocyclic group chosen from 4-7-membered saturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R18 represents hydrogen atom or (C1-C)-alkyl group; X represents -S-, -SO- or -SO2; or N-oxide or S-oxide of this compound; their salt; or solvate of above described compound. Proposed compounds possess the inhibitory activity against producing/secretion of β-amyloid protein and can be used in treatment of such diseases as Alzheimer's disease, Down's disease and other diseases associated with amyloid deposition.

EFFECT: valuable medicinal properties of inhibitors.

7 cl, 1 tbl, 410 ex

 

The technical field

This invention relates to new compounds having inhibitory activity against the production or secretion β-amyloid protein; and a medicinal product for the treatment of various diseases caused by abnormal production or secretion β-amyloid protein such as Alzheimer's disease, down's syndrome and other diseases associated with deposition of amyloid.

Background of the invention

Alzheimer's disease is a neurodegenerative disease with pathological features, such as degeneration or loss of nerve cells, the formation of senile plaques and neurofibrillary plexus (tangles). Alzheimer's disease causes symptoms of dementia, such as the gradual loss of memory, cognitive abilities, thinking, evaluating, or the like, and, ultimately, leads to death. Up to the present time was not known to be an effective method of treating or preventing the disease.

The major protein component of senile plaques deposited in the brain, is β-amyloid protein, which consists of 39-43 amino acids. β-amyloid protein shows cytotoxicity, which presumably induces Alzheimer's disease (Science, 259, 514 (1993)). It is known that β-amyloid protein, the secretory cells, is a polypeptide, ostasis mainly of 40 or 42 amino acids, and, in particular, consisting of 42 amino acids, and quickly deposited in the brain due to the strong ability to aggregation and, in addition, has a strong cytotoxicity (Journal of Biological Chemistry, 270, 7013 (1995)). β-amyloid protein is produced everywhere in vivo, but its function remains unknown.

β-amyloid protein is produced by processing β-amyloid protein precursor (APP), which is a membrane protein. Gene mutation of APP observed in patients suffering from familial Alzheimer's disease. It is known that increasing the number of production or secretion β-amyloid protein found in cells that have this mutated gene is introduced into them. This suggests that the drug inhibiting the production or secretion β-amyloid protein is effective for prevention or treatment of Alzheimer's disease.

In the processing of APP, VASYA (splitting of the RDA in β-site of the enzyme) (Science, 286, 735 (1999)) or Asp1 (Molecular and Cellular Neuroscience, 16, 609 (2000)), each of which is an aspartic protease, are represented as β-secretase for degradation of N-end β-amyloid protein. With considerable certainty, it is assumed that presenilin participates in the events of the C-terminal cleavage γ-secretases (Nature, 398, 513 (1999)). It was reported about the inhibitors secretase (Journal f Medicinal Chemistry, 44, 2039 (2001)), but most of these inhibitors are peptide compounds.

In WO00/50391, SMITH, et al., described compounds having sulfonamidnuyu skeleton and is able to regulate the production of β-amyloid protein. In WO01/79677 (GB 026827) BELANGER, et al., described compounds having bicycloalkanes skeleton and inhibiting γ-secretase.

The purpose of this invention to provide compounds having a structure different from the structures described above are known compounds having excellent inhibitory activity against the production and secretion β-amyloid protein and having desirable properties as pharmaceuticals.

Description of the invention

The authors of this invention have conducted comprehensive research. In the result it was found that derivatives thiomethane, sulfonylmethane or sulfonylmethane represented by the following formula (1), have excellent inhibitory activity against the production or secretion β-amyloid protein and, therefore, useful as pharmaceuticals for the treatment of various diseases resulting from abnormal production or secretion β-amyloid protein, which led to the creation of this invention.

Thus, the present invention features a compound of formula (1):

{where:

X represents-S-, -SO - or-SO2-;

R1is:

-C(R5)(R6)(R7),

[where R5, R6and R7each independently represents a halogen atom, a cyano, a nitro-group or-Q51-Q52-Q53-Q54[where Q51represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q52represents a simple bond, -O-, -O-N(A51)-, -O-N(COA51)-, -N(A51)-, -N(COA51)-, -N(COOA51)-, -N(CON(A51)(A52)-, -N(OA51)-, -N(NA51A52)-, -N(A51)-N(A52)-, -N(COA51)-N(A52)-, -N(A51)-O-, -N(COA51)-O-, -S-, -N=N-, -C(A51)=N-, -C(A51)=N-O-, -C(A51)=N-N(A52)-, -N=C(A51)-, -O-N=C(A51)-, -(NA51)-N=C(A52)- or-C(=NA51)-N(A52)-,

(where a51and52each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy),

Q53represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q54is-A53, OA53, -N(A53)(A54), -SA53, -NA54-OA53, -NA55-N(A53)(A54or-O-N(A53)(A54),

(where a53And54and55each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or heterocyclic group which may have a Deputy), or

R5and R6can be linked together with the formation of the cyclic hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a substituent (when the hydrocarbon group or heterocyclic group formed by linking R5and R6is unsaturated, R7can represent the corresponding unsaturated bond)],

-N(R8)(R9),

[where R8and R9each independently represents-Q81-Q82-Q83-Q84

[where Q81represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q82represents a simple bond, -O-, -O-N(A81)-, -O-N(COA81)-, -N(A81)-, -N(COA81)-, -N(COOA81)-, -N(CON(A81)(A82))-, -N(OA81)-, -N(NA81A82)-, -N(A81)-N(A82)-, -N(COA81)-N(A82)-, -N(A81)-O-, -N(COA81)-O-, -S-, -N=N-, -C(A81)=N-, -C(A81)=N-O-, -C(A81)=N-N(A82)-, -N=C(A81)-, -O-N=C(A81)-, -(NA81)-N=C(A82)- or-C(=NA81)-N(A82)-,

(where a81and82each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy),

Q83represents a simple bond, -what About-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q84is-A83, OA83, -N(A83)(A84), -SA83, -NA84-OA83, -NA85-N(A83)(A84or-O-N(A83)(A84),

(where a83And84and85each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy)]],

-X1R10,

[where X1represents-O - or-S-, and R10represents-Q101-Q102-Q103-Q104,

[where Q101represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q102represents a simple bond, -O-, -O-N(A101)-, -O-N(COA101)-, -N(A101)-, -N(COA101)-, -N(COOA101)-, -N(CON(A101)(A102))-, -N(OA101)-, -N(NA101A102)-, -N(A101)-N(A102)-, -N(COA101)-N(A102)-, -N(A101)-O-, -N(COA101)-O-, -S-, -N=N-, -C(A101)=N-, -C(A101)=N-O-, -C(A101)=N-N(A102)-, -N=C(A101)-, -O-N=C(A101)-, -(NA101)-N=C(A102)- or-C(=NA101)-N(A102)-,

(where a101and102each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy),

Q103represents a simple bond, -CO-, -CS-, -SO-, -SO2 -, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q104is-A103, OA103, -N(A103)(A104), -SA103, -NA104-OA103, -NA105-N(A103)(A104or-O-N(A103)(A104),

(where a103And104and105each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy)]]or

-X2R11,

[where X2is-SO - or-SO2and R11is Q111-Q112-Q113-Q114,

[where Q111represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q112represents a simple bond, -O-, -O-N(A111)-, -O-N(COA111)-, -N(A111)-, -N(COA111)-, -N(COOA111)-, -N(CON(A111)(A112))-, -N(OA111)-, -N(NA111A112)-, -N(A111)-N(A112)-, -N(COA111)-N(A112)-, -N(A111)-O-, -N(COA111)-O-, -S-, -N=N-, -C(A111)=N-, -C(A111)=N-O-, -C(A111)=N-N(A112)-, -N=C(A111)-, -O-N=C(A111)-, -(NA111)-N=C(A112)- or-C(=NA111)-N(A112)-,

(where a111and112each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy),

Q113represents a simple bond, -CO-, -CS-, -SO-, -SO 2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q114is-A113, OA113, -N(A113)(A114), -SA113, -NA114-OA113, -NA115-N(A113)(A114or-O-N(A113)(A114),

(where a113And114and115each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy)]],

R2represents-Q21-Q22-Q23-Q24,

[where Q21represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q22represents a simple bond, -O-, -O-N(A21)-, -O-N(COA21)-, -N(A21)-, -N(COA21)-, -N(COOA21)-, -N(CON(A21)(A22))-, -N(OA21)-, -N(NA21A22)-, -N(A21)-N(A22)-, -N(COA21)-N(A22)-, -N(A21)-O-, -N(COA21)-O-, -S-, -N=N-, -C(A21)=N-, -C(A21)=N-O-, -C(A21)=N-N(A22)-, -N=C(A21)-, -O-N=C(A21)-, -(NA21)-N=C(A22)- or-C(=NA21)-N(A22)-,

(where a21and22each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy),

Q23represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q24is-A23, OA23, -N(A23)A 24), -SA23, -NA24-OA23, -NA25-N(A23)(A24or-O-N(A23)(A24),

(where a23And24and25each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy)], or

R1and R2can be linked together with the formation of the cyclic hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy, or can be linked together with education =CR12R13,

[where R12and R13each independently represents a halogen atom, a cyano, a nitro-group or-Q121-Q122-Q123-Q124,

[where Q121represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q122represents a simple bond, -O-, -O-N(A121)-, -O-N(COA121)-, -N(A121)-, -N(COA121)-, -N(COOA121)-, -N(CON(A121)(A122))-, -N(OA121)-, -N(NA121A122)-, -N(A121)-N(A122)-, -N(COA121)-N(A122)-, -N(A121)-O-, -N(COA121)-O-, -S-, -N=N-, -C(A121)=N-, -C(A121)=N-O-, -C(A121)=N-N(A122)-, -N=C(A121)-, -O-N=C(A121)-, -(NA121)-N=C(A122)- or-C(=NA121)-N(A122)-,

(where a121and122each independently represents a hydrogen atom, a carbohydrate is native group, which may have a Deputy, or a heterocyclic group which may have a Deputy),

Q123represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q124is-A123, OA123, -N(A123)(A124), -SA123, -NA124-OA123, -NA125-N(A123)(A124or-O-N(A123)(A124),

(where a123And124and125each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy)]];

R3represents-Q31-Q32-Q33-Q34[where Q31represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q32represents a simple bond, -O-, -O-N(A31)-, -O-N(COA31)-, -N(A31)-, -N(COA31)-, -N(COOA31)-, -N(CON(A31)(A32))-, -N(OA31)-, -N(NA31A32)-, -N(A31)-N(A32)-, -N(COA31)-N(A32)-, -N(A31)-O-, -N(COA31)-O-, -S-, -N=N-, -C(A31)=N-, -C(A31)=N-O-, -C(A31)=N-N(A32)-, -N=C(A31)-, -O-N=C(A31)-, -(NA31)-N=C(A32)- or-C(=NA31)-N(A32)-,

(where a31and32each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy),/p>

Q33represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q34is-A33, OA33, -N(A33)(A34), -SA33, -NA34-OA33, -NA35-N(A33)(A34or-O-N(A33)(A34),

(where a33And34and35each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy)];

R4represents-Q41-Q42-Q43-Q44,

[where Q41represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q42represents a simple bond, -O-, -O-N(A41)-, -O-N(COA41)-, -N(A41)-, -N(COA41)-, -N(COOA41)-, -N(CON(A41)(A42))-, -N(OA41)-, -N(NA41A42)-, -N(A41)-N(A42)-, -N(COA41)-N(A42)-, -N(A41)-O-, -N(COA41)-O-, -S-, -N=N-, -C(A41)=N-, -C(A41)=N-O-, -C(A41)=N-N(A42)-, -N=C(A41)-, -O-N=C(A41)-, -(NA41)-N=C(A42)- or-C(=NA41)-N(A42)-,

(where a41and42each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy),

Q43represents a simple bond, -CO-, -CS-, -SO-, -SO2-, -CO-CO-, -CO-CS-, -CS-CO - or-CS-CS-,

Q44the stand is made-And 43, OA43, -N(A43)(A44), -SA43, -NA44-OA43, -NA45-N(A43)(A44or-O-N(A43)(A44),

(where a43And44and45each independently represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy)], or

R3and R4can be linked together with the formation of the cyclic hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy}, N-oxide or S-oxide of this compound, salt or MES described above for the connection.

In this invention it is also proposed drug containing as an effective ingredient a compound represented by the formula (1), its N-oxide or S-oxide or salt, or MES.

In this invention it is also proposed pharmaceutical composition comprising a compound represented by the formula (1), its N-oxide or S-oxide or salt, or MES, and a pharmaceutically acceptable carrier.

In this invention a compound represented by the formula (1), its N-oxide or S-oxide, or salt, or MES for the manufacture of a medicinal product.

The present invention also offers a method of treatment of the disease, awsume the Osya a result of abnormal production or secretion β -amyloid protein, comprising introducing an effective amount of the compound represented by formula (1), its N-oxide or S-oxide, or their salts, or their MES.

The best way of carrying out the invention

Next will be described compounds represented by formula (1).

The term "hydrocarbon group" denotes a group containing only atoms of carbon and hydrogen. This group may be any of linear, branched and cyclic groups, or a combination of any two or three of them, and it may be any of saturated and unsaturated groups.

Typical examples of the linear or branched hydrocarbon groups include alkyl, alkeline and alkyline group, and combinations thereof. These linear or branched hydrocarbon group include groups having many double or triple links, or group that has either double or triple bond.

As preferred alkyl groups are linear or branched alkyl group having 1-18 carbon atoms, in particular a linear or branched alkyl group having 1-12 carbon atoms. Specific examples of such alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylpentyl, 2-ethylphenyl, n-hexyl, n-heptyl, is-octyl, n-nonyl, n-decyl, n-undecyl and n-decyl.

As alkenylphenol group, preferred are linear or branched alkeneamine group having 2-18 carbon atoms, in particular a linear or branched alkeneamine group having 2-12 carbon atoms. Specific examples of such alkenylphenol groups include vinyl, allyl, propenyl, butenyl and pentenyl.

As alkenylphenol group, preferred are linear or branched alkyline group having 2-18 carbon atoms, in particular a linear or branched alkyline group having 2-12 carbon atoms. Specific examples of such alkenylphenol groups include ethinyl, 2-butinyl and 3-pentenyl.

Typical cyclic hydrocarbon group include cycloalkyl, cycloalkenyl, aryl, spiropentane, cyclic hydrocarbon with a cross (bridging) ties and condensed polycyclic hydrocarbon group. Apply a combination of them. The cyclic hydrocarbon group include groups having multiple double bonds or triple links, and groups having a double bond and a triple bond.

Examples cycloalkyl groups include cycloalkyl group having 3-7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

An example is cycloalkenyl groups include cycloalkenyl group, having 4-7 carbon atoms, such as cyclopentenyl and cyclohexenyl. Examples cycloalkenyl groups include cycloalkenyl group having 4-7 carbon atoms.

Examples of aryl groups include monocyclic or polycyclic aromatic hydrocarbon group having 6-14 carbon atoms. Specific examples include phenyl, indenyl, naphthyl, anthracene and biphenyl.

Examples spiropentane groups include spiropentane group having 7-11 carbon atoms, such as groups Spiro[3.4]octanol and Spiro[4.5]DECA-1,6-dienyl.

Examples of the cyclic hydrocarbon group with a cross (bridging) ties include cyclic hydrocarbon group with a cross (bridge) bonds having 7-10 carbon atoms, such as groups bicyclo[2.2.1]heptenyl, substituted, bicyclo[3.2.1]octenyl, bicyclo[2.2.1]hept-2-enyl, tricyclo[2.2.1.02.6]heptenyl and bicyclo[4.3.1]decenyl.

Examples of the condensed polycyclic hydrocarbon groups include condensed polycyclic group having 8-14 carbon atoms, such as groups of indanyl, tetrahydronaphthyl, hexahydrobenzyl and octahydronaphthalene.

The term "heterocyclic group denotes a cyclic group having one or more heteroatoms (N, O, S etc) as a component of its cyclic structure,and it can be any of a saturated ring, unsaturated ring, or aromatic ring, or may be either monocyclic or polycyclic group. It also includes a group derived from heterocyclic spiraeoideae or heterocyclic compounds having a cyclic structure with a cross (bridge) connections.

Examples of the saturated monocyclic heterocyclic group include a 3-7-membered groups, each of which has 1 to 4 atoms selected from nitrogen atoms, oxygen and sulfur. Specific examples include groups pyrrolidinyl, tetrahydrofuranyl, oxetanyl, tetrahydrofuryl, piperidinyl, piperazinil, morpholinyl, thiomorpholine, oxiranyl, ciorani, dioxane, aziridinyl, imidazolidinyl, pyrazolidine, tetrahydropyranyl, tetrahydropyranyl, tetrahydrooxazolo, tetrahydrofuryl, tetrahydroisoquinoline, tetrahydrocortisol, DIOXOLANYL and oxathiolanes.

Examples of the unsaturated monocyclic heterocyclic group include a 4-7-membered group having 1-4 atoms selected from nitrogen atoms, oxygen and sulfur. Specific examples include groups pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolin, dihydrooxazolo, dihydrothiazolo, dihydroisoxazole, dihydroisoxazole, pyridyl, pyrimidinyl, triazinyl, tetrazolyl, pyrrolyl, imidazolyl, feast is oliner, thiadiazolyl, oxadiazolyl, dihydrooxazolo, dihydrothiazolo, dihydroisoxazole, dihydroisoxazole, pyrazinyl, pyridazinyl, pyranyl, dihydropyridines, dihydropyrrole, dihydroxyaryl, dihydroimidazole, dihydropyrazolo, dihydropyrazine and dihydropyridines.

Examples of polycyclic heterocyclic groups include 7-14 membered group having 1-4 atoms selected from nitrogen atoms, oxygen and sulfur. Specific examples include groups benzofuranyl, benzothiazolyl, indolyl, hinely, ethanolic, benzopyranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzodioxolyl, benzothiophene, benzisothiazole, benzisoxazole, bromanil, bromanil, Isopropenyl, isopropanol, indolinyl, indazoles, indolizinyl, isoindolyl, isoindolines, hemolysins, honokalani, chinadoll, cinnoline, phthalazine, naphthyridine, purinol, carbazolyl, xantener, acridines, phenazines, phenoxazines, phenothiazines and hinokitiol.

Examples of combinations cycloalkyl and alkyl groups include cycloalkenyl group, and particularly preferred are groups (C3-7cycloalkyl)(C1-12alkyl).

As a combination of aryl and alkyl groups are preferred groups (C6-10aryl)(C1-12alkyl).

Examples of the substituent for these hydrocarbon groups and heterocyclic groups in luchot-Q 201-Q202-Q203-Q204-Q205-Q206-Q207where Q201represents a simple bond, an alkyl group having 1-6 carbon atoms, alkenylphenol group having 2-6 carbon atoms or a heterocyclic group; Q202represents a simple bond, -O-, -NH-, -CH=N-, -C(alkyl)=N-, -N(alkyl)- or-S-; Q203represents a simple bond, -CO-, -CS-, -SO-, -SO2- or-CONH-; Q204represents a simple bond, an alkyl group of 1-6 carbon atoms, alkenylphenol group having 2-6 carbon atoms, cycloalkyl group, cycloalkenyl group, aromatic hydrocarbon group or heterocyclic group; Q205represents a simple bond, -O-, -NH - or-N(alkyl)-; Q206represents a simple bond, -CO-, -CS-, -SO2-, -SO - or-S-; and Q207represents a hydrogen atom, a halogen atom, a hydroxy-group,

oxoprop,1-6alkyl group, a C2-6alkenylphenol group,

With3-8cycloalkyl group1-6alkoxygroup,

With2-6alkenylacyl, asiagraph, cyano, amino group,

With1-6alkylamino, di(C1-6alkyl)amino group,

With2-6alkanolamines, di(C2-6alkanoyl)amino group,

carboxymyoglobin,1-6alkoxycarbonylmethyl,

di(C1-6alkoxy)carbonylation, heterocyclic group,

aromatizes the second hydrocarbon group,

cycloalkenyl group, geterotsiklicheskikh or

aromatic uglevodorodakh.

An alkyl group having 1-6 carbon atoms, Alchemilla group having 2-6 carbon atoms, cycloalkyl group, cycloalkenyl group, heterocyclic group, heterotardigrada, aromatic hydrocarbon group or aromatic uglevodorodakh can be substituted by 1-3 substituents selected from halogen atoms,

With1-6alkyl groups With1-6alkoxygroup,2-6alkenyl groups,

carboxyamide(C1-6alkyl) groups,

(C1-6alkoxy)carbylamine(C1-6alkyl) groups,

formyl group2-6alkanoyl group, carbonyl group,

nitro, ceanography, sidegroup, amidinopropane,

With2-6alkenylacyl, hydroxy-group, carboxyl group,

With7-16Uralkalij groups, tocography,2-7alkanoyl groups,

With2-7thioalcohols groups, tiparillos group, amino group,

With1-6alkylamino, di(C1-6alkyl)amino group,

With1-6alkoxycarbonyl groups, carbamoyl group,

With1-6alkylcarboxylic groups, di(C1-6alkyl)carbamoyl groups,

thiocarbamoyl group1-6alkyldiethanolamine groups,

di(C1-6alkyl)thiocarbamoyl g is PP,

With1-6alkoxycarbonyl groups,

With1-6alkoxycarbonyl(C1-6alkyl)amino, C2-7alkanolamines,

(C2-7alkanoyl)(C1-6alkyl)amino, thio(C2-7alkanoyl)amino groups,

thio(C2-7alkanoyl)(C1-6alkyl)amino group, formylamino,

formyl(C1-6alkyl)amino group, coformulating,

diformyl(C1-6alkyl)amino, C2-7alkanoyloxy,

formyloxy,1-6alkoxycarbonylmethyl,

carbamoyloximes,1-6alkylcarboxylic,

di(C1-6alkyl)carbamoyloximes, aminocarbonylmethyl,

(C1-6alkyl)aminocarbonylmethyl,

di(C1-6alkyl)aminocarbonylmethyl,

aminocarbonyl(C1-6alkyl)amino group,

(C1-6alkyl)aminocarbonyl(C1-6alkyl)amino group,

di(C1-6alkyl)aminocarbonyl(C1-6alkyl)amino group,

mercaptopropyl,1-6alkylthio,1-6alkylsulfonyl groups,

With1-6alkylsulfonyl groups, aminosulfonyl group,

With1-6alkylaminocarbonyl groups,

di(C1-6alkyl)aminosulfonyl groups,

With1-6alkylsulfonamides,

(C1-6alkylsulfonyl(C1-6alkyl)amino group,

aminosulphonylphenyl,1-6alkylaminocarbonyl the Rupp,

di(C1-6alkyl)aminosulfonyl,

aminosulfonyl(C1-6alkyl)amino group,

With1-6alkylaminocarbonyl(C1-6alkyl)amino group and

di(C1-6alkyl)aminosulfonyl(C1-6alkyl)amino group.

Examples of aromatic hydrocarbon groups include6-14aromatic hydrocarbon groups such as phenyl group, naphthyl, indenyl, anthracene and biphenyl. Of them, especially preferred are phenyl and naftalina group. Heterocyclic groups include the above-described saturated or unsaturated, monocyclic or polycyclic heterocyclic group, for example group pyrrolidinyl, tetrahydrofuranyl, oxetanyl, tetrahydrofuryl, piperidinyl, piperazinil, morpholinyl, thiomorpholine, oxiranyl, tylenol, dioxane, pyrrolyl, aziridinyl, imidazolidinyl, pyrazolidine, tetrahydropyranyl, tetrahydropyranyl, tetrahydrooxazolo, tetrahydrofuryl, tetrahydroisoquinoline, tetrahydrocortisol, DIOXOLANYL, oxathiolane, furyl, thienyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolin, dihydrooxazolo, dihydrothiazolo, dihydroisoxazole, dihydroisoxazole, pyridyl, pyrimidinyl, triazinyl, tetrazolyl, pyrrolyl, imidazolyl, pyrazolines, thiadiazoles, oxadiazoles, dihydrooxazolo, dihydrothiazolo is, dihydroisoxazole, dihydroisoxazole, pyrazinyl, pyridazinyl, pyranyl, dihydropyridines, dihydropyrrole, dihydroxyaryl, dihydroimidazole, dihydropyrazolo, dihydropyrazine, dihydropyridines, benzofuranyl, benzothiazolyl, indolyl, hinely, ethanolic, benzopyranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzodioxolyl, benzothiophene, benzisothiazole, benzisoxazole, bromanil, bromanil, Isopropenyl, isopropanol, indolinyl, indazoles, indolizinyl, isoindolyl, isoindolines, hemolysins, honokalani, heatline, cinnoline, phthalazine, naphthyridine, purinol, carbazolyl, xantener, acridines, phenazines, phenoxazines, phenothiazines and hinokitiol. Of them, particularly preferred are a group pyrrolidinyl, tetrahydrofuranyl, oxetanyl, tetrahydrofuryl, piperidinyl, dihydrooxazolo, dihydrothiazolo, dihydroisoxazole, dihydroisoxazole, piperazinil, morpholinyl, thiomorpholine, oxiranyl, dioxane, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolin, pyridyl, pyrimidinyl, triazinyl, tetrazolyl, benzofuranyl, benzothiophene, indolyl, hinely, ethanolic, benzopyranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzodioxolyl, DIOXOLANYL, tetrahydropyranyl, tetrahydropyranyl, oxadiazolyl, thiadiazolyl pyrazinyl, pyridazinyl, dihydropyridines, dihydropyrrole, dihydroxyaryl, dihydroimidazole, dihydropyrazolo, dihydropyrazine, dihydropyridines, tetrahydrooxazolo, bromanil, bromanil, Isopropenyl and isopropanol, and group pyrrolidinyl, piperidinyl, piperazinil, morpholinyl, thiomorpholine, DIOXOLANYL, pyridyl, furyl and thienyl are particularly preferred.

In the formula (1) X represents any radical-S-, -SO - and-SO-2. Of them, preferred are-SO - and-SO-2especially preferred is-SO-2.

In the formula (1) R1represents any radical-C(R5)(R6)(R7), -N(R8)(R9), -X1R10and-X2R11. Of them, preferred is R1that represents-C(R5)(R6)(R7). In particular, preferred is R1that represents-C(R5)(R6)(R7), where R5and R6can be linked together with the formation of the cyclic hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy.

In the formula (1) R2represents-Q21-Q22-Q23-Q24moreover , it is preferable to R2representing-Q21-Q22-Q23-Q24in which Q21, Q22and Q23each question is is th link, and Q24is And23where And23represents a hydrogen atom or alkyl group.

Or R1and R2can be linked together with the formation of the cyclic hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy, or =C(R12)(R13).

In the formula (1) R3represents-Q31-Q32-Q33-Q34moreover , it is preferable to R3representing And33-WITH-A33or-sooa33where And33represents a hydrogen atom, a hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy.

R4represents-Q41-Q42-Q43-Q44moreover , it is preferable to R4representing And43where And43represents a cyclic hydrocarbon group which has a Deputy, or a heterocyclic group which has a Deputy.

The present invention particularly preferred are the compounds of formula (1)in which R1represents a heterocyclic group which may have a Deputy, R2represents a hydrogen atom or a C1-6alkyl group, R3represents a cyclic hydrocarbon group which may have a Deputy, or geterotsiklicheskikh the group, which may have a Deputy, and R4represents a cyclic hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a substituent. These compounds represented by the following formula (3):

(where R15represents a heterocyclic group which may have a Deputy, R16represents a cyclic hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy, R17represents a cyclic hydrocarbon group which may have a Deputy, or a heterocyclic group which may have a Deputy, R18represents a hydrogen atom or a C1-6alkyl group, and X represents-S-, -SO - or-SO2-).

As the heterocyclic group represented by R15, R16or R17as examples can be mentioned the above-described heterocyclic group. As the cyclic hydrocarbon group represented by R16or R17as examples can be mentioned the above-described cyclic hydrocarbon group. As the substituents on these groups as examples can be mentioned the above-described substituents. As X preferred are-SO - or-SO2-p is item especially preferred is-SO 2-.

As the heterocyclic group represented by R15, R16or R17preferred are 3-7-membered saturated or 4-7-membered unsaturated monocyclic heterocyclic group having 1-4 atoms selected from a nitrogen atom, oxygen atom and sulfur atom, and 7 to 14-membered polycyclic heterocyclic group having 1-4 atoms selected from a nitrogen atom, oxygen atom and sulfur atom.

As the cyclic hydrocarbon group represented by R16or R17preferred are cycloalkyl group having 3-7 carbon atoms, cycloalkenyl group having 4-7 carbon atoms, monocyclic or polycyclic aromatic hydrocarbon group having 6-14 carbon atoms, spiropentane group having 7-11 carbon atoms, a cyclic hydrocarbon group with a cross (bridge) bonds having 7-10 carbon atoms, and condensed hydrocarbon group having 8-14 carbon atoms.

As the substituent for the cyclic hydrocarbon group or heterocyclic group, R15, R16or R17as examples can be mentioned groups represented by the above-Q201-Q202-Q203-Q204-Q205-Q206-Q207.

As the cyclic hydrocarbon group, a small town in allenou R 16or R17preferred are monocyclic or polycyclic aromatic hydrocarbon group having 6-14 carbon atoms, and more preferred groups are phenyl, naphthyl, indenyl and anthracenes, and particularly preferred is a phenyl group. These hydrocarbon groups may have 1-3 substituent selected from halogen atoms, With1-6alkyl groups,

With1-6alkoxygroup,2-6alkenyl groups, formyl groups,

With2-6alkanoyl groups, carboxyl groups,

carboxamido-C1-6alkyl groups,

With1-6alkoxycarbonyl-C1-6alkyl groups,

the carbonyl group, nitro group, ceanography, amidinopropane,

With2-7alkenylacyl, hydroxy-group, tocography, amino group,

With1-6alkylamino, di(C1-6alkyl)amino group,

With1-6alkoxycarbonyl groups, carbamoyl group,

With1-6alkylcarboxylic groups, di(C1-6alkyl)carbamoyl groups,

thiocarbamoyl group1-6alkyldiethanolamine groups,

di(C1-6alkyl)thiocarbamoyl groups, mercaptopropyl,

With1-6alkylthio,1-6alkylsulfonyl groups and

With1-6alkylsulfonyl groups.

Examples of the heterocyclic group represented by R16or R171-6alkyl groups,

With1-6alkoxygroup,2-6alkenyl groups, formyl groups,

With2-6alkanoyl groups, carboxyl groups,

carboxamido-C1-6alkyl groups,

With1-6al is oxcarbazepine-C 1-6alkyl groups,

the carbonyl group, nitro group, ceanography, amidinopropane,

With2-7alkenylacyl, hydroxy-group, tocography, amino group,

With1-6alkylamino, di(C1-6alkyl)amino group,

With1-6alkoxycarbonyl groups,

carbamoyl group1-6alkylcarboxylic groups,

di(C1-6alkyl)carbamoyl groups, thiocarbamoyl group,

With1-6alkyldiethanolamine groups,

di(C1-6alkyl)thiocarbamoyl groups,

mercaptopropyl,1-6alkylthio,1-6alkylsulfonyl groups and

With1-6alkylsulfonyl groups.

Examples of the heterocyclic group represented by R15include pyrrolidinyl, tetrahydrofuranyl, oxetanyl, tetrahydrofuryl, piperidinyl, piperazinil, morpholinyl, thiomorpholine, oxiranyl, tylenol, dioxane, pyrrolyl, aziridinyl, imidazolidinyl, pyrazolidine, tetrahydropyranyl, tetrahydropyranyl, tetrahydrooxazolo, tetrahydrofuryl, tetrahydroisoquinoline, tetrahydrocortisol, DIOXOLANYL, oxathiolane, furyl, thienyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolin, dihydrooxazolo, dihydrothiazolo, dihydroisoxazole, dihydroisoxazole, pyridyl, pyrimidinyl, triazinyl, tetrazolyl, pyrrolyl, imidazolyl, pyrazolyl, tiatia is alil, oxadiazolyl, dihydrooxazolo, dihydrothiazolo, dihydroisoxazole, dihydroisoxazole, pyrazinyl, pyridazinyl, pyranyl, dihydropyridines, dihydropyrrole, dihydroxyaryl, dihydroimidazole, dihydropyrazolo, dihydropyrazine, dihydropyridines, benzofuranyl, benzothiazolyl, indolyl, hinely, ethanolic, benzopyranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzodioxolyl, benzothiophene, benzisothiazole, benzisoxazole, bromanil, bromanil, Isopropenyl, isopropanol, indolinyl, indazoles, indolizinyl, isoindolyl, isoindolines, hemolysins, honokalani, hintline, cinnoline, phthalazine, naphthyridine, purinol, carbazolyl, xantener, acridines, phenazines, phenoxazines, and phenothiazinyl hinokitiol, which can be substituted by the above-Q201-Q202-Q203-Q204-Q205-Q206-Q207. Of these groups, preferred are a group pyrrolidinyl, tetrahydrofuranyl, oxetanyl, tetrahydrofuryl, piperidinyl, dihydrooxazolo, dihydrothiazolo, dihydroisoxazole, dihydroisoxazole, piperazinil, morpholinyl, thiomorpholine, oxiranyl, dioxane, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolin, pyridyl, pyrimidinyl, triazinyl, tetrazolyl, benzofuranyl, benzothiophene, indolyl, hinely, ethanolic benzopyranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzodioxolyl, DIOXOLANYL, tetrahydropyranyl, tetrahydropyranyl, oxadiazolyl, thiadiazolyl, piperazinil, pyridazinyl, dihydropyridines, dihydropyrrole, dihydroxyaryl, dihydroimidazole, dihydropyrazolo, dihydropyrazine, dihydropyridines, tetrahydrooxazolo, bromanil, bromanil, Isopropenyl and isopropanol, and particularly preferred are a group tetrahydropyranyl, tetrahydropyranyl, piperidinyl, pyridyl, pyrimidinyl, imidazolyl, thiazolyl, benzimidazolyl and chromenes. These heterocyclic groups may be substituted by halogen atoms, With1-6alkyl group,

With1-6alkoxygroup,2-6alkenylphenol group,

With2-6alkenylacyl, hydroxy-group, a carboxyl group,

carboxy-C1-6alkyl group,

With1-6alkoxycarbonyl-C1-6alkyl group,

With1-6alkoxycarbonyl-C2-6alkenylphenol group,

the hydroxyl-C1-6alkyl group,

(C6-14aromatic hydrocarbon)sulfonyl-C1-6alkyl group,

heterocyclyl-C1-6alkylaminocarbonyl,

heterocyclic group, heterocyclic-C1-6alkyl group,

With6-14aromatic hydrocarbon group,

(C6-14aromatic hydrocarbon) (1-6alkyl is Noi) group,

(C6-14aromatic hydrocarbon)tio1-6alkyl group,

azido-C1-6alkyl group, amino-C1-6alkyl group,

With1-6alkylamino-C1-6alkyl group,

di(C1-6alkylamino)-C1-8alkyl group,

hydroxy(C1-8alkylamino)(C1-6alkyl) group,

With1-6alkoxy(C1-6alkyl)amino-C1-6alkyl group,

(hydroxy-C1-6alkyl)(C1-6alkoxy-C1-6alkyl)amino-C1-6alkyl group,

With2-6alkanolamine-C1-6alkyl group,

(C6-14aromatic hydrocarbon)sulfonylamino-C1-6alkyl group,

(C1-6alkoxy)carbylamine-C1-6alkyl group,

carbamoylating-C1-6alkyl group,

N-alkylcarboxylic-C1-6alkyl group,

N,N-dialkylacrylamide-C1-6alkyl group,

aminosulfonyl-C1-6alkyl group,

N-alkylsulfonamides-C1-6alkyl group,

N,N-diallylmethylamine-C1-6alkyl group,

(C6-14aromatic hydrocarbon) (1-6alkyl)amino group,

heterocyclyl-C1-6alkylaminocarbonyl,

carbamoylated-C1-6alkyl group,

N-allylcarbamate-C1-6alkyl group,

N,N-diallylbarbituric-C1-6alkyl is Noah group,

(C6-14aromatic hydrocarbon) (1-6alkyl)carbamoylated-C1-6alkyl group,

With1-6alkoxycarbonyl-C1-6alkyl group,

(C6-14aromatic hydrocarbon)oxycarbonate-C1-6alkyl group,

(C6-14aromatic hydrocarbon)sulfonylamino-C1-6alkanoyl)amino-C1-6alkyl group,

With1-6alkoxycarbonyl-C1-6alkylaminocarbonyl,

amino-C1-6alkylaminocarbonyl,1-6alkylamino-C1-6alkylaminocarbonyl,

di(C1-6alkyl)amino-C1-6alkylaminocarbonyl,

carboxyamide(C1-6alkyl)group,

With1-6alkoxycarbonyl-C1-6alkyl group,

With1-6alkylsulfonamides-C1-6alkyl group,

amino-C1-6alkylcarboxylic-C1-6alkyl group,

N-(C1-6alkyl)amino-C1-6alkylcarboxylic-C1-6alkyl group,

N,N-di(C1-6alkyl)amino-C1-6alkylcarboxylic-C1-6alkyl group,

heterocalixarenes group,

geterotsiklicheskikh,

(C6-14aromatic hydrocarbon)carbonyl group,

With6-14aromatic carbylamines,

heterocyclyl-C1-6alkylcarboxylic-C1-6alkyl group,

heterocyclyl-C2-6alkene is carbonylative-C 1-6alkyl group,

With6-14aromatic uglevodorodokislyayuschih-C1-6alkyl group,

With6-14aromatic plevothroidonline-C1-6alkyl group,

heterocyclic, carbylamine-C1-6alkyl group,

With1-6alkoxysilane-C1-6alkyl group,

carbamoyl group, N-(C1-6alkyl)carbamoyl group,

N,N-di(C1-6alkyl)carbamoyl group,

With1-6alkyl-C3-8cycloalkylcarbonyl group,

With3-8cycloalkyl-C1-6alkylcarboxylic group,

heterocyclisation group,

With1-6aromatic carbamoyl group,

heterocyclic carbohydratedeficient group,

With6-14aromatic uglevodorodokislyayushchikh group,

With1-6alkylthio-C1-6alkylcarboxylic group,

With1-6alkylsulfonyl-C1-6alkylcarboxylic group,

With1-6alkylsulfonyl-C1-6alkylcarboxylic group,

hydroxyaminopyrimidines group,

hydrazinecarboxamide group or

N-C1-6alkylhydroxylamines group,

toformulate(C6-14aromatic hydrocarbon)thiacarbocyanine-C1-6alkyl group,

diformyl-C1-6alkylamino-C6-14aromaticas what s uglevodorodokislyayuschih-C 1-6alkyl group,

formylamino-(C6-14aromatic hydrocarbon)carbylamine(C1-6alkyl) group,

formyl-C1-6alkylamino(C6-14aromatic hydrocarbon)carbylamine-C1-6alkyl group,

With1-6alcoholpenicillindosage-C1-6alkyl group,

di(C2-6alkanoyl)amino-C1-6alkyl group,

di(C1-6alkoxycarbonyl)amino-C1-6alkyl group,

With1-6alkylchlorosilanes group,

With3-7cycloalkyl-C1-6alkylaminocarbonyl group,

With1-6alkoxycarbonyl group,

(hydroxy)(C1-6alkyl)aminocarbonyl group,

(C1-6alkoxy)(C1-6alkyl)aminocarbonyl group,

N'-C1-6alkylhydroxylamines group,

N',N'-di(C1-6alkyl)hydrazinecarboxamide group,

N,N'-di(C1-6alkyl)hydrazinecarboxamide group,

N,N',N'-three(C1-6alkyl)hydrazinecarboxamide group,

N'-(heterocyclicamines)hydrazinecarboxamide group,

formyl group, hydroxyimino,

With1-6alkoxyimino,

bis(C1-6alkoxy-C1-6alkyl)amino-C1-6alkyl group,

hydroxy-C1-6alkylchlorosilanes group,

With1-6alkoxy-C1-6alkylchlorosilanes group is Oh,

With1-6alkoxycarbonyl-C1-6alkylchlorosilanes group,

amino(C1-6alkyl)heterocyclic group,

N-C1-6alkylamino-C1-6alkylchlorosilanes group,

N,N-di(C1-6alkyl)amino-C1-6alkylchlorosilanes group,

hydroxymetabolites group,

With1-6alkoxycarbonylmethyl group,

carboxy-C2-5alkenylphenol group or

exography,

(where the above With6-14aromatic hydrocarbon group or heterocyclic group may be substituted by a halogen atom, a C1-6alkyl group, a C1-6alkoxygroup,

With2-6alkenylphenol group, formyl group,

With2-6alkanoyloxy group, a carboxyl group,

the group carboxyamide(C1-6alkyl),

group C1-6alkoxycarbonyl(C1-6alkyl),

exography, nitrogroup, cyano, amidinopropane,

With2-6alkenylacyl, hydroxy-group, tocography,

the amino group, With1-6alkylaminocarbonyl, di(C1-6alkyl)amino group,

amino(C1-6alkyl) group, a C1-6alkoxycarbonyl group,

carbamoyl group1-6alkylcarboxylic group,

di(C1-6alkyl)carbamoyl group, thiocarbamoyl group,

With1-6alkylthiol the ilen group,

di(C1-6alkyl)thiocarbamoyl group,

With2-7alkanolamines,2-7alkanoyl(C1-6alkyl)amino group,

tio2-7alkanolamines,

tio2-7alkanoyl-(C1-6alkyl)amino group,

formylamino, formyl(C1-6alkyl)amino group,

coformulations, diformyl(C1-6alkyl)amino group,

With2-7alkanoyloxy, formyloxyethyl, mercaptopropyl,

With1-6alkylthiol,1-6alkylsulfonyl group,

With1-6alkylsulfonyl group, aminosulfonyl group,

With1-6alkylaminocarbonyl group,

di-C1-6alkylaminocarbonyl group,

With1-6alkylsulfonamides or

With1-6alkylsulfonyl(C1-6alkyl)amino group.

The compounds of this invention represented by formula (1)can have stereoisomer or enantiomer, asymmetric derivatives of hydrocarbons. Any of these stereoisomers and enantiomers and their mixtures are included in this invention. S-oxide compounds of the present invention exists when the heterocyclic group contains a sulfur atom. Any of the monoxide and dioxide included in the S-oxide.

There is no specific limitation regarding the salt of the compounds of this invention represented by formula (1)as it is farmacevtichesky acceptable salt. Specific examples of salts include salts of mineral acids, such as hydrochloride, hydrobromide, hydroiodide, phosphate, nitrate and sulfate, benzoate, organic sulfonates, such methanesulfonate, 2-hydroxyethanesulfonic and p-toluensulfonate, and organic carboxylates such as acetate, propanoate, oxalate, malonate, succinate, glutarate, adipate, tartrate, maleate, malate and Mandela.

When the compound represented by formula (1)has an acid group, this salt may be a salt of the alkali metal ion or ion alkaline-earth metal. There are no particular restrictions on the MES, as long as it is pharmaceutically acceptable. Specific examples of it include a hydrate and a solvate of ethanol.

Next will be described the methods for producing the compounds of this invention represented by formula (1).

The compounds of this invention represented by formula (1), or their salts, or their solvate can be obtained using well-known chemical methods of obtaining in combination. Next will be described a typical synthetic methods.

After the synthesis of each of the compounds of this invention, a Deputy, as the nitrogen atom, hydroxyl group or carboxyl group in need of protection may be protected by well-known protective group which can be removed if necessary the spine. This protective group can be removed using conventional organic chemistry, if necessary.

The sulfide compound (1)having S as X, can be obtained by substitution Colnago connections carbon or by the addition of carbon to this toolname connection (the following formulas 2, 4 and 5).

Alvinlee connection (1), having a SO as X, can be obtained by oxidation of the sulfide compound (described below formula 2).

Sulfonylurea compound (1)having SO2as X, can be obtained by condensation sulfonylurea compounds (R1and/or R2and/or R3=N) with substituent (R1and/or R2and/or R3) or by oxidation of the sulfide compound (X is S) or sulfanilimide compounds (X is SO) (the following formulas 1 and 2). It can also be obtained by substitution of the derived sulfanilic acid by carbon or by adding carbon to the derived sulfanilic acid (the following formulas 3, 4 and 5). The application of these methods in combination can also be used for this receipt.

Deputy of the compound (1)thus obtained can be converted to have a different structure. Described specifically, R1and/or R2and/or R3and/or R4can be replaced with another Deputy and the known method.

For example, the compound (1)having as R1and/or R2and/or R3and/or R4alkyl group with a hydroxyl group, a protected vinyl or silyl group, can be converted in connection with the corresponding hydroxyalkyl group removing protection in the usual way. In addition, the hydroxyl part can be introduced into the functional group, such as ester, carbonate, carbamate, halogen or sulfonate, in a known manner. Or some of them can be put into a Vice, such as a hydrocarbon, alkoxy, amine, amide, or sulfide, or a functional group in a conventional manner. Alternatively, with other R1, R2, R3or R4may be formed of the cyclic part of the molecule.

Various functional groups, along with a hydroxyl group, can be obtained by this conversion, and this conversion method can be carried out on the basis of known methods. For these stages of transformation can be used reagent, solvent and reaction conditions known per se in the field.

The method of obtaining sulfonylurea compound (1: X=SO2):

Reaction scheme 1

For example, various compounds (1), characterized by R1can be obtained by reaction of the compound (1)having Alamogordo as R 1and SO2as X, which is known or can be obtained in a known manner, with an electrophilic reagent in the presence of a base in an inert solvent. In reaction R1can be entered as an independent Deputy, using an intramolecular reaction with an electrophilic reagent, but alternatively can be formed cyclic structure together with R2intramolecular reaction with R2having electrophilic functional group in its side chain.

Specifically, this reaction is performed by adding the compound (1: R1=H, X=SO2and at least an equivalent amount of the base to at least equivalent to the amount of the electrophilic reagent in an inert solvent.

The reaction temperature is usually from -78°to 200°C.

The reaction time is usually from 0.5 hour to 1 day.

Examples of inert solvents which can be used in the above reaction include ether solvents, halogenated solvents, aromatic solvents, nitrile solvents, amide solvents. They can be used individually or in combination of two or more solvents. Of them, preferred are tetrahydrofuran, dimethoxyethane, diethyl ether, dimethylformamide, toluol etc.

Examples of the electrophilic reagent used in the reaction described above, include R1-Y (where Y represents an eliminating group), a carbonyl compound such as aldehyde, ketone, ester and amide) and epoxysilane.

Alternative, R2containing Y, a carbonyl group or epoxypropan can be used as an electrophilic functional group.

Examples are groups represented by Y include halogen atoms (such as chlorine, bromine and iodine), alkylsulfonates having 1-6 carbon atoms, which may be galogenirovannyie (for example, methanesulfonate, econsultancy, tripterocalyx), and arylsulfonate, which have 6 to 10 carbon atoms and may have a Deputy. Deputies to arylsulfonate include 1-3 of halogen atom, the alkyl groups of which have 1-6 carbon atoms and may be halogenated, and alkoxygroup having 1-6 carbon atoms.

Specific examples are groups include benzosulfimide-, p-toluensulfonate-, 1 naphthalenesulfonate - and 2-naphthalenesulfonate.

Examples of bases that can be used for the above reaction include alkality (for example, n-utility, second-utility and tert-utility), hydrides of alkali metal or alkaline-C is Mielno metal (such as lithium hydride, sodium hydride, potassium hydride and calcium hydride), amides of an alkali metal or alkaline-earth metal (such as lithium amide, sodium amide, diisopropylamide lithium, dicyclohexylamine lithium hexamethyldisilazide lithium hexamethyldisilazide sodium and hexamethyldisilazide potassium), lower alkoxides of alkali metal and alkaline-earth metal (such as sodium methoxide, ethoxide sodium tert-piperonyl potassium), alkali metal hydroxides, alkaline earth metal or silver (such as silver hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide and barium hydroxide), carbonates of alkali metal, alkaline-earth metal or silver (sodium carbonate, potassium carbonate, cesium carbonate and silver carbonate), bicarbonates, alkali metal (such as sodium bicarbonate and potassium bicarbonate), and silver oxide.

Sulfonylurea compound (1: X=SO2) can also be obtained by reaction of the compound (1), which has a hydrogen atom as R1and SO2as X is known or can be obtained in a known manner, with 1-3 equivalents of R1HE is in the presence of a condensing agent in an inert solvent.

The reaction temperature is usually from -20°to 200°C, preferably from 0°to 150°C.

The reaction time is usually from 0.5 h to 3 days.

Examples of inertiagravity, which can be used in the above reaction include ether solvents, halogenated solvents and aromatic solvents. They can be used individually or in combination of two or more solvents. Of them, preferred are tetrahydrofuran and toluene.

Examples of the condensing agent which can be used in the above reaction include any of cyanomethylphosphonate (such as cyanomethaemoglobin and cyanomethylene-tri-n-butylphosphine), triarylphosphine (such as triphenylphosphine) and trialkylphosphine (such as tributylphosphine) and compounds of azodicarboxylic acids (such as diethylazodicarboxylate, diisopropylsalicylic, piperidinecarboxylate and BidirectionalIterator).

The method of obtaining sulfonylurea compound (1: X=SO2), with SR10as R1

Sulfonylurea compound (1: X=SO2), with SR10as R1can be obtained by reaction of the compound (1), which has a hydrogen atom as R1and SO2as X is known or can be obtained in a known manner, with 1-3 equivalents of R10S-Y (Y has the same meaning as described above) in the presence of 1-3 equivalents of base (such as sodium hydride) in a trade is " a solvent.

The reaction temperature is usually from -20°to 150°C.

The reaction time is usually from 0.5 h to 1 day.

Examples of inert solvents which can be used in the above reaction include ether solvents, halogenated solvents, aromatic solvents and amide solvents. They can be used individually or in combination of two or more solvents. Of them, preferred is dimethylformamide.

The method of obtaining sulfonylurea compound (1: X=SO2), in which R1and R2associated with education =CR12R13

Sulfonylurea connection, in which R1and R2associated with education =CR12R13can be obtained by the action of base on the compound (1)having a hydrogen atom as R1, SO2as X and-CYR12R13(Y has the same meaning as described above) as R2.

More specifically, the compound that has a hydrogen atom as R1, SO2as X and-CYR12R13(Y has the same meaning as described above) and is known or can be obtained in the conventional method, process at least equivalent amount of base in an inert solvent.

The reaction temperature is usually SOS the place from -78° With up to 150°C, preferably from -78°C to 50°C. the reaction Time is usually from 0.5 h to 1 day.

Examples of inert solvents which can be used in the above reaction include alcohol solvents, ether solvents, halogenated solvents, aromatic solvents, nitrile solvents, amide solvents, ketone solvents, sulfoxide solvents and water. They can be used individually or in combination of two or more solvents. Of them, preferred are methylene chloride, tetrahydrofuran and diethyl ether, etc.

Examples of bases that can be used for the above reaction include alkali metal hydrides or alkaline earth metal (such as lithium hydride, sodium hydride, potassium hydride and calcium hydride); amides alkali metal or alkaline-earth metal (such as lithium amide, sodium amide, diisopropylamide lithium, dicyclohexylamine lithium hexamethyldisilazide lithium hexamethyldisilazide sodium and hexamethyldisilazide potassium); lower alkoxides of alkali metal and alkaline-earth metal (such as sodium methoxide, ethoxide sodium tert-piperonyl potassium), alkali metal hydroxides, alkali land metal or silver (such as silver hydroxide, sodium hydroxide, the hydroxide to the lia, the lithium hydroxide and barium hydroxide; alkali metal carbonates, alkaline earth metal or silver (sodium carbonate, potassium carbonate, cesium carbonate and silver carbonate; bicarbonates of alkali metal (such as sodium bicarbonate and potassium bicarbonate); alkality (such as n-utility) or alkalmazasa Grignard reagents (such as methylmagnesium); inorganic bases, such as silver oxide, or amines (such as triethylamine, diisopropylethylamine and N-methylmorpholine); and organic bases such as basic heterocyclic compounds (such as dimethylaminopyridine, pyridine, imidazole, 2,6-lutidine, kallidin, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,4-diazabicyclo[2.2.2]octane).

A method of obtaining a sulfide compound (1: X=S), sulfanilimide compound (1: X=SO), sulfonylurea compound (1: X=SO2)

Reaction scheme 2

1) a method of obtaining a sulfide compound (1: X=S)

The compound (1)having S as X, can be obtained by reaction of the compound (2) with tilenum compound in the presence of a base in an inert solvent.

The compound (2)having a hydroxyl group, can be obtained in a known manner. Hereinafter will be described in various ways and one example. The compound (2)having a hydroxyl group, may be the Holocene addition of ORGANOMETALLIC reagent (as metal typically use lithium or magnesium representative of the Grignard reagent) in the amount equivalent to the excess to the aldehyde or ketone, represented by the formula, R1(C=O)R2in an inert solvent, such as tetrahydrofuran or diethyl ether, to their interaction. ORGANOMETALLIC reagent represented by R3-M, can be obtained, for example, when R3represents an aromatic ring or aromatic heterocycle, adding reagent alkylate or ultilateral Grignard reagent to arivalagan for the exchange of metal, as reported in the article by H. Gilman, et al., J. Org. Chem. 1951, 16, 1788-1791 or article F. Trecourt, et al., Tetrahedron 2000, 56, 1349-1460. The compound (2)having eliminated the group Y can be obtained by conversion of the hydroxyl group of the hydroxyl-containing compound (2) in eliminating group in a known manner.

The compound (1)having S as X, can also be obtained by reaction of the compound (2) with a salt of an alkali metal or alkaline-earth metal (such as lithium, sodium or potassium) Colnago compounds in an inert solvent.

The reaction temperature is usually from -20°C to -200°C, preferably from room temperature to 100°C. When the substituent R of the connection is a three-dimensional Deputy, preferred is sometimes higher temperature than that specified above, or the reaction in a sealed tube.

The reaction time is usually in the range of 0.5 hours to 1 hour.

Examples of the bases of the deposits, which can be used for the above reaction include alkali metal hydrides or alkaline earth metal (such as lithium hydride, sodium hydride, potassium hydride and calcium hydride); amides alkali metal or alkaline-earth metal (such as lithium amide, sodium amide, diisopropylamide lithium, dicyclohexylamine lithium hexamethyldisilazide lithium hexamethyldisilazide sodium and hexamethyldisilazide potassium); lower alkoxides of alkali metal and alkaline-earth metal (such as sodium methoxide, ethoxide sodium tert-piperonyl potassium), alkali metal hydroxides, alkaline earth metal or silver (such as silver hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide and barium hydroxide; alkali metal carbonates, alkaline earth metal or silver (sodium carbonate, potassium carbonate, cesium carbonate and silver carbonate; bicarbonates of alkali metal (such as sodium bicarbonate and potassium bicarbonate); alkality (such as n-utility) or alkalmazasa Grignard reagents (such as methylmagnesium); inorganic bases, such as silver oxide, or amines (such as triethylamine, diisopropylethylamine and N-methylmorpholine); and organic bases such as basic heterocyclic compounds (such as dimethylaminopyridine, pyridine, imidazole, 2,6-lutidine,kallidin, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,4-diazabicyclo[2.2.2]octane).

Examples of inert solvents which can be used in the above reaction include alcohol solvents, ether solvents, halogenated solvents, aromatic solvents, nitrile solvents, amide solvents, ketone solvents, sulfoxide solvents and water. They can be used individually or in combination of two or more solvents. Of them, preferred are methylene chloride, tetrahydrofuran and diethyl ether, etc.

When the compound (2) has a hydroxyl group, instead of eliminating the group Y, the condensate can be obtained using the reaction Mitsunobu.

The compound (1) can be obtained by the reaction of hydroxyl-containing compounds (2), which is known or can be obtained in a known manner, with 1-3 equivalents of the compounds thiophenol in the presence of 1-3 equivalents of triarylphosphine (such as triphenylphosphine) or trialkylphosphine (such as tributylphosphine) and 1-2 equivalents of azodicarboxylic acid derivative (such as diethylazodicarboxylate, diisopropylsalicylic, piperidinecarboxylate or BidirectionalIterator) in an inert solvent.

The reaction temperature is usually about the -20° C to -150°C, preferably from room temperature to 80°C. When the substituent R of the connection is a three-dimensional Deputy, preferred is sometimes higher temperature than that specified above, or the reaction in a sealed tube.

The reaction time is usually in the range from 0.5 hour to 1 day.

Examples of inert solvents which can be used in the above reaction include ether solvents, halogenated solvents and aromatic solvents. Two or more of these solvents may be used in the form of a mixture. Of them, preferred is tetrahydrofuran.

2) the Method of obtaining sulfanilimide compound (1: X=SO)

Alvinlee compound (1: X=SO) can be synthesized by oxidation of the sulfide compound (1: X=S), more specifically, the reaction of the sulfide compound (1) in the presence of an oxidant in an inert solvent.

The reaction temperature is usually from -20°to 200°C, preferably from 0°to 100°C.

Examples of inert solvents which can be used in the above reaction include alcohol solvents, ether solvents, halogenated solvents, aromatic solvents, nitrile solvents, amide solvents, ketone solvents, sulfoxide connected to the I and water. Two or more of these solvents may be used in combination. Of them, preferred are methylene chloride, chloroform, methanol and ethanol.

Examples of oxidizing agents that can be used in the above reaction include hydrogen peroxide, organic percolate compounds (such as peracetic acid and metachlorobenzoic acid), metaperiodate (such as metaperiodate sodium), allniters, nitrogen tetroxide, halogen, N-halogenated derivatives (such as N-chlorosuccinimide and N-bromosuccinimide), hydroperoxides such as tert-butylhydroperoxide), diacetate odensala, dichloride odensala, tert-butylhypochlorite, sulfurylchloride, singlet oxygen, ozone, oxides of selenium and selenium acid. Optically active sulfoxide (1: X=SO) can be obtained using mixtures tetraisopropoxide titanium/diethyltartrate/tert-butylhydroperoxide, tetraisopropoxide titanium/diethyltartrate/peracetic acid or the like

Specifically, the sulfide compound (1: X=S) and 1-2 equivalents of an oxidant, such as metachlorobenzoic acid, periodate sodium or hydrogen peroxide, can be mixed in an inert solvent such as methylene chloride, tetrahydrofuran, water, methanol or the like, 0-100°C for approximately 1 hour to 2 days.

3) the Method of obtaining sulfonylurea connection (: X=SO 2)

Sulfonylurea compound (1: X=SO2) can be synthesized by oxidation of the sulfide compound (1: X=S) or sulfanilimide compound (1: X=SO), more specifically by the reaction of the sulfide compound (1: X=S) or sulfanilimide compound (1: X=SO) in the presence of an oxidant in an inert solvent.

The reaction temperature is usually from -20°to 150°C, preferably from 0°C to 80°C.

Examples of inert solvents which can be used in the above reaction include alcohol solvents, ether solvents, halogenated solvents, aromatic solvents, the solvents are carboxylic acids, nitrile solvents, amide solvents, ketone solvents, sulfoxide compounds and water. Two or more of these solvents may be used in combination. Of them, preferred are methylene chloride, chloroform, methanol, ethanol and acetic acid.

Examples of oxidizing agents which can be used in the above reaction include hydrogen peroxide, hydrogen peroxide - catalyst based on transition metal (such as ammonium molybdate or iron chloride (III), organic percolate compounds (such as peracetic acid and metachlorobenzoic acid), metaperiodate (such as metaperiodate intothree is), peroxosulfates potassium permanganates such as potassium permanganate), perborate sodium, halogen, N-halogenated derivatives (such as N-chlorosuccinimide and N-bromosuccinimide), hydroperoxides such as tert-butylhydroperoxide), diacetate odensala, dichloride odensala, hypochlorites such as sodium hypochlorite or tert-butylhypochlorite), singlet oxygen, ozone, oxides of selenium and selenium acid. A preferred example of these reaction conditions include reaction of the sulfide compound (1: X=S) with 2-5 equivalents of oxidant (such as metachlorobenzoic acid, periodate sodium, hydrogen peroxide or a mixture of hydrogen peroxide/ammonium molybdate) in methylene chloride, a mixture of tetrahydrofuran-water or methanol at 0-100°C for approximately 1 h to 2 days.

The method of obtaining sulfonylurea compound (1: X=SO2):

Reaction scheme 3

Sulfonylurea compound (1: X=SO2) can be synthesized by the introduction sulfonyloxy group in the compound (2), more specifically by the reaction of the compound (2) with a salt of an alkali metal, alkaline earth metal or tetrabutylammonium sulfinol acid.

Specifically, the compound (2) is subjected to interaction with an equivalent to excess amount sulfinol acid or a salt thereof in an inert solvent.

Temperature is RA reaction is usually from -20° With up to 200°C, preferably from room temperature to 100°C. When the substituent R of the connection is a three-dimensional Deputy, preferred is sometimes higher temperature than that specified above, or the reaction in a sealed tube.

The reaction time is usually in the range from 0.5 h to 1 day.

Examples of inert solvents which can be used in the above reaction include alcohol solvents, ether solvents, halogenated solvents, aromatic solvents, nitrile solvents, amide solvents, ketone solvents, sulfoxide solvents and water. Two or more of these solvents may be used in combination. Of them, preferred are butanol and dimethoxyethane.

A method of obtaining a sulfide compound (1: X=S):

Reaction scheme 4

A method of obtaining a sulfide compound (1: X=S).

(1) when Y1and Y2are electron-withdrawing group:

The compound (1) can be obtained by exposure of the compound (4), which is known or can be obtained in a known manner, Michael's reaction, more specifically the reaction of the compound (4) with a thiol (R4SH) in the presence of a base.

Specifically, the compound (4) is subjected to interaction with the share of the CMV thiol from equivalent to excess in an inert solvent in the presence of a base in an amount of from catalytic to an equivalent.

The reaction temperature is usually from -20°to 100°C, preferably at room temperature.

The reaction time is usually in the range from 0.5 h to 1 day.

Examples of electron-withdrawing groups include carbonyl groups such as acyl, ether, carboxylic acid and amide), a cyano, a nitro-group, sulfinyl group and sulfonyloxy group. Examples of inert solvents which can be used in the above reaction include alcohol solvents, ether solvents, halogenated solvents, aromatic solvents, nitrile solvents, amide solvents, ketone solvents, sulfoxide solvents and water. Two or more of these solvents may be used in combination. Of them, preferred are methanol, methylene chloride and tetrahydrofuran, etc.

(2) When R2is alkoxygroup or sulfide group:

The compound (1) can be obtained by treating compound (4), which is known or can be obtained in a known manner, in the presence of an acid catalyst, more specifically, the reaction of the compound (4) with a thiol in the presence of acid.

Specifically, the compound (4) is subjected to interaction with the number of thiol from the equivalent to excess in an inert solvent in the presence of acids is wow catalyst from catalytic to an equivalent.

The reaction temperature is usually from -20°to 100°C, preferably at room temperature.

The reaction time is usually in the range from 0.5 h to 1 day.

Examples of acids which may be used in the above reaction include anhydrous acid, such as paratoluenesulfonyl acid, camphorsulfonic acid, hydrogen chloride, and acidic ion-exchange resin; and as catalysts of the Lewis acid, such as trimethylsilyltrifluoromethane and boron TRIFLUORIDE.

Examples of inert solvents which can be used in the above reaction include ether solvents, halogenated solvents, aromatic solvents, nitrile solvents, amide solvents. Two or more of these solvents may be used in combination. Of them, preferred is methylene chloride.

A method of obtaining a sulfide compound (1: X=S) and sulfonylurea compound (1: X=SO2):

Reaction scheme 5

1) a method of obtaining a sulfide compound (1: X=S)

The compound (1) can be obtained by exposure imine reactions of nucleophilic substitution, more specifically, the interaction imine, or a salt imine, which is compound (5), with the number of thiol from the equivalent to the excess in risotti base or acid in an amount of from catalytic to the equivalent. The compound (5) can be obtained by mixing carbonyl compounds (R2COR3c primary or secondary amine or Amida in a suitable solvent.

The reaction temperature is usually from 0°to 100°C, preferably at room temperature.

The reaction time is usually in the range from 0.5 hour to 1 day.

Examples of bases that can be used for the above reaction include alkali metal hydrides or alkaline earth metal (such as lithium hydride, sodium hydride, potassium hydride and calcium hydride); amides alkali metal or alkaline-earth metal (such as lithium amide, sodium amide, diisopropylamide lithium, dicyclohexylamine lithium hexamethyldisilazide lithium hexamethyldisilazide sodium and hexamethyldisilazide potassium); lower alkoxides of alkali metal and alkaline-earth metal (such as sodium methoxide, ethoxide sodium tert-piperonyl potassium), alkali metal hydroxides, alkali land metal or silver (such as silver hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide and barium hydroxide; alkali metal carbonates, alkaline earth metal or silver (sodium carbonate, potassium carbonate, cesium carbonate and silver carbonate; bicarbonates of alkali metal (such as sodium bicarbonate and potassium bicarbonate); Alki the lithium (such as n-utility) or alkalmazasa Grignard reagents (such as methylmagnesium); inorganic bases, such as silver oxide, or amines (such as triethylamine, diisopropylethylamine and N-methylmorpholine); and organic bases, for example, basic heterocyclic compounds (such as dimethylaminopyridine, pyridine, imidazole, 2,6-lutidine, kallidin, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,4-diazabicyclo[2.2.2]octane).

Examples of acids that can be used in the above reaction include formic acid, acetic acid, benzoic acid, paratoluenesulfonyl acid and chloride-hydrogen acid.

Examples of inert solvents which can be used in the above reaction include alcohol solvents, ether solvents, nitrile solvents, amide solvents, ketone solvents, sulfoxide solvents and water. Two or more of these solvents may be used in the form of a mixture. Of them, preferred is tetrahydrofuran.

2) the Method of obtaining sulfonylurea compound (1: X=SO2)

The compound (1) can be obtained by exposure imine reactions of nucleophilic substitution, more specifically, the interaction imine, or a salt imine, which is compound (5), with the number sulfinol acid equivalent to the excess in the presence of acid in amount from Catalytica is someone equivalent.

The reaction temperature is usually from 0°to 100°C, preferably at room temperature.

The reaction time is usually in the range from 0.5 hour to 1 day.

Examples of acids that can be used in the above reaction include formic acid, acetic acid, benzoic acid, paratoluenesulfonyl acid and chloride-hydrogen acid.

The compound (5) can be obtained by mixing carbonyl compounds (R2COR3c primary or secondary amine or Amida in a suitable solvent.

The compound (1) can also be obtained without isolating the compound (5). For example, it can only be obtained by reaction of an aldehyde with an equivalent amount of amide or sulfinol acid in the presence of excess acid in an inert solvent.

The reaction temperature is usually from 0°to 100°C, preferably at room temperature.

The reaction time is usually in the range from 1 hour to 1 day.

Examples of inert solvents which can be used in the above reaction include alcohol solvents, ether solvents, nitrile solvents, amide solvents, ketone solvents, sulfoxide solvents and water. Two or more of these solvents may be used as MESI. Of them, preferred is tetrahydrofuran.

Compounds (1) of the present invention, in particular, the compounds of formula (3), strongly inhibit the production or secretion β-amyloid protein, so they are useful as a drug for the prevention or treatment of diseases resulting from abnormal production or secretion β-amyloid protein such as Alzheimer's disease and down syndrome, or diseases associated with deposition of amyloid.

When using the compounds of this invention as a pharmaceutical for humans, the dose ranges from 1 mg to 1 g per day for an adult, preferably from 10 mg to 300 mg In the introduction to the animals of this dose varies depending on the purpose of administration (treatment or prevention), the type or size of animal to be treated, the type or degree of bacteria, which was infected with this animal, but the usual daily dose is in the range from 0.1 mg to 200 mg, preferably from 0.5 mg to 100 mg per kg of animal body weight. This daily dose is administered once daily, or two to four servings per day. The daily dose may exceed the above number, if necessary.

A pharmaceutical composition comprising a compound of this invention may be obtained in the desired Faure is e, selected in accordance with the method of administration, using various commonly used methods of obtaining. Examples of forms of pharmaceutical compositions containing the compound of the present invention as a main ingredient, include orally administered drugs, such as tablets, powders, granules, capsules, liquids, syrups, elixirs, oily or aqueous suspensions.

Injectable solutions may contain a stabilizer, an antiseptic agent, solubilizers agent or the like Can also recover the solid product, which was obtained by filling the vessel with a solution containing the agent, and then his lyophilization, before use. The number for a single injection, can be placed in one vessel, or the number of multiple injections can be placed in one container.

Examples of the preparation for external use include liquids, suspensions, emulsions, ointments, gels, creams, lotions, sprays and patches.

The solid preparation contains, together with the compound of the present invention, pharmaceutically acceptable additives. It can be prepared by mixing the compounds of this invention with additives selected from fillers, diluents, binding agents, disintegrators, promoters solubilization, moisturizers and lubricants are substances, if necessary.

P is emery liquid preparations include solutions, suspensions and emulsions. They may contain suspendisse agent or emulsifying agent as an additive.

Examples

The invention will be described hereinafter in detail with reference to variants of the present invention, but should not be construed as limited below options. In addition, all compounds given in the examples below, should be considered as related to the type S or type n unless otherwise specified.

Reference example 1: 1-(2,5-differenl)-1-pentanol

At -78°in argon atmosphere n-utility (1.52 M solution in hexane, 14,5 ml of 22.0 mmol) was added dropwise to a solution of 1,4-diferentialglea (2,84 g, 20.0 mmol) in tetrahydrofuran (40 ml). With stirring, the temperature of the reaction mixture was raised to -20°C for 2 hours. To the reaction mixture were added saturated aqueous solution of ammonium chloride followed by extraction with ethyl acetate. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and then concentrated. Thus obtained residue was purified by chromatography on a column of silica gel (9% ethyl acetate-hexane) to obtain specified in the connection header (2,62 g, 66%) as a pale yellow oil.

1H-NMR (400 MHz, CDCl3) δ: of 0.90 (3H, t, J=7,3 Hz), 1,28 of 1.50 (4H, m), 1.70 to to 1.82 (2H, is), 1,91-of 1.95 (1H, SIRM), to 4.98 (1H, DD, J=11,7, 5,9 Hz), 6,88-7,00 (2H, m), 7,18 (1H, DDD, J=8,8, 5,6, 3,2 Hz).

Example 1: 2-[1-[(4-chlorophenyl)thio]pentyl]-1,4-differenza

When 0°4-chlorbenzoyl (435 mg, 3.00 mmol), triphenylphosphine (798 mg, 3.00 mmol) and diisopropylethylamine (588 μl, 3.00 mmol) was sequentially added to a solution of 1-(2,5-differenl)-1-pentanol (300 mg, 1.50 mmol) in methylene chloride (6 ml). The reaction mixture was stirred at room temperature for 5 hours, diluted with methylene chloride and then washed sequentially 1 N. aqueous sodium hydroxide solution and saturated salt solution. After drying over MgSO4the mixture was concentrated. Thus obtained residue was purified twice by chromatography medium pressure on a column of silica gel (first time with a mixture of 1% ethyl acetate-hexane and once with hexane) to obtain the specified title compound (266 mg, 54%) as a colourless oil.

IR (ATR) ν: 2958, 2931, 1624, 1595, 1574, 1493, 1475, 1425, 1389, 1234, 1215, 1171, 1095, 1012, 874, 814 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 0,86 (3H, t, J=7,3 Hz), 1,22-of 1.41 (4H, m), 1,78-of 1.88 (1H, m), 1,89 of 1.99 (1H, m), 4,48 (1H, DDD, J=8,6, and 6.6, 1.7 Hz), for 6.81-6,86 (1H, m), 6.90 to (1H, TD, J=9,0, 4.6 Hz), 7,06 (1H, DDD, J=9,0, 5,8, a 3.2 Hz), 7,17 (4H, s).

MS (m/z): 326 (M+).

HRMS (EI): C17H17ClF2S (M+).

Calculated: 326,0708.

Found: 326,0696.

Example 2: 2-[1-[(4-chlorophenyl)self the Nile]pentyl]-1,4-differental (isomer 2 and isomer 2-In)

After addition of 3-chloroperbenzoic acid (301 mg, of 1.74 mmol) to a solution of 2-[1-[(4-chlorophenyl)thio]pentyl]-1,4-diferente (515 mg, was 1.58 mmol) in methylene chloride (10 ml) at 0°C, the mixture was stirred for 18 hours at room temperature. After additional 3-chloroperbenzoic acid (100 mg, 0,578 mmol) and the mixture was stirred for 3 hours at room temperature. The reaction mixture was diluted with methylene chloride, washed successively 1 N. aqueous sodium hydroxide solution, water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (10% ethyl acetate-hexane) to obtain specified in the header of isomer 2 (low polarity) and specified in the header of isomer 2 (high polarity) (230 mg, 43%), each as a colourless oil. Then the received specified in the header isomer 2 was recrystallized from hexane and obtained as colorless needle crystals (79,8 mg, 15%).

Isomer 2

Melting point: 108,5-109,0°C.

IR (ATR) ν: 2929, 2854, 1493, 1275, 1132, 1174, 1086, 1043, 1011, 962, 862, 823, 735, 503 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.90 (3H, t, J=7,1 Hz), 1,30-1,50 (4H, m), 1,96 e 2.06 (1H, m), 2,27-of 2.36 (1H, m), a 4.03 (1H, DDD, J=9,6, 6,1, 1.2 Hz), of 6.71 (1H, TD, J=9,1, 4,4 Hz), 6,85-6,92 (1H, m), 7,07 for 7.12 (1H, m), 7,10 (2H, the, J=8.6 Hz), 7,28 (2H, d, J=8.6 Hz).

MS (m/z 343 (M++H).

Elemental analysis for C17H17ClF2OS.

Calculated: C 59,56%; H 5,00%; Cl 10,34%; F 11,08%; S 9,35%.

Found: C 59,27%; H 4,91%; Cl 10,42%; F 11,05%; S 9,45%.

The isomer 2-In

IR (ATR) ν: 3078, 2958, 2931, 2862, 1574, 1495, 1425, 1390, 1213, 1090, 1051, 1012, 818, 741 cm-1.

1H-NMR (400 MHz, CDCl3) δ: or 0.83 (3H, t, J=7,1 Hz), 1,17-of 1.40 (4H, m), 1,94-2,05 (1H, m), 2,24-of 2.34 (1H, m), a 4.03 (1H, DD, J=12,0, a 3.2 Hz), 6.87 in-6,99 (3H, m), 7,26 (2H, d, J=8,3 Hz), 7,35 (2H, d, J=8,3 Hz).

MS (m/z): 343(M++H).

HRMS (FAB) for C17H18OClF2S (M++H).

Calculated: 343,0735.

Found: 343,0750.

Example 3: 2-[1-[(4-chlorophenyl)sulfonyl]pentyl]-1,4-differenza

After addition of 3-chloroperbenzoic acid (98,8 mg, 0,571 mmol) to a solution of 2-[1-[(4-chlorophenyl)sulfinil]pentyl]-1,4-diferente (isomer 2) (150 mg, 0,439 mmol) in methylene chloride (5 ml) the resulting mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with methylene chloride, washed successively 1 N. aqueous sodium hydroxide solution, water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (10% ethyl acetate-hexane) to obtain the specified title compound (122 mg, 77%) as a colourless oil.

IR (ATR) ν: 3089, 2958, 2933, 283, 1583, 1496, 1475, 1427, 1394, 1321, 1279, 1219, 1176, 1149, 1086, 1014, 829, 754 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.85 (3H, t, J=7,3 Hz), 1,15-of 1.40 (4H, m), 2,03 with 2.14 (1H, m), 2,38-2,47 (1H, m), 4,51 (1H, DD, J=10.5V, and 3.7 Hz), 6,83 (1H, TD, J=9,0, 4.6 Hz), 6,94-7,01 (1H, m), 7,25 (1H, DDD, J=8,8, 5,4, 3,2 Hz), 7,38 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

MS (m/z): 359 (M++H).

HRMS (FAB) for C17H18ClF2O2S (M++H).

Calculated: 359,0684.

Found: 359,0688.

Example 4: 2-[(4-chlorophenyl)thiomethyl]-1,4-differenza

Method 1: If 0°4-chlorbenzoyl (of 5.45 g of 38.2 mmol), triphenylphosphine (11.1 g, to 41.6 mmol) and diisopropylethylamine (8,16 ml of 41.6 mmol) were added sequentially to a solution of 2,5-differenziava alcohol (5,00 g, to 34.7 mmol) in tetrahydrofuran (150 ml). The reaction mixture was stirred at room temperature for 4 days, followed by concentration. Thus obtained residue was purified by chromatography on a column of silica gel (1% ethyl acetate-hexane) to obtain specified in the connection header (2,68 g, 29%) as a colourless oil.

Method 2: After adding potassium carbonate (4,00 g, 29,0 mmol) and 2-methyl bromide-1,4-diferente (5,00 g, and 24.2 mmol) to a solution of 4-chlorbenzoyl (3,86 g of 26.6 mmol) in N,N-dimethylformamide (120 ml) and the mixture was stirred for 3 hours at room temperature. To the reaction mixture was added saturated ammonium chloride (50 ml) and water (20 m is) followed by extraction with diethyl ether. The extracts were combined, washed with water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by chromatography on a column of silica gel (1% ethyl acetate-hexane) to obtain specified in the connection header (6,41 g, 98%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: Android 4.04 (2H, s), 6,85-to 7.00 (3H, m), 7.23 percent (4H, s).

Example 5: 2-[(4-chlorophenyl)sulfanilyl]-1,4-differenza

Method 1: If 0°With 3-chloroperbenzoic acid (225 mg, of 1.30 mmol) was added to a solution of 2-[(4-chlorophenyl)thiomethyl]-1,4-diferente (271 mg, 1.00 mmol) in methylene chloride (5 ml). Then the mixture was stirred at room temperature for 15 hours. The reaction mixture was diluted with methylene chloride, washed successively with an aqueous solution of potassium bicarbonate and a saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was dissolved in methylene chloride (5 ml). After cooling to 0°to this solution was added 3-chloroperbenzoic acid (450 mg, 2,60 mmol), and then the mixture was stirred at room temperature for 15 hours. The reaction mixture was diluted with methylene chloride, washed with saturated aqueous solution of potassium bicarbonate and a saturated salt solution, dried over MgSO4, then was concentrated. Received this about the time the residue was purified by chromatography on a column of silica gel (9% ethyl acetate-hexane) to obtain the specified title compound (210 mg, 69%) as a colourless solid.

Method 2: After adding N2On (16.4 ml), 30% N2About2(16.4 ml, 145 mmol) and tetrahydrate hexaminolevulinate (425 mg, 0,344 mmol) to a solution of 2-[(4-chlorophenyl)thiomethyl]-1,4-diferente (6,54 g, 24,1 mmol) in methanol (100 ml) at 0°the mixture was stirred for 1 hour and then stirred additionally for 15 hours at room temperature. Besieged thus, the solid was collected by filtration and the filtrate was concentrated to approximately half its quantity. The resulting aqueous solution was extracted with methylene chloride. Then the solid is washed successively with water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was recrystallized from hexane to obtain specified in the connection header (6,34 g, 87%) as colorless needle crystals.

Method 3: After adding 2-methyl bromide-1,4-diferente (12.3 ml, 95.5 mmol) to a suspension of 4-chlorobenzenesulfonate sodium (19,0 g, 95.5 mmol) in butanol (200 ml) the mixture was heated at the boil under reflux for 5 hours. Besieged thus, the solid was collected by filtration and dissolved in methylene chloride. The resulting solution was washed with saturated salt solution, dried over MgSO4and concentrated. Receive the TES thus the solid is recrystallized from hexane to obtain specified in the title compound (12.3 g, 43%) as colorless needle crystals.

IR (ATR) ν: 3089, 2991, 2943, 1581, 1496, 1315, 1279, 1213, 1149, 1090, 1080, 1012, 958, 816, 779, 756, 729, 708, 646, 517, 469 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 4,36 (2H, s)6,91 (1H, TD, J=9,0, 4,4 Hz), 6,99-7,06 (1H, m), 7,11 (1H, DDD, J=8,3, 5,6, and 3.2 Hz), was 7.45 (2H, d, J=8,8 Hz), a 7.62 (2H, d, J=8,8 Hz).

MS (m/z): 303 (M++H).

Example 6: E-2-[1-[(4-chlorophenyl)sulfonyl]-2-phenylethenyl]-1,4-differenza

In nitrogen atmosphere and at 0°hexamethyldisilazide potassium (0.5 M solution in toluene, 2,20 ml, 1.10 mmol) was added to the solution in tetrahydrofuran (5 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (303 mg, 1.00 mmol)obtained in example 5. The resulting mixture was stirred at 0°C for 1 hour. After addition of benzaldehyde (127 mg, 1.20 mmol) and the mixture was stirred at room temperature for 15 hours. In the reaction mixture were added saturated aqueous solution of ammonium chloride followed by extraction with ethyl acetate. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (10% ethyl acetate-hexane) to obtain the specified title compound (220 mg, 56%) as a colourless solid. The solid is recrystallized from methanol is obtaining a colorless solid (111 mg, 28%). Based on the test observations NOE (nuclear Overhauser effect), it was determined that the olefin specified in the connection header is the E-form.

Melting point: 144,5-145,0°C.

IR (KBr) ν: 3068, 1637, 1581, 1489, 1450, 1419, 1315, 1246, 1155, 1086, 887, 814, 752, 725, 690, 648, 627, 613, 534, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: to 6.88 (1H, TD, J=9,1, 4,4 Hz), 7,06-to 7.18 (4H, m), 7,22-7,28 (2H, m), 7,30 and 7.36 (1H, m), 7,39 (2H, d, J=8,8 Hz), 7,60 (2H, d, J=8,8 Hz), of 8.09 (1H, s).

MS (m/z): 391 (M++H).

Elemental analysis for C20H13ClF2O2S.

Calculated: C 61,46%; H 3,35%; Cl 9,07%; F 9,72%; S To 8.20%.

Found: C 61,39%; H 3,28%; Cl 8,95%; F 9,82%; S 8,30%.

Example 7: 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-pentanon

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, of 1.27 ml, 2.00 mmol) was added to the solution in tetrahydrofuran (10 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (606 mg, 2.00 mmol)obtained in example 5. Then the temperature of the mixture was raised to room temperature. After cooling to -78°to the reaction mixture was added dropwise butyrylcholine (0,218 ml, 2.10 mmol). The reaction mixture was stirred at -78°C for 1.5 hours, and added 1 N. chloride-hydrogen acid (2.0 ml). Then the temperature of the mixture was raised to room temperature. The reaction mixture was extracted with diethyl ether. The extracts were combined, p is washed successively with water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (10% ethyl acetate-hexane). The thus obtained solid substance was recrystallized from hexane to obtain specified in the title compound (330 mg, 44%) as colorless needle crystals.

Melting point: 85,5-86,0°C.

IR (ATR) ν: 2968, 1724, 1581, 1491, 1394, 1335, 1323, 1155, 1088, 1034, 1011, 906, 829, 816, 758, 725, 615, 546, 469 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.90 (3H, t, J=7,6 Hz), 1,52 by 1.68 (2H, m), 2,62 (1H, DDD, J=18,1, with 7.6, 6.8 Hz), 2,84 (1H, DDD, J=18,1, with 7.6, 6.8 Hz), to 5.66 (1H, s), to 6.95 (1H, TD, J=9,0, 4,4 Hz), 7,02-was 7.08 (1H, m), 7,39-the 7.43 (1H, m), 7,43 (2H, d, J=8.5 Hz), 7,56 (2H, d, J=8,5 Hz).

MS (m/z 372 (M+).

Elemental analysis for C17H15ClF2O3S.

Calculated: C 54,77%; H 4,06%; Cl 9,51%; F 10,19%; S 8,60%.

Found: C 54,47%; H To 3.92%; Cl 9,68%; F 10,26%; S 8,76%.

Example 8: 2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)-1-phenyl-1-alanon

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 0,701 ml, 1.10 mmol) was added to the solution in tetrahydrofuran (5 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (303 mg, 1.00 mmol)obtained in example 5. The temperature of the mixture was raised to room temperature and then was stirred for 10 minutes. After cooling to -78°to the reaction mixture were added on the apply the benzoyl chloride (0,140 ml, 1.20 mmol). The reaction mixture was stirred at -78°C for 30 minutes. Then the temperature of the mixture was raised to 0aboutWith over 3 hours. After adding 1 N. chloride-hydrogen acid (2.0 ml) the mixture was extracted with ethyl acetate. The extracts were combined, washed successively with water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over MgSO4and concentrated. The residue was purified by medium pressure chromatography on a column of silica gel (10% ethyl acetate-hexane). The thus obtained solid substance was washed with hexane to obtain specified in the title compound (200 mg, 49%) as a colourless solid.

Melting point: 179,5-180,0°C.

IR (ATR) ν: 1682, 1595, 1579, 1495, 1475, 1315, 1284, 1240, 1209, 1153, 1082, 991, 874, 766, 708, 687, 607, 547, 509, 453 cm-1.

1H-NMR (400 MHz, CDCl3) δ: is 6.54 (1H, s), 7,01-7,10 (2H, m), 7,34-7,38 (1H, m), 7,44 is 7.50 (4H, m), 7,58-the 7.65 (1H, m), to 7.67 (2H, d, J=8,8 Hz), 7,88-to 7.93 (2H, m).

MS (m/z): 406 (M+).

HRMS (EI): C20H13ClF2O3S (M+).

Calculated: 406,0242.

Found: 406,0230.

Example 9: 2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)-1-phenylacrylate

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 0,701 ml, 1.10 mmol) was added to the solution in tetrahydrofuran (5 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-is iptorrents (303 mg, 1.00 mmol)obtained in example 5. The temperature of the mixture was raised to room temperature and then was stirred for 10 minutes. After cooling to -78°to the reaction mixture was added dropwise a benzoyl chloride (0,140 ml, 1.20 mmol). The reaction mixture was stirred at -78°C for 30 minutes. The temperature of the mixture was raised to 0°C for 3 hours. After adding a saturated aqueous solution of ammonium chloride to the reaction mixture, the mixture was extracted with diethyl ether. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and concentrated. The residue was purified by medium pressure chromatography on a column of silica gel (10% ethyl acetate-hexane). The thus obtained solid substance was recrystallized from ethyl acetate to obtain specified in the title compound (80 mg, 26%) as a colourless solid.

Melting point: 224,5-227,0°C.

IR (ATR) ν: 1756, 1610, 1491, 1450, 1325, 1228, 1155, 1092, 1072, 1011, 808, 756, 694, 606, 553, 462 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 6,97 (1H, DDD, J=8,8, 4,4 Hz), 7,02-to 7.09 (1H, m), 7,15-7,21 (3H, m), 7.23 percent-7,30 (3H, m), 7,34 (2H, d, J=8.5 Hz), 7,51-EUR 7.57 (2H, m), to 7.77 (2H, d, J=8.5 Hz), 8,02-of 8.06 (2H, m).

MS (m/z): 528 (M++NH4).

Elemental analysis for C27H17ClF2O4S.

Calculated: C, 63.47 Per Cent; H 3,35%; Cl 6,94%; F 7,44%; S 6,28%.

Found: C 63,04%; H 3,24%; Cl 6,92%; F 7,39; S 6,44%.

Example 10: 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-pentanol

In the atmosphere of nitrogen and at -78°With n-utility (1.6 M solution in hexane, 0,688 ml, 1.10 mmol) was added to the solution in tetrahydrofuran (5 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (303 mg, 1.00 mmol)obtained in example 5. The mixture was stirred at -78°C for 1 hour. After adding butanal (to 0.108 ml, 1.20 mmol) and the mixture was stirred at -78°C for 2 hours. To the reaction mixture were added saturated aqueous solution of ammonium chloride followed by extraction with ethyl acetate. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and concentrated. The residue was purified by medium pressure chromatography on a column of silica gel (10% ethyl acetate-hexane). The thus obtained solid substance was washed with hexane to obtain specified in the connection header (30,5 mg, 8%) as a colourless solid.

Melting point: 134,5-135,0°C.

IR (ATR) ν: 3502, 2966, 2931, 2873, 1585, 1491, 1309, 1277, 1227, 1173, 1147, 1084, 1083, 1014, 810, 756, 721, 613, 542, 445 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.87 (3H, t, J=7,1 Hz), 1,20-of 1.65 (4H, m), 3,06 (1H, d, J=2.2 Hz), 4,48 (1H, s), 4,85-of 4.90 (1H, m), at 6.84 (1H, TD, J=9,1, a 4.7 Hz), of 6.96-7,02 (1H, m), 7,40 (2H, d, J=8.6 Hz), 7,58 (2H, d, J=8.6 Hz), a 7.85 (1H, DDD, J=9,1, 5,4, 3,4 Hz).

MS (m/z): 374 (M+).

HRMS (EI) m/z in view of the C 17H17O3ClF2S (M+).

Calculated: 374,0555.

Found: 374,0540.

Example 11: 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-pentanol

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 7.01 ml, 11.0 mmol) was added to the solution in tetrahydrofuran (50 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (3.03 g, 10.0 mmol)obtained in example 5 and the mixture was stirred at -78°C for 1 hour. To the reaction mixture was added dropwise butanal (1.08 ml of 12.0 mmol). The mixture was stirred for 15 hours to raise its temperature to room temperature. After cooling to 0°and adding a saturated aqueous solution of ammonium chloride, the mixture was extracted with diethyl ether. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and then concentrated. Besieged thus, the solid was collected by filtration and washed with hexane. The hexane filtrate and washing were combined and then concentrated. The residue was purified by medium pressure chromatography on a column of silica gel (10% ethyl acetate-hexane) in the form of high polarity isomer with obtaining a colorless solid. The obtained colorless solid was recrystallized from hexane to obtain specified in is the head of the compound (396 mg, 11%) in the form of colorless needle-like crystals.

Melting point: 76,5-78,0°C.

IR (ATR) ν: 3533, 2960, 1581, 1498, 1394, 1329, 1306, 1242, 1178, 1146, 1082, 987, 887, 754, 712, 644, 594, 515 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.82 (3H, t, J=7,3 Hz), 1,22-of 1.53 (4H, m), of 3.78 (1H, Sirs), 4,55-4,80 (2H, SIRM), at 6.84 (1H, TD, J=9,0, 4,4 Hz), of 6.96? 7.04 baby mortality (1H, m), 7,15-7,26 (1H, Sirs), 7,39 (2H, d, J=8,3 Hz), 7,52 (2H, d, J=8,3 Hz).

MS (m/z): 374 (M+).

Elemental analysis for C17H17ClF2O3S.

Calculated: C 54,47%; H 4,57%; Cl 9,46%; F 10,14%; S 8.55 Percent.

Found: C 54,27%; H 4,51%; Cl 9,44%; F 10,20%; S 8,70%.

Example 12: 2-[1-[(4-chlorophenyl)sulfonyl]-1-penten-1-yl]-1,4-differenza

At 0aboutWith triethylamine (0,131 ml, 0,942 mmol) and methanesulfonamide (0,0665 ml, 0,856 mmol) was added to a solution of 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-pentanol (204 mg, 0,544 mmol) in methylene chloride (10 ml). After stirring at 0°C for 1 hour, the reaction mixture was diluted with methylene chloride, washed successively with a saturated aqueous solution of ammonium chloride, water and a saturated salt solution, dried over MgSO4and then concentrated. The residue was dissolved in tetrahydrofuran (5 ml). After cooling the solution to 0aboutWith added hexamethyldisilazide potassium (0.5 M solution in toluene, of 1.30 ml, 0,650 mmol). The resulting mixture was stirred at 0°C for 3 hours and added to it a saturated solution of chlorine is IDA ammonium. The resulting mixture was extracted with ethyl acetate, washed successively with water and saturated salt solution, dried over MgSO4and then concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (15 % ethyl acetate-hexane). The obtained solid was recrystallized from hexane to obtain specified in the connection header (33,0 mg, 17%) as colorless needle crystals.

Melting point: 95,5-97,0°C.

IR (ATR) ν: 2960, 1645, 1579, 1489, 1421, 1311, 1252, 1198, 1165, 1140, 1086, 1012, 818, 769, 752, 640, 606, 552, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: to 0.89 (3H, t, J=7,3 Hz), 1,45-of 1.56 (2H, m), from 2.00 (2H, Sirs), 6,89 (1H, TD, J=8,3, 4,4 Hz), 7,01-was 7.08 (2H, m), 7,31 (1H, t, J=8,3 Hz), 7,38 (2H, d, J=8.5 Hz), 7,55 (2H, d, J=8,5 Hz).

MS (m/z): 356 (M+).

HRMS (EI): C17H15ClF2O2S (M+).

Calculated: 356,0449.

Found: 356,0450.

Elemental analysis for C17H15ClF2O2S.

Calculated: C 57,22%; H 4,24%; Cl 9,94%; F 10,65%; S 8,99%.

Found: C 56,80%; H Is 4.21%; Cl 10,04%; F 10,65%; S 9,11%.

Example 13: 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-pendimethalin

At 0aboutWith triethylamine (0,300 ml of 2.16 mmol) and methanesulfonamide (0,150 ml of 1.93 mmol) was added to a solution in methylene chloride (10 ml) of 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-pentanol (449 mg, 1.20 mmol), polucen the th in example 11. Then the resulting mixture was stirred at 0°C for 2 hours. The reaction mixture was diluted with methylene chloride, washed successively with a saturated aqueous solution of ammonium chloride, water and a saturated salt solution, dried over MgSO4and then concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (15 % ethyl acetate-hexane) to obtain the specified title compound (503 mg, 93%) as a colourless solid.

IR (ATR) ν: 2966, 1498, 1350, 1176, 1149, 1086, 928, 879, 789, 752, 636, 592, 550, 525, 455 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 0,86 (3H, t, J=7,1 Hz), 1,33-to 1.61 (3H, m), 1,88 is 1.96 (1H, m), 3,21 (3H, d, J=0.7 Hz), to 5.03 (1H, d, J=7,7 Hz), 5,58-to 5.66 (1H, m), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,97-7,05 (1H, m), 7,33-7,40 (1H, m, including 2H, d, J=8,3 Hz to 7.35 ppm), 7,54 (2H, d, J=8,3 Hz).

Example 14: 2-[1-[(4-chlorophenyl)sulfonyl]-1-penten-1-yl]-1,4-differenza

To a solution of 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-pendimethaline (200 mg, 0,442 mmol) in methylene chloride (4 ml) was added 1,8-diazabicyclo[5,4,0]undec-7-ene (69,1 μl, 0,464 mmol) at room temperature. The mixture was stirred for 15 hours. The reaction mixture was concentrated. The residue was purified by medium pressure chromatography on a column of silica gel (8 % ethyl acetate-hexane) to obtain specified in the connection header (72,0 mg, 46%) as the devil is Vatan solids. The obtained solid was recrystallized from hexane to obtain a colorless solid matter (60,0 mg).

Melting point: 99,0-100,0°C.

IR (ATR) ν: 1581, 1496, 1392, 1309, 1279, 1232, 1173, 1149, 1084, 978, 837, 816, 806, 758, 731, 710, 644, 598, 561, 521 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 0,99 (3H, t, J=7,3 Hz), 2,12 (2H, m), is 5.06 (2H, d, J=7,3 Hz), 5,74-to 5.85 (2H, m), 6,92 (1H, TD, J=9,0, 4,4 Hz), 6,97? 7.04 baby mortality (1H, m), 7,32 (1H, DDD, J=8,5, 5,4, 3,2 Hz), the 7.43 (2H, d, J=8.5 Hz), to 7.64 (2H,, d, J=8,5 Hz).

MS (m/z): 374 (M++NH4).

Elemental analysis for C17H15ClF2O2S.

Calculated: C 57,22%; H 4,24%; Cl 9,94%; F 10,65%; S 8,99%.

Found: C 57,15%; H 4,18%; Cl 9,90%; F A 10.74%; S Is 9.09%.

Example 15: 2-[5-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]pentyl]-1,4-differenza

In the atmosphere of argon and at -78°With n-utility (1.5 M solution in hexane, 0,701 ml, 1.10 mmol) was added to the solution in dimethoxyethane (5 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (303 mg, 1.00 mmol)obtained in example 5. The mixture was stirred at -78°C for 1 hour and then at room temperature for 30 minutes. The reaction mixture was cooled to -78°C, followed by adding dropwise 4-(tert-butyldimethylsilyloxy)-1-iodobutane (is 0.260 ml, 1.00 mmol). When the temperature of the reaction mixture to room temperature, stirring was conducted for 15 hours. To the reaction mixture was added to the water followed by extraction with diethyl ether. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (8% ethyl acetate-hexane) to obtain the specified title compound (401 mg, 82%) as a colourless solid. The obtained solid was recrystallized from hexane to obtain colorless needle-like crystals.

IR (ATR) ν: 2945, 2927, 2854, 1583, 1496, 1427, 1392, 1321, 1248, 1144, 1082, 1038, 1012, 941, 822, 775, 748, 708, 623, 542, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: -0,02 (3H, s)-0,02 (3H, s)of 0.82 (9H, s)of 1.23 and 1.33 (2H, m), 1,42 is 1.58 (2H, m), 2.06 to to 2.18 (1H, m), 2,39-2,48 (1H, m), 3,53 (2H, t, J=6.3 Hz), to 4.52 (1H, DD, J=11,6, and 2.6 Hz), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,94-7,00 (1H, m), 7,22-7,26 (1H, m), 7,38 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

MS (m/z): 489 (M++H).

Elemental analysis for C23H31ClF2O3SSi.

Calculated: C 56,48%; H 6,39%; Cl 7,25%; F To 7.77%; S 6,56%.

Found: C 56,29%; H 6,28%; Cl 7,29%; F Of 7.75%; S 6,70%.

Example 16: 2-[5-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-1-methylpentyl]-1,4-differenza

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 0,294 ml, 0,461 mmol) was added to a solution of 2-[5-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]pentyl]-1,4-diferente (205 mg, 0,419 mmol) in tetrahydrofuran (4 ml). A mixture of AC is stirred at room temperature for 1 hour. After cooling to -78°to the reaction mixture was added dropwise itmean (0,339 ml, 0,545 mmol) and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added water, followed by extraction with diethyl ether. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (6% ethyl acetate-hexane) to obtain the specified title compound (168 mg, 80%) as a colourless oil.

IR (ATR) ν: 2952, 2929, 2856, 1583, 1496, 1473, 1392, 1311, 1255, 1192, 1149, 1090, 1014, 833, 760, 710, 629, 552 cm-1.

1H-NMR (400 MHz, CDCl3) δ: -0,01 (3H, s)0,00 (3H, s), is 0.84 (9H, s), 1,05-of 1.18 (1H, m), 1,29-of 1.41 (1H, m), 1,52 is 1.60 (2H, m), is 1.81 (3H, d, J=2,9 Hz), 1,95-2,05 (1H, m), 2,61-a 2.71 (1H, m), of 3.57 (2H, t, J=6,1 Hz), 6,82-6,88 (1H, m), 6,98-7,07 (2H, m), 7,38 (2H, d, J=9.1 Hz), 7,40 (2H, d, J=9.1 Hz).

MS (m/z): 503 (M+).

HRMS (FAB) for C24H34ClF2O3SSi (M++H).

Calculated: 503,1655.

Found: 503,1704.

Example 17: 5-(4-chlorophenylsulfonyl)-5-(2,5-differenl)-1-hexanol

After adding tetrabutylammonium (1 M solution in tetrahydrofuran, 0,978 ml, 0,978 mmol) to a solution of 2-[5-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-1-methylpentyl]-1,4-diferente (164 mg, 0,326 mmol) in tetrahydrof the Ana (4 ml) and the mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with diethyl ether, washed sequentially with saturated ammonium chloride, water and a saturated salt solution, dried over MgSO4and then concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (50% ethyl acetate-hexane) to obtain the specified title compound (122 mg, 96%) as a colourless oil.

IR (ATR) ν: 3516, 3089, 2939, 2870, 1583, 1495, 1475, 1412, 1394, 1306, 1279, 1188, 1146, 1088, 1070, 1012, 823, 758, 710, 679, 649, 602, 546, 474 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 2,09-of 2.20 (1H, m), 1,23 (1H, Sirs), 1,34 of 1.46 (1H, m), and 1.63 (1H, quintet, J=7,1 Hz), equal to 1.82 (3H, d, J=2.7 Hz), 1,98-2,07 (1H, m), 2,71 (1H, TD, J=13,0, 3,4 Hz), 3,63 (2H, t, J=6.4 Hz), 6,83-of 6.90 (1H, m), 6,99-7,06 (2H, m), 7,38 (4H, s).

MS (m/z): 389 (M++H).

HRMS (FAB) for C18H20ClF2O3S (M++H).

Calculated: 389,0790.

Found: 389,0795.

Example 18: 2-[5-(tert-butyldimethylsilyloxy)-1-[4-(tert-butyldimethylsilyloxy)butyl]-1-(4-chlorophenylsulfonyl)pentyl]-1,4-differenza

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 0,358 ml, 0,562 mmol) was added to the solution in tetrahydrofuran (4 ml) of 2-[5-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]pentyl]-1,4-diferente (250 mg, 0,511 mmol)obtained in example 15. The temperatures of the mixture was raised to room temperature. After ohlord is ment to -78° To the reaction mixture was added dropwise 4-(tert-butyldimethylsilyloxy)-1-iodobutane (0,146 ml, 0,562 mmol). The reaction mixture was stirred at room temperature for 3 days. To the reaction mixture was added water, followed by extraction with diethyl ether. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (6% ethyl acetate-hexane) to obtain the specified title compound (167 mg, 48%) as a colourless solid.

IR (ATR) ν: 3082, 2927, 2856, 1583, 1495, 1462, 1308, 1250, 1146, 1080, 1012, 833, 758, 675, 646, 607, 579, 544, 455 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 0,03 (12H, s)of 0.87 (18H, s), 1,25-to 1.70 (8H, m), 2,23-of 2.34 (2H, m), 2.40 a-2,48 (2H, m), to 3.58-3,68 (4H, m), 6,74-PC 6.82 (1H, m), 6,97-7,06 (2H, m), 7,30 (2H, d, J=8,8 Hz), 7,34 (2H, d, J=8,8 Hz).

MS (m/z): 675 (M++H).

HRMS (FAB) for C33H54ClF2O4SSi2(M++H).

Calculated: 675,2938.

Found: 675,2900.

Elemental analysis for C33H53ClF2O4SSi2.

Calculated: C 58,68%; H To $ 7.91%; Cl 5,25%; F 5,63%.

Found: C 58,63%; H To $ 7.91%; Cl 5,32%; F 5,69%.

Example 19: 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1,9-nonanediol

To a solution of 2-[5-(tert-butyldimethylsilyloxy)-1-[4-(tert-butyldimethylsilyloxy)butyl]-1-(4-chlorine is phenylsulfonyl)pentyl]-1,4-diferente (158 mg, 0,234 mmol) in tetrahydrofuran (4 ml) was added tetrabutylammonium (1 M solution in tetrahydrofuran, 0,702 ml, 0,702 mmol). The resulting mixture was stirred at room temperature for 24 hours. After concentrating the reaction mixture, the residue was dissolved in diethyl ether followed by successive washing with water and saturated salt solution, dried over MgSO4and concentration. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (5% methanol-methylene chloride) to give a colorless solid. The obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (97,0 mg, 93%) as a colourless solid.

Melting point: 107,0-108,5°C.

IR (ATR) ν: 3275, 2939, 1572, 1495, 1414, 1306, 1261, 1140, 1078, 1066, 847, 812, 754, 710, 679, 644, 606, 544, 474, 449 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,36-1,82 (10H, m), 2,24 to 2.35 (2H, m), 2,47-to 2.57 (2H, m), 3,70 (4H, t, J=5,9 Hz), 6,79 (1H, DDD, J=12,4, 8,3, 4.6 Hz), 6,97-was 7.08 (2H, m), 7,29 (2H, d, J=8,8 Hz), 7,34 (2H, d, J=8,8 Hz).

MS (m/z): 447 (M++H).

HRMS (FAB) for C21H26ClF2O4S (M++H).

Calculated: 447,1208.

Found: 447,1227.

Elemental analysis for C21H25ClF2O4S·0,25H2O.

Calculated: C 55,87%; H 5,69%; Cl Of 7.85%; F 8,42%; S 7,10%.

Found: C 55,62%; H 5,40%; Cl 7,89%; F 8,58%; S 7,26%.

the example 20: 2-[5-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-1-butylpentyl]-1,4-differenza

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 0,287 ml, 0,450 mmol) was added to the solution in tetrahydrofuran (4 ml) of 2-[5-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]pentyl]-1,4-diferente (200 mg, 0,409 mmol)obtained in example 15. The temperatures of the mixture was raised to room temperature. After cooling to -78°to the reaction mixture was added dropwise triamide hexamethylphosphoric acid (0,214 ml of 1.23 mmol) and iodobutane (51,1 μl, 0,450 mmol). The resulting mixture was stirred at room temperature for 20 hours. To the reaction mixture was added isopropanol (0.5 ml) followed by concentration. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (5% ethyl acetate-hexane) to obtain the specified title compound (163 mg, 73%) as a colourless oil.

IR (ATR) ν: 2954, 2929, 2858, 1583, 1495, 1473, 1412, 1394, 1311, 1255, 1192, 1147, 1090, 1014, 833, 756, 710, 677, 606 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.03 (6H, s)of 0.87 (9H, s)of 0.95 (3H, t, J=7.4 Hz), 1,20-of 1.45 (5H, m), 1,52 is 1.70 (3H, m), 2,21 of-2.32 (2H, m), 2.40 a-2,49 (2H, m)to 3.64 (2H, t, J=6,1 Hz), 6,74-PC 6.82 (1H, m), 6,97-7,07 (2H, m), 7,29 (2H, d, J=8,8 Hz), 7,34 (2H, d, J=8,8 Hz).

MS (m/z): 545 (M+).

HRMS (FAB) for C27H40ClF2O3SSi (M++H).

Calculated: 545,2124.

Found: 545,2087.

Example 21: 5-[(4-chlorophenyl)sulfonyl]-5-(2-differenl)-1-nonanol

After adding tetrabutylammonium (1 M solution in tetrahydrofuran, 0,532 ml, 0,532 mmol) to a solution of 2-[5-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-1-butylpentyl]-1,4-diferente (154 mg, 0,283 mmol) in tetrahydrofuran (4 ml) and the mixture was stirred at room temperature for 18 hours. Then the reaction mixture was concentrated. Thus obtained residue was dissolved in diethyl ether followed by successive washing with water and saturated salt solution, dried over MgSO4and concentration. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (50% ethyl acetate-hexane) to obtain the specified title compound (122 mg, 0,283 mmol) as colourless oil.

IR (ATR) ν: 3539, 2958, 2873, 1583, 1495, 1412, 1308, 1277, 1192, 1146, 1090, 1014, 829, 758, 710, 675, 606, 548, 463 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.95 (3H, t, J=7,3 Hz), 1,19-1,77 (9H, m), 2.21 are of 2.34 (2H, m), 2,38 of $ 2.53 (2H, m), 3,70 (2H, Sirs), 6,75-6,83 (1H, m), 6,98-was 7.08 (2H, m), 7,29 (2H, d, J=8,8 Hz), 7,34 (2H, d, J=8,8 Hz).

MS (m/z): 431 (M++H).

HRMS (EI): as C21H26ClF2O3S (M++H).

Calculated: 431,1259.

Found: 431,1237.

Example 22: 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-3-octanol (isomer 22-a and isomer 22)

In the atmosphere of argon and at -78°With n-butyl the Tille (1.57 M solution in hexane, 0,701 ml, 1.10 mmol) was added to the solution in tetrahydrofuran (5 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (303 mg, 1.00 mmol)obtained in example 5. The temperature of the mixture was raised to room temperature. After cooling to -78°to the reaction mixture was added dropwise a complex trevormoran-ether (of 0.133 ml, 1.05 mmol). The mixture was stirred at room temperature for 2 days. To the reaction mixture was added water, followed by extraction with diethyl ether. The extracts were combined, washed sequentially with saturated aqueous sodium bicarbonate solution, water and saturated salt solution, dried over MgSO4and concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (20% ethyl acetate-hexane) to give isomer a low polarity, mixtures of isomers and isomer high polarity as the first fraction, the second fraction and the third fraction, respectively, in each case in the form of a colorless solid. Isomer a low polarity and high polarity isomer was recrystallized from hexane to obtain specified in the header isomer 22-a (low polarity) (98,0 mg, 24%) and indicated in the title isomer 22 (high polarity) (199 mg, 48%), each in the form of colorless needle-like crystals.

Isomer 22-

Melting point: 84,0-84,5° C.

IR (ATR) ν: 3533, 2933, 2860, 1574, 1495, 1429, 1278, 1240, 1182, 1142, 1092, 1080, 1014, 962, 885, 829, 766, 737, 710, 681, 619, 526, 476 cm-1.

1H-NMR (400 MHz, CDCl3) δ: to 0.88 (3H, t, J=6.8 Hz), 1,20-1,50 (8H, m)of 1.57 (1H, d, J=5,1 Hz)2,07 (1H, DDD, J=14,7, 8,1, 6,8 Hz), 2,70 (1H, DDD, J=14,7, 6,8, and 4.6 Hz), 3,93-4,01 (1H, m), is 4.85 (1H, t, J=6.8 Hz), 6,77 (1H, TD, J=9,0, a 4.4 Hz), 6,91-6,98 (1H, m), 7.24 to 7,30 (1H, m), of 7.36 (2H, d, J=8.5 Hz), 7,51 (2H, d, J=8,5 Hz).

MS (m/z): 417 (M++H).

HRMS (FAB) for C20H24ClF2O3S (M++H).

Calculated: 417,1103.

Found: 417,1102.

Elemental analysis for C20H23ClF2O3S·0,25H2O.

Calculated: C 57,00%; H 5,62%; Cl To 8.41%; F 9,02%; S To 7.61%.

Found: C 57,18%; H 5,38%; Cl To 8.57%; F Which 9.22%; S 7,79%.

Isomer 22

Melting point: 123,0-123,5°C.

IR (ATR) ν: 3502, 2925, 2858, 1583, 1496, 1410, 1304, 1275, 1213, 1184, 1149, 1086, 1045, 1014, 958, 910, 829, 796, 752, 725, 710, 627, 552, 503, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.87 (3H, t, J=7,1 Hz), 1,20-1,60 (9H, m), 2.21 are of 2.30 (1H, m), is 2.41 (1H, DDD, J=13,9, 10,5, 3,4 Hz), 3,23-of 3.32 (1H, m), 4,94 (1H, DD, J=11,7, 2,9 Hz), 6,85 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7.03 is (1H, m), 7.23 percent-7,29 (1H, m), 7,39 (2H, d, J=8.5 Hz), 7,55 (2H, d, J=8,5 Hz).

MS (m/z 417 (M++H).

HRMS (FAB) for C20H24ClF2O3S (M++H).

Calculated: 417,1103.

Found: 417,1122.

Elemental analysis for C20H23ClF2O3S·0,25H2O.

Calculated: C 57,00%; H 5,62%; Cl To 8.41%; F 9,02%; S To 7.61%.

Found: C 57,16%; H 5,34%; Cl 8,55%; F 9,18%; S Of 7.82%.

Example 23: 2-[5-chloro-1-[(4-chlorophenyl)sulfonyl]pentyl]-1,4-Diptera is angry

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, to 3.52 mmol) was added to the solution in dimethoxyethane (30 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (1.52 g, 5,02 mmol)obtained in example 5. The temperature of the mixture was raised to room temperature, at which stirring was continued for 15 minutes. After cooling the reaction mixture to -78°C was added 4-chloro-1-iodobutane (672 μl, 5,52 mmol) and the mixture was stirred at room temperature for 24 hours. To the reaction mixture were added a saturated solution of ammonium chloride, followed by extraction with diethyl ether. The extracts were combined, washed successively with water, saturated aqueous sodium thiosulfate and saturated salt solution, dried over MgSO4and then distilled under reduced pressure to remove solvent. Thus obtained residue was recrystallized from hexane to obtain specified in the title compound (1.64 g, 83%) as colorless needle crystals.

IR (ATR) ν: 2945, 1583, 1495, 1475, 1311, 1277, 1230, 1149, 1142, 1082, 1014, 872, 822, 793, 752, 708, 629, 557, 532, 465 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.33 to 1.48 (2H, m), 1,72-to 1.87 (2H, m), 2,08-to 2.18 (1H, m), 2,43-2,52 (1H, m), 3,44-of 3.53 (2H, m)to 4.52 (1H, DDD, J=11,5, a 3.9, 1.2 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7,02 (1H, m), 7.23 percent-7,28 (1H, m), 7,39 (2H, d, J=8,8 Hz), 7,53 (2H, d, J=8,8 Hz).

MS (m/z): 393 (M ++H).

Elemental analysis for C17H16Cl2F2O2S.

Calculated: C 51,92%; H 4,10%; Cl 18,03%; F To 9.66%; S 8,15%.

Found: C 51,33%; H 4,07%; Cl 17,64%; F 9,72%; S Of 8.25%.

Example 24: Hydrochloride of 1-[5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)pentyl]pyrrolidine

To a solution of 2-[5-chloro-1-[(4-chlorophenyl)sulfonyl]pentyl]-1,4-diferente (200 mg, 0,509 mmol) in acetonitrile (6 ml) was added pyrrolidine (213 μl, 2.55 mmol), potassium carbonate (73,7 mg, 0,534 mmol) and potassium iodide (15 mg). The resulting mixture was heated at 70°C for 18 hours. The temperature of the reaction mixture was cooled again to room temperature. Thus obtained residue was distributed between water and methylene chloride. After separation of the organic layer the aqueous layer was extracted with methylene chloride. The organic layer and the extract were combined, washed with water and saturated salt solution, dried over MgSO4and then concentrated. Thus obtained crude product was subjected to chromatography on a short column (SiO2, methylene chloride-methanol, 10:1). The resulting oil was dissolved in ethanol. After adding a mixture of 1 N. chloride-hydrogen acid-ethanol (2 ml) to the resulting solution and the mixture was concentrated. The thus obtained solid substance was recrystallized from ethyl acetate to obtain specified in the header with the organisations (128 mg, 54%) as a pale yellow solid.

Melting point: 167,0-170,5°C.

IR (ATR) ν: 2960, 2565, 2453, 1583, 1495, 1321, 1277, 1211, 1173, 1145, 1084, 1011, 879, 820, 787, 754, 721, 708, 627, 557, 540, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.31 to 1.47 (2H, m), 1.93 and-of 2.30 (6H, m), 2,42 is 2.51 (1H, m), 2,66-2,78 (2H, m), 2,87-3,03 (2H, m), 3,76 (2H, Sirs), 4,51 (1H, DD, J=10,7, 4,4 Hz), 6,85 (1H, TD, J=8,8, 4,4 Hz), of 6.96-7.03 is (1H, m), 7,22 (1H, DDD, J=8,8, 5,4, 3,2 Hz), 7,40 (2H, d, J=8,3 Hz), 7,54 (2H, d, J=8,3 Hz), 12,54 (1H, Sirs).

MS (m/z): 428 (M++H).

Elemental analysis for C21H24ClF2NO2S·HCl.

Calculated: C 54,31%; H 5,43%; Cl 15,27%; F 8,18%; N, 3.02%, Respectively; S 6,90%.

Found: C, 54.19 Percent; H, 5.37 Percent; Cl 15,07%; F 8,10%; N 3,21%; S 6,98%.

Example 25 Ethyl-3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propionate

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 7,01 mmol) was added to the solution in dimethoxyethane (50 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (3.03 g, 10.0 mmol)obtained in example 5. The temperature of the mixture was raised to room temperature, at which stirring was continued for 15 minutes. After cooling the reaction mixture to -78°With added Bromeliaceae (1,33 ml of 12.0 mmol). The mixture was stirred at room temperature for 3 hours. To the reaction mixture were added a saturated solution of ammonium chloride, followed by extraction with diethyl ether. The extracts were combined, PR is mawali successively with water, saturated aqueous sodium thiosulfate and saturated salt solution, dried over MgSO4and then distilled under reduced pressure to remove solvent. Thus obtained residue was recrystallized from hexane to obtain specified in the connection header (1,95 g, 50%) as colorless needle crystals.

Melting point: 99,5-100,5°C.

IR (ATR) ν: 3078, 2952, 1734, 1587, 1493, 1419, 1377, 1327, 1279, 1213, 1149, 1047, 1014, 829, 779, 754, 727, 611, 542, 453 cm-1.

1H-NMR (CDCl3) δ: to 1.15 (3H, t, J=7,1 Hz), is 3.08 (1H, DD, J=16,6, 10,3 Hz), of 3.46 (1H, DD, J=16,6, 4.6 Hz), 3,99-4,12 (2H, m), is 5.06 (1H, DD, J=10,3, 4.6 Hz), 6,85 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7,02 (1H, m), 7,19 (1H, DDD, J=8,6, 5,4, 3,2 Hz), 7,42 (2H, d, J=8,8 Hz), 7,56 (2H, d, J=8,8 Hz).

MS (m/z): 389 (M++H).

Elemental analysis for C17H15ClF2O4S.

Calculated: C 52,51%; H 3,89%; Cl 9,12%; F 9,77%; S Of 8.25%.

Found: C 52,33%; H 3,86%; Cl 9,10%; F 9,88%; S Of 8.37%.

Example 26: 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylthio)pentyl]-1,4-differenza

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (0,94 g, 3.1 mmol)obtained in example 5 was dissolved in toluene (15 ml). After adding 4-(methylthio)-1-butanol (0.25 ml, 2.1 mmol) and cyanomethylene-n-butylphosphine (1.0 g, 4.1 mmol) the resulting mixture was heated at the boil under reflux for 14 hours in an argon atmosphere. The reaction mixture was allowed to cool. Then add 4(methylthio)-1-butanol (0.25 ml, 2.1 mmol), followed by boiling under reflux for 6 hours in an argon atmosphere. The reaction mixture was allowed to cool and then concentrated under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=10:1) to give colorless oil. The obtained colorless oil was utverjdali hexane to obtain specified in the title compound (0.55 g, 44%) as a white powder.

Melting point: 103-106°C.

IR (ATR) ν: 3066, 2960, 2935, 1583, 1493, 1147, 1082, 1012, 893, 829, 752, 625, 542, 465 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,23-to 1.45 (2H, m), 1,50-1,75 (2H, m), 2,04 (3H, s), 2,04-of 2.20 (1H, m), 2,35-2,60 (3H, m)to 4.52 (1H, DD, J=11,5, 2.4 Hz), 6,78-to 6.88 (1H, m), 6,95-7,01 (1H, m), 7,20-7,30 (1H, m), 7,38 (2H, DM, J=8,4 Hz), 7,53 (2H, DM, J=8,4 Hz).

MS (m/z): 405, 407 (M++H).

HRMS (FAB) for C18H20ClF2O2S2(M++H).

Calculated: 405,0561.

Found: 405,0581.

Example 27: 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]-1,4-differental (compound a) and 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulfinyl)pentyl]-1,4-differental (connection)

In methylene chloride (30 ml) was dissolved 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylthio)pentyl]-1,4-differental (500 mg, of 1.23 mmol). After cooling on ice to the resulting solution was added 3-chloroperbenzoic acid (340 mg, 1.97 mmol). The mixture was stirred at room the Oh temperature for 14 hours. After concentrating the reaction mixture under reduced pressure, the residue was subjected to chromatography on silica gel. From the faction, elyuirovaniya a mixture of hexane:ethyl acetate=10:1, was obtained white solid. Then the solid was washed with a mixture of diethyl ether/methylene chloride to obtain specified in the title compound (211 mg, 30%) as a white powder. Then from the faction, elyuirovaniya a mixture of methylene chloride:methanol=40:1, received a white solid. The solid is washed with a mixture of diethyl ether/methylene chloride to obtain specified in the title compound (144 mg, 30%) as a white powder.

Connection And

Melting point: 145-148°C.

IR (ATR) ν: 1496, 1317, 1292, 1273, 1149, 1124, 1086, 829, 756, 631, 544, 523, 499, 478, 465 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,38 is 1.70 (2H, m), 1,80-2,00 (2H, m), 2.05 is-2,22 (1H, m), 2,45-2,60 (1H, m), is 2.88 (3H, s), 2,96 (2H, TM, J=7,0 Hz), 4,51 (1H, DM, J=7,6 Hz), 6,80-of 6.90 (1H, m), 6,95-7,05 (1H, m), 7,20-to 7.35 (1H, m), 7,39 (2H, d, J=8.7 Hz), 7,53 (2H, d, J=8.7 Hz).

MS (m/z): 437, 439(M++H).

Elemental analysis for C18H19ClF2O4S2.

Calculated: C 49,48%; H Of 4.38%; Cl 8,11%;F 8,70%; S 14,68%.

Found: C 49,50%; H 4,28%; Cl 8,05%; F 8,77%; S 14,70%.

Connection

Melting point: 126-129°C.

IR (ATR) ν: 1495, 1475, 1277, 1147, 1086, 1012, 833, 752, 625, 540, 465 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,32 is 1.70 (2H, m), 1,75-of 1.93 (2H, m), 2,08-2,22 (1H, m), 2,46 is 2.75 (3H, m), of 2.54 (3H, s)to 4.52 (1H, DD, J=11,4, 2.4 Hz), 6,8-of 6.90 (1H, m)6,94? 7.04 baby mortality (1H, m), 7,20-7,30 (1H, m), 7,39 (2H, DD, J=8,5, 1.8 Hz), 7,53 (2H, DD, J=8,5, 2.7 Hz).

MS (m/z): 421, 423 (M++H).

Elemental analysis for C18H19ClF2O3S2.

Calculated: C 51,36%; H 4,55%; Cl 8,42%; F 9,03%; S 15,24%.

Found: C 51,36%; H 4,49%; Cl 8,35%; F 9,00%; S 15,24%.

Example 28: 2-[1-[(4-chlorophenyl)sulfonyl]-5-vinyloxyethyl]-1,4-differenza

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (0,94 g, 3.1 mmol)obtained in example 5 was dissolved in toluene (30 ml). After adding 4-vinyloxy-1-butanol (0.51 ml, 4.2 mmol) and cyanomethylene-n-butylphosphine (1.0 g, 4.1 mmol) the resulting mixture was heated at the boil under reflux for 3 days in an atmosphere of argon. The reaction mixture was allowed to cool and then concentrated under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain white solid. The obtained white solid was washed with hexane to obtain specified in the title compound (0.97 g, 78%) as a white powder.

Melting point: 54-56°C.

IR (ATR) ν: 2943, 1618, 1495, 1475, 1308, 1198, 1147, 1080, 1012, 962, 899, 829, 750, 623, 559, 544, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,25-1,45 (2H, m), 1.55V and 1.80 (2H, m), 2.05 is-2,22 (1H, m), 2.40 a is 2.55 (1H, m), 3,62 (2H, t, J=6.2 Hz), of 3.96 (1H, DD, J=6,8, and 2.1 Hz), of 4.12 (1H, DD, J=14,4, and 2.1 Hz), a 4.53 (1H, DD, J=11,5, 2.7 Hz), to 6.39 (1H, DD, J=14,4 that 6.8 Hz), 6,806,90 (1H, m), 6,95? 7.04 baby mortality (1H, m), 7,20-7,30 (1H, m), 7,39 (2H, d, J=8.6 Hz), 7,54 (2H, d, J=8.6 Hz).

MS (m/z): 418, 420 (M++NH4).

Elemental analysis for C19H19ClF2O3S.

Calculated: C 56,93%; H 4,78%; Cl 8,84%; F 9,48%; S Of 8.00%.

Found: C 56,98%; H A 4.83%; Cl 8,78%; F 9,51%; S 8,13%.

Example 29: 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1-pentanol

In methanol (30 ml) was dissolved 2-[1-[(4-chlorophenyl)sulfonyl]-5-vinyloxyethyl]-1,4-differental (from 0.90 g, 2.3 mmol). After adding monohydrate p-toluensulfonate acid (20 mg, 0.11 mmol) the resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=3:2) to obtain white solid. The obtained white solid is washed with diisopropyl ether to obtain specified in the title compound (0.73 g, 85%) as a white powder.

Melting point: 84-86°C.

IR (ATR) ν: 3325, 2941, 2866, 1583, 1496, 1313, 1151, 1084, 825, 752, 629, 534 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,18-of 1.29 (1H, m), 1,29-of 1.40 (2H, m), 1,40-1,70 (2H, m), 2,08-2,22 (1H, m), 2,42 is 2.55 (1H, m), 3,55-to 3.67 (2H, m), a 4.53 (1H, DD, J=11,4, and 3.8 Hz), 6,78-to 6.88 (1H, m), 6,93-7,03 (1H, m), 7,20-7,30 (1H, m), 7,39 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

MS (m/z): 375, 377 (M++H).

Elemental analysis for C17H17ClF2O3S·0,25H2O.

Vechicle is about: C 53,83%; H 4,65%; Cl 9,35%; F 10,02%; S 8,45%.

Found: C 53,73%; H 4,63%; Cl 9,35%; F There Is A 10.03%; S 8.55 Percent.

Example 30: 2-[1-[(4-chlorophenyl)sulfonyl]cyclopentyl]-1,4-differenza

In toluene (10 ml) was dissolved 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1-pentanol (100 mg, 0,267 mmol). After adding cyanomethylene-n-butylphosphine (130 mg, 0,539 mmol) the resulting mixture was heated at the boil under reflux for 2 days in an atmosphere of argon. The reaction mixture was allowed to cool, and then added cyanomethylene-n-butylphosphate (130 mg, 0,539 mmol). The mixture was boiled under reflux for 3 days in an atmosphere of argon. The reaction mixture was allowed to cool and then concentrated under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=15:1) to obtain white solid. The obtained white solid was washed with hexane to obtain specified in the title compound (35 mg, 37%) as a white powder.

Melting point: 153 to 155°C.

IR (ATR) ν: 2968, 1581, 1489, 1304, 1277, 1138, 1082, 827, 752, 606, 569, 519, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,70-of 1.85 (2H, m), 2.05 is-of 2.20 (2H, m), 2,22 to 2.35 (2H, m), 2,88-of 3.00 (2H, m), 6.75 in-6,83 (1H, m), 6,95-7,05 (2H, m), 7,35 (4H, s).

MS (m/z): 374, 376(M++NH4).

Elemental analysis for C17H15ClF2O2S.

Calculated: C 57,22%; H 4,24%; Cl 9,94%; F 10,65%; 8,99%.

Found: C 56,87%; H 4,14%; Cl 10,28%; F 10,44%; S 9,05%.

Example 31: 2-[6-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]hexyl]-1,4-differenza

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (0,94 g, 3.1 mmol)obtained in example 5 was dissolved in toluene (30 ml) followed by addition of 5-(tert-butyldimethylsilyloxy)-1-pentanol (1.1 ml, 4.6 mmol) and cyanomethylene-n-butylphosphine (1.0 g, 4.1 mmol). The resulting mixture was heated at the boil under reflux for 14 hours in an argon atmosphere. The reaction mixture was allowed to cool and then concentrated under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=15:1) to obtain the specified title compound (1.4 g, 87%) as a colourless oil.

IR (ATR) ν: 2929, 2856, 1583, 1496, 1325, 1151, 1088, 835, 775, 754, 629 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.01 (6H, s)0,86 (9H, s), 1.18 to to 1.60 (6H, m), 2,04-2,17 (1H, m), 2,38-of 2.50 (1H, m), of 3.54 (2H, t, J=6,1 Hz), a 4.53 (1H, DD, J=11,5, 2.7 Hz), 6,78-to 6.88 (1H, m), 6,93-7,03 (1H, m), 7,20-7,30 (1H, m), 7,38 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

MS (m/z): 503, 505 (M++H).

Example 32: 6-[(4-chlorophenyl)sulfonyl]-6-(2,5-differenl)-1-hexanol

2-[6-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]hexyl]-1,4-differental (0,70 g, 1.4 mmol) was dissolved in tetrahydrofuran (30 ml). When the cooling eh what the solution was added in tetrahydrofuran of tetrabutylammonium (1.0 M, of 4.2 ml, 4.2 mmol)and the mixture was stirred at room temperature for 1 hour. After adding water (1.0 ml) to the reaction mixture and the mixture was concentrated under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=3:2) to obtain white solid. The obtained white solid was washed with hexane to obtain specified in the connection header (0,47 g, 86%) as a white powder.

Melting point: 98-99°C.

IR (ATR) ν: 3575, 2929, 1495, 1279, 1146, 1082, 1014, 833, 752, 627, 541, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,18-1,62 (7H, m), 2,04-to 2.18 (1H, m), 2.40 a of $ 2.53 (1H, m)and 3.59 (2H, DD, J=11,5, 6.4 Hz), to 4.52 (1H, DD, J=11,5, 2.7 Hz), 6,78-to 6.88 (1H, m), 6,94? 7.04 baby mortality (1H, m), 7,20-7,30 (1H, m), 7,38 (2H, d, J=8,4 Hz), 7,53 (2H, d, J=8,4 Hz).

MS (m/z): 389, 391 (M++H).

Elemental analysis for C18H19ClF2O3S.

Calculated: C 55,60%; H 4,92%; Cl 9,12%; F 9,77%; S Of 8.25%.

Found: C 55,38%; H 4,75%; Cl Is 9.09%; F 9,81%; S, 8.34 Per Cent.

Example 33: 2-[1-[(4-chlorophenyl)sulfonyl]cyclohexyl]-1,4-differenza

6-[(4-chlorophenyl)sulfonyl]-6-(2,5-differenl)-1-hexanol (200 mg, 0,514 mmol) was dissolved in toluene (20 ml). After adding cyanomethylene-n-butylphosphine (500 mg, 2,07 mmol) the resulting mixture was heated at the boil under reflux for 4 days in an argon atmosphere. The reaction mixture was allowed to cool and then koncentrirane and under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=20:1) to obtain white solid. The obtained solid was washed with hexane/methylene chloride to obtain specified in the title compound (97 mg, 51%) as a white powder.

Melting point: 137-139°C.

IR (ATR) ν: cm-1, 2933, 2862, 1495, 1309, 1144, 1082, 885, 814, 750, 619, 559, 464 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,10-of 1.45 (3H, m)to 1.61 (1H, DM, J=12.0 Hz), is 1.81 (2H, sird, J=13,4 Hz), is 2.09 (2H, shirt, J=13,0 Hz), 2,55-2,95 (2H, m), at 6.84 (1H, DDD, J=12,2, 9,0, a 4.9 Hz), 7,00-7,11 (2H, m), of 7.36 (2H, s), of 7.36 (2H, s).

MS (m/z): 388, 390 (M++NH4).

Elemental analysis for C18H17ClF2O3S.

Calculated: C 58,30%; H 4,62%; Cl 9,56%; F Of 10.25%; S 8,65%.

Found: C 58,01%; H 4,49%; Cl 9,58%; F 10,35%; S 8,82%.

Example 34: 2-[1-[(4-chlorophenyl)sulfonyl]-3-(2-vinyloxyethoxy)propyl]-1,4-differenza

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (520 mg, 1,72 mmol)obtained in example 5 was dissolved in toluene (30 ml). After addition of 2,2-(2-vinyloxyethoxy)ethanol (0,270 ml, 2.10 mmol) and cyanomethylene-n-butylphosphine (500 mg, 2,07 mmol) the resulting mixture was heated at the boil under reflux for 24 hours in an argon atmosphere. Then the reaction mixture was allowed to cool. After adding 2-(2-vinyloxyethoxy)ethanol (0,170 ml, 1.25 mmol) and cyanomethylene ' n ' is utiltarian (300 mg, to 1.24 mmol) the mixture was heated at the boil under reflux for 12 hours in an argon atmosphere. The reaction mixture was allowed to cool and then concentrated under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=7:1) to obtain white solid. The obtained white solid was washed with hexane to obtain specified in the title compound (140 mg, 20%) as a white powder.

Melting point: 55-56°C.

IR (ATR) ν: 2927, 2877, 1621, 1496, 1323, 1198, 1144, 1084, 1012, 829, 752, 633, 542, 469 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 2.20 to 2.35 (1H, m), 2,70-to 2.85 (1H, m), or 3.28 (1H, dt, J=9,5, 4.6 Hz), 3,40-3,50 (1H, m), 3,54-3,68 (2H, m), 3,71 (2H, t, J=4.6 Hz), 3,99 (1H, DD, J=6,7, and 2.1 Hz), 4,14 (1H, DD, J=14,3 and 2.1 Hz), to 4.81 (1H, DD, J=10,9, 4.0 Hz), 6,41 (1H, DD, J=14,3, 6,7 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), 6,94? 7.04 baby mortality (1H, m), 7.18 in-7,30 (1H, m), 7,39 (2H, DM, J=8,3 Hz), 7,56 (2H, DM, J=8,3 Hz).

MS (m/z): 417, 419 (M++H).

Elemental analysis for C19H19ClF2O4S.

Calculated: C 54,74%; H 4,59%; Cl 8,50%; F 9,11%; S Of 7.69%.

Found: C 54,54%; H 4,46%; Cl 8,46%; F 9,02%; S 7,81%.

Example 35: 2-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propoxy]ethanol

2-[1-[(4-chlorophenyl)sulfonyl]-3-(2-vinyloxyethoxy)propyl]-1,4-differental (123 mg, 0,295 mmol) was dissolved in methanol (10 ml). Added monohydrate p-toluensulfonate acid (2.0 mg, to 0.011 mmol) and the mixture was stirred at to the room temperature for 4 hours. After concentration under reduced pressure the residue was purified by chromatography on silica gel (methylene chloride:methanol=50:1) to obtain white solid. The obtained white solid was washed with hexane to obtain specified in the title compound (80 mg, 70%) as a white powder.

Melting point: 41-46°C.

IR (ATR) ν: 3467, 2943, 1495, 1315, 1149, 1086, 1061, 829, 762, 521 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.78 and 1.80 (1H, m), 2,22-of 2.36 (1H, m), 2,75-is 2.88 (1H, m), 3,20-3,40 (2H, m), 3,42-to 3.52 (1H, m), 3,57-to 3.73 (3H, m), to 4.81 (1H, DD, J=10,9, and 3.8 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), 6,94? 7.04 baby mortality (1H, m), 7,22-7,30 (1H, m), 7,39 (2H, DM, J=8,4 Hz), 7,55 (2H, DM, J=8,4 Hz).

MS (m/z): 391, 393 (M++H).

Elemental analysis for C17H17ClF2O4S.

Calculated: C 52,24%; H Of 4.38%; Cl 9,07%; F 9,72%; S To 8.20%.

Found: C 52,12%; H 4,36%; Cl 9,11%; F 9,86%; S 8,32%.

Example 36: 2-[[(4-chlorophenyl)sulfonyl](cyclohexyl)methyl]-1,4-differenza

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (240 mg, 0,793 mmol)obtained in example 5 was dissolved in toluene (20 ml). To the resulting solution was added cyclohexanol (of 0.11 ml, 1.0 mmol) and cyanomethylene-n-butylphosphate (250 mg, 1.0 mmol). The resulting mixture was heated at the boil under reflux for 14 hours in an argon atmosphere. The reaction mixture was allowed to cool and then was added cyclohexanol (to 0.22 ml, 2.1 mmol) and cyanomethylene-n-butylester is h (500 mg, of 2.08 mmol). The mixture was heated at the boil under reflux for 14 hours in an argon atmosphere. The reaction mixture was allowed to cool and was concentrated under reduced pressure, after which the thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=30:1) to obtain white solid. The obtained white solid was washed with hexane to obtain specified in the title compound (188 mg, 62%) as a white powder.

Melting point: 107-109°C.

IR (ATR) ν: 2927, 2858, 1495, 1240, 1138, 1080, 874, 831, 796, 750, 708, 615, 548, 507, 469, 444 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 0,92-1,08 (1H, m), 1,08-1,22 (1H, m), 1,22 of 1.50 (3H, m), 1,60-1,75 (3H, m), 1,75-of 1.88 (1H, m), is 2.37 (1H, sird, J=12,5 Hz), 2,48-2,62 (1H, m), of 4.44 (1H, d, J=7,6 Hz), 6,68-to 6.80 (1H, m), 6,86-to 6.95 (1H, m,), 7,30 (2H, DM, J=8.6 Hz), 7,38-7,52 (1H, m), 7,49 (2H, DM, J=8.6 Hz).

MS (m/z): 402, 404 (M++NH4).

Elemental analysis for C19H19ClF2O2S.

Calculated: C 59,29%; H To 4.98%; Cl Of 9.21%; F 9,87%; S 8,33%.

Found: C 59,11%; H 4.93 Per Cent; Cl 9,18%; F 9,82%; S 8,49%.

Example 37: 2-[6-bromo-1-[(4-chlorophenyl)sulfonyl]hexyl]-1,4-differenza

To tetrahydrofuran (10 ml) was added sodium hydride (60% dispersion in oil, 15 mg, 0.38 mmol). When cooled on ice was added 2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (100 mg, 0,330 mmol)obtained in example 5. After stirring the reaction mixture at the room for the Noah temperature for 30 minutes was added 1,5-dibromethane (0.10 ml, to 0.74 mmol). The reaction mixture was stirred at room temperature for 3 days followed by the addition of sodium hydride (60% dispersion in oil, 15 mg, 0.38 mmol) under cooling on ice. The resulting mixture was stirred at room temperature for 15 minutes and then was added 1,5-dibromethane (0.10 ml, of 0.74 mmol). The mixture was stirred at room temperature for 14 hours and then concentrated under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain white solid. The obtained white solid was washed with hexane to obtain specified in the title compound (51 mg, 30%) as a white powder.

Melting point: 77-79°C.

IR (ATR) ν: 2937, 1495, 1147, 1084, 1014, 893, 833, 795, 752, 708, 627, 559, 536, 465 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.20 and 1.35 (2H, m), 1,37-of 1.55 (2H, m), 1,74-of 1.88 (2H, m), 2.05 is-of 2.20 (1H, m), 2.40 a of $ 2.53 (1H, m)to 3.34 (2H, dt, J=6,6, 1.3 Hz), 4,51 (1H, DD, J=11,5, 2.7 Hz), 6,83 (1H, TD, J=9,0, 4.6 Hz), 6,94? 7.04 baby mortality (1H, m,), 7,20-7,30 (1H, m), 7,38 (2H, d, J=8.7 Hz), 7,53 (2H, d, J=8.7 Hz).

MS (m/z): 468, 470 (M++NH4).

Elemental analysis for C18H18BrClF2O2S.

Calculated: C 47,86%; H Was 4.02%; Br 17,69%; Cl Of 7.85%; F To 8.41%; S 7,10%.

Found: C 47,80%; H 3,83%; Br 17,67%; Cl 7,86%; F 8,65%; S Of 7.25%.

Reference example 2: 4-(tert-butyldiphenylsilyl)-1-methyl-1-butanol

In N,N-dimetil is mamide (200 ml) was dissolved 1,4-pentanediol (10.0 g, 96,0 mmol) and imidazole (6.6 g, a 96.9 mmol). When cooled on ice was added dropwise tert-butylchloroformate of 25.2 ml, 96,4 mmol). After completion of adding dropwise, the reaction mixture was stirred at room temperature for 2 days. To the reaction mixture were added diethyl ether followed by washing with water. The organic layer was dried over anhydrous magnesium sulfate. After filtration, the residue obtained by concentration of the filtrate under reduced pressure was purified by chromatography on silica gel (hexane:ethyl acetate=5:1) to obtain specified in the connection header (32,0 g, 97%) as a colourless oil.

IR (ATR) ν: 3350, 2929, 2856, 1427, 1105, 822, 739, 698, 609, 501 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.05 (9H, s)to 1.19 (3H, d, J=6.3 Hz), 1,46-1,72 (4H, m), 2,02-of 2.08 (1H, m), of 3.69 (2H, t, J=6.0 Hz), 3,78-are 3.90 (1H, m), 7,30 is 7.50 (6H, m), 7,62-7,88 (4H, m).

MS (m/z): 343 (M++H).

Example 38: 2-[5-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differental (isomer 38-a and isomer 38-In)

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (0,94 g, 3.1 mmol)obtained in example 5 was dissolved in toluene (30 ml) followed by addition of 4-(tert-butyldiphenylsilyl)-1-methyl-1-butanol (1.40 g, 4.1 mmol) and cyanomethylene-n-butylphosphine (1.0 g, 4.1 mmol). The resulting mixture was heated at the boil under reflux in ECENA 2 days in an atmosphere of argon. The reaction mixture was allowed to cool and then added cyanomethylene-n-butylphosphate (1.0 g, 4.1 mmol). The mixture was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling the reaction mixture the residue obtained by concentrating the mixture was purified by chromatography on silica gel (hexane:ethyl acetate=60:1) to obtain the specified header isomer 38-A (low polarity) (0.71 g, 37%) and indicated in the title isomer 38-In (high polarity (0.45 g, 23%), each as a colourless oil.

Isomer 38-

IR (ATR) ν: 2931, 2858, 1495, 1322, 1149, 1109, 1088, 1012, 822, 752, 700, 613, 503, 488, 469 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.02 (9H, s)of 1.09 (3H, d, J=6.8 Hz), 1,26-of 1.42 (1H, m), 1,50-1,80 (3H, m), 2,74-of 2.86 (1H, m)to 3.64 (2H, t, J=5.7 Hz), 4,51 (1H, d, J=5.6 Hz), 6,78 (1H, TD, J=9,1, 4.6 Hz), 6.90 to-7,00 (1H, m), 7,30-of 7.48 (8H, m), 7,50-7,58 (3H, m), 7,60-of 7.70 (4H, m).

MS (m/z): 627 (M++H).

Isomer 38-

IR (ATR) ν: 2931, 2858, 1495, 1147, 1107, 1088, 822, 752, 729, 700, 613, 559, 503, 471 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.94 (9H, s), 1,00-1,20 (1H, m)to 1.37 (3H, d, J=6.8 Hz), 1,40-of 1.64 (3H, m), 2,60-to 2.74 (1H, m), 3,48-of 3.60 (2H, m), 4,43 (1H, sird, J=9,3 Hz), 6,69 (1H, TD, J=9,0, 4,4 Hz), 6,84-6,93 (1H, m), 7.24 to 7,45 (9H, m), of 7.48 (2H, d, J=8.6 Hz), 7,52 to 7.62 (4H, m).

MS (m/z): 627 (M++H).

Example 39: 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-4-methyl-1-pentanol

2-[5-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differental (from the measures 38-A) (710 mg, 1.13 mmol)obtained in example 38 was dissolved in methylene chloride (20 ml). When cooled on ice was added dropwise a mixture of hydrogen fluoride-pyridine (0,64 ml). After completion of adding dropwise, the reaction mixture was stirred at room temperature for 14 hours. To the reaction mixture were added saturated aqueous solution (20 ml) of sodium bicarbonate followed by extraction with diethyl ether. The organic layer was washed successively 1 N. chloride-hydrogen acid, saturated aqueous sodium bicarbonate and saturated salt solution and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=2:1) to give colorless oil. The obtained colorless oil was utverjdali hexane to obtain specified in the title compound (283 mg, 64%) as a white powder.

Melting point: 84-86°C.

IR (ATR) ν: 3367, 2937, 1496, 1138, 1084, 1051, 1012, 829, 754, 729, 708, 621, 561, 532, 471 cm-1.

1H-NMR (400 MHz, CDCl3) δwith 1.07 (3H, d, J=6.8 Hz), 1,40-of 1.85 (5H, m), 2,75-2,90 (1H, m), 3,64 of 3.75 (2H, m), of 4.54 (1H, d, J=6.6 Hz), 6,77 (1H, TD, J=9,0, 4,4 Hz), 6.90 to-7,00 (1H, m), 7,33 (2H, d, J=8,4 Hz), 7,43-of 7.60 (1H, m), 7,51 (2H, d, J=8,4 Hz).

MS (m/z): 389, 391 (M++H).

Elemental analysis for C18H19ClF2O3S.

Calculated: C 55,60%; H 4,92; Cl 9,12%; F 9,77%; S Of 8.25%.

Found: C To 55.42%; H A 4.83%; Cl 9,10%; F 9,85%; S 8,30%.

Example 40: 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-4-methyl-1-pentanol

2-[5-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differental (isomer 38) (450 mg, 0,717 mmol)obtained in example 38 was dissolved in methylene chloride (10 ml). When cooled on ice was added dropwise a mixture of hydrogen fluoride-pyridine (0,41 ml). After completion of adding dropwise, the reaction mixture was stirred at room temperature for 14 hours. To the reaction mixture were added saturated aqueous solution (20 ml) of sodium bicarbonate followed by extraction with diethyl ether. The organic layer was washed successively 1 N. chloride-hydrogen acid, saturated aqueous sodium bicarbonate and saturated salt solution and dried over anhydrous magnesium sulfate. After filtration, the residue obtained by concentration of the filtrate under reduced pressure was purified by chromatography on silica gel (hexane:ethyl acetate=2:1) to give colorless oil. The obtained colorless oil was utverjdali hexane to obtain specified in the title compound (194 mg, 70%) as a white powder.

Melting point: 67-69°C.

IR (ATR) ν: 3537, 2933, 2868, 1481, 1308, 1279, 1240, 1144, 1078, 822, 802, 754, 712, 665, 613, 544, 469 cm-1.

1H-NMR (400 is Hz, CDCl3) δ: 1,08-1,22 (1H, m), 1,23 (1H, t, J=5,2 Hz)of 1.36 (3H, d, J=6.8 Hz), 1,45 is 1.70 (3H, m), 2,67 is 2.80 (1H, m), 3,50-the 3.65 (2H, m), of 4.45 (1H, d, J=8,3 Hz), was 6.73 (1H, TD, J=9,0, 4.6 Hz), 6,88-6,97 (1H, m), 7,31 (2H, d, J=8,8 Hz), 7,34-of 7.48 (1H, m), 7,49 (2H, d, J=8,8 Hz).

MS (m/z): 389, 391 (M++H).

Elemental analysis for C18H19ClF2O3S.

Calculated: C 55,60%; H 4,92%; Cl 9,12%; F 9,77%; S Of 8.25%.

Found: C 55,48%; H 4,84%; Cl 9,01%; F 9,76%; S 8,32%.

Example 41: 2-[5-bromo-1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differenza

5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-4-methyl-1-pentanol (290 mg, 0,746 mmol)obtained in example 39, and tetrabromide carbon (290 mg, 0,874 mmol) was dissolved in methylene chloride (8 ml). Under stirring on ice, the solution obtained by dissolution of triphenylphosphine (230 mg, 0,877 mmol) in methylene chloride (2 ml)was added dropwise to the obtained solution. After completion of adding dropwise, the reaction mixture was stirred at room temperature for 3 days. To the reaction mixture was added tetrabromide carbon (290 mg, 0,874 mmol) and triphenylphosphine (230 mg, 0,877 mmol) while cooling on ice, followed by stirring at room temperature for 6 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by chromatography on silica gel (hexane:ethyl acetate=15:1) to obtain the specified title compound (331 mg, 98%) in the de colorless oil.

IR (ATR) ν: 2966, 1495, 1321, 1238, 1147, 1088, 1012, 789, 752, 729, 712, 613, 559, 536, 471 cm-1.

1H-NMR (400 MHz, CDCl3) δwith 1.07 (3H, d, J=6.8 Hz), 1,46 is 1.60 (1H, m), 1.77 in-2,11 (3H, m), 2,74-2,90 (1H, m)to 3.41 (2H, t, J=6,7 Hz), 4,49 (1H, d, J=6.6 Hz), 6,78 (1H, TD, J=9,1, 4.6 Hz), 6.90 to-7,00 (1H, m), 7,33 (2H, d, J=to 8.7 Hz), 7,45-of 7.60 (1H, m), 7,52 (2H, d, J=8.7 Hz).

MS (m/z): 451, 453 (M++H).

Example 42: 2-[5-bromo-1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differenza

5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-4-methyl-1-pentanol (170 mg, 0,437 mmol)obtained in example 40, and tetrabromide carbon (170 mg, 0,648 mmol) was dissolved in methylene chloride (8 ml). Under stirring while cooling on ice to the resulting solution were added triphenylphosphine (135 mg, 0,515 mmol) followed by stirring at room temperature for 14 hours. To the reaction mixture was added tetrabromide carbon (170 mg, 0,437 mmol) and triphenylphosphine (135 mg, 0,515 mmol) under cooling on ice. The reaction mixture was stirred at room temperature for 6 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain the specified title compound (192 mg, 97%) as a colourless oil.

IR (ATR) ν: 3091, 2966, 1496, 1296, 1246, 1142, 1080, 889, 839, 754, 710, 627, 553, 513, 471 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.18 to 1.31 (1H, m), 1,37 3H, d, J=6.8 Hz), 1,50-1,70 (1H, m), 1,78-of 1.92 (2H, m), 2,62 is 2.80 (1H, m), 3,20-3,40 (2H, m), of 4.44 (1H, d, J=8.5 Hz), was 6.73 (1H, TD, J=9,0, 4.5 Hz), 6,88-6,98 (1H, m), 7,30 (2H, d, J=8.6 Hz), 7,30 is 7.50 (1H, m), 7,49 (2H, d, J=8.6 Hz).

MS (m/z): 451, 453 (M++H).

Example 43: 2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylthio)pentyl]-1,4-differental (isomer 43-a and isomer 43)

2-[5-bromo-1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differental (325 mg, 0,719 mmol)obtained in example 41 2-[5-bromo-1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differental (185 mg, 0,410 mmol)obtained in example 42 was dissolved in tetrahydrofuran (25 ml). To the resulting solution was added thiamethoxam sodium (160 mg, 2.28 mmol) under cooling on ice. After stirring at room temperature for 14 hours to the mixture while cooling on ice was added thiamethoxam sodium (190 mg, a 2.71 mmol). The residue obtained by concentrating the reaction mixture under reduced pressure was purified by chromatography on silica gel (hexane:ethyl acetate=30:1) to obtain the specified header isomer 43-A (low polarity) (185 mg, 39%) and indicated in the title isomer 43 (high polarity) (186 mg, 30%), each as a colourless oil.

Isomer 43-And

IR (ATR) ν: 2916, 1493, 1321, 1238, 1146, 1088, 1012, 789, 752, 712, 613, 559, 536, 469 cm-1.

1H-NMR (400 MHz, CDCl3) δ: a 1.08 (3H, d, J=6.9 Hz), 1,40-and 1.54 (1H, m), 1,55-of 1.85 (3H, m), 2,10 (3H, s)of 2.50 (2H, t, J=7.2 Hz), 2,75-2,90 (1H, m), 4,51 (1H, d, J=6,1 Hz), 6,78 (1H, TD, J=9,1, 4,4 Hz), 6.90 to-7,00 (1H, m), 7,33 (2H, d, J=8.6 Hz), 7,45-of 7.60 (1H, m), 7,52 (2H, d, J=8.6 Hz).

MS (m/z): 419, 421(M++H).

HRMS (FAB) for C19H22ClF2O2S2(M++H).

Calculated: 419,0718.

Found: 419,0733.

Isomer 43

IR (ATR) ν: 2952, 2920, 1493, 1308, 1232, 1176, 1149, 1090, 827, 750, 629, 590, 557, 532, 472 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,10-1,30 (1H, m)to 1.37 (3H, d, J=6.6 Hz), 1,50-of 1.65 (3H, m), 2,03 (3H, s), 2,30-of 2.50 (2H, m), 2,64-2,78 (1H, m), of 4.44 (1H, d, J=8.6 Hz), was 6.73 (1H, TD, J=9,0, 4.5 Hz), 6,86-6,98 (1H, m), 7,30 (2H, d, J=8.6 Hz), 7,34-7,46 (1H, m), of 7.48 (2H, d, J=8.6 Hz).

MS (m/z): 419, 421(M++H).

HRMS (FAB) for C19H22ClF2O2S2(M++H).

Calculated: 419,0718.

Found: 419,0715.

Example 44: 2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylsulfinyl)pentyl]-1,4-differenza

2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylthio)pentyl]-1,4-differental (isomer 43-A) (180 mg, 0,430 mmol)obtained in example 43 was dissolved in methylene chloride (10 ml). When cooled on ice was added 3-chloroperbenzoic acid (89 mg, 0.51 mmol) followed by stirring at room temperature for 14 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by chromatography on silica gel (methylene chloride:methanol=40:1) to obtain the specified title compound (172 mg, 92%) as a colourless oil.

IR (ATR) ν : 2920, 1495, 1317, 1279, 1238, 1146, 1086, 1036, 829, 789, 752, 712, 615, 559, 471 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,00-1,10 (3H, m), 1,50-1,75 (1H, m), 1,78 is 2.10 (3H, m)2,60 (1,5H, s), 2,60 (1,5H, s), 2,65-2,90 (3H, m), 4,50 (1H, d, J=7,6 Hz), 6,77 (1H, TD, J=9,2, 4,4 Hz), 6.90 to-7,00 (1H, m), 7,32 (2H, d, J=8.5 Hz), 7,40-of 7.60 (1H, m)to 7.50 (2H, d, J=8,5 Hz).

MS (m/z): 435, 437 (M++H).

HRMS (FAB) for C19H22ClF2O3S2(M++H).

Calculated: 435,0667.

Found: 435,0655.

Example 45: 2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylsulfinyl)pentyl]-1,4-differenza

2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylthio)pentyl]-1,4-differental (isomer 43) (175 mg, 0,418 mmol)obtained in example 43 was dissolved in methylene chloride (10 ml). When cooled on ice was added 3-chloroperbenzoic acid (87 mg, 0.50 mmol), followed by stirring at room temperature for 14 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by chromatography on silica gel (methylene chloride:methanol=40:1) to obtain white solid. The obtained solid was washed with diethyl ether obtaining specified in the title compound (118 mg, 65%) as a white powder.

Melting point: 107-112°C.

IR (ATR) ν: 3087, 2943, 1496, 1315, 1242, 1178, 1149, 1088, 1028, 829, 731, 623, 584, 538, 457 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,15-of 1.40 (4H, m), 1,45 is 2.00 (3H, m), 2,50 and-2.8 (3H, m)to 2.54 (3H, s), 4,46 (1H, d, J=8.1 Hz), 6,78 (1H, TD, J=9,0,4,7 Hz), 6.90 to-7,00 (1H, m), 7,32 (2H, d, J=8,4 Hz), 7,35 is 7.50 (1H, m), 7,49 (2H, d, J=8,4 Hz).

MS (m/z): 435, 437 (m++H).

Elemental analysis for C19H21ClF2O3S2.

Calculated: C 52,47%; H 4,87%; Cl 8,15%; F, A Total Of 8.74%; S 14,74%.

Found: C 52,44%; H 4,85%; Cl 8,17%; F 8,79%; S 14,63%.

Example 46: 2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylsulphonyl)pentyl]-1,4-differenza

2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylsulfinyl)pentyl]-1,4-differental (76 mg, 0.18 mmol)obtained in example 44 was dissolved in methylene chloride (5 ml). When cooled on ice was added 3-chloroperbenzoic acid (36 mg, 0.21 mmol). The resulting mixture was stirred at room temperature for 2 hours. The residue obtained by concentrating the reaction mixture, it was purified by chromatography on silica gel (methylene chloride:methanol=100:1) to obtain a pale yellowish-brown oil. The obtained pale-yellowish-brown oil was utverjdali a mixture of diethyl ether/methylene chloride to obtain specified in the title compound (61 mg, 77%) as a yellow powder.

Melting point: 115-117°C.

IR (ATR) ν: 3078, 2937, 1493, 1311, 1286, 1230, 1151, 1136, 1086, 831, 754, 729, 712, 623, 542, 519, 471, 459 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.03 (3H, d, J=7,1 Hz), 1,60-1,80 (1H, m), 1.85 to of 2.20 (3H, m), 2,70-2,90 (1H, m)to 2.94 (3H, s), of 3.07 (2H, t, J=7.8 Hz), 4,49 (1H, d, J=7.8 Hz), 6,76 (1H, TD, J=9,1, 4.5 Hz, 6,90-7,00 (1H, m), 7,32 (2H, d, J=8.5 Hz), 7,35-of 7.60 (1H, m), 7,49 (2H, d, J=8,5 Hz).

MS (m/z): 451, 453 (m++H).

Elemental analysis for C19H21ClF2O4S2.

Calculated: C 50,61%; H 4,96%; Cl 7,86%; F 8,43%; S 14,22%.

Found: C 50,57%; H 4,74%; Cl Of 7.85%; F 8,58%; S Of 14.25%.

Example 47: 2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylsulphonyl)pentyl]-1,4-differenza

2-[1-[(4-chlorophenyl)sulfonyl]-2-methyl-5-(methylsulfinyl)pentyl]-1,4-differental (66 mg, 0.15 mmol)obtained in example 45 was dissolved in methylene chloride (5 ml). When cooled on ice was added 3-chloroperbenzoic acid (32 mg, 0,19 mmol). The resulting mixture was stirred at room temperature for 3 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by chromatography on silica gel (methylene chloride:methanol=100:1) to obtain white solid. The obtained white solid was washed with a mixture of diethyl ether/methylene chloride to obtain specified in the title compound (52 mg, 76%) as a white powder.

Melting point: 142-144°C.

IR (ATR) ν: 3082, 2937, 1495, 1317, 1290, 1234, 1151, 1130, 1092, 831, 769, 754, 731, 712, 625, 544, 525, 503, 472, 449, 417 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,15-of 1.40 (1H, m)of 1.32 (3H, d, J=6.6 Hz), 1,40-2,05 (3H, m), 2,65-3,10 (3H, m), is 2.88 (3H, s), 4,46 (1H, d, J=7,1 Hz), 6,77 (1H, TD, J=9,1, 4.6 Hz), 6.90 to-7,00 (1H, m), 7,32 (2H, d, J=8,4 Hz), 7,35 is 7.50 (1H, m), 7,49 (2H, d, J=8,4 Hz).

MS (m/z): 451, 453 (m++H).

Elemental analysis for C19H21ClF2O4S2.

Calculated: C 50,61%; H 4,69%; Cl 7,86%; F 8,43%; S 14,22%.

Found: C 50,48%; H 4,59%; Cl 7,93%; F To 8.57%; S 14,09%.

Example 48: 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)tetrahydropyran

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (1.0 g, 3,30 mmol)obtained in example 5 was dissolved in tetrahydrofuran (70 ml). At -78°C was added dropwise a solution in hexane (1.57 M, 5.3 ml, 8.3 mmol) n-utillity. After completion of adding dropwise, the reaction mixture was stirred at -78aboutC for 10 minutes and then stirred for 30 minutes while cooling on ice. At -78°to the reaction mixture was added dropwise 2-bromatology ether (with 0.55 ml, 3.9 mmol). After completion of adding dropwise, the temperature of the reaction mixture was raised to room temperature over 14 hours. To the reaction mixture were added water (2 ml). The residue obtained by concentrating the mixture under reduced pressure was purified by chromatography on silica gel (hexane:ethyl acetate=5:1) to obtain white solid. The obtained white solid was washed with a mixture of diisopropyl ether/methylene chloride to obtain specified in the title compound (317 mg, 26%) as a white powder.

Melting point: 157-160°C.

IR (ATR)ν : 2966, 2862, 1496, 1309, 1188, 1149, 1086, 1012, 899, 841, 808, 750, 710, 629, 592, 569, 536, 515, 471 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 2,40 is 2.80 (4H, m), of 3.32 (2H, t, J=12,5 Hz), was 4.02 (2H, d of t, J=11,8,3,3 Hz), 6,82-to 6.95 (1H, m), 7,05-7,17 (2H, m), 7,38 (2H, s), 7,39 (2H, s).

MS (m/z): 373, 375 (m++H).

Elemental analysis for C17H15ClF2O3S.

Calculated: C 54,77%; H 4,06%; Cl 9,51%; F 10,19%; S 8,60%.

Found: C 54,55%; H 4,00%; Cl RS 9.69%; F 10,33%; S 8,64%.

Example 49: 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)pentyl-1-pyrrolidinecarboxylic

To a solution in methylene chloride (6 ml) 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1-pentanol (390 mg, 1.04 mmol)obtained in example 29, was added triethylamine (152 μl, of 1.09 mmol) and 4-nitrophenylphosphate (220 mg, of 1.09 mmol). The resulting mixture was stirred at room temperature for 24 hours. The reaction mixture was concentrated to obtain crude 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)pentyl-4-nitrophenylarsonic (759 mg). The crude 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)pentyl-4-nitrophenylarsonic (268 mg) was dissolved in methylene chloride (4 ml) followed by the addition of triethylamine (76,7 μl, 0,551 mmol) and pyrrolidine (46,0 μl, 0,551 mmol). The mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated and the residue was dissolved in diethyl ether. The resulting solution was washed on sledovatelno saturated aqueous solution of potassium bicarbonate, saturated aqueous ammonium chloride, water and a saturated salt solution, dried over MgSO4and then concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (40% ethyl acetate-hexane) to obtain the specified title compound (128 mg, 74%) as a pale brown oil.

IR (ATR) ν: 3086, 2954, 2875, 1689, 1583, 1496, 1423, 1321, 1176, 1147, 1084, 1012, 874, 752, 536, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,26-to 1.38 (2H, m), 1,54-of 1.73 (2H, m), of 1.78-1.90 (4H, m), 2,09-of 2.20 (1H, m), 2,42-2,52 (1H, m), 3,19 is 3.40 (4H, m), 3.96 points-of 4.05 (2H, m)to 4.52 (1H, DD, J=11,5, 2.7 Hz), 6,83 (1H, TD, J=9,1, 4,4 Hz), 6,94-7,01 (1H, m), 7,21-7,28 (1H, m), 7,38 (2H, d, J=8.6 Hz), 7,52 (2H, d, J=8.6 Hz).

MS (m/z 472 (m++H).

HRMS (FAB) for C22H24ClF2NO4S (m++H).

Calculated: 472,1161.

Found: 472,1124.

Reference example 3: 4-(methylsulphonyl)-1-butanol

While stirring with cooling on ice 3-chloroperbenzoic acid (3.04 from g, 17.6 mmol) was added to a solution in methylene chloride (100 ml) of 4-(methylthio)-1-butanol (1.01 g, of 8.40 mmol). At room temperature the mixture was stirred for 20 hours. After confirming completion of the reaction the solvent was concentrated under reduced pressure. To the residue was added diethyl ether and water to separate the water layer. The resulting aqueous layer was concentrated under reduced pressure. To the mod who have added methylene chloride. The mixture was dried over anhydrous sodium sulfate and then the solvent was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of methanol:methylene chloride (=1:20)specified in the header connection (1,21 g, 95%) was obtained as a pale yellow oil.

IR (ATR) ν: 3494, 2931, 2877, 1457, 1413, 1282, 1122, 1054, 1029, 966, 827, 765, 518, 462 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1.55V is 1.91 (3H, m), 1.91 a-2,11 (2H, m), of 2.92 (3H, s)to 3.09 (2H, t, J=7.9 Hz), and 3.72 (2H, t, J=6,1 Hz).

MS (m/z): 153 (m++H).

Reference example 4: 4-(methylsulfinyl)-1-butanol

While stirring with cooling on ice periodate sodium (1.24 g, 5,80 mmol) was added to a mixed solution of 4-(methylthio)-1-butanol (465 mg, a 3.87 mmol) in tetrahydrofuran (15 ml) and water (3 ml). At room temperature the resulting mixture was stirred for a 21.5 hours. After confirming completion of the reaction, the reaction mixture was diluted with methylene chloride and then subjected to filtration through celite. The filtrate was concentrated under reduced pressure. To the residue was added methylene chloride. The resulting mixture was dried over anhydrous sodium sulfate and then the solvent was concentrated under reduced pressure. Thus obtained residue was subjected to chromatography on a column of silica gel, and fractions, elyuirovaniya mixture m is tanol:methylene chloride (=1:10), got mentioned in the title compound (160 mg, 30%) as a pale yellow oil.

IR (ATR) ν: 3369, 2937, 2867, 1658, 1452, 1411, 1054, 1006, 941, 694 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,40-of 1.55 (1H, Shir), 1,68 of-1.83 (2H, m), 1.93 and-of 2.08 (2H, m), of 2.92 (3H, s)to 3.09 (2H, t, J=7.9 Hz), and 3.72 (2H, t, J=5,5 Hz).

MS (m/z): 137 (m++H).

Example 50: 1-chloro-4-(benzylmethyl)benzene

4-chlorobenzenesulfonate sodium (306 mg, 1.54 mmol) and benzylbromide (of 0.18 ml, 1.54 mmol) was added to n-butanol (15 ml). The resulting mixture was stirred at 70°C for 5 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate. The resulting mixture was washed successively with water and saturated salt solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=8:1)as specified in the title compound (299 mg, 73%) as a white solid.

Melting point: 147.5 to-148,5°C.

IR (ATR) ν: 3060, 3029, 2994, 2942, 1583, 1571, 1492, 1475, 1454, 1396, 1311, 1294, 1274, 1147, 1087, 1014, 977, 917, 831, 773, 757, 696, 642, 532, 462 cm-1.

1H-NMR (400 MHz, CDCl3) δ: or 4.31 (2H, s), 7.23 percent-7,38 (4H, m), 7,38-7,46 (2H, m), 7,49-7,58 (2H, m).

MS (m/z): 267 (m++H).

Example 51: 1-chloro-4-(5-methylsulphonyl-1-NILPETER)sulfanilate

In an argon atmosphere a solution in toluene (20 ml) of 1-chloro-4-(benzylmethyl)benzene (90 mg, of 0.337 mmol), 4-(methylsulphonyl)-1-butanol (69 mg, 0,453 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (233 mg, 0,965 mmol) was heated at the boil under reflux for 21 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=2:1)were specified in the title compound (44 mg, 33%) as a white solid.

Melting point: 151-152°C.

IR (ATR) ν: 2937, 2867, 1577, 1467, 1396, 1319, 1270, 1203, 1147, 1087, 1058, 1014, 962, 842, 802, 755, 696, 632, 565, 530, 474, 420 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,34-of 1.52 (2H, m), 1,79-of 1.97 (2H, m), 2,13-of 2.28 (2H, m), 2,45-of 2.58 (1H, m), of 2.86 (3H, s), 2,89-of 3.00 (2H, m)to 4.01 (1H, DD, J=11,2, 3,9 Hz), was 7.08 (1H, d, J=8.1 Hz), 7,22-7,47 (8H, m).

MS (m/z): 401 (m++H).

Elemental analysis for C18H21ClO4S2.

Calculated: C 53,92%; H 5,28%; Cl 8,84%; S 16,00%.

Found: C 53,92%; H To 5.21%; Cl 9,05%; S 15,88%.

Example 52: 1-chloro-4-(5-methylsulfinyl-1-fenilpentil)sulfanilate

Solution in toluene (15 ml) of 4-chloro-1-(benzylmethyl)benzene (122 mg, 0,457 mmol)obtained in example 50, 4-(methylsulfinyl)-1-buta is Nola (81 mg, 0,595 mmol)obtained in reference example 4, and cyanomethylene-n-butylphosphine (221 mg, 0,916 mmol) was heated at the boil under reflux for 2 days in an atmosphere of argon. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of methylene chloride:methanol (=100:1), white solid. The obtained white solid was recrystallized from diethyl ether to obtain specified in the title compound (20 mg, 11%) as white needle crystals.

Melting point: 98,5-99,5°C.

IR (ATR) ν: 2935, 2856, 1575, 1473, 1455, 1392, 1309, 1276, 1143, 1081, 1016, 946, 829, 794, 755, 694, 624, 563, 520, 464 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,32 of 1.50 (2H, m), 1,70-1,90 (2H, m), 2,15-of 2.28 (1H, m), 2,45-2,70 (2H, m), 2,52 (3H, s), was 4.02 (1H, DD, J=11,4, and 3.8 Hz), 7,05 for 7.12 (1H, m), 7,20-7,47 (8H, m).

MS (m/z): 385 (m++H).

Elemental analysis for C18H21ClO3S2.

Calculated: C 56,16%; H 5,50%; Cl Of 9.21%; S 16,66%.

Found: C 56,03%; H, 5.37 Percent; Cl 9,29%; S 16.69 Per Cent.

Example 53: 1-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]-2-torbenson

To 4-chlorobenzenesulfonate sodium (203 mg, of 1.02 mmol) and 2-farbensymposium (124 μl, of 1.02 mmol) was added n-butanol (5 ml). The mixture was mixed the ri 70° C for 5 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added methylene chloride, and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue is washed with diisopropyl ether to obtain a white powder (111 mg).

Solution in toluene (10 ml) of the obtained white powder (35 mg), 4-(methylsulphonyl)-1-butanol (38 mg, of 0.250 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (60 mg, 0,246 mmol) was heated at the boil under reflux for 17.5 hours in argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=1:1)were specified in the title compound as a white solid (46 mg).

Melting point: 167-168°C.

IR (ATR) ν: 2948, 2867, 1614, 1579, 1488, 1455, 1396, 1319, 1290, 1268, 1230, 1199, 1149, 1126, 1085, 1014, 962, 829, 792, 767, 752, 713, 628, 572, 532, 495, 458, 430 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,38-of 1.52 (2H, m), 1,80-to 1.98 (2H, m), 2,16-to 2.29 (1H, m), 2,48-2,60 (1H, m), 2,87 (3H, s), 2,96 (2H, t, J=7.9 Hz), 4,55 (1H, DD, J=11,0, 4,2 Hz), 6,85 (1H, TD, J=9,1, 1.1 Hz), 7,17-7,39 (4H, m), 7,43-7,58 (3H, m).

MS (m/z): 419 (m++H).

Elemental analysis for C 18H20ClFO4S2.

Calculated: C 51,61%; H 4,81%; Cl 8,46%; F 4,53%; S 15,31%.

Found: C 51,65%; H 4,74%; Cl 8,33%; F 4,50%; S 15,20%.

Example 54: 1-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]-3-torbenson

4-chlorobenzenesulfonate sodium (216 mg, of 1.09 mmol) and 3-florantyrone (136 μl, of 1.09 mmol) was added to n-butanol (5 ml). The resulting mixture was stirred at 70°C for 5 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added methylene chloride, and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. Thus obtained residue is washed with diisopropyl ether to obtain a white powder (208 mg).

Then a solution in toluene (10 ml) of the obtained white powder (59 mg), 4-(methylsulphonyl)-1-butanol (65 mg, 0,427 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (100 mg, 0,414 mmol) was heated at boiling under reflux in the course of 29.5 hours in argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=2:3)as specified in sagola the ke compound as a white solid (71 mg).

Melting point: 116-117°C.

IR (ATR) ν: 2942, 2875, 1590, 1469, 1394, 1317, 1295, 1270, 1241, 1201, 1145, 1083, 1012, 964, 875, 840, 798, 769, 752, 705, 686, 634, 592, 541, 530, 512, 491, 464 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,34-of 1.52 (2H, m), 1,78 of 1.99 (2H, m), 2,09-2,22 (1H, m), 2,41-of 2.56 (1H, m), 2,81-3,03 (2H, m), is 2.88 (3H, s)to 4.01 (1H, DD, J=11,2, 3,9 Hz), 6,83 (1H, d, J=7,6 Hz), make 6.90 (1H, d, J=9.3 Hz), 7,03 (1H, TD, J=8,1, 2.2 Hz), 7.23 percent (1H, TD, J=7,9, 6,0 Hz), 7,32 is 7.50 (4H, m).

MS (m/z): 419 (m++H).

Elemental analysis for C18H20ClFO4S2.

Calculated: C 51,61%; H 4,81%; Cl 8,31%; F 4,53%; S 15,31%.

Found: C 51,68%; H 4,72%; Cl 8,31%; F To 4.52%; S 15,30%.

Example 55: 1-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]-4-torbenson

4-chlorobenzenesulfonate sodium (183 mg, 0,921 mmol) and 4-florantyrone (112 μl, 0,921 mmol) was added to n-butanol (5 ml). The resulting mixture was stirred at 70°C for 6 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue is washed with diisopropyl ether to obtain a white powder (150 mg).

Then a solution in toluene (10 ml) of the obtained white powder (57 mg), 4-(methylsulphonyl)-1-butanol (62 mg, 0,407 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (97 mg,0.400 mmol) was heated at the boil under reflux for 17 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=2:3)as specified in the title compound as a white solid (58 mg).

Melting point: 141-142°C.

IR (ATR) ν: 2937, 2865, 1606, 1577, 1508, 1467, 1394, 1317, 1292, 1270, 1236, 1147, 1126, 1085, 1014, 962, 838, 825, 755, 721, 626, 574, 553, 514, 482, 455 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,35 of 1.50 (2H, m), 1,80-of 1.97 (2H, m), 2,09-of 2.21 (1H, m), 2,43-of 2.56 (1H, m), is 2.88 (3H, s), 2,90-of 3.00 (2H, m)to 4.01 (1H, DD, J=11,2, 3,9 Hz), 6,97 (2H, t, J=8.5 Hz), 7.03 is-7,11 (2H, m), of 7.36-of 7.48 (4H, m).

MS (m/z): 419 (m++H).

Elemental analysis for C18H20ClFO4S2.

Calculated: C 51,61%; H 4,74%; Cl 8,46%; F 4,53%; S 15,31%.

Found: C 51,74%; H 4,74%; Cl 8,28%; F 4,53%; S 15,36%.

Example 56: 2-[1-[(4-chlorophenyl)sulfonyl]-1-methylthio]methyl-1,4-differenza

In nitrogen atmosphere 2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (82,8 mg, 0.27 mmol)obtained in example 5 was added to a suspension of sodium hydride (12 mg, 0.30 mmol) in N,N-dimethylformamide (2.0 ml) at room temperature. The resulting mixture was stirred for 10 minutes. To the reaction mixture were added methylmethanesulfonate (28,1 mg, 0.27 mmol)and the mixture was stirred for another 30 minutes. In the reaction mixture was added to yenny aqueous solution of sodium bicarbonate (10 ml) followed by extraction with diethyl ether. The organic layer was washed with water and saturated salt solution and dried over anhydrous magnesium sulfate. After filtration, the residue obtained by concentration of the filtrate under reduced pressure was purified by chromatography on silica gel (hexane:diethyl ether=4:1) to obtain the specified title compound (36 mg, 38%) as a white solid.

Melting point: 128-129°C.

IR (ATR) ν: 1489, 1315, 1234, 1147, 1078, 829 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 2,47 (3H, s), with 5.22 (1H, s), to 6.88 (1H, m), 6,97 (1H, m), 7,13 (1H, m), 7,41 (2H, m), 7,60 (2H, m).

MS (m/z): 173 (m+-SO2Ar.

Elemental analysis for C14H11ClF2O2S2.

Calculated: C 48,21%; H 3,18%; S 18,39%; Cl 10,16%; F 10,89%.

Found: C 48,41%; H 3,28%; S 17,88%; Cl 10,41%; F 10,57%.

Example 57: 2-[1-[(4-chlorophenyl)sulfonyl]-1-phenylthio]methyl-1,4-differenza

Similar to the method used in example 56, except for the application phenylenesulfonyl, synthesized specified in the header of the connection.

Melting point: 84-85°C.

IR (ATR) ν: 1492, 1319, 1149, 1086, 825 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 5.53 (1H, s)6,91 (1H, m), 7,01 (1H, m), 7.23 percent-7,31 (4H, m), 7,35-7,40 (4H, m), the 7.65 (2H, m), the 7.65 (2H, m), 7,40-to 7.35 (4H, m), 7,31-of 7.23 (4H, m), 7,01 (1H, m)6,91 (1H, m), of 5.53 (1H, s).

MS (m/z): 235 (M+-SO2Ar.

Elemental analysis for C19H13ClF2O2S2.

In chileno: C 55,54%; H 3,19%; S 15,61%; Cl 8,63%; F 9,25%.

Found: C 55,50%; H 3,18%; S 15,51%; Cl 8,40%; F 9.03 Per Cent.

Example 58: Benzyl[(4-chlorophenyl)sulfonyl-(2,5-differenl)methyl]carbamate

To a solution in tetrahydrofuran (0.4 ml) benzylcarbamoyl (151 mg, 1.0 mmol) was added water (1.0 ml), chlorobenzenesulfonate sodium (199 mg, 1.0 mmol), 2,5-differentally (142 mg, 1.0 mmol) and formic acid (0,24 ml). The resulting mixture was stirred for 19 hours at room temperature. To the reaction mixture, having formed in it a white precipitate, was added diethyl ether and water. The precipitate was collected by filtration and washed successively with diethyl ether obtaining specified in the title compound (251 mg, 51%).

Melting point: 183-184°C.

IR (ATR) ν: 1726, 1518, 1495, 1319, 1230, 1147, 831 cm-1.

1H-NMR (400 MHz, DMSO-d6) δ: 4,91 (1H, d, J=12,4 Hz), equal to 4.97 (1H, d, J=12,4 Hz), and 6.25 (1H, d, J=10.4 Hz), 7,2 was 7.45 (7H, m), of 7.70 (2H, d, J=8,4 Hz), 7,71 (1H, m), 7,78 (2H, d, J=8,4 Hz), was 9.33 (1H, d, J=10.4 Hz).

MS (m/z): 275 (m+-SO2Ar.

Reference example 5: Benzyl-2,5-diferenziabilit

In the atmosphere of nitrogen dicyclohexylcarbodiimide (206 mg, 1.0 mmol) was added to a solution in methylene chloride (10 ml) of 2,5-diferenciales acid (184 mg, 1 mmol), benzyl alcohol (104 ml, 1 mmol) and N,N-dimethylaminopyridine (36 mg, 0.3 mmol) at room temperature and obtained mesh was stirred for 17 hours. After concentrating the reaction mixture under reduced pressure, to the residue was added 10 ml of a mixture of hexane-diethyl ether (4:1). Thus obtained residue was filtered. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=5:1) to obtain the specified title compound (242 mg, 88%).

Melting point: 45-46°C.

IR (ATR) ν: 1712, 1641, 1305, 1167, 692 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 5,24 (c, 2H), is 6.54 (d, 1H, J=16.4 Hz), 7,03 (m, 2H), 7,18 (m, 1H), 7,37 (m, 5H), to 7.77 (d, 1H, J=16.4 Hz).

Example 59: Benzyl-3-(4-chlorophenylsulfonyl)-3-(2,5-differenl)propionate

Under nitrogen atmosphere a solution in hexane (1.57 M, 0.05 ml) n-utility was added to the solution in tetrahydrofuran (10 ml), benzyl-2,5-differentiability (108 mg, 0,39 mmol) and 4-chlorbenzoyl (57 mg, 0,39 mmol) at room temperature. The resulting mixture was stirred for 1 hour. After concentrating the reaction mixture under reduced pressure, the residue was subjected to chromatography on silica gel. Faction elyuirovaniya a mixture of hexane:diethyl ether=10:1), concentrated under reduced pressure.

Then the residue was dissolved in methanol (10 ml). To the resulting solution was added water (1.0 ml), tetrahydrate hexaminolevulinate (5.0 mg) and 30% aqueous hydrogen peroxide (2 ml) at room temperature, followed by stirring for 48 hours the century The reaction mixture was diluted with ethyl acetate (50 ml) and then washed with sufficient water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove solvent. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=8:1) to obtain the specified title compound (33 mg, 19%).

Melting point: 127-128°C.

IR (ATR) ν: 1734, 1498, 1317, 1211, 1170, 1149, 748 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 3.12 (DD, 1H, J=10,4, is 16.8 Hz), 3,48 (DD, 1H, J=4,4, is 16.8 Hz), to 4.98 (d, 1H, J=12.0 Hz), 5,02 (m, 1H), to 5.03 (d, 1H, J=12.0 Hz), 6,79 (m, 1H), for 6.81 (m, 1H), 7,1-7,2 (m, 3H), of 7.23 (m, 3H), 7,38 (d, 2H, J=8,4 Hz), 7,52 (d, 2H, J=8,4 Hz).

Elemental analysis for C22H17ClF2O4S·0,5H2O.

Calculated: C 57,46%; H 3,91%; S 6,97%; Cl 7,70%; F Compared To 8.26%.

Found C 57,60%; H 3,89%; S 7,02%; Cl 7,83%; F 8,31%.

MS (m/z): 450 (m+).

HRMS (EI): C22H17ClF2O4S (M+).

Calculated: 450,0504.

Found: 450,0496.

Example 60: 2-[1-[(4-chlorophenyl)sulfonyl]-2-pentylcyclohexyl]-1,4-differenza

In the atmosphere of nitrogen triethylamine (36,4 μl, 0,262 mmol) and methanesulfonamide (to 18.6 μl, 0,240 mmol) was added to a solution in methylene chloride (4 ml) of a mixture of isomers (91,0 mg, 0,218 mmol) 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-3-octanol, obtained in example 22, in aboutC. the resulting mixture was stirred at 0°C for 2 hours. The reaction mixture was diluted with methylene chloride, washed with water and saturated salt solution, dried over MgSO4and then concentrated. Thus obtained residue was subjected to chromatography on a short column of silica gel. Faction elyuirovaniya a mixture of hexane:ethyl acetate (=3:1), concentrated under reduced pressure to obtain a colorless oil.

The obtained colorless oil was dissolved in tetrahydrofuran (4 ml). In the atmosphere of argon and at -78°to the resulting solution was added n-utility (1.57 M solution, to 0.127 ml, 0,200 mmol) followed by stirring at -78°C for 3 hours. To the reaction mixture were added saturated aqueous solution of ammonium chloride followed by extraction with diethyl ether. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and then concentrated. Thus obtained residue was purified by medium pressure chromatography on a column of silica gel (8% ethyl acetate-hexane) to obtain specified in the connection header of 48.1 mg, 66%) as a colourless oil.

IR (ATR) ν: 2929, 2925, 2858, 1585, 1496, 1317, 1250, 1176, 1146, 1090, 1014, 889, 827, 796, 760, 715, 602, 565, 478 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 0,43-0,62 (1H, m), 0,83-of 0.95 (3H, m), 1,13-1,70 (7,66H, m), 1,82-1,93 (0,33H, m), 1,99 (0,33H, DD, J=9,8, 5,4 G is), 2,07 (0,66H, DD, J=9,8, 5,9 Hz), 2.26 and-2,40 (1H, m), 6,74-6,84 (1H, m)6,91 (0,33H, TD, J=9,0, 4,4 Hz), 6,98-7,05 (1H, m), 7,13 (0,66H, DD d, J=8,6, 5,6, and 3.2 Hz), 7,35 is 7.50 (4H, m).

MS (m/z 399 (M++H).

HRMS (FAB) for C20H22ClF2O2S (M++H).

Calculated: 399,0997.

Found: 399,1006.

Example 61: Tert-butyl 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propionate

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 7.01 ml) was added dropwise to the solution in dimethoxyethane (50 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (3.03 g, 10.0 mmol)obtained in example 5. The temperature of the reaction mixture was raised to room temperature. Then the reaction mixture was cooled to -78°C. After adding tert-butylbromide (1,48 ml, 10.0 mmol) the resulting mixture was stirred at room temperature for 3 hours. In the reaction mixture were added saturated aqueous solution of ammonium chloride followed by extraction with diethyl ether. The extracts were combined, washed successively with water and saturated salt solution, dried over MgSO4and then distilled to remove solvent. Thus obtained residue was subjected to chromatography on a short column of silica gel (hexane-ethyl acetate 3:1). The thus obtained solid substance was recrystallized from hexane to obtain specified in the header is soedineniya (3,30 g, 79%) as a colourless solid.

Melting point: to 140.5-142,5°C.

IR (ATR) ν: 3074, 2983, 1722, 1585, 1496, 1427, 1396, 1369, 1275, 1257, 1215, 1142, 1086, 955, 835, 781, 750, 712, 665, 606, 559, 467 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 1.28 (9H, s)of 3.00 (1H, DD, J=16,4 and 10.7 Hz), 3,37 (1H, DD, J=16,4, 4,4 Hz), 5,00 (1H, DD, J=10,7, 4,4 Hz), 6,85 (1H, TD, J=9,0, 4.6 Hz), of 6.96-7.03 is (1H, m), 7,19 (1H, DDD, J=8,8, 5,6, and 3.2 Hz), 7,41 (2H, d, J=8,3 Hz)to 7.50 (2H, d, J=8,3 Hz).

MS (m/z): 417 (M++H).

HRMS (FAB) for C19H19ClF2O4S (M++H).

Calculated: 416,0661.

Found: 416,0690.

Elemental analysis for C19H19ClF2O4S.

Calculated: C 54,74%; H 4,59%; Cl 8,50%; F 9,11%; S Of 7.69%.

Found: C 54,67%; H 4,55%; Cl 8,54%; F 9,17%; S 7,80%.

Example 62: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propionic acid

When 0°triperoxonane acid (10 ml) was added to a solution in methylene chloride (30 ml) of tert-butyl 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propionate (3,10 g, the 7.43 mmol). The resulting mixture was stirred at room temperature for 2 hours. To the residue obtained by concentrating the reaction mixture, was added toluene and the resulting mixture was concentrated. Thus obtained residue was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (to 2.29 g, 85%) as colorless needle crystals.

Melting point: to 152.0-153,0 C.

IR (ATR) ν: 2956, 1707, 1576, 1496, 1427, 1396, 1321, 1255, 1217, 1115, 1086, 1012, 914, 893, 829, 795, 756, 708, 619, 536, 459 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 3,13 (1H, DD, J=17,1, 10.4 Hz), 3,53 (1H, DD, J=17,1, 4.6 Hz), 5,02 (1H, DD, J=10,4, 4.6 Hz), 6,85 (1H, TD, J=9,0, 4.6 Hz), of 6.96-7.03 is (1H, m), 7,18 (1H, DDD, J=8,5, 5,4, 3,2 Hz), 7,41 (2H, d, J=8,8 Hz), 7,55 (2H, d, J=8,8 Hz).

MS (m/z): 360 (M+).

HRMS (EI): C15H11ClF2O4S (M+).

Calculated: 360,0035.

Found: 360,0026.

Elemental analysis for C15H11ClF2O4S.

Calculated: C 49,94%; H 3,07%; Cl 9,83%; F 10,53%; S 8,89%.

Found: C 49,74%; H 2,99%; Cl 9,88%; F 10,63%; S 8,98%.

Example 63: 1-chloro-2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

4-chlorobenzenesulfonate sodium (205 mg, of 1.03 mmol) and 2-Chlorobenzilate (134 μl, of 1.03 mmol) was added to dimethoxyethane (5 ml). The resulting mixture was stirred at 70°C for 6 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue was washed with hexane to obtain a white powder (231 mg).

Solution in toluene (10 ml) of the obtained white powder (92 mg), 4-(methylsulphonyl)-1-butanol (96 mg, 0,631 mmol)obtained in reference example 3, and cyanomethylene-n-Buti is phosphorane (148 mg, 0,614 mmol) was heated at the boil under reflux for 20 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=1:1)as specified in the title compound (74 mg) as a colourless oil.

IR (ATR) ν: 2931, 2873, 1573, 1475, 1442, 1394, 1313, 1276, 1133, 1083, 1033, 1012, 962, 908, 829, 794, 748, 713, 684, 626, 568, 518, 464 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,33-of 1.52 (2H, m), 1,79-to 1.98 (2H, m), 2,15-of 2.30 (1H, m), 2,50-2,60 (1H, m), of 2.86 (3H, s)to 2.94 (2H, t, J=7.9 Hz), a 4.86 (1H, DD, J=11,0, 3,9 Hz), 7,17-7,29 (3H, m), 7,29-7,38 (2H, m), 7,41-to 7.50 (2H, m,), to 7.67 (1H, d, J=7,8 Hz).

MS (m/z): 435 (M++H).

HRMS (FAB) for C18H21O4Cl2S2(M++H).

Calculated: 435,0258.

Found: 435,0264.

Example 64: 1-chloro-3-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

4-chlorobenzenesulfonate sodium (219 mg, 1.10 mmol) and 3-Chlorobenzilate (142 μl, of 1.03 mmol) was added to dimethoxyethane (5 ml). The resulting mixture was stirred at 70°C for 6 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate and the resulting mixture was filtered, the insoluble substance. The residue obtained by concentration of the filtrate under reduced pressure, washed with hexane to obtain a white powder (304 mg).

Solution in toluene (10 ml) of the obtained white powder (92 mg), 4-(methylsulphonyl)-1-butanol (96 mg, 0,631 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (148 mg, 0,614 mmol) was heated at the boil under reflux for 20 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=2:3)as specified in the title compound (51 mg) as a colourless oil.

IR (ATR) ν: 3089, 3023, 1573, 1475, 1394, 1278, 1195, 1139, 1081, 1012, 962, 885, 829, 804, 750, 694, 626, 578, 530, 462 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,32 of 1.50 (2H, m), 1,79-of 1.97 (2H, m), 2,09-2,22 (1H, m), 2.40 a-2,52 (1H, m), is 2.88 (3H, s), 2,90-of 3.00 (2H, m), 3,98 (1H, DD, J=11,2, 3,9 Hz), of 6.96 (1H, d, J=7,6 Hz), 7,10 (1H, s), 7,20 (1H, t, J=7,6 Hz), 7,28-to 7.32 (1H, m), 7,35-7,47 (4H, m).

MS (m/z): 435 (M++H).

HRMS (FAB): C18H21O4Cl2S2(M++H).

Calculated: 435,0258.

Found: 435,0240.

Example 65: 1-chloro-4-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

4-chlorobenzenesulfonate sodium (211 mg, 1.06 mmol) and 4-Chlorobenzilate (218 μl, 1.06 mmol) was added to dimethoxyethane (5 ml). The resulting mixture plumage is shivali at 70° C for 6 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate and the resulting mixture was filtered, the insoluble substance. The residue obtained by concentration of the filtrate under reduced pressure, washed with hexane to obtain a white powder (274 mg).

Then a solution in toluene (10 ml) of the obtained white powder (61 mg), 4-(methylsulphonyl)-1-butanol (63 mg, 0,414 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (97 mg, 0,403 mmol) was heated at the boil under reflux for 20 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=2:3)as specified in the title compound (37 mg) as a colourless oil.

IR (ATR) ν: 2931, 2871, 1581, 1492, 1475, 1411, 1394, 1276, 1139, 1085, 1012, 962, 908, 827, 752, 713, 661, 620, 566, 518, 470 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,35-is 1.51 (2H, m), a 1.75-to 1.98 (2H, m), 2.05 is was 2.25 (1H, m), 2,42 is 2.55 (1H, m), 2,84-3,10 (2H, m), 2,87 (3H, s)to 3.99 (1H, DD, J=11,0, 3,9 Hz), 6,99-7,10 (2H, m), 7,20-to 7.35 (2H, m), 7,35-of 7.55 (4H, m).

MS (m/z): 435 (M++H).

HRMS (FAB) for C18H21O4Cl2S2(M++H).

Calculated: 435,0258.

On the Deno: 435,0240.

Example 66: 1-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]naphthalene

4-chlorobenzenesulfonate sodium (183 mg, 0,921 mmol) and 1-bromethalin (204 μl, 0,921 mmol) was added to dimethoxyethane (10 ml). The resulting mixture was stirred at 70°C for 6 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate and the resulting mixture was filtered, the insoluble substance. The residue obtained by concentration of the filtrate under reduced pressure, washed with hexane to obtain a white powder (175 mg).

Then a solution in toluene (10 ml) of the obtained white powder (93 mg), 4-(methylsulphonyl)-1-butanol (92 mg, 0,604 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (142 mg, 0,589 mmol) was heated at the boil under reflux for 18 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=1:1)as specified in the title compound (80 mg) as a white solid.

IR (ATR) ν: 2929, 2869, 1577, 1511, 1475, 1394, 1301, 1276, 1137, 1083, 1012, 962, 906, 863, 808, 763, 709, 640, 622, 574, 532, 457 cm-1/sup> .

1H-NMR (400 MHz, CDCl3) δ: 1,35-of 1.55 (2H, m), 1.77 in-1,95 (2H, m), 2,29 is 2.46 (1H, m), 2,62-2,77 (1H, m), 2,80 (3H, s), 2,83-of 3.00 (2H, m), 5,07 (1H, DD, J=10,9, 4.0 Hz), 7,10 (2H, d, J=8,3 Hz), 7,22-of 7.48 (4H, m), 7,51 (1H, t, J=7,7 Hz), to 7.59 (1H, d, J=8.6 Hz), to 7.67 (1H, d, J=7,3 Hz), 7,78 (1H, d, J=8.1 Hz), 7,83 (1H, d, J=8,3 Hz).

MS (m/z): 451 (M++H).

HRMS (FAB) for C22H24O4ClS2(M++H).

Calculated: 451,0805.

Found: 451,0816.

Example 67: 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]naphthalene

4-chlorobenzenesulfonate sodium (211 mg, 1.06 mmol) and 2-bromethalin (235 μl, 1.06 mmol) was added to dimethoxyethane (5 ml). The resulting mixture was stirred at 70aboutC for 5 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate and the resulting mixture was filtered, the insoluble substance. The residue obtained by concentration of the filtrate under reduced pressure, washed with hexane to obtain a white powder (90 mg).

Then a solution in toluene (10 ml) of the obtained white powder (60 mg), 4-(methylsulphonyl)-1-butanol (59 mg, 0,388 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (91 mg, 0,379 mmol) was heated at the boil under reflux for 21 hours in an argon atmosphere. After cooling to room temperature the reaction mixture to which has centriole under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=2:3)as specified in the title compound (62 mg) as a white solid.

Melting point: 146,0-147,0°C.

IR (ATR) ν: 2931, 2861, 1581, 1508, 1473, 1457, 1392, 1359, 1309, 1274, 1191, 1147, 1126, 1081, 1010, 968, 902, 869, 819, 752, 734, 703, 646, 624, 566, 522, 472, 453 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,34-is 1.51 (2H, m), 1,78 of 1.99 (2H, m), 2,25-to 2.40 (1H, m), 2,50-2,62 (1H, m), 2,84 (3H, s), 2,89-3,03 (2H, m), 4,19 (1H, DD, J=11,2, 3,9 Hz), 7,18 and 7.36 (4H, m), 7,39-to 7.61 (4H, m), 7,69-of 7.90 (3H, m).

MS (m/z): 451 (M++H).

Elemental analysis for C22H23ClO4S2.

Calculated: C 58,59%; H 5,14%; Cl 7,86%; S 14,22%.

Found: C 58,46%; H 5,03%; Cl 7,94%; S 14,33%.

Example 68: 2-chloro-1-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]-4-torbenson

4-chlorobenzenesulfonate sodium (197 mg, 0,992 mmol) and 2-chloro-4-florantyrone (222 µl, 0,992 mmol) was added to dimethoxyethane (5 ml). The resulting mixture was stirred at 70°C for 6 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The residue obtained by concentration of the filtrate under reduced pressure, washed with hexane to obtain a white powder (225 mg).

Then a solution in toluene (10 ml) of the obtained white powder (61 mg), 4-(methylsulphonyl)-1-butanol (59 mg, 0,394 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (93 mg, 0.384 mmol) was heated at the boil under reflux for 15 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel with obtaining from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=1:1)as specified in the title compound (38 mg) as a white solid.

Melting point: 124,0-125,0°C.

IR (ATR) ν: 2969, 2933, 1604, 1575, 1492, 1475, 1461, 1396, 1315, 1276, 1230, 1130, 1085, 1049, 1014, 973, 902, 850, 823, 782, 748, 659, 630, 588, 549, 501, 457 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,30-1,50 (2H, m), 1,79-to 1.98 (2H, m), 2,10-of 2.25 (1H, m), 2,48-2,60 (1H, m), 2,87 (3H, s), 2,95 (2H, t, J=7,7 Hz), 4,79 (1H, DD, J=11,1, 4.0 Hz), 6,98 (1H, DD, J=8,3, 2.7 Hz), 7,05-to 7.15 (1H, m), 7,38 (2H, d, J=8,3 Hz), of 7.48 (2H, d, J=8.5 Hz), 7,60-of 7.70 (1H, m).

MS (m/z): 453 (M++H).

Elemental analysis for C18H19Cl2FO4S2.

Calculated: C 47,69%; H 4,22%; Cl 15,64%; F 4,19%; S 14,55%.

Found: C 47,44%; H 4,20%; Cl 15.37 Percent; F 4,07%; S 14,33%.

Example 69: 1,2-dichloro-4-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

4-chlorobenzenesulfonate sodium (208 mg, 1.05 mmol) and 3,4-dichloraniline is (251 μl, 1.05 mmol) was added to dimethoxyethane (5 ml). The resulting mixture was stirred at 70°C for 6 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate and the resulting mixture was filtered, the insoluble substance. The residue obtained by concentration of the filtrate under reduced pressure, washed with hexane to obtain a white powder (270 mg).

Then a solution in toluene (10 ml) of the obtained white powder (66 mg), 4-(methylsulphonyl)-1-butanol (62 mg, 0,407 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (96 mg, 0,397 mmol) was heated at the boil under reflux for 15 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=2:3)were specified in the title compound (70 mg) as a white solid.

Melting point: 143,0-144, 0mm°C.

IR (ATR) ν: 2929, 2865, 1573, 1459, 1392, 1365, 1317, 1299, 1276, 1186, 1145, 1079, 1031, 1010, 975, 900, 823, 748, 709, 655, 626, 588, 563, 518, 474, 439 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,32-1,49 (2H, m), 1,79 is 1.96 (2H, m), 2.05 is-are 2.19 (1H, m), 2,39-of 2.50 (1H, m), is 2.88 (3H, s), 2,90-of 3.00 (2H, m), of 3.97 (1H, DD, J=11,2, 3,9 Hz)6,94 (1H, DD, J=8,3, 2,2 Hz) 7,21 (1H, d, J=2.0 Hz), was 7.36 (1H, d, J=8,3 Hz), the 7.43 (2H, d, J=8,3 Hz), 7,49 (2H, d, J=8.6 Hz).

MS (m/z): 469 (M++H).

Elemental analysis for C18H19Cl3O4S2.

Calculated: C 46,02%; H 4,08%; Cl 22,64%; S 13,65%.

Found: C 45,92%; H 4,06%; Cl To 22.35%; S 13,59%.

Example 70: 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]pyridine

4-chlorobenzenesulfonate sodium (200 mg, 1.01 mmol), hydrochloride of 2-chloromethylpyridine (166 mg, 1.01 mmol) and potassium acetate (198 mg, 2.02 mmol) was added to n-butanol (5 ml). The resulting mixture was stirred at 70°C for 5 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=3:1), obtained white solid (123 mg).

Then a solution in toluene (10 ml) of the obtained solid (49 mg), 4-(methylsulphonyl)-1-butanol (57 mg, 0,374 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (88 mg, 0,366 mmol) was heated at the boil under reflux for 2 days in an atmosphere of argon. After cooling to room temperature the reaction mixture was concentrated the ri reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of methanol:methylene chloride (=1:50)were specified in the title compound (40 mg) as a white solid.

Melting point: 140,0-141,0°C.

IR (ATR) ν: 3012, 2948, 1587, 1471, 1436, 1392, 1321, 1290, 1263, 1197, 1149, 1089, 1006, 960, 825, 750, 703, 624, 565, 528, 499, 474, 410 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,30-of 1.52 (2H, m), 1,79 of 1.99 (2H, m), 2,29-2,49 (2H, m), of 2.86 (3H, s), with 2.93 (2H, t, J=6.8 Hz), 4,33 (1H, DD, J=11,0, 4,2 Hz), 7,20-7,30 (1H, m), 7,32-7,52 (5H, m), to 7.67 for 7.78 (1H, m), 8,40 (1H, d, J=4,9 Hz).

MS (m/z): 402 (M++H).

Elemental analysis for C17H20NClO4S2.

Calculated: C 50,80%; H 5,02%; N 3,48%; Cl 8,82%; S 15,96%.

Found: C 50,67%; H 4,94%; N 3,53%; Cl 8,72%; S 15,90%.

Example 71: 1,4-dichloro-2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

4-chlorobenzenesulfonate sodium (38 mg, 0,192 mmol) and 2,5-dichlorobenzamide (46 μl, 0,192 mmol) was added to dimethoxyethane (5 ml). The resulting mixture was stirred at 70°C for 24 hours. After cooling to room temperature the reaction mixture was subjected to chromatography on a short column (silica gel) and the fraction, elyuirovaniya diethyl ether, concentrated under reduced pressure. Thus obtained residue was dissolved in toluene (5 ml). To the resulting solution was added 4-(methylsulphonyl)-1-butanol(58 mg, 0,381 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (89 mg, 0,370 mmol) followed by heating at boiling under reflux for 23 hours in a nitrogen atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=1:1)were specified in the title compound (32 mg, 35%) as a colourless oil.

IR (ATR) ν: 2933, 2869, 1581, 1465, 1394, 1313, 1278, 1191, 1133, 1083, 1039, 1012, 962, 887, 821, 752, 713, 630, 588, 532, 464 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,33 of 1.50 (2H, m), 1,80 is 1.96 (2H, m), 2,09-of 2.21 (1H, m), 2,48 at 2.59 (1H, m), is 2.88 (3H, s), 2,90-to 2.99 (2H, t, J=11,0, 4,2 Hz), 4,79 (1H, DD, J=11,0, 4,2 Hz), to 7.15 (1H, d, J=8.6 Hz), 7,20-7,29 (1H, m), 7,34-7,40 (2H, m), 7,46-7,52 (2H, m), 7,63 (1H, d, J=2.5 Hz).

MS (m/z): 469, 471 (M++H).

HRMS (FAB) for C18H20O4Cl3S2(M++H).

Calculated: 468,9869.

Found: 468,9907.

Example 72: 1-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]for 3,5-differenza

4-chlorobenzenesulfonate sodium (49 mg, 0,247 mmol) and 3,5-differenziale (32 μl, 0,247 mmol) was added to dimethoxyethane (5 ml). The resulting mixture was stirred at 70°C for 24 hours. After cooling to room temperature the reaction mixture was subjected chrome is adopted on a short column (silica gel) and the fraction, elyuirovaniya diethyl ether, concentrated under reduced pressure. Thus obtained residue was dissolved in toluene (5 ml). To the resulting solution was added 4-(methylsulphonyl)-1-butanol (58 mg, 0,381 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (89 mg, 0,370 mmol). The mixture was heated at the boil under reflux for 23 hours in argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=1:1)were specified in the title compound (39 mg, 36%) as a white solid.

Melting point: 126,0-127,0°C.

IR (ATR) ν: 2940, 1623, 1596, 1463, 1392, 1344, 1319, 1270, 1243, 1203, 1145, 1118, 1081, 1010, 987, 952, 863, 823, 752, 707, 680, 624, 539, 501, 478, 449 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,35-of 1.62 (2H, m), 1,78 of 1.99 (2H, m), 2.05 is-are 2.19 (1H, m), 2,39 is 2.51 (1H, m), is 2.88 (3H, s), 2,90 was 3.05 (2H, m), 3,98 (1H, DD, J=10,9, 4.0 Hz), 6,62 to 6.75 (2H, m), 6.75 in-6,85 (1H, m), 7,38-7,58 (4H, m).

MS (m/z): 436 (m++H).

Elemental analysis for C18H19F2O4S2.

Calculated: C 49,48%; H Of 4.38%; Cl 8,11%; F 8,70%; S 14,68%.

Found: C 49,45%; H 4,33%; Cl 8,10%; F 8,88%; S 14,69%.

Example 73: 3-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]pyridine

4-chlorbenzol hint sodium (207 mg, 1.04 mmol), hydrochloride of 3-chloromethylpyridine (171 mg, 1.04 mmol) and potassium acetate (204 mg, of 2.08 mmol) was added to n-butanol (5 ml). The resulting mixture was stirred at 70°C for 5 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel and the fractions elyuirovaniya a mixture of hexane:ethyl acetate (=2:3), received a white solid (98 mg).

Then a solution in toluene (10 ml) of the obtained solid (29 mg), 4-(methylsulphonyl)-1-butanol (102 mg, 0,670 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (156 mg, 0,650 mmol) was heated at the boil under reflux for 2 days in an atmosphere of argon. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added a mixture of 1 N. chloride-hydrogen acid/ethanol and the mixture was concentrated under reduced pressure. The residue was washed with diethyl ether. To the residue was added saturated aqueous sodium bicarbonate solution followed by extraction with ethyl acetate. After drying the organic layer over anhydrous sodium sulfate, the solvent conc who was narrowly under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel. From the faction, elyuirovaniya a mixture of methanol:methylene chloride (=1:50)were specified in the title compound (38 mg) as a pale yellow oil.

IR (ATR) ν: 2929, 2873, 1575, 1477, 1425, 1394, 1276, 1178, 1132, 1083, 1012, 964, 908, 823, 757, 711, 651, 622, 563, 518, 458 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,35-of 1.52 (2H, m), 1,80-1,99 (2H, m), 2,13-of 2.26 (1H, m), 2.49 USD at 2.59 (1H, m), is 2.88 (3H, s), 2,90-to 2.99 (2H, m), of 4.05 (1H, DD, J=11,1, 4.0 Hz), 7,30 (1H, DD, J=7,8, and 4.9 Hz), 7,38-of 7.48 (4H, m), of 7.64 (1H, dt, J=8,1,2,0 Hz), 8,16 (1H, d, J=2.0 Hz), to 8.57 (1H, DD, J=4,8, 1,6 Hz).

MS (m/z): 402 (M++H).

HRMS (FAB) for C17H21O4NClS2(M++H).

Calculated: 402,0601.

Found: 402,0596.

Example 74: 4-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]pyridine

4-chlorobenzenesulfonate sodium (207 mg, 1.04 mmol), hydrochloride of 3-chloromethylpyridine (171 mg, 1.04 mmol) and potassium acetate (204 mg, of 2.08 mmol) was added to n-butanol (5 ml). The resulting mixture was stirred at 70°C for 5 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel and the fractions elyuirovaniya a mixture of hexane:ethyl shall zitat (=2:3), received a white solid (117 mg).

Then a solution in toluene (10 ml) of the obtained solid (52 mg), 4-(methylsulphonyl)-1-butanol (90 mg, 0,592 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (140 mg, 0,582 mmol) was heated at the boil under reflux for 2 days in an atmosphere of argon. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added a mixture of 1 N. chloride-hydrogen acid/ethanol. After concentration under reduced pressure the residue was washed with diethyl ether. To the residue was added saturated aqueous sodium bicarbonate solution followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was concentrated under reduced pressure. The residue was subjected to medium pressure chromatography on a column of silica gel and the fractions elyuirovaniya a mixture of methanol:methylene chloride (=1:50)were specified in the title compound as a white solid (62 mg).

Melting point: 181,0-182,0°C.

IR (ATR) ν: 2942, 2863, 1590, 1467, 1415, 1311, 1272, 1241, 1201, 1147, 1085, 1002, 960, 908, 831, 755, 703, 632, 568, 530, 476, 453 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,30-of 1.53 (2H, m), 1,76 of 1.99 (2H, m), 2,10-of 2.25 (1H, m), 2.40 a-to 2.57 (1H, m), is 2.88 (3H, s), 2,90-to 3.02 (2H, m)4,00 (1H, DD, J=11,1, 4.0 Hz), 6,95-to 7.09 (2H, m), 7,32-of 7.55 (4H, m), 8,43 at 8.60 (2H, m).

MS (m/z): 402 (M++H).

Elemental analysis for C17H20NClO4S2.

Calculated: C 50,80%; H 5,02%; N 3,48%; Cl 8,82%; S 15,96%.

Found: C 50,70%; H 4.93 Per Cent; N 3,55%; Cl 8,10%; S 15,83%.

Example 75: 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]quinoline

4-chlorobenzenesulfonate sodium (196 mg, 0,987 mmol), hydrochloride of 2-chloromethylpyridine (211 mg, 0,987 mmol) and potassium acetate (194 mg, 1.97 mmol) was added to n-butanol (5 ml). The resulting mixture was stirred at 70°C for 5 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The residue obtained by concentration of the filtrate under reduced pressure was subjected to chromatography on a column of silica gel and the fractions elyuirovaniya a mixture of hexane:ethyl acetate (=1:1), obtained white solid (97 mg).

Then a solution in toluene (10 ml) of the obtained solid (42 mg), 4-(methylsulphonyl)-1-butanol (104 mg, 0,684 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (160 mg, 0,666 mmol) was heated at the boil under reflux for 2 days in an atmosphere of argon. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The balance of what was vergili the medium pressure chromatography on a column of silica gel, and from the faction, elyuirovaniya a mixture of hexane:ethyl acetate (=1:3)were specified in the title compound (49 mg) as a colourless oil.

IR (ATR) ν: 2931, 2869, 1596, 1581, 1504, 1463, 1428, 1394, 1297, 1278, 1133, 1083, 1012, 960, 875, 829, 755, 705, 663, 624, 568, 516, 457 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,30-1,60 (2H, m), 1,79-of 1.95 (2H, m), 2.40 a-2,50 (2H, m), and 2.83 (3H, s), only 2.91 (2H, t, J=7.2 Hz), to 4.52 (1H, DD, J=9,9, a 5.3 Hz), 7,28-to 7.32 (2H, m), 7,39-7,46 (2H, m), 7,55-to 7.61 (2H, m), to 7.67-7,73 (1H, m,), to 7.77-7,87 (2H, m), 8,19 (1H, d, J=8.6 Hz).

MS (m/z): 452 (M++H).

HRMS (FAB) for C21H23O4NClS2(m++H).

Calculated: 452,0757.

Found: 452,0744.

Example 76: 4-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-1,2-differenza

4-chlorobenzenesulfonate sodium (45 mg, 0,227 mmol) and 3,4-differenziale (29 mg, 0,227 mmol) was added to dimethoxyethane (5 ml). The resulting mixture was stirred at 70°C for 24 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. Thus obtained residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the ether eluate was concentrated under reduced pressure. A solution of the residue in toluene (5 ml), 4-(methylsulphonyl)-1-butanol (1 mg, 0,454 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (110 mg, 0,454 mmol) was heated at the boil under reflux for 16 hours in an argon atmosphere. After cooling to room temperature was added 4-(methylsulphonyl)-1-butanol (71 mg, 0,454 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (110 mg, 0,454 mmol) followed by heating at boiling under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:3)was concentrated under reduced pressure to obtain specified in the title compound (12 mg, 12%) as a white solid. The solid was washed with hexane-ether and collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 122-124°C.

IR (ATR) ν: 2940, 2873, 1610, 1575, 1519, 1467, 1434, 1394, 1317, 1280, 1268, 1205, 1145, 1126, 1083, 1012, 962, 877, 819, 765, 754, 707, 632, 592, 549, 526, 514, 507, 484, 451, 404 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,32 of 1.50 (2H, m), 1,79-of 1.97 (2H, m), 2,03-to 2.18 (1H, m), 2.40 a-2,50 (1H, m), is 2.88 (3H, c), 2,90-of 3.00 (2H, m), 3,98 (1H, DD, J=11,0, 3,9 Hz), 6,77-for 6.81 (1H, m), 6,99-7,10 (2H, m), 7,38-7,53 (4H, m).

MS (m/z): 437 (the ++H).

HRMS (FAB) for C18H20O4ClF2S2(M++H).

Calculated: 437,0460.

Found: 437,0494.

Example 77: 1-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-2,3-differenza

To dimethoxyethane (5 ml) was added 4-chlorobenzenesulfonate sodium (45 mg, 0,227 mmol) and 2,3-differenziale (29 μl, 0,227 mmol). The resulting mixture was stirred at 70°C for 24 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. The fraction obtained from the ether eluate was concentrated under reduced pressure. A solution of the residue in toluene (10 ml), 4-(methylsulphonyl)-1-butanol (71 mg, 0,454 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (110 mg, 0,454 mmol) was heated at the boil under reflux for 15 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of 55% ethyl acetate/hexane, koncentrirane and under reduced pressure to obtain specified in the title compound (37 mg, 37%) as a white solid. The solid was washed with hexane-ether and filtered to obtain specified in the title compound as a white powder.

Melting point: 141-143°C.

IR (ATR) ν: 2948, 2867, 1625, 1575, 1484, 1396, 1317, 1272, 1230, 1199, 1149, 1124, 1085, 1012, 966, 935, 894, 808, 761, 717, 659, 628, 584, 547, 518, 472, 443 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,37-to 1.60 (2H, m), 1,81 is 1.96 (2H, m), 2,11-of 2.25 (1H, m), 2,45-to 2.57 (1H, m), is 2.88 (3H, s), 2,96 (2H, t, J=7.9 Hz), a 4.53 (1H, DD, J=11,1, 4.0 Hz), 7,10-7,19 (2H, m), 7,22-7,33 (1H, m), 7,39-7,44 (2H, m,), 7,49-rate of 7.54 (2H, m).

MS (m/z): 437 (M++H).

Elemental analysis for C18H19ClF2O4S2.

Calculated: C 49,48%; H Of 4.38%; Cl 8,11%; F 8,70%; S 14,68%.

Found: C 49,38%; H 4,34%; Cl 8,13%; F 8,60%; S 14,56%.

Example 78: 1-chloro-3-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-2-torbenson

To dimethoxyethane (5 ml) was added 3-chlorobenzenesulfonate sodium (45 mg, 0,227 mmol) and 3-chloro-2-florantyrone (51 mg, 0,227 mmol). The resulting mixture was stirred at 70°C for 24 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the ether eluate, the end of which was tarawali under reduced pressure. Solution in toluene (5 ml) of the obtained residue, 4-(methylsulphonyl)-1-butanol (71 mg, 0,454 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (110 mg, 0,454 mmol) was heated at the boil under reflux for 5 days in an atmosphere of argon. After cooling to room temperature, to the reaction mixture were added 4-(methylsulphonyl)-1-butanol (71 mg, 0,454 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (110 mg, 0,454 mmol) followed by heating at boiling under reflux for 12.5 hours in argon atmosphere. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (42 mg, 41%) as a white solid. The obtained solid was washed with hexane-ether and collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 131-132°C.

IR (ATR) ν: 3038, 2938, 1579, 1459, 1392, 1313, 1286, 1234, 1151, 1120, 1085, 1010, 966, 914, 811, 750, 719, 671, 620, 584, 522, 458 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,33-to 1.60 (2H, m), 1,80-to 1.98 (2H, m), 2,11-of 2.25 (1H, m), 2,42-of 2.56 (1H, m), and 2.8 (3H, c), 2,96 (2H, t, J=7.9 Hz), a 4.53 (1H, DD, J=11,1, a 4.3 Hz), 7,11-7,20 (1H, m), 7,33-7,46 (4H, m), 7,46-7,56 (2H, m).

MS (m/z): 453 (M++H).

Elemental analysis for C18H19Cl2FO4S2.

Calculated: C 47,69%; H 4,22%; Cl 15,64%; F 4,19%; S 14,15%.

Found: C 47,40%; H 4,18%; Cl 15,42%; F 4,16%; S 14,08%.

Example 79: 4-chloro-2-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-1-torbenson

To dimethoxyethane (5 ml) was added 4-chlorobenzenesulfonate sodium (45 mg, 0,227 mmol) and 2-methyl bromide-4-chloro-1-torbenson (51 mg, 0,227 mmol). The resulting mixture was stirred at 70°C for 24 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the ether eluate was concentrated under reduced pressure. Solution in toluene (5 ml) thus obtained residue, 4-(methylsulphonyl)-1-butanol (71 mg, 0,454 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (110 mg, 0,454 mmol) was heated at the boil under reflux for 16 hours in an argon atmosphere. After cooling to room temperature, to the reaction mixture were added 4-(methylsulphonyl-1-butanol (71 mg, 0,454 mmol) and cyanomethylene-n-butylphosphate (110 mg, 0,454 mmol) followed by heating at boiling under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (53 mg, 51%) as a white solid. The obtained solid was washed with hexane-ether and collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 116-117°C.

IR (ATR) ν: 3097, 2946, 1577, 1490, 1407, 1317, 1278, 1240, 1174, 1147, 1083, 1047, 1012, 956, 916, 881, 823, 754, 711, 649, 626, 566, 538, 474, 433 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,38-of 1.52 (2H, m), 1,81 of 1.99 (2H, m), 2,09-of 2.21 (1H, m), 2,45-to 2.57 (1H, m), 2,89 (3H, s), 2.91 in-to 3.02 (2H, m), 4,48-a 4.53 (1H, m), 6,83 (1H, t, J=8,9 Hz), 7.23 percent-7,30 (1H, m), 7,38 was 7.45 (2H, m), 7,46-to 7.59 (3H, m).

MS (m/z): 453 (M++H).

Elemental analysis for C18H19Cl2FO4S2.

Calculated: C 47,69%; H 4,22%; Cl 15,64%; F 4,19%; S 14,15%.

Found: C 47,52%; H 4,19%; Cl 15,47%; F 4,24%; S 14,08%.

Reference example 7: 1-iodine-4-(methylsulphonyl)Bhutan

Iodine (1,87 g of 7.35 mmol) was added to the solution in the stands who chloride (30 ml) of 4-(methylsulphonyl)-1-butanol (746 mg, the 4.90 mmol)obtained in reference example 3, imidazole (500 mg, of 7.35 mmol), and triphenylphosphine (1,93 g of 7.35 mmol)and the resulting mixture was stirred for 3 hours at room temperature. To the reaction mixture were added saturated aqueous solution of sodium thiosulfate. The resulting mixture was extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of methanol:methylene chloride (=1:100), concentrated under reduced pressure to obtain specified in the title compound (1.18 g, 92%) as a pale yellow solid.

1H-NMR (400 MHz, CDCl3) δ: 1,92-of 2.08 (4H, m), with 2.93 (3H, s), 3.00 and-3,10 (2H, m), 3,18 of 3.28 (2H, m).

MS (m/z): 263 (M++H).

Example 80: 2-(4-chlorophenylsulfonyl)-1,3-differenza

To dimethoxyethane (10 ml) was added 4-chlorobenzenesulfonate sodium (205 mg, of 1.03 mmol) and 2,6-differenziale (214 mg, of 1.03 mmol). The resulting mixture was stirred at 70°C for 18 hours. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the resulting mixture was filtered, the insoluble substance. The filtrate koncentrira is whether under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the ether eluate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=10:1), concentrated under reduced pressure to obtain specified in the title compound (289 mg, 93%) as a white solid.

IR (ATR) ν: 3097, 2989, 1625, 1575, 1509, 1473, 1407, 1392, 1319, 1272, 1245, 1197, 1182, 1132, 1083, 998, 889, 854, 831, 802, 777, 742, 719, 686, 626, 566, 512, 478, 449, 418 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 4,48 (2H, s), to 6.88 (2H, t, J=7.9 Hz), 7,29-7,39 (1H, m), 7,47 (2H, d, J=8.6 Hz), to 7.68 (2H, d, J=8.6 Hz).

MS (m/z): 303 (M++H).

Example 81: 2-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-1,3-differenza

At -78°utility (1.57 M solution in hexane; 0,55 ml, 0,864 mmol) was added dropwise to the solution in dimethoxyethane (10 ml) of 2-(4-chlorophenylsulfonyl)-1,3-diferente (218 mg, determined as 0.720 mmol). After stirring at -78°C for 30 minutes was added dropwise a solution of dimethoxyethane (5 ml), 1-iodine-4-(methylsulphonyl)butane (226 mg, 0,864 mmol)obtained in reference example 7. The temperature of the reaction mixture was raised gradually to room temperature, and at room temperature the mixture was stirred for 15 hours. To the reaction mixture we use is water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of 55% ethyl acetate/hexane, concentrated under reduced pressure to obtain specified in the title compound (53 mg, 17%) as a white solid. The obtained solid was washed with hexane and collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 118-119°C.

IR (ATR) ν: 2946, 1621, 1585, 1471, 1459, 1396, 1355, 1322, 1301, 1274, 1226, 1151, 1132, 1087, 1012, 989, 958, 925, 829, 773, 761, 752, 717, 624, 572, 522, 485, 458, 406 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,35-of 1.55 (2H, m), 1,81-of 1.95 (2H, m), 2,48-of 2.58 (2H, m), is 2.88 (3H, s), 2.91 in-3,10 (2H, m), of 2.97 (1H, DD, J=15,8, 6,7 Hz), 's 6.75 to 7.00 (2H, m), 7,25-to 7.35 (1H, m), 7,42 (2H, d, J=8.6 Hz), 8,30 (2H, d, J=8,3 Hz).

MS (m/z): 437 (M++H).

Elemental analysis for C18H19ClF2O4S2.

Calculated: C 49,48%; H Of 4.38%; Cl 8,11%; F 8,70%; S 14,68%.

Found: C 49,25%; H 4.32 Percent; Cl 8,02%; F 8,50%; S 14,70%.

Example 82: 1-(4-chlorophenylsulfonyl)-3-methoxybenzoyl

Suspension in dimethoxyethane (10 ml) 4-chlorobenzenesulfonate sodium (210 mg, 1.06 mmol) is 3-methoxybenzylamine (154 μl, 1.06 mmol) was stirred at 70°C for 16 hours. After cooling to room temperature was added butanol (2 ml) and tetrabutylammonium (45 mg), and the resulting mixture was stirred further at 70°C for 16 hours. After cooling the reaction mixture to room temperature, the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate. The mixture was washed successively with water and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=5:1), concentrated under reduced pressure to obtain specified in the title compound (216 mg, 69%) as a white solid.

IR (ATR) ν: 3064, 2979, 2842, 1598, 1488, 1469, 1434, 1392, 1313, 1268, 1176, 1130, 1085, 1033, 1012, 941, 879, 823, 792, 765, 742, 692, 620, 574, 528, 455 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 3,74 (3H, s), 4,27 (2H, s), 6,59 of 6.68 (2H, m), 6,82-of 6.90 (1H, m), 7,17 (1H, t, J=7.8 Hz), 7,42 (2H, d, J=8.6 Hz), 7,56 (2H, d, J=8.6 Hz).

MS (m/z): 297 (M++H).

Example 83: 1-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-3-methoxybenzoyl

Solution in toluene (10 ml) of 1-(4-chlorophenylsulfonyl)-3-methoxybenzene (80 mg, 0,269 mmol), 4-(methylsulphonyl)-butanol (62 mg, 0,404 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (98 mg, 0,404 mmol) was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of ethyl acetate/hexane (=1:1), concentrated under reduced pressure to obtain specified in the title compound (61 mg, 52%) as a white solid. The solid is washed with hexane and collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 91-93°C.

IR (ATR) ν: 2967, 2929, 1594, 1494, 1469, 1455, 1394, 1315, 1272, 1255, 1222, 1189, 1145, 1132, 1085, 1037, 1012, 970, 879, 850, 804, 759, 705, 688, 632, 603, 532, 493, 464 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,37 of 1.50 (2H, m), 1,79-of 1.93 (2H, m), 2,10-of 2.23 (1H, m), 2.40 a-2,52 (1H, m), of 2.86 (3H, s), 2,89 are 2.98 (2H, m), of 3.73 (3H, s), of 3.97 (1H, DD, J=11,1, 3.8 Hz), 6,59 is 6.67 (2H, m), 6,80-6,89 (1H, m), 7,15 (1H, d, J=8.0 Hz), 7,35 (2H, d, J=8.6 Hz), 7,44 (2H, d, J=8.6 Hz).

MS (m/z): 431 (M++H).

Elemental analysis for C19H23ClO5S2.

Calculated: C 52,95%; H 5,38%; Cl 8,23%; S 14,88%.

Found: C 52,89%; H 5,25%; Cl 8,33%; S 14,87%.

Example 84: 1-(4-chlorophenylsulfonyl)-4-methoxybenzoyl

Suspension in butanol (5 ml) of 4-chlorobenzenesulfonate sodium (264 mg, of 1.33 mmol), 4-methoxybenzylamine (181 μl, of 1.33 mmol) and tetrabutylammonium (24 mg) was stirred at 70°C for 3 days. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the mixture was washed successively with water and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=5:1), concentrated under reduced pressure to obtain specified in the title compound (90 mg, 23%) as a white solid.

IR (ATR) ν: 3072, 2996, 2942, 2836, 1608, 1583, 1509, 1467, 1396, 1309, 1292, 1240, 1176, 1147, 1089, 1031, 1016, 977, 956, 887, 829, 767, 715, 630, 532, 474, 431 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 3.80 (3H, s), 4,25 (2H, s), to 6.80 (2H, d, J=8,8 Hz), 7,00 (2H, d, J=8.6 Hz), 7,42 (2H, d, J=8,3 Hz), 7,54 (2H, d, J=8.6 Hz).

Example 85: 1-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-4-methoxybenzoyl

Solution in toluene (10 ml) of 1-(4-chlorophenylsulfonyl)-4-methoxybenzene (72 mg, 0,243 mmol), 4-(methylsulphonyl)-1-butanol (70 mg, 0,460 mmol)obtained in reference example 3, and cyanomethylene-n-BU is infostrada (111 mg, 0,460 mmol) was heated at the boil under reflux for 15 hours in an argon atmosphere. After cooling to room temperature, to the reaction mixture were added 4-(methylsulphonyl)-1-butanol (70 mg, 0,460 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (111 mg, 0,460 mmol)and the mixture was heated at the boil under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (33 mg, 32%) as a white solid. The obtained white solid was washed with hexane and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 136-138°C.

IR (ATR) ν: 3012, 2937, 1608, 1583, 1511, 1471, 1392, 1319, 1292, 1268, 1253, 1178, 1145, 1130, 1085, 1029, 1012, 964, 833, 823, 771, 754, 723, 628, 574, 551, 530, 497, 472, 439 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,37 of 1.50 (2H, m), 1,79-of 1.93 (2H, m), 2,10-of 2.23 (1H, m), 2.40 a-2,52 (1H, m), of 2.86 (3H, s), 2,89 are 2.98 (2H, m), of 3.73 (3H, s), of 3.97 (1H, DD, J=11,1, 3.8 Hz), 6,59 is 6.67 (2H, m), 6,80-6,89 (1H, m), 7,15 (1H, d, J=8.0 Hz), 7,35 (2H, d, J=8.6 Hz), 7,44 (2H, d, J=8.6 Hz).

MS (m/z: 431 (M ++H).

Elemental analysis for C19H23ClO5S2.

Calculated: C 52,95%; H 5,38%; Cl 8,23%; S 14,88%.

Found: C 52,99%; H Of 5.29%; Cl 8,29%; S 14,82%.

Referential example 8: Methyl-3-(N,N-dimethylcarbamoyl)benzoate

To a solution in methylene chloride (20 ml) monomethylaniline (317 mg, of 1.76 mmol) was added dimethylamine hydrochloride (172 mg, 2,11 mmol), 1-hydroxybenzotriazole (287 mg, of 1.76 mmol), hydrochloride of 1-ethyl-3-(2-dimethylaminopropyl)carbodiimide (404 mg, 2,11 mmol) and N-methylmorpholin (0,23 ml, 2,11 mmol)and the resulting mixture was stirred at room temperature for 21 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate. The resulting mixture was washed successively 1 N. chloride-hydrogen acid, saturated aqueous sodium bicarbonate and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of methanol:methylene chloride (=1:50), concentrated under reduced pressure to obtain specified in the title compound (290 mg, 80%) as a colourless oil.

IR (ATR) ν: 1720, 1633, 1583, 1500, 1436, 1392, 1286, 1255, 1205, 1112, 1076, 979, 933, 823, 773, 730, 696, 669, 638, 580, 489, 439 cm-1.

1 H-NMR (400 MHz, CDCl3) δ: 2,99 (3H, s), of 3.13 (3H, s), 3,93 (3H, s), 7,49 (1H, t, J=8,2 Hz), 7,63 (1H, t, J=7,6 Hz), 8,05-of 8.15 (2H, m).

MS (m/z): 208 (M++H).

Referential example 9: 3-hydroxymethyl-N,N-dimethylbenzamide

While cooling on ice, sodium borohydride (264 mg, 6,97 mmol) was added to a solution in ethanol (15 ml) of methyl-3-(N,N-dimethylcarbamoyl)benzoate (289 mg, of 1.39 mmol). The temperature of the resulting mixture was allowed to rise again to room temperature, and then stirring was carried out at 50°C for 14 hours. After cooling the reaction mixture back to room temperature, cooled on ice. Was added sodium borohydride (264 mg, 6,97 mmol)and the mixture was stirred at 50°C for 6 hours. The reaction mixture was cooled on ice, and then added water, followed by concentration under reduced pressure. To the thus obtained residue was added water, followed by extraction with methylene chloride. The extract was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of methanol:methylene chloride (=1:30), concentrated under reduced pressure to obtain specified in the title compound (196 mg, 79%) as a colourless oil.

IR (ATR) ν: 3367, 2929, 269, 1600, 1583, 1508, 1479, 1452, 1394, 1267, 1236, 1170, 1097, 1079, 1049, 898, 800, 746, 719, 694, 642, 431 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 2,46 (1H, Sirs), of 2.97 (3H, s), 3,11 (3H, s), of 4.67 (2H, sird, J=2,9 Hz), 7.23 percent-of 7.48 (4H, m).

MS (m/z): 180 (M++H).

Example 86: 3-(4-chlorophenylsulfonyl)-N,N-dimethylbenzamide

To a solution in methylene chloride (15 ml) of 3-hydroxymethyl-N,N-dimethylbenzamide (184 mg, of 1.03 mmol) was added tetrabromide carbon (511 mg, of 1.59 mmol) and triphenylphosphine (404 mg, 1.54 mmol). The resulting mixture was stirred at room temperature for 4.5 hours. The reaction mixture was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1) was concentrated under reduced pressure to obtain a colorless oil (239 mg).

Suspension in dimethoxyethane (15 ml) of the obtained colorless oil (239 mg, 0,987 mmol) and 4-chlorobenzenesulfonate sodium (234 mg, 1.18 mmol) was stirred at 70°C for 3 days. After cooling the reaction mixture to room temperature, the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate, and the mixture was washed successively with water and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated at below the nom pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of 70% ethyl acetate/hexane, concentrated under reduced pressure to obtain specified in the title compound (125 mg, 37%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 2,89 (3H, s)to 3.09 (3H, s), 4,32 (2H, s), 7,10-to 7.50 (6H, m), to 7.59 (2H, d, J=8.6 Hz).

MS (m/z): 338 (M++H).

Example 87: 3-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-N,N-dimethylbenzamide

Solution in toluene (10 ml) of 3-(4-chlorophenylsulfonyl)-N,N-dimethylbenzamide (69 mg, 0,204 mmol), 4-(methylsulphonyl)-1-butanol (62 mg, 0,409 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (99 mg, 0,409 mmol) was heated at the boil under reflux for 15 hours in an argon atmosphere. After cooling to room temperature was added 4-(methylsulphonyl)-1-butanol (62 mg, 0,504 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (99 mg, 0,504 mmol). The reaction mixture was heated at the boil under reflux for 23 hours in argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using the receiving methanol:methylene chloride (=1:50), concentrated under reduced pressure to obtain specified in the title compound (37 mg, 38%) as an amorphous substance.

IR (ATR) ν: 2927, 1625, 1581, 1504, 1475, 1394, 1276, 1172, 1141, 1083, 1012, 964, 908, 819, 754, 705, 626, 551, 516, 468 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,32-1,49 (2H, m), 1,78-of 1.92 (2H, m), 2,12-of 2.28 (1H, m), 2.40 a-2,50 (1H, m), and 2.83 (3H, Sirs), 2,87 (3H, s), 2,90 are 2.98 (2H, m), is 3.08 (3H, Sirs), of 4.05 (1H, DD, J=11,1, 3.8 Hz), 7,12 (1H, Sirs), 7,19-of 7.25 (1H, m,), 7,32-7,40 (4H, m), of 7.48 (2H, d, J=8.6 Hz).

MS (m/z): 472 (M++H).

HRMS (FAB) for C21H27O5NClS2(M++H).

Calculated: 472,1019.

Found: 472,1010.

Example 88: 2-(4-chlorophenylsulfonyl)-N,N-dimethylbenzamide

To a solution in methanol (5 ml) phthalide (639 mg, 4.76 mmol) was added 50% aqueous solution (2 ml) of dimethylamine, and the mixture was stirred at 70°C for 14 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added methylene chloride. The mixture was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of methanol:methylene chloride (=1:40), concentrated under reduced pressure to obtain a colorless oil (248 mg, 29%). To a solution in methylene chloride (10 ml) bestsitegames (238 mg, of 1.33 mmol) was added triphenylphosphine (522 mg, 1,99 mmol) and tetrabromide carbon (660 mg, 1,99 mmol)and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=3:2)was concentrated under reduced pressure. The residue was dissolved in butanol (10 ml) and then added to a solution of 4-chlorobenzenesulfonate sodium (264 mg, of 1.33 mmol). The mixture was stirred at 70°C for 2 days. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate, followed by successive washing with water and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate with hexane:ethyl acetate (=3:2)was concentrated under reduced pressure to obtain specified in the title compound (216 mg, 48%) as an amorphous substance.

1H-NMR (400 MHz, CDCl3) δ: of 2.97 (3H, s), of 3.13 (3H, s)to 7.50 (2H, d, J=8,8 Hz), 7,73 (2H, d, J=8.6 Hz).

IR (ATR) ν: 2931, 1621, 1598, 1581, 1504, 1475, 1444, 1392, 1317, 1278, 1191, 1151, 1083, 1068, 1012, 879, 827, 777, 757, 740, 705, 636, 607, 56, 536, 466, 447 cm-1.

MS (m/z): 338 (M++H).

Example 89: 2-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-N,N-dimethylbenzamide

Solution in toluene (5 ml) of 2-(4-chlorophenylsulfonyl)-N,N-dimethylbenzamide (161 mg, 0,477 mmol), 4-(methylsulphonyl)-1-butanol (100 mg, 0,657 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (159 mg, 0,657 mmol) was heated at the boil under reflux for 17 hours in an argon atmosphere. After cooling to room temperature was added 4-(methylsulphonyl)-1-butanol (100 mg, 0,657 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (159 mg, 0,657 mmol). The mixture was heated at the boil under reflux for 24 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of 80% ethyl acetate/hexane, concentrated under reduced pressure to obtain specified in the title compound (79 mg, 35%) as an amorphous substance.

1H-NMR (400 MHz, CDCl3) δ: 1,25-for 1.49 (2H, m), 1,63 and 1.80 (1H, m), 1,80-of 1.93 (1H, m), 2.00 in of 2.20 (2H, m), was 2.76-2.95 points (2H, m), 2,82 (3H, s)2,84 (3H, s), 3,11 (3H, s), 4,70-4,82 (1H, m), 7,22 (1H, d, J=7,3 Hz), 7,32-7,46 (3H, m), 7,49 (2H, d, J=8.6 Hz), 7,63 (2H, d, J=8.6 Hz).

And the (ATR) ν : 2931, 2873, 1621, 1581, 1506, 1475, 1448, 1394, 1278, 1222, 1182, 1137, 1083, 1012, 962, 823, 755, 707, 630, 561, 518, 460 cm-1.

MS: 472 (M++H).

HRMS (FAB) for C21H27O5NClS2(M++H).

Calculated: 472,1019.

Found: 472,1023.

Example 90: 3-(4-chlorophenylsulfonyl)benzonitrile

Suspension in dimethoxyethane (15 ml) of 4-chlorobenzenesulfonate sodium (270 mg, of 1.36 mmol) and 3-bromomethylbiphenyl (222 μl, 1.13 mmol) was stirred at 70°C for 3 days. After cooling to room temperature the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate. The mixture was washed successively with water and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=3:1), concentrated under reduced pressure to obtain specified in the title compound (318 mg, 96%) as a white solid.

IR (ATR) ν: 3087, 2985, 2229, 1581, 1581, 1475, 1432, 1394, 1317, 1282, 1265, 1228, 1145, 1081, 1012, 929, 904, 885, 844, 811, 798, 763, 723, 686, 651, 626, 578, 545, 522, 484, 462 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 4,32 (2H, s), 7,38-7,52 (5H, m), 7,60 (2H, d, J=8,8 Hz), 7,66 (1H, d, J=7,6 Hz).

MS (m/z): 292 (M++H).

Example 91: 3-[1-[(4-chlorophenyl)with Lionel]-5-(methylsulphonyl)pentyl]benzonitrile

Solution in toluene (10 ml) of 3-(4-chlorophenylsulfonyl)benzonitrile (60 mg, 0,204 mmol), 4-(methylsulphonyl)-1-butanol (62 mg, 0,409 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (99 mg, 0,409 mmol) was heated at the boil under reflux for 15 hours in an argon atmosphere. After cooling to room temperature was added 4-(methylsulphonyl)-1-butanol (62 mg, 0,504 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (99 mg, 0,504 mmol) followed by heating at boiling under reflux for 23 hours in argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:2)was concentrated under reduced pressure to obtain specified in the title compound (69 mg, 79%) as an amorphous substance.

IR (ATR) ν: 2931, 2229, 1579, 1475, 1432, 1394, 1278, 1137, 1083, 1051, 1012, 964, 914, 813, 752, 688, 649, 613, 549, 516, 466 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,30-1,50 (2H, m), 1,79-of 1.97 (2H, m), 2,10-2,22 (1H, m), 2.40 a is 2.51 (1H, m), 2,89 (3H, s), 2,90-of 3.00 (2H, m)4,06 (1H, DD, J=11,1, 4.0 Hz), 7,35 is 7.50 (7H, m), of 7.64 (1H, d, J=7,3 Hz).

MS (m/z): 426 (M++H).

Elemental analysis for C19H20ClNO4 2·0,25H2O.

Calculated: C 53,02%; H 4,80%; Cl 8,24%; N, 3.25%Milkfat; S 14.90 Per Cent.

Found: C 52,94%; H 4,85%; Cl 8,54%; N, 3.25%Milkfat; S 14,93%.

Example 92: 2-(4-chlorophenylsulfonyl)benzonitrile

Suspension in dimethoxyethane (5 ml) of 4-chlorobenzenesulfonate sodium (218 mg, 1.10 mmol) and 2-bromomethylbiphenyl (215 mg, 1.10 mmol) was stirred at 70°C for 17 hours. After cooling the reaction mixture to room temperature, the solvent was concentrated under reduced pressure. Thus obtained residue was subjected to chromatography on a short column of silica gel, and the fraction obtained from the ether eluate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=3:1), concentrated under reduced pressure to obtain white solid. The obtained white solid was washed with ether and collected by filtration to obtain specified in the title compound (226 mg, 70%) as a white powder.

IR (ATR) ν: 3079, 2979, 2227, 1573, 1488, 1473, 1450, 1425, 1392, 1321, 1299, 1280, 1253, 1209, 1174, 1143, 1081, 1010, 946, 904, 879, 829, 781, 759, 711, 682, 632, 593, 532, 480, 451 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 4,58 (2H, s), 7,43-7,51 (3H, m), 7,56-to 7.68 (5H, m).

Example 93: 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzonitrile

Solution in toluene (5 ml) of 2-(4-chlorophenylsulfonyl)benzonitrile (96 mg, 0,329 mmol), 4-(methylsulphonyl)-1-butanol (100 mg, 0,657 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (159 mg, 0,657 mmol) was heated at the boil under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of 60% ethyl acetate/hexane, concentrated under reduced pressure to obtain specified in the title compound (139 mg, 99%) as an amorphous substance.

IR (ATR) ν: 3089, 2931, 2225, 1575, 1475, 1448, 1394, 1315, 1295, 1278, 1214, 1176, 1139, 1124, 1083, 1012, 962, 908, 827, 794, 754, 711, 628, 553, 516, 470 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,30-and 1.54 (2H, m), 1,81-to 1.98 (2H, m), 2,20-2,31 (1H, m), 2,47 at 2.59 (1H, m), is 2.88 (3H, s), 2,90-of 3.00 (2H, m), 4,63 (1H, DD, J=11,0, 4,2 Hz), 7,38-of 7.60 (6H, m), to 7.67-7,73 (1H, m), 7,79 (1H, d, J=8,1 Hz).

MS (m/z): 426 (M++H).

HRMS (FAB) for C19H21O4NClS2(M++H).

Calculated: 426,0601.

Found: 426,0636.

Example 94: 1-chloro-4-(cyclohexanesulfonyl)benzene

To a solution in acetonitrile (10 ml) 4-chlorbenzoyl (230 mg, of 1.59 mmol) and cyclohexylethylamine (222 μl, of 1.59 mmol) was added potassium carbonate (329 mg, 2,38 the mole), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added hexane, and the insoluble substance was filtered. The filtrate was concentrated under reduced pressure. Thus obtained residue was dissolved in methylene chloride (20 ml) followed by addition of 3-chloroperbenzoic acid (576 mg, to 3.34 mmol). The mixture was stirred at room temperature for 17.5 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate, and the mixture was washed successively with saturated aqueous sodium bicarbonate solution and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was dissolved in methylene chloride. To the resulting solution was added 1 N. aqueous sodium hydroxide solution to separate the organic layer. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=15:1), concentrated under reduced pressure to obtain specified in the title compound (301 mg, 69%) as a white solid.

p> IR (ATR) ν: 2921, 2850, 1583, 1475, 1446, 1394, 1305, 1274, 1172, 1143, 1083, 1014, 964, 892, 846, 831, 782, 761, 744, 703, 669, 632, 559, 528, 478, 426 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,00-of 1.35 (5H, m), 1,60 to 1.76 (3H, m), 1,80-of 2.08 (3H, m), 2,97 (2H, d, J=6,1 Hz), 7,54 (2H, d, J=8.6 Hz), the 7.85 (2H, d, J=8.6 Hz).

MS (m/z): 273 (M++H).

Example 95: 1-chloro-4-[1-cyclohexyl-5-(methylsulphonyl)peterculter]benzene

At -78°utility (1.57 M solution in hexane; of 0.60 ml, 0,937 mmol) was added dropwise to the solution in dimethoxyethane (3 ml) of 1-chloro-4-(cyclohexanesulfonyl)benzene (213 mg, 0,781 mmol). After stirring at -78°C for 40 minutes, was added dropwise a solution of dimethoxyethane (5 ml), 1-iodine-4-(methylsulphonyl)butane (246 mg, 0,937 mmol)obtained in reference example 7. The temperature of the reaction mixture was raised gradually to room temperature, and at room temperature, stirring was carried out for 3 hours. To the reaction mixture were added water and then extracted with ethyl acetate. The organic layer was washed with saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced Yes the tion. The residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (54 mg, 17%) as a white solid. The obtained solid was washed with hexane and collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 104-106°C.

IR (ATR) ν: 2925, 2854, 1583, 1475, 1444, 1423, 1392, 1309, 1288, 1268, 1209, 1176, 1145, 1133, 1128, 1083, 1012, 960, 892, 825, 763, 727, 636, 609, 561, 528, 495, 478, 453, 430 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,02-1,32 (5H, m), 1,44 is 2.00 (12H, m), was 2.76-and 2.83 (1H, m), 2,89 (3H, s), of 2.97 (2H, t, J=7.0 Hz), 7,56 (2H, d, J=8,3 Hz), 7,82 (2H, d, J=8,3 Hz).

MS (m/z): 407 (M++H).

Elemental analysis for C18H27ClO4S2.

Calculated: C 53,12%; H, 6.69 Per Cent; Cl 8,71%; S 15,76%.

Found: C 53,11%; H Of 6.49%; Cl 8,83%; S 15,73%.

Example 96: 1-chloro-4-(2-phenylethylamine)benzene

To a solution in acetonitrile (10 ml) 4-chlorbenzoyl (347 mg, of 2.40 mmol) and (2-bromacil)benzene (329 μl, of 2.40 mmol) was added potassium carbonate (498 mg, of 3.60 mmol). The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added hexane, and the insoluble substance was filtered. The filtrate was concentrated under reduced pressure. Received the same the way the residue was dissolved in methylene chloride (20 ml). To the resulting solution was added 3-chloroperbenzoic acid (870 mg, 5,04 mmol)and the mixture was stirred at room temperature for 19 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate. The mixture was washed successively with saturated aqueous sodium bicarbonate solution and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was dissolved in methylene chloride and then adding 1 N. aqueous sodium hydroxide solution to separate the organic layer. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=10:1), concentrated under reduced pressure to obtain specified in the title compound (599 mg, 89%) as a white solid.

IR (ATR) ν: 3023, 2923, 1600, 1581, 1496, 1473, 1454, 1394, 1299, 1276, 1240, 1145, 1083, 1012, 971, 908, 823, 777, 755, 732, 694, 636, 593, 570, 526, 455 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 2,98-3,10 (2H, m), 3,29-of 3.42 (2H, m), 7,02-to 7.32 (5H, m), 7,55 (2H, d, J=8.6 Hz), 7,86 (2H, d, J=8,5 Hz).

MS (m/z): 281 (M++H).

Example 97: 4-[1-benzyl-5-(metalinsulator)peterculter]-1-chlorobenzene

At -78°utility (1.57 M solution in hexane; or 0.57 ml, 0,902 mmol) was added dropwise to the solution in dimethoxyethane (3 ml) of 1-chloro-4-(2-phenylethylamine)benzene (211 mg, 0,752 mmol). After stirring at -78°C for 1 hour was added dropwise a solution of dimethoxyethane (6 ml), 1-iodine-4-(methylsulphonyl)butane (236 mg, 0,902 mmol)obtained in reference example 7. The temperature of the reaction mixture was raised gradually to room temperature, and at room temperature, stirring was carried out for 3 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure. The residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (72 mg, 23%) as a white solid. The obtained solid was washed with hexane and collected by filtration to obtain specified in the title compound as a white powder is A.

Melting point: 68-70°C.

IR (ATR) ν: 3029, 2937, 2867, 1581, 1496, 1421, 1394, 1303, 1280, 1253, 1187, 1133, 1083, 1041, 1012, 964, 848, 825, 759, 690, 649, 588, 553, 522, 493, 455 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,40-1,77 (5H, m), 1,82 is 1.96 (1H, m), 2,60-2,70 (1H, m), 2,75-only 2.91 (2H, m), and 2.83 (3H, s), 3,18 to be 3.29 (2H, m),? 7.04 baby mortality (2H, d, J=8,3 Hz), 7,19-7,31 (3H, m), 7,56 (2H, d, J=8.6 Hz), to 7.84 (2H, d, J=8,6 Hz).

MS (m/z): 415 (M++H).

Elemental analysis for C19H23ClO4S2.

Calculated: C 54,99%; H 5,59%; Cl 8,54%; S 15,45%.

Found: C 55,10%; H 5,62%; Cl 8,50%; S 15,56%.

Reference example 10: (2-chloropyridin-3-yl)methanol

At -78°With diisobutylaluminium (1.0 M solution in toluene; and 4.68 ml) was added dropwise to a solution in methylene chloride (10 ml) of ethyl-2-chloronicotinate (347 mg, of 1.87 mmol). After thirty minutes the reaction mixture was cooled on ice, followed by stirring for 15 minutes. After confirming completion of the reaction to the reaction mixture were added a saturated solution of salt, and the temperature of the resulting mixture was allowed to rise to room temperature. The reaction mixture was filtered through celite. The filtrate was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under ponie nom pressure obtaining specified in the title compound (211 mg, 79%) as a white solid.

IR (ATR) ν: 3245, 2827, 1587, 1571, 1452, 1407, 1324, 1251, 1193, 1118, 1087, 1041, 796, 732, 713, 655, 593, 511, 466, 414 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 2.21 (1H, t, J=5.6 Hz), 4,80 (2H, d, J=5,1 Hz), 7,25 and 7.36 (1H, m), a 7.85-7,98 (1H, m), 8,32 (1H, DD, J=4,6, 1.5 Hz).

MS (m/z): 144 (M++H).

Example 98: 2-chloro-3-(4-chlorophenylsulfonyl)pyridine

The solution in chloroform (10 ml) (2-chloropyridin-3-yl)methanol (204 mg, of 1.42 ml) and thionyl chloride (0.31 in ml, 4.26 deaths mmol) was stirred at 50aboutWith over 8.5 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was dissolved in butanol (15 ml) followed by addition of 4-chlorobenzenesulfonate sodium (423 mg, 2,13 mmol) and potassium acetate (418 mg, 4.26 deaths mmol). The mixture was stirred at 70-80°C for 15 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate, and the mixture was washed successively with saturated aqueous sodium bicarbonate solution and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:1), koncentrira is whether under reduced pressure to obtain specified in the title compound (252 mg, 59%) as a white solid.

IR (ATR) ν: 3093, 2992, 2931, 1579, 1562, 1473, 1450, 1407, 1321, 1278, 1249, 1195, 1153, 1133, 1116, 1083, 1060, 1010, 962, 887, 840, 813, 759, 719, 686, 636, 566, 541, 501, 466, 441 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 4.54 (2H, s), 7,33 (1H, DD, J=8,8, 4,8 Hz), 7,46 (2H, d, J=8.6 Hz), 7,58 (2H, d, J=8,3 Hz), 7,92 (1H, DD, J=7,7, 1.8 Hz), 8,39 (1H, DD, J=4,8, 1.8 Hz).

MS (m/z): 302 (M++H).

Example 99: 2-chloro-3-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]pyridine

Solution in toluene (10 ml) of 2-chloro-3-(4-chlorophenylsulfonyl)pyridine (56 mg, 0,184 mmol), 4-(methylsulphonyl)-1-butanol (56 mg, 0,368 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (89 mg, 0,368 mmol) was heated at the boil under reflux for 19 hours in an argon atmosphere. After cooling to room temperature, to the reaction mixture were added 4-(methylsulphonyl)-1-butanol (56 mg, 0,368 mmol) and cyanomethylene-n-butylphosphate (89 mg, 0,368 mmol) followed by heating at boiling under reflux for 5 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:2)was concentrated under reduced pressure to obtain decree of the frame in the title compound (76 mg, 95%) as an amorphous substance.

IR (ATR) ν: 3085, 2931, 1579, 1562, 1475, 1407, 1278, 1184, 1139, 1083, 1012, 962, 908, 821, 752, 732, 690, 626, 574, 520, 466 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,32-of 1.55 (2H, m), 1,80-1,99 (2H, m), 2,10-of 2.25 (1H, m), 2.40 a-2,63 (1H, m), is 2.88 (3H, s), 2,96 (2H, t, J=7.8 Hz), 4,79 (1H, DD, J=11,0, 4,2 Hz), 7,32-7,42 (3H, m), of 7.48 (2H, d, J=8,3 Hz), of 8.04 (1H, DD, J=7,8) and 1.7 Hz), at 8.36 (1H, DD, J=4,8, 1.8 Hz).

MS (m/z): 436 (M++H).

HRMS (FAB) for C17H20O4NCl2S2(M++H).

Calculated: 436,0211.

Found: 436,0195.

Referential example 11: (2-herperidin-3-yl)methanol

While cooling on ice trimethylsilyldiazomethane (to 0.72 ml) was added to a solution of 2-fornicating acid (210 mg, 1,49 mmol) in tetrahydrofuran (15 ml) and methanol (1 ml)and the mixture was stirred for 30 minutes. The reaction mixture was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=4:1), concentrated under reduced pressure.

At -78°With diisobutylaluminium (1.0 M solution in toluene and 1.60 ml) was added dropwise to a solution in methylene chloride (10 ml) of the residue (95 mg, 0,612 mmol). Fifteen minutes later the reaction mixture was cooled on ice and was stirred for 15 minutes. After confirming completion of the reaction to the reaction mixture were added a saturated solution with the and, and the temperature of the resulting mixture was allowed to rise again to room temperature. The reaction mixture was filtered through celite. The filtrate was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:1), concentrated under reduced pressure to obtain specified in the title compound (55 mg, 71%) as a white solid.

IR (ATR) ν: 3338, 2873, 1650, 1608, 1430, 1365, 1241, 1176, 1108, 1045, 1020, 858, 800, 775, 744, 619, 572, 539, 520 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 4,78 (2H, s), 7.18 in-to 7.25 (1H, m), a 7.85-of 7.97 (1H, m)to 8.14 (1H, d, J=4,9 Hz).

MS (m/z): 128 (M++H).

Example 100: 3-(4-chlorophenylsulfonyl)-2-herperidin

The solution in chloroform (10 ml) (2-herperidin-3-yl)methanol (49 mg, 0,385 ml) and thionyl chloride (0,14 ml of 1.93 mmol) was stirred at 50°C for 3.5 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. Thus obtained residue was dissolved in butanol (5 ml) followed by addition of 4-chlorobenzenesulfonate sodium (92 mg, 0,462 mmol) and potassium acetate (76 mg, 0,770 mmol). The mixture was stirred at 70-80°C for 12 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate, and the mixture was washed successively with saturated aqueous sodium bicarbonate solution and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:1), concentrated under reduced pressure to obtain specified in the title compound (59 mg, 54%) as a white solid.

IR (ATR) ν: 3097, 2989, 2933, 1643, 1606, 1573, 1469, 1434, 1409, 1392, 1321, 1276, 1240, 1184, 1170, 1149, 1083, 1010, 956, 902, 842, 813, 779, 763, 725, 696, 640, 582, 541, 522, 480, 445 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 4.38 (2H, s), 7,21-7,30 (1H, m), 7,47 (2H, d, J=8,8 Hz), to 7.61 (2H, d, J=8,8 Hz), 7,87-7,94 (1H, m), 8,19-of 8.25 (1H, m).

MS (m/z): 286 (M++H).

Example 101: 3-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]-2-herperidin

Solution in toluene (10 ml) of 3-(4-chlorophenylsulfonyl)-2-herperidin (53 mg, 0.185 mmol), 4-(methylsulphonyl)-1-butanol (56 mg, 0,370 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (89 mg, 0,370 mmol) was heated at the boil under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. About what's headed the remainder was subjected to flash chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:2)was concentrated under reduced pressure to obtain specified in the title compound (42 mg, 54%) as an amorphous substance.

IR (ATR) ν: 3089, 2950, 2865, 1604, 1573, 1467, 1434, 1394, 1313, 1290, 1270, 1249, 1199, 1147, 1126, 1083, 1012, 960, 906, 854, 815, 757, 738, 703, 628, 576, 536, 464, 437 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,38-of 1.55 (2H, m), 1.85 to 1,99 (2H, m), 2,14-of 2.28 (1H, m), 2,45-2,60 (1H, m), is 2.88 (3H, s), 2,96 (2H, t, J=7.8 Hz), 4,46 (1H, DD, J=11,2, 4,2 Hz), 7,25-to 7.32 (1H, m), 7,41 (2H, d, J=8.6 Hz), to 7.50 (2H, d, J=8,3 Hz), 7,98-of 8.04 (1H, m), to 8.20 (1H, d, J=4,9 Hz).

MS (m/z): 420 (M++H).

HRMS (FAB) for C17H20O4NClFS2(M++H).

Calculated: 420,0506.

Found: 420,0509.

Example 102: 2,5-dichloro-3-(4-chlorophenylsulfonyl)pyridine

At -78°With diisobutylaluminium (1 M solution in hexane; 1,92 ml) was added dropwise to a solution in methylene chloride (10 ml) methyl-2,5-dichloronicotinic (188 mg, 0,912 mmol). The resulting mixture was stirred for 30 minutes. To the reaction mixture were added a saturated salt solution, and the mixture was filtered through celite. The filtrate was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=3:1), concentrated the ri reduced pressure. To a solution in chloroform (10 ml) of the residue (128 mg) was added thionyl chloride (0.26 per ml, of 3.60 mmol) followed by stirring at 50aboutC for 6.5 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was dissolved in butanol (10 ml). To the resulting solution were added 4-chlorobenzenesulfonate sodium (171 mg, 0,863 mmol) and potassium acetate (212 mg, of 2.16 mmol)and the mixture was stirred at 70aboutC for 19 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate, and the mixture was washed successively with water and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The obtained solid was washed with hexane-diisopropyl ether and collected by filtration to obtain specified in the title compound (108 mg, 36%) as a white powder.

IR (ATR) ν: 3091, 3064, 2998, 2933, 1581, 1550, 1473, 1419, 1392, 1317, 1280, 1255, 1234, 1170, 1135, 1085, 1068, 1010, 910, 833, 821, 767, 727, 709, 646, 582, 539, 507, 464, 430 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 4.49 (2H, s), 7,49 (2H, d, J=8.6 Hz), a 7.62 (2H, d, J=8,8 Hz), of 7.90 (1H, d, J=2.5 Hz), 8,35 (1H, d, J=2.5 Hz).

MS (m/z): 336 (M++H).

Example 103: 2,5-dichloro-3-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]pyridine

Solution in toluene (10 ml) of 2,5-dichloro-3-(4-chlorophenylsulfonyl)pyridine (70 mg, 0,208 mmol), 4-(methylsulphonyl)-1-butanol (95 mg, 0,624 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (151 mg, 0,624 mmol) was heated at the boil under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (74 mg, 76%) as an amorphous substance.

IR (ATR) ν: 3091, 3060, 2931, 1581, 1546, 1475, 1413, 1313, 1278, 1209, 1124, 1083, 1049, 1012, 964, 906, 871, 831, 754, 705, 628, 588, 532, 468 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,38-of 1.52 (2H, m), 1,83-to 1.98 (2H, m), 2,08-of 2.20 (1H, m), 2,49-2,60 (1H, m), is 2.88 (3H, s), of 2.97 (2H, t, J=7.8 Hz), 4.72 in (1H, DD, J=10,9, 4.0 Hz), the 7.43 (2H, d, J=8.6 Hz), 7,53 (2H, d, J=8.6 Hz), 8,00 (1H, d, J=2.5 Hz), 8,31 (1H, d, J=2.5 Hz).

MS (m/z): 470 (M++H).

Elemental analysis for C17H18Cl3NO4S2·0,25H2O.

Calculated: C 42,96%; H To 3.92%; Cl 22,38%; N 2,95%; S 13,49%.

Found: C 43,02%; H 3,81%; Cl 22,54%; N 3,01%; S 13,50%.

Example 104: 4-chloro-3-(4-chlorophenylsulfonyl)pyridine

Suspension in carbon tetrachloride (15 ml) hydrochloride-chloro-3-methylpyridine (402 mg, 2.45 mmol), imide N-charentenay acid (327 mg, 2.45 mmol) and 2,2'-azobis(2-methylpropionitrile) (30 mg, 0,183 mmol) was heated at the boil under reflux for 13 hours in a nitrogen atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was dissolved in butanol (10 ml) followed by addition of 4-chlorobenzenesulfonate sodium (487 mg, 2.45 mmol) and potassium acetate (481 mg, of 4.90 mmol). The mixture was stirred at 70°C for 24 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate. The mixture was washed successively with saturated aqueous sodium bicarbonate solution and saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:1), concentrated under reduced pressure to obtain specified in the title compound (130 mg, 18%) as a white solid.

IR (ATR) ν: 3060, 2917, 1708, 1573, 1556, 1475, 1413, 1403, 1311, 1280, 1232, 1189, 1155, 1120, 1079, 1012, 933, 890, 854, 833, 817, 777, 744, 721, 694, 632, 574, 557, 514, 460 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 4,56 (2H, s), 7,28 (1H, d, J=5.4 Hz), of 7.48 (2H, d, J=8,3 Hz, 7,63 (2H, d, J=8.5 Hz), 8,49 (1H, d, J=5.4 Hz), 8,54 (1H, s).

MS (m/z): 302 (M++H).

Example 105: 4-chloro-3-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]pyridine

Solution in toluene (10 ml) of 4-chloro-3-(4-chlorophenylsulfonyl)pyridine (80 mg, 0,265 mmol), 4-(methylsulphonyl)-1-butanol (81 mg, 0,529 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (128 mg, 0,529 mmol) was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:5), concentrated under reduced pressure to obtain specified in the title compound (74 mg, 64%) as a white solid. The obtained solid was washed with ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 156-157°C.

IR (ATR) ν: 3087, 3064, 3018, 2933, 1571, 1473, 1409, 1311, 1270, 1207, 1149, 1076, 1014, 968, 906, 831, 794, 752, 700, 617, 576, 536, 497, 466 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,35-to 1.60 (2H, m), 1,80-1,99 (2H, m), 2,20-of 2.33 (1H, m), of 2.51-to 2.65 (1H, m), is 2.88 (3H, s), 2,90-of 3.00 (2H, m), 4,80 (1H, DD, J=10,9, and 3.8 Hz), 7,20 (1H, d, J=5.4 Hz), 7,40 (2H, d, J=8.5 Hz), 7,52 (2H, d, J=8.6 Hz), 8,46 (1H, d, J=5.4 Hz), 8,80 (1H, s).

MS (m/z): 436 (M++H).

Elemental analysis for C17H19Cl2NO4S2.

Calculated: C 46,79%; H 4,39%; Cl 16,25%; N 3,21%; S 14,70%.

Found: C 46,88%; H 4,40%; Cl 16,14%; N 3,30%; S 14,52%.

Example 106: 3-[6-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]hexyl]-2-chloropyridin

Solution in toluene (5 ml) of 2-chloro-3-(4-chlorophenylsulfonyl)pyridine (200 mg, to 0.662 mmol)obtained in example 98, 5-(tert-butyldimethylsilyloxy)pentanol (288 mg, 1,32 mmol) and cyanomethylene-n-butylphosphine (318 mg, 1,32 mmol) was heated at the boil under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of 15% ethyl acetate/hexane, concentrated under reduced pressure to obtain specified in the title compound (307 mg, 92%) as a colourless oil.

IR (ATR) ν: 2929, 2856, 1581, 1562, 1473, 1409, 1394, 1359, 1321, 1278, 1253, 1184, 1149, 1083, 1058, 1012, 985, 921, 833, 775, 752, 734, 690, 626, 570, 534, 466 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 0.01 (6H, s)0,86 (9H, s), 1,12-of 1.50 (6H, m), 2,07-of 2.20 (1H, m), 2,45-to 2.57 (1H, m), 3,53 (2H, t, J=6,1 Hz), 4,78 (1H, DD, J=11,4, and 3.8 Hz), 7,31-7,40 (3H, m), 8,79 (2H, d, J=7.5 Hz), 8,03 (1H, DD, J=7,8, 2.0 Hz), a 8.34 (1H, DD, J=4,6, 2.0 Hz).

MS (m/z): 502 (M +H).

Example 107: 6-(4-chlorophenylsulfonyl)-6-(2-chloropyridin-3-yl)-1-hexanol

While cooling on ice tetrabutylammonium (1 mol/l solution in tetrahydrofuran; 0,70 ml) was added to the solution in tetrahydrofuran (10 ml) of 3-[6-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]hexyl]-2-chloropyridine (294 mg, 0,585 mmol). The resulting mixture was stirred at room temperature for 24 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate, and the mixture was washed with water and saturated salt solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (212 mg, 93%) as a colourless oil.

IR (ATR) ν: 3400, 2933, 2859, 1579, 1562, 1475, 1407, 1394, 1315, 1278, 1184, 1145, 1083, 1058, 1012, 821, 752, 734, 690, 626, 605, 570, 534, 466, 412 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,15-of 1.65 (8H, m), 2,07-of 2.20 (1H, m), 2,47-of 2.58 (1H, m)and 3.59 (2H, t, J=6.4 Hz), 4,79 (1H, DD, J=11,4, and 3.8 Hz), 7,30-7,42 (3H, m), of 7.48 (2H, d, J=8,8 Hz), 8,03 (1H, DD, J=7,8, 2.0 Hz), a 8.34 (1H, DD, J=4,1, 1,7 Hz).

MS (m/z): 388 (M++H).

HRMS (FAB) for C17H20O3NCl2S (M++H).

Calculated 388,0541.

Found: 388,0561.

Example 108: 2-chloro-3-[1-(4-chlorophenylsulfonyl)cycloheptyl]pyridine

At -78°utility (1.57 M solution in hexane; and 0.62 ml, 0,966 mmol) was added dropwise to the solution in dimethoxyethane (5 ml) of 2-chloro-3-(4-chlorophenylsulfonyl)pyridine (146 mg, 0,483 mmol)obtained in example 98. At -78°the resulting mixture was stirred for 20 minutes followed by the addition of 1,6-diiodohexane (0,095 ml, 0,580 mmol). The temperature of the reaction mixture was raised gradually to room temperature, and at room temperature, stirring was carried out for 4 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of 15% ethyl acetate:hexane, concentrated under reduced pressure. Thus obtained residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (60 mg, 32%) as a white solid. The obtained solid vases which was washed with hexane-ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 168-169°C.

IR (ATR) ν: 2929, 2861, 1573, 1558, 1473, 1454, 1394, 1303, 1276, 1139, 1083, 1066, 1008, 840, 800, 748, 711, 646, 613, 574, 522, 470, 412 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,30-1,50 (4H, m), 1,50-of 1.66 (2H, m), 1.85 to to 1.98 (2H, m), 2,33-2,48 (2H, m), 2,94-3,10 (2H, m), 7,28-7,37 (3H, m), 7,40 (2H, d, J=8,8 Hz), to 7.93 (1H, DD, J=8,1) and 1.7 Hz), scored 8.38 (1H, DD, J=4,5, 1.8 Hz).

MS (m/z): 384 (M++H).

Elemental analysis for C18H19Cl2NO2S.

Calculated: C 56,25%; H To 4.98%; Cl Of 18.45%; N 3,64%; S, 8.34 Per Cent.

Found: C 56,20%; H 4,85%; Cl 18,50%; N To 3.73%; S 8,46%.

Example 109: 2-chloro-3-[1-(4-chlorophenylsulfonyl)cyclohexyl]pyridin

At -78°utility (1.57 M solution in hexane; 0,66 ml of 1.03 mmol) was added dropwise to the solution in dimethoxyethane (5 ml) of 2-chloro-3-(4-chlorophenylsulfonyl)pyridine (156 mg, 0,516 mmol)obtained in example 98. At -78°the resulting mixture was stirred for 20 minutes followed by the addition of 1.5-diiodopentane (0,092 ml, 0,619 mmol). The temperature of the reaction mixture was raised gradually to room temperature, and at room temperature, stirring was conducted for 15 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chrome is adopted on a column of silica gel and the fraction, obtained from the eluate using a mixture of 15% ethyl acetate:hexane, concentrated under reduced pressure. Thus obtained residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (72 mg, 38%) as a white solid. The obtained solid was washed with hexane-ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 129-131°C.

IR (ATR) ν: 2929, 2861, 1575, 1558, 1475, 1446, 1392, 1303, 1278, 1143, 1130, 1083, 1054, 1010, 910, 875, 833, 809, 754, 742, 742, 732, 703, 646, 617, 580, 495, 458 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,05-1,30 (2H, m), 1,33 of 1.50 (1H, m), 1,52 is 1.70 (1H, m), 1,75-1,90 (2H, m), 2,02-of 2.30 (2H, m), 2,65-of 3.60 (2H, m), 7,29-7,39 (3H, m), 7,41 (2H, d, J=8,8 Hz), with 8.05 (1H, DD, J=8,1) and 1.7 Hz), 8,39 (1H, DD, J=4,5, 1.8 Hz).

MS (m/z): 370 (M++H).

Elemental analysis for C17H17Cl2NO2S.

Calculated: C 55,14%; H 4,63%; Cl 19,15%; N Of 3.78%; S 8,66%.

Found: C 55,06%; H 4,55%; Cl 19,15%; N A 3.87%; S 8,76%.

Example 110: 4-chloro-3-[1-(4-chlorophenylsulfonyl)cyclohexyl]pyridin

At -78°utility (1.57 M solution in hexane; of 0.58 ml, 0,913 mmol) was added dropwise to the solution in dimethoxyethane (5 ml) of 4-chloro-3-(4-chlorophenylsulfonyl)pyridine (138 mg, 0,457 mmol)obtained in examples is E104. At -78°the resulting mixture was stirred for 20 minutes and then was added 1,5-diiodopentane (0,068 ml, 0,457 mmol). The temperature of the reaction mixture was raised gradually to room temperature, and at room temperature, stirring was carried out for 17 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:1), concentrated under reduced pressure. Thus obtained residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (30 mg, 18%) as a white solid. The obtained solid was washed with ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 145-147°C.

IR (ATR) ν: 2929, 2863, 1579, 1469, 1452, 1392, 1346, 1305, 1280, 1270, 1211, 1143, 1081, 1012, 975, 937, 910, 871, 823, 794, 754, 725, 680, 617, 582, 563, 547, 507, 468 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,10-1,30 (2H, m), 1,32 of 1.50 (1H, m) 1,60 was 1.69 (1H, m), 1,78-1,89 (2H, m), 2,01-2,22 (2H, m), 2.70 height is 3.00 (1H, m), 3,30-3,70 (1H, m), 7.23 percent (1H, d, J=5.4 Hz), 7,35 (2H, d, J=8,8 Hz), 7,40 (2H, d, J=8,8 Hz), to 8.41 (1H, d, J=5,1 Hz), to 8.57 (1H, s).

MS (m/z): 370 (M++H).

Elemental analysis for C17H17Cl2NO2S.

Calculated: C 55,14%; H 4,63%; Cl 19,15%; N Of 3.78%; S 8,66%.

Found: C 54,99%; H Br4.61%; Cl 19,06%; N To 3.89%; S 8,72%.

Example 111: 4-(4-chlorophenylsulfonyl)thiazole

To 1-propanol (10 ml) was added 4-chlorobenzenesulfonate sodium (359 mg, is 1.81 mmol), hydrochloride of 4-(chloromethyl)thiazole (307 mg, is 1.81 mmol) and potassium acetate (354 mg, 3.61 mmol)and the mixture was stirred at 70°C for 21 hours. After cooling the reaction mixture to room temperature, the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate. The mixture was washed successively with water and saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=3:2)was concentrated under reduced pressure. The obtained solid was washed with hexane-ether and then collected by filtration to obtain specified in the title compound (154 mg, 31%) as a white powder.

IR (ATR) ν: 3102, 2969, 2917, 1575, 1504, 1473, 1413, 1396, 1334, 309, 1257, 1220, 1159, 1122, 1081, 1012, 948, 898, 875, 831, 821, 784, 723, 657, 593, 561, 541, 478, 451, 418 cm-1.

1H-NMR (400 MHz, CDCl3) δ: with 4.64 (2H, s), 7,40-to 7.50 (3H, m), a 7.62 (2H, d, J=8,8 Hz), 8,66 (1H, s).

MS (m/z): 274 (M++H).

Example 112: 4-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]thiazole

To butanol (5 ml) was added 4-chlorobenzenesulfonate sodium (113 mg, 0,569 mmol), hydrochloride of 4-(chloromethyl)thiazole (97 mg, 0,569 mmol) and potassium acetate (112 mg, to 1.14 mmol)and the resulting mixture was stirred at 70°C for 11 hours. After cooling the reaction mixture to room temperature, the solvent was concentrated under reduced pressure. To the residue was added ethyl acetate. The resulting mixture was washed with saturated aqueous sodium bicarbonate solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Solution in toluene (10 ml) of the obtained residue, 4-(methylsulphonyl)-1-butanol (130 mg, 0,853 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (206 mg, 0,853 mmol) was heated at the boil under reflux for 15 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate with and is using a mixture of hexane:ethyl acetate (=1:3), concentrated under reduced pressure to obtain specified in the title compound (111 mg, 48%) as a white solid. White solid was washed with hexane-ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 123-125°C.

IR (ATR) ν: 3102, 2937, 1581, 1508, 1475, 1421, 1392, 1311, 1295, 1274, 1234, 1197, 1145, 1130, 1085, 1014, 964, 931, 877, 850, 821, 767, 750, 709, 665, 557, 530, 487, 455, 420 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,35-of 1.55 (2H, m), 1,80-to 1.98 (2H, m), 2,24-2,39 (1H, m), 2,39-of 2.50 (1H, m), 2,87 (3H, s), 2.91 in-a 3.01 (2H, m), 4,48 (1H, DD, J=11,2, 3,9 Hz), 7,38 was 7.45 (3H, m), 7,47 (2H, d, J=8.6 Hz), 8,65 (1H, s).

MS (m/z): 408 (M++H).

Elemental analysis for C15H18ClNO4S3.

Calculated: C 44,16%; H 4,45%; Cl 8,69%; N 3,43%; S 23,58%.

Found: C 44,25%; H 4,34%; Cl 8,58%; N 3,54%; S 23,82%.

Example 113: 5-(4-chlorophenylsulfonyl)thiazole

Suspension in carbon tetrachloride (15 ml) of 5-methylthiazole (380 mg, a 3.83 mmol), imide N-charentenay acid (511 mg, 0,383 mmol), 2,2'-azobis(2-methylpropionitrile) (62 mg, 0,380 mmol) and acetic acid (0,22 ml, a 3.83 mmol) was heated at the boil under reflux for 18 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The obtained residue was dissolved in butanol (10 ml). To the resulting solution is added 4-chlorobenzenesulfonate sodium (761 mg, a 3.83 mmol) and potassium acetate (376 mg, a 3.83 mmol) followed by stirring at 70°C for 23 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate. The mixture was washed successively with water and saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (76 mg, 7,2%) as a pale yellow solid.

IR (ATR) ν: 3085, 2975, 2915, 1671, 1577, 1521, 1473, 1392, 1313, 1253, 1193, 1143, 1081, 1012, 968, 894, 873, 836, 773, 728, 705, 651, 620, 605, 565, 543, 476, 443 cm-1.

1H-NMR (400 MHz, CDCl3) δ: of 4.57 (2H, s), 7,49 (2H, d, J=8,8 Hz), EUR 7.57 (1H, s), the 7.65 (2H, d, J=8.6 Hz), 8,81 (1H, s).

MS (m/z): 274 (M++H).

Example 114: 5-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]thiazole

Solution in toluene (10 ml) of 5-(4-chlorophenylsulfonyl)thiazole (51 mg, 0,186 mmol), 4-(methylsulphonyl)-1-butanol (57 mg, 0,372 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (90 mg, 0,372 mmol) was heated at the boil under reflux for 21 h is in the atmosphere of argon. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of methylene chloride:ethyl acetate (=1:2)was concentrated under reduced pressure to obtain specified in the title compound (53 mg, 70%) as a white solid. The obtained solid was washed with hexane-ether and then filtered to obtain specified in the title compound as a white powder.

Melting point: 95-96°C.

IR (ATR) ν: 3099, 3021, 2942, 1575, 1513, 1473, 1392, 1351, 1299, 1272, 1240, 1201, 1174, 1137, 1085, 1012, 966, 914, 873, 827, 777, 746, 703, 634, 613, 566, 528, 470 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,445-to 1.60 (2H, m), 1,81 of 1.99 (2H, m), 2.00 in a 2.12 (1H, m), 2,50-2,61 (1H, m), 2,89 (3H, s), 2,92-a 3.01 (2H, m)to 4.41 (1H, DD, J=11,1, 3.5 Hz), the 7.43 (2H, d, J=8.5 Hz), 7,47 (1H, s), 7,52 (2H, d, J=8,5 Hz), 8,82 (1H, s).

MS (m/z): 408 (M++H).

Elemental analysis for C15H18ClNO4S3.

Calculated: C 44,16%; H 4,45%; Cl 8,69%; N 3,43%; S 23,58%.

Found: C 44,44%; H Of 4.38%; Cl 8,75%; N 3,53%; S 23,41%.

Reference example 12: Thiazole-2-methanol

While stirring with cooling on ice, sodium borohydride (242 mg, 6,40 mmol) was added to a solution in methanol (10 ml) of 2-formulate (483 mg, 4,27 mmol). After confirming completion of the reaction to the reaction mixture were added in the U. The resulting mixture was concentrated under reduced pressure. To the residue were added water and ethyl acetate to separate an organic layer. The organic layer was washed with saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (324 mg, 66%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: 3,30-3,70 (1H, m), 5,14 (2H, s), 7,32 (1H, d, J=3,4 Hz), 7,74 (1H, d, J=3.2 Hz).

MS (m/z): 116 (M++H).

Example 115: 2-(4-chlorophenylsulfonyl)thiazole

To a solution in chloroform (15 ml) thiazole-2-methanol (171 mg, 1,49 ml) was added thionyl chloride (0.33 ml, 4,47 mmol) and the resulting mixture was stirred at 50°C for 11 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was dissolved in butanol (10 ml). To the resulting solution were added 4-chlorobenzenesulfonate sodium (296 mg, 1,49 mmol) and potassium acetate (292 mg, 2,98 mmol). The mixture was stirred at 70°C for 24 hours. After cooling to room temperature the reaction mixture conc the Wali under reduced pressure. To the residue was added ethyl acetate. The mixture was washed successively with water and saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (169 mg, 41%) as a pale yellow solid.

IR (ATR) ν: 2967, 2913, 1573, 1498, 1475, 1394, 1317, 1280, 1218, 1184, 1147, 1081, 1062, 1012, 966, 887, 825, 775, 763, 730, 700, 630, 599, 563, 549, 478, 447 cm-1.

1H-NMR (400 MHz, CDCl3) δ: rate 4.79 (2H, s), 7,42 (1H, d, J=3.2 Hz), 7,47 (2H, d, J=8.6 Hz), to 7.64 (2H, d, J=8,8 Hz), 7,72 (1H, d, J=3,4 Hz).

MS (m/z): 274 (M++H).

Example 116: 2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]thiazole

Solution in toluene (10 ml) of 2-(4-chlorophenylsulfonyl)thiazole (75 mg, 0,274 mmol), 4-(methylsulphonyl)-1-butanol (83 mg, 0,548 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (132 mg, 0,548 mmol) was heated at the boil under reflux for 20 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel. is raccio, obtained from the eluate using a mixture of methylene chloride:ethyl acetate (=1:2)was concentrated under reduced pressure to obtain specified in the title compound (87 mg, 78%) as a white solid. The obtained solid was washed with ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 118-119°C.

IR (ATR) ν: 3137, 3006, 2913, 1583, 1496, 1471, 1388, 1357, 1315, 1284, 1238, 1203, 1135, 1083, 1043, 1010, 975, 877, 842, 804, 765, 736, 705, 642, 601, 572, 526, 468, 439 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,40-of 1.62 (2H, m), 1,80-1,99 (2H, m), 2,22 to 2.35 (1H, m), 2,48-of 2.58 (1H, m), is 2.88 (3H, s), 2,92-of 3.00 (2H, m), br4.61 (1H, DD, J=11,2, and 3.7 Hz), 7,39-7,47 (3H, m), 7,51 (2H, d, J=8.5 Hz), to 7.68 (1H, d, J=3,4 Hz).

MS (m/z): 408 (M++H).

Elemental analysis for C15H18ClNO4S3.

Calculated: C 44,16%; H 4,45%; Cl 8,69%; N 3,43%; S 23,58%.

Found: C 44,32%; H 4,40%; Cl, A Total Of 8.74%; N 3,54%; S 24,04%.

Example 117: 5-(4-chlorophenylsulfonyl)oxazol

Thionyl chloride (188 μl, 2.57 mmol) was added to a solution in chloroform (10 ml) oxala-5-ylmethanol (85 mg, 0,858 mmol). The resulting mixture was stirred at 50°C for 1.5 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. Thus obtained residue was dissolved in butanol (10 ml). To the resulting solution were added 4-chlorbenzoyl the NAT sodium (170 mg, 0,858 mmol), potassium acetate (252 mg, 2.57 mmol) and tetrabutylammonium (15 mg), followed by stirring at 70°C for 3 days. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. To the residue was added ethyl acetate. The mixture was washed successively with water and saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:1), concentrated under reduced pressure to obtain specified in the title compound (81 mg, 37%) as a white solid.

IR (ATR) ν: 3141, 3085, 2983, 2921, 1475, 1506, 1490, 1475, 1396, 1319, 1284, 1263, 1213, 1178, 1151, 1110, 968, 923, 869, 823, 769, 746, 700, 644, 559, 541, 482, 455, 422 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 4,47 (2H, s), 7,02 (1H, s), 7,52 (2H, d, J=8,8 Hz), of 7.70 (2H, d, J=8,8 Hz), 7,82 (1H, s).

MS (m/z): 258 (M++H).

Example 118: 5-[1-(4-chlorophenylsulfonyl)-5-(methylsulphonyl)pentyl]oxazol

Solution in toluene (10 ml) of 5-(4-chlorophenylsulfonyl)oxazole (65 mg, 0,504 mmol), 4-(methylsulphonyl)-1-butanol (77 mg, 0,504 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphine (122 mg, 0,504 mmol) was heated at the boiling milk products is the first refrigerator for 15 hours in an argon atmosphere. After cooling to room temperature, to the reaction mixture were added 4-(methylsulphonyl)-1-butanol (77 mg, 0,504 mmol)obtained in reference example 3, and cyanomethylene-n-butylphosphate (122 mg, 0,504 mmol) followed by heating at boiling under reflux for 25 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=1:3)was concentrated under reduced pressure to obtain specified in the title compound (82 mg, 83%) as a white solid. The obtained white solid was washed with hexane and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 164-166°C.

IR (ATR) ν: 3139, 2937, 1583, 1504, 1475, 1394, 1311, 1276, 1193, 1147, 1128, 1108, 1085, 1054, 1012, 968, 946, 919, 871, 854, 831, 771, 754, 707, 649, 622, 553, 532, 491, 462 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,43-to 1.60 (2H, m), 1,80-1,99 (2H, m), 2.06 to of 2.20 (1H, m), 2,39-2,49 (1H, m), 2,89 (3H, s), 2,94-a 3.01 (2H, m), the 4.29 (1H, DD, J=11,1, 4.0 Hz), of 6.96 (1H, s)of 7.48 (2H, d, J=8,3 Hz), EUR 7.57 (2H, d, J=8,6 Hz), 7,79 (1H, s).

MS (m/z): 392 (M++H).

Elemental analysis for C15H18ClNO5S2.

Calculated: C 45,97%; H 4,63%; Cl 9,05%; N 3,57%; S 16,36%.

Found: C 45,98%; H 4,79%; l 8,96%; N 3,66%; S 16,29%.

Example 119: 4-(4-chlorophenylsulfonyl)pyridine

When heated solution in 1-propanol (50 ml) of the hydrochloride of 4-chloromethylpyridine (1.26 g, 7,65 mmol), 4-chlorobenzenesulfonate sodium (1.52 g, 7,65 mmol) and potassium acetate (1.50 g, and 15.3 mmol) was stirred at 70°C for 8 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was filtered through a short column (silica gel, ethyl acetate), and the eluate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:3)was concentrated under reduced pressure to obtain specified in the title compound (1.26 g, 62%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: the 4.29 (2H, s), 7,06 (2H, d, J=6,1 Hz), 7,47 (2H, d, J=8,8 Hz), to 7.59 (2H, d, J=8.5 Hz), to 8.57 (2H, d, J=6,1 Hz).

MS (m/z): 268 (M++H).

Example 120: 4-[1-(4-chlorophenylsulfonyl)pentyl]pyridine

At -78°utility (1.57 M solution in hexane; to 0.29 ml, 0,448 mmol) was added dropwise to the solution in tetrahydrofuran (5 ml) of 4-(4-chlorophenylsulfonyl)pyridine (100 mg, 0,374 mmol). At -78°the resulting mixture was stirred for 10 minutes. Then add iodobutane (51 μl, 0,448 mmol). Temp is the temperature of the reaction mixture was raised gradually to room temperature, and at room temperature, stirring was carried out for 16 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated salt solution and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:1), concentrated under reduced pressure to obtain specified in the title compound (76 mg, 63%) as a white solid. The obtained solid was washed with hexane-ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 109-111°C.

IR (ATR) ν: 2933, 2859, 1596, 1575, 1558, 1473, 1415, 1392, 1322, 1280, 1238, 1209, 1172, 1145, 1083, 1010, 991, 970, 885, 844, 821, 767, 754, 730, 703, 667, 630, 599, 565, 520, 466, 410 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 0,84 (3H, t, J=7,3 Hz), 1,09-of 1.40 (4H, m), 2,07-2,10 (1H, m), is 2.37-2.49 USD (1H, m), 3,98 (1H, DD, J=11,6, 3.5 Hz), 7,06 (1H, d, J=6,1 Hz), 7,39 (2H, d, J=8,8 Hz), of 7.48 (2H, d, J=8.6 Hz), 8,53 (2H, d, J=6,1 Hz).

MS (m/z): 324 (M++H).

Elemental analysis for C16H18ClNO2S.

Calculated: C 59,34%; H Ceiling Of 5.60%; Cl 10,95%; N 4,33%; S 9,90%.

Found: C 59,41%; H 5.54 Percent; Cl 11,18%; N 4,47%; S Of 10.09%.

Example 121: 4-[(4-chlorophenylsulfonyl)(cyclopentyl)methyl]pyridine

Solution in toluene (5 ml) of 4-(4-chlorophenylsulfonyl)pyridine (70 mg, 0,261 mmol)obtained in example 119, Cyclopentanol (49 μl, 0,538 mmol) and cyanomethylene-n-butylphosphine (129 mg, 0,538 mmol) was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling to room temperature, to the reaction mixture was added Cyclopentanol (49 μl, 0,538 mmol) and cyanomethylene-n-butylphosphate (129 mg, 0,538 mmol). The mixture was heated at the boil under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:1), concentrated under reduced pressure to obtain specified in the title compound (77 mg, 88%) as a white solid. The obtained white solid was washed with hexane-ether and collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 133-135°C.

IR (ATR) ν: 2960, 2867, 1594, 1577, 1558, 1473, 1415, 1392, 1342, 1319, 1278, 1224, 1143, 1083, 1010, 993, 954, 902, 840, 821, 767, 750, 705, 642, 592, 551, 507, 464 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 0,92-1,08 (1H, m), 1,44 of-1.83 (6H, m), 2,33 at 2.45 (1H, m), 2,78-2,90 (1H, m), 3,88 (1H, d, J=10.3 Hz) 7,03 (2H, d, J=5,1 Hz), 7,32 (2H, d, J=8.6 Hz), the 7.43 (2H, d, J=8.6 Hz), 8,46 (2H, d, J=5.6 Hz).

MS (m/z): 336 (M++H).

Elemental analysis for C17H18ClNO2S.

Calculated: C 60,80%; H 5,40%; Cl 10,56%; N 4,17%; S Of 9.55%.

Found: C 60,76%; H 5,44%; Cl Is 10.68%; N 4,20%; S Being 9.61%.

Example 122: 4-[(4-chlorophenylsulfonyl)(tetrahydropyran-4-yl)methyl]pyridine

Solution in toluene (5 ml) of 4-(4-chlorophenylsulfonyl)pyridine (70 mg, 0,261 mmol)obtained in example 119, tetrahydropyran-4-ol (51 μl, 0,538 mmol) and cyanomethylene-n-butylphosphine (129 mg, 0,538 mmol) was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling to room temperature, to the reaction mixture were added tetrahydropyran-4-ol (51 μl, 0,538 mmol) and cyanomethylene-n-butylphosphate (129 mg, 0,538 mmol) followed by heating at boiling under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate (=2:1), concentrated under reduced pressure to obtain specified in the title compound (65 mg, 71%) as a white solid. The obtained white solid was washed with hexane-EF the R and collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 208-209°C.

IR (ATR) ν: 2846, 1594, 1573, 1560, 1475, 1440, 1417, 1394, 1371, 1315, 1278, 1245, 1211, 1180, 1143, 1083, 989, 877, 835, 773, 752, 703, 630, 603, 565, 524, 478, 451 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,22-of 1.42 (2H, m), 1,60-1,75 (1H, m), 2,30-to 2.40 (1H, m), 2,78-a 3.01 (1H, m)to 3.41 (1H, TD, J=11,7, 2.4 Hz), 3,51 (1H, TD, J=11,9, 2.0 Hz), 3,80-3,93 (1H, m), a 3.87 (1H, d, J=8.6 Hz), 3,98-4,06 (1H, m), 7,00 for 7.12 (2H, m), 7,30 (2H, d, J=8,8 Hz), the 7.43 (2H, d, J=8.6 Hz), of 8.47 (2H, d, J=5.4 Hz).

MS (m/z): 352 (M++H).

Example 123: 4-[(1-benzylpiperidine-4-yl)(4-chlorophenylsulfonyl)methyl]pyridine

Solution in toluene (5 ml) of 4-(4-chlorophenylsulfonyl)pyridine (70 mg, 0,261 mmol)obtained in example 119, 1-benzylpiperidine-4-ol (103 mg, 0,538 mmol) and cyanomethylene-n-butylphosphine (129 mg, 0,538 mmol) was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling to room temperature, to the reaction mixture were added 1-benzylpiperidine-4-ol (103 mg, 0,538 mmol) and cyanomethylene-n-butylphosphate (129 mg, 0,538 mmol) followed by heating at boiling under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel. The fraction obtained from the eluate using a mixture of methanol:methylene chloride (=1:10), concentrated PR is the reduced pressure. Thus obtained residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (40 mg, 35%) as an amorphous substance.

IR (ATR) ν: 2938, 2803, 2763, 1594, 1560, 1475, 1452, 1415, 1367, 1317, 1280, 1218, 1176, 1143, 1085, 1012, 975, 825, 750, 742, 698, 617, 566, 536, 464 cm-1.

1H-NMR (400 MHz, CDCl3) δ: to 1.21 to 1.37 (2H, m), 1,49 is 1.70 (1H, m), 1,92 is 2.01 (1H, m), 2,03 with 2.14 (1H, m), of 2.25 to 2.35 (1H, m), 2,52-to 2.65 (1H, m), 2,79-to 2.85 (1H, m), 2,90-of 3.00 (1H, m), 3,47 (2H, s), 3,86 (1H, d, J=8.1 Hz), 7,02-7,12 (2H, m), 7,20-7,38 (7H, m), the 7.43 (2H, d, J=8.5 Hz), to 8.45 (2H, d, J=5.4 Hz).

MS (m/z): 441 (M++H).

HRMS (FAB): C24H26O2N2ClS (M++H).

Calculated: 441,1404.

Found: 441,1387.

Example 124: 4-[(4-chlorophenylsulfonyl)(1 methylpiperidin-4-yl)methyl]pyridine

Solution in toluene (5 ml) of 4-(4-chlorophenylsulfonyl)pyridine (70 mg, 0,261 mmol)obtained in example 119, 1 methylpiperidin-4-ol (62 μl, 0,538 mmol) and cyanomethylene-n-butylphosphine (129 mg, 0,538 mmol) was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling to room temperature, to the reaction mixture were added 1-methylpiperidin-4-ol (62 μl, 0,538 mmol) and cyanomethylene-n-butylphosphate (129 mg, 0,538 mmol) followed by heating at boiling under reflux in ECENA 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel, and the fraction obtained from the eluate using a mixture of methanol:methylene chloride (=1:50), concentrated under reduced pressure. Thus obtained residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (31 mg, 33%) as a white solid. The obtained solid was washed with hexane-ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 176-177°C.

IR (ATR) ν: 3077, 2935, 2856, 2786, 2740, 1594, 1556, 1465, 1450, 1413, 1380, 1346, 1315, 1280, 1241, 1145, 1085, 1008, 973, 850, 835, 798, 750, 705, 617, 561, 528, 476, 464, 424 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,22-to 1.38 (2H, m), 1.50 is by 1.68 (1H, m), 1,88 of 1.99 (1H, m), 2,00-2,10 (1H, m), of 2.25 (3H, s), 2,30-to 2.40 (1H, m), 2,50-2,63 (1H, m), 2,74-and 2.83 (1H, m), 2,89-2,95 (1H, m), 3,86 (1H, d, J=8,3 Hz), was 7.08 (2H,, d, J=4.6 Hz), 7,30 (2H, d, J=8.6 Hz), 7,44 (2H, d, J=8.6 Hz), 8,46 (2H, d, J=5.6 Hz).

MS (m/z): 365 (M++H).

Elemental analysis for C18H21ClN2O2S.

Calculated: C 59,25%; H 5,80%; Cl 9,72%; N 7,68%; S 8,79%.

Found: C 59,00%; H 5,76%; Cl 9,75%; N To 7.61%; S 8,77%.

Example 125: 4-(4-chlorophenylsulfonyl)-N,N-dimethyl-4-(pyridin-4-yl)butylamine

Solution in toluene (5 ml) of 4-(4-chlorophenylsulfonyl)pyridine (70 mg, 0,261 mmol)obtained in example 119, 3-dimethylamino-1-propanol (62 μl, 0,538 mmol) and cyanomethylene-n-butylphosphine (129 mg, 0,538 mmol) was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling to room temperature, to the reaction mixture were added 3-dimethylaminopropan-1-ol (62 μl, 0,538 mmol) and cyanomethylene-n-butylphosphate (129 mg, 0,538 mmol) followed by heating at boiling under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of methanol:methylene chloride (=1:10), concentrated under reduced pressure. Thus obtained residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (44 mg, 48%) as a white solid. The obtained solid was washed with hexane-ether and then collected by filtration to obtain specified in the title compound as a white powder.

Point PLA is ing: 78-80° C.

IR (ATR) ν: 3089, 2985, 2937, 2809, 2757, 2596, 1587, 1455, 1413, 1392, 1322, 1278, 1203, 1145, 1083, 1041, 1010, 991, 962, 846, 821, 767, 754, 703, 628, 578, 539, 514, 472 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 1,38 was 1.43 (2H, m), 2.05 is-to 2.29 (3H, m), 2,11 (6H, s), 2,39-of 2.50 (1H, m), 4,05 is 4.13 (1H, m), 7,07 (2H, d, J=6,1 Hz), 7,40 (2H, d, J=8.5 Hz), of 7.48 (2H, d, J=8.6 Hz), 8,53 (2H, d, J=6,1 Hz).

MS (m/z): 353 (M++H).

Elemental analysis for C17H21ClN2O2S.

Calculated: C 57,86%; H 6,00%; Cl Of 10.05%; N 7,94%; S Is 9.09%.

Found: C 57,62%; H Of 5.92%; Cl 9,89%; N To $ 7.91%; S 9,12%.

Example 126: 3-(4-chlorophenylsulfonyl)-N,N-dimethyl-3-(pyridin-4-yl)Propylamine

Solution in toluene (5 ml) of 4-(4-chlorophenylsulfonyl)pyridine (70 mg, 0,261 mmol)obtained in example 119, 2-dimethylaminoethanol (54 μl, 0,538 mmol) and cyanomethylene-n-butylphosphine (129 mg, 0,538 mmol) was heated at the boil under reflux for 3 days in an atmosphere of argon. After cooling to room temperature, to the reaction mixture were added 2-dimethylaminoethanol (54 μl, 0,538 mmol) and cyanomethylene-n-butylphosphate (129 mg, 0,538 mmol) followed by heating at boiling under reflux for 22 hours in an argon atmosphere. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using sm is si methanol:methylene chloride (=1:10), concentrated under reduced pressure. Thus obtained residue was purified by high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to obtain the specified title compound (49 mg, 55%) as a white solid. The obtained solid was washed with hexane-ether and then collected by filtration to obtain specified in the title compound as a white powder.

Melting point: 91-92°C.

IR (ATR) ν: 3031, 2975, 2940, 2857, 2821, 2790, 1587, 1575, 1554, 1459, 1413, 1384, 1313, 1280, 1249, 1143, 1083, 1045, 1008, 991, 842, 821, 759, 723, 703, 630, 570, 526, 468 cm-1.

1H-NMR (400 MHz, CDCl3) δ: 2,05-of 2.20 (2H, m), 2,11 (6H, s), 2, 59-2,70 (1H, m), 4,35 (1H, DD, J=10.5V, and 3.2 Hz), 7,11 (2H, d, J=6,1 Hz), 7,39 (2H, d, J=8.6 Hz), to 7.59 (2H, d, J=8.6 Hz), 8,53 (2H, d, J=6,1 Hz).

MS (m/z): 339 (M++H).

Elemental analysis for C16H19ClN2O2S.

Calculated: C 56,71%; H 5,65%; Cl 10,46%; N 8,27%; S 9,46%,

Found: C 56,64%; H 5,61%; Cl 10,51%; N Compared To 8.26%; S To 9.57%.

Reference example 13: 2-[(2,5-differenl)hydroxymethyl]pyridine

In an argon atmosphere a solution in hexane n-utility (1,53M, to 3.92 ml, 6 mmol) was added dropwise to the solution in tetrahydrofuran (10 ml) of 2-bromopyridine (572 μl, 6 mmol) at -78°and the mixture was stirred for 30 minutes. To the resulting brown solution was added dropwise 2.5-differental egid (655 μl, 6 mmol), and the temperature of the mixture was gradually raised to room temperature. To the reaction mixture was added water, followed by extraction with ethyl acetate. After drying of the solvent the residue obtained under reduced pressure, was purified by chromatography on silica gel with obtaining specified in the title compound (120 mg, 9%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: the 5.45 (1H, Shir), between 6.08 (1H, s), 6.87 in-to 7.15 (3H, m), 7,2-7,3 (2H, m), the 7.65 (1H, m), 8,56 (1H, m)

TPL: 65-66°C.

Reference example 14: Hydrochloride of 2-[chloro-(2,5-differenl)methyl]-3-methylpyridine

In an argon atmosphere a solution in tetrahydrofuran (1.5 ml, 3 mmol) isopropylacrylamide was added dropwise to the solution in tetrahydrofuran (2 ml) of 2-bromo-3-methylpyridine (510 mg, 3 mmol) under cooling on ice, and the mixture was stirred at room temperature for 60 minutes. While cooling on ice to the resulting brown solution was added dropwise 2.5-differentally (328 μl, 3 mmol). Then the temperature of the reaction mixture was gradually raised to room temperature. After adding a saturated aqueous solution of ammonium chloride the mixture was extracted with ethyl acetate. After drying of the solvent the residue obtained by concentration under reduced pressure was purified by chromatography on silica gel (Huck is an:ethyl acetate=8:1) to obtain a mixture, containing specified in the header connection. To the mixture was added thionyl chloride (2.0 ml) and a drop of dimethylformamide, followed by stirring at room temperature for 14 hours. Distillation of excess thionyl chloride under reduced pressure gave a white precipitate. The obtained white precipitate was washed with hexane and diethyl ether to obtain specified in the title compound (101 mg, 12%).

1H-NMR (400 MHz, CDCl3) δ: is 2.37 (3H, s), 6,95-7,10 (2H, m), 7,28 (1H, s), 7,7-7,8 (2H, m), 8,11 (1H, d, J=6.3 Hz), 8,72 (1H, d, J=4,9 Hz).

IR (ATR) cm-1: 1612, 1496, 1294, 1232, 821.

TPL: 118-119°C.

MS m/z: 254 (M++H).

Reference example 15: 2-[(2,5-differenl)hydroxymethyl]-5-methylpyridin

In an argon atmosphere a solution in tetrahydrofuran (1.5 ml, 3 mmol) isopropylacrylamide was added dropwise to the solution in tetrahydrofuran (2 ml) of 2-bromo-5-methylpyridine (510 mg, 3 mmol) under ice cooling, and the mixture was stirred at room temperature for 60 minutes. While cooling on ice to the resulting brown solution was added dropwise 2.5-differentally (328 μl, 3 mmol). Then the temperature of the reaction mixture was gradually raised to room temperature. After adding a saturated aqueous solution of ammonium chloride the mixture was extracted with ethyl acetate. After drying of the solvent on who headed the remainder of that obtained by concentration under reduced pressure was purified by chromatography on silica gel (hexane:ethyl acetate=5:1) to obtain the specified title compound (130 mg, 18%) as oil.

1H-NMR (400 MHz, CDCl3) δ: 2,31 (3H, s)5,38 (1H, Shir), 6,04 (1H, s), 6,83-to 7.18 (4H, m), 7,44 (1H, DD, J=2,0, 8.0 Hz), of 8.37 (1H, m).

IR (ATR) cm-1: 1485, 1178, 1132, 814.

MS m/z: 236 (M++H).

Reference example 16: 2-[(2,5-differenl)hydroxymethyl]-4-methylpyridin

In an argon atmosphere a solution in tetrahydrofuran (1.5 ml, 3 mmol) isopropylacrylamide was added dropwise to the solution in tetrahydrofuran (2 ml) of 2-bromo-4-methylpyridine (334 μl, 3 mmol) under cooling on ice, and the mixture was stirred at room temperature for 60 minutes. While cooling on ice to the resulting brown solution was added dropwise 2.5-differentally (328 μl, 3 mmol). Then the temperature of the reaction mixture was gradually raised to room temperature. After adding a saturated aqueous solution of ammonium chloride to the reaction mixture, the resulting mixture was extracted with ethyl acetate. After drying of the solvent the residue obtained by concentration under reduced pressure was purified by chromatography on silica gel (hexane:ethyl acetate=5:1) to obtain the specified title compound (456 mg, 65%) as needle crystals.

1 H-NMR (400 MHz, CDCl3) δ: 2,30 (3H, s), of 5.48 (1H, Sirs), of 6.02 (1H, s), 6,83-7,13 (5H, m), scored 8.38 (1H, m).

IR (ATR) cm-1: 3162, 1610, 1481, 1054, 825.

TPL: 105-106°C.

MS m/z: 236 (M++H).

Reference example 17: 2-bromo-3-methoxypyridine

In the atmosphere of nitrogen, 60% oil dispersion of sodium hydride (605 mg, 15.1 mmol) was added in portions to a methanol (10 ml) under cooling on ice. Twenty minutes later, to the mixture was added to the solution in dimethylformamide (20 ml) of 2-bromo-3-hydroxypyridine (2.5 g, 14.4 mmol). The reaction mixture is kept under reduced pressure to remove methanol and the residue was added methyliodide (0,94 ml, 15.1 mmol). The mixture was stirred at room temperature for 3 hours.

After concentrating the reaction mixture to dryness the residue was added water (50 ml) and ether (50 ml). The organic layer obtained by separation of the layers was washed with saturated aqueous sodium bicarbonate solution and saturated salt solution. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Then the residue was purified by chromatography on silica gel (hexane:ethyl acetate=8:1) to obtain the specified title compound (1.51 g, 56%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 3,90 (3H, s), 7,12 (1H, m), 7,21 (1H, DD, J=4,8, 8.0 Hz), of 7.97 (1H, m).

IR (ATR) cm-1: 1556, 1410, 1076, 1049, 788.

TPL: 34°C.

Reference example 18: 3-allyloxy-2-bromopyridin

Similar to the method used for the synthesis of 2-bromo-3-methoxypyridine specified in the title compound (2.35 g, 76%) was obtained as oil.

1H-NMR (400 MHz, CDCl3) δ: to 4.62 (2H, m), 5,33 (1H, DD, J=1,2, 10.4 Hz), vs. 5.47 (1H, DD, J=1,2, 17.6 Hz), the 6.06 (1H, m), 7,11 (1H, DD, J=1.2 Hz, 8.0 Hz), 7,18 (1H, DD, J=4,8, 8.0 Hz), 7,98 (1H, m).

IR (ATR) cm-1: 1562, 1408, 1282, 1052, 790.

MS m/z: 215 (M++H).

Reference example 19: 2-[(2,5-differenl)hydroxymethyl]-3-methoxypyridine

In an argon atmosphere a solution in tetrahydrofuran (1.5 ml, 3 mmol) isopropylacrylamide was added dropwise to the solution in tetrahydrofuran (2 ml) of 2-bromo-3-methylpyridine (564 mg, 3 mmol) under cooling on ice. The resulting mixture was stirred at room temperature for 60 minutes. While cooling on ice to the resulting brown solution was added dropwise 2.5-differentally (328 μl, 3 mmol). Then the temperature of the reaction mixture was gradually raised to room temperature. To the reaction mixture were added saturated aqueous solution of ammonium chloride followed by extraction with ethyl acetate. The solvent was dried, followed by concentration under reduced pressure to obtain needle-like crystals. The obtained needle-shaped crystals are triturated with Gex is nom obtaining specified in the title compound (660 mg, 88%).

1H-NMR (400 MHz, CDCl3) δ: 3,71 (3H, s)to 5.56 (1H, Shir, J=6.0 Hz), 6,16 (1H, d, J=6.0 Hz), 's 6.75 to 7.00 (3H, m), 7,14 (1H, m), 7,26 (1H, m), 8,18 (1H, m).

IR (ATR) cm-1: 3384, 1577, 1488, 1284, 810.

TPL: 94-95°C.

MS m/z: 252 (M++H).

Reference example 20: 3-allyloxy-2-[(2,5-differenl)hydroxymethyl]pyridine

In an argon atmosphere a solution in tetrahydrofuran (1.5 ml, 3 mmol) isopropylacrylamide was added dropwise to the solution in tetrahydrofuran (2 ml) of 3-allyloxy-2-bromopyridine (642 mg, 3 mmol) under cooling on ice. The resulting mixture was stirred at room temperature for 60 minutes. While cooling on ice to the resulting brown solution was added dropwise 2.5-differentally (328 μl, 3 mmol). Then the temperature of the reaction mixture was gradually raised to room temperature. After adding a saturated aqueous solution of ammonium chloride to the reaction mixture, the resulting mixture was extracted with ethyl acetate. The solvent was dried, followed by concentration under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=4:1) to obtain the specified title compound (375 mg, 45%) as oil.

1H-NMR (400 MHz, CDCl3) δ: of 4.38 (1H, m), of 4.44 (1H, m), 5,16 (1H, m), is 5.18 (1H, m), 5,61 (1H, Shir., J=6.4 Hz), 5,78 (1H, m), 6,17 (1H, d, J=6.0 Hz), 6.73 x-of 6.96 (3H, m), 7,10 (1H, m), 7,22 (1H, is), 8,19 (1H, m).

IR (ATR) cm-1: 3367, 1575, 1490, 1276, 1180, 795.

MS m/z: 278 ( M++H).

Reference example 21: 3-[(2,5-differenl)hydroxymethyl]pyridine

In an argon atmosphere a solution in tetrahydrofuran (1.5 ml, 3 mmol) isopropylacrylamide was added dropwise to the solution in tetrahydrofuran (2 ml) of 3-bromopyridine (286 μl, 3 mmol) under cooling on ice. The resulting mixture was stirred at room temperature for 60 minutes. While cooling on ice to the resulting brown solution was added dropwise 2.5-differentally (328 μl, 3 mmol). Then the temperature of the reaction mixture was gradually raised to room temperature. To the reaction mixture were added saturated aqueous solution of ammonium chloride, and then the mixture was extracted with ethyl acetate. The solvent was dried, followed by concentration under reduced pressure. Thus obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate=1:1) to obtain the specified title compound (296 mg, 45%) as needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 3,76 (1H, W), 6,10 (1H, s), 6,88-6,98 (2H, m), 7,20-7,30 (2H, m), of 7.70 (1H, m), 8,42 (1H, d, J=4,8 Hz), 8,53 (1H, m).

IR (ATR) cm-1: 1486, 1429, 1178, 1130, 739, 707.

TPL: 79-80°C.

Reference example 22: 4-[(2,5-differenl)hydroxymethyl]pyridine

Like what yodice reference example 21, except for using 4-bromopyridine specified in the title compound (79 mg, 8%) was obtained in the form of needle crystals.

1H-NMR (400 MHz, CDCl3) δ: between 6.08 (1H, s), 6.90 to-7,00 (2H, m), to 7.15 (1H, m), 7,32 (1H, DD, J=1,6, and 8.4 Hz), 8,48 (1H, DD, J=1,6, 8,4 Hz).

IR (ATR) cm-1: 1602, 1489, 1415, 1174, 1049, 711.

TPL: 120-121°C.

MS m/z: 221 (M+).

Reference example 23: 5-[(2,5-differenl)hydroxymethyl]pyrimidine

Similar to the method of reference example 21, except for using 5-bromopyrimidine specified in the title compound (117 mg, 18%) was obtained as oil.

1H-NMR (400 MHz, CDCl3) δ: 6,12 (1H, s), 6.90 to-7,02 (2H, m), 7,26 (1H, m), to 8.70 (2H, s), 9,04 (1H, s).

IR (ATR) cm-1: 3219, 1566, 1489, 1408, 1180, 715.

MS m/z: 205 (M+-OH).

Example 127: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]pyridine

2-[(2,5-differenl)hydroxymethyl]pyridine (88 mg, 0.40 mmol)obtained in reference example 13, was dissolved in thionyl chloride (2.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide, followed by stirring for 15 hours.

The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the mixture was concentrated further. The residue was dissolved in dimethylformamide (5 ml) followed by addition of 4-chlorbenzoyl (79 mg, 0.55, which IMO is ü) and potassium carbonate (226 mg, of 1.64 mmol) under nitrogen atmosphere. The resulting mixture was stirred at 50°C for 1 hour. After cooling to room temperature, to the reaction mixture were added diethyl ether (50 ml). The mixture was washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain the specified title compound (128 mg, 92%) as oil.

1H-NMR (400 MHz, CDCl3) δ: of 5.89 (1H, s), 6,80-7,27 (7H, m), 7,38 (1H, d, J=7,6 Hz), of 7.48 (1H, m), the 7.65 (1H, m), 8,63 (1H, m).

IR (ATR) cm-1: 1585, 1488, 1432, 1093, 810.

MS m/z: 348 (M++H).

Example 128: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-3-methylpyridin

To a solution in dimethylformamide (5 ml) of the hydrochloride of 2-[chloro(2,5-differenl)methyl]-3-methylpyridine (94 mg, 0.32 mmol)obtained in reference example 14 was added 4-chlorbenzoyl (70 mg, 0.49 mmol) and potassium carbonate (265 mg, 1.92 mmol) under nitrogen atmosphere. The resulting mixture was stirred at 50°C for 1 hour. After cooling to room temperature, to the reaction mixture were added diethyl ether (50 ml). The resulting mixture was washed with water and saturated salt solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to what cromatografia on silica gel (hexane:ethyl acetate=10:1) to obtain the specified title compound (103 mg, 89%) as oil.

1H-NMR (400 MHz, CDCl3) δ: of 2.21 (3H, s), by 5.87 (1H, s), 6,77 (1H, m), 7,00-7,19 (5H, m), of 7.36 (1H, m), 7,45 (1H, m), to 8.45 (1H, DD, J=1,2, 4,8 Hz).

IR (ATR) cm-1: 1572, 1489, 1093, 810.

MS m/z: 362 (M++H).

Example 129: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-5-methylpyridin

2-[(2,5-differenl)hydroxymethyl]-5-methylpyridin (125 mg, of 0.53 mmol)obtained in reference example 15, was dissolved in thionyl chloride (1.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide, followed by stirring for 14 hours.

The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the mixture was concentrated further. The obtained residue was dissolved in dimethylformamide (5 ml) followed by addition of 4-chlorbenzoyl (115 mg, 0.80 mmol) and potassium carbonate (438 mg, 3,18 mmol) under nitrogen atmosphere. The mixture was stirred at 50°C for 1 hour. After cooling to room temperature, to the reaction mixture were added diethyl ether (50 ml). The mixture was washed with water and saturated salt solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain the specified title compound (120 mg, 66%) as oil.

1H-NMR (400 MHz, CDCl ) δ: to 2.29 (3H, s), of 5.83 (1H, s), 6,80-6,93 (2H, m), 7,16 (2H, m), 7,20 (2H, m), 7,28 (1H, m), the 7.43 (1H, m), to 8.41 (1H, d, J=0.8 Hz).

IR (ATR) cm-1: 1475, 1095, 814.

MS m/z: 362 (M++H).

Example 130: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-4-methylpyridin

2-[(2,5-differenl)hydroxymethyl]-4-methylpyridin (235 mg, of 0.53 mmol)obtained in reference example 16, was dissolved in thionyl chloride (2.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide, and the mixture was stirred for 16 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the mixture was concentrated separately.

The residue was dissolved in dimethylformamide (10 ml) followed by addition of 4-chlorbenzoyl (217 mg, 1.5 mmol) and potassium carbonate (828 mg, 6.0 mmol) under nitrogen atmosphere. The mixture was stirred at 50°C for 1 hour. After cooling to room temperature was added diethyl ether (50 ml)and the mixture was washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain the specified title compound (290 mg, 80%) as oil.

1H-NMR (400 MHz, CDCl3) δ: 2,31 (3H, s), of 5.82 (1H, s), 6,80-7,0 (3H, m), to 7.15 (2H, d, J=8,8 Hz), 7,16 (1H, m), 7,21 (2H, d, J=8,8 Hz), and 7.5 (1H, m)to 8.45 (1H, d, J=5.6 Hz).

IR (ATR) cm-1: 1600, 1489, 1475, 1093, 812.

MS m/z: 362 (M++H).

Example 131: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-3-methoxypyridine

2-[(2,5-differenl)hydroxymethyl]-3-methoxypyridine (251 mg, 1.0 mmol)obtained in reference example 19 was dissolved in thionyl chloride (2.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide, and the mixture was stirred for 16 hours.

The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the mixture was concentrated separately.

The residue was dissolved in dimethylformamide (10 ml) followed by addition of 4-chlorbenzoyl (289 mg, 2.0 mmol) and potassium carbonate (1,10 mg, 8.0 mmol) under nitrogen atmosphere. The resulting mixture was stirred at 50°C for 1 hour. After cooling to room temperature, to the reaction mixture were added diethyl ether (50 ml)and the mixture was washed with water and saturated salt solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain the specified title compound (256 mg, 58%) as oil.

1H-NMR (400 MHz, CDCl3) δ: of 3.77 (3H, s), and 6.25 (1H, s), PC 6.82 (2H, m), to 7.15 (2H, d, J=8,4 Hz), 7,10-7,20 (2H, m), 7,25 (2H, d, J=8,8 Hz), 7,52 (1H, m), 8,24 (1H, m).

IR (ATR) with the -1: 1489, 1423, 1273, 1091, 831.

MS m/z: 378 (M++H).

Example 132: 3 allyloxy-2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]pyridine

3 allyloxy-2-[(2,5-differenl)hydroxymethyl]pyridine (370 mg, of 1.33 mmol)obtained in reference example 20 was dissolved in thionyl chloride (2.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide, followed by stirring for 16 hours.

The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the mixture was concentrated separately.

The residue was dissolved in dimethylformamide (10 ml) followed by addition of 4-chlorbenzoyl (217 mg, 1.5 mmol) and potassium carbonate (828 mg, 6.0 mmol) under nitrogen atmosphere. The mixture was stirred at 50°C for 1 hour. After cooling to room temperature, to the reaction mixture were added diethyl ether (50 ml)and the mixture was washed with water and saturated salt solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain the specified title compound (256 mg, 68%) as oil.

1H-NMR (400 MHz, CDCl3) δ: to 4.46 (2H, m), of 5.24 (1H, d, J=a 10.6 Hz), 5,28 (1H, d, J=and 17.2 Hz), 5,90 (1H, m), of 6.29 (1H, d, J=1.2 Hz), PC 6.82 (2H, m), to 7.15 (2H, d, J=8,4 Hz), 7,06-7,20 (2H, m), from 7.24 (2H, d, J=8,4 Hz)to 7.50 (1H, m), 8,24 (1H, m)

IR (ATR) cm-1: 1572, 1489, 1438, 1276, 1093, 814.

MS m/z: 404 (M++H).

Example 133: 3-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]pyridine

3-[(2,5-differenl)hydroxymethyl]pyridine (87 mg, 0,39 mmol)obtained in reference example 21 was dissolved in thionyl chloride (2.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide, and the mixture was stirred for 14 hours.

The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the mixture was concentrated separately.

Thus obtained residue was dissolved in dimethylformamide (5 ml) followed by addition of 4-chlorbenzoyl (84 mg, of 0.58 mmol) and potassium carbonate (323 mg, 2.34 mmol) under nitrogen atmosphere. The mixture was stirred at 50°C for 1 hour. After cooling to room temperature, to the reaction mixture were added diethyl ether (50 ml)and the mixture was washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel (hexane:ethyl acetate=1:1) to obtain the specified title compound (131 mg, 96%) as oil.

1H-NMR (400 MHz, CDCl3) δ: 5,73 (1H, s), 6,84-of 6.96 (2H, m), 7,18 (2H, m), 7,19 (2H, m), 7,15-7,22 (2H, m), 7,71 (1H, m), 8,49 (1H, DD, J=1,6, 4,8 Hz), 8,58 (1H, d, J=2.0 Hz).

IR (ATR) cm- : 1489, 1093, 814, 710.

MS m/z: 348 (M++H).

Example 134: 5-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]pyrimidine

5-[(2,5-differenl)hydroxymethyl]pyrimidine (111 mg, 0.5 mmol)obtained in reference example 23 was dissolved in thionyl chloride (1.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide, and the mixture was stirred for 16 hours.

The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the mixture was concentrated separately.

The residue was dissolved in dimethylformamide (5 ml) followed by addition of 4-chlorbenzoyl (108 mg, 0.75 mmol) and potassium carbonate (414 mg, 3.0 mmol) under nitrogen atmosphere. The mixture was stirred at 50°C for 1 hour. After cooling to room temperature, to the reaction mixture were added diethyl ether (50 ml)and the mixture was washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel (hexane:ethyl acetate=4:1) mixture (202 mg) specified in the connection header and unidentified compounds in the form of oil.

1H-NMR (400 MHz, CDCl3) δ: to 5.66 (1H, s), of 6.96 (2H, m), 7,17-7,34 (5H, d), to 8.70 (2H, s), which is 9.09 (1H, s).

MS m/z: 349 (M++H).

Example 135: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-di is terphenyl)methyl]pyridine

To a solution in methanol (12 ml) of 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]pyridine (120 mg, 0,345 mmol)obtained in example 127 was added tetrahydrate hexaminolevulinate (80 mg) followed by addition of 30% aqueous hydrogen peroxide (6 ml). The resulting mixture was stirred for 24 hours. Thus obtained precipitate was collected by filtration and recrystallized from ethanol to obtain specified in the title compound (96 mg, 73%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: to 5.93 (1H, s), 6.87 in-7,00 (2H, m), 7,28 (1H, m), 7,37 (2H, d, J=8,8 Hz), 7,53 (2H, d, J=8,8 Hz), 7,60 (1H, d, J=8.0 Hz), 7,71 (1H, m), 8,00 (1H, m), 8,59 (1H, m).

IR (ATR) cm-1: 1585, 1484, 1434, 1321, 1147, 817.

TPL: 171-172°C.

MS m/z: 380 (M++H)

Elemental analysis. Calculated for C18H12ClF2NO2S: C 56,92%; H 3,18%; N 3,69%; S 8,44%; Cl Was 9.33%; F 10,00%. Found: C 56,76%; H 3,19%; N Of 3.77%; S 8,55%; Cl 9,27%; F 10,02%.

Fab-MS: 380,0309 (calculated for C18H13ClF2NO2S: 380,0324).

Example 136: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-3-methylpyridin

Similar to the method of example 135, specified in the title compound (35 mg, 35%) was obtained as colorless needle-like crystals using 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-3-methylpyridine obtained in example 128, and cleaning chromatog what afia on silica gel (hexane:ethyl acetate=5:1).

1H-NMR (400 MHz, CDCl3) δ: a 2.36 (3H, s), 6,18 (1H, s), 6.89 in-7,02 (2H, m), 7,17 (1H, m), 7,37 (2H, d, J=8,4 Hz), 7,46 (1H, d, J=7,2 Hz), 7,53 (2H, d, J=8,4 Hz), of 8.06 (1H, m), 8,53 (1H, d, J=4.0 Hz).

IR (ATR) cm-1: 1571, 1477, 1321, 1151, 1080, 816.

TPL: 142-143°C.

MS m/z: 394 (M++H).

Elemental analysis. Calculated for C19H14ClF2NO2S: C 57,94%; H To 3.58%; N 3,56%; S 8,12%; Cl 9,00%; F 9,65%. Found: C 58,03%; H 3,66%; N Of 3.78%; S 8,12%; Cl 9,13%; F 9,59%.

Example 137: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-5-methylpyridin

Similar to the method of example 135 except using 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-5-methylpyridine obtained in example 129, specified in the title compound (91 mg, 73%) was obtained as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: of 2.33 (3H, s), of 5.89 (1H, s), 6,88-7,01 (2H, m), 7,37 (2H, d, J=8,8 Hz), of 7.48-7,56 (2H, m), 7,53 (2H, d, J=8,8 Hz), to 7.99 (1H, m), 8,42 (1H, s).

IR (ATR) cm-1: 1574, 1477, 1319, 1147, 1093, 822.

TPL: 159-160°C.

MS m/z: 394 (M++H).

Elemental analysis. Calculated for C19H14ClF2NO2S: C 57,94%; H To 3.58%; N 3,56%; S 8,12%; Cl 9,00%; F 9,56%. Found: C 57,88%; H 3,61%; N 3,68%; S Of 8.27%; Cl 9,11%; F 9,70%.

Example 138: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-4-methylpyridin

Similar to the method of example 135, specified in the title compound (140 mg, 95%) was obtained as colorless needle-like crystal is in using 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-4-methylpyridine, obtained in example 130, and purification by chromatography on silica gel (hexane:ethyl acetate=3:1).

1H-NMR (400 MHz, CDCl3) δ: a 2.36 (3H, s), 5,88 (1H, s), 6,88-7,02 (2H, m), to 7.09 (1H, d, J=5,2 Hz), 7,37 (2H, d, J=8,8 Hz), 7,41 (1H, m), 7,52 (2H, d, J=8,8 Hz), of 7.97 (1H, m), 8,43 (1H, d, J=5,2 Hz).

IR (ATR) cm-1: 1600, 1484, 1322, 1149, 1080, 827.

TPL: 116-117°C.

MS m/z: 394 (M++H).

Elemental analysis. Calculated for C19H14ClF2NO2S: C 57,94%; H To 3.58%; N 3,56%; S 8,12%; Cl 9,00%; F 9,65%. Found: C 57,80%; H 3,66%; N, 3.72 Per Cent; S 8,29%; Cl 9,05%; F 9,71%.

Example 139: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-3-methoxypyridine

Similar to the method of example 135, specified in the title compound (71 mg, 87%) was obtained as colorless columnar crystals using 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-3-methoxypyridine obtained in example 131, and recrystallization from ethanol.

1H-NMR (400 MHz, CDCl3) δ: and 3.72 (3H, s), 6,62 (1H, s), 6.90 to? 7.04 baby mortality (2H, m), to 7.09 (1H, m), 7,24 (1H, m), 7,35 (2H, d, J=8,8 Hz), 7,53 (2H, d, J=8,8 Hz), 8,18 (1H, m), 8,30 (1H, m).

IR (ATR) cm-1: 1576, 1491, 1429, 1323, 1281, 1147, 796.

TPL: 184-185°C.

MS m/z: 410 (M++H).

Elemental analysis. Calculated for C19H14ClF2NO3S: C 55,68%; H 3,44%; N 3,42%; S Of 7.82%; Cl 8,65%; F 9,27%. Found: C 55,68%; H 3,45%; N 3,60%; S 7,98%; Cl, A Total Of 8.74%; F 9,23%.

Example 140: 3 allyloxy-2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]pyridine

Similar to the method of example 135, specified in the title compound (135 mg, 80%) was obtained as colorless needle-like crystals synthesis using 3-allyloxy-2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]pyridine obtained in example 132, and crystallization from ethanol.

1H-NMR (400 MHz, CDCl3) δ: of 4.38 (1H, m), 4,46 (1H, m), from 5.29 (1H, DD, J=1,2, 10.4 Hz), to 5.35 (1H, DD, J=1,2, and 17.2 Hz), to 5.93 (1H, m), of 6.68 (1H, s), 6,91? 7.04 baby mortality (2H, m), was 7.08 (1H, m), 7,22 (1H, DD, J=4,8, and 8.4 Hz), 7,34 (2H, d, J=8,8 Hz), 7,53 (2H, d, J=8,8 Hz), 8,17 (1H, m), 8,31 (1H, m).

IR (ATR) cm-1: 1577, 1493, 1319, 1151, 822.

TPL: 119-120°C.

MS m/z: 436 (M++H).

Elemental analysis. Calculated for C21H16ClF2NO3S: C 57,87%; H 3,70%; N 3,21%; S Of 7.36%; Cl 8,13%; F 8,72%. Found: C 57,90%; H 3,75%; N 3,37%; S 7,51%; Cl 8,20%; F 8,73%.

Example 141: 3-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]pyridine

Similar to the method of example 135, specified in the title compound (118 mg, 86%) was obtained as colorless needle-like crystals synthesis using 3-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]pyridine obtained in example 133, and purification by chromatography on silica gel (hexane:ethyl acetate=4:1).

1H-NMR (400 MHz, CDCl3) δ: of 5.68 (1H, s), 6,91-7,07 (2H, m), 7,34 (1H, m), 7,40 (2H, d, J=8,4 Hz), EUR 7.57 (2H, d, J=8,4 Hz), 7,76 (1H, m), of 8.04 (1H, m), 8,53 (1H, d, J=2.0 Hz), 8,59 (1H, m).

IR (ATR) cm-1: 1574, 1491, 1421, 1327, 1144, 816.

TPL: 130-131°C.

MS m/z: 380 (M++H).

elementry analysis. Calculated for C18H12ClF2NO2S: C 56,92%; H 3,18%; N 3,69%; S 8,44%; Cl Was 9.33%; F 10,00%, Found: C 56,87%; H 3,16%; N 3,74%; S 8,51%; Cl 9,34%; F Of 10.00%.

Example 142: 4-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]pyridine

4-[(2,5-differenl)hydroxymethyl]pyridine (75 mg, 0.34 mmol)obtained in reference example 22 was dissolved in thionyl chloride (1.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide. The resulting mixture was stirred for 14 hours.

The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the mixture was concentrated separately.

The residue was dissolved in dimethylformamide (5 ml) followed by addition of 4-chlorbenzoyl (74 mg, 0.51 mmol) and potassium carbonate (281 mg, 2.04 mmol) under nitrogen atmosphere. The mixture was stirred at 50°C for 1 hour. After cooling to room temperature, to the reaction mixture were added diethyl ether (50 ml)and the mixture was washed with water and saturated salt solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel (hexane:ethyl acetate=1:1) to obtain a mixture containing 4-[[(4-chlorophenyl)thio]-(2,5-differenl)]pyridine.

To a solution in methanol (12 ml) of the obtained compound was added tetrahydrate of hexaamminecobalt the date (60 mg) followed by addition of 30% aqueous hydrogen peroxide (6 ml). The resulting mixture was stirred for 65 hours. To the reaction mixture were added ethyl acetate (80 ml). The mixture was washed with water and saturated salt solution and then dried over anhydrous magnesium sulfate. The mixture was concentrated under reduced pressure to remove solvent. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=4:1-1:1) to obtain the specified title compound (51 mg, 39%). The compound was recrystallized from ethanol to obtain colorless needle-like crystals.

1H-NMR (400 MHz, CDCl3) δ: 5,64 (1H, s), 6,91-7,06 (2H, m), 7,40 (2H, d, J=8.0 Hz), was 7.45 (2H, d, J=4,8 Hz), 7,58 (2H, d, J=8.0 Hz), of 7.70 (1H, s), 8,61 (2H, d, J=4,8 Hz).

IR (ATR) cm-1: 1595, 1493, 1315, 1147, 1082, 823.

TPL: 126-127°C.

MS m/z: 380 (M++H).

Elemental analysis. Calculated for C18H12ClF2NO2S: C 56,92%; H 3,18%; N 3,69%; S 8,44%; Cl Was 9.33%; F 10,00%. Found: C 56,66%; H 3,16%; N 3,83%; S 8,58%; Cl To 9.32%; F 9,99%.

Example 143: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]pyrimidine

Similar to the method of example 135, specified in the title compound (71 mg, yield 87%: two stages of 5-[(2,5-differenl)hydroxymethyl]pyrimidine from reference example 23) was obtained as colorless columnar crystals using 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]pyrimidine obtained in example 134, and purification by chromatography on silica gel (hexane:this is the acetate=5:1).

1H-NMR (400 MHz, CDCl3) δ: the 5.65 (1H, s), 6,93-7,10 (2H, m), the 7.43 (2H, d, J=8,8 Hz), to 7.61 (2H, d, J=8,8 Hz), 7,73 (1H, m), of 8.90 (2H, s), of 9.21 (1H, s).

IR (ATR) cm-1: 1560, 1490, 1141, 1080, 825.

TPL: 136-137°C.

MS m/z: 381 (M++H).

Elemental analysis. Calculated for C17H11ClF2N2O2S: C 53,62%; H 2,91%; N Of 7.36%; S 8,42%; Cl 9,31%; F 9,98%. Found: C 53,64%; H 2,83%; N 7,44%; S 8,61%; Cl 9,34%; F 9,96%.

Example 144: 3-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-4-hydroxypropan-2-he

At room temperature, glacial acetic acid (60 mg, 1 mmol) and pyridine (80,5 μl, 1 mmol) was added to a solution in ethanol (4 ml) of 2,5-diferentialglea (109 μl, 1 mmol), 4-hydroxycoumarin (162 mg, 1 mmol) and 4-chlorothiophenol (144,6 mg, 1 mmol)and the mixture was stirred for 24 hours. Thus obtained precipitate was collected by filtration and washed with a small amount of ethanol to obtain specified in the title compound (345 mg, 80%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: 6,16 (1H, s), 6,95 for 7.12 (3H, m), 7.24 to 7,27 (1H, m), 7,27 (2H, d, J=8,8 Hz), 7,32 (1H, t, J=7,6 Hz), the 7.43 (2H, d, J=8,8 Hz), 7,56 (1H, m), 7,94 (1H, DD, J=1,6, 7,6 Hz).

IR (ATR) cm-1: 1668, 1620, 1481, 1194, 818.

TPL: 146-147°C.

MS m/z: 431 (M++H).

Example 145: 3-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-4-methoxypropan-2-on (compound a) and 3-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-2-methoxypropan-4-one (the unity)

To a solution in a mixture of benzene-methanol (10:1) 3-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-4-hydroxypropan-2-she (118 mg, 0,274 mmol) was added to the solution in hexane (0,41 ml, 0,822 mmol) 2 N. trimethylsilyldiazomethane portions at room temperature, and the mixture was stirred for 5 minutes. To the reaction mixture was added acetic acid until then, until the solution became colorless. Then the reaction mixture was concentrated under reduced pressure.

The residue was dissolved in methanol (12 ml) followed by addition of 30% aqueous hydrogen peroxide solution (6 ml) and tetrahydrate hexaminolevulinate (60 mg). The resulting mixture was stirred for 20 hours. To the reaction mixture were added ethyl acetate (50 ml). The mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=5:1-3:1) to obtain the non-polar compound (22 mg, 17%) as needle crystals and polar compounds (9.0 mg, 7%) as white solids after curing hexane. In the NOE-test (nuclear Overhauser effect) in nonpolar compound NOE was observed between the methoxy and 5-hydrogen chromenone. On the other hand, in polar connection NOE was observed between the methoxy and hydrogen aromaticheskim ring chromanone, but observed between methoxy and 6-hydrogen diftorbenzofenon ring. Thus, the structure of non-polar compounds and polar compounds were identified as 3-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-4-methoxypropan-2-on (compound a) and 3-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-2-methoxypropan-4-one (compound), respectively.

Connection And

1H-NMR (400 MHz, CDCl3) δ: 4,13 (3H, s), to 6.39 (1H, s), to 6.88 (1H, m), 6,98 (1H, m), 7.3 to 7.4 (2H, m), the 7.43 (2H, d, J=8,8 Hz), 7,58 (1H, m), of 7.70 (2H, d, J=8,8 Hz), 7,73 (1H, m), of 8.09 (1H, m).

IR (ATR) cm-1: 1726, 1606, 1493, 1360, 1184, 1085, 768.

TPL: 178-179°C.

MS m/z: 477 (M++H).

Elemental analysis. Calculated for C23H15ClF2O3S: C 57,93%; H 3,17%; S 6,72%; Cl 7,43%; F Of 7.97%. Found: C 57,59%; H 3,14%; S 6,85%; Cl 7,52%; F 8,01%,

FAB-MS: 477,0393 (calculated for C23H16ClF2O5S: 477,0375).

Connection

1H-NMR (400 MHz, CDCl3) δ: to 4.23 (3H, s), is 6.54 (1H, s), 6.89 in (1H, m), of 6.96 (1H, m), 7,41 (2H, d, J=8,4 Hz), 7,4-7,46 (2H, m), 7,63 (1H, m), 7,73 (2H, d, J=8,4 Hz), 8,02 (1H, m)to 8.14 (1H, DD, J=1,6, 8.0 Hz).

IR (ATR) cm-1: 1621, 1565, 1461, 1384, 1141, 980.

TPL: 162-163°C.

MS m/z: 477 (M++H).

FAB-MS: 477,0366 (calculated for C23H16ClF2O5S: 477,0375).

Reference example 24: 2-[(tert-butoxycarbonylamino)(2.5-differenl)methyl]-1-methyl-1H-benzimidazole

Solution in acetonitrile (3 ml) of 2,5-diferentialglea (164 μl, 5 mmol), 1-methylbenzimidazole (132 mg, 1 mmol), di-tert-BUTYLCARBAMATE (252 μl, 1.1 mmol) was stirred at room temperature for 20 hours. Formed thus precipitate was collected by filtration and triturated with hexane to obtain specified in the title compound (310 mg, 83%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: of 1.45 (9H, s), 3,86 (3H, s), the 6.9 to 7.0 (2H, m), 7,12 (1H, s), 7,22-to 7.35 (3H, m), 7,45 (1H, m), to 7.77 (1H, d, J=8.0 Hz).

IR (ATR) cm-1: 1733, 1492, 1270, 1257, 1137, 852.

TPL: 163-164°C.

MS m/z: 375 (M++H).

Reference example 25: 2-[(tert-butoxycarbonylamino)(2.5-differenl)methyl]-1-methyl-5-chloro-1H-benzimidazole

Solution in acetonitrile (6 ml) of 2,5-diferentialglea (327 μl, 3 mmol), 5-chloro-1-methylbenzimidazole (187 mg, 2 mmol) and di-tert-BUTYLCARBAMATE (504 μl, 2.2 mmol) was stirred at room temperature for 20 hours. Formed in this way the residue was collected by filtration and triturated with hexane to obtain specified in the title compound (472 mg, 66%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: to 1.48 (9H, s)to 3.67 (3H, s), 6,88 and 7.1 (4H, m), 7,39 (1H, m).

IR (ATR) cm-1: 1739, 1496, 1257, 1149, 1080, 858.

TPL: 125-126°C.

MS m/z: 359 (M++H).

Reference example 26: 2-[(2,5-differenl)hydroxymethyl]thiazole

To the solution of those is rageragerage (10 ml) of 2-bromothiazole (180 mg, 2 mmol) was added dropwise a solution of hexane n-utility (1,57M, 1,40 ml, 2.2 mmol) at -78°C. After stirring for 10 minutes was added 2,5-differentally (238 μl, 2.2 mmol), and under stirring the temperature of the mixture was gradually raised to 0°C. Then the reaction was suppressed by addition of an aqueous solution of ammonium chloride followed by the addition of ether. The ether layer was washed with water and saturated salt solution and then dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=1:1) to obtain the specified title compound (358 mg, 79%) as oil.

1H-NMR (400 MHz, CDCl3) δ: of 3.77 (1H, d, J=4.0 Hz), 6,33 (1H, d, J=4.0 Hz), 6,95-7,10 (2H, m), 7,24 (1H, m), 7,34 (1H, d, J=3.6 Hz), of 7.75 (1H, d, J=3.6 Hz).

IR (ATR) cm-1: 3224, 1489, 1238, 1172, 1128, 818.

MS m/z: 228 (M++H).

Reference example 27: 2-[(tert-butoxycarbonylamino)(2.5-differenl)methyl]-1-(4-methoxyphenyl)-1H-benzimidazole

Solution in acetonitrile (6 ml) of 2,5-diferentialglea (327 μl, 3 mmol), 1-(4-methoxyphenyl)imidazole (348 mg, 2 mmol), di-tert-BUTYLCARBAMATE (504 μl, 2.2 mmol) was stirred at room temperature for 20 hours. The reaction mixture was concentrated and then the residue was purified by chromatography on silica gel (hexane:etelaat is=5:1-1:1) to obtain the specified title compound (774 mg, 93%) in the form of oil

1H-NMR (400 MHz, CDCl3) δ: of 1.40 (9H, s), 3,86 (3H, s)6,76 (1H, s), 6.90 to-7,00 (4H, m), 7,02 (1H, s), 7,11 (1H, s), 7,26 (2H, m), 7,33 (1H, m).

IR (ATR) cm-1: 1741, 1513, 1494, 1243, 1155, 858, 835.

MS m/z: 417 (M++H).

Example 146: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-1-methyl-1H-benzimidazole

Triperoxonane acid (2.0 ml) was added to 2-[(tert-butoxycarbonylamino)(2.5-differenl)methyl]-1-methyl-1H-benzimidazole (204 mg, 0,545 mmol)obtained in reference example 24, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by concentration under reduced pressure.

The residue was dissolved in thionyl chloride (1.0 ml). To the resulting solution was added a drop of dimethylformamide, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by concentration under reduced pressure.

The residue was dissolved in dimethylformamide (5.0 ml). To the resulting solution were added 4-chlorbenzoyl (118 mg, 0.82 mmol) and potassium carbonate (451 mg, of 3.27 mmol)and the mixture was stirred at 50°C for 2 hours. The reaction mixture was allowed to cool to room temperature. Then to the reaction mixture were added ethyl is a new ether (60 ml). The mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=10:1-5:1) to obtain the specified title compound (195 mg, 89%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: to 3.67 (3H, s), 5,91 (1H, s), 6.87 in-6,93 (2H, m), 7,19 (2H, d, J=8,8 Hz), 7,27 (2H, d, J=8,8 Hz), 7,25-7,33 (3H, m), 7,60 (1H, m), a 7.85 (1H, m).

IR (ATR) cm-1: 1492, 1388, 1238, 193, 820.

MS m/z: 401 (M++H).

Example 147: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-1-methyl-5-chloro-1H-imidazol

Triperoxonane acid (10 ml) was added to 2-[(tert-butoxycarbonylamino)(2.5-differenl)methyl]-1-methyl-5-chloro-1H-imidazole (404 mg, 1.13 mmol)obtained in reference example 25, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by concentration under reduced pressure.

The residue was dissolved in thionyl chloride (2.0 ml). To the resulting solution was added a drop of dimethylformamide, and the mixture was stirred at room temperature for 17 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by concentration under reduced pressure.

The remainder of the Rast is oral in dimethylformamide (5.0 ml). To the resulting solution were added 4-chlorbenzoyl (244 mg, was 1.69 mmol) and potassium carbonate (936 mg, of 6.78 mmol). The mixture was stirred at 50°C for 2 hours. The reaction mixture was allowed to cool to room temperature and then was added ethyl ether (60 ml). The mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=10:1-5:1) to obtain the specified title compound (195 mg, 89%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: of 3.57 (3H, s), 5,67 (1H, s), 6.89 in-6,95 (2H, m), 6,97 (1H, s), 7,20 (2H, d, J=8,4 Hz), 7,21 (2H, d, J=8,4 Hz), 7,54 (1H, m).

IR (ATR) cm-1: 1490, 1473, 1162, 1012, 821, 806.

MS m/z: 386 (M++H).

Example 148: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]thiazole

In thionyl chloride (1.5 ml) was dissolved 2-[(2,5-differenl)hydroxymethyl]thiazole (348 mg, 1.53 mmol)obtained in reference example 26. To the resulting solution was added a drop of dimethylformamide, and the mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by concentration under reduced pressure.

The residue was dissolved in dimethylformamide (10.0 ml). To the resulting solution were added 4-chlorbenzoyl (332 m is, 2.3 mmol) and potassium carbonate (845 mg, 6.12 mmol)and the mixture was stirred at 50°C for 2 hours. The reaction mixture was allowed to cool to room temperature and then was added ethyl ether (60 ml). The mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=10:1-6:1) to obtain the specified title compound (130 mg, 24%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 6,04 (1H, s), 6.90 to-7,06 (2H, m), 7,22 (2H, d, J=8,4 Hz), 7,30 (2H, d, J=8,4 Hz), 7,15-to 7.35 (2H, m), 7,76 (1H, d, J=3.2 Hz).

IR (ATR) cm-1: 1489, 1475, 1093, 1012, 817, 725.

MS m/z: 354 (M++H).

Example 149: 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-1-(4-methoxyphenyl)-1H-imidazol

Triperoxonane acid (10 ml) was added to 2-[(tert-butoxycarbonylamino)(2.5-differenl)methyl]-1-(4-methoxyphenyl)-1H-imidazole (667 mg, 1.6 mmol)obtained in reference example 27, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by concentration under reduced pressure.

The residue was dissolved in thionyl chloride (2.0 ml)and the resulting solution was added a drop of dimethylformamide. The mixture was stirred at room Tempe is the atur for 17 hours. Then the reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by concentration under reduced pressure.

The residue was dissolved in dimethylformamide (5.0 ml)and the resulting solution was added 4-chlorbenzoyl (347 mg, 2.4 mmol) and potassium carbonate (1,32 mg, 9.6 mmol). The mixture was stirred at 50°C for 2 hours. The reaction mixture was allowed to cool to room temperature and then was added ethyl ether (60 ml). The mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=10:1-5:1) and was led from ethanol to obtain specified in the title compound (535 mg, 75%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 3,86 (3H, s), to 5.57 (1H, s), 6.8 or 6.9 (3H, m)6,91 (2H, d, J=8,4 Hz), 7,00 (2H, d, J=8,4 Hz), 7,06 (2H, d, J=6.8 Hz), 7,11 (2H, d, J=6.8 Hz), 7,16 (1H, s), 7,81 (1H, m).

IR (ATR) cm-1: 1513, 1475, 1240, 1037, 821.

MS m/z: 443 (M++H).

Example 150: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-1-methyl-1H-benzimidazole (compound a) and 2-[[(4-chlorophenyl)sulfinil]-(2,5-differenl)methyl]-1-methyl-1H-benzimidazole (compound)

Tetrahydrate hexaminolevulinate (60 mg) was added to a solution in methanol 2-[[(4-chlorophenyl)thio]-(2,5-is afterfeel)methyl]-1-methyl-1H-benzimidazole (190 mg, 0,474 mmol)obtained in example 146. To the mixture was added 30% aqueous hydrogen peroxide solution (6 ml) followed by stirring for 17 hours. To the reaction mixture were added ethyl acetate (60 ml). The resulting mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane:ethyl acetate=6:1-4:1) to obtain the non-polar compounds (compounds A) (48 mg, 23%) as needle crystals and polar compounds (compounds) (23 mg, 12%) as a white solid.

Connection And

1H-NMR (400 MHz, CDCl3) δ: 3,90 (3H, s), 6,14 (1H, s), 6,9-7,1 (2H, m), 7,26-7,42 (3H, m), 7,39 (2H, d, J=8,8 Hz), 7,46 (2H, d, J=8,8 Hz), 7,81 (1H, d, J=8.0 Hz), 8,16 (1H, m).

IR (ATR) cm-1: 1726, 1606, 1493, 1360, 1184, 1085, 768.

TPL: 213-214°C.

MS m/z: 433 (M++H).

Elemental analysis. Calculated for C21H15ClF2N2OS: C 58,27%; H 3,49%; N 6,47%; S 7,41%; Cl 8,19%; F 8,78%. Found: C 58,08%; H 3,62%; N 6,53%; S 7,35%; Cl 8,10%; F, A Total Of 8.74%.

Connection

1H-NMR (400 MHz, CDCl3) δ: 3,35 (1/2*3H, s), 3,78 (1/2*3H, s)5,52 (1/2*1H, s), 5,57 (1/2*1H, s), 6,78 and 7.1 (2H, m), 7,2-7,4 (7H, m), 7,76-of 7.95 (2H, m).

IR (ATR) cm-1: 1490, 1238, 1054, 820, 731.

TPL: 130-131°C.

MS m/z: 417 (M++H).

FAB-MS: 477,0646 (calculated for C21H16ClF2N2OS: 477,0640).

Example 151: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-deltorphin the l)methyl]-1-methyl-5-chloro-1H-imidazol

To a solution in methanol (12 ml) of 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-1-methyl-5-chloro-1H-imidazole (141 mg, and 0.37 mmol)obtained in example 147 was added tetrahydrate hexaminolevulinate (60 mg). To the mixture was added 30% aqueous hydrogen peroxide solution (6 ml) followed by stirring for 64 hours. Added ethyl acetate (60 ml)and the mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. Then the residue was led from ethanol to obtain specified in the title compound (103 mg, 67%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 3,71 (3H, s), 5,88 (1H, s), 6,93-was 7.08 (2H, m), 7,03 (1H, s), the 7.43 (4H, s), 7,98 (1H, m).

IR (ATR) cm-1: 1490, 1467, 1313, 1149, 1079, 818, 729.

TPL: 179-180°C.

MS m/z: 417 (M++H).

Elemental analysis. Calculated for C17H12Cl2F2N2O2S: C 48,90%; H 2,93%; N Of 6.71%; S 7,68%; Cl 16,99%; F 9,11%. Found: C 48,90%; H 2,93%; N 6,77%; S 7,80%; Cl 17,02%; F 9,19%

Example 152: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]thiazole

To a solution in methanol (6 ml) of 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]thiazole (124 mg, 0.35 mmol)obtained in example 148, added tetrahydrate hexaminolevulinate (30 mg). To the mixture was added to the 30% aqueous hydrogen peroxide solution (3 ml) followed by stirring for 15 hours. Then added ethyl acetate (60 ml), the mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was led from ethanol to obtain specified in the title compound (91 mg, 67%) as colorless columnar crystals.

1H-NMR (400 MHz, CDCl3) δ: 6,21 (1H, s), 6,92-was 7.08 (2H, m), 7,41 (2H, d, J=8,8 Hz), was 7.45 (1H, d, J=3.6 Hz), 7,56 (2H, d, J=8,8 Hz), 7,86 (1H, d, J=3.6 Hz), 7,94 (1H, m).

IR (ATR) cm-1: 1488, 1319, 1149, 1076, 817, 727.

TPL: 163-164°C.

MS m/z: 386 (M++H).

Elemental analysis. Calculated for C16H10ClF2NO2S2: C 49,81%; H 2,61%; N 3,63%; S 16,62%; Cl 9,19%; F 9,85%. Found: C 49,98%; H 2,61%; N Of 3.77%; S 16,60%; Cl 9,25%; F 9,87%.

Example 153: 2-[[(4-chlorophenyl)sulfonyl]-(2,5-differenl)methyl]-1-(4-methoxyphenyl)-1H-imidazol

To a solution in methanol (12 ml) of 2-[[(4-chlorophenyl)thio]-(2,5-differenl)methyl]-1-(4-methoxyphenyl)-1H-benzimidazole (118 mg, 0.27 mmol)obtained in example 149, added tetrahydrate hexaminolevulinate (60 mg). To the mixture was added 30% aqueous hydrogen peroxide solution (6 ml) followed by stirring for 64 hours. Added ethyl acetate (60 ml), the mixture was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The remainder of crystalliza is Ali from ethanol to obtain specified in the title compound (76 mg, 60%) in the form of colorless needle-like crystals.

1H-NMR (400 MHz, CDCl3) δ: to 3.89 (3H, s), of 5.83 (1H, s), 6,93-7,05 (4H, m), 6,97 (2H, d, J=8,8 Hz), 7,01 (2H, d, J=8,8 Hz), 7,38 (2H, d, J=8,8 Hz), 7,41 (2H, d, J=8,8 Hz), 8,15 (1H, m).

IR (ATR) cm-1: 1513, 1492, 1332, 1155, 836.

TPL: 150-151°C.

MS m/z: 475 (M++H).

Elemental analysis. Calculated for C23H17ClF2N2O3S: C 58,13%; H 3,61%; N 5,90%; S 6,75%; Cl 7,47%; F 8,00%. Found: C 58,09%; H 3,51%; N Of 5.99%; S 6,88%; Cl Of 7.48%; F Of 8.06%.

Reference example 28: 5-(methylsulphonyl)-1-pentanol

To a solution in dichloromethane (25 ml), 5-(methylthio)-1-pentanol (682 mg, 5.08 mmol) was added 3-chloroperbenzoic acid (2.10 g, 12.2 mmol)and the resulting mixture was stirred at room temperature for 2 hours. After concentration under reduced pressure, to the residue was added diethyl ether, and the mixture was extracted with water. After extraction of the organic layer twice with water the aqueous layers were combined and concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of dichloromethane:methanol=19:1 was concentrated under reduced pressure to obtain specified in the title compound (517 mg, 3.11 mmol, 61%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,50-to 1.67 (4H, m), 1,84-of 1.94 (2H, m), 2,90 (3H, s), 3,03 (2H, t,J=8.0 Hz), 3,68 (2H, t, J=6,1 Hz).

Reference example 29: 5-(methylsulphonyl)pentanal

To a solution in dichloromethane (15 ml) of 5-(methylsulphonyl)-1-pentanol (344 mg, 2,07 mmol), dimethyl sulfoxide (0,441 ml, 6.21 mmol) and triethylamine (1,15 ml of 8.28 mmol) was added to the complex of sulfur trioxide-pyridine (659 mg, 4.14 mmol) at 0°and the mixture was stirred at room temperature for 3 hours. After washing the reaction mixture with water the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using ethyl acetate, concentrated under reduced pressure to obtain specified in the title compound (183 mg, 1.11 mmol, 54%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,76-of 1.97 (4H, m)to 2.55 (2H, t, J=7,1 Hz), only 2.91 (3H, s), totaling 3.04 (2H, t, J=7.8 Hz), 9,79 (1H, s).

Reference example 30: 1-(2,5-differenl)-5-(methylsulphonyl)-1-pentanol

Solution in tetrahydrofuran (5 ml) of 1-bromo-2,5-diferente (0,151 ml of 1.34 mmol) was stirred at -78°C. To the mixture was added to the solution in hexane (0,843 ml of 1.34 mmol) n-utillity. The reaction mixture was added to the solution in tetrahydrofuran (5 ml) of 5-(methylsulphonyl)pentanal (183 mg, 1.11 mmol) at -78°and remesiana continued at the same temperature for 30 minutes. After increasing the temperature of the reaction mixture to room temperature was added diethyl ether. The resulting mixture was washed successively with a saturated aqueous solution of ammonium chloride and saturated aqueous sodium bicarbonate. Then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:2, was concentrated under reduced pressure to obtain specified in the title compound (116 mg, 0.42 mmol, 37%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,49 was 1.69 (2H, m), 1,71-of 1.97 (4H, m), 2,89 (3H, s), a 3.01 (2H, t, J=8.1 Hz), 5,02 (1H, t, J=6.2 Hz), 6,88-7,01 (2H, m), 7,16-7,22 (1H, m).

MS m/z: 296 (M++NH4).

Reference example 31: 1-(2,5-differenl)-5-(methylsulphonyl)pendimethalin

To a solution in dichloromethane (5 ml) of 1-(2,5-differenl)-5-(methylsulphonyl)-1-pentanol (278 mg, 1.00 mmol) was sequentially added triethylamine (0,209 ml, 1.50 mmol) and methanesulfonamide (0,115 ml, 1.50 mmol) at 0°C. the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate solution. Then the organic layer was dried over betwo the major sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain specified in the title compound (278 mg, 0.78 mmol, 78%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,48-1,71 (2H, m), 1.85 to to 1.98 (3H, m), 2,03 and 2.13 (1H, m), 2,90 (3H, s), 2,90 (3H, s), to 3.02 (2H, t, J=7.8 Hz), of 5.82 (1H, DD, J=8,6, 5,1 Hz), 7,01-7,19 (3H, m).

MS m/z: 374 (M++NH4).

Example 154: 1,4-debtor-2-[1-[(4-methoxyphenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

To a solution in N,N-dimethylformamide (2 ml), 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (139 mg, 0,39 mmol) was sequentially added 4-methoxybenzoyl (0,058 ml, 0.47 mmol) and potassium carbonate (81 mg, 0.59 mmol). The resulting mixture was shaken at room temperature for 15 hours. To the residue was added ethyl acetate. The mixture was washed with a saturated aqueous solution of ammonium chloride. Then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

Thus obtained residue was dissolved in methanol (2 ml) followed by addition of solution in water (2 ml) Oxone (connection peroxymonosulfate potassium, 2KHSO5.KHSO 4.K2SO4) (480 mg, 0.78 mmol) at 0°C. After shaking at room temperature for 3 hours was added dichloromethane, and the mixture was washed with water. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified preparative high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid). The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the title compound (86 mg, 0.20 mmol, 51%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: 1,34-of 1.52 (2H, m), 1,79-of 1.95 (2H, m), 2.05 is-of 2.16 (1H, m), 2,42-2,52 (1H, m), 2,87 (3H, s), 2,92-to 2.99 (2H, m), 3,85 (3H, s), 4,48 (1H, DD, J=11,0, 2,9 Hz), 6,80-6,89 (1H, m), 6.87 in (2H, d, J=8,8 Hz), 6,94-7,00 (1H, m), 7,19-of 7.25 (1H, m), 7,51 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 2951, 1595, 1496, 1271, 1132, 1084, 1022, 970.

Elemental analysis. Calculated for C19H22F2O5S2: C, 52,76; H, 5,13; F, 8,79. Found: C, 52,57; H, 5,13; F, 8,71.

MS m/z: 433 (M++H).

Example 155: 1,4-debtor-2-[5-(methylsulphonyl)-1-(phenylsulfonyl)pentyl]benzene

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol), specified in the title compound (83 mg, 0.21 in the mol, 58%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,34-of 1.52 (2H, m), 1,79-of 1.97 (2H, m), 2,07-of 2.20 (1H, m), 2,44 is 2.55 (1H, m), 2,87 (3H, s), 2,90-a 3.01 (2H, m), 4,51 (1H, DD, J=10,9, 3.6 Hz), 6.75 in-6,84 (1H, m), 6,92-7,00 (1H, m), 7,19-7,27 (1H, m), 7,38-7,46 (2H, m), 7,55-the 7.65 (3H, m).

MS m/z: 420 (M++NH4).

Example 156: 1,4-debtor-2-[1-[(4-were)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (139 mg, 0,39 mmol) and p-colortool (58 mg, 0.47 mmol), specified in the title compound (65 mg, 0.16 mmol, 40%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,33-is 1.51 (2H, m), 1.77 in is 1.96 (2H, m), 2,03-of 2.16 (1H, m), 2,37 is 2.51 (1H, m), is 2.40 (3H, s), 2,87 (3H, s), 2,90-of 3.00 (2H, m), 4,49 (1H, DD, J=11,1, 3.8 Hz), 6,79-to 6.88 (1H, m), 6,94-7,02 (1H, m), 7,19-7,26 (1H, m), 7,21 (2H, d, J=7.8 Hz), of 7.48 (2H, d, J=7,8 Hz).

IR (ATR) cm-1: 2943, 1597, 1498, 1269, 1142, 1084, 957, 868.

Elemental analysis. Calculated for C19H22F2O4S2: C, 54,79; H, 5,32; F, 9,12. Found: C, 54,67; H, 5,30; F, 9,10.

MS m/z: 417 (M++H).

Example 157: 2-[1-[(3-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]-1,4-differenza

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 3-chlorobenzoyl level (0.041 ml, 0.36 mmol), specified in the header with the Association (6.3 mg, 0.014 mmol, 4%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,34-and 1.54 (2H, m), 1,79-of 1.97 (2H, m), 2,08-of 2.21 (1H, m), 2,41-of 2.56 (1H, m), is 2.88 (3H, s), 2,90-3,03 (2H, m), 4,51 (1H, DD, J=10,6, 3,4 Hz), 6,78-of 6.90 (1H, m), 6,95-7,06 (1H, m), 7,19-7,29 (1H, m), of 7.36 (1H, t, J=7.8 Hz), 7,49 (1H, d, J=7.8 Hz), 7,55 (1H, d, J=7.8 Hz), 7,56 (1H, s).

MS m/z: 437 (M++H).

Example 158: 1,4-debtor-2-[1-[(3-were)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and m-colortool (0,043 ml, 0.36 mmol), specified in the title compound (26 mg, 0,062 mmol, 17%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,33-of 1.52 (2H, m), 1,78 is 1.96 (2H, m), 2,03-2,19 (1H, m), of 2.34 (3H, s), 2,39 is 2.51 (1H, m), 2,87 (3H, s), 2.91 in-2,99 (2H, m), 4,50 (1H, DD, J=11,0, 3,4 Hz), 6,78-6,86 (1H, m), 6,93-7,02 (1H, m), 7,19-7,33 (2H, m), of 7.36-7,44 (3H, m).

MS m/z: 417 (M++H).

Example 159: 1,4-debtor-2-[1-[(3-methoxyphenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 3-methoxybenzamide (0,044 ml, 0.36 mmol), specified in the title compound (25 mg, 0,059 mmol, 16%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,34-is 1.51 (2H, m), 1,79-of 1.95 (2H, m), 2.06 to to 2.18 (1H, m), 2,42-2,52 (1H, m), and 2.8 (3H, C)2,90-of 3.00 (2H, m in), 3.75 (3H, s)to 4.52 (1H, DD, J=11,5, 4.6 Hz), 6,80-6,87 (1H, m), 6,94-7,01 (1H, m), 7,05 (1H, s), 7,10 (1H, d, J=8.1 Hz), 7,21 (1H, d, J=8.1 Hz), 7,21-7,29 (1H, m), 7,32 (1H, t, J=8,1 Hz).

MS m/z: 433 (M++H).

Example 160: 1,4-debtor-2-[1-[(4-forfinal)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 4-fermentative (0,038 ml, 0.36 mmol), specified in the title compound (35 mg, 0,083 mmol, 23%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,38-of 1.53 (2H, m), 1,82-of 1.97 (2H, m), 2,08-of 2.20 (1H, m), 2,47-to 2.57 (1H, m), is 2.88 (3H, s), 2,92-to 3.02 (2H, m), 4,50 (1H, DD, J=11,0, 4,4 Hz), 6,78-to 6.88 (1H, m), 6,95-7,02 (1H, m), 7,05-7,13 (2H, m), 7,22-to 7.32 (1H, m), EUR 7.57-to 7.64 (2H, m).

MS m/z: 438 (M++NH4).

Example 161: 4-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]phenol

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 4-mercaptoethanol (45 mg, 0.36 mmol), specified in the title compound (63 mg, 0.15 mmol, 42%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,34-of 1.52 (2H, m), 1,80-of 1.93 (2H, m), 2,03-to 2.18 (1H, m), 2,42-2,52 (1H, m), is 2.88 (3H, s), 2,90-of 3.00 (2H, m), 4,47 (1H, DD, J=10,8, and 3.2 Hz), 5,44 (1H, s), is 6.78-6.87 in (1H, m), for 6.81 (2H, d, J=8,8 Hz), 6,94-7,01 (1H, m), 7,19-7,28 (1H, m), of 7.48 (2H, d, J=8,8 Hz).

MS m/z: 419 (M++).

Example 162: 1-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]naphthalene

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 1-naphthalenethiol (57 mg, 0.36 mmol), specified in the title compound (48 mg, 0.11 mmol, 29%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,29 of 1.46 (2H, m), 1,72-1,90 (2H, m), 2,13-of 2.26 (1H, m), 2,29-to 2.40 (1H, m), and 2.83 (3H, s), 2,82-of 2.93 (2H, m), 4,79 (1H, DD, J=11,3, 3,9 Hz), 6,66 to 6.75 (1H, m), 6.87 in-6,94 (1H, m), 7.24 to 7,31 (1H, m), 7,45 (1H, t, J=7,6 Hz), 7,58 to 7.62 (2H, m), 7,94 (1H, d, J=8.1 Hz), 8,01 (1H, d, J=7,6 Hz), 8,08 (1H, d, J=8.1 Hz), 8,73 (1H, d, J=8.6 Hz).

MS m/z: 453 (M++H).

Example 163: 2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]-1H-benzimidazole

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 2-mercaptobenzimidazole (54 mg, 0.36 mmol), specified in the title compound (62 mg, 0.14 mmol, 39%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,28-of 1.53 (2H, m), 1,78 is 1.96 (2H, m), 2,17-of 2.30 (1H, m), 2,42 of $ 2.53 (1H, m), of 2.86 (3H, s), 2,88-to 3.02 (2H, m), of 5.03 (1H, DD, J=11,3, 3,9 Hz), 6.90 to? 7.04 baby mortality (2H, m), 7,13-7,20 (1H, m), 7,39-7,47 (2H, m), 7,50 (1H, Sirs), of 7.90 (1H, Sirs), 10,08 (1H, Sirs).

MS m/z: 443 (M++H).

Example 164: 4-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]pyridine

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 4-mercaptopyridine (40 mg, 0.36 mmol), specified in the title compound (38 mg, 0,093 mmol, 26%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,27-to 1.60 (2H, m), 1,70-1,90 (2H, m), 2.00 in to 2.13 (1H, m), 2,35-2,48 (1H, m), is 2.88 (3H, s), 2,90 totaling 3.04 (2H, m), 4,56 (1H, DD, J=10,6, a 4.3 Hz), 6,78-6,85 (1H, m), 6,95-7,03 (1H, m), 7,22-7,30 (1H, m), 7,45 (2H, d, J=5,2 Hz), the rate of 8.75 (2H, d, J=5,2 Hz).

MS m/z: 404 (M++H).

Example 165: 2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]pyridine

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 2-mercaptopyridine (40 mg, 0.36 mmol), specified in the title compound (72 mg, 0.18 mmol, 50%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,36-of 1.52 (2H, m), 1,78 is 1.96 (2H, m), 2,10-of 2.21 (1H, m), 2,35 is 2.46 (1H, m), 2,87 (3H, s), 2,90-3,03 (2H, m), 5,11 (1H, DD, J=10,9, and 3.8 Hz), 6,82-6,91 (1H, m), 6,92-6,98 (1H, m), 7.24 to 7,31 (1H, m), of 7.48-rate of 7.54 (1H, m), 7,79-7,87 (2H, m), is 8.75 (1H, d, J=4,6 Hz).

MS m/z: 404 (M++H).

Example 166: 2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]quinoline

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 2-quinoline is Iola (58 mg, 0.36 mmol)specified in the title compound (90 mg, 0.20 mmol, 55%) was obtained as a colourless foam.

1H-NMR (400 MHz, CDCl3) δ: 1,39-to 1.59 (2H, m), 1,80-1,99 (2H, m), 2,13-of 2.26 (1H, m), 2,42 of $ 2.53 (1H, m), of 2.86 (3H, s), 2.91 in-to 3.02 (2H, m), 5,33 (1H, DD, J=11,1, 3.1 Hz), 6,74-PC 6.82 (1H, m), 6,88-of 6.96 (1H, m), 7,31 and 7.36 (1H, m), 7,72 (1H, t, J=7,1 Hz), 7,86-a 7.92 (3H, m), 8,24 (1H, d, J=8.5 Hz), 8,29 (1H, d, J=8,8 Hz).

MS m/z: 454 (M++H).

Example 167: 2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]pyrimidine

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 2-mercaptopyrimidine (40 mg, 0.36 mmol), specified in the title compound (55 mg, 0.14 mmol, 38%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,38-to 1.60 (2H, m), 1,79-to 1.98 (2H, m), 2,11-of 2.25 (1H, m), 2,37-2,47 (1H, m), is 2.88 (3H, s), 2,90-to 3.02 (2H, m), 5,31 (1H, DD, J=10,5, 3,4 Hz), 6.89 in-7,02 (2H, m), 7,33-7,39 (1H, m), 7,52 (1H, t, J=4,9 Hz), 8,91 (2H, d, J=4,9 Hz).

MS m/z: 405 (M++H).

Example 168: 5-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]-1-methyl-1H-tetrazol

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 1-methyl-5-mercapto-1,2,3,4-tetrazole (42 mg, 0.36 mmol), specified in the title compound (75 mg, 0.18 mmol, 52%) was obtained as a colourless oil.

1H-NMR (40 MHz, CDCl3) δ: 1,43-of 1.65 (2H, m), 1,82 is 2.01 (2H, m), 2,18-2,31 (1H, m), 2,49-2,60 (1H, m), 2,90 (3H, s), 2,92-of 3.06 (2H, m), 4,10 (3H, s), 5,12 (1H, DD, J=11.0 in, and 3.7 Hz), 7.03 is-7,22 (3H, m).

MS m/z: 409 (M++H).

Example 169: 2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfinil]-1-methyl-1H-imidazole (compound a) and 2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]-1-methyl-1H-imidazole (compound)

Similar to the method of example 154, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 2-mercapto-1-methylimidazole (41 mg, 0.36 mmol), specified in the title compound (45 mg, 0.12 mmol, 32%) and indicated in the title compound (47 mg, 0.11 mmol, 32%) was obtained as a yellow oil in the form of a colorless oil, respectively.

Connection And

1H-NMR (400 MHz, CDCl3) δ: 1,45-to 1.67 (2H, m), 1,82-2,02 (2H, m), 2,09-of 2.21 (1H, m), 2,41-2,52 (1H, m), 2,89 (3H, s), 2,92-is 3.08 (2H, m), 3,66 (3H, s), 4,91 (1H, DD, J=11,1, 4.5 Hz), 6,78-6,84 (1H, m), 6.90 to (1H, s), 6,93-7,01 (2H,, m), 7,12 (1H, s).

MS m/z: 391 (M++H).

Connection

1H-NMR (400 MHz, CDCl3) δ: 1,37-of 1.66 (2H, m), 1,81 is 1.96 (2H, m), 2,12-of 2.23 (1H, m), 2,45-of 2.56 (1H, m), is 2.88 (3H, s), 2.91 in-3,03 (2H, m)and 3.59 (3H, s), 4,89 (1H, DD, J=10,9, 4.0 Hz), 6,93 (1H, d, J=0.7 Hz), 6,97-was 7.08 (3H, m), 7,19 (1H, d, J=0.7 Hz).

MS m/z: 407 (M++H).

Example 170: 2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfinil]-1,3-benzothiazol

Similar to the method of example 154, IP the connection using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 2-mercaptobenzothiazoles (60 mg, 0.36 mmol), specified in the title compound (78 mg, 0.18 mmol, 49%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 1.37 to 1.48 (2H, m), 1,72 is 1.91 (2H, m), 2,09-to 2.29 (2H, m), and 2.83 (3H, s), 2,85-2,95 (2H, m), of 4.66 (1H, DD, J=10,5, 4,1 Hz), 7,01-was 7.08 (3H, m), of 7.48-to 7.50 (2H, m), 7,87-8,08 (2H, m).

MS m/z: 444 (M++H).

Example 171: 2-[1-[(2-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]-1,4-differenza

To a solution in N,N-dimethylformamide (2 ml), 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol)obtained in reference example 31, was sequentially added 2-chlorobenzoyl level (0.041 ml, 0.36 mmol) and potassium carbonate (62 mg, 0.45 mmol). The resulting mixture was shaken at room temperature for 4 hours. To the reaction mixture were added ethyl acetate. The mixture was washed with water, and then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

Thus obtained residue was dissolved in methanol (2 ml) followed by addition of solution in water (2 ml) Oxone (connection peroxymonosulfate potassium, 2KHSO5.KHSO4.K2SO4) (480 mg, 0.78 mmol) at 0°C. After shaking at room temperature for 14 hours to the reaction mixture was added dichloromethane, and the mixture was washed with water. Organic is Loy was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

Thus obtained residue was dissolved in dichloromethane (4 ml)and at 0°to the resulting solution was added 3-chloroperbenzoic acid (95 mg, 0.36 mmol). The reaction mixture was shaken at room temperature for 4 hours and then washed with 1 N. a solution of sodium hydroxide. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified preparative high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid). The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the title compound (59 mg, 0.14 mmol, 38%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,39-to 1.60 (2H, m), 1,82-of 1.97 (2H, m), 2,10-2,22 (1H, m), 2,37-2,48 (1H, m), 2,87 (3H, s), 2.91 in-to 3.02 (2H, m), 5,13 (1H, DD, J=10,7, and 3.7 Hz), 6,79-6,87 (1H, m), 6.90 to-6,97 (1H, m), 7.23 percent-7,33 (2H, m), 7,46-at 7.55 (2H, m), is 8.75 (1H, DD, J=7,9, 1,6 Hz).

MS m/z: 437 (M++H).

Example 172: 1,4-debtor-2-[1-[(2-forfinal)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

Similar to the method of example 171, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 2-fermentative (0,040 mg, 036 mmol), specified in the title compound (71 mg, 0,17 mmol, 47%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,39-to 1.60 (2H, m), 1,80-to 1.98 (2H, m), 2,10-2,22 (1H, m), 2,44-of 2.54 (1H, m), is 2.88 (3H, s), 2,96 (2H, t, J=7.4 Hz), 4,84 (1H, DD, J=10,7, 4,4 Hz), 6,78-6,85 (1H, m), 6.90 to-of 6.96 (1H, m), 7,10-7,21 (2H, m,), 7,22-7,29 (1H, m), 7,52-of 7.60 (2H, m).

MS m/z: 421 (M++H).

Example 173: 1,4-debtor-2-[1-[(2-were)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

Similar to the method of example 171, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and o-colortool (0.042 mg, 0.36 mmol), specified in the title compound (38 mg, 0,091 mmol, 25%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,33-of 1.55 (2H, m), 1,79-of 1.95 (2H, m), 2,09-of 2.21 (1H, m), 2,37-2,47 (1H, m), 2.63 in (3H, s), 2,87 (3H, s), 2,92 are 2.98 (2H, m), br4.61 (1H, DD, J=11,2, 3,4 Hz), 6.75 in-PC 6.82 (1H, m), 6.89 in-6,97 (1H, m), 7,16 (1H, t, J=7,6 Hz), 7,22-7,31 (2H, m), the 7.43 (1H, t, J=7,6 Hz), the 7.43 (1H, t, J=8.0 Hz).

MS m/z: 417 (M++H).

Example 174: 1,4-debtor-2-[1-[(2-methoxyphenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzene

Similar to the method of example 171, except for using 1-(2,5-differenl)-5-(methylsulphonyl)pendimethaline (127 mg, 0.36 mmol) and 2-methoxybenzoyl (0,044 mg, 0.36 mmol), specified in the title compound (52 mg, 0.12 mmol, 33%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: ,33-1,55 (2H, m), 1,78 is 1.96 (2H, m), 2.06 to 2,17 (1H, m), a 2.36-2,47 (1H, m), 2,87 (3H, s), 2,90-of 3.00 (2H, m)4,00 (3H, s)to 5.13 (1H, DD, J=11,2, a 3.2 Hz), 6,78-to 6.95 (3H, m), 6,98 (1H, d, J=7.8 Hz), 7,27-7,33 (1H, m), 7,46-7,53 (1H, m), 7,63 (1H, DD, J=8.0 a, 1,7 Hz).

MS m/z: 433 (M++H).

Example 175: 2-[1-[(4-chlorophenyl)sulfonyl]-6-(methylsulphonyl)hexyl]-1,4-differenza

To a solution in toluene (2 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (100 mg, 0.33 mmol)obtained in example 5, and 5-(methylsulphonyl)-1-pentanol (110 mg, 0.66 mmol)obtained in reference example 28 was added a solution in toluene of cyanomethylene-n-butylphosphine (177 mg, 0.66 mmol). The resulting mixture was heated at the boil under reflux for 16 hours. After cooling the reaction mixture to room temperature, concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:2, was concentrated under reduced pressure. The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the title compound (140 mg, 0.31 mmol, 94%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,22-to 1.38 (2H, m), 1,39-of 1.56 (2H, m), 1,73 is 1.86 (2H, m), 2,03-of 2.16 (1H, m), 2,41-2,52 (1H, m), is 2.88 (3H, s), 2,95 (2H, t, J=7.9 Hz), 4,50 (1H, DD, J=11,5, a 3.2 Hz), 6,80-6,89 (1H, m), 6,95? 7.04 baby mortality (1H, m,), 7,22-7,28 (1H, is), 7,38 (2H, d, J=8.5 Hz), 7,52 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 2949, 1500, 1475, 1317, 1294, 1275, 1136, 1084, 964, 752.

Elemental analysis. Calculated for C19H21ClF2O4S2: C, 50,61; H, 4,69; Cl, 7,86; F, 8,43; S, 14,22. Found: C, 50,59; H, 4,67; Cl, 8,04; F, 8,39; S, 14,15.

Reference example 32: 5-chloro-2-pyridinyl

After adding thiourea (152 mg, 2.00 mmol) to a solution in ethanol (4 ml) of 2,5-dichloropyridine (296 mg, 2.00 mmol) the resulting mixture was heated at the boil under reflux for 18 hours. The reaction mixture was cooled to room temperature followed by the addition of a solution in water (1 ml) of potassium hydroxide (198 mg, 3.00 mmol). The resulting mixture was heated at the boil under reflux for 3 hours. After cooling to room temperature, to the reaction mixture was added water, and the mixture is then washed with dichloromethane. The aqueous layer was acidified to acid reaction of acetic acid followed by extraction with dichloromethane. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the title compound (83 mg, or 0.57 mmol, 29%) as a yellow powder.

1H-NMR (400 MHz, CDCl3) δ: to 7.35 (1H, DD, J=9,3, 2.4 Hz), 7,46 1H, d, J=9.3 Hz), to 7.64 (1H, d, J=2,4 Hz).

MS m/z: 146 (M++H).

Example 176: 5-chloro-2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]thio]pyridine

To a solution in dichloromethane (5 ml) of 1-(2,5-differenl)-5-(methylsulphonyl)-1-pentanol (100 mg, 0.36 mmol)obtained in reference example 30, was sequentially added triethylamine (to 0.060 ml, 0.43 mmol) and methanesulfonamide (0,033 ml, 0.43 mmol) at 0°C. the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was washed with water, and the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

To a solution in N,N-dimethylformamide (4 ml) and the obtained residue was sequentially added 5-chloro-2-pyridinethiol (52 mg, 0.36 mmol) and potassium carbonate (62 mg, 0.45 mmol). The resulting mixture was stirred at room temperature for 3 hours. To the reaction mixture were added ethyl acetate. After washing with water, the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain specified in the title compound (116 mg, 0,29 mm is l, 79%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,39-of 1.64 (2H, m), 1,83-2,17 (4H, m), is 2.88 (3H, s), 2,92-of 3.06 (2H, m), 5,20 (1H, t, J=7,6 Hz), 6,84-6,92 (1H, m), of 6.96-7,02 (1H, m), 7,05 (1H, DD, J=8,6, 0.7 Hz), 7,11-to 7.18 (1H, m), the 7.43 (1H, DD, J=to 8.6, 2.5 Hz), of 8.37 (1H, DD, J=2.5 and 0.7 Hz).

MS m/z: 406 (M++H).

Example 177: 5-chloro-2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]pyridine

To a solution in methanol (2 ml) of 5-chloro-2-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]thio]pyridine (100 mg, 0.25 mmol) was added to the solution in water (2 ml) Oxone (connection peroxymonosulfate potassium, 2KHSO5.KHSO4.K2SO4) (303 mg, 0.49 mmol) at 0°C. After shaking at room temperature for 22 hours to the reaction mixture was added dichloromethane, and the mixture was washed with water. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain specified in the title compound (61 mg, 0.14 mmol, 56%) as a colourless foam.

1H-NMR (400 MHz, CDCl3) δ: 1,37-of 1.53 (2H, m), 1,80-of 1.97 (2H, m), 2,09-of 2.20 (1H, m), a 2.36-2,48 (1H, m), is 2.88 (3H, s), 2,96 (2H, t, J=7.5 Hz), 5,07 (1H, DD, J=11,1, 3.8 Hz), 6,86-7,02 (2H, m), 7.23 percent-7,31 (1H, m), 7,74 (1H, d, J=8,3 Hz), 7,79 (1H, d is, J=of 8.3 and 2.2 Hz), 8,67 (1H, d, J=2.2 Hz),

Elemental analysis. Calculated for C17H18ClF2NO4S2·0,25H2O: C, 46,15; H, 4,21; F, 8,59; N, 3,17; S, 14,50. Found: C, 46,38; H, 4,11, F, Of 8.40; N, 3,20; S, 14,22.

MS m/z: 438 (M++H).

Reference example 33: S-(6-chloro-3-pyridyl)-O-ethyl-dithiocarbonate

1 N. chloride-hydrogen acid (10 ml) was dissolved 5-amino-2-chloropyridine (643 mg, 3.00 mmol). The solution in water (1 ml) of sodium nitrite (207 mg, 3.00 mmol) was added dropwise to the obtained solution at -5°C. After stirring the reaction mixture at 60aboutC for 30 minutes the solution in water (1 ml), O-utilityservice potassium (481 mg, 3.00 mmol) was added dropwise to the reaction mixture at the same temperature. Then the reaction mixture was stirred at 80°C for 1 hour and then cooled to room temperature. Added ethyl acetate, and the resulting mixture was washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=49:1 was concentrated under reduced pressure to obtain specified in the title compound (148 mg, 0,63 mmol, 21%) as a yellow the oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.37 (3H, t, J=7,1 Hz), 4,63 (2H, t, J=7,1 Hz), 7,41 (1H, d, J=8,3 Hz), 7,76 (1H, DD, J=8,3, 2.4 Hz), to 8.45 (1H, d, J=2,4 Hz).

MS m/z: 234 (M++H).

Example 178: 2-chloro-5-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]pyridine

To a solution in ethanol (3 ml) S-(6-chloro-3-pyridyl)-O-utilityservice (145 mg, of 0.62 mmol) was added 1 N. aqueous solution (3 ml) of sodium hydroxide, followed by stirring at 80°C for 2 hours. After cooling to room temperature, to the reaction mixture was added water, and the mixture is then washed with dichloromethane. The aqueous layer was acidified to acidic with acetic acid and then was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 6-chloro-3-pyridinol in the form of a yellow solid.

To a solution in dichloromethane (5 ml) of 1-(2,5-differenl)-5-(methylsulphonyl)-1-pentanol (173 mg, of 0.62 mmol)obtained in reference example 30, was sequentially added triethylamine (0,130 ml of 0.93 mmol) and methanesulfonamide (to 0.060 ml, 0.78 mmol) at 0°C. the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sulfate is m sodium. After filtration, the filtrate was concentrated under reduced pressure.

To a solution in N,N-dimethylformamide (6 ml) of the residue was sequentially added 6-chloro-3-pyridinyl and potassium carbonate (107 mg, 0.78 mmol). The resulting mixture was stirred at room temperature for 2 hours. After adding ethyl acetate and washing with water, the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

The residue was dissolved in dichloromethane (5 ml) followed by addition of 3-chloroperbenzoic acid (214 mg, 1,24 mmol) at 0°C. the Mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with 1 N. aqueous sodium hydroxide solution, and then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=2:1 was concentrated under reduced pressure. The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the title compound (187 mg, 0.43 mmol, 69%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,40-of 1.57 (2H, m), 1,84-to 1.98 (2H, m), 2,11-2,22 (1H, m), 2,50-2,60 (1H, m), 2,89 (3H, s), 2,93-to 3.02 (2H, m), 4,48 (1H, DD, J=10,4, 3.8 Hz), 6,82-6,91 (1H, m), 7,00-7,07 (1H, m), 7.24 to 7,29 (1H, m), 7,38 (1H, d, J=8,3 Hz), 7,79 (1H, DD, J=8,3, 2.4 Hz), 8,48 (1H, d, J=2,4 Hz).

IR (ATR) cm-1: 3059, 1566, 1495, 1446, 1279, 1161, 1107, 829.

Elemental analysis. Calculated for C17H18ClF2NO4S2: C, 46,63; H, 4,14; Cl, 8,10, F, 8,68; N, 3,20; S, 14,64. Found: C, 46,36; H, 4,29; Cl, 8,08; F, 8,65; N, 3,25; S Of 14.57.

MS m/z: 438 (M++H).

Example 179: 2-[1-(cyclohexylcarbonyl)-5-(methylsulphonyl)pentyl]-1,4-differenza

To a solution in dichloromethane (3 ml) of 1-(2,5-differenl)-5-(methylsulphonyl)-1-pentanol (100 mg, 0.36 mmol)obtained in reference example 30, was sequentially added triethylamine (0,072 ml, 0.52 mmol) and methanesulfonamide (0,033 ml, 0.43 mmol) at 0°C. the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

To a solution in acetonitrile (3 ml) and the obtained residue was sequentially added cyclohexanol (of 0.066 ml, 0.54 mmol) and cesium carbonate (176 mg, 0.54 mmol). The resulting mixture was stirred at room temperature for 2 hours. To the reaction mixture were added dichloromethane and washed with saturated salt solution, and then the organic layer was dried over anhydrous Sul is the sodium atom. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=2:1 was concentrated under reduced pressure.

The residue was dissolved in dichloromethane (3 ml) followed by addition of 3-chloroperbenzoic acid (113 mg, 0.43 mmol) at 0°and the mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with 1 N. aqueous sodium hydroxide solution, and then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:2, was concentrated under reduced pressure. The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the title compound (53 mg, 0.13 mmol, 36%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,03-of 1.27 (3H, m), 1,30-1,70 (5H, m), 1,78 is 2.10 (7H, m), 2,40-2,60 (2H, m), is 2.88 (3H, s), 2,90-to 3.02 (2H, m), of 4.54 (1H, DD, J=11,1, 2.6 Hz),? 7.04 baby mortality-to 7.15 (2H, m), of 7.36-7,42 (1H, m).

IR (ATR) cm-1: 2931, 1495, 1273, 1126, 1117, 976.

Elemental analysis. Calculated for C18H26F2O4S2: C, 52,92; H, 6,41; F, OF 9.30; S, 15,70. Found: C, 52,85; H, Of 6.31; F, 9,34; S, 15,53.

The m/z: 409 (M ++H).

Example 180: 4-[4-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]phenyl]morpholine

To a solution in dimethyl sulfoxide (0.5 ml) 1,4-debtor-2-[1-[(4-forfinal)sulfonyl]-5-(methylsulphonyl)pentyl]benzene (40 mg, 0,095 mmol)obtained in example 160, has consistently added morpholine (0,012 ml, 0.14 mmol) and 1-methylpiperidin (0.17 ml, 0.14 mmol). The resulting mixture was allowed to stand at 80aboutWith in 24 hours. The reaction mixture was purified preparative high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid). The obtained solid is washed with diethyl ether and collected by filtration to obtain specified in the title compound (43 mg, 0.88 mmol) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,31-is 1.51 (2H, m), 1.77 in-of 1.94 (2H, m), 2,02 with 2.14 (1H, m), 2,38-of 2.50 (1H, m), is 2.88 (3H, s), 2,90-of 3.00 (2H, m), or 3.28 (4H, t, J=4.9 Hz), 3,85 (4H, t, J=4.9 Hz), 4,47 (1H, DD, J=10,6, 3.5 Hz), 6,78 (2H, d, J=9.0 Hz), 6,83-of 6.90 (1H, m), 6,94-7,01 (1H, m), 7,19-7,24 (1H, m), 7,44 (2H, d, J=9.0 Hz).

IR (ATR) cm-1: 2962, 1591, 1498, 1271, 1131, 1090, 976, 926.

Elemental analysis. Calculated for C22H27F2NO5S2: C TO 54.19; H, 5,58; F, 7,79; N, 2,87; S, 13,15. Found: C, 53,93; H, Of 5.53; F, Of 7.90; N, 2,87; S, 13,17.

MS m/z: 488 (M++H).

Example 181: 1-[4-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]phenyl]piperidine

Similar to the method of example 180, except for using 1,4-debtor-2-[1-[(4-forfinal)sulfonyl]-5-(methylsulphonyl)pentyl]benzene (100 mg, 0.24 mmol) and piperidine (or 0.035 ml, 0.36 mmol), specified in the title compound (83 mg, 0,17 mmol, 71%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,30-is 1.51 (2H, m), 1.56 to 1,72 (6H, m), 1,76-of 1.93 (2H, m), 2,01 and 2.13 (1H, m), a 2.36-2,48 (1H, m), 2,87 (3H, s), 2,88-of 3.00 (2H, m)to 3.34 (4H, Sirs), of 4.45 (1H, DD, J=11,5, 3,4 Hz), to 6.75 (2H, d, J=9.0 Hz), 6,82-of 6.90 (1H, m), 6,92-7,00 (1H, m), 7,16-of 7.23 (1H, m), 7,38 (2H, d, J=9.0 Hz).

IR (ATR) cm-1: 2935, 1591, 1495, 1282, 1122, 1090.

Elemental analysis. Calculated for C23H29F2NO4S2: C, 56,89; H, 6,02, F, OF 7.82; N, 2,88; S, 13,21. Found: C, 56,73; H, 5,99; F, 7,88; N, 2,93; S, 13,22.

MS m/z: 486 (M++H).

Example 182: 4-[1-(2,5-differenl)-5-methylsulfonylbenzoyl]-N,N-dimethylaniline

Similar to the method of example 180, except for using 1,4-debtor-2-[1-[(4-forfinal)sulfonyl]-5-(methylsulphonyl)pentyl]benzene (100 mg, 0.24 mmol) and dimethylamine hydrochloride (58 ml, 0.71 mmol), specified in the title compound (83 mg, 0,19 mmol, 78%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,30-1,50 (2H, m), 1,76-of 1.93 (2H, m), 2,01-2,12 (1H, m), a 2.36-2,48 (1H, m), 2,87 (3H, s), 2,88-of 3.00 (2H, m), 3,03 (6H, s), of 4.45 (1H, DD, J=11,2, 2,9 Hz), 6,55 (2H, d, J=9.0 Hz), 6,82-6,91 (1H, m), 6,93-7,01 (1H, m), 7.18 in-7,24 (1H, m), 7,38 (2H, d, J=9.0 Hz).

IR (ATR) cm-1: 2941, 1603, 1496, 1284, 1269, 1230, 1138, 108.

Elemental analysis. Calculated for C20H25F2NO4S: C, 53,91; H, 5,66; F, 8,53; N, 3,14; S, 14,39. Found: C, 53,61; H, 5,61; F, 8,51; N, A 3.06; S, 14,35.

MS m/z: 446 (M++H).

Example 183: 1-[4-[[1-(2,5-differenl)-5-(methylsulphonyl)pentyl]sulfonyl]phenyl]-4-methylpiperazin

Similar to the method of example 180, except for using 1,4-debtor-2-[1-[(4-forfinal)sulfonyl]-5-(methylsulphonyl)pentyl]benzene (100 mg, 0.24 mmol) and 1-methylpiperazine (0,040 ml, 0.36 mmol), specified in the title compound (68 mg, 0.14 mmol, 57%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,31-is 1.51 (2H, m), 1.77 in-of 1.94 (2H, m), 2,02 and 2.13 (1H, m)to 2.35 (3H, s), a 2.36-2,48 (1H, m), of 2.53 (4H, t, J=5,1 Hz), 2,87 (3H, s), 2,88-of 3.00 (2H, m)to 3.34 (4H, t, J=5,1 Hz), 4,46 (1H, DD, J=11,0, 3,7 Hz), 6,77 (2H, d, J=9.0 Hz), 6,82-of 6.90 (1H, m), 6,92-7,01 (1H, m), 7.18 in-of 7.23 (1H, m), 7,41 (2H, d, J=9.0 Hz).

IR (ATR) cm-1: 1595, 1495, 1292, 1134, 1090, 1003, 968.

Elemental analysis. Calculated for C23H30F2N2O4S2: C, 55,18; H, 6,04, F, TO 7.59; N, THE CEILING OF 5.60; S, 12,81. Found: C, 54,92; H, Of 5.92; F, 7,66; N, The Ceiling Of 5.60; S 12,80.

MS m/z: 501 (M++H).

Example 184 N-benzyl-4-[1-(2,5-differenl)-5-methylsulfonylbenzoyl]-N-methylaniline

Similar to the method of example 180, except for using 1,4-debtor-2-[1-[(4-forfinal)sulfonyl]-5-(methylsulphonyl)pentyl]benzene (100 mg, 0.24 mmol) and N-benzylmethylamine (0,046 ml, 0.36 mmol), specified in the compound (34 mg, 0,065 mmol, 27%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,30-1,50 (2H, m), 1,76-of 1.93 (2H, m), 2,01 and 2.13 (1H, m), a 2.36-2,48 (1H, m), 2,87 (3H, s), 2,88-of 3.00 (2H, m), 3,11 (3H, s), 4,46 (1H, DD, J=11,4, 3.5 Hz), 4,58 (1H, d, J=17.5 Hz), 4,63 (1H, d, J=17,5 Hz), 6,60 (2H, d, J=9.0 Hz), 6,78-6,86 (1H, m), 6.89 in-6,98 (1H, m), 7,12 (2H, d, J=7,1 Hz), 7,13-7,20 (1H, m), 7.24 to to 7.35 (3H, m), 7,35 (2H, d, J=9.0 Hz),

IR (ATR) cm-1: 1593, 1493, 1390, 1281, 1124, 1088.

Elemental analysis. Calculated for C26H29F2NO4S2: C, 59,86; H, The Ceiling Of 5.60; F, 7,28; N, 2,69; S, 12,29, Found: C, 59,74; H, 5,52; F, 7,35; N, Was 2.76; S, To 12.44.

MS m/z: 522 (M++H).

Example 185 N-benzyl-4-[1-(2,5-differenl)-5-methylsulfonylbenzoyl]aniline

Similar to the method of example 180, except for using 1,4-debtor-2-[1-[(4-forfinal)sulfonyl]-5-(methylsulphonyl)pentyl]benzene (100 mg, 0.24 mmol) and benzylamine (0,039 ml, 0.36 mmol), specified in the title compound (49 mg, 0,097 mmol, 41%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,31 of 1.50 (2H, m), 1,78-of 1.93 (2H, m), 2,01 and 2.13 (1H, m), 2,37-2,48 (1H, m), 2,87 (3H, s), 2,89-of 3.00 (2H, m), 4,36 (2H, sird, J=3,7 Hz), 4,46 (1H, DD, J=11,2, a 3.2 Hz), br4.61 (1H, Sirs), 6,51 (2H, d, J=9,0 Hz), 6,80-6,87 (1H, m), 6.90 to-6,98 (1H, m), 7,15-7,22 (1H, m), 7,29-7,40 (5H, m), 7,34 (2H, d, J=9.0 Hz).

IR (ATR) cm-1: 3411, 1597, 1495, 1282, 1142, 1086, 870.

Elemental analysis. Calculated for C25H27F2NO4S2·0,25H2O: C, 58,63; H, 5,41; F, 7,42; N, 2,74; S, TO 12.52. Found: C, 58,59; H, 5,27; F, 7,49; N, 2,78; S, 12,61.

MS m/z: 508 (M ++H).

Reference example 34: 6-(tert-butyldiphenylsilyl)-1-(2,5-differenl)-1-hexanol

Solution in tetrahydrofuran (30 ml) of 1-bromo-2,5-diferente (0,956 ml, 8,46 mmol) was stirred at -78°C. To the reaction mixture solution was added to hexane (6,46 ml, 10.2 mmol) n-utillity. The reaction mixture was added to the solution in tetrahydrofuran (20 ml) of 6-(tert-butyldiphenylsilyl)hexanes (2.50 g, 7.05 mmol) at -78°and the mixture was stirred at the same temperature for 30 minutes. After increasing the temperature of the reaction mixture to room temperature was added diethyl ether. The mixture was washed with a saturated aqueous solution of ammonium chloride, and the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=9:1 was concentrated under reduced pressure to obtain specified in the connection header (2,92 g and 4.65 mmol, 88%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: was 1.04 (9H, m), 1,21-1,90 (8H, m)to 3.64 (2H, t, J=6.3 Hz), 4,96 (1H, t, J=6.5 Hz), 6,86-7,01 (2H, m), 7,13-7,20 (1H, m), 7,32 was 7.45 (6H, m), 7,62-of 7.70 (4H, m).

Example 186: 6-[(5-[chloro-2-pyridyl)sulfonyl]-(2,5-differenl)-1-hexanol

To a solution of the dichloromethane (20 ml) of 6-(tert-butyldiphenylsilyl)hydroxy-1-(2,5-differenl)-1-hexanol (1,04 mg, 2.22 mmol) was sequentially added triethylamine (0,619 ml of 4.44 mmol) and methanesulfonamide (0,258 ml of 3.33 mmol) at 0°C. the Mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate, and the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

To a solution in N,N-dimethylformamide (20 ml) of the residue was sequentially added 5-chloro-2-pyridinethiol (323 mg, 2.22 mmol)obtained in reference example 32, and potassium carbonate (368 mg, of 2.66 mmol). The resulting mixture was stirred at room temperature for 3 hours. To the reaction mixture were added ethyl acetate. After washing with water, the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

Thus obtained residue was dissolved in dichloromethane (20 ml) was added 3-chloroperbenzoic acid (1.18 g, of 4.44 mmol) at 0°to the resulting solution. The mixture was stirred at room temperature for 3 hours. The reaction mixture was washed with 1 N. aqueous sodium hydroxide solution. Then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

To a solution in tetrahydrofuran (10 ml) OS the Atka was added to the solution in tetrahydrofuran of 3.33 ml, of 3.33 mmol) tetrabutylammonium and the mixture was stirred at room temperature for 8 hours. After concentrating the reaction mixture under reduced pressure, the residue was dissolved in ethyl acetate followed by washing with water. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=7:3 was concentrated under reduced pressure to obtain specified in the title compound (477 mg, 1,22 mmol, 55%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,17-to 1.59 (6H, m), 2,04-2,17 (1H, m), 2,30-to 2.42 (1H, m)and 3.59 (2H, t, J=6.3 Hz), 5,07 (1H, DD, J=11,6, 2,8 Hz), 6,84-6,92 (1H, m), 6,93-7,01 (1H, m), 7,26-to 7.32 (1H, m), 7,74 (1H, DD, J=8,3, 0.7 Hz), for 7.78 (1H, DD, J=8,3, 2.2 Hz), 8,67 (1H, DD, J=2,2, 0.7 Hz).

MS m/z: 390 (M++H).

Example 187: 5-chloro-2-[[1-(2,5-differenl)cyclohexyl]sulfonyl]pyridine

To a solution in toluene (5 ml) of 6-[(5-chloro-2-pyridyl)sulfonyl]-(2,5-differenl)-1-hexanol (308 mg, of 0.79 mmol) was added a solution in toluene (3 ml) and cyanomethylene-n-butylphosphine (424 mg, was 1.58 mmol). The resulting mixture was heated at the boil under reflux for 16 hours. After cooling to room temperature the reaction mixture was concentrated under pony is hinnon pressure. Thus obtained residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=9:1 was concentrated under reduced pressure. The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the title compound (96 mg, 0.26 mmol, 33%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,12-of 1.42 (3H, m), 1,58-of 1.66 (1H, m), 1.77 in-to 1.86 (2H, m), 2,11-of 2.25 (2H, m), 2.91 in (2H, Sirs), 6,79-6,89 (1H, m), 6,97? 7.04 baby mortality (1H, m), 7,06-7,13 (1H, m)to 7.50 (1H, d, J=8,3 Hz), 7,72 (1H, DD, J=8,3, 2,4 Hz), 8,65 (1H, DD, J=2,4 Hz).

IR (ATR) cm-1: 2933, 2862, 1493, 1302, 1190, 1153, 1107, 1012.

Elemental analysis. Calculated for C17H16ClF2NO2S: C, 54,91; H, 4,34; Cl, At 9.53; F, 10,22; N, Of 3.77; S, 8,62. Found: C, 54,88; H, 4,50; Cl, 9,65; F, 10,35; N, 3,80; S 8,76.

MS m/z: 372 (M++H).

Reference example 35: 7-(tert-butyldiphenylsilyl)-1-(2,5-differenl)-1-heptanol

Solution in tetrahydrofuran (40 ml) of 1-bromo-2,5-diferente (1.25 ml, about 10.7 mmol) was stirred at -78°With the subsequent addition of a solution in hexane (8,50 ml of 13.4 mmol) n-utillity. The reaction mixture was added to the solution in tetrahydrofuran (20 ml) of 7-(tert-butyldiphenylsilyl)heptanal (3.28 g, of 8.90 mmol) at -78°and the mixture was stirred at the same temperature for 30 minutes. After increasing the temperature of the reaction mixture on the room temperature was added diethyl ether. The mixture was washed with a saturated aqueous solution of ammonium chloride. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=9:1 was concentrated under reduced pressure to obtain specified in the title compound (3.88 g, of 8.04 mmol, 90%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: was 1.04 (9H, m), 1,21-of 1.92 (10H, m)to 3.64 (2H, t, J=6.5 Hz), equal to 4.97 (1H, t, J=6.5 Hz), 6,86-7,00 (2H, m), 7,13-7,20 (1H, m), 7,33-7,44 (6H, m), 7,62-of 7.70 (4H, m).

Example 188: 7-[(5-chloro-2-pyridyl)sulfonyl]-(2,5-differenl)-1-heptanal

To a solution in dichloromethane (20 ml) of 7-(tert-butyldiphenylsilyl)-1-(2,5-differenl)-1-heptanol (1.04 g, of 2.15 mmol) was sequentially added triethylamine (0,601 ml, or 4.31 mmol) and methanesulfonamide (0,250 ml of 3.23 mmol) at 0aboutC. the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate solution and then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

To a solution in N,N-dimethylformamide (20 ml) of the residue was sequentially added 5-chloro-2-pyridinethiol (314 mg, 2,15 the mole), obtained in reference example 32, and potassium carbonate (357 mg, at 2.59 mmol)and the resulting mixture was stirred at room temperature for 3 hours. To the reaction mixture was added ethyl acetate, and the mixture was washed with water. Then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

To a solution in dichloromethane (20 ml) of the obtained residue was added 3-chloroperbenzoic acid (1,14 g, or 4.31 mmol) at 0°and the mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with 1 N. aqueous sodium hydroxide solution. Then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

The obtained residue was dissolved in tetrahydrofuran (10 ml) followed by the addition of a solution in tetrahydrofuran (3,23 ml of 3.23 mmol) tetrabutylammonium. The resulting mixture was stirred at room temperature for 8 hours. After concentrating the reaction mixture under reduced pressure, the residue was dissolved in ethyl acetate, and the solution was washed with water. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from elua is using a mixture of hexane:ethyl acetate=7:3, concentrated under reduced pressure to obtain specified in the title compound (595 mg, about 1.47 mmol, 69%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,14-of 1.66 (8H, m), 2,03-2,17 (1H, m), 2,29-to 2.40 (1H, m), of 3.60 (2H, t, J=6.6 Hz), is 5.06 (1H, DD, J=11,6, 3.1 Hz), 6,84-6,91 (1H, m), 6,92-7,00 (1H, m), 7,25-7,31 (1H, m), 7,74 (1H, DD, J=8,3 Hz), 7,78 (1H, DD, J=8,3, 2.2 Hz), 8,67 (1H, DD, J=2.2 Hz).

MS m/z: 404 (M++H).

Example 189: 5-chloro-2-[[1-(2,5-differenl)cycloheptyl]sulfonyl]pyridine

To a solution in toluene (8 ml) of 7-[(5-chloro-2-pyridyl)sulfonyl]-(2,5-differenl)-1-heptanol (436 mg, of 1.08 mmol) was added a solution in toluene (3 ml) and cyanomethylene-n-butylphosphine (579 mg, of 2.16 mmol). The resulting mixture was heated at the boil under reflux for 16 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=9:1 was concentrated under reduced pressure. The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the title compound (79 mg, 0.20 mmol, 19%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,32-to 1.63 (6H, m), 1,82-of 1.94 (2H, m), 2,42-2,52 (2H, m), 2,79-2,90 (2H, m), for 6.81-6.90 to (1H, m), 697-7,07 (2H, m)of 7.48 (1H, d, J=8.6 Hz), 7,71 (1H, DD, J=8,6, 2,5 Hz), 8,65 (1H, DD, J=2.5 Hz),

IR (ATR) cm-1: 2933, 2864, 1493, 1308, 1188, 1159, 1107, 1011.

Elemental analysis. Calculated for C18H18ClF2NO2S: C, 56,03; H, 4,70; Cl, 9,19; F, 9,85; N, 3,63; S, 8,31. Found: C, 55,92; H, 4,77; Cl, 9,23; F, 9,90; N, 3,67; S, To 8.41.

MS m/z: 386 (M++H).

Reference example 36: 2.5-differenl-4-pyridinemethanol

Solution in tetrahydrofuran (30 ml) of 1-bromo-2,5-diferente (1.08 ml, 9,60 mmol) was stirred at -78°With the subsequent addition of a solution in hexane (7,32 ml, 11.5 mmol) n-utillity. To the mixture was added a solution of tetrahydrofuran (10 ml) of 4-pyridinecarboxamide (0,764 ml of 8.00 mmol) at -78°and the mixture was stirred at the same temperature for 30 minutes. After increasing the temperature of the reaction mixture to room temperature was added diethyl ether. The mixture was washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=7:3 was concentrated under reduced pressure. The obtained solid is washed with diisopropyl ether and then collected by filtration to obtain specified in zag is lowke connection (1,15 g, 5,20 mmol, 65%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 4.25 (1H, Sirs), 6,09 (1H, s), 6.89 in-7,05 (2H, m), 7,14-of 7.23 (1H, m), 7,34 (2H, d, J=5.4 Hz), 8,44 (2H, d, J=5.4 Hz).

Example 190: 5-chloro-2-[(2,5-differenl-4-pyridylmethyl)thio]pyridine

To a solution in dichloromethane (10 ml) (2.5-differenl-4 pyridinemethanol (221 mg, 1.00 mmol) was sequentially added triethylamine (0,279 ml, 2.00 mmol) and methanesulfonamide (0,116 ml, 1.50 mmol) at 0°C. the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate solution and then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.

To a solution in N,N-dimethylformamide (10 ml) and the obtained residue was sequentially added 5-chloro-2-pyridinethiol (145 mg, 1.00 mmol)obtained in reference example 32, and potassium carbonate (166 mg, 1.20 mmol). The resulting mixture was stirred at room temperature for 2 hours. To the mixture was added ethyl acetate, and the mixture was washed with water. Then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:etilize is t=17:3, concentrated under reduced pressure to obtain specified in the title compound (267 mg, 0.77 mmol, 77%) as a yellow solid.

1H-NMR (400 MHz, CDCl3) δ: of 6.52 (1H, s), 6,92-6,98 (1H, m), 6,99-7,06 (1H, m), of 7.48 (1H, DD, J=8,5,0,7 Hz), 7,17-of 7.23 (1H, m), 7,34 (2H, d, J=6,1 Hz), 7,47 (1H, DD, J=8,5, 2.4 Hz), with 8.33 (1H, DD, J=2,4, 0.7 Hz), 8,54 (2H, d, J=6,1 Hz).

MS m/z: 349 (M++H).

Example 191: 5-chloro-2-[(2,5-differenl-4-pyridylmethyl)sulfonyl]pyridine

To a solution in methanol (6 ml) 5-chloro-2-[[1-(2,5-differenl-4-pyridylmethyl)thio]pyridine (239 mg, of 0.68 mmol) was added to the solution in water (12 ml) Oxone (connection peroxymonosulfate potassium, 2KHSO5.KHSO4.K2SO4) (631 mg, 1,03 mmol) at 0°C. After stirring at room temperature for 3 days the reaction mixture was added dichloromethane, and the mixture was washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified preparative high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid). The obtained solid was washed with hexane/diisopropyl ether and then collected by filtration to obtain specified in the title compound (67 mg, 0.18 mmol who, 26%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 6,44 (1H, s), of 6.96-was 7.08 (2H, m), of 7.48 (2H, d, J=6.3 Hz), 7,70-to 7.77 (1H, m), 7,79 (1H, DD, J=8,3, 2.2 Hz), to 7.84 (1H, DD, J=8,3, 0.7 Hz), 8,61 (2H, d, J=6.3 Hz), 8,67 (1H, DD, J=2,2, 0.7 Hz).

IR (ATR) cm-1: 1591, 1493, 1329, 1161, 1107, 1014.

Elemental analysis. Calculated for C17H11ClF2N2O2S: C, 53,62; H, 2.91 IN; F, 9,98; N, OF 7.36; S, 8,42. Found: C, 53,55; H, 2,87; F, 10,10, N, 7,40; S, 8,55.

MS m/z: 381 (M++H).

Example 192: 5-(4-chlorobenzenesulfonyl)-1H-tetrazol

To a solution in N,N-dimethylformamide (100 ml) of 4-chlorophenylsulfonyl (2,81 g, 13,0 mmol) and triethylamine hydrochloride (4,24 g, to 65.2 mmol) was added sodium azide (10.8 g, 78.2 mmol)and the mixture was stirred at 80°C for 16 hours. Then the reaction mixture was cooled to room temperature. Added ethyl acetate, and the mixture was washed with a saturated aqueous solution of ammonium chloride. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The obtained solid is washed with diethyl ether and then collected by filtration to obtain specified in the connection header (2,53 g, 9,78 mmol, 75%) as a white solid.

1H-NMR (400 MHz, CD3OD) δ: 5,02 (2H, s), a 7.62 (1H, d, J=8.6 Hz), 7,73 (2H, d, J=8.6 Hz).

MS m/z: 300 (M++H+CH3CN).

Example 193: 1-benzyl-5-(4-chlorine is benzosulfimide)-1H-tetrazol (isomer 193-a) and 2-benzyl-5-(4-chlorobenzenesulfonyl)-2H-tetrazol (isomer 193-In)

To a solution in a mixture of dichloromethane/tetrahydrofuran (1:1) (20 ml) of 5-(4-chlorophenylsulfonyl)-1H-tetrazole (837 mg, 3,24 mmol) and benzyl alcohol (0,335 ml, 3,24 mmol) was added triphenylphosphine (849 mg, 3,24 mmol) under cooling on ice. Then was added dropwise azodicarboxylate (0,510 ml, 3,24 mmol) at the same temperature. The reaction mixture was stirred at room temperature for 16 hours, followed by concentration under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1 was concentrated under reduced pressure to obtain specified in the header isomer 193-A (406 mg, of 1.16 mmol, 36%) and indicated in the title isomer 193-In (317 mg, of 0.91 mmol, 28%), each in the form of a white solid.

On the basis of tests of NOE (nuclear Overhauser effect) was determined the structure of each isomer 193-a and isomer 193-Century

Isomer 193-

1H-NMR (400 MHz, CDCl3) δ: to 4.46 (2H, s), 5,88 (2H, s), 7,22-the 7.43 (5H, m), 7,51 (2H, d, J=8.7 Hz), EUR 7.57 (2H, d, J=8.7 Hz).

MS m/z: 349 (M++H).

Isomer 193-

1H-NMR (400 MHz, CDCl3) δ: and 4.68 (2H, s)5,72 (2H, s), 7,22 was 7.45 (5H, m), 7,33 (2H, d, J=8.6 Hz), 7,55 (2H, d, J=8.6 Hz).

MS m/z: 349 (M++H).

Example 194: 6-(1-benzyl-1H-tetrazol-5-yl)-6-[(4-chlorophenyl)sulfonyl]-1-hexanol

To a solution in toluene (5 ml) of 1-benzyl-5-(4-chlorobenzenesulfonyl)-1H-tetrazole (isomer 193) (174 mg, 0.50 mmol) and 5-(tert-butyldimethylsilyloxy)-1-pentanol (146 mg, of 0.60 mmol) was added cyanomethylene-n-butylphosphate (161 mg, of 0.60 mmol). The resulting mixture was heated at the boil under reflux for 8 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=87:13, concentrated under reduced pressure.

The residue was dissolved in tetrahydrofuran (5 ml) followed by the addition of a solution in tetrahydrofuran (0,410 ml, 0.41 mmol) Tetra-n-butylammonium. The resulting mixture was stirred at room temperature for 4 hours. After concentrating the reaction mixture under reduced pressure, to the residue was added ethyl acetate. The mixture was washed with a saturated aqueous solution of ammonium chloride. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain specified in C is the coupling head (115 mg, 0.26 mmol, 54%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 0,54-0,67 (1H, m), 0.79, which is of 1.02 (3H, m)1,08 (1H, t, J=5,9 Hz), 1,19-1,32 (2H, m), 1,94-2,05 (1H, m), 2.06 to of 2.16 (1H, m), of 3.43 (2H, q, J=5,9 Hz), is 4.21 (1H, DD, J=11,5, 3,4 Hz), 5,72 (1H, d, J=15,5 Hz), 6,04 (1H, d, J=15,5 Hz), 7,21-7,28 (2H, m), 7,37-7,44 (3H, m), 7,42 (2H, d, J=8.5 Hz), to 7.50 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3402, 2935, 1581, 1456, 1321, 1151, 1084, 1012, 725.

MS m/z: 435 (M++H).

FAB-MS: 435,1240 (calculated for C20H24ClN4O3S: 435,1258).

Example 195: 1-benzyl-5-[1-(4-chlorobenzenesulfonyl)cyclohexyl]-1H-tetrazol

To a solution in toluene (3 ml) of 6-(1-benzyl-1H-tetrazol-5-yl)-6-[(4-chlorophenyl)sulfonyl)-1-hexanol (104 mg, 0.24 mmol) was added a solution in toluene (2 ml) and cyanomethylene-n-butylphosphine (128 mg, 0.48 mmol). The resulting mixture was heated at the boil under reflux for 7 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1 was concentrated under reduced pressure. The obtained solid was washed with hexane/diethyl ether and then collected by filtration to obtain specified in the title compound (51 mg, 0.12 mmol, 51%) as a white solid.

1H-NMR (400 MHz, CDCl3) ; : 0,45-0,93 (2H, m), 1,07-to 1.21 (1H, m), 1,31 of 1.50 (3H, m), 2,07-of 2.20 (2H, m), 2,58 of 2.68 (2H, m), 6,13 (2H, s), 7,21 (2H, d, J=8,8 Hz), 7,28-7,39 (5H, m), 7,41 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 2941, 1574, 1460, 1392, 1302, 1282, 1142, 1080, 1011, 831.

TPL: 154-155°C.

Elemental analysis. Calculated for C20H21ClN4O2S: C, 57,62; H 5,08; Cl, Of 8.50; N, 13,44. Found: C, 57,47; H, 5,07; Cl, 8,53; N, 13,45.

MS m/z: 417 (M++H).

Example 196: 6-(2-benzyl-2H-tetrazol-5-yl)-6-[(4-chlorophenyl)sulfonyl]-1-hexanol

To a solution in toluene (5 ml) of 2-benzyl-5-(4-chlorobenzenesulfonyl)-2H-tetrazole (isomer 193) (174 mg, 0.50 mmol)obtained in example 193, and 5-(tert-butyldimethylsilyloxy)-1-pentanol was added cyanomethylene-n-butylphosphate (161 mg, of 0.60 mmol). The resulting mixture was heated at the boil under reflux for 8 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=17:3 was concentrated under reduced pressure.

Thus obtained residue was dissolved in tetrahydrofuran (5 ml) followed by the addition of a solution in tetrahydrofuran (0,574 ml, or 0.57 mmol) of Tetra-n-butylammonium, and the mixture was stirred at room temperature for 4 hours. After concentration of the reactions is authorized mixture under reduced pressure, to the residue was added ethyl acetate. The resulting mixture was washed with a saturated aqueous solution of ammonium chloride. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain specified in the title compound (155 mg, 0.36 mmol, 71%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,12-1,64 (7H, m), 2,22-of 2.34 (1H, m), a 2.36-2,48 (1H, m), of 3.56 (2H, Sirs), is 4.21 (1H, DD, J=11,4, and 3.8 Hz), 5,69 (1H, d, J=14.4 Hz), 5,73 (1H, d, J=14.4 Hz), 7,20 (2H, d, J=8,3 Hz), 7,28-of 7.48 (5H, m), 7,37 (2H, d, J=8,3 Hz).

IR (ATR) cm-1: 3543, 2933, 1581, 1475, 1394, 1321, 1149, 1088, 1012, 723.

MS m/z: 435 (M++H).

FAB-MS: 435,1252 (calculated for C20H24ClN4O3S: 435,1258).

Example 197: 2-benzyl-5-[1-(4-chlorobenzenesulfonyl)cyclohexyl]-2H-tetrazol

To a solution in toluene (3 ml) of 6-(2-benzyl-2H-tetrazol-5-yl)-6-[(4-chlorophenyl)sulfonyl)-1-hexanol (145 mg, 0.33 mmol) was added a solution in toluene (3 ml) and cyanomethylene-n-butylphosphine (179 mg, 0.67 mmol). The resulting mixture was heated at the boil under reflux for 7 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chrome is ographie on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1 was concentrated under reduced pressure. The obtained solid was washed with hexane/diethyl ether and then collected by filtration to obtain specified in the title compound (78 mg, 0,19 mmol, 56%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: 0,99-to 1.14 (2H, m), 1,21-of 1.36 (1H, m), 1,52-of 1.62 (1H, m), a 1.75-to 1.82 (2H, m), 2,15 was 2.25 (2H, m), 2,69 was 2.76 (2H, m), 5,72 (2H, s), 7,07 (2H, d, J=8,8 Hz), 7,11 (2H, d, J=8,8 Hz), 7,34-7,47 (5H, m).

IR (ATR) cm-1: 2939, 1579, 1477, 1396, 1317, 1144, 1084, 1012, 756.

TPL: 133-134°C.

Elemental analysis. Calculated for C20H21ClN4O2S: C, 57,62; H 5,08; Cl, Of 8.50; N, 13,44. Found: C, 57,74; H, 5,14; Cl, 8,51; N, 13,37.

MS m/z: 417 (M++H).

Example 198: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-(1-pyrrolidinyl)-1-propanone

In dichloromethane (6 ml) was dissolved 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propionic acid (200 mg, 0,554 mmol)obtained in example 62. To the resulting solution was added thionyl chloride (162 μl, 2.22 mmol). The resulting mixture was stirred at room temperature for 24 hours. Then the reaction mixture was concentrated to dryness. Thus obtained residue was dissolved in dichloromethane (6 ml) and the resulting solution was added pyrrolidine (185 μl, 2.22 mmol) and triethylamine (309 μl, 2.22 mmol). Poluchennymi was stirred at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane, washed successively with water, saturated aqueous ammonium chloride and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated. Thus obtained colorless solid was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (192 mg, 0,463 mmol, 84%) as colorless needle crystals.

1H-NMR (CDCl3) δ: 1,80-1,90 (2H, m), 1,96-2,03 (2H, m), 3,06 (1H, DD, J=16,4, 9.8 Hz), 3,28 is 3.57 (5H, m), 5.25-inch (1H, DD, J=9,8, and 3.7 Hz), for 6.81 (1H, TD, J=9,1, 4,4 Hz), 6,91-6,98 (1H, m), 7,18 (1H, DDD, J=8,6, 5,4, 3,2 Hz), 7,38 (2H, d, J=8.6 Hz), 7,53 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 2949, 1633, 1583, 1495, 1442, 1396, 1346, 1308, 1277, 1211, 1147, 1014, 822, 769, 708, 615, 536, 472.

TPL: 122-125°C.

MC m/z: 414 (M++H).

FAB-MS: 414,0769 (calculated for C19H19ClF2NO3S: 414,0742).

Elemental analysis. Calculated for C19H18ClF2NO3S: C, 55,14; H, To 4.38; Cl, To 8.57; F, 9,18; N, 3,38; S 7,75. Found: C, 55,22; H, 4,50; Cl, 8,44; F, 9,00; N, 3,39; S, 7,78.

Example 199: Tert-butyl 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyrate

In N,N-dimethylformamide (4 ml) was dissolved 2-[(4-chlorophenyl)sulfanilyl]-14-differental (101 mg, of 0.333 mmol)obtained in example 5. Once added to a solution of tert-butyl acrylate (146 μl, 1.00 mmol) and 1,8-diazabicyclo[5,4,0]undec-7-ene (151 μl, 1.00 mmol) stirring was carried out at room temperature for 1 week. Then the reaction mixture was concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1, was concentrated to obtain specified in the title compound (142 mg, 0,329 mmol, 99%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.40 (9H, s), 2,10-of 2.20 (1H, m), 2,23 to 2.35 (2H, m), 2,65 was 2.76 (1H, m), of 4.67 (1H, DD, J=10,3, 4,4 Hz), 6,85 (1H, TD, J=10,3, 4,4 Hz), of 6.96-7.03 is (1H, m), 7,24 (1H, DDD, J=8,6, 5,4, 3,2 Hz), 7,40 (2H, d, J=8,3 Hz), 7,56 (2H, d, J=8,3 Hz).

IR (ATR) cm-1: 2978, 1724, 1583, 1496, 1367, 1321, 1232, 1146, 1084, 1014, 829, 756, 710, 642, 629, 555, 471.

MS m/z: 431 (M++H).

FAB-MS: 431,0904 (calculated for C20H22ClF2O4S: 431,0895).

Example 200: 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyric acid

To a solution in dichloromethane (10 ml) of tert-butyl 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyrate (1,25 g of 3.33 mmol) was added triperoxonane acid (5 ml). The resulting mixture was stirred at room temperature for 4 hours. The solid obtained by concentrating the reaction mixture, paracrystalline is Ali from ethyl acetate to obtain specified in the title compound (595 mg, to 1.59 mmol, 48%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 2,32-of 2.50 (3H, m), 2.71 to of 2.81 (1H, m), and 4.68 (1H, DD, J=9,3, a 4.9 Hz), 6,86 (1H, TD, J=9,3, 4,4 Hz), 6,97? 7.04 baby mortality (1H, m), 7,21-7,27 (1H, m), 7,40 (2H, d, J=8.6 Hz), 7,56 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 2942, 1710, 1571, 1495, 1427, 1327, 1240, 1151, 1084, 1012, 916, 831, 789, 752, 710, 636, 555, 528, 463, 417.

TPL: 157-158°C.

MS m/z: 375 (M++H).

Elemental analysis. Calculated for C16H13ClF2O4S: C, 51,27; H, 3,50; Cl, 9,46; F, 10,14; S, 8,56. Found: C, 51,18; H, 3,47; Cl, 9,45; F, 10,32; S, 8,60.

Example 201: 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-(1-pyrrolidinyl)-1-butanone

To a solution in tetrahydrofuran (4 ml) of 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyric acid (150 mg, 0.400 mmol) was added pyrrolidine (40,1 ál, to 0.480 mmol), triethylamine (61,2 μl, 0,440 mmol), 4-dimethylaminopyridine (10.0 mg, 0,0820 mmol) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (84,5 mg, 0,440 mmol). The resulting mixture was stirred at room temperature for 18 hours. The solvent drove away. Thus obtained residue was washed in ethyl acetate. The resulting solution was washed with a saturated aqueous solution of ammonium chloride and a saturated salt solution, dried over anhydrous sodium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction, p is obtained from the eluate using a mixture of hexane:ethyl acetate=3:7, was concentrated. The obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (97,0 mg, 0,227 mmol, 57%) as colorless plate crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,78-of 1.93 (4H, m), 2,20 is 2.43 (3H, m), 2,69-2,78 (1H, m), 3.15 and 3.21-in (1H, m), 3.25 to 3,30 (1H, m)to 3.41 (2H, t, J=6.8 Hz), 4,84 (1H, DD, J=8,5, 5.6 Hz), 6,86 (1H, TD, J=9,0, 4.6 Hz), 6,95-7,02 (1H, m), from 7.24 (1H, DDD, J=8,8, 5,6, 3,4 Hz), 7,40 (2H, d, J=8.5 Hz), to 7.59 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3072, 2973, 2875, 1635, 1496, 1444, 1421, 1317, 1234, 1173, 1146, 1082, 1011, 877, 760, 737, 619, 559, 509, 469,

TPL: 134-135°C.

MS m/z: 428 (M++H).

Elemental analysis. Calculated for C20H20ClF2NO3S: C, 56,14; H, 4,71; Cl, 8,29; F, 8,88; N, 3,27; S, 7,49. Found: C, 56,01; H, 4,68; Cl, 8,03; F, 8,64; N, 3,35; S, 7,63.

Example 202: 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1-valeric acid

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 578 μl, 0,908 mmol) was added to the solution in dimethoxyethane (5 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (250 mg, 0,825 mmol)obtained in example 5. After increasing the temperature of the reaction mixture to room temperature, the mixture was again cooled to -78°C. was Added ethyl-4-bromobutyrate (142 mg, 0,990 mmol)and the mixture was stirred at room temperature for 5 hours. To the reaction mixture was added water, followed by extraction of dihl what Rotana. The extracts were combined, washed with water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was dissolved in tetrahydrofuran (4 ml). To the mixture was added an aqueous solution (2 ml) of lithium hydroxide (to 19.8 mg, 0,825 mmol). The mixture was stirred at room temperature for 15 hours. After adding 1 N. chloride-hydrogen acid for acidification of the mixture to the sour reaction was extracted with dichloromethane. The extracts were combined, washed with saturated salt solution, dried over magnesium sulfate and then concentrated. The obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (139 mg, 0,357 mmol, 43%) as a colourless solid.

1H-NMR (400 MHz, CDCl3) δ: 1,53-of 1.55 (2H, m), 2,12-of 2.23 (1H, m), 2,32-of 2.54 (3H, m)to 4.52 (1H, DD, J=11,5, and 3.7 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7,02 (1H, m), 7.23 percent-7,28 (1H, m), 7,38 (2H, d, J=8,3 Hz), 7,53 (2H, d, J=8,3 Hz).

IR (ATR) cm-1: 2945, 1693, 1585, 1495, 1427, 1323, 1296, 1238, 1211, 1153, 1086, 1012, 949, 829, 750, 708, 628, 542, 463,

MP: 151-152°C.

MS m/z: 389 (M++H).

Elemental analysis. Calculated for C17H15ClF2O4S: C, 52,51; H, 3,89; Cl, 9,12; F, 9,77; S, 8,25. Found: C, 52,36; H, 3,88; Cl, 9,14; F, 9,75; S Of 8.37.

Example 203: 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1-(1-pyrrolidinyl)-1-pentanone

In the atmosphere the ore argon at -15 aboutWith N-methylmorpholin (a 38.5 μl, 0.351 mmol) and isobutylparaben (45,8 μl, 0.351 mmol) was added to the solution in tetrahydrofuran (4 ml) of 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1-valerianic acid (130 mg, 0,334 mmol). The mixture was stirred for 5 minutes at -15°C. was Added pyrrolidine (33,5 μl, 0,401 mmol)and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane, washed with saturated aqueous ammonium chloride and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:2, was concentrated. The obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (128 mg, 0,290 mmol, 87%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,52-of 1.66 (2H, m), 1,80-of 1.88 (2H, m), 1.91 a-to 1.98 (2H, m), 2,15-of 2.34 (3H, m), 2,41-of 2.50 (1H, m)to 3.34 (2H, dt, J=6,8,2,4 Hz)to 3.41 (2H, t, J=6.8 Hz), 4,55 (1H, DD, J=11,7, 2,9 Hz), for 6.81 (1H, TD, J=9,0, 4,4 Hz), 6,93-7,00 (1H, m), 7,22-7,28 (1H, m), 7,38 (2H, d, J=8.5 Hz), 7,52 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 2941, 2883, 1635, 1583, 1496, 1441, 1315, 1277, 1244, 1215, 1180, 1146, 1082, 1038, 1014, 829, 787, 752, 710, 631, 548, 519, 480, 440.

TPL: 125-126°C.

MS m/z: 442 (M++H).

Elemental analysis. The calculated C 21H22ClF2NO3S: C, 57,07; H, 5,02; Cl, 8,02; F, At 8.60; N, 3,17; S, 7,26. Found: C, 57,04; H, 5,13; Cl, 8,03; F, 8,64; N, 3,29; S, 7,39.

Reference example 37: 5-bromo-1-(1-pyrrolidinyl)-1-pentanone

In an argon atmosphere N-methylmorpholin (606 μl, 5,52 mmol) and isobutylparaben (757 μl, 5,80 mmol) was added to the solution in tetrahydrofuran (35 ml) 6-bombalurina acid (1,00 g, 5,52 mmol) at -15aboutC. the resulting mixture was stirred for 5 minutes at -15°C. was Added pyrrolidine (484 μl, 5,80 mmol)and the resulting mixture was stirred at -15°C for 5 minutes and then at room temperature for 1 hour. Added ice water, and the mixture was extracted with dichloromethane. The extract was washed with saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:2, was concentrated to obtain specified in the title compound (1.18 g, 5,04 mmol, 91%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,77 is 2.00 (8H, m)to 2.29 (2H, t, J=7,3 Hz), 3,39-of 3.48 (6H, m).

MS m/z: 234 (M++H).

Example 204: 6-[(4-chlorophenyl)sulfonyl]-6-(2,5-differenl)-1-hexanone

In the atmosphere of argon and at -78°With n-utility (1.57 M dissolve the in hexane, 701 µl, 1.10 mmol) was added to the solution in dimethoxyethane (6 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (303 mg, 1.00 mmol)obtained in example 5. After increasing the temperature of the reaction mixture to room temperature, the mixture was again cooled to -78°C. After addition of 5-bromo-1-(1-pyrrolidinyl)-1-pentanone (281 mg, 1.20 mmol) the resulting mixture was stirred at room temperature for 20 hours. To the reaction mixture were added water and then diluted with dichloromethane. Thus obtained solution was washed successively with water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:2, was concentrated. The obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (385 mg, services, 0.844 mmol, 84%) as a colourless solid.

1H-NMR (400 MHz, CDCl3) δ: of 1.25 to 1.37 (2H, m), 1,58 is 1.75 (2H, m), 1,80-of 1.88 (2H, m), 1,91-of 1.97 (2H, m), 2,07-of 2.16 (1H, m), of 2.20 (2H, dt, J=7,6, and 3.2 Hz), 2,41-of 2.50 (1H, m)to 3.35 (2H, t, J=6.8 Hz), of 3.43 (2H, t, J=6.8 Hz), 4,50-4,56 (1H, m), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,94-7,01 (1H, m), 7,24 (1H, DDD, J=8,8, 5,4, 3,2 Hz), 7,38 (2H, d, J=8,8 Hz), 7,53 (2H, d, J=8,8 Hz),

IR (ATR) cm-1: 2952, 1626, 1493, 1441, 1321, 1232, 1149, 1086, 1014, 820, 768, 631, 528, 469.

TPL: 135-136#x000B0; C.

MS m/z: 456 (M++H).

Elemental analysis. Calculated for C22H24ClF2NO3S: C, 57,95; H, 5,31; Cl, 7,78; F, Of 8.33; N, 3,07; S, 7,03. Found: C, 57,73; H, 5,20; Cl, 7,76; F, 8,31; N, 3,13; S, 7,14.

Example 205: 7-[(4-chlorophenyl)sulfonyl]-7-(2,5-differenl)heptane acid

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 2,31 ml, 3.63 mmol) was added to the solution in dimethoxyethane (20 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (1.00 mg, 3,30 mmol)obtained in example 5. After increasing the temperature of the reaction mixture to room temperature, again cooled to -78°C. To the reaction mixture were added ethyl-6-Bromhexine (706 μl, of 3.96 mmol) followed by stirring the mixture at room temperature for 18 hours. To the reaction mixture was added water, and then the mixture was extracted with dichloromethane. The extracts were combined, washed with saturated salt solution, dried over magnesium sulfate and then concentrated to obtain the ether compound as a crude product. The obtained ether compound was dissolved in tetrahydrofuran (20 ml). To the resulting solution was added an aqueous solution (6 ml) of lithium hydroxide (96.0 mg, 4.00 mmol). The mixture was stirred at room temperature for 18 hours. After acidification of the reaction mixture until the acid reaction of 1 N. chloris the o-hydrogen acid acidic mixture was extracted with dichloromethane. The extracts were combined, washed with saturated salt solution, dried over magnesium sulfate and then concentrated. The obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (931 mg, of 2.23 mmol, 68%) as a colourless solid.

1H-NMR (400 MHz, CDCl3) δ: 1,22-1,90 (7H, m), is 2.30 (2H, t, J=7,3 Hz), 2.40 a-2,48 (1H, m), 4,51 (1H, DD, J=11,7, 2,9 Hz), 6,83 (1H, TD, J=9,0,4,4 Hz), 6,94-7,01 (1H, m), 7,22-7,26 (1H, m), 7,38 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3487, 2941, 2860, 1728, 1496, 1414, 1321, 1217, 1176, 1149, 1086, 1014, 818, 787, 756, 633, 536, 478.

TPL: 72-76°C.

MS m/z: 417 (M++H).

Elemental analysis. Calculated for C19H19ClF2O4S·0,5H2O: C, 53,59; H, 4,73; Cl, 8,32; F, 8,92; S, 7,53. Found: C, 53,83; H, 4,67; Cl, 8,39; F, 8,94; S 7,72.

Example 206: 7-[(4-chlorophenyl)sulfonyl]-7-(2,5-differenl)-1-(1-pyrrolidinyl)-1-heptanone

In an argon atmosphere and at -15aboutWith N-methylmorpholin (53,9 μl, 0,491 mmol) and isobutylparaben (64,1 μl, 0,491 mmol) was added to the solution in tetrahydrofuran (5 ml) of 7-[(4-chlorophenyl)sulfonyl]-7-(2,5-differenl)heptane acid (195 mg, 0,468 mmol). The resulting mixture was stirred for 5 minutes at -15°C. was Added pyrrolidine (46,9 μl, 0,562 mmol)and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane, washed sledovatelno saturated aqueous sodium bicarbonate, water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:7, was concentrated. The obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (171 mg, 0,364 mmol, 78%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: 1,21 was 1.43 (4H, m), 1,54-to 1.67 (2H, m), 1,80-to 1.98 (4H, m), 2,03-to 2.15 (1H, m), 2,19 (2H, t, J=7,6 Hz), 2,38 is 2.46 (1H, m)to 3.36 (2H, t, J=6.8 Hz), 3,44 (2H, t, J=6.8 Hz), 4,51 (1H, DD, J=11,5, 2,9 Hz), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,94-7,01 (1H, m), 7.23 percent (1H, DDD, J=8,8, 5,4, 3,2 Hz), 7,38 (2H, d, J=8,8 Hz), 7,53 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 2960, 1630, 1583, 1496, 1442, 1315, 1228, 1196, 1149, 1086, 1011, 872, 841, 822, 787, 756, 633, 536, 467.

TPL: 106-106°C.

MS m/z: 470 (M++H).

Elemental analysis. Calculated for C23H26ClF2NO3S: C, 58,78; H, 5,58; Cl, 7,54; F, 8,08; N, 2,98; S 6,82. Found: C, 58,53; H, 5,49; Cl, 7,66; F, 8,19; N, A 3.06; S, 8,82.

Example 207: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol

Method 1: If 0°With sociallyengaged (1.0 M solution in tetrahydrofuran, 6,74 ml, 6,74 mmol) was added dropwise to the solution in tetrahydrofuran (10 ml), ethyl-3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propionate (1.31 g, 3,37 mmol)obtained in example 25. C is the mixture stirred at room temperature for 3 hours. After cooling the reaction mixture to 0°and adding a saturated aqueous solution of ammonium chloride and the mixture was stirred at room temperature for 15 hours. Besieged thus, the solid was filtered. Thus obtained solution was diluted with ether, washed with saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (397 mg, to 1.14 mmol, 34%) as a colourless solid.

Method 2: In an argon atmosphere and at -78°With n-utility (1.57 M solution in hexane, to 4.62 ml, 7,26 mmol) was added to the solution in dimethoxyethane (50 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (2,00 mg, 6,60 mmol)obtained in example 5. The temperature of the mixture was raised to room temperature and stirring was performed for 15 minutes. After cooling the reaction mixture to -78°solution was added in dimethoxyethane (5 ml) of tert-butyl(2-idetrorce)dimethylsilane (2,08 g, 7,26 mmol). The resulting mixture was stirred at room temperature for 15 hours. To the reaction mixture was added water, followed by extraction with ether. The extracts were combined, washed successively with water and saturated salt solution, dried over magnesium sulfate and ZAT is concentrated. Thus obtained residue was subjected to shortened chromatography on silica gel (hexane-ethyl acetate=7:1) to remove impurities high polarity. The resulting oil was dissolved in tetrahydrofuran (50 ml)and the resulting solution was added tetrabutylammonium (1 M solution in tetrahydrofuran, of 14.5 ml, 14.5 mmol). After stirring for 2 days the solvent drove away. Thus obtained residue was dissolved in dichloromethane followed by successive washing 1 N. chloride-hydrogen acid, water and saturated salt solution, drying over magnesium sulfate and concentration. Thus obtained residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated to obtain specified in the connection header (2,07 g of 5.82 mmol, 88%) as a colourless solid.

1H-NMR (CDCl3) δ and 2.27 (1H, DD d, J=19,3, 10,3, 5,1 Hz), of 2.72 (1H, DD d, J=19,3, 9,0, 3,9 Hz), 3,48 (1H, TD, J=10,5, 4,4 Hz), 3,85 (1H, TD, J=10,5, 5,1 Hz), is 4.85 (1H, DD, J=10,3, 3,9 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), 6,95-7,02 (1H, m), 7.23 percent-7,27 (1H, m), 7,31 (2H, d, J=8.5 Hz), 7,55 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3519, 3043, 2964, 2922, 2875, 1576, 1495, 1427, 1396, 1308, 1186, 1147, 1084, 1036, 957, 895, 818, 786, 752, 708, 625, 521, 467.

TPL: 147-149°C.

MS m/z: 347 (M++H).

Elemental analysis. Calculated for C15H13ClF2O3S: C, 51,95; H, 3,78;Cl, 10,22; F, 10,96; S, 9,25. Found: C, 51.89ˆ; H, 3,75; Cl, 10,15; F, 10,90; S, 9,36.

Example 208: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl-1-pyrrolidinecarboxylic

In dichloromethane (4 ml) was dissolved 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (150 mg, 0,432 mmol) followed by the addition of triethylamine (63,2 μl, 0,454 mmol) and 4-nitrophenylphosphate (91,7 mg, 0,454 mmol). The resulting mixture was stirred at room temperature for 20 hours. Added pyrrolidine (43,2 μl, 0,518 mmol) and triethylamine (72,1 μl, 0,518 mmol)and the mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:2, was concentrated. The obtained colorless solid was recrystallized from hexane to obtain specified in the connection header (84,0 mg, 0,189 mmol, 44%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,77-of 1.88 (4H, m), 2,37-2,47 (1H, m), 2,75-a-3.84 (1H, m), 3,09-3,20 (2H, m), 3,28-to 3.34 (2H, m)to 3.89 (1H, DD d, J=11,3, 8,3, 4,4 Hz), 4,22 (1H, dt, J=11,3, 5.6 Hz), 4,70 (1H, DD, J=11,3, 3.6 Hz), 6,83 (1H, TD, J=9,1, 4,4 Hz), 6,95-7,02 (1H, m), 7,20-7,26 (1H, m), 7,39 (2H, d, J=8.6 Hz), 7,54 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 2974, 2879, 1685, 1585, 1496, 1427, 1373, 1306, 1178, 1149, 1091, 816, 766, 754, 710, 631, 553, 523, 467, 444.

MP.: 109-110° C.

MS m/z: 444 (M++H).

Elemental analysis. Calculated for C20H20ClF2NO4S: C, 54,12; H, 4,54; Cl, 7,99; F, 8,56; N, 3,16; S, 7,37. Found: C, 53,93; H, 4,49; Cl, 8,00; F, Of 8.50; N, 3,22; S, 7,37.

Example 209: Hydrochloride 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl-4-benzyl-1-piperidinecarboxylate

3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (150 mg, 0,432 mmol)obtained in example 207, was dissolved in dichloromethane (4 ml) followed by the addition of triethylamine (63,2 μl, 0,454 mmol) and 4-nitrophenylphosphate (91,7 mg, 0,454 mmol). The resulting mixture was stirred at room temperature for 18 hours. To the reaction mixture were added N-benzylpiperazine (90,3 μl, 0,518 mmol) and triethylamine (72,1 μl, 0,518 mmol)and the mixture was stirred at room temperature for 24 hours. Then the reaction mixture was concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated. The obtained colorless solid was dissolved in ethanol and then adding 1 N. chloride-hydrogen acid (0.5 ml). The mixture is then concentrated to dryness. The obtained solid was recrystallized from ethanol to obtain specified in the title compound (132 mg, 0,226 mmol, 52%) in sidebusting solids.

1H-NMR (400 MHz, CDCl3) δ: 2,35-of 2.45 (1H, SIRM), 2,56-of 2.72 (2H, SIRM), 2,79-is 2.88 (1H, m), 3,28 is 3.40 (2H, m), 3,63-4,28 (8H, m), 4,60 (1H, DD, J=10,8, 3,9 Hz), PC 6.82 (1H, TD, J=9,1, 4,4 Hz), of 6.96-7,02 (1H, m), 7.18 in-7,26 (1H, SIRM), 7,39 (2H,, d, J=8.6 Hz), 7,45-7,53 (5H, m), 7,58-to 7.64 (2H, Shir).

IR (ATR) cm-1: 2958, 2708, 2675, 1701, 1583, 1495, 1423, 1321, 1255, 1217, 1153, 1142, 1092, 951, 827, 752, 700, 627, 555, 525, 468.

TPL: 184-189°C.

MS m/z: 549 (M++H).

Elemental analysis. Calculated for C27H27ClF2N2O4S·HCl: C, 55,39; H, 4,82; Cl, 12,11; F, Of 6.49; N, 4,78; S, 5,48. Found: C, 55,11; H, 4,80; Cl, 11,92, F, 6,36; N, 4,85; S, 5,54.

Example 210: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl-N-(2-hydroxyethyl)-N-methylcarbamate

In dichloromethane (4 ml) was dissolved 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (150 mg, 0,432 mmol)obtained in example 207, followed by the addition of triethylamine (63,2 μl, 0,454 mmol) and 4-nitrophenylphosphate (91,7 mg, 0,454 mmol). The resulting mixture was stirred at room temperature for 20 hours. To the reaction mixture were added N-methylethanolamine (to 41.6 μl, 0,518 mmol) and triethylamine (72,1 μl, 0,518 mmol)and the resulting mixture was stirred at room temperature for 24 hours. Then the reaction mixture was concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:etilize is t=1:2, concentrated with obtaining specified in the title compound (136 mg, 0,304 mmol, 70%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 2,33-2,48 (1H, SIRM), 2.77-to of 2.97 (4H, m), 3.27 to of 3.43 (2H, SIRM), 3,68-of 3.78 (2H, Sirs), a 3.87-3,98 (1H, SIRM), 4,19-4,30 (1H, SIRM)and 4.65-of 4.77 (1H, SIRM), at 6.84 (1H, TD, J=9,1, 4,4 Hz), 6,95-7,02 (1H, m), 7,21-7,26 (1H, m), 7,39 (2H, d, J=8,8 Hz), 7,54 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 3423, 2943, 1685, 1583, 1495, 1317, 1279, 1215, 1147, 1080, 1012, 827, 754, 708, 627, 555, 467.

MS m/z: 448 (M++H).

EI-MS: 447,0699 (calculated for C19H20ClF2NO5S: 447,0719).

Example 211: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl-4-morpholinylcarbonyl

In dichloromethane (4 ml) was dissolved 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (150 mg, 0,432 mmol)obtained in example 207, followed by the addition of triethylamine (63,2 μl, 0,454 mmol) and 4-nitrophenylphosphate (91,7 mg, 0,454 mmol). The resulting mixture was stirred at room temperature for 20 hours. To the reaction mixture was added morpholine (45,1 μl, 0,518 mmol) and triethylamine (72,1 μl, 0,518 mmol). The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane, washed sequentially with saturated aqueous sodium bicarbonate solution and saturated salt solution, dried over anhydrous magnesium sulfate and then concentrated. Obtained is m, the residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:2, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (123 mg, 0,267 mmol, 62%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 2,39-2,48 (1H, m), 2,79-is 2.88 (1H, m), 3,19-3,47 (4H, W), 3,52-3,70 (4H, Sirs), of 3.97 (1H, DD d, J=11,2, 8,3, 5,1 Hz)to 4.23 (1H, dt, J=11,2, 5,6 Hz)and 4.65 (1H, DD, J=11,2, 3,4 Hz), at 6.84 (1H, TD, J=9,0, 4.6 Hz), 6,97-7,03 (1H, m), 7,22-7,26 (1H, m), 7,40 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3086, 2864, 1684, 1576, 1498, 1469, 1427, 1311, 1281, 1240, 1221, 1178, 1142, 1080, 837, 773, 752, 710, 633, 557, 528, 471.

TPL: 140-141°C.

MS m/z: 460 (M++H).

Elemental analysis. Calculated for C20H20ClF2NO5S: C, 52,23; H, To 4.38; Cl, 7,71; F, Compared To 8.26; N, 3,05; S 6,97. Found: C, 51,95; H, 4,29; Cl, 7,80; F, 8,32; N, 3,12; S, 7,12.

Example 212: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl-4-phenyl-1-piperidinecarboxylate

3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (150 mg, 0,432 mmol)obtained in example 207, was dissolved in dichloromethane (6 ml) followed by the addition of triethylamine (63,2 μl, 0,454 mmol) and 4-nitrophenylphosphate (91,7 mg, 0,454 mmol). The resulting mixture was stirred at room temperature for 18 hours. To the reaction mixture were added N-phenylpiperazin (79,1 μl, 0,518 mmol) and triethylamine(72,1 μl, 0,518 mmol)and the mixture was stirred at room temperature for 4 hours. The reaction mixture was diluted with dichloromethane, washed sequentially with saturated aqueous sodium bicarbonate solution and saturated salt solution, dried over anhydrous magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1 concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (158 mg, 0,295 mmol, 68%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 2,40-of 2.50 (1H, m), 2,80-2,89 (1H, m), 3.00 and-3,15 (4H, Sirs), 3,37-the 3.65 (4H, m), 3,98 (1H, DDD, J=11,2, 8,3, 5,1 Hz), 4,24 (1H, dt, J=11,2, 5.6 Hz), of 4.67 (1H, DD, J=11,2, 3,9 Hz), at 6.84 (1H, TD, J=9,0, 4.6 Hz), 6,89-6,93 (3H, m), 6,95-7,03 (1H, m), 7.23 percent-to 7.32 (3H, m), 7,39 (2H, d, J=8,3 Hz), 7,54 (2H, d, J=8,3 Hz).

IR (ATR) cm-1: 2829, 1687, 1599, 1581, 1495, 1437, 1321, 1223, 1151, 1130, 1084, 1001, 930, 814, 758, 692, 634, 552, 469.

TPL: 127-129°C.

MS m/z: 535 (M++H).

Elemental analysis. Calculated for C26H25ClF2N2O4S: C, 58,37; H, 4,71; Cl, 6,63; F, 7,10; N, 5,24; S 5,99. Found: C, 58,28; H, 4,86; Cl, 6,56; F, 7,17; N, 5,30; S, 6,13.

Example 213: Hydrochloride 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl-4-methyl-1-piperidinecarboxylate

3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (150 mg, 0,432 mmol)obtained in example 207, was dissolved in dichloromethane (4 ml) followed by the addition of triethylamine (63,2 μl, 0,454 mmol) and 4-nitrophenylphosphate (91,7 mg, 0,454 mmol). The resulting mixture was stirred at room temperature for 18 hours. To the reaction mixture were added N-methylpiperazine (57,4 μl, 0,518 mmol) and triethylamine (72,1 μl, 0,518 mmol)and the mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with dichloromethane, washed sequentially with saturated aqueous sodium bicarbonate solution and saturated salt solution, dried over sodium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of dichloromethane:methanol=30:1 was concentrated. The thus obtained solid substance was dissolved in ethanol. After adding a mixture of 1 N. chloride-hydrogen acid-ethanol (2 ml) the resulting mixture was concentrated to dryness. The thus obtained solid substance was washed with ethyl acetate to obtain specified in the connection header (to 96.9 mg, 0,189 mmol, 44%) as a pale yellow solid.

1H-NMR (400 MHz, CDCl3) δ: 2,37-2,47 (1H, m), 2,60 of 2.92 (8H, m), 3,20-4,30 (6H, m), to 4.62 (1H, DD, J=10,0, 3,4 Hz), 6,85 1H, TD, J=9,0, 4,4 Hz), 6,98-7,05 (1H, m), 7,19-7,28 (1H, m), 7,39 (2H, d, J=8,8 Hz), 7,51 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 2387, 1699, 1583, 1496, 1473, 1425, 1317, 1255, 1232, 1176, 1149, 1084, 978, 829, 758, 710, 629, 555, 467.

MS m/z: 473 (M++H).

Elemental analysis. Calculated for C21H23ClF2N2O4S·HCl·0,25H2O: C, 49,08; H, 4,81; Cl, 13,80; F, 7,39; N, The 5.45; S, 6,24. Found: C, 49,03; H, 5,01; Cl, 13,31; F, 7,31; N, 5,54; S, 6,28.

Example 214: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propellernet

3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (200 mg, 0,576 mmol)obtained in example 207, was dissolved in dichloromethane (4 ml) followed by the addition of triethylamine (84,2 μl, 0,605 mmol) and 4-nitrophenylphosphate (122 mg, 0,605 mmol). The resulting mixture was stirred at room temperature for 18 hours. To the reaction mixture was added concentrated aqueous ammonia (2.5 ml)and the mixture was stirred intensively at room temperature for 3 hours. After separation of the aqueous layer, the organic layer was washed with water and saturated salt solution, dried over sodium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated. The thus obtained solid substance was recrystallized from mesitylacetate-hexane to obtain specified in the title compound (156 mg, 0,353 mmol, 61%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 2,34 is 2.44 (1H, m), 2.77-to of 2.86 (1H, m)to 3.89 (1H, DDD, J=11,0, 9,0, 5,1 Hz), 4,19 (1H, dt, J=11,0, 5.6 Hz), a 4.53 (2H, Sirs), 4,69 (1H, DD, J=11,0, 3,9 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), 6,97-7,03 (1H, m), 7,24 (1H, DDD, J=8,8, 5,4, 3,2 Hz), 7,40 (2H, d, J=8.5 Hz), 7,54 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3452, 3263, 1734, 1606, 1493, 1396, 1313, 1230, 1144, 1080, 1051, 957, 829, 795, 752, 623, 553, 465.

TPL: 139-140°C.

MS m/z: 390 (M++H).

Elemental analysis. Calculated for C16H14ClF2NO4S: C, At 49.30; H, 3,62; Cl, 9,10; F, Of 9.75; N, 3,59; S, 8,23. Found: C, 49,13; H, 3,53; Cl, 9,19; F, 9,86; N, 3,68; S, 8,35.

Example 215: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl-N-methylcarbamate

3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (200 mg, 0,576 mmol)obtained in example 207, was dissolved in dichloromethane (4 ml) followed by the addition of triethylamine (84,2 μl, 0,605 mmol) and 4-nitrophenylphosphate (122 mg, 0,605 mmol). The resulting mixture was stirred at room temperature for 15 hours. After addition of methylamine (2.00 M solution in tetrahydrofuran, 2.0 ml, 4.00 mmol) and the mixture was stirred at room temperature for 24 hours. Added methylamine (2.00 M solution in tetrahydrofuran, 3.0 ml, 4.00 mmol)and the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with dichloromethane, washed successively nasy the n aqueous solution of sodium bicarbonate, water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:2, was concentrated. The obtained concentrate was purified advanced high-performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to produce specified in the connection header (62,1 mg, 0,154 mmol, 27%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 2,32-of 2.45 (1H, m), 2,60-to 2.85 (4H, m), 3,83-are 3.90 (1H, m), 4,19 (1H, dt, J=11,0, a 5.4 Hz), 4,49 (1H, Sirs), and 4.68 (1H, m), at 6.84 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7,02 (1H, m), 7,20-7,26 (1H, m), 7,39 (2H, d, J=8,5 Hz), 7,54 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3403, 1709, 1527, 1496, 1477, 1317, 1248, 1147, 1086, 1012, 827, 754, 629, 555, 467.

MS m/z: 404 (M++H).

FAB-MS: 404,0551 (calculated for C17H17ClF2NO4S: 404,0535).

Example 216: 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl-N,N-dimethylcarbamate

3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)-1-propanol (200 mg, 0,576 mmol)obtained in example 207, was dissolved in dichloromethane (4 ml) followed by the addition of triethylamine (84,2 μl, 0,605 mmol) and 4-nitrophenylphosphate (122 mg, 0,605 mmol). The resulting mixture was stirred at room temperature for 6 hours. To actionnow mixture was added 50% aqueous solution of dimethylamine (2 ml). The mixture was stirred at room temperature for 15 hours. After further addition of 50% aqueous dimethylamine (1 ml) and stirring continued at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane, washed with 1 N. sodium hydroxide, water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:2, was concentrated to obtain specified in the title compound (151 mg, 0,362 mmol, 63%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 2,38 is 2.46 (1H, m), 2,70-2,88 (7H, m)to 3.89 (1H, DDD, J=11,2, 8,3, a 4.9 Hz), is 4.21 (1H, dt, J=11,2, 5.6 Hz), 4,69 (1H, DD, J=11,2, 3,9 Hz), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,95-7,02 (1H, m), 7.23 percent (1H, DDD, J=8,8, 5,4, 3,4 Hz), 7,39 (2H, d, J=8.5 Hz), 7,54 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 2943, 1697, 1583, 1495, 1402, 1319, 1279, 1223, 1180, 1147, 1082, 1012, 829, 754, 710, 623, 555, 525, 467.

MS m/z: 418 (M++H).

FAB-MS: 418,0692 (calculated for C18H19ClF2NO4S: 418,0691).

Example 217: 2-[1-[(4-chlorophenyl)sulfonyl]-2-phenylethyl]-1,4-differenza

In the atmosphere of argon and at -78°With n-utility (1.60 M hexane solution, 459 μl, 0,734 mmol) was added to the solution in dimethoxyethane (50 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-gifthorse the ash (202 mg, 0,667 mmol)obtained in example 5. Then the temperature of the mixture was raised to room temperature. After cooling the reaction mixture to -78°C was added dropwise benzylbromide (87,2 μl, 0,734 mmol). When the temperature of the reaction mixture to room temperature, stirring is continued for 15 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The extracts were combined, washed with saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=6:1, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (125 mg, 0,318 mmol, 48%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: of 3.32 (1H, DD, J=13,9, 11.7 Hz), a-3.84 (1H, DD, J=13,9, 3,4 Hz), to 4.81 (1H, DD, J=11,7, 3,4 Hz), 6,69 (1H, TD, J=9,3, 4,4 Hz), 6.87 in-6,94 (1H, m), 7,00-7,05 (2H, m), 7,12-7,20 (3H, m), 7,38-the 7.43 (3H, m), EUR 7.57 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 1574, 1493, 1303, 1279, 1219, 1144, 1083, 1011, 879, 825, 785, 742, 698, 633, 555, 526, 467.

TPL: 160-161°C.

MS m/z: 393 (M++H).

Elemental analysis. Calculated for C20H15ClF2NO2S: C, 61,15; H, 3,85; Cl, 9,02; F, 9,67; S, 8,16. Found: C, 61,07; H, A 3.87; Cl,8,95; F, 9,95; S, 8,30.

Example 218: 2-[2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)ethyl]pyridine

In an argon atmosphere 2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (150 mg, 0,495 mmol)obtained in example 5 and 2-pyridinemethanol (95,5 μl, 0,990 mmol) was dissolved in toluene (5 ml) followed by addition of cyanomethylene-n-butylphosphine (239 mg, 0,990 mmol). The resulting mixture was heated at the boil under reflux for 18 hours in an argon atmosphere. Then the reaction mixture was concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (96,6 mg, 0,245 mmol, 49%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 3,49 (1H, DD, J=14,7, to 10.7 Hz), 3,95 (1H, DD, J=14,7, 4.6 Hz), lower than the 5.37 (1H, DD, J=11,0, 4,2 Hz), was 6.73 (1H, TD, J=9,0, 4,4 Hz), 6,86-6,94 (1H, m), 7.03 is-7,07 (2H, m), 7,33 (1H, DDD, J=8,8, 5,4, 3,2 Hz), 7,39 (2H, d, J=8.5 Hz), 7,49 (1H, TD, J=7,8) and 1.7 Hz), 7,60 (2H, d, J=8.5 Hz), to 8.41 (1H, d, J=4.4 Hz).

IR (ATR) cm-1: 3041, 1585, 1496, 1433, 1321, 1277, 1149, 1086, 910, 825, 779, 746, 644, 536, 461, 436.

TPL: 105-107°C.

MS m/z: 394 (M++H).

Elemental analysis. Calculated for C19H14ClF2NO2S C, 57,94; H, To 3.58; Cl, 9,00; F, 9,65; N, 3,56; S, 8,14. Found: C, 57,85; H, 3,59; Cl, 8,97; F, 9,52; N, 3,69; S, 8,28.

Example 219: 3-[2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)ethyl]pyridine

In an argon atmosphere 2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (120 mg, 0,396 mmol)obtained in example 5, and 3-pyridinemethanol (50,1 μl, 0,515 mmol) was dissolved in toluene (4 ml) followed by addition of cyanomethylene-n-butylphosphine (124 mg, 0,515 mmol). The resulting mixture was heated at the boil under reflux for 18 hours in an argon atmosphere. Then the reaction mixture was concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:7, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (to 90.3 mg, 0,229 mmol, 58%) as colorless columnar crystals.

1H-NMR (400 MHz, CDCl3) δ: 3,35 (1H, DD, J=14,4, 11.7 Hz), 3,85 (1H, DD, J=14,4, 3,9 Hz), of 4.77 (1H, DD, J=11,7, a 3.2 Hz), of 6.71 (1H, TD, J=9,0, 4,4 Hz), 6.90 to-6,97 (1H, m), 7,13 (1H, DD, J=8,1, 4.9 Hz), 7,37 was 7.45 (4H, m), EUR 7.57 (2H, d, J=8,8 Hz), 8,30 (1H, d, J=2.0 Hz), to 8.41 (1H, DD, J=4,9, 1.5 Hz).

IR (ATR) cm-1: 3078, 1577, 1495, 1427, 1313, 1279, 1217, 1144, 1082, 1012, 823, 775, 752, 706, 646, 557, 532, 464.

TPL: 162-163°C.

MS m/z: 394 (M++H).

Elemental analysis. Vice the Leno for C 19H14ClF2NO2S: C, 57,94; H, To 3.58; Cl, 9,00; F, 9,65; N, 3,56; S, 8,14. Found: C, 57,80; H, 3,51; Cl, 9,06; F, At 9.53; N, 3,71; S, By 8.22.

Example 220: 4-[2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)ethyl]pyridine

In an argon atmosphere 2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (200 mg, 0,660 mmol)obtained in example 5 and 4-pyridinemethanol (144 mg, 1,32 mmol) was dissolved in toluene (6 ml) followed by addition of cyanomethylene-n-butylphosphine (318 mg, of 1.32 mmol). The resulting mixture was heated at the boil under reflux for 15 hours in an argon atmosphere. Then the reaction mixture was concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate with the use of ethyl acetate, and concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (81,4 mg, 0,207 mmol, 31%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: to 3.34 (1H, DD, J=14,2, 12.0 Hz), a-3.84 (1H, DD, J=14,2, 3,4 Hz), to 4.81 (1H, DD, J=12,0, 3,4 Hz), 6,72 (1H, TD, J=9,0, 4.6 Hz), 6,91-of 6.96 (1H, m), 6,97 (2H, d, J=6,1 Hz), 7,34-7,39 (1H, m), 7,40 (2H, d, J=8.5 Hz), 7,56 (2H, d, J=8.5 Hz), 8,42 (2H, DD, J=4,4, 1.5 Hz).

IR (ATR) cm-1: 1597, 1493, 1417, 1301, 1277, 1219, 1174, 1144, 1082, 1012, 985, 883, 850, 808, 754, 706, 631, 606, 557, 524, 469.

TPL: 129°C.

MS m/z: 394 (M++H).

elementry analysis. Calculated for C19H14ClF2NO2S: C, 57,94; H, To 3.58; Cl, 9,00; F, 9,65; N, 3,56; S, 8,14. Found: C, 57,67; H, 3,45; Cl, 9,00; F, 9,78; N, 3,64; S, 8,31.

Example 221: 2-[3-(4-chlorophenylsulfonyl)-3-(2,5-differenl)propyl]thiophene

In an argon atmosphere 2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (100 mg, 0,330 mmol)obtained in example 5 and 2-(2-thienyl)ethanol (144 μl, of 1.32 mmol) was dissolved in toluene (3 ml) followed by addition of cyanomethylene-n-butylphosphine (159 mg, 0,660 mmol). The resulting mixture was heated at the boil under reflux for 15 hours under nitrogen atmosphere. Then the reaction mixture was concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=12:1, was concentrated to obtain specified in the connection header (90,0 mg, 0,218 mmol, 53%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 2,42-2,52 (1H, m), 2,68-and 2.83 (2H, m), 2,85 of 2.92 (1H, m), of 4.54 (1H, DD, J=11,2, 2.4 Hz), 6,70 (1H, d, J=2.7 Hz), 6,86 (1H, TD, J=9,0, 4,4 Hz), make 6.90 (1H, DD, J=5,1, 3,4 Hz), 6,97-7,05 (1H, m), 7,14 (1H, DD, J=5,1, 1.2 Hz), 7.24 to 7,29 (1H, m), 7,38 (2H, d, J=8.5 Hz), 7,51 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3086, 1583, 1495, 1425, 1394, 1317, 1277, 1147, 1084, 1012, 827, 754, 694, 627, 555, 465.

MS m/z: 413 (M++H).

FAB-MS: 413,0251 (calculated for C19H16ClF2O2S: 413,0248).

Example 222: Ethyl-N-[3-[(4-chlorphen the l)sulfonyl]-3-(2,5-differenl)propyl]carbamate

In nitrogen atmosphere and at 0aboutWith triethylamine (81,5 μl, 0,586 mmol) and azide diphenylphosphinic acid (126 μl, 0,586 mmol) was added to a solution in toluene (5 ml) of 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyric acid (200 mg, of 0.533 mmol)obtained in example 200, followed by stirring at 0°C for 2 hours. The reaction mixture was heated at the boil under reflux for 3 hours. After cooling to room temperature, and add ethanol (2 ml) the mixture was heated at the boil under reflux for 2 hours. Then the reaction mixture was concentrated. Thus obtained residue was dissolved in dichloromethane. The resulting solution was washed sequentially with a saturated aqueous solution of potassium bicarbonate, water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:3, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (129 mg, 0,309 mmol, 58%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: to 1.21 (3H, t, J=7,1 Hz), 2,24-of 2.36 (1H, m), 2.0 to 2,70 (1H, m), 3,10-to 3.33 (2H, m)4,06 (2H, q, J=7,1 Hz), 4,60 (1H, DD, J=11,0, 4.6 Hz), 4,70 (1H, Sirs), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,95-7,02 (1H, m), 7,21-7,26 (1H, m), 7,38 (2H, d, J=8,3 Hz), 7,52 (2H, d, J=8,3 Hz).

IR (ATR) cm-1: 3394, 1691, 1576, 1525, 1496, 1396, 1304, 1281, 1250, 1225, 1149, 1086, 1028, 1012, 974, 885, 829, 791, 766, 752, 629, 553, 465.

TPL: 121-122°C.

MS m/z: 418 (M++H).

Elemental analysis. Calculated for C18H18ClF2NO4S: C, 51,74; H, 4,34; Cl, 8,48; F, Which Is 9.09; N, 3,35; S, To 7.67. Found: C, 51,49; H, 4,43; Cl, 8,55; F, 9,13; N 3,61; S 7,75.

Example 223: Ethyl-N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl]-N-methylcarbamate

In tetrahydrofuran (4 ml) was dissolved ethyl-N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl]carbamate (100 mg, 0,239 mmol) followed by the addition of sodium hydride (60% dispersion in mineral oil, and 11.5 mg, 0,287 mmol). The resulting mixture was stirred at room temperature for 3 hours. Added itmean (17,8 μl, 0,287 mmol)and the mixture was stirred at room temperature for 15 hours. Was added sodium hydride (60% dispersion in mineral oil, 5,00 mg, 0.125 mmol) and itmean (10,0 ál, 0,161 mmol) followed by stirring at room temperature for 24 hours. Was added water (5 ml)and the mixture was concentrated. Thus obtained residue was extracted with ethyl acetate. The extract was washed with saturated salt solution, dried over magnesium sulfate and then concentrated thus Obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:1, was concentrated to obtain specified in the connection header (83,2 mg, rate of 0.193 mmol, 81%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,11-of 1.27 (3H, SIRM), of 2.20 to 2.35 (1H, SIRM), 2,68-2,90 (4H, m), 3,18-to 3.35 (2H, m), 3,93-4,12 (2H, SIRM), 4,51 (1H, Sirs), PC 6.82 (1H, TD, J=9,0, 4.6 Hz), of 6.96? 7.04 baby mortality (1H, SIRM), 7,21-7,27 (1H, SIRM), 7,38 (2H, d, J=8,5 Hz), 7,51 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 2983, 1693, 1583, 1495, 1319, 1182, 1147, 1084, 1012, 883, 827, 754, 710, 629, 555, 467.

MS m/z: 432 (M++H).

FAB-MS: 432,0838 (calculated for C19H21ClF2NO4S: 432,0848).

Example 224: 2-Iodate-N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyl]carbamate

In nitrogen atmosphere and at 0aboutWith triethylamine (157 μl, 1.13 mmol) and azide diphenylphosphinic acid (243 μl, 1.13 mmol) was added to a solution in toluene (5 ml) of 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)valerianic acid (400 mg, of 1.03 mmol)obtained in example 202. The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was heated at the boil under reflux for 3 hours. After cooling to room temperature and add 2-idechannel (160 μl, of 2.06 mmol) the mixture was heated at the boil under reflux for 1.5 hours. The reaction mixture was diluted with ethyl acetate and then washed p is therefore saturated aqueous sodium bicarbonate, water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:1, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (300 mg, 0,538 mmol, 52%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,44-to 1.60 (2H, m), 2.05 is-2,17 (1H, m), 2,44 is 2.55 (1H, m), 3,19 (2H, q, J=6.4 Hz), or 3.28 (2H, t, J=6.8 Hz), the 4.29 (2H, t, J=6.8 Hz), of 4.57 (1H, SIRM), was 4.76 (1H, Sirs), at 6.84 (1H, TD, J=9,0, 4,4 Hz), 6,95-7,02 (1H, m), 7.23 percent-7,28 (1H, m), 7,39 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3406, 1722, 1585, 1516, 1493, 1306, 1238, 1147, 1009, 872, 822, 781, 752, 708, 627, 546, 525, 463.

TPL: 100-101°C.

MS m/z: 558 (M++H).

Elemental analysis. Calculated for C19H19ClF2INO4S: C, 40,91; H, 3.43 Points; Cl, 6,36; F, For 6.81; N, Of 2.51; S 5,75. Found: C, 40,79; H, 3,40; Cl, 6,41; F, Of 6.96; N, 2,61; S 5,85.

Example 225: 3-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyl]-2-oxazolidinone

In nitrogen atmosphere and at 0aboutWith sodium hydride (60% dispersion in mineral oil, 13,6 mg, 0,340 mmol) was added to the solution in tetrahydrofuran (5 ml) of 2-Iodate-N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyl]carbamate (158 mg, 0,283 mmol). Poluchenno the mixture was stirred at room temperature for 18 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The extract was washed with saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:2, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (52.1 mg, 0,121 mmol, 43%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,52-to 1.63 (2H, m), 2.05 is-of 2.16 (1H, m), 2,42 is 2.51 (1H, m), 3,18-to 3.35 (2H, m), 3,50 (2H, t, J=8,3 Hz), or 4.31 (2H, DD, J=8,8, 7,1 Hz), 4,60 (1H, DD, J=10,3, a 4.9 Hz), 6,85 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7,02 (1H, m), 7,22-7,28 (1H, m), 7,39 (2H, d, J=8.5 Hz), 7,54 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 2918, 1734, 1583, 1487, 1425, 1308, 1265, 1182, 1130, 1086, 1012, 895, 804, 758, 708, 594, 577, 538, 478, 444.

TPL: 156-159°C.

MS m/z: 430 (M++H).

Elemental analysis. Calculated for C19H18ClF2NO4S: C, 53,09; H, 4,22; Cl, 8,25; F, 8,84; N, 3,26; S 7,46. Found: C, Of 52.84; H, 4,15; Cl, 8,40; F, 8,96; N, 3,33; S, 7,58.

Example 226: tert-butyl N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyl]carbamate

In the atmosphere of nitrogen triethylamine (126 μl, 0,907 mmol) and azide diphenylphosphinic acid (195 μl, 0,907 mmol) was added to a solution in toluene (6 ml) 5-[(4-chlorphen is)sulfonyl]-5-(2,5-differenl)valerianic acid (294 mg, of 0.533 mmol)obtained in example 202. The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was heated at the boil under reflux for 3 hours. After cooling to room temperature and add 2-methyl-2-propanol (1 ml) the mixture was heated at 80°With a further 18 hours. Then the reaction mixture was concentrated, and the thus obtained residue was dissolved in dichloromethane. The resulting solution was washed sequentially with saturated aqueous sodium bicarbonate solution, water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1, was concentrated to obtain specified in the title compound (171 mg, 0,383 mmol, 51%) as a white solid. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain colorless needle-like crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,40-1,49 (11H, s), 2.05 is with 2.14 (1H, m), 2,43-2,52 (1H, m), 3,07-3,17 (2H, m), 4,48-4,60 (2H, m), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,94-7,01 (1H, m), 7,24 (1H, DDD, J=8,8, 5,4, 3,2 Hz), 7,38 (2H, d, J=8,5 Hz), 7,53 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3392, 2960, 1695, 1583, 1514, 1493, 1365, 1313, 1248, 1174, 1147, 1084, 999, 827, 752, 644, 548, 528, 451.

TPL: 119-120°C.

p> MS m/z: 460 (M++H).

Elemental analysis. Calculated for C21H24ClF2NO4S: C, 54,84; H, 5,26; Cl, 7,71; F, Compared To 8.26; N, 3,05; S 6,97. Found: C, 54,84; H, 5,31; Cl, 7,06; F, At 8.36; N, 3,16; S, 7,14.

Example 227: Hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butylamine

Concentrated chloride-hydrogen acid (2 ml) was added to a solution in ethanol (2 ml) of tert-butyl N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyl]carbamate (104 mg, 0,226 mmol) followed by stirring at room temperature for 2 hours. Then the reaction mixture was concentrated. Thus obtained residue was recrystallized from a mixture of ethanol-ethyl acetate to obtain specified in the connection header (78,9 mg, 0,199 mmol, 88%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,51-to 1.60 (1H, m), 1,63 is 1.75 (1H, m), 2,18-of 2.28 (1H, m), 2,45-of 2.54 (1H, m), 2,95 (2H, DDD, J=8,5, to 6.8, 3.2 Hz), was 4.76 (1H, DD, J=11,0, 4.6 Hz), 6,98 (1H, TD, J=9,3, 4,4 Hz), 7,09-7,17 (1H, m), 7,32 (1H, DDD, J=9,0, 5,6, 3,4 Hz), 7,52 (2H, d, J=8,8 Hz), 7,60 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 2951, 2871, 1583, 1496, 1427, 1396, 1311, 1279, 1219, 1147, 1081, 1011, 870, 825, 742, 706, 629, 536, 463.

TPL: 232-233°C.

MS m/z: 360 (M++H).

Elemental analysis. Calculated for C16H16ClF2NO2S·HCl: C, 48,49; H, 4,32; Cl, 17,89; F, 9,59; N, 3,53; S 8,09. Found: C, 48,20; H, 4,27; Cl, 17,84; F, Being 9.61; N, 3,63; S, 8,15.

Example 228: Hydrochloride of N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-d is forfinal)butyl]nicotinamide

In nitrogen atmosphere and at 0°N-methylmorpholin (44,6 μl, 0,406 mmol) and acid chloride hydrochloride nicotinic acid (36,1 mg, 0,203 mmol) was added to a solution in dichloromethane (4 ml) of the hydrochloride of 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butylamine (67,0 mg, 0,169 mmol). After stirring at room temperature for 3 hours, the reaction mixture was diluted with dichloromethane, washed sequentially with a saturated aqueous solution of ammonium chloride and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:3, was concentrated. The obtained solid substance was dissolved in ethanol. To the resulting solution was added a mixture of 1 N. chloride-hydrogen acid-ethanol (0.5 ml). The thus obtained solid substance was recrystallized from a mixture of ethanol-ethyl acetate to obtain specified in the connection header (67,1 mg, 0,134 mmol, 79%) as a white solid.

1H-NMR (400 MHz, CD3OD) δ: 1,58-to 1.67 (2H, m), 2,18-of 2.28 (1H, m), 2,42-2,52 (1H, m), 3,40 (1H, dt, J=13,7, and 6.6 Hz), 3,51 (1H, dt, J=13,7, 6,8 Hz), to 4.81 (1H, m), 6,98 (1H, TD, J=9,3, 4,4 Hz), 7,08-to 7.15 (1H, m), 7,30 (1H, DDD, J=9,0, 5,6, 3,4 Hz)to 7.50 (2H, d, J=8,8 Hz), a 7.62 (2H, d, J=8,8 Hz), 8,18 (1H, DD, J=8,1, 5,9 Hz), of 8.92 (1H, DD, J=8,1, 1.5 Hz), 8,99 (1H, d, J=5,9 Hz), which 9.22 (1H, d, J=1.2 Hz).

IR (ATR) cm-1: 3282, 2457 2096, 1977, 1666, 1547, 1493, 1302, 1234, 1173, 1147, 1092, 1016, 883, 829, 760, 733, 673, 623, 528.

TPL: 154-157°C.

MS m/z: 465 (M++H).

Elemental analysis. Calculated for C22H19ClF2N2O3S·HCl: C, 52,70; H, was 4.02; Cl, 14,14; F, 7,58; N, 5,59; S, 6,40. Found: C, 52,59; H, 4,01; Cl, 14,19; F, 7,72; N, 5,73; S, 6,56.

Example 229: 1-[4-(4-chlorophenylsulfonyl]-4-(2,5-differenl)butyl]-2-pyrrolidinone

To a solution in dichloromethane (6 ml) of the hydrochloride of 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butylamine (120 mg, 0,303 mmol)obtained in example 227 was added N-methylmorpholine (250 μl, 2,69 mmol) and the acid chloride 4-harpalani acid (40,7 μl, 0,364 mmol). After stirring at room temperature for 1 hour, the reaction mixture was diluted with dichloromethane, washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was dissolved in tetrahydrofuran (5 ml) followed by the addition of sodium hydride (60% dispersion in mineral oil, 14,2 mg, 0,356 mmol) and N,N-dimethylformamide (2 drops). The resulting mixture was stirred at room temperature for 24 hours. Was added water, and the resulting mixture was extracted with ethyl acetate. The extracts were combined, washed with saturated salt solution, dried over magnesium sulfate and then what was koncentrirebuli. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated to obtain specified in the title compound (105 mg, 0,245 mmol, 82%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,43-of 1.65 (2H, m), 1,97-2,12 (3H, m), 2,32 is 2.43 (3H, m), and 3.16 (1H, dt, J=13,7, 6,8 Hz), 3,28-of 3.42 (3H, m), of 4.67 (1H, DD, J=10,9, 3,4 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), 6,95-7,02 (1H, m), 7,22-7,28 (1H, m,), 7,39 (2H, d, J=8.5 Hz), 7,56 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 2941, 1676, 1583, 1495, 1425, 1394, 1319, 1279, 1147, 1084, 1012, 827, 754, 707, 625, 555, 467.

MS m/z: 428 (M++H).

FAB-MS: 428,0885 (calculated for C20H21ClF2NO3S: 428,0899).

Example 230 N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butyl]methanesulfonamide

In nitrogen atmosphere N-methylmorpholin (51,0 μl, 0,465 mmol) and methanesulfonamide (18,8 μl, 0,242 mmol) was added to a solution in dichloromethane (4 ml) of the hydrochloride of 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)butylamine (80.0 mg, 0,202 mmol)obtained in example 227. After stirring at room temperature for 15 hours was added N-methylmorpholine (156 μl, of 1.42 mmol) and methanesulfonamide (10,0 ál, 0,129 mmol). The resulting mixture was stirred at room temperature for 2 hours. After dilution with dichloromethane, the mixture was sequentially washed with saturated aq is m solution of ammonium chloride, water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (71,5 mg, 0,163 mmol, 81%) as colorless plate crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,50-to 1.67 (2H, m), 2,09-of 2.20 (1H, m), 2,50 at 2.59 (1H, m), 2,95 (3H, s), 3,12-is 3.21 (2H, m), 4,30 (1H, t, J=6.3 Hz), 4,56 (1H, DD, J=10,7, 4,4 Hz), at 6.84 (1H, TD, J=9,0, 4.6 Hz), of 6.96-7.03 is (1H, m), 7.23 percent-7,28 (1H, m), 7,39 (2H, d, J=8.0 Hz), 7,53 (2H, d, J=8.0 Hz).

IR (ATR) cm-1: 3269, 1585, 1498, 1308, 1252, 1217, 1140, 1090, 1082, 976, 870, 787, 750, 627, 517, 467.

TPL: 128°C.

MS m/z: 438 (M++H).

Elemental analysis. Calculated for C17H18ClF2NO4S2: C, 46,63; H, 4,14; Cl, 8,10, F, 8,68; N, 3,20; S, 14,64. Found: C, 46,62; H, 4,08; Cl, 8,15; F, 8,69; N, 3,27; S, 14,71.

Example 231: 2-[1-(4-chlorophenylsulfonyl)-5-terpencil]-1,4-differenza

5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1-pentanol (152 mg, 0,404 mmol)obtained in example 29 was dissolved in dichloromethane (4 ml) followed by addition of N-methylmorpholine (58,0 μl, 0,528 mmol) and methanesulfonamide (37,8 μl, 0,487 mmol) at 0°C. the resulting mixture AC is stirred at 0° C for 2 hours and then at room temperature for additional 3 hours. After dilution with dichloromethane, the mixture was sequentially washed with a saturated aqueous solution of ammonium chloride, water and a saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was dissolved in tetrahydrofuran (4 ml). To the resulting solution was added to the solution in tetrahydrofuran (1.0 M, 0,487 ml, 0,487 mmol) tetrabutylammonium at room temperature. The resulting mixture was stirred at 60°C for 4 hours. After cooling to room temperature and dilute with ethyl acetate and the mixture was washed with water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=9:1, was concentrated. The thus obtained solid substance was recrystallized from hexane to obtain specified in the connection header (30,3 mg, 0,0804 mmol, 20%) as colorless plate crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,34-of 1.42 (2H, m), 1,64 and 1.80 (2H, m), 2,09-of 2.20 (1H, m), 2,45 of $ 2.53 (1H, m), 4,39 (2H, dt, J=47,1, 5,9 Hz)to 4.52 (1H, DD, J=11,2, 2,9 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7,02 (1H, m), 7.23 percent-7,28 (1H, m,), 7,38 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

TPL: 77-78�B0; C.

IR (ATR) cm-1: 2941, 1585, 1495, 1429, 1396, 1321, 1279, 1242, 1186, 1149, 1092, 1084, 962, 874, 829, 777, 752, 710, 633, 557, 536, 474.

MS m/z: 377 (M++H).

Elemental analysis. Calculated for C17H16ClF3O2S: C, To 54.19; H, 4,28; Cl, 9,41; F, 15,13; S, 8,51. Found: C, 54,27; H, 4,22; Cl, 9,44; F, The 14.90; S, 8,68.

Example 232: 2-[1-[(4-chlorophenyl)sulfonyl]-1-methylethyl]-1,4-differenza

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 450 μl, 0,707 mmol) was added to the solution in tetrahydrofuran (4 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (200 mg, 0,660 mmol)obtained in example 5. After stirring for 5 minutes was added itmean (103 μl, of 1.65 mmol). The resulting mixture was stirred for 10 minutes and then was added n-utility (1.57 M solution in hexane, 474 μl, 0,744 mmol). After increasing the temperature of the reaction mixture to room temperature, stirring was carried out for 2 hours. Was added water, followed by extraction with ethyl acetate. The extracts were combined, washed with saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (163 mg, 0,492 mmol, 75%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: of 1.87 (3H, s), a 1.88 (3H, s), 86 (1H, DDD, J=11,9, 9,0, a 4.9 Hz), 6,98-7,05 (1H, m), 7,10 (1H, DDD, J=9,8, 6,6, 3,4 Hz), 7,39 (2H, d, J=8.5 Hz), 7,44 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 1574, 1489, 1475, 1412, 1304, 1219, 1184, 1155, 1124, 1068, 1011, 887, 867, 827, 756, 712, 660, 623, 600, 571, 532, 511, 474, 432.

TPL: 147-148°C.

MS m/z: 331 (M++H).

Elemental analysis. Calculated for C15H13ClF2O2S: C, 54,47; H, 3.96 Points; Cl, Of 10.72; F, 11,49; S, RS 9.69. Found: C, 54,39; H, 3,92; Cl, Is 10.68; F, 11,51; S 9,78.

Example 233: 2-[1-[(4-chlorophenyl)sulfonyl]cyclopropyl]-1,4-differenza

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 600 μl, 0,942 mmol) was added to the solution in tetrahydrofuran (4 ml) of 3-[(4-chlorophenyl)sulfanilyl]-3-(2,5-differenl)-1-propanol (300 mg, 0,865 mmol)obtained in example 207. After stirring for 5 minutes was added methanesulfonamide (70,6 μl, 0,908 mmol). The resulting mixture was stirred for 5 minutes and then was added n-utility (1.57 M solution in hexane, 601 μl, 0,944 mmol). The temperature of the reaction mixture was raised to room temperature and at this temperature, stirring was carried out for 18 hours. After cooling to -78°C was added n-utility (1.57 M solution in hexane, 400 ál, 2,255 mmol). The reaction mixture was stirred at room temperature for 3 hours. Was added water, followed by extraction with ethyl acetate. The extracts were combined, washed with saturated RA is tworoom salt, was dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=19:1, was concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (161 mg, 0,489 mmol, 57%) as colorless plate crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,31 (2H, DD, J=7,6, 5,1 Hz), 2,02 (2H, DD, J=7,6, 5,1 Hz), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,97-7,03 (1H, m), 7,06 (1H, DDD, J=8,3, 5,4, 3,2 Hz), 7,41 (2H, d, J=8.6 Hz), 7,49 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 3089, 1583, 1496, 1477, 1429, 1308, 1279, 1252, 1211, 1184, 1142, 1086, 1012, 893, 827, 769, 758, 737, 663, 625, 596, 559, 546, 492, 476, 451, 411.

TPL: 177-179°C.

MS m/z: 329 (M++H).

Elemental analysis. Calculated for C15H11ClF2O2S: C, 54,80; H, 3,37; Cl, 10,78; F, To 11.56; S, 9,75. Found: C, 54,72; H, 3,31; Cl, 10,71; F, 11,58; S 9,87.

Reference example 38: 5-(tert-butyldimethylsilyloxy)pentanal

In nitrogen atmosphere and at 0aboutWith dimethyl sulfoxide (7,81 ml, 110 mmol), triethylamine (9,60 ml of 69.0 mmol) and a complex of a sulfur trioxide-pyridine (4,39 g, 27.6 mmol) was added to a solution in dichloromethane (80 ml) of 5-(tert-butyldimethylsilyloxy)pentanol (3.00 g, of 13.8 mmol). The resulting mixture was stirred at 0°C for 30 minutes, and then when the room is Noah temperature for another 3 hours. After cooling to 0°With added saturated aqueous solution of ammonium chloride. Dichloromethane person to distil under reduced pressure. To the residue was added ethyl acetate. After separation of the aqueous layer, the organic layer was washed with water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=20:1 was concentrated to obtain specified in the connection header (2,42 g, and 11.2 mmol, 81%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: of 0.05 (3H, s), 0,05 (3H, s)to 0.89 (9H, s), 1,50-1,60 (2H, m)of 1.65 and 1.75 (2H, m), 2,46 (2H, t, J=6.8 Hz), 3,63 (2H, t, J=6.3 Hz), made up 9.77 (1H, s).

MS m/z: 217 (M++H).

Example 234: 6-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-hexanol (isomer 234-a and isomer 234-In)

In the atmosphere of argon and at -78°With n-utility (1.57 M solution in hexane, 1,40 ml of 2.20 mmol) was added to a solution in dichloromethane (10 ml) of 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (606 mg, 2.00 mmol)obtained in example 5. After adding dropwise 5-(tert-butyldimethylsilyloxy)pentanal (475 mg, of 2.20 mmol) the resulting mixture was stirred at room temperature for 3 days. The reaction mixture was cooled to 0°C. To floor the obtained mixture was added water and then ethyl acetate. After separation of the aqueous layer, the organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=10:1 was concentrated to obtain specified in the header isomer 234-A (low polarity) (to 43.1 mg, is 0.102 mmol, 5%) and indicated in the title isomer 234 (high polarity) (120 mg, 0,231 mmol, 12%), each as a colourless oil.

Isomer 234-

1H-NMR (400 MHz, CDCl3) δ: 0,00 (3H, s)0,00 (3H, s)of 0.85 (9H, s), 1,25-to 1.70 (6H, m), 3,12 (1H, d, J=3.2 Hz), 3,55 (2H, t, J=5,9 Hz), 4,48 (1H, s), a 4.83-4,88 (1H, m), 6,83 (1H, TD, J=9,0, 4.6 Hz), 6,95-7,02 (1H, m), 7,39 (2H, d, J=8.5 Hz), EUR 7.57 (2H, d, J=8.5 Hz), to 7.84 (1H, DDD, J=9,0, 5,9, 3,4 Hz).

MS m/z: 519 (M++H).

Isomer 234-

1H-NMR (400 MHz, CDCl3) δ: -0,04 (3H, s)-0,01 (3H, s)of 0.85 (9H, s), 1.30 and of 1.54 (6H, m), 3,50 is 3.57 (2H, m), 3,81 (1H, Sirs), 4,58-4,80 (2H, m), at 6.84 (1H, TD, J=9,0, 4.6 Hz), of 6.96-7,06 (1H, m), 7,15-7,27 (1H, m), 7,39 (2H, d, J=8,5 Hz), 7,52 (2H, d, J=8,5 Hz).

MS m/z: 519 (M++H).

Example 235: 6-[(4-chlorophenyl)sulfonyl]-6-(2,5-differenl)-1,5-hexanediol

6-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-hexanol (isomer 234-A) (42,0 mg, 0,0809 mmol)obtained in example 234, the solution is whether in tetrahydrofuran (2 ml) followed by addition of a mixture of hydrogen fluoride-pyridine (0.2 ml). The resulting mixture was stirred at room temperature for 6 hours. The solution was diluted with ethyl acetate, washed with water and saturated salt solution, dried over magnesium sulfate. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (16,7 mg, 0,0412 mmol, 51%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,25-to 1.70 (7H, m), 3,15 (1H, s), 3,55-the 3.65 (2H, m), 4,49 (1H, s), a 4.86-of 4.90 (1H, m), 6,85 (1H, TD, J=9,0, 4,4 Hz), 6,97-7,03 (1H, m), 7,40 (2H, d, J=8,8 Hz), 7,58 (2H, d, J=8,8 Hz), the 7.85 (1H, DDD, J=9,0, 5,9, 3,4 Hz).

IR (ATR) cm-1: 3232, 1576, 1491, 1396, 1306, 1236, 1217, 1147, 1093, 1012, 891, 814, 756, 719, 615, 548, 467.

TPL: 108-109°C.

MS m/z: 405 (M++H).

FAB-MS: 405,0756 (calculated for C18H19ClF2O4S: 405,0739).

Elemental analysis. Calculated for C18H19ClF2O4S·0,5H2O: C, 52,24; H, 4,87; S 7,75. Found: C, 52,33; H, 4,84; S, 7,83.

Example 236: 6-[(4-chlorophenyl)sulfonyl]-6-(2,5-differenl)-1,5-hexanediol

6-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-2-hexanol (isomer 234) (120 mg, 0,231 mmol)obtained in example 234, was dissolved in tetrahydrofuran (5 ml) followed by addition of a mixture of hydrogen fluoride-pyridine (0.5 ml). The resulting mixture was stirred at room temperature for 20 hours. The reaction mixture was diluted what dilatatum, washed successively with water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated the thus Obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (51.3 mg, to 0.127 mmol, 55%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,25-1,67 (7H, m), 3,53-3,63 (2H, m), 3,91 (1H, Sirs), 4,59-4,78 (2H, m), 6,85 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7.03 is (1H, m), 7,16-7,27 (1H, SIRM), 7,39 (2H, d, J=8.5 Hz), 7,52 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3496, 2956, 1579, 1496, 1425, 1392, 1305, 1275, 1180, 1144, 1080, 1011, 966, 922, 833, 810, 756, 737, 650, 536, 521, 461.

TPL: 105-107°C.

MS m/z: 405 (M++H).

Elemental analysis. Calculated for C18H19ClF2O4S: C, 53,40; H, 4,73; Cl, 8,76; F, 9,39; S 7,92. Found: C, 53,20; H, Br4.61; Cl, 8,77; F, 9,20; S 8,03.

Reference example 39: 4-(tert-butyldimethylsilyloxy)-2-butanol

In N,N-dimethylformamide (30 ml) was dissolved 1,3-butanediol (3.00 g, 33.3 mmol) followed by the addition dropwise of a solution in N,N-dimethylformamide (30 ml), imidazole (2,72 g, 40.0 mmol) and tert-butylcholinesterase (5.29 g, 35,0 mmol). After stirring at room te is the temperature within 24 hours to the reaction mixture was added ether, and besieged thus white solid was filtered. The obtained ether solution was washed with water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=5:1 was concentrated to obtain specified in the connection header (5,43 g of 26.6 mmol, 80%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: of 0.08 (6H, s)of 0.90 (9H, d, J=1.0 Hz), 1,19 (3H, d, J=6.4 Hz), 1,59-of 1.73 (2H, m), 3,78-3,93 (2H, m), 3,98-4,07 (1H, SIRM).

MS m/z: 205 (M++H).

Example 237: 2-[4-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-2-methylbutyl]-1,4-differental (compound (isomer a) and the compound (isomer B)) and 2-[4-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]pentyl]-1,4-differental (connection)

In nitrogen atmosphere 2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (303 mg, 1.00 mmol)obtained in example 5 and 4-(tert-butyldimethylsilyloxy)-2-butanol (408 mg, 2.00 mmol) was dissolved in toluene (4 ml). After adding cyanomethylene-n-butylphosphine (482 mg, 2.00 mmol) the resulting mixture was heated at the boil under reflux for 15 hours under nitrogen atmosphere. Then the reaction mixture was concentrated. Received this the way the residue was subjected to flash chromatography on a column of silica gel (hexane:ethyl acetate=50:1) to obtain the specified title compound (isomer A) (low polarity) (109 mg, 0,222 mmol, 22%)as specified in the title compound (isomer B) (high polarity) (102 mg, 0,209 mmol, 21%)as specified in the title compound (234 mg, 0,479 mmol, 48%), each as a colourless oil.

Compound (isomer A)

1H-NMR (400 MHz, CDCl3) δ: of 0.05 (3H, s), 0,05 (3H, s)to 0.89 (9H, s)to 1.14 (3H, d, J=6.8 Hz), to 1.38 to 1.47 (1H, m), 1,79-1,89 (1H, m), 2.91 in-to 3.02 (1H, m), 3,63-to 3.73 (2H, m), 4,56 (1H, d, J=5,9 Hz), for 6.81 (1H, TD, J=9,0, 4.6 Hz), 6,92-6,98 (1H, m), 7,34 (2H, d, J=8,3 Hz), 7,51-EUR 7.57 (1H, m), 7,55 (2H, d, J=8,3 Hz).

MS m/z: 489 (M++H).

Compound (isomer B)

1H-NMR (400 MHz, CDCl3) δ: -0,01 (3H, s)0,00 (3H, s), 0,85 with 0.93 (9H, m), 1,19 of 1.28 (1H, m)to 1.38 (3H, d, J=6.6 Hz), 1,64-of 1.73 (1H, m), 2,78-is 2.88 (1H, m), 3,61 (2H, DD, J=7,6, a 4.9 Hz), 4,46 (1H, d, J=9.0 Hz), 6,72 (1H, TD, J=9,0, 4,4 Hz), 6.87 in-6,93 (1H, m), 7,30 (2H, d, J=8,3 Hz), 7,34-7,41 (1H, m), 7,49 (2H, d, J=8,3 Hz).

MS m/z: 489 (M++H).

Connection

1H-NMR (400 MHz, CDCl3) δ: -0,01 (1,5H, C)0,01 (1,5H, s)0,02 (1,5H, s)0,04 (1,5H, C)0,84 (4,5H, m)0,86 (4,5H, m), 1.04 million-1,10 (3H, m), 1,15-of 1.40 (2H, m), 1,99-2,11 (0,5H, m), 2,11-2,22 (0,5H, m), 2,35 of $ 2.53 (1H, m), 3.72 points-is 3.82 (1H, m), of 4.44-to 4.52 (1H, m), 6,82-to 6.88 (1H, m), 6,93-7,02 (1H, m), 7,16-7,26 (1H, m), 7,37-7,42 (2H, m), 7,51-7,58 (2H, m).

MS m/z: 489 (M++H).

Example 238: 4-(4-chlorophenylsulfonyl]-4-(2,5-differenl)-3-methyl-1-butanol

2-[4-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-2-methylbutyl]-1,4-differental (compound (isomer A)) (109 mg, 0,223 mmol)obtained in example 237, was dissolved in tetrahydrofuran (3 ml) followed by relax the mixture of hydrogen fluoride-pyridine (0.5 ml). The resulting mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with ethyl acetate, washed with water, saturated aqueous sodium bicarbonate and saturated salt solution and dried over magnesium sulfate. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (61,1 mg, 0,163 mmol, 73%) as colorless columnar crystals.

1H-NMR (400 MHz, CDCl3) δ: a 1.08 (3H, d, J=7,1 Hz), 1,59-of 1.62 (1H, m), 1,74-of 1.84 (1H, m), 1,96-2,05 (1H, m), 2.93 which was 3.05 (1H, m), 3.75 to the 3.89 (2H, m), and 4.68 (1H, d, J=6.8 Hz), 6,77 (1H, TD, J=9,0, 4.6 Hz), 6,91-6,97 (1H, m), 7,33 (2H, d, J=8,3 Hz), 7,45-7,51 (1H, m), 7,51 (2H, d, J=8,3 Hz).

IR (ATR) cm-1: 3527, 2935, 2897, 1583, 1487, 1315, 1267, 1232, 1188, 1144, 1086, 1068, 1049, 1012, 889, 864, 829, 789, 750, 715, 654, 611, 551, 490, 467.

TPL: 111-112°C.

MS m/z: 375 (M++H).

Elemental analysis. Calculated for C17H17ClF2O3S: C, 54,47; H, 4,57; Cl, 9,46; F, 10,14; S, 8,55. Found: C, 54,44; H, 4,55; Cl, 9,44; F, 10,08; S, 8,75.

Example 239: 4-(4-chlorophenylsulfonyl]-4-(2,5-differenl)-3-methyl-1-butanol

2-[4-(tert-butyldimethylsilyloxy)-1-[(4-chlorophenyl)sulfonyl]-2-methylbutyl]-1,4-differental (compound (isomer B)) (102 mg, 0,209 mmol)obtained in example 237, was dissolved in tetrahydrofuran (3 ml) followed by addition of a mixture of hydrogen fluoride-pyridine (0.5 ml). The mixture of paramashiva and at room temperature for 15 hours. The reaction mixture was diluted with ethyl acetate, washed with water and saturated salt solution and then dried over magnesium sulfate. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (36,1 mg, 0,0963 mmol, 46%) as colorless columnar crystals.

1H-NMR (400 MHz, CDCl3) δ: 1,23-of 1.40 (2H, m)of 1.35 (3H, d, J=6.6 Hz), 1,81-1,90 (1H, m), 2,84-of 2.93 (1H, m), 3,63-of 3.78 (2H, m), 4,51 (1H, d, J=8.1 Hz), 6.75 in (1H, TD, J=9,0, 4.6 Hz), 6,89-of 6.96 (1H, m), 7,31 (2H, d, J=8,5 Hz), 7,40-7,47 (1H, m), 7,51 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3525, 2954, 1655, 1493, 1477, 1427, 1394, 1306, 1279, 1240, 1180, 1144, 1080, 1055, 1014, 943, 887, 822, 754, 712, 665, 609, 559, 542, 453.

TPL: 65-67°C.

MS m/z: 375 (M++H).

Elemental analysis. Calculated for C17H17ClF2O3S·0,5H2O: C, 53,20; H, 4,73; Cl, 9,24; F, 9,90; S, 8,35. Found: C, 53,17; H, 4,86; Cl, 9,29; F, 10,00; S, 8,50.

Example 240: 1-[(4-chlorophenyl)sulfonyl]-1-(2,5-differenl)-4-pentanol (isomer 240-a and isomer 240-In)

2-[4-(tert-butyldimethylsilyloxy)-1-(4-chlorophenylsulfonyl)pentyl]-1,4-differental (compound) (230 mg, 0,470 mmol)obtained in example 237, was dissolved in tetrahydrofuran (4 ml) followed by the addition of a solution in tetrahydrofuran (1.0 M, 0,564 ml, 0,564 mmol) tetrabutylammonium. The resulting mixture was stirred at room temperature for 18 hours. The reaction mixture Rabaul the Lee ethyl acetate, washed with water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel (hexane:ethyl acetate=2:1) to give isomer a low polarity and high polarity, each in the form of a white solid. The obtained isomer a low polarity recrystallized from hexane to obtain specified in the header isomer 240 (low polarity) (48,0 mg, 0,128 mmol, 27%) as colorless needle crystals. On the other hand, the obtained high polarity isomer was recrystallized from hexane to obtain specified in the header isomer 240 (high polarity) (48,8 mg, 0,130 mmol, 28%) as colorless needle crystals.

Isomer 240 And

1H-NMR (400 MHz, CDCl3) δ: of 1.17 (3H, d, J=6,1 Hz), of 1.28 to 1.48 (3H, m), 2,18-to 2.29 (1H, m), 2,47-of 2.56 (1H, m), of 3.77-of 3.85 (1H, m), 4.53-in-4,58 (1H, m), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,95-7,01 (1H, m), 7,22-7,28 (1H, m), 7,38 (2H, d, J=8.5 Hz), 7,53 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3370, 3087, 2925, 1587, 1574, 1496, 1475, 1423, 1396, 1311, 1279, 1234, 1178, 1149, 1128, 1086, 1014, 949, 874, 827, 789, 760, 735, 710, 679, 631, 584, 559, 525, 469.

TPL: 97-98°C.

MS m/z: 375 (M++H).

Elemental analysis. Calculated for C17H17ClF2NO3S: C, 54,47; H, 4,57; Cl, 9,46; F, 10,14; S, 8,55. Found: C, 54,35; H, 4,69; Cl, For 9.64; F, 10,31; S 8,80.

Isomer 240-

1H-NMR (400 MHz, CDCl3) δ: of 1.17 (3H, d, J=6,1 Hz), 1,29-of 1.45 (3H, m), 2,07-to 2.18 (1H, m), 2,58-to 2.67 (1H, m), of 3.77-of 3.85 (1H, m), 4,59 (1H, DD, J=11,2, 2,9 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), 6,95-7,02 (1H, m), 7.23 percent-7,27 (1H, m), 7,38 (2H, d, J=8.5 Hz), 7,54 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3504, 3390, 2960, 2925, 1585, 1493, 1475, 1427, 1396, 1302, 1275, 1227, 1174, 1146, 1082, 1036, 1014, 823, 752, 723, 708, 625, 555, 530, 463.

TPL: 89°C.

MS m/z: 375 (M++H).

Elemental analysis. Calculated for C17H17ClF2NO3S: C, 54,47; H, 4,57; Cl, 9,46; F, 10,14; S, 8,55. Found: C, 54,25; H, 4,46; Cl, 9,51; F, 10,41; S, 8,66.

Example 241: Tert-butyl N-[5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)pentyl]-N-methylsulfonylamino

5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-1-pentanol (115 mg, 0,307 mmol)obtained in example 29, tert-butyl-N-methylsulfonylamino (120 mg, 0,614 mmol) and triphenylphosphine (163 mg, 0,614 mmol) was dissolved in tetrahydrofuran (3 ml). At room temperature to the resulting solution was added diisopropylethylamine (120 μl, 0,614 mmol). After stirring the mixture for 18 hours at room temperature the reaction mixture was diluted with ethyl acetate, washed with water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:1, was concentrated to obtain specified in the connection header (mg, 0,304 mmol, 99%) as a colorless amorphous substance.

1H-NMR (400 MHz, CDCl3) δ: 1,22-of 1.35 (2H, m)of 1.50 (9H, m), 1,58-of 1.73 (2H, m), 2,08-to 2.18 (1H, m), 2,39-2,49 (1H, m), up 3.22 (3H, s)and 3.59 (2H, DDD, J=8,1, to 6.6, 3.9 Hz), a 4.53 (1H, DD, J=11,2, 2,9 Hz), 6,83 (1H, TD, J=9,0, 4,4 Hz), 6,95-7,01 (1H, m), 7,22-7,27 (1H, m), 7,39 (2H, d, J=8.5 Hz), 7,54 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 1722, 1583, 1496, 1350, 1321, 1281, 1149, 1087, 1012, 966, 831, 754, 710, 629, 517.

MS m/z: 452 (M+-Boc), 496 (M+-t-Bu), 574 (M++Na).

FAB-MS: 574,0932 (calculated for C23H28ClF2NO6S2Na: 574,0912).

Example 242 N-[5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)pentyl]methanesulfonamido

In dichloromethane (4 ml) was dissolved tert-butyl-N-[5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)pentyl]-N-methylsulfonylamino (108 mg, 0,196 mmol) followed by the addition triperoxonane acid (1 ml) at room temperature. The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with dichloromethane, washed successively with water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1, was concentrated, the resulting solid is th substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (75,5 mg, 0,167 mmol, 85%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,28-to 1.38 (2H, m), 1,55 by 1.68 (2H, m), 2.06 to to 2.18 (1H, m), 2,43-2,52 (1H, m), of 2.92 (3H, s)to 3.09 (2H, DD, J=13,4, 6,8 Hz), 4,15-4,24 (1H, m), 4,51 (1H, DD, J=11,5, 3,4 Hz), at 6.84 (1H, TD, J=9,0, 4,4 Hz), of 6.96-7.03 is (1H, m), 7,22-7,28 (1H, m), 7,39 (2H, d, J=8.5 Hz), 7,52 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3219, 2871, 1583, 1495, 1425, 1300, 1248, 1167, 1144, 1084, 1068, 978, 893, 835, 752, 725, 706, 629, 545, 525, 471.

TPL: 106-107°C.

MS m/z: 452 (M++H).

Elemental analysis. Calculated for C18H20ClF2NO4S2: C 47,84; H, 4,46; Cl, 7,84; F, To 8.41; N, 3,10; S, 14,19. Found: C, 47,75; H, 4,47; Cl, 7,94; F, 8,54; N, 3,14; S, 14,25.

Example 243: Tert-butyl N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-3-methylbutyl]-N-methylsulfonylamino

4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-3-methyl-1-butanol (97,2 mg, 0,259 mmol)obtained in example 239, tert-butyl-N-methylsulfonylamino (101 mg, 0,518 mmol) and triphenylphosphine (138 mg, 0,518 mmol) was dissolved in tetrahydrofuran (3 ml) followed by the addition of diisopropylcarbodiimide (102 μl, 0,518 mmol) at room temperature. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous ammonium chloride, water and a saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to the lash-chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:2, was concentrated to obtain specified in the title compound (136 mg, 0,246 mmol, 95%) as a colorless amorphous substance.

1H-NMR (400 MHz, CDCl3) δ: of 1.33 (3H, d, J=6.8 Hz), 1,35-1,45 (1H, m), of 1.52 (9H, s), 1,99-of 2.08 (1H, m), 2,70-2,78 (1H, m), with 3.27 (3H, s), 3,65 is 3.76 (2H, m), of 4.45 (1H, d, J=7,6 Hz), 6,77 (1H, TD, J=9,0, 4.6 Hz), 6,91-6,97 (1H, m)to 7.32 (2H, d, J=8.5 Hz), 7,38 was 7.45 (1H, m)to 7.50 (2H, d, J=8,5 Hz).

MS m/z: 552 (M++H), 574 (M++Na).

FAB-MS: 552,1070 (Calculated for C23H29ClF2NO6S2: 552,1093), 574,0875 (Calculated for C23H28ClF2NO6S2Na: 574,0912).

Example 244 N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-3-methylbutyl]methanesulfonamide

Tert-butyl N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-3-methylbutyl]-N-methylsulfonylamino (136 mg, 0,246 mmol)obtained in example 243, was dissolved in dichloromethane (4 ml) followed by the addition triperoxonane acid (1 ml) at room temperature. After stirring at room temperature for 6 hours, the reaction mixture was diluted with dichloromethane, washed successively with water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over magnesium sulfate and then concentrated. The thus obtained solid substance was recrystallized issuesi ethyl acetate-hexane to obtain specified in the connection header (99,5 mg, 0,220 mmol, 89%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: of 1.27 (3H, d, J=6.8 Hz), 1,35-of 1.44 (1H, m), 1,95-2,05 (1H, m), 2,82-is 2.88 (1H, m), 2,95 (3H, s), 3,10-3,19 (1H, m), 3,22-3,30 (1H, m), 4,21-to 4.28 (1H, SIRM), of 4.49 (1H, t, J=6.6 Hz), for 6.81 (1H, TD, J=9,0, 4,4 Hz), 6,93-7,00 (1H, m), 7,34 (2H, d, J=8.5 Hz), 7,42-of 7.48 (1H, m), 7,52 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3251, 3076, 1581, 1495, 1473, 1317, 1244, 1140, 881, 837, 781, 750, 729, 710, 665, 617, 553, 521, 465.

TPL: 163°C.

MS m/z: 452 (M++H).

Elemental analysis. Calculated for C18H20ClF2NO4S2: C 47,84; H, 4,46; Cl, 7,84; F, To 8.41; N, 3,10; S, 14,19. Found: C, 47,88; H, 4,45; Cl, To $ 7.91; F, 8,51; N, 3,16; S, 14,23.

Example 245 N-[3-(4-chlorophenylsulfonyl)-3-(2,5-differenl)propyl]methanesulfonamide

3-(4-chlorophenylsulfonyl)-3-(2,5-differenl)-1-propanol (120 mg, 0,307 mmol)obtained in example 207, tert-butyl-N-methylsulfonylamino (101 mg, 0,519 mmol) and triphenylphosphine (138 mg, 0,519 mmol) was dissolved in tetrahydrofuran (3 ml) followed by the addition of diisopropylcarbodiimide (102 μl. 0,519 mmol) at room temperature. The resulting mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate, washed with water and saturated salt solution, dried over magnesium sulfate and then concentrated. Thus obtained residue was subjected to chromatography on a column of silica gel (hexane:ethyl acetate=4:1) Claudine a by-product of high polarity. Thus obtained crude product was dissolved in dichloromethane (4 ml) followed by the addition triperoxonane acid (2 ml). The resulting mixture was stirred at room temperature for 6 hours. The reaction mixture was diluted with dichloromethane, washed successively with water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over magnesium sulfate and then concentrated. The thus obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the connection header (90,2 mg, 0,213 mmol, 62%) as colorless needle crystals.

1H-NMR (400 MHz, CDCl3) δ: 2,29-2,39 (1H, m), 2,69-2,78 (1H, m), with 2.93 (3H, s), of 3.10-3.20 (1H, m), 3,35-3,44 (1H, m), of 4.44-4,50 (1H, SIRM), 4,74 (1H, DD, J=9,0, 6,1 Hz), at 6.84 (1H, TD, J=9,0, 4.6 Hz), 6,97? 7.04 baby mortality (1H, m), 7.23 percent (1H, DDD, J=8,5, 5,4, 3,2 Hz), 7,39 (2H, d, J=8.5 Hz), 7,52 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 3257, 3087, 2947, 1587, 1496, 1475, 1308, 1090, 1279, 1147, 1086, 1014, 962, 879, 827, 760, 737, 679, 621, 523, 463, 413.

TPL: 131-134°C.

MS m/z: 424 (M++H).

Elemental analysis. Calculated for C16H16ClF2NO4S2: C, 45,34; H, 3,80; Cl, At 8.36; F, 8,96; N, 3,30; S, 15,13. Found: C, 45,22; H, 3,67; Cl, 8.34 Per; F, 8,98; N, 3,38; S, 15,16.

Reference example 40: 4-(tert-butyldiphenylsilyl)-2-butene-1-ol

In a mixture of dichloromethane/N,N-dimethylformamide (200 ml/200 ml) was dissolved 2-butene-1,4-diol (10.0 g, 113 mmol who) and imidazole (4,70 g, 69,0 mmol), followed by adding dropwise tert-butylchloroformate (30,0 ml, 115 mmol) at room temperature. After completion of adding dropwise, the mixture was stirred at room temperature for 4 days. To the residue obtained by concentrating the reaction mixture under reduced pressure, was added diethyl ether. The resulting mixture was filtered, the insoluble substance. A layer of diethyl ether was washed with water and then the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=2:1 was concentrated under reduced pressure to obtain specified in the title compound (15.3 g, 46,9 mmol, 42%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.06 (9H, s)4,01 (0,5H, sird, J=6,1 Hz), 4,15 (1,5H, sird, J=4,9 Hz), 4,18-4.26 deaths (1,5H, m), 4.26 deaths (0,5H, DM, J=5,9 Hz), the ceiling of 5.60-of 5.75 (1H, m), 5,78 (3H, DM, J=15,4 Hz), 7,34-7,52 (5H, m), of 7.64-7,76 (4H, m).

MS m/z: 327 (M++H).

Example 246: (Z)-2-[5-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]-3-pentenyl]-1,4-differental (isomer 246-a) and (E)-2-[5-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]-3-pentenyl]-1,4-differental (isomer 246-In)

2-[(4-chlorp the Nile)sulfanilyl]-1,4-differental (400 mg, of 1.32 mmol)obtained in example 5 and 4-(tert-butyldiphenylsilyl)-2-butene-1-ol (660 mg, 2.02 mmol) was dissolved in toluene (6 ml) followed by addition of cyanomethylene-n-butylphosphine (480 mg, 1,99 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 6 hours. After cooling the reaction mixture the residue obtained by concentrating the reaction mixture under reduced pressure was separated and purified flash chromatography on silica gel (hexane:ethyl acetate=80:1) to obtain the specified header isomer 246 (low polarity) (149 mg, 0,244 mmol, 18%) and indicated in the title isomer 246 (high polarity) (468 mg, 0,766 mmol, 58%), each as a colourless oil.

Isomer 246-

1H-NMR (400 MHz, CDCl3) δ: was 1.04 (9H, s), 2,64-2,78 (1H, m), 2.95 and-is 3.08 (1H, m), 4.09 to (1H, DDM, J=13,5, 5.6 Hz), 4,15 (1H, DDM, J=13,5, 6.3 Hz), of 4.45 (1H, DDM, J=11,0, 3,4 Hz), 5,12 (1H, DTM, J=11,0, 7,3 Hz), 5,62 (1H, DTM, J=11,0, 6,3 Hz), 6,80-to 6.88 (1H, m), 6.90 to-7,00 (1H, m), 7,02-7,21 (1H, m), 7,30-7,60 (10 H, m), 7,60-7,72 (4H, m).

IR (ATR) cm-1: 2931, 2856, 1583, 1496, 1473, 1427, 1327, 1151, 1111, 1088, 823, 754, 702, 615, 505.

MS m/z: 611 (M++H), 633 (M++Na).

Isomer 246-

1H-NMR (400 MHz, CDCl3) δ: of 0.93 (9H, s), 2,80 of 2.92 (1H, m), 3,14-3,26 (1H, m), 3,98-of 4.05 (2H, m)to 4.01 (1H, DD, J=11,5, and 3.7 Hz), 5,43 (1H, DTM, J=15,0,7,3 Hz), 5,59 (1H, DTM, J=15,0, 4,4 Hz), 6.75 in-to 6.88 (1H, m), 6,92-7,01 (1H, m), 7,22-to 7.50 (9H, m), 7,50-the 7.65 (6H, m).

IR (ATR) cm-1: 2931, 2856, 1583, 1496, 1427, 1321, 1149, 1111, 1084, 1012, 822, 754, 700, 503.

The m/z: 611 (M ++H), 633 (M++Na).

Example 247: (Z)-5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-2-penten-1-ol

In tetrahydrofuran (5 ml) was dissolved (Z)-2-[5-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]-3-pentenyl]-1,4-differental (isomer 246) (145 mg, 0,237 mmol). After adding dropwise a solution in tetrahydrofuran (1.0 M, 0.5 ml, 0.5 mmol) tetrabutylammonium the mixture was stirred at room temperature for 2 hours. To the reaction mixture were added water (0.2 ml) followed by concentration under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=2:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with hexane to obtain specified in the title compound (51 mg, 0,137 mmol, 58%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 1.35 (1H, Sirs), 2,82-2,95 (1H, m), 3,22-of 3.32 (1H, m), 4,08-4,18 (1H, m), 4,18-to 4.28 (1H, m), 4,56 (1H, DDM, J=10,6,4,5 Hz), from 5.29 (1H, DTM, J=11,0,7,5 Hz), 5,67 (1H, DTM, J=11,0,6,6 Hz), 6,77-to 6.88 (1H, m), 6,92-7,02 (1H, m), 7,22-to 7.32 (1H, m), 7,39 (2H, d, J=8.7 Hz), 7,54 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 3560, 3016, 1585, 1495, 1475, 1427, 1396, 1308, 1277, 1218, 879, 827, 789, 752, 708, 679, 627, 467, 420.

TPL: 60-63°C.

MS m/z: 390 (M++NH4).

Elemental analysis. The calculated d the I C 17H15ClF2O3S: C, 54,77; H, 4,06; Cl, 9,51; F, 10,19; S, At 8.60. Found: C, 54,57; H, 4,08; Cl, 9,41; F, 10,27; S, A Total Of 8.74.

Example 248: (E)-5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-2-penten-1-ol

(E)-2-[5-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]-3-pentenyl]-1,4-differental (isomer 246-B) (465 mg, 0,761 mmol)obtained in example 246, was dissolved in tetrahydrofuran (10 ml) followed by the addition dropwise of a solution in tetrahydrofuran (1.0 M, 1.5 ml, 1.5 mmol) tetrabutylammonium. The mixture was stirred at room temperature for 1 hour. After adding water (0.2 ml) of the residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=2:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with hexane to obtain specified in the title compound (225 mg, 0,605 mmol, 80%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,21 (1H, shirt, J=5.5 Hz), 2,80 of 2.92 (1H, m), 3,18 of 3.28 (1H, m), 3.96 points-4,06 (2H, m), of 4.57 (1H, DDM, J=11,2,3,9 Hz), 5,44 (1H, DTM, J=15,2,7,3 Hz), 5,70 (1H, DTM, J=15,2,5,4 Hz), 6,78-to 6.88 (1H, m), 6,95-7,03 (1H, m), 7,22-7,30 (1H, m), 7,39 (2H, d, J=8.7 Hz), 7,54 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 3552, 3087, 1583, 1495, 1427, 1396, 1309, 1281, 1219, 1186, 1142, 1082, 1016, 984, 874, 831, 775, 756, 710, 619, 553, 34, 467.

TPL: 108-109°C.

MS m/z: 395 (M++Na).

Elemental analysis. Calculated for C17H15ClF2O3S: C, 54,77; H, 4,06; Cl, 9,51; F, 10,19; S, At 8.60. Found: C, 54,59; H, 4,03; Cl, At 9.53; F, 10,17; S, 8,71.

Reference example 41: 2-[2-(tert-butyldiphenylsilyl)ethylthio]ethanol

In dichloromethane (200 ml) was dissolved 2,2'-thiodiethanol (10.0 g, 81,8 mmol) and imidazole (4,70 g, 60,0 mmol), followed by adding dropwise tert-butylchloroformate (15.0 ml, 57,7 mmol) at room temperature. After completion of adding dropwise, the reaction mixture was stirred at room temperature for 14 hours. After concentration under reduced pressure, to the residue was added diethyl ether. Then the insoluble substance was filtered. The residue obtained by concentration of the filtrate under reduced pressure was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:1 was concentrated under reduced pressure to obtain specified in the title compound (11.3 g, 31,3 mmol, 54%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.06 (9H, s), 2,19 (1H, Sirs), 2,62-of 2.72 (4H, m), 3,63 (2H, shirt, J=5.5 Hz), 3,80 (2H, t, J=6.8 Hz), 7,32-7,52 (6H, m), 7,66 to 7.75 (4H, m).

IR (ATR) cm-1: 3400, 2929, 2856, 1427, 1105, 822, 735, 700, 611, 503.

MS m/z: 383 (M++Na).

Example 249: 2-[3-[2-(tert-b is chillipadililian)ethylthio]-1-[(4-chlorophenyl)sulfonyl]propyl]-1,4-differenza

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (900 mg, of 2.97 mmol)obtained in example 5 and 2-[2-(tert-butyldiphenylsilyl)ethylthio]ethanol (1.64 g, of 4.45 mmol) was dissolved in toluene (20 ml) followed by addition of cyanomethylene-n-butylphosphine (1.26 g, with 5.22 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 9 hours. After cooling, the reaction mixture was added 2-{2-(tert-butyldiphenylsilyl)ethylthio]ethanol (500 mg, of 1.39 mmol) and cyanomethylene-n-butylphosphate (400 mg, of 1.66 mmol). In argon atmosphere, the mixture was heated at the boil under reflux for 14 hours. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=10:1 was concentrated under reduced pressure to obtain specified in the connection header (1,82 g, 2.82 mmol, 95%) as pale yellowish-brown oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.02 (9H, s), of 2.20 to 2.35 (2H, m), 2,50-to 2.74 (4H, m), 3,65-of 3.80 (2H, m), 4.72 in-4,80 (1H, m), 6,77-6,85 (1H, m), 6,92-7,00 (1H, m), 7,15-of 7.23 (1H, m), 7,35-of 7.48 (8H, m), 7,52 (2H, d, J=8,8 Hz), to 7.64 (4H, d, J=8,1 Hz).

IR (ATR) cm-1: 2931, 2858, 1583, 1496, 1323, 1149, 1105, 1084, 754, 700, 503.

MS m/z 667 (M++Na).

Example 250: 2-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-di is terphenyl)propylthio]ethanol

In tetrahydrofuran (30 ml) was dissolved 2-[3-[2-(tert-butyldiphenylsilyl)ethylthio]-1-[(4-chlorophenyl)sulfonyl]propyl]-1,4-differental (1,81 g, 2,80 mmol). While cooling on ice to the resulting solution was added dropwise a solution in tetrahydrofuran (1.0 M, 8.0 ml, 8.0 mmol) of tetrabutylammonium, followed by stirring at room temperature for 2 hours. To the reaction mixture were added water (3 ml) followed by concentration under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=2:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with hexane to obtain specified in the header of the compound (977 mg, of 2.40 mmol, 86%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 1.97 (1H, t, J=6,1 Hz), 2,30 at 2.45 (2H, m), 2,60 is 2.80 (4H, m), 3,60-of 3.78 (2H, m), to 4.81 (1H, DD, J=9,6, 3.5 Hz), 6,80-of 6.90 (1H, m), of 6.96-7,05 (1H, m), 7,20-7,30 (1H, m), 7,39 (2H, d, J=8,8 Hz), 7,54 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 3564, 3072, 1583, 1496, 1275, 1144, 1082, 835, 810, 762, 627, 534, 480.

TPL: 108-110°C.

MS m/z: 424 (M++NH4).

Elemental analysis. Calculated for C17H17ClF2O3S2: C, 50,18; H, 4,21; Cl, 8,71; F, 9,34; S, 15,76. Found: C, 49,94; H, 4,20; Cl, 8,84; F, 9,41; S, 15,70.

Example 251:4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)tetrahydrothiopyran

In toluene (50 ml) was dissolved 2-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propylthio]ethanol (800 mg, 2.00 mmol) followed by addition of cyanomethylene-n-butylphosphine (1.50 g, from 6.22 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=15:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with hexane to obtain specified in the title compound (504 mg, 1.28 mmol, 64% in the form of a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,46 (2H, shirt, J=13,4 Hz), 2.57 m-2,78 (4H, m)to 3.09 (2H, Sirs), 6,85-to 6.95 (1H, m), 7,02-to 7.15 (2H, m), 7,37 (2H, d, J=8.7 Hz), 7,40 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 2927, 1574, 1495, 1306, 1267, 1147, 1080, 877, 825, 750, 710, 619, 561, 472.

TPL: 188-190°C.

MS m/z: 389 (M++H).

Elemental analysis. Calculated for C17H15ClF2O2S2·0,25H2O: C, Better Than Anticipated At 51.90; H, 3,97; Cl, 9,01; F, 9,66; S, 16,30. Found: C, 52,20; H, 3,91; Cl, 9,20; F, 9,85; S, 16,36.

Example 252: 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)tetrahydrothiopyran-1-he

In dichloromethane (30 ml) was dissolved 4-[(4-chlorophenyl)su is hanil]-4-(2,5-differenl)tetrahydrothiopyran (200 mg, 0.508 mmol). When cooled on ice was added 3-chloroperbenzoic acid (106 mg, 0,614 mmol). After stirring at room temperature for 14 hours, the reaction mixture was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with diethyl ether obtaining specified in the title compound (163 mg, 0,403 mmol, 79%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,30-3,55 (8H, m), 6,85? 7.04 baby mortality (1H, m), 7,05-7,20 (2H, m), 7,33 (0,8H, d, J=8,3 Hz), 7,40 (0,8H, d, J=8,3 Hz), 7,44 (1,2H, d, J=8,8 Hz), 7,47 (1,2H, d, J=8,8 Hz).

IR (ATR) cm-1: 3095, 1576, 1491, 1308, 1279, 1146, 1082, 879, 818, 800, 752, 712, 621, 565, 474.

TPL: 173-182°C.

MS m/z: 405 (M++H).

Elemental analysis. Calculated for C17H15ClF2O3S2: C, 50,43; H, To 3.73; Cl, 8,76; F, 9,38; S, 15,85. Found: C, 50,60; H, 3,76; Cl, 8,81; F, 9,48; S 15,92.

Example 253: 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)tetrahydrothiopyran-1,1-dioxide

4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)tetrahydrothiopyran (100 mg, 0,254 mmol)obtained in example 251, was dissolved in dichloromethane (15 ml) followed by addition of 3-chloroperbenzoic acid (110 mg, 0,637 mmol cooling on ice. After stirring at room temperature for 5 hours was added diethyl ether. The resulting mixture was washed with 1 N. aqueous sodium hydroxide solution and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with diethyl ether obtaining specified in the title compound (89 mg, 0,211 mmol, 83%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,80-to 3.02 (4H, m), 3,02-3,24 (4H, m), 6,91-7,01 (1H, m), 7,06-7,13 (1H, m), 7,14-7,22 (1H, m), 7,39 (2H, d, J=8.7 Hz), 7,44 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 1577, 1496, 1473, 1415, 1311, 1201, 1149, 1122, 1080, 874, 854, 822, 754, 708, 623, 567, 474.

TPL: 204-206°C.

MS m/z: 421 (M++H).

Elemental analysis. Calculated for C17H15ClF2O4S2: C, 48,51; H, 3,59; Cl, 8,42; F, 9,03; S, 15,24. Found: C, 48,61; H, 3,60; Cl, 8,44; F, 9,05; S, 15,21.

Example 254: 2-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propylsulfonyl]ethanol

2-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propylthio]ethanol (65 mg, 0.16 mmol)obtained in example 250, was dissolved in dichloromethane 5 ml) followed by addition of 3-chloroperbenzoic acid (33 mg, 0,19 mmol) under cooling on ice. The resulting mixture was stirred at room temperature for 14 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of dichloromethane:methanol=30:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with diethyl ether obtaining specified in the title compound (50 mg, 0.12 mmol, 74%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,52-to 2.65 (2H, m), 2,80-to 3.02 (5H, m), 4,11-4,22 (2H, m), 4,68-4,78 (1H, m), 6,80-of 6.90 (1H, m), 6,97? 7.04 baby mortality (1H, m), 7,21-7,30 (1H, m), 7,38-7,44 (2H, m), 7,50-7,58 (2H, m).

IR (ATR) cm-1: 3421, 3259, 1585, 1496, 1319, 1147, 1086, 1028, 989, 833, 756, 555, 534, 480, 463.

TPL: 124-132°C.

MS m/z: 423 (M++H).

Elemental analysis. Calculated for C17H17ClF2O4S2: C, 48,28; H, 4,05; Cl, 8,42; F, 9,03; S, 15,24. Found: C, 48,03; H, 4,01; Cl, 8,33; F, 8,93; S, 15,06.

Example 255: 2-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propylsulfonyl]ethanol

2-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propylthio]ethanol (65 mg, 0.16 mmol)obtained in example 250, was dissolved in dichloromethane (5 ml) followed by addition of 3-chloroperbenzoic acid (66 mg, 0.38 mmol) under cooling on ice. At room temperature the mixture is PE is amasyali within 14 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane-ethyl acetate=1:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with diethyl ether obtaining specified in the title compound (53 mg, 0.12 mmol, 76%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,19 (1H, t, J=5,1 Hz), 2,56-2,70 (1H, m), 2,97-3,10 (1H, m), 3,12 of 3.28 (4H, m), of 4.12 (2H, q, J=5,1 Hz), of 4.77 (1H, DD, J=9,4, 5.7 Hz), 6,82-6,92 (1H, m), 6,98-7,07 (1H, m), 7,20-7,30 (1H, m), 7,41 (2H, d, J=8.7 Hz), 7,54 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 3525, 3076, 1576, 1496, 1315, 1279, 1146, 1128, 1082, 1034, 1011, 997, 835, 758, 631, 559, 542, 523, 488, 467, 430.

TPL: 111-113°C.

MS m/z: 439 (M++H).

Elemental analysis. Calculated for C17H17ClF2O5S2: C, 46,52; H, 3,90; Cl, 8,08; F, 8,66; S, 14,61. Found: C, 46,46; H, 3,82; Cl, 8,15; F, 8,66; S, 14,55.

Reference example 42: Tert-butyl N-[2-(tert-butyldiphenylsilyl)ethyl]-N-(2-hydroxyethyl)carbamate

In a mixture of dichloromethane/N,N-dimethylformamide (70 ml/70 ml) was dissolved tert-butyl-N,N-bis(2-hydroxyethyl)carbamate (9.00 g, while 43.8 mmol) and imidazole (2,60 g of 38.2 mmol), followed by adding dropwise tert-butylchloroformate (8.1 ml, 31 mmol) at room temperature. After completion of adding dropwise actionnow the mixture was stirred at room temperature for 14 days. To the residue obtained by concentrating the reaction mixture under reduced pressure, was added diethyl ether. The resulting mixture was washed with water, and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on a column of silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=2:1 was concentrated under reduced pressure to obtain specified in the connection header (7,41 g, and 16.7 mmol, 54%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.05 (9H, c), 1,30-1,60 (9H, m), 3,30-to 3.52 (4H, m), 3,68-are 3.90 (4H, m), 7,34-to 7.50 (6H, m), 7,60-7,72 (4H, m).

IR (ATR) cm-1: 2931, 2858, 1693, 1670, 1408, 1365, 1171, 1144, 1105, 1051, 933, 822, 737, 700, 613, 501.

MS m/z: 444 (M++H).

Example 256: Tert-butyl N-[2-(tert-butyldiphenylsilyl)ethyl]-N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl]carbamate

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (500 mg, of 1.65 mmol)obtained in example 5, and tert-butyl N-[2-(tert-butyldiphenylsilyl)ethyl]-N-(2-hydroxyethyl)carbamate (950 mg, 2.14 mmol) was dissolved in toluene (20 ml) followed by addition of cyanomethylene-n-butylphosphine (600 mg, 2.49 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux in the course is E. 9 hours. After cooling, the reaction mixture was added tert-butyl N-[2-(tert-butyldiphenylsilyl)ethyl]-N-(2-hydroxyethyl)carbamate (500 mg, 1.13 mmol) and cyanomethylene-n-butylphosphate (300 mg, of 1.24 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling the reaction mixture the residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=15:1 was concentrated under reduced pressure to obtain specified in the connection header (1,14 g, 1.57 mmol, 95%) as pale yellowish-brown foam.

1H-NMR (400 MHz, CDCl3) δ: 0,97 (9H, c), 1,20-1,50 (9H, m)to 2.29 (1H, Sirs), 2,62-2,78 (1H, m), 3,05-to 3.50 (4H, m), 3,66 (2H, Sirs), 4,40-4,60 (1H, m), for 6.81 (1H, Sirs), 6,98 (1H, Sirs), 7,18-7,70 (15H, m).

IR (ATR) cm-1: 2931, 1689, 1585, 1496, 1473, 1323, 1149, 1086, 737, 700, 613, 467, 426.

MS m/z: 726 (M++H).

Example 257: Tert-butyl N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl]-N-(2-hydroxyethyl)carbamate

In tetrahydrofuran (20 ml) was dissolved tert-butyl-N-[2-(tert-butyldiphenylsilyl)ethyl]-N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl]carbamate (1.13 g, 1.55 mmol). When cooled on ice was added dropwise a solution in tetrahydrofuran (1.0 M, 5.0 ml, 5.0 mmol) those whom roboticassisted. The resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture were added water. The residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain specified in the header of the compound (651 mg, 1,32 mmol, 85%) as a white foam.

1H-NMR (400 MHz, CDCl3) δ: of 1.39 (9H, s), 2,28-to 2.42 (1H, m), 2.70 height is 2.80 (1H, m), 3,15-of 3.32 (3H, m), 3,40 (1H, Sirs), 3,68-of 3.80 (2H, m), of 4.54 (1H, Sirs), 6,78-to 6.88 (1H, m), 6,95-7,03 (1H, m), 7,20-7,31 (1H, m), 7,39 (2H, d, J=8.7 Hz), 7,52 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 3438, 2976, 2933, 1685, 1583, 1496, 1475, 1319, 1279, 1147, 1084, 1012, 827, 756, 710, 629, 555, 525, 467.

MS m/z: 490 (M++H), 512 (M++Na).

Elemental analysis. Calculated for C22H26ClF2NO5S·0,25H2O: C, 53,44; H, Of 5.40; Cl, 7,17; F, To 7.68; N, 2,83; S, 6.48 In. Found: C, 53,39; H, The 5.45; Cl, 7,21; F, Of 7.48; N, 2,95; S, 6,51.

Example 258: Hydrochloride of 2-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propylamino]ethanol

In dichloromethane (5 ml) was dissolved tert-butyl-N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl]-N-(2-hydroxyethyl)carbamate (300 mg, 0,607 mmol), and triperoxonane acid (0.5 ml) was added dropwise to the obtained solution under cooling on ice. After stirring at room temperature for 2 hours the reaction mixture was concentrated under reduced pressure. To the precipitate was added a 1N solution (5 ml) of hydrochloric acid in ethanol, followed by concentration under reduced pressure to obtain white solid. The thus obtained solid substance was washed with diethyl ether obtaining specified in the title compound (249 mg, 0,579 mmol, 95%) as a white powder.

1H-NMR (400 MHz, CD3OD) δ: 2,42-of 2.58 (1H, m), 2.77-to 2,90 (1H, m), 2,96 (1H, TD, J=11.8 in, 4,8 Hz), 3,06 is 3.15 (2H, m), up 3.22 (1H, dt, J=11.8 in, 5,1 Hz in), 3.75 (2H, DD, J=5,7, and 4.5 Hz), 4,89 (1H, DD, J=9,6, a 5.3 Hz), 6,98 (1H, TD, J=9,3, a 4.4 Hz), 7,10-7,20 (1H, m), 7,26-7,34 (1H, m), 7,54 (2H, d, J=8,8 Hz), to 7.61 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 3535, 2956, 2902, 2677, 1576, 1496, 1306, 1232, 1192, 1146, 1084, 1016, 822, 754, 710, 633, 548, 521, 472, 442.

TPL: 216-220°C.

MS m/z: 390 (M++H).

Elemental analysis. Calculated for C17H18ClF2NO3S·HCl·0,25H2O: C, 47,40; H, 4,56; Cl, 16,46; F, 8,82; N, 3,25; S, 7,44. Found: C, 47,52; H, 4,47; Cl, 16,47; F, 9,06; N, 3,36; S, 7,58.

Example 259: Tert-butyl 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-piperidinecarboxylate

Tert-butyl N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-differenl)propyl]-N-(2-hydroxyethyl)carbamate (200 mg, 0,404 mmol)obtained in example 257, was dissolved in toluene (10 ml) followed by addition of cyanomethylene-n-butylphosphine (200 mg, 0,829 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 8 choose cooling, the reaction mixture was added cyanomethylene-n-butylphosphate (200 mg, 0,829 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling the reaction mixture the residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with diethyl ether obtaining specified in the title compound (140 mg, 0,297 mmol, 74%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 1.43 (9H, s), and 2.27 (2H, shirt, J=14,2 Hz)to 2.67 (4H, Sirs), 4,18 (2H, Sirs), 6,82-6,92 (1H, m), 7.03 is-7,16 (2H, m), of 7.36 (2H, d, J=8.7 Hz), 7,40 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 2979, 1682, 1583, 1410, 1315, 1244, 1188, 1144, 1088, 831, 754, 623, 563, 534, 474.

TPL: 101-106°C.

MS m/z: 472 ( M++H).

Elemental analysis. Calculated for C22H24ClF2NO4S: C, 55,99; H, 5,13; Cl, 7,51; F, With 8.05; N, 2,97; S 6,79. Found: C, 55,89; H, 5,19; Cl, 7,35; F, Of 7.97; N, 3,02; S 6,80.

Example 260: Hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine

In dichloromethane (100 ml) was dissolved tert-butyl 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-piperidinecarboxylate (3,17 g, 6,72 mmol), followed by adding dropwise triperoxonane acid (10.0 ml) under cooling on ice is. After stirring at room temperature for 2 hours the reaction mixture was concentrated under reduced pressure. To the thus obtained residue was added 1 n solution (30 ml) chloride-hydrogen acid in ethanol. The resulting mixture was concentrated under reduced pressure to obtain white solid. Thus obtained white solid was washed with diethyl ether obtaining specified in the connection header (2,74 g of 6.71 mmol, yield quantitative) as a white powder.

1H-NMR (400 MHz, CD3OD) δ: to 2.57 (2H, TM, J=14.1 Hz), 2,85 (2H, TM, J=12,6 Hz), 2,98 (2H, Sirs), of 3.54 (2H, DM, J=13,7 Hz), 7,02 for 7.12 (1H, m), 7,22-7,31 (2H, m), the 7.43 (2H, d, J=8,8 Hz), 7,55 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 3338, 2943, 2713, 1579, 1495, 1469, 1311, 1196, 1144, 1082, 1012, 893, 818, 750, 623, 567.

TPL: 239-246°C (decomp.).

MS m/z: 372 (M++H).

Elemental analysis. Calculated for C17H16ClF2NO2S·HCl·0,75H2O: C, 48,41; H, 4,42; Cl, The Value Of 16,81; F, 9,01; N, 3,32; S, 7,60. Found: C, 48,60; H, Or 4.31; Cl, 16,33; F, 9,16; N, 3.46 In; S, 7,80.

Example 261: 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-methylpiperidin

To dichlormethane (5 ml) were added hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (100 mg, 0,245 mmol), triethylamine (0,070 ml, 0.50 mmol) and 37% aqueous formaldehyde solution (to 0.060 ml, 0,739 mmol) followed by the addition of triacetoxyborohydride 220 mg, 1.04 mmol) at room temperature. After stirring at room temperature for 14 hours was added 1 N. aqueous sodium hydroxide solution (6.0 ml). The mixture was stirred at room temperature for 30 minutes. To the reaction mixture were added diethyl ether, and the mixture was washed 1 N. aqueous sodium hydroxide solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate dichloromethane:methanol=30:1 was concentrated under reduced pressure to obtain white solid. Thus obtained white solid is washed with diisopropyl ether to obtain specified in the title compound (70 mg, 0.18 mmol, 74%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,90 (2H, TM, J=12,5 Hz), 2,17 (3H, s), 2,42 (2H, TM, J=11.8 Hz), 2,50-2,90 (2H, m), 2,89 (2H, dt, J=12,0,2,9 Hz), 6,82-6,92 (1H, m), 7.03 is-7,16 (2H, m), 7,38 (2H, d, J=9.0 Hz), 7,42 (2H, d, J=9.0 Hz).

IR (ATR) cm-1: 3084, 3006, 2943, 2850, 2796, 1577, 1496, 1462, 1313, 1281, 1184, 1147, 1086, 814, 752, 712, 631, 571, 534, 474, 440.

TPL: 172-175°C.

MS m/z: 386 (M++H).

Elemental analysis. Calculated for C18H18ClF2NO2S: C, 56,03; H, 4,70; Cl, 9,19; F, 9,85; N, 3,63; S, 8,31. Found: C, 55,92; H, 4,72; Cl, 9,10; F, To 9.91; N, 3,67; S, 8,39.

Example 262: 1-benzyl-4-[(4-chloro who enyl)sulfonyl]-4-(2,5-differenl)piperidine

Hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (100 mg, 0,245 mmol)obtained in example 260, triethylamine (0,070 ml, 0.50 mmol) and benzaldehyde (0,050 ml, 0,428 mmol) was added to dichloromethane (5 ml) followed by the addition of triacetoxyborohydride sodium (110 mg, 0,500 mmol) at room temperature. The resulting mixture was stirred at room temperature for 14 hours. Then added 1 N. aqueous sodium hydroxide solution (3.0 ml). The resulting mixture was stirred at room temperature for 30 minutes. After adding diethyl ether to the resulting mixture was washed with 1 N. aqueous sodium hydroxide solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate dichloromethane:methanol=50:1 was concentrated under reduced pressure to obtain specified in the title compound (87 mg, 0,19 mmol, 77%) as a white foam.

1H-NMR (400 MHz, CDCl3) δ: of 1.93 (2H, shirt, J=12,5 Hz), 2,46 (2H, shirt, J=11,6 Hz), 2,65 (2H, Sirs), with 2.93 (2H, DM, J=12,5 Hz)to 3.36 (2H, s), for 6.81-6,94 (1H, m), 7,00-to 7.15 (2H, m), 7,20-7,34 (5H, m), 7,37 (4H, s).

IR (ATR) cm-1: 2812, 2769, 1583, 1495, 1313, 1259, 1188, 1144, 1088, 810, 752, 698, 629, 571, 542, 469.

MS m/z: 462 (M++H).

Element EN is Liz. Calculated for C24H22ClF2NO2S: C, 62,40; H, 4,80; Cl, To 7.67; F, 8,23; N, 3,03; S 6,94. Found: C, 62,50; H, 4,98; Cl, 7,50; F, With 8.05; N, 3.04 From; S 6,90.

Example 263: 1-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidino]-1-alanon

Hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (90 mg, 0.22 mmol)obtained in example 260, and triethylamine (0,092 ml, 0.66 mmol) was dissolved in dichloromethane (4 ml) followed by the addition of acetylchloride (0,024 ml, 0.34 mmol) at room temperature. After stirring at room temperature for 14 hours was added saturated aqueous sodium bicarbonate solution (0.5 ml). The residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of dichloromethane:methanol=30:1 was concentrated under reduced pressure to obtain white solid. The thus obtained solid substance was washed with hexane to obtain specified in the title compound (48 mg, 0.12 mmol, 53%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 2.08 (3H, s), 2,20-to 2.42 (2H, m), 2.49 USD (1H, shirt, J=13,0 Hz), 2,60-of 2.75 (1H, m), 2,75-2,90 (1H, m), 3,01 (1H, shirt, J=13,2 Hz), 3,92 (1H, DM, J=13,4 Hz), 4,70 (1H, DM, J=a 13.9 Hz), 6,85-6,94 (1H, m), 7,50-7,60 (2H, m), of 7.36 (2H, d, J=8,8 Hz), 7,40 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 3084, 1653, 1496, 1427, 1309, 1279, 1244, 1144, 108, 993, 754, 627, 563, 474.

TPL: 159-160°C.

MS m/z: 414 (M++H).

Elemental analysis. Calculated for C19H18ClF2NO3S: C, 55,14; H, To 4.38; Cl, To 8.57; F, 9,18; N, 3,38; S 7,75. Found: C, 55,07; H, 4,49; Cl, 8,69; F, Of 9.30; N, 3,41; S, To 7.77.

Example 264: [4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidino](4-pyridyl)metano

Similar to the method of example 263, except hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (80 mg, 0.20 mmol)obtained in example 260, and hydrochloride of isonicotinohydrazide (60 mg, 0.34 mmol) specified in the title compound (84 mg, 0.18 mmol, 90%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,24-to 2.55 (2H, m), 2,60-2,90 (3H, m), 2,90-3,10 (1H, m), 3,70-3,82 (1H, m), 4,74-of 4.90 (1H, m), 6,84-6,92 (1H, m),? 7.04 baby mortality-7,14 (2H, m), 7.18 in-to 7.25 (2H, m), 7,34 (2H, d, J=8.5 Hz), 7,39 (2H, d, J=8,5 Hz), to 8.70 (2H, d, J=5,9 Hz).

IR (ATR) cm-1: 3032, 1630, 1496, 1439, 1311, 1279, 1146, 1086, 1013, 810, 752, 625, 561, 505.

TPL: 245-248°C.

MS m/z: 477 (M++H).

FAB-MS: 477,0839 (calculated for C23H20ClF2N2O3S: 477,0851).

Example 265: [4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidino](3-pyridyl)metano

Similar to the method of example 263, except hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (90 mg, 0.22 mmol)obtained in example 260, and hydrochloride nicotinoyl is Yes (60 mg, 0.34 mmol) specified in the title compound (75 mg, 0.16 mmol, 71%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,20-4,90 (8H, m), 6,85-to 6.95 (1H, m), 7,08-to 7.18 (2H, m), 7,32-the 7.43 (1H, m), 7,35 (2H, d, J=8,9 Hz), 7,40 (2H, d, J=8,9 Hz), 7,73 (1H, dt, J=7,8,2,0 Hz), to 8.62 (1H, DD, J=2.0 a, 1.0 Hz), 8,68 (1H, DD, J=4,9, 2.0 Hz).

IR (ATR) cm-1: 1631, 1585, 1493, 1444, 1315, 1144, 1088, 831, 756, 625, 557, 505, 474.

TPL: 119-124°C.

MS m/z: 477 (M++H).

Elemental analysis. Calculated for C23H19ClF2N2O3S: C, 57,92; H, Was 4.02; Cl, 7,43, F, Of 7.97; N, By 5.87; S, 6,72. Found: C, 57,69; H, 4,08; Cl, 7,33; F, Of 7.97; N, 5,94; S, 6,78.

Example 266: [4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidino](2-pyridyl)metano

Similar to the method of example 263, except hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (80 mg, 0.22 mmol)obtained in example 260, and hydrochloride of ptolemaida (60 mg, 0.34 mmol) specified in the title compound (77 mg, 0.16 mmol, 82%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,35-2,52 (2H, m), 2,60-2,90 (3H, m)to 3.09 (1H, shirt, J=13.1 Hz), is 4.21 (1H, DM, J=13.5 Hz), a 4.83 (1H, DM, J=14,0 Hz), 6,82-to 6.95 (1H, m),? 7.04 baby mortality-to 7.18 (2H, m), 7,30 was 7.45 (5H, m), the 7.65 (1H, DM, J=7.8 Hz), 7,80 (1H, TD, J=7,8) and 1.7 Hz), 8,55 (1H, DM, J=4,9 Hz).

IR (ATR) cm-1: 3084, 1635, 1496, 1311, 1146, 1086, 1007, 843, 804, 752, 629, 555, 467.

TPL: 193-196°C.

MS m/z: 477 (M++H).

Elemental analysis. Calculated for C23H19ClF2N 2O3S: C, 57,92; H, Was 4.02; Cl, 7,43, F, Of 7.97; N, By 5.87; S, 6,72. Found: C, 57,94; H, 4,08; Cl, Of 7.48; F, To 7.99; N, Of 5.92; S, For 6.81.

Example 267: Methyl-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-piperidinecarboxylate

Similar to the method of example 263, except hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (90 mg, 0.22 mmol)obtained in example 260, and methylchloroform (0,026 ml, 0.34 mmol) specified in the title compound (62 mg, 0.14 mmol, 65%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: to 2.29 (2H, TM, J=12.1 Hz), 2,55-to 2.85 (4H, m), 3,68 (3H, s), 4,22 (2H, Sirs), 6,82-6,92 (1H, m), 7,05-to 7.15 (2H, m), of 7.36 (2H, d, J=8,8 Hz), 7,40 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 1695, 1493, 1450, 1400, 1248, 1188, 1142, 1090, 901, 825, 623, 565, 534, 474.

TPL: 123-126°C.

MS m/z: 430 (M++H).

Elemental analysis. Calculated for C19H18ClF2NO4S: C, 53,09; H, 4,22; Cl, 8,25; F, 8,84; N, 3,26; S 7,46. Found: C, 52,89; H, 4,20; Cl, 8,27, F, Of 8.90; N, 3,35; S, 7,58.

Example 268: N,N-dimethyl-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-piperazinecarboxamide

Similar to the method of example 263, except hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (90 mg, 0.22 mmol)obtained in example 260, and N,N-dimethylammoniumchloride (0,031 ml, 0.34 mmol) specified in the title compound (81 mg, 0.18 mmol, 83%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,40 (2H, shirt, J=12.1 Hz), 2,60 is 2.80 (4H, m), of 2.81 (6H, s), and 3.72 (2H, DM, J=13,7 Hz), 6,82-6,92 (1H, m),? 7.04 baby mortality-7,14 (2H, m), 7,35 (2H, d, J=9.0 Hz), 7,39 (2H, d, J=9.0 Hz).

IR (ATR) cm-1: 1651, 1576, 1496, 1469, 1365, 1308, 1190, 1146, 1074, 1034, 914, 814, 758, 752, 617, 561, 474.

TPL: 143-146°C.

MS m/z: 443 (M++H).

Elemental analysis. Calculated for C20H21ClF2N2O3S: C, 54,24; H, 4,78; Cl, 8,00; F, 8,58; N, 6,32; S, 7,24. Found: C, 53,96; H, 4,73; Cl, 8,14; F, 8,64; N, 6,34; S, 7,32.

Example 269: 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-(methylsulphonyl)piperidine

Similar to the method of example 263, except hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (90 mg, 0.22 mmol)obtained in example 260, and methanesulfonanilide (0,026 ml, 0.34 mmol) specified in the title compound (72 mg, 0.16 mmol, 73%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,48 (2H, shirt, J=12.1 Hz), 2,60-2,90 (4H, m), of 2.72 (3H, s), 3,88 (2H, DM, J=12.9 Hz), 6,88-of 6.96 (1H, m),? 7.04 baby mortality-7,14 (2H, m), 7,37 (2H, d, J=8,9 Hz), 7,42 (2H, d, J=8,9 Hz).

IR (ATR) cm-1: 1579, 1495, 1308, 1257, 1138, 966, 814, 752, 623, 565, 513.

TPL: 176-178°C.

MS m/z: 450 (M++H).

Elemental analysis. Calculated for C18H18ClF2NO3S: C, 48,05; H, 4,03; Cl, 7,88; F, To 8.45; N, 3,11; S, 14,25. Found: C, 48,02; H; 4,00; Cl, To $ 7.91; F, Charged 8.52; N, 3,22; S Of 14.28.

Example 270: N,N-dimethyl-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-piperidinylidene

Similar to the method of example 263, except hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (90 mg, 0.22 mmol)obtained in example 260, and N,N-dimethylsulfoxide (0.036 ml, 0.34 mmol) specified in the title compound (84 mg, 0.18 mmol, 80%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 2.45 (2H, shirt, J=12,5 Hz), 2,68-2,90 (4H, m), and 2.79 (6H, s), of 3.73 (2H, DM, J=13,4 Hz), 6,80-6,92 (1H, m), 7,05-7,14 (2H, m), 7,34 (2H, d, J=8,8 Hz), 7,40 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 1576, 1493, 1469, 1315, 1144, 984, 904, 808, 742, 621, 553, 519, 472.

TPL: 125-129°C.

MS m/z: 479 (M++H).

Elemental analysis. Calculated for C19H21ClF2N2O4S2: C, 47,65; H, 4,42; Cl, 7,40; F, To 7.93; N, 5,85; S, 13,39. Found: C, 47,62; H, 4,40; Cl, 7,42; F, 8,03; N, 5,95; S, 13,43.

Example 271: 1-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidino]-2-(dimethylamino)-1-alanon

Hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (100 mg, 0,245 mmol)obtained in example 260, N,N-dimethylglycine (40 mg, 0,39 mmol) and N-methylmorpholin (0,142 ml of 1.29 mmol) was dissolved in dichloromethane (5 ml) followed by addition of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (80 mg, 0.42 mmol) at room temperature. After stirring at room temperature for 14 hours was added a saturated aqueous solution (0.5 ml) bicarbonate is the atrium. The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using dichloromethane:methanol=30:1 was concentrated under reduced pressure to obtain white solid. The obtained solid is washed with diisopropyl ether to obtain specified in the title compound (70 mg, 0.15 mmol, 62%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 2,15-to 2.40 (2H, m), of 2.25 (6H, s)of 2.50 (1H, shirt, J=12.9 Hz), 2,60-to 2.85 (2H, m), with 2.93 (1H, shirt, J=12.0 Hz), 3,03 (1H, d, J=13,2 Hz), 3,13 (1H, d, J=13,2 Hz), 4,32 (1H, sird, J=14.4 Hz), of 4.67 (1H, sird, J=13,7 Hz), 6,83-6,93 (1H, m), 7,02-7,16 (2H, m), of 7.36 (2H, d, J=8,8 Hz), 7,40 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 2829, 2773, 1635, 1460, 1313, 1142, 1090, 827, 806, 754, 625, 561, 523, 474.

TPL: 88-92°C.

MS m/z: 457 (M++H).

Elemental analysis. Calculated for C21H23ClF2N2O3S: C, 55,20; H, 5,07; Cl, 7,76; F, 8,32; N, 6,13; S 7,02. Found: C, 55,15; H, 5,18; Cl, 7,76; F, Of 8.40; N, 6,13; S, 7,13.

Example 272 N-ethyl-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)-1-piperazinecarboxamide

Hydrochloride 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-differenl)piperidine (80 mg, 0.20 mmol)obtained in example 260, and triethylamine (0,092 ml, 0.66 mmol) was dissolved in dichloromethane (4 ml) followed by the addition utilizationof (0,027 mg, 0.34 mmol) at room temperature. After re is eshiwani at room temperature for 6 hours was added saturated aqueous sodium bicarbonate solution (0.5 ml). The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate dichloromethane:methanol=50:1 was concentrated under reduced pressure to obtain white solid. The obtained solid is washed with diisopropyl ether to obtain specified in the title compound (74 mg, 0,17 mmol, 85%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 1.12 (3H, t, J=7.2 Hz), 2,33 (2H, shirt, J=11.8 Hz), of 2.72 (4H, shirt, J=12.0 Hz), 3,18-3,30 (2H, m)to 3.99 (2H, DM, J=13,4 Hz), 4,30-and 4.40 (1H, m), 6,84-to 6.95 (1H, m), 7,05-to 7.15 (2H, m), 7,37 (2H, d, J=8,8 Hz), 7,40 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 3286, 1622, 1496, 1309, 1265, 1144, 1090, 889, 825, 752, 629, 567, 542, 474.

TPL: 172-174°C.

MS m/z: 443 (M++H).

Elemental analysis. Calculated for C20H21ClF2N2O3S: C, 54,24; H, 4,78; Cl, 8,00; F, 8,58; N, 6,32; S, 7,24. Found: C, 54,18; H, 4,76; Cl, 8,15; F, To 8.70; N, 6,41; S, 7,39.

Example 273: 2-[7-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]heptyl]-1,4-differenza

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (470 mg, 1.55 mmol)obtained in example 5, and 6(tert-butyldiphenylsilyl)-1-hexanol (740 mg, of 2.08 mmol) was dissolved in toluene (20 ml) followed by addition of cyanomethylene-n-butylphosphine (500 mg, 2,07 mmol). In the atmosphere of argon, the mixture was heated at the boiling reverse the m refrigerator for 7 hours. After cooling the reaction mixture the residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=10:1 was concentrated under reduced pressure to obtain specified in the connection header (786 mg, of 1.23 mmol, 79%) as pale yellowish-brown oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.02 (9H, s), 1,10-1,40 (6H, m), 1,42-of 1.55 (2H, m), 2.00 in and 2.14 (1H, m), 2,35-2,48 (1H, m), of 3.60 (2H, t, J=6.5 Hz), 4,49 (1H, DD, J=11,6, and 2.6 Hz), 6,76-6,89 (1H, m), 6,94-7,03 (1H, m), 7,20-7,30 (1H, m,), 7,34-to 7.50 (8H, m), 7,53 (2H, d, J=8.6 Hz), to 7.64 (4H, DM, J=8,1 Hz).

IR (ATR) cm-1: 2931, 2856, 1583, 1496, 1427, 1323, 1149, 1105, 1084, 822, 700, 627, 613, 503, 486, 467.

MS m/z: 641 (M++H).

Example 274: 7-[(4-chlorophenyl)sulfonyl]-7-(2,5-differenl)-1-heptanol

In tetrahydrofuran (20 ml) was dissolved 2-[7-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]heptyl]-1,4-differental (786 mg, of 1.23 mmol), followed by adding dropwise while cooling on ice solution in tetrahydrofuran (1.0 M, 4.0 ml, 4.0 mmol) tetrabutylammonium. The resulting mixture was stirred at room temperature for 14 hours. After adding water (2 ml) and the mixture was concentrated under reduced pressure. Thus obtained residue was subjected to flash chromatography on silica gel, and the fraction, polucen the Yu from the eluate using a mixture of hexane:ethyl acetate=2:1, concentrated under reduced pressure to obtain white solid. White solid was washed with hexane to obtain specified in the title compound (403 mg, 1.00 mmol, 81%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,10-of 1.75 (9H, m), 2,02-of 2.20 (1H, m), 2,38-2,52 (1H, m), of 3.60 (2H, t, J=6.4 Hz), 4,50 (1H, DD, J=11,7, a 3.2 Hz), 6,78-of 6.90 (1H, m), 6,92-7,05 (1H, m), 7,20-to 7.35 (1H, m), 7,38 (2H, d, J=8,4 Hz), 7,53 (2H, d, J=8,4 Hz).

IR (ATR) cm-1: 3338, 2935, 2860, 1583, 1495, 1325, 1149, 1082, 1012, 752, 631, 542, 467.

TPL: 77-79°C.

MS m/z: 403 (M++H), 420 (M++NH4).

Elemental analysis. Calculated for C19H21ClF2O3S: C, 56,64; H, 5.25-Inch; Cl, 8,80; F, 9,43; S Of 7.96. Found: C, 56,16; H, 5,18; Cl, 8,80; F, 9,36; S 8,00.

Example 275: 2-[1-[(4-chlorophenyl)sulfonyl]cycloheptyl-1,4-differenza

In toluene (5 ml) was dissolved 7-[(4-chlorophenyl)sulfonyl]-7-(2,5-differenl)-1-heptanol (200 mg, 0,496 mmol) followed by addition of cyanomethylene-n-butylphosphine (400 mg, 2,07 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling the reaction mixture the residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=10:1 was concentrated under reduced pressure with what rucenim white solid. White solid was washed with hexane to obtain specified in the title compound (111 mg, in 0.288 mmol, 58%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,34 of 1.50 (4H, m), 1.50 is by 1.68 (2H, m), 1,82-to 1.98 (2H, m), a 2.36 (2H, TM, J=12,5 Hz), 2,65-2,78 (2H, m), 6,84-6,94 (1H, m), 6,97-was 7.08 (2H, m), 7,34 (2H, d, J=9.0 Hz), 7,37 (2H, d, J=9.0 Hz).

IR (ATR) cm-1: 2931, 2856, 1577, 1493, 1473, 1308, 1277, 1186, 1140, 1086, 1012, 881, 818, 748, 710, 615, 559, 467.

TPL: 101-103°C.

MS m/z: 402 (M++NH4).

Elemental analysis. Calculated for C19H19ClF2O2S: C, 59,29; H, 4,98; Cl, Of 9.21; F, 9,87; S, 8,33. Found: C, 59,21; H, 4,86; Cl, 9,25; F, 9,96; S, 8,48.

Example 276: 2-[2-[2-[(tert-butyldiphenylsilyl)methyl]phenyl]-1-[(4-chlorophenyl)sulfonyl]ethyl]-1,4-differenza

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (600 mg, to 1.98 mmol)obtained in example 5, and [2-[(tert-butyldiphenylsilyl)methyl]phenyl]methanol (1,00 g of 2.66 mmol) was dissolved in toluene (20 ml) followed by addition of cyanomethylene-n-butylphosphine (640 mg, to 2.65 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling, the reaction mixture was added [2-[(tert-butyldiphenylsilyl)methyl]phenyl]methanol (400 mg, 1.06 mmol) and cyanomethylene-n-butylphosphate (400 mg, of 1.66 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux in the course is the development of 14 hours. After cooling the reaction mixture the residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=15:1 was concentrated under reduced pressure to obtain specified in the title compound (1.13 g, 1,71 mmol, 86%) as pale yellowish-brown oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.09 (9H, s), 3,30 (1H, DD, J=14,7, 11.2 Hz), 3,80 (1H, DD, J=14,7, 3,4 Hz)and 4.65 (1H, d, J=12.9 Hz), 4,70-4,85 (2H, m), 6,64-6,74 (1H, m), PC 6.82 (1H, d, J=6.8 Hz), 6,85-6,94 (1H, m), 7,03 (1H, TD, J=of 7.5 and 1.4 Hz), to 7.15 (1H, TD, J=7,5, 1.2 Hz), 7,20-of 7.55 (12H, m), 7,65-7,76 (4H, m).

IR (ATR) cm-1: 2931, 2856, 1583, 1496, 1473, 1427, 1319, 1149, 1111, 1082, 822, 740, 700, 634, 501.

MS m/z 661 (M++H), 683 (M++Na).

Example 277: [2-[2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)ethyl]phenyl]methanol

In tetrahydrofuran (20 ml) was dissolved 2-[2-[2-[(tert-butyldiphenylsilyl)methyl]phenyl]-1-[(4-chlorophenyl)sulfonyl]ethyl]-1,4-differental (1.10 g, of 1.66 mmol) followed by the addition dropwise of a solution in tetrahydrofuran (1.0 M, 5.0 ml, 5.0 mmol) tetrabutylammonium while cooling on ice. The resulting mixture was stirred at room temperature for 14 hours. After adding water (3 ml) of the residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on when likehere. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain white solid. The white solid is washed with diisopropyl ether to obtain specified in the title compound (595 mg, of 1.41 mmol, 85%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,92 (1H, DD, J=6,1, a 4.9 Hz), the 3.35 (1H, DD, J=14,1, 10,0 Hz), 4,00 (1H, DD, J=14,1, 3,4 Hz), of 4.66 (1H, DD, J=12,3, a 4.9 Hz), to 4.81 (1H, DD, J=12,3, 6,1 Hz), 5,10 (1H, DM, J=10.0 Hz), 6,66 to 6.75 (1H, m), PC 6.82 (1H, d, J=7.5 Hz), 6.89 in-6,98 (1H, m), 7,06 (1H, TD, J=7,5, 1.5 Hz), 7,17 (1H, TD, J=7,5, 1.2 Hz), 7,29 (1H, DD, J=7,5, 1.2 Hz), 7,38 (2H, d, J=8.7 Hz), 7,50 (1H, Sirs), 7,58 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 3506, 1576, 1493, 1313, 1279, 1213, 1144, 1080, 1014, 829, 750, 708, 634, 536, 471.

TPL: 107-108°C.

MS m/z: 422 (M+).

Elemental analysis. Calculated for C21H17ClF2O3S: C, 59,65; H, 4,05; Cl, Scored 8.38; F, 8,99; S, 7,58. Found: C, 59,46; H, 3,97; Cl, To 8.41; F, 9,05; S, To 7.67.

Example 278: 2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)indan

In toluene (5 ml) was dissolved [2-[2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)ethyl]phenyl]methanol (80 mg, 0,19 mmol) followed by addition of cyanomethylene-n-butylphosphine (140 mg, 0,580 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 8 hours. After cooling the reaction mixture the residue obtained by concentration of the reaction mixtures and under reduced pressure, was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=5:1 was concentrated under reduced pressure to obtain white solid. The white solid is washed with diisopropyl ether to obtain specified in the title compound (32 mg, 0.079 in mmol, 42%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: and 3.72 (2H, DM, J=17.6 Hz), 4,18 (2H, DD, J=17,6, 2,9 Hz), 6,95? 7.04 baby mortality (1H, m),? 7.04 baby mortality for 7.12 (4H, m), 7,12-7,21 (1H, m), 7,21-7,30 (1H, m), 7.23 percent (2H, d, J=8.7 Hz), was 7.45 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 1572, 1495, 1306, 1138, 1078, 821, 754, 656, 598, 571, 525, 478, 451.

TPL: 209-210°C (decomp.).

MS m/z: 422 (M++NH4).

Example 279: 2-[1-[(4-chlorophenyl)sulfonyl]-2-Methylcyclopentane]-1,4-differenza

2-[5-(tert-butyldiphenylsilyl)-1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differental (mixture of isomers) (1.40 g, of 2.23 mmol)obtained in example 38 was dissolved in tetrahydrofuran (30 ml) followed by the addition of a solution in tetrahydrofuran (1.0 M, 5.0 ml, 5.0 mmol) tetrabutylammonium while cooling on ice. The resulting mixture was stirred at room temperature for 14 hours. After adding water (3 ml) of the residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate used with the mixture of hexane:ethyl acetate=2:1, concentrated under reduced pressure to obtain 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-4-methyl-1-pentanol (mixture of isomers) (879 mg, yield quantitative) as a colourless oil.

Obtained 5-[(4-chlorophenyl)sulfonyl]-5-(2,5-differenl)-4-methyl-1-pentanol (mixture of isomers) was dissolved in toluene (10 ml) followed by addition of cyanomethylene-n-butylphosphine (1,00 g, 4.14 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling the reaction mixture the residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=20:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with hexane to obtain specified in the title compound (423 mg, to 1.14 mmol, 51%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 0,85 (1H, d, J=6.8 Hz), 1,50-1,80 (1,67H, m), 1,72 (2H, d, J=7,1 Hz), 1,84-of 2.50 (3H, m), 2,62 was 3.05 (2H, m), 3,30-3,45 (0,33H, m), 6,72-6,92 (1,33H, m), 6,92-7,06 (1H, m), 7,12-7,22 (0,67H, m), 7,27-7,40 (4H, m).

IR (ATR) cm-1: 1579, 1493, 1300, 1263, 1190, 1136, 1092, 1080, 1012, 839, 823, 756, 746, 712, 638, 600, 579, 546, 517, 472.

TPL: 105-109°C.

MS m/z: 393 (M++Na).

Elemental analysis. Calculated for C18H17ClF2O2S: C, 58,30; H, 4,57;Cl, 9,71; F, 10,15; S 8,79. Found: C, 58,27; H, 4,57; Cl, 9,71; F, 10,15; S 8,79.

Reference example 43: (2 bromoethylamine)tert-butyldiphenylsilyl

In dichloromethane (50 ml) was dissolved [2-[(tert-butyldiphenylsilyl)methyl]phenyl]methanol (3.00 g, of 7.97 mmol) and tetrabromide carbon (3,40 g of 10.3 mmol). Under ice cooling was added dropwise a solution in dichloromethane (5 ml) of triphenylphosphine (2.70 g, or 10.3 mmol). After stirring at room temperature for 14 hours, the reaction mixture was concentrated under reduced pressure. Thus obtained residue was subjected to chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=30:1 was concentrated under reduced pressure to obtain specified in the title compound (3.12 g, 7,10 mmol, 89%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.05 (9H, s), 4,51 (2H, s), 4,88 (2H, s), 7,20-7,51 (10H, m), 7,68 (4H, DD, J=7,6, 1.2 Hz).

IR (ATR) cm-1: 2929, 2856, 1427, 1105, 1068, 822, 739, 698, 607, 501.

Example 280: Tert-butyl-[[2-[[(4-chlorophenyl)sulfonyl]methyl]benzyl]oxy]diphenylsilane

In propanol (20 ml) was dissolved (2 bromoethylamine)-tert-butyldiphenylsilyl (3,10 g, 7.05 mmol) followed by addition of 4-chlorobenzenesulfonate sodium (1.80 g, 9,06 mmol). When 90aboutWith the resulting mixture was stirred for 14 hours. After the slyvania the reaction mixture to a residue, obtained by concentrating the reaction mixture under reduced pressure, was added ethyl acetate. The resulting mixture was washed with water and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain specified in the connection header (3,90 g, yield quantitative) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: of 1.03 (9H, s), 4,43 (2H, s), 4,47 (2H, s), 7,20-7,28 (1H, m), 7,28-7,37 (4H, m), 7,37-7,52 (9H, m), 7,60 (4H, DD, J=7,8, 1.5 Hz).

MS m/z: 535 (M++H).

Example 281: Tert-butyl-[[2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzyl]oxy]diphenylsilane

In toluene (5 ml) was dissolved tert-butyl-[[2-[[(4-chlorophenyl)sulfonyl]methyl]benzyl]oxy]diphenylsilane (350 mg, 0,654 mmol) and 4-(methylsulphonyl)-1-butanol (200 mg, 1,31 mmol)obtained in reference example 3, followed by the addition of cyanomethylene-n-butylphosphine (350 mg, 1,45 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling, the reaction mixture was added cyanomethylene-n-butylphosphate (300 mg, of 1.24 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentration of the mixture of PR is the reduced pressure, was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=3:2, was concentrated under reduced pressure to obtain specified in the title compound (175 mg, 0,261 mmol, 40%) as pale yellowish-brown oil.

1H-NMR (400 MHz, CDCl3) δ: of 1.05 (9H, s), 1,18-of 1.30 (1H, m), 1.30 and the 1.44 (1H, m), 1.70 to of 1.84 (2H, m), 2,08-of 2.24 (1H, m), 2,35-2,48 (1H, m), 2,74-to 2.85 (2H, m), 2,80 (3H, s), 4,13 (1H, d, J=a 12.7 Hz), 4,35 (1H, d, J=a 12.7 Hz), 4,51 (1H, DD, J=10,8, 4,4 Hz), 7.18 in-to 7.25 (3H, m), 7,25 was 7.45 (8H, m), 7,45-7,53 (3H, m), 7,55-to 7.68 (4H, m).

IR (ATR) cm-1: 2929, 2856, 1583, 1473, 1321, 1147, 1105, 1088, 833, 775, 741, 702, 623, 569, 503.

MS m/z 669 (M++H), 691 (M++Na).

Example 282: [2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]phenyl]methanol

In tetrahydrofuran (5 ml) was dissolved tert-butyl-[[2-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulphonyl)pentyl]benzyl]oxy]diphenylsilane (175 mg, 0,261 mmol). While cooling on ice to the resulting solution was added dropwise a solution in tetrahydrofuran (1.0 M, 0.6 ml, 0.6 mmol) tetrabutylammonium. Then the resulting mixture was stirred at room temperature for 1 hour. After adding water (0.5 ml) of the residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of dichloromethane:methanol:1, concentrated under reduced pressure to obtain specified in the title compound (87 mg, 0.20 mmol, 61%) as pale yellowish-brown oil.

1H-NMR (400 MHz, CDCl3) δ: 1,20-1,60 (2H, m), 1,65-of 1.95 (2H, m), 2,10-to 2.40 (3H, m), 2.70 height is 3.00 (2H, m), 2,82 (3H, s), 4,43 (2H, d, J=4.9 Hz), to 4.81 (1H, DD, J=11,1, 4.0 Hz), 7,15-7,30 (1H, m), 7,30 is 7.50 (5H, m), 7,56 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 3506, 2931, 1579, 1475, 1394, 1277, 1138, 1084, 1012, 964, 829, 798, 756, 712, 629, 563, 519, 463.

MS m/z: 448 (M++NH4), 453 (M++Na).

Example 283: Tert-butyl-[[6-[2-[(tert-butyldiphenylsilyl)methyl]phenyl]-6-[(4-chlorophenyl)sulfonyl]hexyl]oxy]dimethylsilane

Tert-butyl-[[2-[[(4-chlorophenyl)sulfonyl]methyl]benzyl]oxy]diphenylsilane (1,00 g of 1.87 mmol)obtained in example 280, and 5-(tert-butyldiphenylsilyl)-1-pentanol (0.68 ml, 2.8 mmol) was dissolved in toluene (7 ml) followed by addition of cyanomethylene-n-butylphosphine (650 mg, 2,69 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling, the reaction mixture was added 5-(tert-butyldiphenylsilyl)-1-pentanol (0,34 ml, 1.4 mmol) and cyanomethylene-n-butylphosphate (300 mg, of 1.24 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 10 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentration of re is klonoa mixture under reduced pressure, was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=15:1 was concentrated under reduced pressure to obtain specified in the connection header (932 mg, of 1.27 mmol, 68%) as pale yellowish-brown oil.

1H-NMR (400 MHz, CDCl3) δ: 0,00 (6H, s), 0,80-1,60 (6H, m)0,86 (9H, s), was 1.04 (9H, s), 2,04-of 2.20 (1H, m), 2,28-to 2.40 (1H, m), of 3.48 (2H, t, J=6.3 Hz), 4,10 (1H, d, J=12.9 Hz), 4,35-4,48 (2H, m), 7,16-of 7.23 (2H, m), 7.23 percent-of 7.55 (12H, m), 7,55-of 7.70 (4H, m).

IR (ATR) cm-1: 2929, 2856, 1583, 1473, 1321, 1147, 1103, 1088, 1014, 831, 775, 741, 700, 623, 567, 503.

MS m/z: 735 (M++H), 757 (M++Na).

Example 284: 6-[2-(tert-butyldiphenylsilyl)were]-6-[(4-chlorophenyl)sulfonyl]-1-hexanol

In methanol (30 ml) was dissolved tert-butyl-[[6-[2-[(tert-butyldiphenylsilyl)methyl]phenyl]-6-[(4-chlorophenyl)sulfonyl]hexyl]oxy]dimethylsilane (830 mg, 1.13 mmol) followed by the addition monohydrate p-toluensulfonate acid (25 mg, 0.13 mmol). The resulting mixture was stirred at room temperature for 2 hours. Was added triethylamine (0,080 ml, or 0.57 mmol), and then the residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of dichloromethane:methanol=100:1 was concentrated under reduced pressure to obtain specified in is the head of the compound (580 mg, 0,934 mmol, 83%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: was 1.04 (9H, s), 1,10-1,50 (7H, m), 2,08-of 2.20 (1H, m), 2,30-to 2.42 (1H, m), 3.45 points of 3.56 (2H, m), 4,11 (1H, d, J=a 12.7 Hz), and 4.40 (1H, d, J=a 12.7 Hz), of 4.44 (1H, DD, J=11,0, 4,2 Hz), 7,15-7,22 (2H, m), 7,22 and 7.36 (5H, m), of 7.36-7,51 (7H, m), 7,58 (2H, DD, J=8,1, 1.5 Hz), 7,63 (2H, DD, J=8,1, 1.5 Hz).

MS m/z: 621 (M++H), 638 (M++Na).

Example 285: 6-[(4-chlorophenyl)sulfonyl]-6-(2-hydroxymethylene)-1-hexanol

In tetrahydrofuran (5 ml) was dissolved 6-[2-(tert-butyldiphenylsilyl)were]-6-[(4-chlorophenyl)sulfonyl]-1-hexanol (200 mg, 0,322 mmol) followed by the addition dropwise of a solution in tetrahydrofuran (1.0 M, 0.7 ml, 0.7 mmol) tetrabutylammonium while cooling on ice. The resulting mixture was stirred at room temperature for 1 hour. Then added water (0.2 ml). The residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=30:1 was concentrated under reduced pressure to obtain specified in the title compound (86 mg, 0.23 mmol, 70%) as a colourless oil.

1H-NMR (400 MHz, CDCl3) δ: 1,10-to 1.60 (7H, m), 2,08-of 2.30 (2H, m), is 2.37 (1H, Sirs), 3,45-of 3.60 (2H, m), of 4.44-4,60 (2H, m), 4,78 (1H, DD, J=11,0, 4,2 Hz), 7,28-to 7.50 (4H, m), the 7.43 (2H, d, J=8,8 Hz), 7,60 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 3367, 2935, 2862, 1579, 1475, 1392, 1308, 1277, 112, 1082, 1012, 756, 631, 565, 461.

MS m/z: 735 (M++H), 757 (M++Na).

FAB-MS: 383,1098 (calculated for C19H24ClO4S: 383,1084).

Example 286: [2-[1-[(4-chlorophenyl)sulfonyl]cyclohexyl]phenyl]methanol

6-[2-(tert-butyldiphenylsilyl)were]-6-[(4-chlorophenyl)sulfonyl]-1-hexanol (447 mg, 0,719 mmol)obtained in example 284, was dissolved in toluene (5 ml) followed by addition of cyanomethylene-n-butylphosphine (350 mg, 0,145 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=15:1 was concentrated under reduced pressure to obtain a colorless oil (190 mg).

The obtained colorless oil was dissolved in tetrahydrofuran (5 ml). When cooled on ice was added dropwise a solution in tetrahydrofuran (1.0 M, 0.6 ml, 0.6 mmol) tetrabutylammonium. At room temperature the resulting mixture was stirred for 2 hours. Then to the reaction mixture were added water (1.0 ml). The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on Sealy is agile. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with hexane to obtain specified in the title compound (40 mg, 0.11 mmol, 15%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,15-of 1.45 (3H, m)of 1.45 and 1.80 (2H, m), 1,80-to 1.98 (1H, m), 2,00-2,25 (2H, m), 2,40-2,60 (1H, m), 3,05-of 3.25 (2H, m), 4,70-of 4.90 (1H, m), 5,03-5,20 (1H, m), 6,85 (1H, DM, J=7,6 Hz), to 7.09 (1H, TM, J=7,7 Hz), 7,24-7,40 (5H, m), a 7.62 (1H, DD, J=7,7, 1,6 Hz).

IR (ATR) cm-1: 3575, 2925, 1574, 1471, 1448, 1389, 1296, 1275, 1136, 1082, 1011, 989, 835, 785, 706, 615, 577, 467.

TPL: 148-150°C (decomp.).

MS m/z: 382 (M++NH4).

Elemental analysis. Calculated for C19H21ClO3S: C, 62,54; H, 5,80; Cl, 9,72; S 8,79. Found: C, 62,54; H, 5,73; Cl, 9,70; S 8,93.

Example 287: 4-[[(4-chlorophenyl)sulfonyl](2.5-differenl)methyl]tetrahydropyran

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (200 mg, 0,661 mmol)obtained in example 5, and tetrahydro-4H-Piran-4-ol (0,13 ml of 1.36 mmol) was dissolved in toluene (10 ml) followed by addition of cyanomethylene-n-butylphosphine (330 mg, 1.37 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling, the reaction mixture was added cyanomethylene-n-butylphosphate (200 mg, 0,829 mmol). In argon atmosphere, the mixture was heated the ri boiling under reflux for 14 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentrating the mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=4:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with hexane to obtain specified in the title compound (157 mg, 0,406 mmol, 61%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 1.28 to 1.48 (2H, m), 1,71 (1H, DD d, J=25,3,11,7,4,3 Hz), is 2.37 (1H, sird, J=a 12.7 Hz), 2,70-is 2.88 (1H, m), 3,40 (1H, TD, J=11,7, 2,5 Hz), 3,50 (1H, TD, J=12,0, 2.2 Hz), 3,91 (1H, DM, J=11.2 Hz), was 4.02 (1H, DM, J=11.7 Hz), to 4.46 (1H, d, J=8,8 Hz), 6,68-to 6.80 (1H, m), 6,88-6,98 (1H, m), 7,31 (2H, d, J=8.5 Hz), of 7.36 was 7.45 (1H, m), 7,49 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 2952, 2833, 1576, 1495, 1308, 1275, 1236, 1144, 1082, 879, 829, 788, 752, 733, 710, 615, 602, 559, 519, 465, 447.

TPL: 150-152°C.

MS m/z: 387 (M++H).

Elemental analysis. Calculated for C18H17ClF2O3S: C, 55,89; H, 4,43; Cl, 9,16; F, 9,82; S, 8,29. Found: C, Of 55.64; H, 4,27; Cl, 9,41; F, 9,89; S, 8,28.

Reference example 44: Tetrahydrothiopyran-4-ol

Tetrahydrothiopyran-4-one (5,00 g, 43,0 mmol) was dissolved in methanol (100 ml). When cooled on ice was added sodium borohydride (1.6 g, of 42.3 mmol)and the resulting mixture was stirred at room temperature for 14 hours. To the residue obtained by concentration of the reaction the mixture under reduced pressure, was added water (50 ml). The mixture was made slightly acidic using 1-ad chloride-hydrogen acid and then was extracted with diethyl ether. The extract was washed successively 1 N. chloride-hydrogen acid, saturated aqueous sodium bicarbonate and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain specified in the connection header (4,40 g that 37.2 mmol, 87%) as pale yellowish-brown solid.

1H-NMR (400 MHz, CDCl3) δ: 1,47 (1H, Sirs), 1,64 and 1.80 (2H, m), 2,10-of 2.24 (2H, m), 2,55-2,70 (2H, m), 2,73-is 2.88 (2H, m), 3,60 of 3.75 (1H, m).

MS m/z: 119 (M++H).

Example 288: 4-[[(4-chlorophenyl)sulfonyl](2.5-differenl)methyl]tetrahydrothiopyran

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (500 mg, of 1.65 mmol)obtained in example 5, and tetrahydrothiopyran-4-ol (400 mg, to 3.38 mmol) was dissolved in toluene (20 ml) followed by addition of cyanomethylene-n-butylphosphine (800 mg, and 3.31 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. After cooling, the reaction mixture was added cyanomethylene-n-butylphosphate (400 mg, of 1.66 mmol). In argon atmosphere, the mixture was heated at the boil under reflux in those who tell 14 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=15:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with hexane-diisopropyl ether to obtain specified in the title compound (404 mg, 1.0 mmol, 61%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,47 (1H, DDD, J=23,4, 10,0, 3,3 Hz), 1,68 (1H, DDD, J=25,0, 11,4, and 3.3 Hz), 2,13 (1H, DM, J=11,4 Hz), 2,50-2,78 (5H, m), 2,82 (1H, TD, J=12,8, and 2.6 Hz), 4,47 (1H, d, J=7,3 Hz), 6,72-PC 6.82 (1H, m), 6.90 to-7,00 (1H, m), 7,31 (2H, d, J=8,8 Hz), 7,40-of 7.60 (1H, m), 7,49 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 2939, 2887, 1576, 1493, 1425, 1317, 1281, 1240, 1142, 1084, 1012, 866, 831, 781, 750, 731, 710, 631, 615, 548, 467.

TPL: 150-152°C.

MS m/z: 403 (M++H).

Elemental analysis. Calculated for C18H17ClF2O2S2: C, 53,66; H, 4,25; Cl, 8,80; F, 9,43; S 15,92. Found: C, 53,52; H, 4,21; Cl, 9,00; F, 9,54; S 15,88.

Example 289: 4-[[(4-chlorophenyl)sulfonyl](2.5-differenl)methyl]tetrahydrothiopyran-1,1-dioxide (compound a) and 4-[[(4-chlorophenyl)sulfonyl](2.5-differenl)methyl]tetrahydrothiopyran-1-oxide (compound (isomer a) and compound B (isomer B))

In dichloromethane (15 ml) was dissolved 4-[[(4-chlorophenyl)sulfonyl](2.5-differenl)IU is Il]tetrahydrothiopyran (360 mg, 0,893 mmol). While cooling on ice to the solution was added 3-chloroperbenzoic acid. The resulting mixture was stirred at room temperature for 14 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel, and the fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain white solid. White solid was dissolved in dichloromethane. The resulting solution was washed sequentially 1 N. aqueous sodium hydroxide solution and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain white solid. White solid was washed with diethyl ether obtaining specified in the title compound (187 mg, 0,430 mmol, 48%) as a white powder. The fraction obtained from the eluate using dichloromethane:methanol=50:1 was concentrated under reduced pressure to obtain a mixture specified in the title compound (isomer a) and specified in the title compound (isomer B) as a white solid. The resulting mixture was separated and purified flash chromatography on silica gel (dichloromethane:methanol=80:1). White solids flushing and (each), diethyl ether obtaining specified in the title compound (isomer A) (low polarity) (78 mg, 0,19 mmol, 21%) and indicated in the title compound (isomer B) (high polarity) (69 mg, 0,17 mmol, 19%) as a white powder.

Connection And

1H-NMR (400 MHz, CDCl3) δ: 1,85 is 2.00 (1H, m), 2,18 to 2.35 (2H, m), 2,68-only 2.91 (2H, m), 2,98-3,10 (2H, m), 3,10-of 3.28 (2H, m), of 4.54 (1H, sird, J=7,1 Hz), 6,74-of 6.90 (1H, m), 6,94-7,06 (1H, m), 7,33 (2H, d, J=8.7 Hz), 7,35-of 7.55 (1H, m,), 7,49 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 1576, 1493, 1290, 1146, 1120, 1080, 874, 829, 752, 735, 710, 631, 623, 592, 552, 530, 498, 471, 424.

TPL: 245-248°C.

MS m/z: 435 (M++H).

Elemental analysis. Calculated for C18H17ClF2O4S2: C, 49,71; H, 3,94; Cl, 8,15; F, A Total Of 8.74; S, 14,75. Found: C, 49,38; H, A 3.87; Cl, 8,50; F, 8,86; S, 14,62.

Compound B (isomer A)

1H-NMR (400 MHz, CDCl3) δ: 1,76 (1H, sird, J=13,4 Hz), 2,18 (1H, DDM, J=25,4,12,5 Hz), 2,32-2,70 (4H, m), 2,74-2,90 (1H, m), 2,98 (1H, DM, J=14,0 Hz)to 3.09 (1H, DM, J=14.4 Hz), a 4.53 (1H, d, J=7,3 Hz), 6,72-6,86 (1H, m), 6.90 to-7,02 (1H, m,), to 7.32 (2H, d, J=8.5 Hz), 7,40-of 7.60 (1H, m), 7,49 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 1585, 1495, 1315, 1300, 1242, 1220, 1147, 1086, 1049, 997, 874, 831, 752, 733, 625, 596, 553, 525, 482.

TPL: 255-256°C.

MS m/z: 419 (M++H).

Elemental analysis. Calculated for C18H17ClF2O3S2: C, 51,61; H, 4.09 To; Cl, 8,46; F, 9,07; S, 15,31. Found: C, 51,51; H, 4.04 The; Cl, 8,69; F, 9,15; S, 15,20.

Compound B (isomer B)

1H-NMR (400 MHz, CDCl3) δ: of 1.42 (1H, DDM, J=22,3,11,7 Hz), with 1.92 (1H, DDM, J=11,7, and 11.0 Hz), 2,14-of 2.27 (1H, m)to 2.66 (1H, TD, J=12,2, 2.7 Hz), 2,70-2,90 (3H, m), 3,10-3,24 (1H, m), 3,32-3,44 (1H, m), 4,49 (1H, d, J=8.1 Hz), 6,72-6,85 (1H, m), 6.90 to-7,02 (1H, m), 7,32 (2H, d, J=8.5 Hz), 7,347,50 (1H, m)of 7.48 (2H, d, J=8,5 Hz).

IR (ATR) cm-1: 2912, 1574, 1496, 1298, 1246, 1144, 1080, 1001, 800, 752, 735, 714, 619, 561, 552, 517, 469.

TPL: 184-187°C.

MS m/z: 419 (M++H).

Elemental analysis. Calculated for C18H17ClF2O3S2: C, 51,61; H, 4.09 To; Cl, 8,46; F, 9,07; S, 15,31. Found: C, 51,82; H, 4,23; Cl, 8,42; F, 9,12; S, 15,07.

Example 290: Tert-butyl 4-[[(4-chlorophenyl)sulfonyl](2.5-differenl)methyl]-1-piperidinecarboxylate

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (1,25 g of 4.13 mmol)obtained in example 5, and tert-butyl-4-hydroxy-1-piperidinecarboxylate (1.70 g, 8,44 mmol) was dissolved in toluene (50 ml) followed by addition of cyanomethylene-n-butylphosphine (2,00 mg, 8,21 mmol). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. The reaction mixture was allowed to cool. The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash chromatography on silica gel. The fraction obtained from the eluate using a mixture of hexane:ethyl acetate=1:1 was concentrated under reduced pressure to obtain white solid. White solid was washed with diethyl ether obtaining specified in the title compound (1.68 g, 3.46 mmol, 84%) as a white powder.

1H-NMR (400 MHz, CDCl3) δ: 1,10-1,25 (1H, m), 1,40-1,70 (2H, m)of 1.44 (9H, s), 2,30-of 2.50 (1H, m), 2,60-2,5 (3H, m)4,00-of 4.25 (2H, m), of 4.45 (1H, d, J=7.8 Hz), 6,69-to 6.80 (1H, m), 6,88-6,98 (1H, m), 7,31 (2H, d, J=8.6 Hz), 7,35 is 7.50 (1H, m), 7,49 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 2979, 2935, 1682, 1583, 1493, 1421, 1319, 1281, 1240, 1165, 1122, 1078, 881, 835, 793, 752, 634, 534, 472.

TPL: 193-196°C.

MS m/z: 486 (M++H), 508 (M++Na).

Elemental analysis. Calculated for C23H26ClF2NO4S: C, 56,84; H, 5,39; Cl, 7,30, F, Of 7.82; N, 2,88; S, 6,60. Found: C, 56,41; H, 5,43; Cl, To 7.77; F, To 7.61; N, 2,99; S, 6,58.

Example 291: Hydrochloride 4-[(4-chlorophenyl)sulfonyl](2.5-differenl)methyl]piperidine

In dichloromethane (50 ml) was dissolved tert-butyl 4-[[(4-chlorophenyl)sulfonyl](2.5-differenl)methyl]-1-piperidinecarboxylate (1.56 g, is 3.21 mmol). While cooling on ice to the resulting solution was added dropwise triperoxonane acid. After stirring at room temperature for 2 hours the reaction mixture was concentrated under reduced pressure. Added dichloromethane (10 ml) and 1 n solution in ethanol (10 ml) chloride-hydrogen acid, followed by concentration under reduced pressure to obtain white solid. The obtained solid was washed with diethyl ether obtaining specified in the connection header (1,36 g of 3.12 mmol, 97%) as a white powder.

1H-NMR (400 MHz, CD3OD) δ: 1,38-of 1.52 (1H, m), 1.70 to of 1.92 (2H, m), 2,73 (1H, sird, J=14,2 Hz), 2,86-of 3.00 (1H, m), 3,05 (1H, TD, J=12,9, 3.1 Hz), 3,13 (1H, TD, J=13,1, 3.1 Hz), 3,30 is 3.40 (1H, m), of 3.48 (1H, DM, J=13,0 Hz), 4.72 in (1H, d, J=8.6 Hz), 6,82-6,98 (1H, m),? 7.04 baby mortality for 7.12 (1H, m), 7,40-of 7.55 (1H, m), 7,44 (2H, d, J=8.6 Hz), EUR 7.57 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 2950, 2719, 1583, 1491, 1317, 1146, 1084, 831, 752, 617, 596, 552, 470.

TPL: 184-190°C.

MS m/z: 386 (M++H).

Elemental analysis. Calculated for C18H18ClF2NO2S·HCl·0,75H2O: C, 49,61; H, 4,74; Cl, 16,27; F, 8,72; N, 3,21; S Of 7.36. Found: C, 49,57; H, 4.75 V; Cl, 15,79; F, 9,16; N, 3,34; S, 7,25.

Example 292: 2-[1-[(4-chlorophenyl)sulfonyl]-2-methylpentyl]-1,4-differental (isomer 292-a and isomer 292-In)

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (200 mg, 0,661 mmol)obtained in example 5 and 2-pentanol (0,144 ml of 1.33 mmol) was dissolved in toluene (3 ml) followed by addition of cyanomethylene-n-butylphosphine (0,320 ml). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentrating the reaction mixture under reduced pressure was separated and purified flash chromatography on silica gel (hexane:ethyl acetate=50:1) to obtain the specified header isomer 292 (low polarity) (67 mg, 0.18 mmol, 27%) as a white powder and is specified in the header isomer 292 (high polarity) (45 mg, 0.12 mmol, 19%) as a white solid.

Isomer 292-

1H-NMR (400 MHz, CDCl3) δ: of 0.91 (3H, t, J=7,1 Hz), a 1.08 (3H, d, J=6 Hz), 1,20-of 1.52 (3H, m), 1,52 by 1.68 (1H, m), 2,72-2,90 (1H, m), 4,51 (1H, d, J=5,9 Hz), 6.73 x-6,85 (1H, m), 6,88-6,99 (1H, m), 7,32 (2H, d, J=8.6 Hz), 7,46-of 7.60 (1H, m), 7,52 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 2970, 2866, 1583, 1496, 1475, 1394, 1303, 1277, 1234, 1176, 1140, 1078, 1014, 883, 831, 790, 752, 727, 708, 621, 598, 561, 534, 472.

TPL: 85-87°C.

MS m/z: 373 (M++H), 395 (M++Na).

Elemental analysis. Calculated for C18H19ClF2O2S: C, 57,89; H, 5,14; Cl, 9,51; F, 10,19; S, 8,61. Found: C, 57,96; H, 5,14; Cl, 9,44; F, 10,19; S, 8,75.

Isomer V

1H-NMR (400 MHz, CDCl3) δ: 0,81 (3H, t, J=7.2 Hz), 1.00 and by 1.12 (1H, m), 1,15-of 1.45 (3H, m)of 1.34 (3H, d, J=6.6 Hz), 2,60-of 2.72 (1H, m), 4,43 (1H, d, J=8,8 Hz), 6,67-of 6.78 (1H, m), 6,88-to 6.95 (1H, m), 7,29 (2H, d, J=8.6 Hz), of 7.36 was 7.45 (1H, m), of 7.48 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 2976, 2933, 1585, 1495, 1394, 1323, 1238, 1178, 1149, 1086, 1014, 868, 829, 783, 754, 729, 710, 625, 559, 528, 472.

TPL: 47-50°C.

MS m/z: 373 (M++H), 395 (M++Na).

Elemental analysis. Calculated for C18H19ClF2O2S: C, 57,89; H, 5,14; Cl, 9,51; F, 10,19; S, 8,61. Found: C, 57,97; H, 5,11; Cl, 9,45; F, Of 10.21; S 8,69.

Example 293: 2-[1-[(4-chlorophenyl)sulfonyl]-2-ethylphenyl]-1,4-differental (isomer 293-a and a mixture of isomers)

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (200 mg, 0,661 mmol)obtained in example 5, and 3-hexanol (0,150 ml, 1.35 mmol) was dissolved in toluene (3 ml) followed by addition of cyanomethylene-n-butylphosphine (0,320 ml). In the atmosphere of argon, the mixture was heated at the boil under reflux in the course is the development of 14 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentrating the reaction mixture under reduced pressure was separated and purified flash chromatography on silica gel (hexane:ethyl acetate=200:1) to obtain the specified header isomer 293-A (low polarity) (37 mg, 0,096 mmol, 15%) and indicated in the title of a mixture of isomers (44 mg, 0.11 mmol, 17%) as a white powder.

Isomer 293-

1H-NMR (400 MHz, CDCl3) δ: 0,84 (3H, t, J=7.5 Hz), of 0.95 (3H, t, J=7,3 Hz), 1.00 and is 1.16 (1H, m), 1,30-1,50 (2H, m), 1,55-1,90 (3H, m), 2,50-2,63 (1H, m), 4,59 (1H, d, J=7,6 Hz), 6,69-to 6.80 (1H, m), 6,88-to 6.95 (1H, m), 7,31 (2H, d, J=8,4 Hz), 7,40-7,50 (1H, m)to 7.50 (2H, d, J=8,4 Hz).

IR (ATR) cm-1: 2966, 1583, 1496, 1475, 1306, 1277, 1242, 1176, 1140, 1086, 881, 831, 802, 752, 725, 710, 621, 561, 538, 478, 462, 451.

TPL: 85-89°C.

MS m/z: 387 (M++H), 409 (M++Na).

Elemental analysis. Calculated for C19H21ClF2O2S: C, 58,98; H, 5,47; Cl, 9,16; F, 9,82; S, 8,29. Found: C, 59,18; H, 5,65; Cl, 9,16; F, 9,83; S, Scored 8.38.

The mixture of isomers

1H-NMR (400 MHz, CDCl3) δ: 0,84 (3H, t, J=7.5 Hz), 0,90-1,00 (3H, m), 1.00 and is 1.16 (1H, m), 1,20-1,50 (2H, m), 1,55-1,90 (3H, m), 2,50-2,63 (1H, m), 4,55 with 4.65 (1H, m), 6,69-to 6.80 (1H, m), 6,88-to 6.95 (1H, m), 7,31 (2H, d, J=8,4 Hz), 7,40-7,50 (1H, m)to 7.50 (2H, d, J=8,4 Hz).

IR (ATR) cm-1: 2956, 1583, 1572, 1495, 1479, 1319, 1298, 1279, 1230, 1142, 1090, 1016, 887, 812, 752, 715, 660, 615, 563, 534, 469.

TPL: 95-99°C.

MS m/z: 387 (M++H), 409 (M++Na).

Elemental analysis. Calculated for C19H21ClF2O2S: C, 58,98; H, 5,47; Cl, 9,16; F, 9,82; S, 8,29. Found: C, 58,99 H, Lower Than The 5.37; Cl, 9,19; F, 9,88; S, 8,43.

Example 294: 2-[2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)ethyl]tetrahydrofuran (isomer 294-a and isomer 294-In)

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (200 mg, 0,661 mmol)obtained in example 5, and tetrahydrofurfuryl alcohol (0,13 ml of 1.34 mmol) was dissolved in toluene (3 ml) followed by addition of cyanomethylene-n-butylphosphine (0,320 ml). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentrating the reaction mixture under reduced pressure was separated and purified flash chromatography on silica gel (using a mixed solvent of hexane:ethyl acetate) to obtain white solid. White solid was washed with hexane to obtain specified in the header isomer 294 (low polarity) (102 mg, 0,264 mmol, 40%) and indicated in the title isomer 294 (high polarity) (39 mg, 0.10 mmol, 15%), each in the form of a white powder.

Isomer 294-

1H-NMR (400 MHz, CDCl3) δ: 1,50-of 1.65 (1H, m), 1,75-2,05 (3H, m), and 2.26 (1H, TM, J=12.9 Hz), 2,48 (1H, TM, J=10.4 Hz), 3,50-3,60 (1H, m), 3,60-3,70 (1H, m), 3,76-3,88 (1H, m), a 4.86 (1H, DM, J=and 12.2 Hz), 6,78-of 6.90 (1H, m), 6,92-7,01 (1H, m), 7,20-7,30 (1H, m), 7,38 (2H, d, J=8.6 Hz), 7,54 (2H, d, J=8.6 Hz).

IR (ATR) cm-1: 2960, 2852, 1576, 1493, 1309, 1281, 1194, 1132, 1084, 1065, 1012, 903, 831, 810, 775, 746, 727, 708, 596, 55, 536, 471, 436.

TPL: 99-105°C.

MS m/z: 387 (M++H).

Elemental analysis. Calculated for C18H17ClF2O3S: C, 55,89; H, 4,43; Cl, 9,16; F, 9,82; S, 8,29. Found: C, 56,28; H, 4,80; Cl, 8,94; F, 9,63; S, 8,19.

Isomer 294-

1H-NMR (400 MHz, CDCl3) δ: 1,42 is 1.58 (1H, m), 1,76 was 1.04 (3H, m), 2,22 is 2.33 (1H, m), 2,58-2,70 (1H, m), 3,60-3,70 (1H, m), 3,70-of 3.80 (1H, m), 3,88-to 3.99 (1H, m), with 4.64-to 4.73 (1H, m), 6.75 in-to 6.88 (1H, m), 6,92-7,01 (1H, m), 7,20-7,30 (1H, m), 7,38 (2H, d, J=8.7 Hz), 7,52 (2H, d, J=8.7 Hz).

IR (ATR) cm-1: 2976, 1585, 1496, 1311, 1277, 1221, 1153, 1088, 1061, 922, 879, 829, 779, 752, 712, 629, 607, 561, 532, 472.

TPL: 98-105°C.

MS m/z: 387 (M++H).

Elemental analysis. Calculated for C18H17ClF2O3S: C, 55,89; H, 4,43; Cl, 9,16; F, 9,82; S, 8,29. Found: C, 55,88; H, 4,54; Cl, Which 9.22; F, 9,96; S, 8,42.

Example 295: 2-[2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)ethyl]thiophene

2-[(4-chlorophenyl)sulfanilyl]-1,4-differental (100 mg, 0,330 mmol)obtained in example 5 and 2-thiophenemethyl (0,065 ml, 0.69 mmol) was dissolved in toluene (3 ml) followed by addition of cyanomethylene-n-butylphosphine (1,160 ml). In the atmosphere of argon, the mixture was heated at the boil under reflux for 14 hours. Then the reaction mixture was allowed to cool. The residue obtained by concentrating the reaction mixture under reduced pressure was separated and purified flash chromatography on silica gel (using a solvent mixture of hexane:utilized the t) to obtain white solid. The obtained white solid was washed with hexane to obtain specified in the title compound (92 mg, 0.23 mmol, 70%) as a white solid.

1H-NMR (400 MHz, CDCl3) δ: of 3.60 (1H, DD, J=15,1, to 11.9 Hz), was 4.02 (1H, DM, J=15.1 Hz), 4,80 (1H, DD, J=11,9, 2,5 Hz), 6,69 (1H, DD, J=3,5, 1.1 Hz), 6,70-6,84 (2H, m), 6,92-7,00 (1H, m),? 7.04 baby mortality (1H, DD, J=5,3, 1.1 Hz), 7,32-7,44 (1H, m), 7,39 (2H, d, J=8,8 Hz), EUR 7.57 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 1496, 1319, 1244, 1219, 1149, 1084, 1014, 881, 825, 775, 758, 694, 629, 532, 467.

TPL: 127-130°C.

MS m/z: 399 (M++H).

Elemental analysis. Calculated for C18H13ClF2O2S2: C, 54,20; H, 3,29; Cl, 8,89; F, At 9.53; S 16,08. Found: C, To 54.19; H, 3,31; Cl, 9,20; F, 9,51; S, 16,24.

Example 296: 2-[2-[(4-chlorophenyl)sulfonyl]-2-(2,5-differenl)ethyl]furan

Similar to the method of example 295, except using 2-[(4-chlorophenyl)sulfanilyl]-1,4-diferente (100 mg, 0,330 mmol)obtained in example 5, and furfuryl alcohol (to 0.060 ml, 0.69 mmol) specified in the title compound (26 mg, 0,068 mmol, 21%) was obtained as a white powder.

1H-NMR (400 MHz, CDCl3) δ: of 3.43 (1H, DD, J=15,4, the 11.6 Hz), of 3.78 (1H, DD, J=15,4, and 3.7 Hz), is 4.93 (1H, DD, J=11,6, and 3.7 Hz), of 5.89-5,91 (1H, m), 6,14 (1H, DD, J=3.2, and 1.7 Hz), 6.73 x-PC 6.82 (1H, m), 6.90 to-6,99 (1H, m), 7,19 (1H, DD, J=1,7, 0,7 Hz), 7,25-7,34 (1H, m), 7,40 (2H, d, J=8,8 Hz), 7,58 (2H, d, J=8,8 Hz).

IR (ATR) cm-1: 1585, 1495, 1319