Derivatives of pyrazole or their pharmaceutically acceptable acid salt additive

 

(57) Abstract:

Usage: in the pharmaceutical industry. The essence of the invention: derivatives of pyrazole f-crystals, are given in the text description, which has anti-inflammatory action. 6 C. p. F.-ly, 2 tab.

The invention relates to new derivatives of pyrazole and their pharmaceutically acceptable salts.

In particular, it relates to new derivatives of pyrazole and their pharmaceutically acceptable salts, which have anti-inflammatory, analgesic and antithrombotic activity, to processes for their preparation, to pharmaceutical compositions containing such derivatives and salts, and to methods for their therapeutic use in the treatment and/or prevention of inflammatory conditions, various pains, collagenases, autoimmune diseases, various diseases of immunity and thrombosis in humans or animals, and more particularly to a method of treatment and/or prevention of inflammation and pain in joints and muscles (e.g., rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, podagricheskih arthritis and so on), inflammatory skin conditions (e.g. sunburn, eczema and so on), inflammatory eye condition (e.g., chonju disease pigeon lovers, asthmatic bronchitis agricultural workers and so on), condition of the gastrointestinal tract associated with inflammation (e.g., attorney ulcers, Crohn's disease, atrophic gastritis, variolaris forms of gastritis, ulcerative colitis, debilitating diarrhea of young children, regionalnego ileitis, irritable bowel syndrome, and so on), inflammation of the gums, inflammation, pain and swelling after surgery or injury, fever, pain and other conditions associated with inflammation, particularly those in which the products of lipoxygenase and cyclooxygenase are characteristic of systemic lupus erythematosus, scleroderma, polymyositis, nadeznogo periarteritis, rheumatoid arthritis, Sjogren syndrome, disease, Beset, thyroiditis, diabetes type I, nephrotic syndrome, aplastic anemia, malignant gravis, uveitis, contact dermatitis, psoriasis, Kawasaki disease, sarcoidosis, Hodgkin's disease, etc. in Addition, it was found that the proposed connection is useful for use as therapeutic and/or prophylactic agent for a cardiovascular disease or cardiovascular diseases brain diseases caused by hyperglycemia and hyperlipemia.

One is x salts, who would possess anti-inflammatory, analgesic and antithrombotic action.

Another objective of the invention is to provide a pharmaceutical composition containing as an active ingredient referred to pyrazole derivatives and their pharmaceutically acceptable salts.

And another aim of the invention is to provide a therapeutic method for the treatment and/or prevention of inflammatory conditions, various pains, and other mentioned diseases by applying the mentioned derivatives of pyrazole and their pharmaceutically acceptable salts.

Already known some pyrazole derivatives having anti-inflammatory and analgesic action, such as described, for example, in the description of the patent in Canada, No. 1 130 808 and the publication of the European patent N 272 704 and 293 220.

Target pyrazole derivatives according to the invention are new and can be represented by the General formula I

where R1aryl which may be substituted by substituent(s) selected(s) from the group consisting of lower alkyl, halogen, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylsulfonyl, hydrocity, lower alkylsulfonate, NY hydrogen; methyl, substituted amino, lower alkylamino, halogen or acyloxy; acyl; acylamino; cyano; halogen; lower alkylthio; lower alkylsulfonyl; or a heterocyclic group; and

R3aryl, substituted lower alkyl, lower alkylthio, lower alkylsulfonyl, halogen, amino, lower alkylamino, acylamino, lower alkyl(acyl)amino, lower alkoxy, cyano, hydroxy or acyl; or a heterocyclic group which may be substituted by a lower alkylthio, lower alkylsulfonyl or lower alkylsulfonyl, and when R2carboxy, esterified carboxy or three(halo)methyl, R3aryl, substituted lower alkylthio, lower alkylsulfonyl, amino, lower alkylamino, acylamino, lower alkyl(acyl)amino, hydroxy or acyl; or a heterocyclic group, a substituted lower alkylthio, lower alkylsulfonyl or lower alkylsulfonyl; or R1aryl substituted by substituent(s) selected(s) from the group consisting of lower alkylthio, lower alkylsulfonyl, lower alkylsulfonyl, hydroxy, lower alkylsulfonate, nitro, amino, lower alkylamino, acylamino or lower alkyl(acyl)amino; or a heterocyclic group; and their pharmaceutically acceptable salts.

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Method 2

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Method 3

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Method 4

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Method 5

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Method 6

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Method 7

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Method 8

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Method 9

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Method 10

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Method 11

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Way 12

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Way 13

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Way 14

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Way 15

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Way 16

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Method 17

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Method 18

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Method 19

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Method 20

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Method 21

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Method 22

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Method 23

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Method 24

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Method 25

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where R1, R2and R3each in accordance with this definition;

Ra3aryl or heterocyclic group, each of which is substituted by lower alkylthio; Rb3aryl or heterocyclic group, each of which is substituted by lower alkylsulfonyl or lower alkylsulfonyl; Ra2esterified carboxy; Rb2carbarnoyl, which may be substituted by substituent(s) selected(s) from the group consisting of lower alkyl, aryl, cyclo(lower)alkyl and hydroxy; or N-containing heterocyclic carbonyl; Rc2carbarnoyl, which may be substituted by lower alkyl; RIl, which may be substituted by substituent(s) selected(s) from the group consisting of lower alkyl, halogen, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylsulfonyl, hydroxy, lower alkylsulfonate, nitro, lower alkylamino, acylamino and lower alkyl(acyl)amino; or a heterocyclic group; Rb1aryl, replaced lower alkylthio; Rc1aryl, substituted lower alkylsulfonyl or lower alkylsulfonyl; Rd1aryl, substituted nitro; Re1aryl, substituted amino; Rf1aryl which may be substituted by substituent(s) selected(s) from the group consisting of lower alkyl, halogen, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylsulfonyl, lower alkylsulfonate, nitro, acylamino and lower alkyl(acyl)amino; or a heterocyclic group, Re2acylamino; Rg1aryl, substituted amino or acylamino; Rh1aryl, substituted lower alkylamino or lower alkyl(acyl)amino; Rc3aryl, substituted amino; Rd3aryl, substituted acylamino; Ri1aryl, substituted amino; Rj1aryl, substituted acylamino; Realkyl(acyl)amino; Rk1aryl, substituted acylamino or lower alkyl(acyl)amino; Rl1aryl, substituted amino or lower alkylamino; Rg3aryl, substituted acylamino, or lower alkyl(acyl)amino; Rh3aryl, substituted amino or lower alkylamino; X is halogen and R6lower alkylthio.

Below is the detailed explanation given in the preceding and subsequent parts of the description of the invention, suitable examples of the various definitions.

It is implied that the term "lower" means a group having 1-6 carbon atoms, unless otherwise stated.

Suitable "lower alkyl" and lower alkyl part in terms of "lower alkylthio", "lower alkylsulfonyl", "lower alkyl(acyl)amino", "lower alkylsulfonyl" and "lower alkylsulfonate" may be alkyl straight or branched chain such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl or etc., and preferred is methyl.

Suitable "lower alkoxy" may be methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, etc., and preferred is methoxy.

Suitable "aryl" may be phenyl, naphthyl, and so substituents, mentioned above, and the aryl group for R3replace 1-5 substituents mentioned above, and the preferred number of substituents is a number in the range 1-3.

Suitable "heterocyclic group" may be saturated or unsaturated, monocyclic or polycyclic group containing at least one heteroatom such as nitrogen atom, oxygen atom or sulfur atom.

Preferred examples of such heterocyclic groups can serve unsaturated 3-8-membered (more preferably 5 or 6-membered) heterophilically group containing 1-4 nitrogen atom, for example, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, N-oxide pyridyl, dihydropyridin, tetrahydropyranyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl, triazolyl, tetrazines, tetrazolyl etc., saturated 3 to 8-membered (more preferably 5 or 6-membered) heterophilically group containing 1-4 nitrogen atom, for example, pyrrolidinyl, imidazolidinyl, piperidino, piperazinil etc., unsaturated condensed heterocyclic group containing 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, hinely, ethanolic, indazoles, benzotriazolyl and so measures oxazolyl, isoxazolyl, oxadiazolyl etc. saturated 3-8-Canna heterophilically group containing 1-2 oxygen atoms and 1-3 nitrogen atom, for example, morpholino, Sydney etc., unsaturated condensed heterocyclic group containing 1-2 oxygen atoms and 1-3 nitrogen atom, for example, benzoxazolyl, benzoxadiazole etc. unsaturated 3-8-membered heterophilically group containing 1-2 sulfur atom and 1 to 3 nitrogen, for example, thiazolyl, isothiazolin, thiadiazolyl etc. unsaturated 3-8-membered heterophilically group containing 1-2 sulfur atom, for example thienyl etc., unsaturated condensed heterocyclic group containing 1-2 sulfur atom and 1 to 3 nitrogen atom, for example, benzothiazolyl, benzothiadiazole etc. unsaturated 3-8-membered heterophilically group containing an oxygen atom, such as furyl, etc. unsaturated condensed heterocyclic group containing 1-2 sulfur atom, for example, benzothiazyl etc., unsaturated condensed heterocyclic group containing 1-2 oxygen atom, for example, benzofuranyl etc. or the like.

The above-mentioned "heterocyclic group may be substituted by lower alkyl in the above examples the ptx2">

Suitable "cyclo(lower)alkyl" may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc., and is preferred cyclopropyl. Suitable "halogen" may be fluorine, chlorine, bromine and iodine, of which preferred is fluorine. Suitable "lower alkylamino(lower)alkyl" may be mono - or di(lower alkyl)amino, substituted lower alkyl, such as methylaminomethyl, methylaminomethyl, methylaminopropyl, methylaminomethyl, ethylaminomethyl, acylaminoacyl, ethylaminomethyl, acylaminoacyl, dimethylaminomethyl, dimethylaminoethyl, dimethylaminopropyl, diethylaminoethyl, diethylaminomethyl, diethylaminoethyl, diethylaminopropyl, diethylaminoethyl or similar Suitable "lower alkylamino and lower alkylamino part in the term "lower acylaminoacyl" may be mono - or di(lower)alkylamino, such as methylamino, ethylamino, dimethylamino, diethylamino or similar Suitable "halo(lower)alkyl" can be chloromethyl, vermeil, methyl bromide, deformity, dichloromethyl, trifluoromethyl, trichloromethyl, 2-foradil etc.

Suitable "acyl" and acyl part in terms of "acyloxy", "acylamino", and "lower alkyl(acyl)amino" may be carboxy; esterified carboxy; carbasse)alkyl, aryl and hydroxy; lower alkanoyl, optionally substituted lower alkoxy; a heterocyclic carbonyl; lower alkylsulfonyl, etc.

Esterified carboxy may be substituted or unsubstituted lower alkoxycarbonyl (for example, methoxycarbonyl, etoxycarbonyl, propoxycarbonyl, butoxycarbonyl, hexyloxyphenyl, 2-iodoxybenzoic, 2,2,2-trichloroethanol and so on ), substituted or unsubstituted aryloxyalkyl (for example, phenoxycarbonyl, 4-nitrophenoxide, 2-naphthaleneboronic, and so on ), substituted or unsubstituted ar(lower)alkoxycarbonyl (for example, benzoyloxymethyl, ventilatsioonil, benzylaminocarbonyl, 4-nitrobenzenesulfonyl and so on), etc.

Lowest alkanoyl may be formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl and the like. Heterocyclic part in the term "heterocyclic carbonyl" may be the same as in the examples of the "heterocyclic group". Suitable "heterocyclic carbonyl" may be N-containing heterocyclic carbonyl such as pyrrolidinylcarbonyl, imidazolidinedione, piperidinylcarbonyl, piperazinylcarbonyl, N-methylpiperazine or so on them alkylsulfonyl" can be methylsulphonyl, ethylsulfonyl, propylsulfonyl, etc. is preferably methylsulphonyl.

Suitable "lower alkylsulfonyl" can be methylsulfinyl, ethylsulfinyl, propylsulfonyl, etc. and is preferred methylsulfinyl. on ar(lower)alkoxycarbonyl (for example, benzoyloxymethyl, ventilatsioonil, benzylaminocarbonyl, 4-nitrobenzenesulfonyl and so on), etc.

Lowest alkanoyl may be formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl and the like. Heterocyclic part in the term "heterocyclic carbonyl" may be the same as in the examples of the "heterocyclic group". Suitable "heterocyclic carbonyl" may be N-containing heterocyclic carbonyl such as pyrrolidinylcarbonyl, imidazolidinedione, piperidinylcarbonyl, piperazinylcarbonyl, N-methylpiperazine or etc., of which is preferable pyrrolidinylcarbonyl or N-methylpiperazine. Suitable "lower alkylsulfonyl" can be methylsulphonyl, ethylsulfonyl, propylsulfonyl, etc. is preferably methylsulphonyl.

Suitable "lower alkylsulfonyl.

Suitable pharmaceutically acceptable salts of the target compounds I are conventional non-toxic salts and include salt accession acid such as salt accession inorganic acid (e.g. hydrochloride, hydrobromide, sulfate, phosphate, and so on), salt accession of organic acids (e.g., format, acetate, triptorelin, maleate, tartrate, methanesulfonate, bansilalpet, toluensulfonate and so on ), a salt with an amino acid (e.g. arginine salt, salt asparginase acid, salt of glutamic acid and so on), metal salt such as a salt of an alkali metal (for example, sodium salt, potassium salt, etc. and alkali earth metal salt (e.g. calcium salt, mol magnesium and so on), ammonium salt, salt accession of organic bases (for example, salt of trimethylamine salt of triethylamine and so on), etc.

Below is given a detailed explanation of the methods of obtaining the target compound I.

Method 1.

Compound Ia or its salt and/or compound Ib or its salt can be obtained by interaction of compounds IIa or its salt with the compound III or its salt.

Suitable salts of the compounds IIa and compound III may be the same as specified in ka the AK alcohol (for example, methanol, ethanol and so on), dioxane, tetrahydrofuran, acetic acid or any other organic solvent not having a harmful effect on the reaction.

The reaction temperature is not strictly regulated and the reaction is usually carried out under heating.

Method 2. Compound Ic or its salt and/or connection Id or its salt can be obtained by interaction of compounds IIb or its salt with the compound III or its salt.

Suitable salts of the compounds IIb and III may be the same salt that is listed as an example for the connection I.

The reaction can be carried out essentially in the same way as in method I, and therefore against the regime and conditions (e.g. solvent, reaction temperature and so on) this reaction should refer to method 1.

Method 3:

Connection S or its salt and/or connection If or its salt can be obtained by interaction of the compound IIc or its salt with the compound III or its salt.

Suitable salts of the compounds IIc and III may be the same salt that is listed as an example for the connection I.

This reaction can be carried out essentially in the same way as in method 1 and pot the turn to method 1.

Method 4.

Compound Ih or its salt can be obtained by communicating connection Ig or its salt with an oxidizing agent.

A suitable oxidizing agent may be hydrogen peroxide, reagent Jones, percolate (e.g., peracetic acid, derbentina acid, metachlorobenzoic acid, etc.). chromic acid, potassium permanganate, periodic alkali metal (for example, periodate sodium and so on), etc.

This reaction is usually conducted in a solvent, not rendering it harmful effects, such as acetic acid, dichloromethane, acetone, ethyl acetate, chloroform, water, alcohol (e.g. methanol, ethanol and so on), their mixture, or etc.

The reaction temperature is not strictly regulated, and the reaction is usually carried out under conditions of from cooling to moderate heat.

When this reaction in the case when the starting compound is used as a compound Ig with aryl, substituted lower alkylthio, instead of R1and/or lower alkylthio instead of R2in accordance with the reaction conditions can be obtained compound I, having the aryl, substituted lower alkylsulfonyl or lower alkylsulfonyl instead of R1and/or lower alkylsulfonyl or S="ptx2">

Connection Ij and its salt can be obtained by deesterification of compound (Ii) or its salt.

The reaction is carried out in the traditional method, such as hydrolysis, repair, or etc.

The hydrolysis is preferably carried out in the presence of a base or an acid including Lewis acid. Suitable base may include inorganic and organic bases, such as alkali metal (e.g. sodium, potassium etc), alkaline earth metal (e.g. magnesium, calcium and so on), hydroxide, carbonate or bicarbonate, trialkylamine (for example, trimethylamine, triethylamine and so on), picoline, 1,5-diazabicyclo 4,3,0 non-5-ene, 1,4-diazabicyclo 2,2,2 octane, 1,8-diazabicyclo 5,4,0 undec-7-ene, or similar Suitable acid may include an organic acid (e.g. formic, acetic, propionic, trichloroacetic, triperoxonane and so on), inorganic acid (e.g. hydrochloric, Hydrobromic, idiscovered, sulfur and so on) and a Lewis acid (for example, tribromide boron and so on).

The reaction is usually conducted in a solvent such as water, alcohol (e.g. methanol, ethanol and so on), methylene chloride, tetrahydrofuran, a mixture thereof or any other solvent that is not harmful to wliicli is not strictly regulated, and the reaction is usually carried out under conditions of from cooling to moderate heat.

The reaction can be preferably applied to ether cleavage fragment, such as 4-nitrobenzyl, 2-Iodate, 2,2,2-trichloroethyl or similar recovery Method used for the cleavage reaction may include chemical reduction and catalytic reduction.

Suitable reducing agents used in chemical reduction are a combination of metal (e.g. tin, zinc, iron, and so on) or metallic compound (e.g. chromium chloride, chromium acetate, and so on) and an organic or inorganic acid (e.g. formic, acetic, propionic, triperoxonane, paratoluenesulfonyl, hydrochloric, Hydrobromic, and so on).

Suitable catalysts used in catalytic reduction are conventional catalysts, such as platinum catalyst (e.g. platinum plate, spongy platinum, platinum black, colloidal platinum, platinum oxide, platinum wire, and so on), palladium catalyst (e.g., spongy palladium, palladium black, palladium oxide, palladium on carbon, colloidal palladium, fell the Nickel, Nickel oxide, Raney Nickel, etc.), cobalt catalyst (for example, the recovered cobalt, Raney cobalt, and so on), metal catalyst (e.g. reduced iron, Raney iron, and so on), a copper catalyst (for example, the recovered copper, Raney copper, copper of Ullman and so on), or etc.

Recovery is usually carried out in a solvent not having a harmful effect on the reaction, such as water, alcohol (e.g. methanol, ethanol, propanol, etc.), N,N-dimethylformamide or a mixture thereof. In addition, in the case where the above-mentioned acid used in chemical reduction are in liquid form, they can also be used as solvent. As mentioned solvent may be used as a suitable solvent used in the catalytic reduction, and other traditional solvents, such as simple diethyl ether, dioxane, tetrahydrofuran, etc. or a mixture thereof.

The reaction temperature recovery is not strictly regulated, and the reaction is usually carried out under conditions ranging from cooling to moderate heat.

When this reaction in the case when the starting compound used Ii with aryl, substituted lower allendy hydroxy, instead of R1. This case is also included in the scope of the proposed reactions.

Method 6.

Connection Ik or its salt can be obtained by interaction of the compound I or its reactive derivative at the carboxy group or its salt with an amine or with formamide and an alkoxide of an alkali metal.

Appropriate amine include ammonia, lower alkylamine, arylamine, cyclo(lower)alkylamino, lower alkylhydroxylamines, amino, N-containing heterocyclics connection, etc.

Lowest alkylamino may be mono - or di(lower)alkylamine, such as methylamine, ethylamine, Propylamine, Isopropylamine, butylamine, isobutylamine, pentylamine, hexylamine, dimethylamine, diethylamine, dipropylamine, dibutylamine, Diisopropylamine, dimentianon, digoxigenin or etc., is preferably methylamine or dimethylamine. Arylamino can be aniline, naphtylamine, etc., Cyclo (lower) alkylamino can be cyclopropylamine, cyclobutylamine, cyclopentylamine, cyclohexylamine, etc. and predpochteniem is cyclopropylamine. Lowest alkylhydroxylamines can be methylhydroxylamine, ethylhydroxylamine, propelleraksler, butylhydroxyanisole glycine, alanine, -alanine, isoleucine, tyrosine, etc., is preferably glycine.

N-containing heterocyclic compound may be a saturated 5 or 6-membered N-, or N - and S-, or N - and O-containing heterocyclic compound, such as pyrrolidine, imidazolidine, piperidine, piperazine, N-(lower)alkylpiperazine (for example, N-methylpiperazine, N-ethylpiperazine and so on), morpholine, thiomorpholine or etc., of which is preferable pyrrolidine or N-methylpiperazine.

Appropriate alkoxide of an alkali metal may be sodium methoxide, ethoxide sodium tert-piperonyl potassium, etc.

Suitable reactive derivative at a carboxyl group of compound Ij may include ester, halogenmethyl, acid anhydride, etc., Suitable examples of the reactive derivatives may be gelegenheid (e.g., acid chloride, bromohydrin and so on); a symmetrical acid anhydride; a mixed anhydride with 1,1'-carbonyl diimidazol or acid, such as aliphatic acid (e.g. acetic, trimethyllysine and so on), substituted phosphoric acid (e.g., dialkylphosphinate, diphenylphosphine and so on); an ester, such as lower alkilany ether (for example, IR (for example, benzyl, benzhydryl, parahlorfenilovy and so on), substituted or unsubstituted arrowy ether (for example, phenyl, trilogy, 4-nitrophenyloctyl, 2,4-dinitrophenoxy, pentachlorphenol, nattily and so on) or an ester with N,N-dimethylhydroxylamine, N-hydroxysuccinimide, N-hydroxyphthalimide or 1-hydroxy-6-chloro-1H-benzotriazole, or etc.

The reaction is usually carried out in a conventional solvent such as water, acetone, dioxane, chloroform, methylene chloride, telengard, tetrahydrofuran, formamide, ethyl acetate, N, N-dimethylformamide, pyridine or any other organic solvent not having a harmful effect on the reaction. Of these solvents, hydrophilic solvents may be used in mixture with water.

When using connection Ij in the reaction in the form of the free acid the reaction is preferably carried out in the presence of a conventional condensing agent such as N,N'-dicyclohexylcarbodiimide, N-cyclohexyl-N-morfolinoetilrutin - imide, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide, thionyl chloride, oxalicacid, lower alkoxycarbonylmethyl (for example, ethylchloride, isobutylparaben and so on ), 1-(parachlorobenzotrifluoride)-6 - chloro-1H-BGO, as triethylamine, pyridine, nutrigenomic or etc.

The reaction temperature is not strictly regulated, and the reaction can be conducted under conditions ranging from cooling to intense heat.

Method 7.

Connection Im or its salt can be obtained by communicating connection Il salts thereof with a dehydrating reagent.

Suitable dehydrating reagent may be a compound of phosphorus (for example, phosphorus pentoxide, pentachloride phosphorus oxychloride phosphorus and so on ), tinyload, the acid anhydride (e.g. acetic anhydride, and so on), phosgene, arylsulfonyl (for example, benzosulphochloride, paratoluenesulfonyl and so on), methansulfonate, sulfamic acid, ammoniumsulfate, N, N'-dicyclohexylcarbodiimide, lower alkoxycarbonylmethyl (for example, ethylchloride and so on), etc.

The reaction is usually carried out in a conventional solvent such as acetonitrile, methylene chloride, telengard, benzene, M,N-dimethylformamide, pyridine or any other organic solvent not having a harmful effect on the reaction.

In addition, if the aforementioned dehydrating reagents are in liquid form, they are also the Oia preferably carried out at moderate or intense heat.

In this reaction, when as hydrating reagent use methylsulfonylamino, and as the source of the connection use the connection Il with aryl, substituted hydroxy, instead of R1and/or aryl substituted amino, instead of R3in accordance with the reaction conditions can be obtained connection Im having aryl, substituted methylsulfonate, instead of R1and/or aryl substituted methylsulfonylamino, instead of R3. These cases are also included within the scope of the proposed reactions.

Method 8.

Connection Io or its salt can be obtained by communicating connection In or its salt with a reducing agent. Suitable reducing agent may be DIBORANE, sociallyengaged, etc., the Reaction is usually carried out in a conventional solvent such as simple diethyl ether, tetrahydrofuran or any other organic solvent not having a harmful effect on the reaction.

The reaction temperature is not strictly regulated and the reaction can be conducted under conditions ranging from cooling to intense heat.

Method 9. Ip connection can be obtained as follows.

First exercise vzaimodei IV, and then the obtained product causes to participate in the hydrolysis reaction. Suitable reactive derivative at a carboxyl group of compound I can be gelegenheid (e.g., acid chloride, bromohydrin and so on), etc. In the first stage reaction is preferably carried out in the presence of a base, such as alkali metal (e.g. lithium, sodium, potassium etc), alkaline earth metal (e.g. calcium, magnesium, and so on), alkali metal hydride (for example, natriuretic and so on), hydride alkaline-earth metal (for example, kalsilite and so on), alkali metal alkoxide (for example, the sodium methoxide, ethoxide sodium tert-piperonyl potassium and so on), the alkoxide of the alkali earth metal (e.g. magnesium methoxide, ethoxide magnesium and so on), etc.

The reaction is usually carried out in a solvent, not rendering it harmful effects, such as simple diethyl ether, tetrahydrofuran, dioxane, etc.

The reaction temperature is not strictly regulated and the reaction is carried out under conditions of from cooling to intense heat.

When this reaction can be obtained the compounds of formula

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(Iz) or its salt, where R1, R3and R4each according to OPIE Ip or its salt.

The hydrolysis is preferably carried out in the presence of acid.

Suitable acid may be the same acid that is indicated as an example in the above-mentioned method 5.

The mode and conditions of this hydrolysis reaction can be the same as in the above-mentioned method 5.

Method 10.

The connection Iq or its salt can be obtained by communicating connection IP or its salt with the compound (V).

This reaction is preferably carried out in the presence of salts of thallium (III), such as nitrate thallium (III), etc. etc.

The reaction is usually conducted in a solvent such as dioxane. tetrahydrofuran or any other organic solvent not having a harmful effect on the reaction. The reaction temperature is not strictly regulated and the reaction is preferably carried out at ambient temperature or under heating from mild to strong.

Method 11.

The Ir connection or mol can be obtained by interaction of the compound (VIa) or its salt with nitrate compound. Suitable salt of the compound (VIa) can be the same salt that is listed as an example for compound (I). Approaching lilnited (for example, tert-butylnitrite and so on), etc.

This reaction is usually carried out in the presence of chloride copper (II), phosphonoacetic acid, etc.

The reaction is usually conducted in a solvent such as dioxane, tetrahydrofuran, acetonitrile or any other organic solvent not having a harmful effect on the reaction.

The reaction temperature is not strictly regulated, and the reaction can be conducted under conditions ranging from cooling to intense heat.

The reaction is usually conducted in a solvent such as dioxane, tetrahydrofuran or any other organic solvent not having a harmful effect on the reaction. The reaction temperature is not strictly regulated and the reaction is preferably carried out at ambient temperature or under heating from mild to strong.

Method 11.

The Ir connection or mol can be obtained by interaction of the compound (VIa) or its salt with nitrate compound. Suitable salt of the compound (VIa) can be the same salt that is listed as an example for compound (I). Suitable nitrite compound may be an alkali metal nitrite (e.g. sodium nitrite, the effect in the presence of copper chloride, (II) phosphonoacetic acid, etc.

The reaction is usually conducted in a solvent such as dioxane, tetrahydrofuran, acetonitrile or any other organic solvent not having a harmful effect on the reaction.

The reaction temperature is not strictly regulated, and the reaction can be conducted under conditions ranging from cooling to intense heat.

Method 12.

Join It or its salt can be obtained by communicating connection Is or its salt with an oxidizing agent.

This reaction can be carried out essentially the same as the reaction of method 4, and therefore against the regime and conditions (e.g. solvent, reaction temperature and so on) this reaction should go to method 4.

When this reaction in the case when the initial connection using the connection Is with a lower alkylthio instead of R2and/or the aryl or heterocyclic group, each of which is substituted by lower alkylthio, instead of R3in accordance with the reaction conditions can be obtained compound Is having the lowest alkylsulfonyl or lower alkylsulfonyl instead of R2and/or aryl or heterocyclic group, each of the s in the scope of this reaction.

Way 13.

Compound Iv or its salt can be obtained by reconnection Iu or its salts.

The reaction may include chemical reduction and catalytic reduction, which carry out the traditional way.

Suitable reducing agents used in chemical reduction are a metal (e.g. tin, zinc, iron, and so on), a combination of such metal and/or metallic compound (e.g. chromium chloride, chromium acetate, and so on) with an organic or inorganic acid (e.g. formic, acetic, propionic, triperoxonane, paratoluenesulfonyl, hydrochloric, Hydrobromic, and so on), a combination of such metal and/or metal compound with a base (e.g. ammonia, ammoniacloridegas, nutrigenomics and so on), metallovedenie connection, such as aluminiumallee connection (for example, sociallyengaged, natroalunite, aluminiumhydride, three-tert-butoxyaniline lithium, and so on), bromodiolone connection (for example, natrojarosite, itibariyle, nutritionrelated, Tetramethylammonium, borane, DIBORANE, and so on), the connection of phosphorus (for example, pasport is used in the catalytic reduction, are traditional catalysts, such as platinum catalyst (e.g. platinum plate, spongy platinum, platinum black, colloidal platinum, platinum oxide, platinum wire, and so on), palladium catalyst (e.g., spongy palladium, palladium black, palladium oxide, palladium on carbon, colloidal palladium, palladium on barium sulfate, palladium on barium carbonate, and so on), Nickel catalyst (e.g., the recovered Nickel, Nickel oxide, Raney Nickel, etc.), cobalt catalyst (for example, the recovered cobalt, the Raney cobalt, and so on), metal catalyst (e.g. reduced iron, Raney iron, and so on), a copper catalyst (for example, the recovered copper, Raney copper, copper of Ullman and so on), or etc.

Recovery is usually carried out in a solvent. Suitable for use with solvent may be water, alcohol (e.g. methanol, ethanol, propanol, etc.), acetonitrile or any other traditional organic solvent, such as simple diethyl ether. dioxane, tetrahydrofuran, etc. or a mixture thereof.

The reaction temperature is not strictly regulated, and the reaction is preferably carried out by heating from moderate to Silnov is inane VIb or its salt with allermuir reagent.

Suitable salt of the compound VIb can serve the same salt that is listed as an example for compound (I).

Allerease reagent may include an organic acid represented by the formula, R5-OH, where R5acyl, such as above, or its reactive derivative.

Suitable reactive derivative of an organic acid may be a traditional derivative, such as gelegenheid (e.g., acid chloride, bromohydrin and so on), acid azide, acid anhydride, activated amide, an activated ester or etc.

When used as Alliluyeva reagent free acid acylation reaction can preferably carried out in the presence of a conventional condensing means, such as N,N'-dicyclohexylcarbodiimide or etc.

The reaction is usually carried out in a conventional solvent such as water, acetone, dioxane, chloroform, methylene chloride, acetonitrile, telengard, tetrahydrofuran, ethyl acetate, N,N-dimethylformamide, pyridine or any other organic solvent not having a harmful effect on the reaction, or a mixture. The reaction is also preferably conducted in the presence of a cent is strictly regulated, the reaction can be carried out both during cooling and during heating.

Method 15.

Compound IV or its salt can be obtained by interaction of compounds Ix or its salt with an alkylating reagent. Suitable alkylating reagent may be lower alkylhalogenide (for example, methyliodide, ethylbromide and so on), the combination of carbonyl compounds, such as aliphatic ketone (e.g. acetone, ethylmethylketone and so on), a carbaldehyde (for example, formaldehyde, ethanol and so on), ether orthocarbonic acid (for example, triethylorthoformate and so on) or similar with reducing agents, including chemical and catalytic reducing agents (for example, formic acid, natrojarosite, nutritionrelated, palladium on coal and so on).

When used as an alkylating reagent of the lower alkylhalogenide reaction is preferably carried out in the presence of a base, such as alkali metal (e.g. sodium, potassium etc), alkaline earth metal (e.g. magnesium, calcium and so on), or a hydride, hydroxide, carbonate or bicarbonate. The reaction is usually carried out in a conventional solvent does not render it harmful influences, such as water, dioxane, alcohol (on the mentioned alkylating reagent is in liquid form, it can also be used as solvent.

The reaction temperature is not strictly regulated, and the reaction can be carried out both during cooling and during heating.

When this reaction in the case when the starting compound is used as a compound Ix with aminomethyl instead of R2and/or aryl substituted amino or acylamino, instead of R3in accordance with the reaction conditions can be obtained compound IV having the lowest acylaminoacyl instead of R2and/or aryl substituted lower alkylamino or lower alkyl(acyl)amino, instead of R3. These cases are included in the scope of this reaction.

Way 16.

The compound (1-2) or its salt can be obtained by interaction of the compound (1-1) or its salt with allermuir reagent. This reaction can be conducted essentially the same as the reaction method, 14 and therefore against the regime and conditions (e.g. solvent, reaction temperature and so on) this reaction should refer to method 14.

When this reaction in the case when the starting compound is used as a compound (I-I) with aryl, substituted amino or hydroxy, instead of R1and/or aminomethyl instead of the amino or acyloxy, instead of R1and/or acylaminoacyl instead of R2. These cases are included in the scope of this reaction.

Method 17.

The compound (1-4) or its salt can be obtained by interaction of the compound (1-3) or its salt with allermuir reagent. The reaction can be carried out essentially in the same way as the reaction method, 14 and therefore against the regime and conditions (e.g. solvent, reaction temperature and so on) this reaction should refer to method 14.

When this reaction in the case when the starting compound is used as a compound (1-3) with aryl, substituted amino or hydroxy, instead of R3and/or aminomethyl instead of R2in accordance with the reaction conditions can be obtained compound (1-4) with aryl, substituted acylamino or acyloxy, instead of R3and/or acylaminoacyl instead of R2. These cases are included in the scope of this reaction.

Method 18.

The compound (1-6) or its salt can be obtained by interaction of the compound (1-5) or its salt with an alkylating reagent. This reaction can be carried out essentially in the same way as the reaction method, 15 and therefore against the regime and conditions (for example, the solvent is este parent compound is used as a compound (1-5), having aminomethyl instead of R2and/or aryl substituted amino or acylamino, instead of R1in accordance with the reaction conditions can be obtained compound (1-6), with the lowest acylaminoacyl instead of R2and/or aryl substituted lower alkylamino or lower alkyl(acyl)amino, instead of R1. These cases are included in the scope of this reaction.

Method 19.

The compound (1-8) or its salt can be obtained by diallylamine compounds (1-7) or its salt. This reaction may preferably be carried out in the presence of inorganic acids (e.g. hydrochloric, Hydrobromic and so on) and organic acids (for example, triperoxonane, methansulfonate, toluenesulfonic acid and so on).

The reaction is usually carried out in a conventional solvent such as water, alcohol (e.g. methanol, ethanol and so on), tetrahydrofuran, dioxane or any other organic solvent not having a harmful effect on the reaction, or a mixture. The reaction temperature is not strictly regulated, and the reaction may be conducted under cooling, and heating. When this reaction in the case when the initial substance use substance (1-7) with aryl, substituted on the compound (1-8), having aryl, substituted amino or lower alkylamino, instead of R3. This case is included in the scope of this reaction.

The method 20.

The compound (1-10) or its salt can be obtained by diallylamine compounds (1-9) or its salt. This reaction can be carried out essentially in the same way as the reaction method, 19 and therefore against the regime and conditions (e.g. solvent, reaction temperature and so on) this reaction should refer to method 19. When this reaction in the case when the starting compound is used as a compound (1-9) with aryl, substituted acylamino or lower alkyl(acyl)amino, instead of R1in accordance with the reaction conditions can be obtained compound (1-10) with aryl, substituted amino or lower alkylamino, instead of R1. This case is included in the scope of this reaction.

Method 21.

The compound (1-11) or its salt can be obtained by communicating connection Im or its salt with an azide compound. Suitable azide compound may be an alkali metal azide (e.g. sodium azide, potassium azide, and so on), azide alkaline earth metal (e.g. calcium azide, and so on), hydrogen azide, etc., the Reaction is usually conducted in the Trad is the solvent, not having a harmful effect on the reaction. The reaction temperature is not strictly regulated, and the reaction can be carried out by heating from mild to strong.

Method 22.

The compound (1-12) can be obtained as follows.

First carry out the interaction of the compound (VI) or its salt with nitrite compound, and then the obtained product is forced to interact with a halide of copper (I). Suitable salt of the compounds (VI) can be the same salt that is listed as an example for compound (I). Suitable nitrite compound may be an alkali metal nitrite (e.g. sodium nitrite, potassium nitrite, and so on), alkylated (for example, tert-butylnitrite and so on), etc., Appropriate halide of copper (I) can be chloride, copper (I) bromide copper (I), etc.

In the first stage reaction is preferably carried out in the presence of acid (e.g. sulfuric acid and so on).

The reaction is usually conducted in a solvent such as water, tetrahydrofuran, dioxane, acetonitrile or any other organic solvent that does not have a harmful effect on the solvent or their mixture. The reaction temperature is not strictly regulated and the reaction can be ostwalt in the presence of a halide of an alkali metal (for example, sodium bromide and so on) and inorganic acid (such as Hydrobromic, and so on). The reaction is usually carried out in a solvent such as water, tetrahydrofuran, dioxane or any other organic solvent not having a harmful effect on the reaction. The reaction temperature is not strictly regulated, and the reaction can be carried out by heating from mild to strong.

Way 23.

Connection Im or its salt can be obtained by interaction of the compound (1-12) or its salt with copper cyanide (I).

The reaction is usually carried out in a conventional solvent such as pyridine, quinoline, N,N-dimethylformamide, N is an organic or any other organic solvent not having a harmful effect on the reaction or without solvent. The reaction temperature is not strictly regulated, and the reaction can be carried out by heating from mild to strong.

Method 24.

The compound (1-12) or its salt can be obtained by interaction of the compound (1-13) or its salt with a halide. The reaction is usually carried out in a conventional solvent such as dichloromethane, chloroform, carbon tetrachloride or any friend who was normalized, the reaction can be carried out under conditions of from cooling to moderate heat.

Method 25.

Compound Ia or its salt and/or compound Ib or its salt can be obtained by interaction of the compound (VII) or its salt with the compound (III) or its salt. Suitable salts of the compounds (III) or (VII) can be the same salt that is listed as an example for compound (I). This reaction can be carried out essentially the same as the reaction of method 1, and therefore against the regime and conditions (e.g. solvent, reaction temperature and so on) this reaction should refer to method 1.

Compounds obtained by the above methods can be isolated and purified by the conventional method, such as poroshkovaya, recrystallization, column chromatography, re-deposition, or etc.

The target compound (I) and its pharmaceutically acceptable salts possess strong anti-inflammatory, analgesic and antithrombotic effect and are useful for the treatment and/or prevention of inflammatory conditions, various pains, collagenases, autoimmune diseases, various diseases of immunity and thrombosis in humans or animals, and more particularly Ave is rheumatoid spondylitis, osteoarthritis, gouty arthritis and so on), inflammatory skin conditions (e.g. sunburn, eczema and so on), inflammatory eye condition (e.g., conjunctivitis, and so on ), disorder of the lungs in which there is inflammation (e.g. asthma, bronchitis, diseases of pigeon lovers, asthmatic bronchitis agricultural workers and so on), condition of the gastrointestinal tract associated with inflammation (e.g., attorney ulcers, Crohn's disease, atrophic gastritis, variolaris forms of gastritis, ulcerative colitis, debilitating diarrhea of young children, regionalnego ileitis, irritable bowel syndrome, and so on), inflammation of the gums, inflammation, pain and swelling after surgery or injury, fever, pain and other conditions associated with inflammation, particularly those in which the products of lipoxygenase and cyclooxygenase are characteristic of systemic lupus erythematosus, scleroderma, polymyositis, nadeznogo periarteritis, rheumatoid arthritis, Sjogren syndrome, disease, Beset, thyroiditis, diabetes type I, nephrotic syndrome, aplastic anemia, malignant gravis, uveitis, contact dermatitis, psoriasis, Kawasaki disease, sarcoidosis, illness and/or prophylactic agent for a cardiovascular disease or vascular diseases of the brain, diseases caused by hyperglycemia and hyperlipemia.

In order to illustrate the usefulness of the target compound (I), the following data pharmacological tests.

(A) anti-Inflammatory effect.

The effect on induced arthritis in rats.

Test method.

Used ten female rats Sprague Dawley on the group. In the right hind paw was injected subcutaneously dose of 0.5 mg tubercle Bacillus Mycobacretium tubereulosis (strain Aoyama B) suspended in 0.05 ml of liquid paraffin. Injection of microbial growth stimulator called the local inflammatory lesions (primary lesion), and then, after about 10 days, secondary lesions in both injected and penjelasannya) legs. The difference in the volumes of both legs before and after injection of the stimulant was a measure of arthritis. The drug was administered orally (oral) once a day for 23 days in a row,starting from the first day.

The results are presented in table.1 and 3.

(C) Analgesic effect.

Inflammatory hyperalgesia (increased pain sensitivity) caused by yeast in rats.

Test method.

Used ten rats-Xie. After 3 h after injection of yeast have identified pain threshold by application of pressure to the foot and check the pressure at which the rat withdrew his paw.

After 2 h after injection of the yeast introduced inside medicine. The threshold of pain sensitivity in the treated animals compared to the pain threshold of the control animals.

The test results are given in table.2.

(C) anti-Rheumatic effect.

The effect on the induced collagen arthritis in mice.

Test method.

It was used by eight of male mice DBA/1 on the group. Bovine collagen type II was dissolved in 0.1 M acetic acid and emulsiable in full stimulator's adjuvant (FA). In mice were injected intradermally at the base of the tail 0.2 mg of collagen type II in FA. After 21 days, mice were subjected to the control of infection using the same procedure. Starting 10 days after infection control, was administered orally (oral) tablets once a day for 3 weeks, and each week the mice were examined for visible signs of arthritis. We used the index of arthritis to characterize the legs by degrees 0-3, representing the swelling and redness of the joint (degree 1), see the Oia are given in table.4.

(D) Antithrombotic effect.

Effect on platelet aggregation induced by collagen.

Test method.

From human blood prepared platelet-rich plasma (PRP) containing 3x108platelets per milliliter. To 245 μl of PRP was added 5 μl of drug solution (the test compounds dissolved in dimethyl sulfoxide) and then mixed for 2 min at 37aboutC. To the solution was added 5 μl of collagen (0.5 μg/ml), which serves as the causative agent of aggregation. Aggregation was measured by aggregometer (NKK RACER 1). Activity inhibitors (test compounds) expressed through the values of the IC50, i.e. the dose required to suppress (inhibit) reactions of platelet aggregation by 50%

The test results below.

Test connection example 6 IC50(M) 5.3 x 10-6< / BR>
(E) effect on the reaction of the delayed type hypersensitivity to bovine collagen type II.

Test method.

For this test was used in all seven mice male DBA/1. Mice were senzibilizirani at the base of the tail 125 μg collagen type II emulsified in complete stimulator's adjuvant containing Mycobacterium tuberc the CSOs infection dose of 0.04 ml collagen (2.5 mg/ml) of type II is equipped with phosphate buffer saline (PBS) into the plantar region of right hind leg and 0.04 PBS in the left rear leg. After 24 h after control of infection, measured the volume of both hind legs through the volume measuring device (Muromachi MK-550).

Immediately after sensitization was introduced inside the medicine every day, excluding holidays.

The test results were expressed as percent inhibition compared to the control experiment for each study.

The test results are given in table. 5.

For therapeutic purposes the compound (1) and its pharmaceutically acceptable salt according to the invention can be used in the form of pharmaceutical preparation containing one of these compounds as an active ingredient in a mixture with pharmaceutically acceptable carrier (molding material) such as organic or inorganic solid or liquid excipient suitable for domestic, parenteral or external use. The pharmaceutical preparations can be in the form of capsules, tablets, pills, granules, means for inhalations, suppositories, solution, suspensions, emulsions, or so on, If necessary, within a specified drugs can be introduced excipients, stabilizers, moisturizers or emulsifying agents, buffers and other widely IPhO, but the average single dose of about 0,1, 1, 10, 50, 100, 250, 500 and 1000 mg of the compound (1) may be effective for treatment of these diseases. In General, you can assign 0.1 to 1000 mg per person per day.

For the purpose of illustrating the present invention are given below following preparations and examples.

Preparation 1.

A mixture of 4-(methylthio)acetophenone (1 g) and nutrigenie (60% 288 MS) in N, N-dimethylformamide (7 ml) were mixed at ambient temperature for 30 minutes the Mixture was cooled to 0aboutAnd dropwise added to it diethyloxalate (0,98 ml). The resulting mixture was mixed at ambient temperature for 3 h, poured into ice water and acidified using dilute hydrochloric acid. Precipitation was filtered, washed with water and dried under reduced pressure, resulting in a pale-brown powder ethyl-4-4-(methylthio)phenyl-2,4-dioxaborinane (1.6 g).

Immediately after sensitization was introduced inside the medicine every day, excluding holidays.

The test results were expressed as percent inhibition compared to the control experiment for each study.

The test results are given in table. 5.

For terapevticheskii in the form of a pharmaceutical preparation, containing one of these compounds as an active ingredient in a mixture with pharmaceutically acceptable carrier (molding material), such as organic or inorganic solid or liquid excipient suitable for domestic, parenteral or external use. The pharmaceutical preparations can be in the form of capsules, tablets, pills, granules, means for inhalations, suppositories, solution, suspensions, emulsions, or so on, If necessary, within a specified drugs can be introduced excipients, stabilizers, moisturizers or emulsifying agents, buffers, and other commonly used additives.

The dosage of the compound (1) change depending on the age and condition of the patient, but the average single dose of about 0,1, 1, 10, 50, 100, 250, 500 and 1000 mg of the compound (1) may be effective for treatment of these diseases. In General, you can assign 0.1 to 1000 mg per person per day.

For the purpose of illustrating the present invention are given below following preparations and examples.

Preparation 1.

A mixture of 4-(methylthio)acetophenone (1 g) and nutrigenie (60% 288 mg) in N, N-dimethylformamide (7 ml) were mixed at ambient temperature for 30 minutes was Smeely at ambient temperature for 3 h, poured into ice water and acidified using dilute hydrochloric acid. Precipitation was filtered, washed with water and dried under reduced pressure, resulting in a pale-brown powder ethyl-4-4-(methylthio)phenyl-2,4-dioxaborolane (1.6 g).

Melting point: 91-97aboutC.

IR range (nujol): 3420, 1735, 1620, 1595, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 1.29 (3H, T. J 7 Hz), of 2.54 (3H, s), 4,25 (2H, square J7 Hz), 6,78 (1H, s), 7,35 (2H, d J 8.5 Hz), to $ 7.91 (2H, d J 8.5 Hz).

Mass spectrum (m/z): 266 (M+), 193.

The following compounds (preparations from 2-1 to 2-7) were obtained similar to preparation 1.

Preparation 2.

1) 1-[4-(methylthio)phenyl]-4,4,4-triptorelin-1,3-dione.

Melting point: 79-83aboutC.

IR-spectrum (nujol): 1590 (W), 1490 cm-1.

NMR spectrum (DMSO-d6, ): to 2.57 (3H, s), 7,0 (1H, s), 7,42 (2H, d, J 8.6 Hz), of 8.06 (2H, d, J 8.6 Hz).

Mass spectrum (m/z): 262 (M+).

2) Ethyl-4-[5-(methylthio)-2-thienyl]-2,4-dioxaborolan.

Melting point: 33-45aboutC.

IR-spectrum (nujol): 1730, 1620, 1560, 1510 cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, T. J 7 Hz), of 2.64 (3H, s), to 4.38 (2H, square J 7 Hz), at 6.84 (1H, s), to 6.95 (1H, d, J 4 Hz), 7,27 who butanoate.

Melting point: 171-174aboutC (decomp.).

IR-spectrum (nujol): 3300, 1730, 1700, 1600, 1525 cm-1.

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

4) Ethyl-4-(4-acetylphenyl)-2,4-dioxouranium.

Melting point: 81-82aboutC.

IR-spectrum (nujol): 1725, 1690, 1600 cm-1.

The NMR spectrum (CDCl3, ): USD 1.43 (3H, T. J 7 Hz), to 2.67 (3H, s), 4,42 (2H, square J 7 Hz), 7,11 (1H, s), 8,0-8,2 (4H, m), 15,13 (1H, s).

Mass spectrum (m/z): 262 (M+).

5) Ethyl-4[3,5-di(tert-butyl)-4-hydroxyphenyl]-2,4-dioxouranium.

Melting point: 128-131aboutC.

IR-spectrum (nujol): 3600, 1730, 1630, 1595 cm-1.

NMR spectrum (DMSO-d6, ): of 1.35 (3H, T. J 7 Hz), 1,43 (N, S.), 4,32 (2H, square J 7 Hz), of 6.99 (1H, s), 7,74 (2H, s).

6) 4-Fluoro-1-[4-(methylthio)phenyl]butane-1,3-dione.

Melting point: 64-68aboutC.

IR-spectrum (nujol): 1675, 1595, 1550 cm-1.

The NMR spectrum (CDCl3, ): 2,49 (3H, s), 4,33 (1H, s), 5,11 (1H, s), 6,38 (1H, d J 3 Hz), 7,17 (2H, d J9 Hz), 7,74 (2H, d, J 9 Hz).

7) 4,4-Debtor-1-[4-(methylthio)phenyl]butane-1,3-dione.

IR-spectrum: 1640, 1595 cm-1.

Mass spectrum (m/z: 244 (M+).

Preparation of 3.

The solution Diethylenetriamine (5,3 ml) was tetrahydropyrimidine at the 5aboutC for 15 minutes To the mixture was added a solution of 4-(methylthio)benzaldehyde (5 g) in tetrahydrofuran (10 ml) at 5-10aboutC. the Mixture was mixed at ambient temperature for 5 h, diluted with ethyl acetate and washed with water. The organic layer was dried and concentrated under reduced pressure. The residue is washed with a small amount of diethyl ether and dried, resulting in a pale-brown crystals of 3-[4-(methylthio)phenyl] Acrylonitrile (4.7 g).

IR-spectrum (nujol): 2220, 1615, 1590, 1490 cm-1.

NMR spectrum (DMSO-d6, ): of 2.51 (3H, s), 6,40 (1H, d J 16,7 Hz), of 7.2 to 7.7 (5H, m).

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

Preparation 4.

4-Tortenelmitradiciokban (4 g) was added to a solution of sodium (1.13 g) in ethanol (50 ml) and the mixture was heated under reflux for 1 h To a cooled mixture was added 3,4-(methylthio)phenyl Acrylonitrile (4.3 g) and the resulting mixture was heated under reflux overnight. Added ethyl acetate, water and the organic layer was separated, dried and concentrated. Oily residue (7.6 g) was subjected to purification by column chromatography on silica gel (76 g), elwira mixture of toluene and ethyl acetate (2: 1), and the result is the atur melting point: 100-110aboutC.

Mass spectrum (m/z): 301 (M+).

Preparation 5.

A mixture of 4,5-dihydro-1-(4-forfinal)-5-4-(methylthio)phenyl pyrazole-3-amine (1 g) and oxide (1,16 g) of manganese (IV) in dichloromethane (100 ml) was mixed at ambient temperature for 2 hours, the Insoluble substance was filtered, and the filtrate concentrated to dryness. The residue (1 g) was purified by column chromatography on silica gel (16 g), elwira with a mixture of chloroform and ethyl acetate (5:1), and the obtained pale-brown powder of 1-(4-forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-amine (0.64 g).

IR-spectrum (nujol): 3400, 1600, 1565, 1515 cm-1.

NMR spectrum (DMSO-d6, ): the 2.46 (3H, s), equal to 4.97 (2H, s), of 5.82 (1H, s), 7,0 is 7.3 (8H, m).

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

Preparation of 6.

The solution nutrientrich (3.6 g) in water (18 ml) was added dropwise to ice with salt to a solution of 4-fluoro-2-nitroaniline (7 g) in concentrated hydrochloric acid (45 ml) in the interval of 30 minutes and Then to the mixture was added dropwise a solution of dihydrate (28.6 g) dvuhgolosnogo tin in concentrated hydrochloric acid (24 ml) at a temperature below 5aboutWith in the time interval. Precipitation was collected by filtration and washed diet the temperature melting point: 260aboutC.

Mass spectrum (m/z): 171 (M+).

Preparation 7.

The solution perodically (4.6 g) in tetrahydrofuran (60 ml) was added dropwise to a mixture of 4-(methylthio)acetophenone (10 g) and 60% nutrigenie (4.8 g) in tetrahydrofuran (100 ml) at ambient temperature in a time interval. The mixture was mixed at 40aboutC for 2 h and added to it a solution of iodomethane (17.1 g) in tetrahydrofuran (60 ml). The resulting mixture was mixed at 40aboutC for 1 h and heated under reflux for 1 h was added To the mixture of water and chloroform. The organic layer was washed with water, dried and subjected to evaporation in a vacuum. The residue was washed with methanol and received in the crystals of 1-[4-(methylthio)phenyl]-3,3-bis(methylthio)-2-propen-1-it (10,5 g).

Melting point: 119-122aboutC.

IR-spectrum (nujol): 1620, 1590, 1550, 1495 cm-1.

The NMR spectrum (CDCl3): 2,52 (3H, s), of 2.53 (3H, s), of 2.56 (3H, s), 6,74 (1H, s), 7,26 (2H, d, J 7 Hz), 7,83 (2H, d, J 7 Hz).

Mass spectrum (m/z): 270 (M+).

Preparation of 8.

A mixture of ethyl-4-(4-tolyl)-2,4-dioxaborinane (4.7 g) and 4-tortenelmitradiciokban (3.6 g) in dioxane (35 ml) and ethanol (35 ml) was boiled under reflux for TEM column chromatography on silica gel (130 g) with elution by chloroform, in the result, received oil ethyl-1-(4-forfinal)-5-(4-tolyl)pyrazole-3-carboxy - LVL (2.7 g).

IR spectrum (film): 1720, 1610, 1510 cm-1.

NMR-spectrum (DCl3, ): of 1.42 (3H, T. J7 Hz), 2,31 (3H, s), and 4.40 (2H, square J 7 Hz), 6,8-7,4 (N, m).

The following compounds (preparations from 9-1 to 9-3) were obtained similar to preparation 8.

Preparation of 9.

1) Ethyl-1-(4-forfinal)-5-(4-methoxyphenyl)pyrazole-3-carboxylate.

Melting point: 91-93aboutC.

IR-spectrum (nujol): 1715, 1610, 1510 cm-1.

The NMR spectrum (CDCl3, ): to 1.38 (3H, T. J7 Hz), 3,81 (3H, s), of 4.45 (2H, square J 7 Hz), 6,8-7,4 (N, m).

Mass spectrum (m/z): 340 (M+).

2) Ethyl-1,5-bis(4-methoxyphenyl)pyrazole-3-carboxylate.

IR spectrum (film): 1730, 1610, 1510 cm-1.

3) Ethyl-5-(4-tianfeng)-1-(4-forfinal)pyrazole-3-carboxylate.

Melting point: 147-148aboutC.

IR-spectrum (nujol): 2230, 1735, 1610, 1510 cm-1.

The NMR spectrum (CDCl3, ): USD 1.43 (3H, T. J7 Hz), 4,46 (2H, square J 7 Hz), 7,0-7,8 (N, m),

Mass spectrum (m/z): 335 (M+).

Preparation 10.

A mixture of ethyl-1-(4-forfinal)-5-(4-tolyl)pyrazole-3-carboxylate (2.7 g) and caliginosity (1.1 g) in methanol (40 is washed with ethyl acetate. The aqueous layer was acidified with diluted hydrochloric acid and was extracted with ethyl acetate. The extract was washed with water, dried and concentrated, resulting in crystals of 1-(4-forfinal)-5-(4-tolyl)pyrazole-3-carbon - howl acid (2.1 g).

Melting point: 170-173aboutC.

IR-spectrum (nujol): 2750, 2600, 1690, 1600, 1510 cm-1.

Mass spectrum (m/z): 296 (M+).

P R I m e R 1. A mixture of ethyl-4-[4-(methylthio)phenyl]-2,4-dioxaborinane (1 g) and 4-tortenelmitradiciokban (0,67 g) in ethanol (10 ml) and dioxane (10 ml) was boiled under reflux for 5 hours, the Solvent is boiled away and the residue was dissolved in chloroform and washed with water. The organic layer was dried over maniculatus and concentrated the Residue (1.6 g) was subjected to purification by column chromatography on silica gel (30 g) with elution with a mixture of toluene and ethyl acetate (20: 1) and received in the ethyl-1-(4-forfinal)-3-[4-(methylthio)phenyl]pyrazole-5-carboxylate (0.11 g).

Melting point: 100-104aboutC.

IR-spectrum (nujol): 1730, 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): of 1.29 (3H, T. J7 Hz), of 2.51 (3H, s), 4,27 (2H, square J 7 Hz), 7,1-7,9 (N, m).

Mass spectrum (m/z): 356 (M+).

In addition, the same what about the brown crystals ethyl-1-(4-forfinal)-5-[4-(methylthio)phenyl] pyrazole-3-carboxylate (1.1 g).

Melting point: 100-102aboutC.

IR-spectrum (nujol): 1710, 1600, cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, T. J7 Hz), 2,48 (3H, s) of 4.45 (2H, square J 7 Hz), 7,0-7,4 (N, m).

Mass spectrum (m/z): 356 (M+).

P R I m m e R 2. A solution of ethyl-1-(4-forfinal)-5-[4-(methyltin)phenyl]pyrazole-3-CT - barcelata and solution (0,79 ml ) of hydrogen peroxide in acetic acid (9.5 ml) was mixed with 70aboutC for 3 hours the Mixture was cooled in an ice water bath and the precipitation was filtered and washed with ethanol, luciw resulting colorless crystals of ethyl-1-(4-forfinal)-5-[4-(methylsulphonyl) phenyl]pyrazole-3-carboxylate (0,94 g).

Melting point: 210-212aboutC.

IR-spectrum (nujol): 1715, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): 1,32 (3H, T. J 7 Hz) at 3.25 (3H, s), 4,35 (2H, square J 7 Hz), 7.3 to 7.4 (7H,m), 7,92 (2H, d J 8.5 Hz).

Mass spectrum (m/z): 338 (M+).

P R I m e R 3. A mixture of ethyl-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxylate (4.4 g) and 4 nutrigenomics (5.7 ml) in tetrahydrofuran (20 ml), ethanol (10 ml) and dioxane (20 ml) were mixed at ambient temperature throughout the night. To the mixture was added water (50 ml) and was acidified its hydrochloric acid. The precipitate was filtered and proove acid (4.1 g).

Melting point: 232-234aboutC.

IR-spectrum (nujol): 1695, 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), 7,2-7,6 (7H, m), 7,92 (2H, d J 8,3 Hz), 13,1 (1H, s).

Mass spectrum (m/z): 360 (M+).

P R I m e R 4. A mixture of 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-car - oil acid (1.1 g) and phosphorochloridate (0,67 g) in toluene (16 ml) and tetrahydrofuran (9 ml) was mixed at ambient temperature for 2 hours, the Insoluble substance was filtered, and the filtrate was concentrated, resulting in oil 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]-pyrazole-3-carbonylchloride (1,37 g).

MK-spectrum (film): 1760, 1605, 1510 cm-1.

To the above acid chloride acid was added a mixture of 25% aqueous solution (2 ml) of methylamine, ice water (5 ml) and tetrahydrofuran (10 ml). The mixture was stirred overnight. The precipitate was filtered, and the filtrate was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue (0.21 g) and the precipitate (0,83 g) were combined and recrystallized from a mixture of ethyl acetate and ethanol, resulting in colorless crystals of 1-(4-forfinal)-N-methyl-5-[4-(methylsulphonyl)phenyl] pyrazole-3-carboxamide 1.0 g).

Temperatur (DMSO-d6, ): 2078 (3H, d, J 6 Hz) at 3.25 (3H, s), 7,16 (1H, s), 7.3 to 7.6 for (6N, m), to $ 7.91 (2H, d J 8,3 Hz), 8,35 (1H, square J 4.6 Hz).

Mass spectrum (m/z): 373 (M+).

The following compounds (examples 5-1 to 5-12) were obtained analogichnym example 4.

P R I m e R 5.

1) 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxamide.

Melting point: 215-217aboutC.

IR-spectrum (nujol): 3470, 3200, 1680, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s,), 7,16 (1H, s), 7,2-7,6 (7H, m), to 7.77 (1H, s), to $ 7.91 (2H, d J 8.5 Hz).

Mass spectrum (m/z): 359 (M+), 341.

2) 1-4-Forfinal)-N, N-dimethyl-3-[4-(methylsulphonyl)phenyl] -pyrazole-5 - carboxamide.

Melting point: 192-193aboutC.

IR-spectrum (nujol): 1640, 1605, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,95 (3H, s), 2096 (3H, s), with 3.27 (3H, s), is 7.3-8.3 (N, m).

Mass spectrum (m/z): 387 (M+). oil acid (1.1 g) and phosphorochloridate (0,67 g) in toluene (16 ml) and tetrahydrofuran (9 ml) was mixed at ambient temperature for 2 hours, the Insoluble substance was filtered, and the filtrate was concentrated, resulting in oil 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]-pyrazole-3-carbonylchloride (1,37 g).

IR Drogo solution (2 ml) of methylamine, ice water (5 ml) and tetrahydrofuran (10 ml). The mixture was stirred overnight. The precipitate was filtered, and the filtrate was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue (0.21 g) and the precipitate (0,83 g) were combined and recrystallized from a mixture of ethyl acetate and ethanol, resulting in colorless crystals of 1-(4-forfinal)-N-methyl-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbox - Samid 1.0 g).

Melting point: 271-273aboutC.

IR-spectrum (nujol): 3400, 1660, 1605, 1550, 1535, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,78 (3H, d, J 6 Hz) at 3.25 (3H, s), 7,16 (1H, s), 7.3 to 7.6 for (6N, m), to $ 7.91 (2H, d J 8,3 Hz), 8,35 (1H, square J4,6 Hz).

Mass spectrum (m/z): 373 (M+).

The following compounds (examples 5-1 to 5-12) were obtained analogichnym example 4.

P R I m e R 5.

1) 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxamide.

Melting point: 215-217aboutC.

IR-spectrum (nujol): 3470, 3200, 1680, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s,), 7,16 (1H, s), 7,2-7,6 (7H, m), to 7.77 (1H, s), to $ 7.91 (2H, d J 8.5 Hz).

Mass spectrum (m/z): 359 (M+), 341.

2) 1-(4-Forfinal)-N, N-dimethyl-3-[4-(methylsulphonyl)phenyl] -pyrazole-5 - LASS="ptx2">

NMR spectrum (DMSO-d6, ): 2,95 (3H, s), 2096 (3H, s), with 3.27 (3H, s), is 7.3-8.3 (N, m).

Mass spectrum (m/z): 387 (M+).

3) 1-(4-Forfinal)-3-[4-(methylsulphonyl)phenyl]pyrazole-5-carboxamide.

Melting point: 270-271aboutC.

IR-spectrum (nujol): 3380, 3200, 1670, 1625, 1605, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 3,26 (3H, s), 7,2-8,2 (11N, m).

Mass spectrum (m/z): 359 (M+).

4) 5-[3,5-Di(tert-butyl)-4-hydroxyphenyl] -1-(4-forfinal)pyrazole-3-carboxy - MFA.

Melting point: 247-249aboutC.

IR-spectrum (nujol): 3650, 3500, 3350, 1660, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 1,26 (N, S.), 6,98 (3H, s), of 7.2 to 7.7 (6N, m).

Mass spectrum (m/z): 409 (M+).

5) N-phenyl-1-(4-forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-carboxamide.

Melting point: 200-205aboutC (decomp.).

IR-spectrum (nujol): 3400, 1680, 1595, 1530, 1510 cm-1.

NMR spectrum (DMSO-d6, ): the 2.46 (3H, s), of 7.0 and 7.6 (N, m), 7,83 (2H, J 8 Hz), 10,19 (1H, s).

Mass spectrum (m/z): 409 (M+).

6) 1-(4-Forfinal)-5-[4-(methylthio)phenyl] -3-(1-pyrrolidinylcarbonyl)pyrazole.

Melting point: 139-140aboutC.

IR-spectrum (nujol): 1615, 1515 cm-1.

IR-spectrum (CDC).

7) N-Cyclopropyl-1-(4-forfinal)-5-[4-(methylthio)phenyl] pyrazole-3-carboxamide.

Melting point: 147-148aboutC.

IR-spectrum (nujol): 3360, 1675, 1600, 1510 cm-1.

The NMR spectrum (CDCl3, ): 0.6 to 0.9 (4H, m), 2,48 (3H, s), 2.8 to 3.0 (1H, m ), 7,0-7,4 (N, m).

Mass spectrum (m/z): 367 (M+).

8) 1-(4-Forfinal)-3-(4-methyl-1-piperazinylcarbonyl)-5-[4-(methylsulphonyl) phenyl]pyrazole.

Melting point: 170-173aboutC.

IR-spectrum (nujol): 1620, 1520, 1500 cm-1.

The NMR spectrum (CDCl3, ): of 2.34 (3H, s), 2,4-2,6 (4H, m), is 3.08 (3H, s), 3,8-4,2 (4H, m), the 6.9 to 7.5 (7H, m). to $ 7.91 (2H, d, J 8 Hz).

Mass spectrum (m/z): 442 (M+).

9) N-Hydroxy-N-methyl-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl] pyrazole-3-carboxamide.

Melting point: 185-188aboutWith (Razlog.).

IR-spectrum (nujol): 3420, 1720, 1645, 1560, 1510 cm-1.

The NMR spectrum (CDCl3, ): to 3.09 (3H, s), 3,86 (3H, s), 7,0-7,5 (7H, m), to $ 7.91 (2H, d, J 8 Hz).

Mass spectrum (m/z): 389 (M+).

10) N-{1-(4-Forfinal)-5-[4-(methylsulphonyl)phenyl]-3-pyrazolyl-carbonyl} gli - Qing.

Melting point: 258-260aboutWith (Razlog.).

IR-spectrum (nujol): 3420, 1720, 1645, 1560, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 3,25 .

11) N-Methyl-1-[4-(N-formylmethionine)phenyl]-5-[4-(methylsulphonyl) phenyl] pyrazole-3-carboxamide.

IR-spectrum (nujol): 3350, 1660, 1605, 1550, 1515 cm-1.

Mass spectrum (m/z): 412 (M+).

12) N, N-Dimethyl-1-[4-(N-formylmethionine)phenyl] -5-[4-(methylsulphonyl) phenyl]pyrazole-3-carboxamide.

Mass spectrum (m/z): 426 (M+).

P R I m e R 6. A mixture of 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-CT - oxamide (2.7 g) and methanesulfonamide (3.4 ml) in pyridine (25 ml) was mixed with 50aboutC for 6 hours, the Solvent is boiled away and to the residue was added ethyl acetate and water. The precipitate was filtered and washed with water and ethyl acetate. The filtrate was separated and the organic layer was washed with diluted hydrochloric acid, dried and concentrated to dryness. The remainder of the first and the precipitate were combined and recrystallize from a mixture of ethanol and ethyl acetate, resulting in colorless crystals of 1-(4-forfinal)-5-4-(methylsulphonyl)phenyl pyrazole-3-carbonitrile (2.4 g).

Melting point: 194-196aboutC.

IR-spectrum (nujol): 2240, 1600, cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), and 7.3 and 7.6 (7H, m), 7,95 (2H, d J ) of 6.7 Hz).

Mass spectrum (m/z): 341 (M+).

The following compounds is arvanil)-5-[4-(methylthio)phenyl]pyrazole-3-carboxylic acid.

IR-spectrum (nujol): 3500, 1695, 1600, 1515 cm-1.

2) 1-(4-forfinal)-3-[4-(methylsulphonyl)phenyl]pyrazole-5-carboxylic acid.

Melting point: 259-260aboutWith (Razlog.).

IR-spectrum (nujol): 1705, 1605, 1515 cm-1.

NMR spectrum (DMSO-d6, ): 3,26 (3H, s), is 7.3-8.3 N, m).

Mass spectrum (m/z): 360 (M+).

3) 5-[3,5-Di(tert-butyl)-4-hydroxyphenyl] -1-(4-forfinal)pyrazole-3-carboxylic acid.

Melting point: 239-242aboutC.

IR-spectrum (nujol): 3550, 1690, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 1,25 (N, S.) of 6.96 (2H, s), 7,03 (1H, s), 7,25 was 7.45 (4H, m).

4) 1-[4-(N-formylmethionine)phenyl] -5-4-(methylsulphonyl)phenyl pyrazole-3-carboxylic acid.

IR-spectrum (nujol): 1720, 1665, 1605, 1520 cm-1.

Mass spectrum (m/z): 399 (M+).

P R I m e R 8. A mixture of 1-(4-forfinal)-5-[4-(methylthio)phenyl] pyrazole-3-carboxylic acid (3 g) and 1,1-carbonyldiimidazole (1.6 g) in tetrahydrofuran (39 ml) was boiled under reflux for 1 h Added dimethylaminohydrolase (1.04 g) and callicarpenal (1,33 g) and the resulting mixture was stirred and boiled under reflux for 3 hours the Mixture was diluted with ethyl acetate, washed successively with water, woodvale, with a pale brown oil of 1-(4-forfinal)-N, N-dimethyl-5-[4-(methylthio)phenyl]PIR - evil-3-carboxamide (2.6 g).

IR spectrum (film): 1620, 1510 cm-1.

P R I m e R 9. A mixture of 1-(4-forfinal)-N,N-dimethyl-5-[4-(methylthio)phenyl] pyrazole-3 - carboxamide (1 g) and meta-chloroperbenzoic acid (1.8 g) in dichloromethane (17 ml) was stirred over night at ambient temperature. The insoluble substance was filtered and the filtrate is washed with an aqueous solution of attributableto, dried and concentrated to dryness. The residual oil (1.4 g) was subjected to purification by column chromatography on silica gel (30 g) with elution with a mixture of chloroform and methanol (20:1). The oil obtained (1.0 g) crystallized from a simple broadcast and received as a result of colorless crystals of N,N-dimethyl-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3 - carboxamide (0,69 g).

Melting point: 171-173aboutC.

IR-spectrum (nujol): 1620, 1510 cm-1.

NMR spectrum (DMSO-d6, ): to 3.02 (3H, s), of 3.25 (3H, s), of 3.32 (3H, s), was 7.08 (1H, s), 7,2-8,0 (8H, m).

Mass spectrum (m/z): 387 (M+).

P R I m e R 10. A mixture of 1-(4-forfinal)-N,N-dimethyl-5-[4-(methylthio)phenyl] PIR - evil-3-carboxamide (1.6 g) and sociallyengaged was added To the mixture dropwise 4n. nutrigenomic (10 ml), and added ethyl acetate (20 ml). The insoluble substance was filtered and the filtrate separated. The organic layer was washed with water, dried and concentrated. The residue (1.2 g) was subjected to purification by column chromatography on silica gel (30 g) with elution with a mixture of ethyl acetate and methanol (5:1) and the obtained pale-brown oil 3-(N,N-dimethylaminomethyl)-1-(4-forfinal)-5-[4-(methylthio)phenyl]Pirat - La 0,69 g).

IR spectrum (film): 2820, 2770, 1600, 1560, 1510 cm-1.

Mass spectrum (m/z): 341 (M+), 298.

The following compounds (examples 11-1 to 11-3) were obtained similar to example 9.

P R I m e R 11.

1) 3-(N,N-Dimethylaminomethyl)-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl] pyrazolidinone.

Melting point: 157-160aboutWith (Razlog.).

IR-spectrum (nujol): 3350, 2580, 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), 3,54 (6N, S.), at 4.99 (2H, s), 7,07 (1H, s), 7,2-8,0 (8H, m), and 12.9 (1H, s).

Mass spectrum (m/z): 373 (M+), 330.

2) Ethyl-1-(4-forfinal)-3-[4-(methylsulphonyl)phenyl]pyrazole-5-carboxylate.

Melting point: 203-205aboutC.

IR-spectrum (nujol): 1725, 1605, 1515 cm-1.

SUP>).

3) 1-(4-Forfinal)-5-[4-(methylsulphonyl)phenyl]-3-(trifluoromethyl)pyrazole.

Melting point: 210-212aboutC.

IR-spectrum (nujol): 3150, 1605, 1520, 1505 cm-1.

NMR spectrum (DMSO-d6, ): 3,26 (3H, s), and 7.3 and 7.6 (7H, m), of 7.96 (2H, d J 8,3 Hz.

Mass spectrum (m/z): 384 (M+).

P R I m e R 12. A mixture of 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-car - oil acid (6.4 g) and thionyl chloride (30 ml) in tetrahydrofuran (60 ml) was boiled under reflux for 1 hour and concentrated under reduced pressure, resulting in 1-(4-forfinal)-5-4-(methylsulphonyl)phenyl pyrazole-3-carbonylchloride.

A solution of diethylmalonate (of 3.46 g ) and ethanol (1,96 ml) in ethyl ether (19.6 ml) was added dropwise to a stirred mixture of magnesium (518 mg), ethanol (0,785 ml) and carbon tetrachloride (1,18 ml) in ether (19.6 ml) in nitrogen atmosphere. The resulting mixture was mixed at ambient temperature for 100 min and boiled under reflux for 25 minutes a Solution of the above acid chloride in tetrahydrofuran (24 ml) was added in portions to the mixture. The mixture was mixed at room temperature for 85 minutes and boiled under reflux for 70 minutes, the Reaction mixture is maniculatus. The solvent is boiled away under reduced pressure and obtained as a result of 3-bis(etoxycarbonyl)acetyl-1-(4-perfe - nil)-5-[4-(methylsulphonyl) phenyl]pyrazole.

3-bis(etoxycarbonyl)acetyl-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl] pyrazole was added to a mixture of sulfuric acid (3.9 ml), acetic acid (23,6 ml) and water (19.6 ml). The mixture was boiled under reflux for 5 h and concentrated. The residue was dissolved in ethyl acetate and the solution washed with water, dried and concentrated. The residue was subjected to purification by column chromatography on silica gel (150 g) with elution with a mixture of chloroform and ethyl acetate (3:1) and the obtained pale-brown crystals of 3-acetyl-1-(4-forfinal)-5-[4-(metralha - nil)phenyl]pyrazole (4,2 g).

Melting point: 207-209aboutC.

IR-spectrum (nujol): 1690, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): to 2.57 (3H, s) of 3.25 (3H, s), 7,2-8,0 (N, m).

Mass spectrum (m/z): 358 (M+).

P R I m e p 13. A mixture of 3-acetyl-1-(4-forfinal)-5-[4-methylsulphonyl)phenyl]Pirat - La (1.1 g) Narathiwat (1.6 g) of thallium (III) and perchloric acid (70% and 3.3 ml) in methanol (16 ml) and dioxane (8 ml) were mixed at ambient temperature throughout the night. Insoluble substance AHP crystal growth is cleaned by column chromatography on silica gel (100 g) with elution with a mixture of toluene and ethyl acetate (2:1) and was obtained as pale-brown crystals of 1-(4-forfinal)-3-(methoxyacetyl)-5-[4-(IU - tilsley)phenyl]pyrazole (0,13 g).

Melting point: 151-154aboutC.

IR-spectrum (nujol): 1705, 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), 3,39 (3H, s), to 4.81 (2H, s,), 7,2-8,0 (N, m).

The following compounds (examples 14-1 to 14-26) were obtained similarly to example 1.

P R I m e R 14.

1) 1-(4-Forfinal)-5-[4(methylthio)phenyl]-3-(trifluoromethyl)pyrazole.

IR spectrum (film): 1605, 1515, 1500 cm-1.

The NMR spectrum (CDCl3, ): 2,48 (3H, s), 6,72 (1H, s), 7,0-7,4 (8H, m).

Mass spectrum (m/z): 352 (M+).

2) Ethyl-5-[4-)methylthio)phenyl] -1-(4-pyridyl)pyrazole-3-carboxylate hydrochloride.

Melting point: 181-186aboutC.

IR-spectrum (nujol): 1720, 1630, 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): of 1.34 (3H, T. J7 Hz), of 2.51 (3H, s), 4,37 (2H, square J 7 Hz), 7,21 (1H, s), 7,33 (4H, s), 7,72 (2H, L. J5 Hz), cent to 8.85 (2H, d, J 5 Hz).

Mass spectrum (m/z): 339 (M+).

3) Ethyl-1-(2-forfinal)-5-[4-(methylthio)phenyl]-3-carboxylate.

IR spectrum (film): 1725, 1600, 1510 cm-1.

The NMR spectrum (CDCl3, ): of 1.39 (3H, so J=7 Hz), 2,42 (3H, s), 4,42 (2H, square J 7 Hz), 6.9 and 7.6 (N, m).

4) Ethyl-1-(2,4-differenl)-5-[4-(methyltin/phenyl]pyrazole-3-carboxylate.

IR spectrum (film): 1720, 1605, 1515 cm-1

IR spectrum (film): 1720, 1605, 1490 cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, T. J7 Hz), 2,44 (3H, s), 4,42 (2H, square J 7 Hz) and 6.9-7.5 (M, m).

6) Ethyl-5-[4-(methylthio)phenyl]-1-phenylpyrazol-3-carboxylate.

IR spectrum (film): 1705, 1600, 1560, 1500 cm-1.

The NMR spectrum (CDCl3, ): of 1.40 (3H, T. J7 Hz), a 2.45 (3H, s), 4,42 (2H, square J 7 Hz), of the 6.9 to 7.5 (10H, m).

7) Ethyl-1-(4-methoxyphenyl)-5-[4-(methylthio)phenyl]pyrazole-3-carboxylate.

IR spectrum (film): 1720, 1605, 1510 cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, T. J7 Hz), 2.47 (3H, s), 3,86 (3H, s ), of 4.45 (2H, square J 7 Hz), 6,8-7,4 (N, m).

8) Ethyl-1-(4-were)-5-[4-(methylthio)phenyl]pyrazole-3-carboxylate.

IR spectrum (film): 1720, 1605, 1520 cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, T. J7 Hz), is 2.37 (3H, s), 2,47 (3H, s ), of 4.45 (2H, square J 7 Hz). of 7.00 (1H, s), 7,0-7,4 (8H, m).

9) Ethyl-5-(4-forfinal)-1-[4-(methylthio)phenyl]pyrazole-3-carboxylate.

Melting point: 95-96,5aboutC.

IR-spectrum (nujol): 1710, 1610, 1545, 1495 cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, T. J7 Hz), 2.49 USD (3H, s), of 4.45 (2H, square J 7 Hz). the 6.9 and 7.3 (N, m).

Mass spectrum (m/z): 356 (M+).

10) Ethyl-5-[4-(methylthio)phenyl]-1-(4-nitrophenyl)pyrazole-3-carboxylate.

Melting point: 15

11) Ethyl-1-(4-forfinal)-5-[5-(methylthio)-2-thienyl]pyrazole-3-carboxylate.

IR spectrum (film); 1720, 1600, 1510 cm-1.

NMR-spectrum (DCl3, ): of 1.39 (3H, T. J7 Hz), 2,44 (3H, s), 4,42 (2H, square J 7 Hz), compared to 6.6-7.4 (7H, m).

12) Ethyl-1-(4-forfinal)-5-[4-(formylamino)phenyl]pyrazole-3-carboxylate.

Melting point: 184-188aboutC.

IR-spectrum (nujol): 3300, 1730, 1720, 1690, 1600, 1510 cm-1.

Mass spectrum (m/z): 353 (M+).

13) Ethyl-5-[5-(methylthio)-2-thienyl]-1-(4-nitrophenyl)pyrazole-3-carboxylate.

IR spectrum (film): 1725, 1600, 1525, 1500 cm-1.

14) Ethyl-1-(4-nitrophenyl)-5-(4-tolyl)pyrazole-3-carboxylate.

Melting point: 147-149aboutC.

IR-spectrum (nujol): 1715, 1595, 1525, 1500 cm-1.

The NMR spectrum (CDCl3, ): USD 1.43 (3H, T. J7 Hz), 2,39 (3H, s), 4,43 (2H, square J 7 Hz) and 6.9 to 8.3 (N, m).

Mass spectrum (m/z): 351 (M+).

15) Ethyl-5-(4-methoxyphenyl)-1-(4-nitrophenyl)pyrazole-3-carboxylate.

Melting point: 161-162aboutC.

IR-spectrum (nujol): 1710, 1615, 1595, 1525, 1500 cm-1.

Mass spectrum (m/z): 367 (M+).

16) Ethyl-5-(4-acetylphenyl)-1-(4-forfinal)pyrazole-3-carboxylate.

Melting point: 220-222aboutC.

Melting point: 173-174aboutC.

IR-spectrum (nujol): 3550, 1730, 1605, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 1,25 (N, S.), of 1.31 (3H, T. J 8 Hz), 4,32 (2H, square J 8 Hz), of 6.96 (2H, s), was 7.08 (1H, s), 7,2-7,5 (4H, m).

Mass spectrum (m/z): 438 (M+).

18) Ethyl-1-(2,5-differenl)-5-[4-(methylthio)phenyl]pyrazole-3-carboxylate.

Melting point: 81-84aboutC.

IR-spectrum (nujol): 1730, 1600, 1510 cm-1.

The NMR spectrum (CDCl3, ): USD 1.43 (3H, T. J7 Hz), 2,47 (3H, s), 4,46 (2H, square J 7 Hz), 7,0-7,4 (8H, m).

Mass spectrum (m/z): 374 (M+)

19) Ethyl-5-[4-(methylthio)phenyl]-1-(2-nitrophenyl)pyrazole-3-carboxylate.

Melting point: 155-157aboutC.

IR-spectrum (nujol): 1715, 1605, 1535 cm-1.

The NMR spectrum (CDCl3, ): of 1.41 (3H, T. J 7 Hz), a 2.45 (3H, s), of 4.44 (2H, square J 7 Hz), 7,0-8,1 (N, m).

Mass spectrum (m/z): 383 (M+).

20) Ethyl-1-(4-fluoro-2-nitrophenyl)-5-[4(methylthio)phenyl]pyrazole-3-carboxylate.

IR spectrum (film): 1725, 1590, 1545, 1510 cm-1.

The NMR spectrum (CDCl3, ): of 1.41 (3H, T. J7 Hz), the 2.46 (3H, s,), 4,36 (2H, square J 7 Hz) and 6.9 to 8.0 (8H, m).

Mass spectrum (m/z): 401 (M+).

21) 5-[4-(Methylthio/phenyl]-1-(4-nitrophenyl)-3-(trifluoromethyl)pyrazole.

The temperature of the melt is 4-(methylthio)phenyl]pyrazole.

IR spectrum (film): 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): 2,44 (3H, s), 5,14 (1H, s), 5,67 (1H, s,), 6,53 (1H, s), of 6.8 to 7.3 (8H, m).

Mass spectrum (m/z): 316 (M+).

23) 3-(Permitil)-5-[4-(methylthio)phenyl]-1-(4-nitrophenyl)pyrazole.

Melting point: 165-167aboutC.

IR-spectrum (nujol): 1600, 1520, 1500 cm-1.

The NMR spectrum (CDCl3, ): 2,50 (3H, s), are 5.36 (1H, s), ceiling of 5.60 (1H, s), only 6.64 (1H, s), and 7.1 to 8.3 (8H, m).

Mass spectrum (m/z): 343 (M+).

24) 3-(Deformity)-1-(4-nitrophenyl)- -5-[4-(methylthio) phenyl]pyrazole.

Melting point: 124-129aboutC.

IR-spectrum (nujol): 1600, 1520 cm-1.

The NMR spectrum (CDCl3, ): 2,50 (3H, s), 6,5-8,5 (10H, m).

Mass spectrum (m/z): 361 (M+).

25) 3-(Deformity)-1-(4-forfinal)-5-[4-(methylthio)phenyl]pyrazole.

Melting point: 70-71aboutC.

IR-spectrum (nujol): 1600, 1520 cm-1.

The NMR spectrum (CDCl3, ): 2,48 (3H, s), of 6.7 to 7.4 (10H, m).

Mass spectrum (m/z): 334 (M+).

26) Ethyl-1-(2-chlorophenyl)-5-[4-(methylthio)phenyl]pyrazole-3-carboxylate.

Melting point: 119-120aboutC.

IR-spectrum (nujol): 1715, 1605 cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, IgE compounds (examples 15-1 to 15-29) were obtained analogous to example 6.

P R I m e R 15.

1) 1-(4-Forfinal)-3-[4-(methylsulphonyl)phenyl]pyrazole-5-carbonitrile.

Melting point: 200-202aboutC.

IR-spectrum (nujol): 2240, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 3.28 (3H, s), 7,4-8,3 (N, m).

Mass spectrum (m/z): 341 (M+).

2) 1-(4-Forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-carbonitrile.

Melting point: 106-107aboutC.

IR-spectrum (nujol): 2250, 1600, 1510 cm-1.

NMR-spectrum (DCl3, ): 2,48 (3H, s), at 6.84 (1H, s), 7,0-7,4 (8H, m).

Mass spectrum (m/z): 309 (M+).

3) 5-[4-Methylsulphonyl)phenyl]-1-(4-pyridyl)pyrazole-3-carbonitrile.

Melting point: 194-195aboutC.

IR-spectrum (nujol): 2250, 1585, 1500 cm-1.

NMR spectrum (DMSO-d6, ): of 3.27 (3H, s,), and 7.3 and 8.1 (7H, m), to 8.70 (2H, d, J 5 Hz).

Mass spectrum (m/z): 324 (M+).

4) 5-[4-(methylthio)phenyl]-1-(4-pyridyl)pyrazole-3-carbonitrided.

Melting point: 185-188aboutC.

IR-spectrum (nujol): 2350, 2250, 2120, 2020, 1630, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,50 (3H, s,), a 7.1 to 7.6 (7H, m), is 8.75 (2H, d, J 6 Hz).

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

5) 1-(2-Forfinal)-5-[4-(methylsulphonyl)phenyl]00 cm-1.

The NMR spectrum (CDCl3, ): of 3.07 (3H, s,), of 7.00 (1H, s), 7,0-8,0 (8H, m).

Mass spectrum (m/z): 341 (M+).

6) 1-(2,4-Differenl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 129-130aboutC.

IR-spectrum (nujol): 2250, 1610, 1520 cm-1.

The NMR spectrum (CDCl3, ): is 3.08 (3H, s), 6,8-8,0 (8H, m)

Mass spectrum (m/z): 359 (M+).

7) 1-(3-Forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 167-168aboutC.

IR-spectrum (nujol): 2250, 1600, 1495 cm-1.

NMR spectrum (DMSO-d6, ): 3,26 (3H, s), 7,2-8,0 (N, m).

Mass spectrum (m/z): 341 (M+).

8) 5-[4-(Methylsulphonyl)phenyl]-1-phenylpyrazol-3-carbonitrile.

Melting point: 179-180aboutC.

IR-spectrum (nujol): 2250, 1600, 1500 cm-1.

NMR spectrum (DMSO-d3, ): of 3.25 (3H, s), of 7.3 to 8.0 (10H, m).

Mass spectrum (m/z): 323 (M+).

9) 1-(4-Methoxyphenyl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 153-154aboutC.

IR-spectrum (nujol); 2250, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), of 3.80 (3H, s), 7,0-8,0 (N, m).

Mass spectrum (m/z): 353 (M+exercise: 210-211aboutC.

IR-spectrum (nujol): 2250, 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): to 2.41 (3H, s), is 3.08 (3H, s), of 6.96, (1H, s), and 7.1 to 8.0 (8H, m).

11) 5-(4-Forfinal)-1-[4-(methylthio)phenyl]pyrazole-3-carbonitrile.

Melting point: 82-83aboutC.

IR-spectrum (nujol): 2250, 1610, 1545, 1500, cm-1.

Mass spectrum (m/z): 309 (M+).

12) 5-[4-(methyl)phenyl]-1-(4-nitrophenyl)pyrazole-3-carbonitrile.

Melting point: 165-166aboutC.

IR-spectrum (eusol): 2250, 1600, 1520, 1480 cm-1.

Mass spectrum (m/z): 336 (M+).

13) 1-(4-Forfinal)-5-[5-(methylthio)-2-thienyl]pyrazole-3-carbonitrile.

IR spectrum (film): 2250, 1600, 1510 cm-1.

14) 5-[5-(methylthio)-2-thienyl]-1-(4-nitrophenyl)pyrazole-3-carbonitrile.

IR spectrum (film): 2250, 1600, 1525, 1500 cm-1.

15) 1-(4-Forfinal)-5-[4-(N-formylmethionine)phenyl]pyrazole-3-carbonitrile.

Melting point: 147-148aboutC.

IR-spectrum (nujol): 2250, 1675, 1615, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 3,19 (3H, s), of 7.2 to 7.7 (N, m), 8,64 (1H, s).

Mass spectrum (m/z): 320.

16) 5-[4-(Acetamido)phenyl]-1-(4-forfinal)pyrazole-3-carbonitrile.

Melting point: 96-98aboutOF 7.1 AND 7.6 (N, m), 10,10 (1H, s ).

Mass spectrum (m/z): 320 (M+).

17) 1-[4-(N-Formylmethionine)phenyl]-5-(4-tolyl)pyrazole-3-carbonitrile.

IR spectrum (film): 2250, 1680, 1610, 1515 cm-1.

The NMR spectrum (CDCl3, ): of 2.38 (3H, s), to 3.33 (3H, s), 6,8-7,4 (N, m), 8,55 (1H, s).

18) 1-(forfinal)-5-(4-methoxyphenyl)pyrazole-3-carbonitrile.

Melting point: 122-123aboutC.

IR-spectrum (nujol): 2250, 1610, 1500 cm-1.

The NMR spectrum (CDCl3, ): is 3.82 (3H, s,), 6,8-7,4 (N, m).

Mass spectrum (m/z): 293 (M+).

19) 5-(4-Methoxyphenyl)-1-(4-nitrophenyl)pyrazole-3-carbonitrile.

Melting point: 125-126aboutC.

IR-spectrum (nujol): 2250, 1615, 1520, 1500 cm-1.

Mass spectrum (m/z): 320 (M+).

20) 1,5-Bis(4-methoxyphenyl)pyrazole-3-carbonitrile.

Melting point: 79-80aboutC.

IR-spectrum (nujol): 2250, 1610, 1515 cm-1.

The NMR spectrum (CDCl3, ): 3,81 (3H, s), 3,83 (3H, s), 6,7-7,3 (N, m).

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

21) 5-(4-Tianfeng(-1-(4-forfinal)pyrazole-3-carbonitrile.

Melting point: 154-156aboutC.

IR-spectrum (nujol): 2250, 2230, 1615, 1510 cm-1.

The NMR spectrum (CDCl3, ): of 6.96 4-forfinal)pyrazole-3-Carboni - home to the thrill.

Melting point: 189-190aboutC.

IR-spectrum (nujol): 3600, 2250, 1600, 1500 cm-1.

NMR spectrum (DMSO-d6, ): 1,24 (N, S.), of 6.96 (2H, s). 7,3-7,5 (5H, m ).

Mass spectrum (m/z): 391 (M+), 376.

23) 1-(2-Forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-carbonitrile.

Melting point: 76-77aboutC.

IR-spectrum (nujol): 2250, 1600, 1505 cm-1.

The NMR spectrum (CDCl3, ): the 2.46 (3H, s), 6.87 in (1H, s), 7,0-7,0 (8H, m).

Mass spectrum (m/z): 309 (M+).

24) 1-(2,4-Differenl)-5-[4-(methylthio)phenyl]pyrazole-3-carbonitrile.

Melting point: 74-75aboutC.

IR-spectrum (nujol): 2250, 1600, 1520 cm-1.

NMR-spectrum (DCl3, ): 2,47 (3H, s), of 6.8 to 7.6 (8H, m).

Mass spectrum (m/z): 327 (M+).

25) 1-(2,5-Differenl)-5-[4-(methylthio)phenyl]pyrazole-3-carbonitrile.

IR spectrum (film): 2250, 1625, 1600, 1510 cm-1.

26) 1-[4-(N-Formylmethionine)phenyl] -5-[4-(methylthio)phenyl] pyrazole-3-Carboni - home to the thrill.

Melting point: 132-134aboutC.

IR-spectrum (nujol): 2250, 1670, 1600, 1515 cm-1.

Mass spectrum (m/z): 348 (M+).

27) 5-[4-(Methylthio)phenyl]-1-(2-nitrophenyl)pyrazole-3-carbonitrile.

IR-spectrum (PLU>/P>IR spectrum (film): 2250, 1590, 1510 cm-1.

29) 1-(2-Chlorophenyl)-5-[4-(methylthio)phenyl]pyrazole-3-carbonitrile.

Melting point; 124-125aboutC.

IR-spectrum (nujol): 2250, 1600 cm-1.

The NMR spectrum (CDCl3, ): of 2.45 (3H, s), to 6.88 (1H, s), 7,0-7,5 (8H, m).

Mass spectrum (m/z): 325 (M+).

P R I m e R 16. A mixture of 1-(4-forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-amine (3 g), chloride (1.6 g) copper (1.6 g) and tert-butylnitrite (1,14 g) in acetonitrile (50 ml) and dioxane (20 ml) were mixed at ambient temperature for 4 hours, the Insoluble substance was filtered and to the filtrate was added ethyl acetate and water. The organic layer was separated, washed with diluted hydrochloric acid, dried and concentrated. Oily residue was subjected to purification by column chromatography on silica gel (40 g) with elution with a mixture of toluene and ethyl acetate (10:1) and the obtained brown oil (1-(4-forfinal)-5-[4-(methylthio)phenyl]pyrazole (1.4 g).

IR spectrum (film): 1600, 1510 cm-1.

The NMR spectrum (CDCl3, ): 2,48 (3H, s), 6.48 in (1H, d, J 1.8 Hz) and 6.9 to 7.4 (8H, m), of 7.70 (1H, d, J 1.8 Hz).

Mass spectrum (m/z): 284 (M+).

The following compounds (examples 17-1 to 17-30) were implemented]pyrazole.

Melting point: 110-112aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), 6,83 (1H, d, J 1.9 Hz), 7,2-8,0 (N, m).

Mass spectrum (m/z): 316 (M+).

2) 1-(4-Forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 197aboutC.

IR-spectrum (nujol): 2240, 1600, 1515 cm-1.

3) Ethyl-5-[4-(methylsulphonyl)phenyl]-1-(4-pyridyl)pyrazole-3-carboxylate.

Melting point: 195-199aboutC.

IR-spectrum (nujol): 1715, 1585, 1500 cm-1.

NMR spectrum (DMSO-d6, ): of 1.33 (3H, T. J 7 Hz), or 3.28 (3H, s), 4,37 (2H, square J 7 Hz), 7,2-7,4 (3H, m), a 7.62 (2H, d J 8.5 Hz), of 7.97 (2H, d J 8.5 Hz), 8,68 (2H, Shir. C.).

Mass spectrum (m/z): 371 (M+).

4) Ethyl-1-(2-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxylate.

Melting point: 165-167aboutC.

IR-spectrum (nujol): 1725, 1600, 1500 cm-1.

The NMR spectrum (CDCl3, ): USD 1.43 (3H, T. J7 Hz), 3,06 (3H, s), 4,47 (2H, square J 7 Hz), 7,0-7,9 (N, m).

Mass spectrum (m/z): 388 (M+), 316.

5) Ethyl-1-(2,4-differenl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxy - lat.

Melting point: 184-185aboutC.

IR-spectrum (nujol): 1730, 1605, 1-range (m/z): 406 (M+).

6) Ethyl-1-(3-forfinal)-5-[4-(methysulfonyl)phenyl]pyrazole-3-carboxylate.

Melting point: 110-112aboutC.

IR-spectrum (nujol): 1720, 1605, 1490 cm-1.

The NMR spectrum (CDCl3, ): USD 1.43 (3H, T. J7 Hz), to 3.09 (3H, s), 4,47 (2H, square J 7 Hz), of 7.0 and 8.1 (1H, m).

Mass spectrum (m/z): 388 (M+).

7) Ethyl-5-[4-(methylsulphonyl)phenyl]-1-phenylpyrazol-3-carboxylate.

IR spectrum (film): 1720, 1600, 1500 cm-1.

8) Ethyl-1-(4-methoxyphenyl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxylate.

Melting point: 122-125aboutC.

IR-spectrum (nujol): 1715, 1610, 1590, 1515 cm-1.

Mass spectrum (m/z: 400 (M+).

9) Ethyl-1-(4-were)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxylate.

Melting point: 149-151aboutC.

IR-spectrum (nujol): 1720, 1600, 1520 cm-1.

Mass spectrum (m/z): 384 (M+).

10) 5-[4-Methylsulphonyl)phenyl]-1-(4-nitrophenyl)pyrazole-3-carbonitrile.

Melting point: 199-200aboutC.

IR-spectrum (nujol): 2250, 1600, 1530, 1500 cm-1.

Mass spectrum (m/z): 368 (M+).

11) 1-(4-Forfinal)-5-[5-(methylsulphonyl)-2-thienyl]pyrazole-3-carbonitrile.

UB>, ):3,35 (3H, c.), 7,3 one-7.8 (7H, m).

Mass spectrum (m/z): 347 (M+).

12) 5-[5-(Methylsulphonyl)-2-thienyl] -1-(4-nitrophenyl)pyrazole-3-carbonitrile.

Melting point: 98-106aboutC.

IR-spectrum (nujol):2250, 1615, 1595, 1530 cm-1.

Mass spectrum (m/z): 374 (M+).

13) 1-(2,5-Differenl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 139-140aboutC.

IR-spectrum (nujol): 2250, 1620, 1605, 1505 cm-1.

NMR spectrum (DMSO-d6, ): 3,26 (3H, s), 7,4-8,0 (8H, m).

Mass spectrum (m/z): 359 (M+).

14) 1-[4-(N-Formylmethionine)phenyl] -5-[4-(methylsulphonyl)phenyl] pyrazole-3 - carbonitrile.

Melting point: 170-173aboutC.

IR-spectrum (nujol): 2250, 1610, 1520 cm-1.

NMR-spectrum (DMS-d6, ): 3,23 (3H, s), 3,26 (3H, s), 7,4-8,0 (N, m), 8,68 (1H, s).

Mass spectrum (m/z): 380 (M+).

15) 5-[4-(Methylsulphonyl)phenyl]-1-(2-nitrophenyl)pyrazole-3-carbonitrile.

Melting point: 123-125aboutC.

IR-spectrum (nujol): 2250, 1605. 1535 cm-1.

Mass spectrum (m/z): 368 (M+).

16) 1-(4-fluoro-2-nitrophenyl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-Carboni - home to the thrill.

Temperature M+).

17) 5-[4-(Methylsulphonyl)phenyl]-1-(4-nitrophenyl)-3-(trifluoromethyl)pyrazole.

Melting point: 163-164aboutC.

IR-spectrum (nujol): 1600, 1535 cm-1.

Mass spectrum (m/z): 411 (M+).

18) 3-Bromo-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole.

Melting point: 185-186aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): 3,24 (3H, s), 7,03 (1H, s). of 7.2 to 8.0 (8H, m).

Mass spectrum (m/z): 396, 394.

19) N-Cyclopropyl-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-CT - boxlid.

Melting point: 185-186aboutC.

IR-spectrum (nujol); 3350, 1660, 1605, 1545, 1535, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 0,6-1,0 (4H, m), 2.8 to 3.0 (1H, m), is 3.08 (1H, s), 7,0-7,5 (8H, m), of 7.90 (2H, d, J 8 Hz).

Mass spectrum (m/z): 399 (M+).

20) Ethyl-5-[4-(methylsulphonyl)phenyl]-1-[4-nitrophenyl]pyrazole-3-carboxylate.

Melting point: 209-210aboutC.

IR-spectrum (nujol): 1710, 1600, 1525 cm-1.

NMR spectrum (DMSO-d6, ): of 1.33 (3H, T. J 7 Hz), 3,26 (3H, s), 4,37 (2H, square J 7 Hz), and 7.3 (1H, s), 7.5 to 8.4 and (8H, m).

Mass spectrum (m/z): 415 (M+).

21) 3-(Permitil)-1-(4-forfinal)-5-[4-(methylsulphonyl)CLASS="ptx2">

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), to 5.35 (1H, s), 5,59 (1H,s), of 6.9 to 8.0 (8H, m).

Mass spectrum (m/z): 348.

22) 1-(4-Forfinal)-5-[4-(methylsulphonyl)phenyl]-3-pyrazolylborate.

Melting point: 102-103aboutC.

IR-spectrum (nujol): 1740, 1720, 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): and 2.14 (3H, s,), of 3.07 (3, C), 5,10 (2H, s), of 6.66 (1H, s), 7,0-8,0 (8H, m).

Mass spectrum (m/z): 388 (M+), 345.

23) 3-(Chloromethyl)-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole.

Melting point: 155-156aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), 4,82 (2H, s), 6,91 (1H, s), 7,2-8,0 (8H, m).

Mass spectrum (m/z): 364 (M+).

24) 3-(Permitil)-5-[4-(methylsulphonyl)phenyl]-1-(4-nitrophenyl)pyrazole.

Melting point: 152-153aboutC.

IR-spectrum (nujol): 1600, 1525 cm-1.

Mass spectrum (m/z): 375 (M+).

25) 3-(Deformity)-1-[4-(methylamino)phenyl] -5-4-(methylsulphonyl)phenyl pyrazole.

Melting point: 175-176aboutC.

IR-spectrum (nujol): 3430, 1615, 1540 cm-1.

The NMR spectrum (CDCl3, ): of 2.72 (3H, s), of 3.07 (3H, s), of 3.97 (1H, s), the 6.5 to 8.1 (10H, m).

Mass spectrum (m/z): 277 (M+aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): is 3.08 (3H, s), of 6.5 to 8.0 (10H, m).

Mass spectrum (m/z): 366 (M+).

27) 4-Bromo-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole.

Melting point: 169-170aboutC.

IR-spectrum (nujol): 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 3,10 (3H, C. E., 7,0-98.0 (N, m).

Mass spectrum (m/z): 396, 394.

28) N-phenyl-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxy - MFA.

Melting point: 232-233aboutC.

IR-spectrum (nujol): 3350, 1680, 1595, 1535, 1505 cm-1.

NMR-spectrum (DMSP-d6, ): 3,26 (3H, s), 7,0-8,0 (1H, m), 10.26 (N C. ).

Mass spectrum (m/z): 435.

29= 1-(4-Forfinal)-5-[4-(methylsulphonyl)phenyl]-3-(1-pyrrolidinyl-carbonyl/ pyrazole.

Melting point: 229-230aboutC.

IR-spectrum (CDCl3, ): 1,77-2,07 (4H, m), of 3.00 (3H, s), to 3.67 (2H, T. J 6 Hz), 3,97 N, so J 6 Hz), the 6.9 to 7.5 (7H, m). 7,87 (2H, d, J 8 Hz).

Mass spectrum (m/z): 413 (M+).

30) 1-(2-Chlorophenyl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 151-152aboutC.

IR-spectrum (CDCl3, ): 3,05 (3H, s), 7,02 (1H, s), of 7.3 to 8.0 (8H, m).

Mass spectrum (m/z)S="ptx2">

28) N-phenyl-1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxy - MFA.

Melting point: 232-233aboutC.

IR-spectrum (nujol): 3350, 1680, 1595, 1535, 1505 cm-1.

NMR spectrum (DMSO-d6, ): 3,26 (3H, s), 7,0-8,0 (1H, m), 10,26 (1H, s ).

Mass spectrum (m/z): 435.

29) 1-(4-Forfinal)-5-[4-(methylsulphonyl)phenyl]-3-(1-pyrrolidinyl-carbonyl/ pyrazole.

Melting point: 229-230aboutC.

IR-spectrum (nujol): 1615, 1515, 1500 cm-1.

The NMR spectrum (CDCl3, ): 1,77-2,07 (4H, m), of 3.00 (3H, s), to 3.67 (2H, T. J 6 Hz), of 3.97 (2H, T. J 6 Hz), the 6.9 to 7.5 (7H, m). 7,87 (2H, d, J8 Hz).

Mass spectrum (m/z): 413 (M+).

30) 1-(2-Chlorophenyl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 151-152aboutC.

IR-spectrum (nujol):2250, 1610, 1545, 1490 cm-1.

The NMR spectrum (CDCl3, ): 3,05 (3H, s), 7,02 (1H, s), of 7.3 to 8.0 (8H, m).

Mass spectrum (m/z): 357 (M+).

P R I m e R 18. A mixture of ethyl-1-(4-forfinal)-5-[4-(methylthio)phenyl] pyrazole-3-carboxylate (3.6 g) and caliginosity (2 g) in methanol (50 ml) was boiled under reflux for 30 minutes, the Solvent is boiled away. The residue was dissolved in water and washed with chloroform. The aqueous layer was acidified using dilute hlom and concentrated. Obtained residue was recrystallize from ethanol, resulting in crystals of 1-(4-forfinal)-5-[4-(methylthio)phenyl]PIR - evil-3-carboxylic acid (2 g).

Melting point: 199-200aboutC.

IR-spectrum (nujol): 3550, 3300, 2500, 1710, 1680, 1600, 1515 cm-1.

Mass spectrum (m/z): 328 (M+).

The following compounds (examples 19-1 to 19-11) were obtained analogous to example 18.

P R I m e R 19.

1) 5-[4-(methylsulphonyl)phenyl] -1-(4-pyridine)pyrazole-3-carboxylic acid.

Melting point: 270-271aboutWith (Razlog.).

IR-spectrum (nujol): 1690, 1610, 1510 cm-1.

NMR spectrum (DMSO-d6, ): of 3.28 (3H, s), 7,2-8,0 (7H, m) 8,66 (2H, Shir. C.), 13,25 (1H, s).

Mass spectrum (m/z): 343 (M+).

2) 5-[4-(Methylthio)phenyl]-1-(4-pyridyl/pyrazole-3-carboxylic acid.

Melting point: 225-227aboutC.

IR-spectrum (nujol): 3400, 2400, 1700, 1600, 1510 cm-1.

Mass spectrum (m/z): 311 (M+).

3) 1-(2-Forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxylic acid.

Melting point: 228-229aboutWith (Razlog.).

IR-spectrum (nujol): 2600, 1700, 1600, 1500 cm-1.

NMR spectrum (DMSO-d6, ): 3,25 (nmethylaniline)phenyl] pyrazole-3-carboxylic acid.

Melting point: 231-233aboutWith (Razlog.).

IR-spectrum (nujol): 2600, 1700, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), of 7.3 to 8.0 (8H, m), 13,20 (1H, s ).

Mass spectrum (m/z): 378 (M+).

5) 1-(3-Forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxylic acid.

IR-spectrum (nujol): 2630, 1705, 1600, 1490 cm-1.

NMR spectrum (DMSO-d6, ): 3,26 (3H, s), 7,1-8,0 (N, m).

Mass spectrum (m/z): 360 (M+).

6) 5-[4-(Methylsulphonyl)phenyl]-1-phenylpyrazol-3-carboxylic acid.

Melting point: 203-205aboutC.

IR-spectrum (nujol): 2625, 1700, 1600, 1495 cm-1.

Mass spectrum (m/z): 342 (M+).

7) 1-(4-Methoxyphenyl)-5-[4-)methylsulphonyl)phenyl] pyrazole-3-carboxylic acid.

Melting point: 197-199aboutC.

IR-spectrum (nujol): 1700, 1600, 1515 cm-1.

Mass spectrum (m/z): 372 (M+).

8) 1-(4-Were)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxylic acid.

Melting point: 185-187aboutC.

IR-spectrum (nujol): 2600, 1700, 1600, 1510 cm-1.

Mass spectrum (m/z): 356 (M+).

9) 5-(4-Forfinal)-1-[4-methylthio)phenyl]pyrazole-3-carboxylic acid.

+).

10) 5-[4-(Methylthio)phenyl]-1-(4-nitrophenyl)pyrazole-3-carboxylic acid.

Melting point: 188-189aboutC.

IR-spectrum (nujol): 1690, 1595, 1520 cm-1.

Mass spectrum (m/z): 355 (M+).

11) 1-(2,4-Differenl)-5-[4-(methylthio)phenyl] pyrazole-3-carboxylic acid.

Melting point: 188-190aboutC.

IR-spectrum (nujol): 3300, 2500, 1705, 1680, 1600, 1520 cm-1.

Mass spectrum (m/z): 346 (M+).

P R I m e R 20. A mixture of ethyl-1-(4-methoxyphenyl)-5-[4-(methylsulphonyl)phenyl] PIR - evil-3-carboxylate (2 g), and itestosterone acid (57%, 5 ml) in acetic acid (10 ml) was boiled under reflux for 5 hours, the Reaction mixture was concentrated, and the residue was subjected to poroshkovaya in an aqueous solution of nutribiotic, resulting in a powder. This crude powder was subjected to purification by column chromatography on silica gel (80 g) with elution with a mixture of chloroform and methanol and the obtained powder 1-(4-hydroxyphenyl)-5-[4-(methylsulphonyl) phenyl]pyrazole-3-carboxylic acid (0,86 g).

Melting point: 233-236aboutC (decomp.).

IR-spectrum (nujol): 3550, 3250, 1700, 1600, 1515 cm-1.

Mass spectrum (m/z): 358 (is Inishmore 910 ml) in dichloroethane (30 ml) was boiled under reflux in techenie hours. The mixture was concentrated and the obtained oil 1-(4-forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-carbonylchloride.

IR spectrum (film): 1760, 1605, 1510 cm-1.

The solution of the above chloride in tetrahydrofuran (50 ml) was added dropwise to a mixture of 28% ammonia water and tetrahydrofuran (50 ml) at 5-10aboutC. the Mixture was mixed for 1 h at ambient temperature. The solvent is boiled away and the residue was subjected to poroshkovaya water, resulting in crystals of 1-(4-forfinal)-5-[4-(methylthio)phenyl] PIR - evil-3-carboxamide (11.2 g).

Melting point: 180-181aboutC.

IR-spectrum (nujol): 3500, 3425, 1670, 1600, 1510 cm-1.

The NMR spectrum (CDCl3, ): 2,48 (3H, s), 5,70 (1H, s), 6.87 in (1H, s), 7,0-7,4 (N, m).

Mass spectrum (m/z): 327 (M+).

The following compounds (examples 22-1 to 22-13) were obtained analogous to example 21.

P R I m e R 22.

1) 5-[4-(Methylsulphonyl)phenyl]-1-(4-pyridyl)pyrazole-3-carboxamide.

Melting point: 286-288aboutC.

IR-spectrum (nujol): 3550, 3300, 3200, 1690, 1595, 1500 cm-1.

NMR spectrum (DMSO-d6, ): of 3.28 (3H, s), 7,18 (1H, s), of 7.3 to 8.0 (8H, m), 8,66 (2H, d 5 Hz).

2) 5-[4-(methylthio)phenyl]-1-(4-pyridyl)the 1595 cm-1.

3) 1-(2-Forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxamide.

Melting point: 198-199aboutC.

IR-spectrum (nujol): 3500, 3150, 1690, 1600, 1510 cm-1.

The NMR spectrum (CDCl3, )): a 3.06 (3H, s), of 5.68 (1H, s), 6,86 (1H, s), 7,1-7,9 (N, m).

Mass spectrum (m/z): 359 (M+).

4) 1-(2,4-Differenl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxamide.

Melting point: 213-214aboutC.

IR-spectrum (nujol): 3440, 3150, 1685, 1610, 1520 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), 7.23 percent (1H, s), of 7.3 to 8.0 (7H, m).

Mass spectrum (m/z): 377 (M+).

5) 1-(3-Forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxamide.

Melting point: 217-218aboutC.

IR-spectrum (nujol):3460, 3220, 1680, 1600, 1490 cm-1.

NMR=spectrum (DMSO-d6, ): 3,26 (3H, s), 7,1-8,0 (11N, m).

Mass spectrum (m/z): 359 (M+).

6) 5-[4-(Methylsulphonyl)phenyl]-1-phenylpyrazol-3-carboxamide.

Melting point: 265-266aboutC.

IR-spectrum (nujol): 3475, 3200, 1680, 1600, 1495 cm-1.

NMR-spectrum (DMSO d6, ): 3,24 (3H, s), 7,16 (1H, s), 7.3 to 8.0 in (11N, m ).

Mass spectrum (m/z): 331 (M+).

7) 1-(4-Methoxyphenyl)-5-[4-(matilal the Youghal): 3480, 3310, 3230, 1675, 1590, 1515 cm-1.

NMR spectrum (DMSO-d6, ): 3,24 (3H, s), with 3.79 (3H, s), 6,9-8,0 (11N, m ).

Mass spectrum (m/z): 371 (M+).

8) 1-(4-Hydroxyphenyl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxamide.

Melting point: 269-271aboutC.

IR-spectrum (nujol): 3550, 3460, 3200, 1680, 1600, 1520 cm-1.

Mass spectrum (m/z): 357 (M+).

9) 1-(4-Were)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxamide.

Melting point: 125-130aboutC.

IR-spectrum (nujol):3470, 3200, 1680, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): 2,35 (3H, s), 3,24 (3H, s), 7,1-8,0 (11N, m ).

Mass spectrum (m/z): 355 (M+).

10) 5-(4-Forfinal)-1-[4-(methylthio)phenyl]pyrazole-3-carboxamide.

Melting point: 157-159aboutC.

IR-spectrum (nujol): 3460, 3270, 1670, 1610, 1595, 1545, 11495 cm-1.

Mass spectrum (m/z): 327 (M+).

11) 5-[4-(methylthio)phenyl]-1-(4-nitrophenyl)pyrazole-3-carboxamide.

Melting point: 192-194aboutC.

IR-spectrum (nujol): 3480, 3150, 1690, 1610, 1595, 1520 cm-1.

Mass spectrum (m/z): 354 (M+).

12) 1-(4-Forfinal)-5-(4-tolyl)pyrazole-3-carboxamide.

Melting point: 183-186 who, C.), 6,8-7,5 (N, m), 7,68 (2H, s).

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

13) 1-(2,4-Differenl)-5-[4-(methylthio)phenyl]pyrazole-3-carboxamide.

Melting point: 171-173aboutC.

IR-spectrum (nujol): 3440, 3200, 1665, 1600, 1515 cm-1.

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

P R I m e R 23. A mixture of 1-(4-hydroxyphenyl)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxamide (1.3 g) and methanesulfonamide (2.5 g) in pyridine (20 ml) was mixed with 50aboutC for 5 hours, the Solvent is boiled away, and to the residue was added dilute hydrochloric acid and ethyl acetate. The organic layer was washed with water, dried and concentrated. The residue was subjected to purification by column chromatography on silica gel (20 g) with elution with a mixture of chloroform and methanol (20: 1) and the obtained crystals of 5-[4-(methylsulphonyl)phenyl] -1-[4-(methylsulfonyl - si)phenyl] pyrazole - 3-carbonitrile (0,79 g).

Melting point: 195-196aboutC.

IR-spectrum (nujol): 2250, 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 3,10 (3H, s), of 3.45 (3H, s), 7,4-8,0 (N, m).

Mass spectrum (m/z): 417 (M+).

P R I m e R 24. The solution retryperiod (0.7 g) in water (5 ml) was added to a cooled with ice to a solution of 1-(4-Portnoy temperature for 8 hours The insoluble substance was filtered, and the filtrate was concentrated. Obtained residue was dissolved in ethyl acetate and washed with an aqueous solution of matrilineality and water. The organic layer was dried and concentrated, resulting in an oily residue (0.6 g). The residue was purified by column chromatography on silica gel (13 g) with elution with a mixture of chloroform and methanol (50:1). The purified product crystallized from a mixture of hexane and ethanol, resulting in crystals of 1-(4-forfinal)-5-[4-(methylsulfinyl)phenyl]pyrazole-3-carbonitrile (0.45 g).

Melting point: 104-105aboutC.

IR-spectrum (nujol): 2250, 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): was 2.76 (3H, s), 6,94 (1H, s), of 7.0 to 7.7 (8H, m).

Mass spectrum (m/z): 325 (M+), 310.

P R I m e R 25. A mixture of 5-(4-forfinal)-1-[4-(methylthio)phenyl]pyrazole-3-carbonite - La (0.75 g) and 30% hydrogen peroxide solution (1.4 ml) in acetic acid (10 ml) was mixed with 50aboutC for 4 h, the Reaction mixture was concentrated, and the residue was recrystallize from ethanol, resulting in crystals of 5-(4-forfinal)-1-[4-(methylsulphonyl)phenyl)PIR - evil-3-carbonitrile (0.66 g).

Melting point: 162-163aboutC.

IR-Spa is tx2">

Mass spectrum (m/z): 341 (M+).

P R I m e R 26. A mixture of 5-[4-(methylsulphonyl)phenyl]-1-(4-nitrophenyl)pyrazole-3-CT - lonitrile (1.1 g), iron powder (1.1 g) and ameriglide (0.11 g) in ethanol (20 ml) and water (7 ml) was boiled under reflux for 1 h, the Solvent is boiled away, and the residue was filtered, washed with water and dissolved in hot ethyl acetate. The solution was filtered, and the filtrate was concentrated. The obtained residue was recrystallized from ethyl acetate and received in the crystals of 1-(4-AMINOPHENYL-5-[4-(methylsulphonyl)phenyl]PIR - evil-3-carbonitrile (0,83 g).

Melting point: 228-229aboutC.

IR-spectrum (nujol): 3480, 3400, 3150, 2250, 1645, 1605, 1520 cm-1.

NMR spectrum (DMSO-d6, ): of 3.25 (3H, s), to 5.57 (2H, s), 6,5-8,0 (N, m).

Mass spectrum (m/z): 338 (M+).

P R I m e R 27. A mixture of 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-amine (0.7 g) and acetic anhydride (0,22 ml) in dichloromethane (15 ml) was mixed at ambient temperature for 3 h and concentrated. The residue was subjected to purification by column chromatography on silica gel (15 g) with elution with a mixture of toluene and ethyl acetate (2:1). Target product (0,63 g) was recrystallize from ethanol and obtained in S="ptx2">

Melting point: 203-205aboutC.

IR-spectrum (nujol): 3350, 1690, 1580, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,05 (3H, s), 3,21 (3H, s), 6,98 (1H, s,), 7,2-7,6 (6N, m), 7,89 (2H, d, J 8 Hz), of 10.72 (1H, s);

Mass spectrum (m/z): 373 (M+), 331.

P R I m e R 28. Methylchloroform (0,163 ml) in acetonitrile (0.7 ml) was added dropwise to a stirred solution of 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl] PIR - evil-3-amine (0.7 g) and pyridine (0,171 ml) in acetonitrile (6 ml) and tetrahydrofuran (7 ml) at -20aboutC. the Mixture was mixed with 5aboutC for one hour, diluted with ethyl acetate, washed with water, dried and concentrated. The residue (0.9 g) was recrystallize from a mixture of chloroform and ethanol and has obtained pale-brown crystals of methyl N-{1-(4-forfinal)-5-[4-(matilal - radioactive)phenyl]-3-pyrazolyl}carbamate (0.51 g).

Melting point: 225-227aboutC.

IR-spectrum (nujol): 3320, 1730, 1585, 1510 cm-1.

NMR spectrum (DMSO-d6, ): and 3.16 (3H, s), 3,62 (3H, s), of 6.73 (1H, s), 7,1-7,5 (6N,m), to 7.84 (2H, d, J 8 Hz), 10,22 (1H, s).

Mass spectrum (m/z): 389 (M+), 357.

P R I m e R 29. A mixture of 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-amine (0.8 g) and methanesulfonamide (0,224 ml) in pyridine (8 ml) was mixed with temperating hydrochloric acid, dried and concentrated. The residual oil (1.1 g) was subjected to purification by column chromatography on silica gel (20 g) with elution with a mixture of toluene and ethyl acetate (2:1). The product (0.74 g) was recrystallize from ethanol and obtained as pale-brown crystals of N-{ 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl] -3-pyrazolyl} methanesulfonamide (0,62 g).

Melting point: 186-187aboutC.

IR-spectrum (nujol): 3150, 1555, 1520 cm-1.

NMR spectrum (DMSO-d6, ): 3,17 (3H, s), 3,24 (3H, s), 6,55 (1H, s), 7,2-7,6 (6N, m), to $ 7.91 (2H, d, J 8.5 Hz), 10,37 (1H, s).

Mass spectrum (m/z): 409 (M+).

P R I m e R 30. A mixture of 1-(4-AMINOPHENYL)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-CT - lonitrile (0.7 g) and formic acid (1 ml) formalin (37%, 5 ml) was heated under reflux for 30 minutes was Added chloroform and the mixture was washed with water, dried and concentrated. The residual oil was subjected to purification by column chromatography on silica gel with elution with a mixture of ethyl acetate and toluene (2:1). The resulting product was recrystallize from ethyl acetate and received in the crystals of 1-[4-(dimethylamino)phenyl] -5-4-(methylsulphonyl)phenyl]PI razol-3-carbonitrile (0,46 g).

Melting point:171-172about< the R and m e R 31. A mixture of 1-(4-AMINOPHENYL)-5-[4-(methylsulphonyl)phenyl pyrazole-3-carbonitrile (1 g), under the conditions (0,42 g) and callicarpenal (0.6 g) in N, N-dimethylformamide (10 ml) was mixed at ambient temperature for 1 h the Mixture was poured into water and was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue (1.2 g) was subjected to purification by column chromatographie on silica gel (20 g) using elution chloroform, and received in the crystals of 1-[4-(methylamino)phenyl] -5-[4-(methylsulphonyl)phenyl] pyrazole-3-carbonitrile (0.31 g).

Melting point: 166-168aboutC.

IR-spectrum (nujol): 3450, 2240, 1610, 1530 cm-1.

NMR spectrum (DMSO-d6, ): of 2.51 (3H, d, J 5 Hz) at 3.25 (3H, s), 6,17 (1H, square J 5 Hz), 6,5-8,0 (N, m).

The following compound (example 32) was obtained similar to example 10.

P R I m e R 32. 1-(4-Forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-ylmethylamino.

IR spectrum (film): 3400, 3300, 1600, 1500 cm-1.

The NMR spectrum (CDCl3, ): 1,85 (2H, s), 2,47 (3H, s), of 3.96 (2H, s), to 6.43 (1H, s), 7,0-7,4 (8H, m).

Mass spectrum (m/z): 313 (M+).

The following compounds (examples from 33-1 to 33-7) were obtained similar to example 24.

P R Lavinia: 139-140aboutC.

IR-spectrum (nujol): 2250, 1600, 1500 cm-1.

The NMR spectrum (CDCl3, ): 2,73 (3H, s), of 6.96 (1H, s), of 7.0 to 7.7 (8H, m).

Mass spectrum (m/z): 325 (M+), 310.

2) 1-(2,4-Differenl)-5-[4-(methylsulfinyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 136-137aboutC.

IR-spectrum (nujol): 2260, 1615, 1520 cm-1.

The NMR spectrum (CDCl3, ): is 2.74 (3H, s), 6,8-in 7.7 (8H, m).

Mass spectrum (m/z): 343 (M+), 328.

3) 1-[4-(N-formylmethionine)phenyl]-5-[4-(methylsulfinyl)phenyl]pyrazole-3 carbonitrile.

IR spectrum (film): 2250, 1680, 1610, 1515 cm-1.

4) 5-[4-Methylsulfinyl)phenyl]-1-(4-nitrophenyl)-3-(trifluoromethyl)pyrazole.

Melting point: 167-168aboutC.

IR spectrum (m/z): 395 (M+).

5) 3-(Permitil)-1-(4-forfinal)-5-[4-(methylsulfinyl)phenyl]pyrazole.

Melting point: 130-131aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): 2,75 (3H, s), are 5.36 (1H, s), ceiling of 5.60 (1H, s)9 6,69 (1H, s), of 7.0 to 7.7 (8H, m).

Mass spectrum (m/z): 332 (M+).

6) 3-(Chloromethyl)-1-(4-forfinal)-5-[4-(methylsulfinyl)phenyl]pyrazole.

Melting point: 96-97aboutC.

IR-spectrum (nujol): 1600, 1515 the (m/z): 348 (M+).

7) 3-(Deformity)-1-(4-forfinal)-5-[4-(methylsulfinyl)phenyl]pyrazole.

Melting point: 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): 2,75 (3H, s), about 6.5 to 7.7 (10H, m).

Mass spectrum (m/z): 350 (M+), 335.

The following compounds (examples from 34-1 to 34-13) were obtained similar to example 26.

P R I m e R 34.

1) 1-(4-AMINOPHENYL)-5-[-(methylsulphonyl)-2-thienyl]pyrazole-3-carbonitrile.

Melting point: 200-203aboutC.

IR-spectrum (nujol): 3500, 3420, 2250, 1620, 1520 cm-1.

Mass spectrum (m/z): 344 (M+).

2) Ethyl-1-(4-AMINOPHENYL)-5-(4-tolyl)pyrazole-3-carboxylate.

Melting point: 174-175aboutC.

IR-spectrum (nujol): 3460, 3380, 1730, 1700, 1635, 1520 cm-1.

Mass spectrum (m/z): 321 (M+).

3) 1-(4-AMINOPHENYL)-1-(4-methoxyphenyl)pyrazole-3-carbonitrile.

Melting point: 175-177aboutC.

IR-spectrum (nujol): 3420, 3350, 2250, 1640, 1610, 1520 cm-1.

Mass spectrum (m/z): 290 (M+).

4) Ethyl-1-(4-AMINOPHENYL)-5-[4-(methylthio)phenyl]pyrazole-3-carboxylate.

Melting point: 153 to 155aboutC.

IR-spectrum (nujol): 3450, 3350, 3230, 1715, 1635, 1610, 1520 see

Melting point: 191-192aboutC.

IR-spectrum (nujol): 3500, 3400, 2250, 1635, 1600, 1500 cm-1.

Mass spectrum (m/z): 338 (M3).

6) 1-(2-Amino-4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 206-208aboutC.

IR-spectrum (nujol): 3500, 3400, 2250, 1630, 1510 cm-1.

Mass spectrum (m/z): 356 (M+).

7) 1-(4-AMINOPHENYL)-5-[4-(methylthio)phenyl]-3-(trifluoromethyl)pyrazole.

Melting point: 112-113aboutC.

IR-spectrum (nujol): 3500, 3400, 1625, 1600, 1520, 1500 cm-1.

Mass spectrum (m/z): 349 (M+).

P R I m e R 33.

1) 1-(2-Forfinal)-5-[4-(methylsulfinyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 139-140aboutC.

IR-spectrum (nujol): 2250, 1600, 1500 cm-1.

The NMR spectrum (CDCl3, ): 2,73 (3H, s), of 6.96 (1H, s), of 7.0 to 7.7 (8H, m).

Mass spectrum (m/z): 325 (M+), 310.

2) 1-(2,4-Differenl)-5-[4-(methylsulfinyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 136-137aboutC.

IR-spectrum (nujol): 2260, 1615, 1520 cm-1.

The NMR spectrum (CDCl3, ): is 2.74 (3H, s), 6,8-in 7.7 (8H, m).

Mass spectrum (m/z): 343 (M+), 328.

3) 1-[4-(N-formulate -1
.

4) 5-[4-Methylsulfinyl)phenyl]-1-(4-nitrophenyl)-3-(trifluoromethyl)pyrazole.

Melting point: 167-168aboutC.

IR-spectrum (nujol):1600, 1530, 1495 cm-1.

Mass spectrum (m/z): 395 (M+).

5) 3-(Permitil)-1-(4-forfinal)-5-[4-(methylsulfinyl)phenyl]pyrazole.

Melting point: 130-131aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): 2,75 (3H, s), are 5.36 (1H, s), ceiling of 5.60 (1H, s), 6,69 (1H, s), of 7.0 to 7.7 (8H, m).

Mass spectrum (m/z): 332 (M+).

6) 3-(Chloromethyl)-1-(4-forfinal)-5-[4-(methylsulfinyl)phenyl]pyrazole.

Melting point: 96-97aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): 2,75 (3H, s ), 4,70 (2H, s), of 6.65 (1H,s), of 7.0 to 7.7 (8H, m).

Mass spectrum (m/z): 348 (M+).

7) 3-(Deformity)-1-(4-forfinal)-5-[4-(methylsulfinyl)phenyl]pyrazole.

Melting point: 165-166aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): 2,75 (3H, s), about 6.5 to 7.7 (10H, m).

Mass spectrum (m/z): 350 (M+), 335.

The following compounds (examples from 34-1 to 34-13) were obtained similar to example 26.

P R I m e R 34.

IR-spectrum (nujol): 3500, 3420, 2250, 1620, 1520 cm-1.

Mass spectrum (m/z): 344 (M+).

2) Ethyl-1-(4-AMINOPHENYL)-5-(4-tolyl)pyrazole-3-carboxylate.

Melting point: 174-175aboutC.

IR-spectrum (nujol): 3460, 3380, 1730, 1700, 1635, 1520 cm-1.

Mass spectrum (m/z): 321 (M+).

3) 1-(4-AMINOPHENYL)-1-(4-methoxyphenyl)pyrazole-3-carbonitrile.

Melting point: 175-177aboutC.

IR-spectrum (nujol): 3420, 3350, 2250, 1640, 1610, 1520 cm-1.

Mass spectrum (m/z): 290 (M+).

4) Ethyl-1-(4-AMINOPHENYL)-5-[4-(methylthio)phenyl]pyrazole-3-carboxylate.

Melting point: 153 to 155aboutC.

IR-spectrum (nujol): 3450, 3350, 3230, 1715, 1635, 1610, 1520 cm-1.

Mass spectrum (m/z): 353 (M+).

5) 1-(2-AMINOPHENYL)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 191-192aboutC.

IR-spectrum (nujol): 3500, 3400, 2250, 1635, 1600, 1500 cm-1.

Mass spectrum (m/z): 338 (M+).

6) 1-(2-Amino-4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 206-208aboutC.

IR-spectrum (nujol): 3500, 3400, 2250, 1630, 1510 cm-1.

Mass-Spa is temperature melting point: 112-113aboutC.

IR-spectrum (nujol): 3500, 3400, 1625, 1600, 1520, 1500 cm-1.

Mass spectrum (m/z): 349 (M+).

8) 1-(4-AMINOPHENYL)-5-[4-(methylsulphonyl)phenyl]-3-(trifluoromethyl)pyrazole.

Melting point: 250-251aboutC.

IR-spectrum (nujol): 3500, 2400, 1640, 1600, 1520, 1500 cm-1.

Mass spectrum (m/z): 381 (M+).

9) 1-(4-AMINOPHENYL)-5-[4-(methylsulfinyl)phenyl]-3-(trifluoromethyl)pyrazole.

Melting point: 213-214aboutC.

IR-spectrum (nujol): 3500, 3380, 3250, 1645, 1610, 1525, 1505 cm-1.

Mass spectrum (m/z): 335 (M+).

10) 1-(4-AMINOPHENYL)-3-(methylsulphonyl)-5-[4-(methylsulphonyl)phenyl]pyrazole.

Melting point: 208-210aboutC.

IR-spectrum (nujol): 3500, 3400, 1635, 1605, 1520 cm-1.

Mass spectrum (m/z): 391 (M+).

11) 1-(4-AMINOPHENYL)-3-(permitil)-5-[4-(methylsulphonyl)phenyl]pyrazole.

Melting point: wing 112-116aboutC.

IR-spectrum (nujol): 3420, 3240, 1610, 1520 cm-1.

12) 1-(4-AMINOPHENYL)-3-(deformity)-5-[4-methylthio)phenyl]pyrazole.

IR spectrum (film): 3500, 3380, 1625, 1520 cm-1.

13) Ethyl-1-(4-AMINOPHENYL)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxylate.

Temperatur (DMSO-d6, ): 1,32 (3H, T. J 7 Hz), 3.24 (3H, s), 4.33 (2H, square J 7 Hz), the 5.51 (2H, s), 6,5-8,0 (N, m).

Mass spectrum (m/z): 385 (M+).

The following compounds (examples 35-1 and 35-2) were obtained analogous to example 27.

P R I m e R 35.

1) 5-[4-(Acetamido)phenyl]-1-(4-forfinal)pyrazole-3-carboxamide.

Melting point: 273-275aboutC.

IR-spectrum (nujol): 3500, 3200, 1670, 1600, 1550, 1510 cm-1.

Mass spectrum (m/z): 338 (M+).

2) 1-[4-(Acetamido)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 206-207aboutC.

IR-spectrum (nujol): 3270, 2250, 1690, 1670, 1605, 1555, 1515 cm-1.

NMR spectrum (DMSO-d6, ): 2,07 (3H, s), of 3.25 (3H, s), 7.3 to 8.0 a (N, m), of 10.21 (1H, s).

Mass spectrum (m/z): 380 (M+).

The following compound (example 36) was obtained analogous to example 29.

P R I m e R 36. 1-[4-(Methylsulfonylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]PI razol-3 - carbonitrile.

Melting point: 232-233aboutC.

IR-spectrum (nujol): 3240, 2250, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): to 3.09 (3H, s), 3,26 (3H, s), 7,2-8,0 (N, m), 10,17 (1H, s).

Mass spectrum (m/z): 416 (M+).

Follow the P CLASS="ptx2">

1) 1-[4-(Dimethylamino)phenyl]-5-[5-(methylsulphonyl)-2-thienyl]pyrazole-3-Carbo - nitrile.

Melting point: 168-169aboutC.

IR-spectrum (nujol): 2250, 1610, 1525 cm-1.

NMR spectrum (DMSO-d6, ): 3,01 (6N, C.), to 3.33 (3H, s), 6,7-7,8 (7H, m).

Mass spectrum (m/z): 372 (M+).

2) 1-[4-(Ethylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 167-168aboutC.

IR-spectrum (nujol): 3400, 2240, 1610, 1525 cm-1.

The NMR spectrum (CDCl3, ): of 1.28 (3H, T. J7 Hz), of 3.07 (3H, s), of 3.13 (2H, square J 7 Hz), 6,5-8,0 (N, m).

Mass spectrum (m/z): 366 (M+), 351.

3) 1-[4-(Diethylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-Carboni - home to the thrill.

Melting point: 155-156aboutC.

IR-spectrum (nujol): 2240, 1610, 1520 cm-1.

NMR spectrum (DMSO-d6, ): 1,18 (6N, T. J 7 Hz), of 3.07 (3H, s), 3,37 (4H, square J 7 Hz), 6,5-8,0 (N, m).

Mass spectrum (m/z): 394 (M+), 379.

4) 3-(Permitil)-1-[4-(methylamino)phenyl[-5-[4-(methylsulphonyl)phenyl]pyrazole.

Melting point: 151-153aboutC.

IR-spectrum (nujol): 3425, 1615, 1535 cm-1.

The NMR spectrum (CDCl3, ): 2,85 (3H, s), 3.06 (3H, s), of 3.94 (1H, s), are 5.36 (1H, s), ceiling of 5.60 (1H, s), 6,5-8,0 (N, m).

Kar - barcelata (2.1 g) and nutrimetics (895 mg) in formamide (10 ml) was mixed with 100aboutC for 1 h To the reaction mixture was added water, and the precipitate was collected, washed with water and dried under vacuum, resulting in crystals of 1-(4-forfinal)-5-[5-(methylthio)-2-thienyl] pyrazole-3-carboxamide (1.6 g).

Melting point: 132-140aboutC.

IR-spectrum (nujol): 3500, 3300, 3200, 1700, 1665, 1600, 1510 cm-1.

Mass spectrum (m/z): 333 (M+).

The following compounds (examples from 39-1 to 39-16) were obtained analogous to example 38.

P R I m e R 39.

1) 5-[5-(Methylthio)-2-thienyl]-1-(4-nitrophenyl)pyrazole-3-carboxamide.

IR-spectrum (nujol): 3350, 3180, 1675, 1595, 1520 cm-1.

2) 1-(4-Forfinal)-5-[4-(N-formylmethionine)phenyl]pyrazole-3-carboxamide.

Melting point: 222-224aboutC.

IR-spectrum (nujol): 3500, 3430, 3200, 1660, 1615, 1510 cm-1.

Mass spectrum (m/z): 338 (M+).

3) 5-(4-AMINOPHENYL)-1-(4-forfinal)pyrazole-3-carboxamide.

Melting point: 195-199aboutC.

IR-spectrum (nujol): 3500, 3360, 3200, 1675, 1630, 1610, 1510 cm-1.

Mass spectrum (m/z): 296 (M+).

4) 1-[4-(N-Formylmethionine)phenyl]-5-(4-tolyl)pyrazole-3-carboxamide.

Melting point: 202-206aboutC.

IR-with whom-(4-methoxyphenyl)pyrazole-3-carboxamide.

Melting point: 136-142aboutC.

IR-spectrum (nujol): 3500, 3350, 3200, 1705, 1690, 1665, 1610, 1510 cm-1.

Mass spectrum (m/z): 311 (M+).

6) 5-(4-Methoxyphenyl)-1-(4-nitrophenyl)pyrazole-3-carboxamide.

Melting point: 200-202aboutC.

IR-spectrum (nujol): 3400, 3170, 1680, 1610, 1595, 1520 cm-1.

Mass spectrum (m/z): 338 (M+).

7) 1,5-Bis(4-methoxyphenyl)pyrazole-3-carboxamide.

Melting point: 130-131aboutC.

IR-spectrum (nujol): 3450, 3300, 3250, 1675, 1660, 1610, 1515 cm-1.

NMR spectrum (DMSO-d6, ): of 3.75 (3H, s), of 3.78 (3H, s), 6,7-7,6 (11N, m ).

Mass spectrum (m/z): 323 (M+).

8) 5-4-Acetylphenyl)-1-(4-forfinal)pyrazole-3-carboxamide.

Melting point: 300aboutC.

IR-spectrum (nujol): 3500, 3420, 1675, 1590, 1510 cm-1.

9) 5-(4-Tianfeng)-1-(4-forfinal)pyrazole-3-carboxamide.

Melting point: 181-185aboutC.

IR-spectrum (nujol): 3500, 3350, 2240, 1660, 1600, 1510 cm-1.

Mass spectrum (m/z): 306 (M+).

10) 1-(2-forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-carboxamide.

Melting point: 140-146aboutC.

IR-spectrum (nujol): 3400, 3300, 1670, 1600, 1500 cm-1the foreign Ministry.

Melting point: 185-187aboutC.

IR-spectrum (nujol): 3450, 3300, 3150, 1690, 1610, 1510 cm-1.

NMR spectrum (DMSO-d6, ): the 2.46 (3H, s), 7,0-7,8 (10H, m).

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

12) 1-[4-(N-formylmethionine)phenyl] -5-[4-(methylthio)phenyl] pyrazole-3 - carboxamide.

Melting point: 183-189oC.

IR-spectrum (nujol): 3350, 3200, 1670, 1655, 1605, 1520 cm-1.

Mass spectrum (m/z): 366 (M+).

13) 5-[4-(Methylthio)phenyl]-1-(2-nitrophenyl)pyrazole-3-carboxamide.

Melting point: 196 to 199aboutC (decomp.).

IR-spectrum (nujol): 3500, 3160, 1690, 1610, 1530 cm-1.

Mass spectrum (m/z): 354 (M+).

14) 1-(4-fluoro-2-nitrophenyl)-5-[4-(methylthio)phenyl]pyrazole-3-carboxamide.

IR-spectrum (nujol): 3430, 3200, 1670, 1590, 1540, 1510 cm-1.

15) 1-[4-(N,N-Formylmethionine)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole - 3-carboxamide.

Melting point: 278-283aboutC (decomp.).

IR-spectrum (nujol): 3350, 1665, 1600, 1520 cm-1.

Mass spectrum (m/z): 398 (M+).

16) 1-(2-Chlorophenyl)-5-[4-(methylthio)phenyl]pyrazole-3-carboxamide.

Melting point: 195-201aboutC.

IR-spectrum (nujol): 3450, 3150, 1690, 1610, 1590 hanil)-2-thienyl] pyrazole-3-carbonitrile (1.1 g) and formic acid (5 ml) was heated under reflux for 30 minutes The mixture was concentrated, and the residue was subjected to poroshkovaya in the water, resulting in the obtained crystals of 1-[4-(formylamino)phenyl] -5-[5-(metralha - Neil)-2-thienyl]pyrazole-3-carbonitrile (1.1 g).

Melting point: 152-158aboutC.

IR-spectrum (nujol): 3260, 2250, 1675, 1605, 1515 cm-1.

Mass spectrum (m/z): 372 (M+).

The following compounds (examples from 41-1 to 41-11) were obtained analogous to example 40.

P R I m e R 41.

1) Ethyl-1-[4-(formylamino)phenyl]-5-(4-tolyl)pyrazole-3-carboxylate.

Melting point: 201-203aboutC.

IR-spectrum (nujol): 3260, 1730, 1690, 1600, 1530 cm-1.

2) 1-[4-(Formylamino)phenyl]-5-(4-methoxyphenyl)pyrazole-3-carbonitrile.

IR spectrum (film): 3300, 2250, 1690, 1610, 1515 cm-1.

3) Ethyl-1-[4-(formylamino)phenyl] -5-[4-(methylthio)phenyl] pyrazole-3-carboxylate.

Melting point: 190-192aboutC.

IR-spectrum (nujol): 3250, 1730, 1690, 1605, 1520 cm-1.

4) 1-[4-(Formylamino)phenyl] -5-[4-(methylsulphonyl)phenyl]pyrazole-3-Carboni - home to the thrill.

Melting point: 195-197aboutC.

IR-spectrum (nujol): 3270, 2240, 1690, 1670, 1605, 1550, 1515 cm-1.

NMR spectrum DMSO-d6, ): 3,26 (3H, ] -5-[4-(methylsulphonyl)phenyl]pyrazole-3-Carboni - home to the thrill.

Melting point: 109-118aboutC.

IR-spectrum (nujol): 3330, 2250, 1700, 1600, 1520 cm-1.

Mass spectrum (m/z): 366 (M+), 338.

6) 1-[4-(Formylamino)phenyl]-5-[4-(methylthio)phenyl]-3-(trifluoromethyl)pyrazole.

Melting point: 134-135aboutC.

IR-spectrum (nujol): 3370, 1700, 1605, 1530 cm-1.

Mass spectrum (m/z): 377 (M+).

7) 1-[4-(Formylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]-3-(trifluoromethyl) pyrazole.

Melting point: 163-166aboutC.

IR-spectrum (nujol): 3270, 1680, 1610, 1550, 1520, 1500 cm-1.

Mass spectrum (m/z): 409 (M+).

8) 1-[4-(Formylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]-3-(trifluoromethyl) pyrazole.

IR spectrum (film): 3270, 1690, 1610, 1525, 1500 cm-1.

9) 1-[4-(Formylamino)phenyl]-3-(methylsulphonyl)-5-[4-(methylsulphonyl)phenyl] pyrazole.

Melting point: 193-195aboutC.

IR-spectrum (nujol): 3380, 1700, 1670, 1605, 1535 cm-1.

Mass spectrum (m/z): 419 (M+).

10) 3-(Deformity)-1-[4-(formylamino(phenyl]-5-[4-(methylthio)phenyl]pyrazole.

Melting point: 127-131aboutC.

IR-spectrum (nujol): 3300, 1680, 1670, 1610, 1520 cm-1.

Mass spectrum (m/z: 359 (Mmperature melting point: 214-216aboutC.

IR-spectrum (nujol): 3270, 1740, 1670, 1605, 1555, 1510 cm-1.

Mass spectrum (m/z): 413 (M+).

P R I m e R 42. A solution of 1-[4-(formylamino)phenyl]-5-[5-(methylsulphonyl)-2-thienyl] pyrazole-3 - carbonitrile (1.1 g) in N,N-dimethylformamide (3 ml) was added dropwise to a suspension of nutrigenie (60% 118 mg) in N, N-dimethylformamide (2 ml). The mixture was mixed at 0aboutC for 30 minutes To the mixture was added dropwise a solution of iodomethane (0.84 g) in N,N-dimethylformamide (2 ml) at 0aboutC. the resulting mixture was mixed at 0aboutC for 1 h, poured into a chilled ice-dilute hydrochloric acid and was extracted with ethyl acetate. The extract was washed with water, dried over maniculatus and evaporated in vacuum. The residue was recrystallize from ethanol and obtained as a result, the crystals of 1-[4-(N-formylmethionine)phenyl]-5-[5-(matilal - radioactive)-2-thienyl] pyrazole-3-carbonite - La (1 g).

Melting point: 170-173aboutC.

IR-spectrum (nujol): 2250, 1675, 1600, 1520 cm-1.

Mass spectrum (m/z): 386 (M+).

The following compounds (examples from 43-1 to 43-12) were obtained analogous to example 42.

P R I m e R 43.

1) Ethyl-1-(4-forfinal)-5-[4-(N-formylmethionine)phenyl]piraso the-1.

The NMR spectrum (CDCl3, ): USD 1.43 (3H, T. J7 Hz), 3,32 (3H, s), 4,46 (2H, square J GC), 7,0-7,5 (N, m), cent to 8.85 (1H, s).

Mass spectrum (m/z): 367 (M+).

2) Ethyl-1-[4-(N-formylmethionine)phenyl]-5-(4-tolyl)pyrazole-3-carboxylate.

IR spectrum (film): 1720, 1675, 1610, 1515 cm-1.

NMR-spectrum (SMSO-d6, ): of 1.39 (3H, T. J 7 Hz), 2,32 (3H, s), or 3.28 (3H, s), 4,42 (2H, square J 7 Hz) and 6.9-7.5 (M, m), 8,42 (1H, s).

3) 1-[4-(N-formylmethionine)phenyl]-5-(4-methoxyphenyl)pyrazole-3-carbonitrile.

IR spectrum (film): 2250, 1680, 1610, 1515 cm-1.

4) Ethyl-1-[4-(N-formylmethionine)phenyl] -5-[4-(methylthio)phenyl]pyrazole-3-CT - boxylic.

IR spectrum (film): 1720, 1680, 1605, 1520 cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, T. J7 Hz), 2,47 (3H, s), or 3.28 (3H, s, ), 4,42 (2H, square J 7 Hz). the 6.9 to 7.4 (N, m), of 8.37 (1H, s).

5) 1-[4-(N-formylmethionine)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-CT - bontril.

Mass spectrum (m/z):380 (M+).

6) 1-[2-(N-formylmethionine]phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-CT - bontril.

Melting point: 172-173aboutC.

IR-spectrum (nujol): 2250, 1670, 1600, 1500 cm-1.

Mass spectrum (m/z): 380 (M+), 352.

7) 1-[4-(N-Formylmethionine)phenyl]-5-[4-(methylthio)phenyl]-3-(trips-1.

Mass spectrum (m/z): 391

8) 1-[4+(N-Formylmethionine)phenyl] -5-[4-(methylsulphonyl)phenyl] -3- (trifluoromethyl)pyrazole.

Melting point: 118-120aboutC.

IR-spectrum (nujol): 1660, 1610, 1520, 1500 cm-1.

Mass spectrum (m/z): 423 (M+).

9) 1-[4-(N-Formylmethionine)phenyl] -5-[4-(methylsulphonyl)phenyl] -3-(trifluoromethyl) pyrazole.

IR spectrum (film): 1675, 1610, 1520, 1500 cm-1.

10) 1-[4-(N-Formylmethionine)phenyl]-3-(methylsulphonyl)-5-[4-(methylsulphonyl) phenyl]pyrazole.

Melting point: 146-150aboutC.

IR-spectrum (nujol): 1675, 1605, 1520 cm-1.

Mass spectrum (m/z): 433 (M+).

11) 3-(Deformity)-1-[4-(N-formylmethionine)phenyl]-5-[4-(methylthio)phenyl] pyrazole.

Melting point: 109-115aboutC.

IR-spectrum (nujol): 1680, 1605, 1520 cm-1.

Mass spectrum (m/z): 373 (M+).

12) Ethyl-1-[4-(N-formylmethionine)phenyl] -5-[4-(methylsulphonyl)phenyl] pyrazole - 3-carboxylate.

IR-spectrum (nujol); 1745, 1725, 1680, 1600, 1520 cm-1.

Mass spectrum (m/z): 427 (M+).

P R I m e R 44. A mixture of 1-[4-(N-formylmethionine)phenyl]-5-[5-(methylsulphonyl)-2-thienyl] pyrazole-3 - carbonitrile (1 g) and 10% floristry, and the filtrate concentrated in vacuo. The residue was washed with ethanol and received in the crystals of 1-[4-(methylamino)phenyl]-5-[5-(methylsulphonyl)-2-thienyl]pyrazole-3 - carbonitrided (0,89 g).

Melting point: 205-207aboutC.

IR-spectrum (nujol): 2600, 2450, 2250, 1510 cm-1.

NMR spectrum (DMSO-d6, ): was 2.76 (3H, s), to 3.33 (3H, s,), 6,77 (2H, d, J 8 Hz), 7,26 (2H, d, J 8 Hz), 7,43 (1H. D. J 3 Hz), a 7.62 (1H, s), 7,78 (1H, d J 3 Hz).

Mass spectrum (m/z): 358 (M+).

The following compounds (examples from 45-1 to 45-14) were obtained analogous to example 44.

P R I m e R 45.

1) 1-(4-Forfinal)-5-[4-(methylamino)phenyl]pyrazole-3-carboniteservice - Reid.

Melting point: 189-191aboutC.

IR-spectrum (nujol): 2650, 2450, 2250, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,73 (3H, s), 6,8-7,5 (N, m).

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

2) 1-[4-(Methylamino)phenyl]-5-(4-tolyl)pyrazole-3-carbonitrided.

Melting point: 199-201aboutC.

IR-spectrum (nujol): 2600, 2450, 1610, 1520 cm-1.

NMR spectrum (DMSO-d6, ): to 2.29 (3H, s), was 2.76 (3H, s), and 6.9-7.5 (N, m,), a 7.62 (2H, s).

Mass spectrum (m/z):288 (M+).

3) 1-[4-(Methylamino)phenyl]-.

IR-spectrum (nujol): 3450, 2650, 2460, 2250, 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,70 (3H, s), of 3.25 (3H, s), 5,46 (2H, s), 6,5-8,0 (N, m)

Mass spectrum (m/z): 352 (M+).

4) 1-[4-(Methylamino)phenyl] -5-[4-(methylthio)phenyl]pyrazole-3-carbonitrile hydrochloride.

Melting point: 113-120aboutC.

IR-spectrum (nujol): 3400, 2650, 2450, 2250, 1600, 1515 cm-1.

NMR-spectrum (DMSP-d6, ): the 2.46 (3H, s), is 2.74 (3H, s), to 6.57 (2H, s), 6,5-7,4 (N, m).

Mass spectrum (m/z): 330 (M+).

5) 1-[4-(Methylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile chloride.

Melting point: 175-177aboutC (decomp.).

IR-spectrum (nujol): 2630, 2450, 2250, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): is 2.74 (3H, s), was 2.76 (3H, s), 6,53 (2H, s) 6,7-7,8 (N, m).

Mass spectrum (m/z): 336 (M+), 319.

Melting point: 118-120aboutC.

IR-spectrum (nujol): 1660, 1610, 1520, 1500 cm-1.

Mass spectrum (m/z): 423 (M+).

9) 1-[4-(N-Formylmethionine)phenyl] -5-[4-(methylsulphonyl)phenyl] -3-(trifluoromethyl) pyrazole.

IR spectrum (film): 1675, 1610, 1520, 1500 cm-1.

10) 1-[4-(N-Formylmethionine)phenyl]-3-(methylsulphonyl)-5-[4-(methylsulphonyl) phenyl]pyrazole.

+).

11) 3-(Deformity)-1-[4-(N-formylmethionine)phenyl]-5-[4-(methylthio)phenyl] pyrazole.

Melting point: 109-115aboutC.

IR-spectrum (nujol): 1680, 1605, 1520 cm-1.

Mass spectrum (m/z): 373 (M+).

12) Ethyl-1-[4-(N-formylmethionine)phenyl] -5-[4-(methylsulphonyl)phenyl] pyrazole - 3-carboxylate.

IR-spectrum (nujol); 1745, 1725, 1680, 1600, 1520 cm-1.

Mass spectrum (m/z): 427 (M+).

P R I m e R 44. A mixture of 1-[4-(N-formylmethionine)phenyl]-5-[5-(methylsulphonyl)-2-thienyl] pyrazole-3 - carbonitrile (1 g) and 10% hydrochloric acid (3 ml) in methanol (15 ml) was mixed at 60aboutC for 3 hours Cooled, the mixture was filtered, and the filtrate was concentrated in vacuum. The residue was washed with ethanol and received in the crystals of 1-[4-(methylamino)phenyl]-5-[5-(methylsulphonyl)-2-thienyl]PIR - evil-3 - carbonitrided (0,89 g).

Melting point: 205-207aboutC.

IR-spectrum (nujol): 2600, 2450, 2250, 1510 cm-1.

NMR spectrum (DMSO-d6, ): was 2.76 (3H, s), to 3.33 (3H, s,), 6,77 (2H, d, J 8 Hz), 7,26 (2H, d, J 8 Hz), 7,43 (1H. D. J 3 Hz), 7,72 (1H, s), 7,78 (1H, d J 3 Hz).

Mass spectrum (m/z): 358 (M+).

The following compounds (examples from 45-1 to 45-14) were obtained analabonita - Reid.

Melting point: 189-191aboutC.

IR-spectrum (nujol): 2650, 2450, 2250, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,73 (3H, s), 6,8-7,5 (N, m).

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

2) 1-[4-(Methylamino)phenyl]-5-(4-tolyl)pyrazole-3-carbonitrided.

Melting point: 199-201aboutC.

IR-spectrum (nujol): 2600, 2450, 2250, 1610, 1520 cm-1.

NMR spectrum (DMSO-d6, ): to 2.29 (3H, s), was 2.76 (3H, s), 6,9-7,4 (N, m,), a 7.62 (2H, s).

Mass spectrum (m/z):288 (M+).

3) 1-[4-(Methylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile hydrochloride.

Melting point: 218 to 221aboutC.

IR-spectrum (nujol): 3450, 2650, 2460, 2250, 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,70 (3H, s), of 3.25 (3H, s), 5,46 (2H, s), 6,5-8,0 (N, m)

Mass spectrum (m/z): 352 (M+).

4) 1-[4-(Methylamino)phenyl]-5-[4-(methylthio)phenyl]pyrazole-3-carbonitrile - chloride.

Melting point: 113-120aboutC.

IR-spectrum (nujol): 3400, 2650, 2450, 2250, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): the 2.46 (3H, s), is 2.74 (3H, s), to 6.57 (2H, s), 6,5-7,4 (N, m).

Mass spectrum (m/z): 330 (M+).

5) 1-[4-(Methylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbon is, 250, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): is 2.74 (3H, s), was 2.76 (3H, s), 6,53 (2H, s) 6,7-7,8 (N, m).

Mass spectrum (m/z): 336 (M+), 319.

6) 1-[2-(Methylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3-carbonitrile.

Melting point: 192-193aboutWITH,

IR-spectrum (nujol): 3450, 2250, 1610, 1520 cm-1.

NMR spectrum (DMSO-d6, ): to 2.66 (3H, d, J 5 Hz), up 3.22 (3H, s), 5,33 (1H, square J 5 Hz), 6,5-8,0 (N, m).

Mass spectrum (m/z): 352 (M+).

7) 1-[4-(Methylamino)phenyl]-5-[4-(methylthio)phenyl]-3-(trifluoromethyl)pyrazole.

Melting point: 168-169aboutC.

IR-spectrum (nujol): 3400, 1610, 1535, 1500 cm-1.

The NMR spectrum (CDCl3, ): 2,47 (3H, s), 2,84 (3H, s), 6,5-7,3 (N, m).

Mass spectrum (m/z): 363 (M+).

8) 1-[4-(Methylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]-3-(trifluoromethyl) pyrazolylborate.

Melting point: 200-202aboutC.

IR-spectrum (nujol): 2725, 2600, 2450, 1600, 1520, 1500 cm-1.

NMR spectrum (DMSO-d6, ): 2,75 (3H, s), 3,26 (3H, s), 6,8-8,0 (N, m), 8,42 (2H, s).

Mass spectrum (m/z): 395 (M+).

9) 1-[4-(Methylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]-3-(trifluoromethyl) pyrazolylborate.

Melting point: 171-172about

Mass spectrum (m/z): 379 (M+).

10) 1-[4-(Methylamino)phenyl]-3-(methylsulphonyl)-5-[4-(methylsulphonyl)phenyl] pyrazolidinone.

Melting point:209-211aboutC.

IR-spectrum (nujol): 2650, 2450, 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): is 2.74 (3H, s), 3,26 (3H, s,). the 3.35 (3H, s), 6,7-8,0 (N. m).

Mass spectrum (m/z): 405 (M+).

11) 3-(Deformity)-1-[4-(methylamino)phenyl]-5-[4-(methylthio)phenyl]pyrazole.

Melting point: 128-129aboutC.

IR-spectrum (nujol): 3360, 1610, 1530 cm-1.

The NMR spectrum (CDCl3, ): 2,47 (3H, s), 2,84 (3H, s), from 6.4 to 7.2 (10H, m).

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

12) N-Methyl-1-[4-(methylamino)phenyl] -5-[4-(methylsulphonyl)phenyl] pyrazole-3-CT - boxlid.

Melting point: 187-188aboutC.

IR-spectrum (nujol): 3400, 1670, 1650, 1610, 1560, 1525 cm-1.

The NMR spectrum (CDCl3, ): of 2.86 (3H, s), of 2.92 (3H, d, J 5 Hz), 3,06 (3H, s ), a 4.03 (1H, s), of 6.5 to 8.0 (10H, m).

Mass spectrum (m/z): 384 (M+).

13) N,N-Dimethyl-1-[4-(methylamino)phenyl]-5-[4-(methylsulphonyl)phenyl]pyrazole-3 - carboxamide.

Melting point: 204-205aboutC.

IR-spectrum (nujol): 3420, 1620, 1530 cm-1.

The NMR spectrum (CDCl3, ): 2,86) 1-[4-(Methylamino)phenyl] -5-[4-(methylsulphonyl)phenyl]pyrazole-3-carboxy - MFA.

Melting point: 215-216aboutC.

IR-spectrum (nujol): 3470, 3370, 3160, 1675, 1610, 1530 cm-1.

NMR spectrum (DMSO-d6, ): 2,69 (3H, d, J 5 Hz), 3,24 (3H, s), 6,07 (1H, square J 5 Hz), 6,55 (2H, d, J 9 Hz), 7,0-8,0 (N, m).

Mass spectrum (m/z): 370 (M+).

P R I m e R 46. Ethyl-1-[4-(methylamino)phenyl]-5-[4-(methylsulphonyl)phenyl] pyrazole-3 - carboxylate obtained analogously to example 44, was introduced into a reaction similar to example 3 by the way and got in the result of 1-[4-(methylamino)phenyl] -5-[4-(metralha - nil)phenyl] pyrazole-3-carboxylic acid.

Melting point: 235-240aboutC (decomp.).

IR-spectrum (nujol): 3400, 1715, 1610, 1530 cm-1.

NMR spectrum (DMSO-d6, ): 2,69 (3H, s), 3,24 (3H, s), 6,09 (1H, s), 6,55 (2H, d J=9 Hz), 7,05 (2H, d, J 9 Hz), 7,17 (1H, s), 7,53 (2H. D. J 8 Hz), 7,89 (2H, d, J 8 Hz).

Mass spectrum (m/z): 371 (M+).

P R I m e R 47. A mixture of 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-CT - lonitrile (1 g), ameriglide (0.25 g) and nutriasia (0.24 g) in N, N-dimethylformamide (10 ml) was mixed with 105aboutC for 10 h, the Mixture was poured into ice water and the precipitate was collected, washed with water and recrystallize from a mixture of ethanol and tetrahydrofuran, resulting in crystals of 1-(4-forfinal)-5-[4-(methylsulphonyl)Fe - IO): 3150, 1655, 1620, 1600, 1510 cm-1.

NMR spectrum (DMSO-d6, ): of 3.27 (3H, s,), and 7.3 and 7.6 (7H, m), 7,95 (2H, d, J 8 Hz).

Mass spectrum (m/z): 384 (M+).

The following compounds (examples 48-1 and 48-2) were obtained analogous to example 47.

P R I m e R 48.

1) 1-(4-Forfinal)-5-[4-(methylthio)phenyl]-3-(5-tetrazolyl)pyrazole.

Melting point: 242-243aboutC (decomp.).

IR-spectrum (nujol): 1605, 1510 cm-1.

NMR spectrum (DMSO-d6, ): 2,48 (3H, s), a 7.1 to 7.6 (N, S.).

Mass spectrum (m/z): 352 (M+).

2) 1-(4-Forfinal)-5-[4-(methylsulfinyl)phenyl]-3-(5-tetrazolyl)pyrazole.

Melting point: 272-273aboutC (decomp.).

IR-spectrum (nujol): 1615, 1510 cm-1.

NMR spectrum (DMSO-d6, ): and 2.79 (3H, s), 7.3 to 7.8 for (N, m).

Mass spectrum (m/z): 368 (M+).

P R I m e R 49. A mixture of ethyl-4-[4-(formylamino)phenyl]-2,4-dioxaborinane (6 g) and 4-tortenelmitradiciokban (4.1 g) in acetic acid (30 ml) was mixed with 100aboutC for 2 h the Mixture was concentrated, and the residue was treated with 10% hydrochloric acid (10 ml) and methanol (40 ml) at 60aboutC for 2 h, the Solvent is boiled away, and the residue was dissolved in water. The resulting solution neutralizable ethanol, resulting in crystals of ethyl-5-(4-AMINOPHENYL)-1-(4-forfinal)pyrazole-3-Carbo - celata (3.4 g).

Melting point: 158-160aboutC.

IR-spectrum (nujol): 3450, 3350, 3250, 1720, 1640, 1610, 1510 cm-1.

The NMR spectrum (CDCl3, ): of 1.42 (3H, T. J7 Hz), of 4.44 (2H, square J 7 Hz), 6,5-7,4 (N, m).

Mass spectrum (m/z): 325 (M+).

P R I m e R 50. The solution nutrientrich (0.26 g) in water (0.3 ml) was added to an ice salt mixture of 1-(4-forfinal)-5-[4-(methylthio)phenyl]-3-pyrazoline (1 g), acetonitrile (1 ml), sulfuric acid (0.6 ml) and water (1.6 ml). The mixture was mixed at 0aboutC for 30 minutes the resulting mixture is added in portions to a mixture of bromide (645 mg) copper (1) bromide (582 mg) sodium, Hydrobromic acid (1.7 ml) and water (3 ml) at 80aboutC. the Mixture was mixed at 80aboutC for 30 min and extracted with toluene. The extract was washed with water, dried and evaporated in vacuum. The obtained residue was subjected to purification by column chromatography on silica gel (10 g) and the obtained crystals of 3-bromo-1-(4-forfinal)-5-[4-(methylthio)phenyl] pyrazole (0.35 g).

Melting point: 98-99aboutC.

IR-spectrum (nujol): 1600, 1510, 1680 cm-1.

The NMR spectrum (CDCl3, ): 2,48 (3H, s), of 6.49 (notitia)phenyl]pyrazole (1.9 grams) and cyanide (0.7 g) copper (1) was heated at 200aboutC for 6 h the Mixture was extracted with ethyl acetate, and the extract was concentrated in vacuum. The residue (0.95 g) was subjected to purification by column chromatography on silica gel (20 g) using elution chloroform, and the obtained crystals of 1-(4-forfinal)-5-[4-(methylthio)phenyl]pyrazole-4-carbonitrile (0.95 g).

Melting point: 122-123aboutC.

IR-spectrum (nujol): 2230, 1600, 1505 cm-1.

The NMR spectrum (CDCl3, ): 2,50 (3H, s), 7,0-7,8 (8H, m). of 8.00 (1H, s).

Mass spectrum (m/z): 309 (M+).

P R I m e R 52. A solution of bromine (0.9 g) in dichloromethane (2 ml) was added dropwise to a cooled with ice to a solution of 1-(4-forfinal)-5-[4-(methylthio)phenyl] pyrazole (16 g) in dichloromethane (10 ml). The mixture was mixed with 5aboutC for 1 h, washed with a solution of nutribiotic and water, dried and concentrated in vacuum. The residue (1.9 g) was recrystallize from ethanol and obtained as a result, the crystals of 4-bromo-1-(4-forfinal)-5-[4-(methylthio)phenyl] -pyrazole (1.3 g).

Melting point: 85-87aboutC.

IR-spectrum (nujol): 1600, 1510 cm-1.

Mass spectrum (m/z): 364, 362.

P R I m e R 53. A mixture of 1-[4-(methylthio)phenyl]-3,3-bis(methylthio)-2-propen-1-she (2.7 g) and 4-torvenyesseget who worked in ethanol. The insoluble substance was filtered, and the filtrate was concentrated in vacuum. The residue was subjected to purification by column chromatography on silica gel (25 g) using elution chloroform, and the obtained oil 1-(4-forfinal)-3-(methylthio)-5-[4-)methylthio)phenyl]PI - razole (0.73 g).

IR-spectrum (nujol): 1590, 1510 cm-1.

The NMR spectrum (CDCl3, ): 2,48 (3H, s), 2,59 (3H, s), 6,40 (1H, s), of 6.9 to 7.4 (8H, m).

The following compound (example 54) was obtained similar to example 53.

P R I m e R 54. 3-(Methylthio)-5-[4-(methylthio)phenyl]-1-(4-nitrophenyl)pyrazole.

Melting point: 71-73aboutC.

IR-spectrum (nujol): 1595, 1515, 1500 cm-1.

Mass spectrum (m/z): 357 (M+).

P R I m e R 55. A mixture of 5-(4-AMINOPHENYL)-1-(4-forfinal)pyrazole-3-carboxamide (0.27 g) and methanesulfonamide (0,63 g) in pyridine (5 ml) was mixed at 60aboutC for 5 hours, the Solvent is boiled away and the residue was dissolved in a mixture of ethyl acetate and water. The organic layer was separated, washed with water, dried and concentrated in vacuum. The residue was led from ethanol, resulting in 1-(4-forfinal)-5-[4-(methylsulfonylamino)phenyl]pyrazole-3 - carbonitrile (0,19 g).

The temperature of the UB>, ): 3,05 (3H, s), 7,1-7,5 (N, m), 10,06 (1H, s).

Mass spectrum (m/z): 356 (M+), 277,

P R I m e R 56. A mixture of 1-(2-amino-4-forfinal)-5-[4-(methylsulphonyl)phenyl] PIR - evil-3-carbonitrile (0.87 g), under the conditions (0,69 g) and callicarpenal (0.27 g) in N,N-dimethylformamide (5 ml) were mixed at 45aboutC for 19 h the Mixture was poured into water and was extracted with ethyl acetate. The extract was washed with water, dried and concentrated in vacuum. The residue (1 g) was subjected to purification by column chromatography on silica gel (15 g) using elution chloroform.

From the first eluate obtained 1-[2-(dimethylamino)-4-forfinal] -5-[4-(metralha - nil)phenyl]pyrazole-3 - carbonitrile (0.11 g).

Melting point: 200-202aboutC.

IR-spectrum (nujol): 2250, 1620, 1500 cm-1.

NMR spectrum (DMSO-d6, ): 2,11 (6N, S.), 3,21 (3H, s), 6,7-7,9 (8H, m).

Mass spectrum (m/z): 384 (M+).

From the second eluate obtained 1-[4-fluoro-2-(methylamino)phenyl] -5-[4-(metralha - nil)phenyl]pyrazole-3 - carbonitrile (0,44 g).

Melting point: 192-193aboutC.

IR-spectrum (nujol): 3450, 2250, 1620, 1530 cm-1.

NMR spectrum (DMSO-d6, ): to 2.65 (3H, d, J 3 Hz), 3,23 (3H, s), of 5.68 (1H, square J 3 Hz), 6,3-8,0 (8H, m).

Mass spectrum (m/z): 370 (M+aboutC for 4 h, the Solvent is boiled away and the residue was dissolved in ethyl acetate. The solution was washed successively with an aqueous solution of nitrobenzoate and water, dried and concentrated. The residue was recrystallize from a mixture of ethyl acetate and ethanol, resulting in crystals of 1-(4-forfinal)-3-(methylsulphonyl)-5-[4-(IU - tilsley)phenyl]pyrazole (0.54 g).

Melting point: 209-210aboutC.

IR-spectrum (nujol): 1600, 1515 cm-1.

NMR spectrum (DMSO-d6, ): 3,26 (3H, s), 3,88 (3H, s), 7.3 to 8.0 a (N, m),

Mass spectrum (m/z): 394 (M+).

The following compound (example 58) was prepared analogous to example 57.

P R I m e R 58. 3-(Methylsulphonyl)-5-[4-(methylsulphonyl)phenyl]-1-(4-nitrophenyl)pyrazole.

Melting point: 187-189aboutC.

IR-spectrum (nujol): 1600, 1530, 1500 cm-1.

Mass spectrum (m/z): 421.

P R I m e R 59. A mixture of 4-fluoro-1-[4-(methylthio)phenyl]butane-1,3-dione (2 g) and 4-tortenelmitradiciokban (1.6 g) in acetic acid (10 ml) was heated under reflux for 5 hours, the Solvent is boiled away and the residue was dissolved in ethyl acetate. The resulting solution was washed with an aqueous solution of attributableto, dried and Lesova for elution of chloroform. From the first eluate obtained oil 3-(chloromethyl)-1-(4-forfinal)-5-[4-(methylthio)Fe - Neil]pyrazole (1.3 g).

IR spectrum (film): 1600, 1510 cm-1.

The NMR spectrum (CDCl3, ): 2,44 (3H, s), with 4.64 (2H, s), of 6.49 (2H, s), of 6.8 to 7.3 (8H, m).

Mass spectrum (m/z): 332 (M+).

From the second eluate obtained oil 1-(4-forfinal)-5-4-(methylthio)phenyl-3-PIR seletracetam (0.6 kg).

IR spectrum (film): 1740, 1600, 1515 cm-1.

The NMR spectrum (CDCl3, ): 2,11 (3H, s), is 2.44 (3H, s), 5,14 (2H, s), 6,46 (1H, s), of 6.8 to 7.3 (8H, m).

P R I m e R 60. The solution acetylchloride (0,48 g) in ethyl acetate (10 ml) was added dropwise to a cooled with ice to a solution of 1-(4-forfinal)-5-4-(methylthio)phenyl pyrazole-3-ylmethylamino (106 g) and triethylamine (1 g) in ethyl acetate (50 ml). The mixture was mixed with 5aboutC for 1 h, successively washed with diluted hydrochloric acid, a solution of attributableto and water, dried and concentrated in vacuum. A mixture of the above residue (2.5 g) containing N-{1-(4-forfinal)-5-[4-(methylthio)phenyl]pyrazole-3-ylmethyl} aceta - MFA and meta-chloroperbenzoic acid (2.8 g) in dichloromethane (50 ml), mixed at room temperature throughout the night. The mixture was washed with a solution of attributableto and concentrated the} ndimethylacetamide, added ethanol and concentrated hydrochloric acid (15 ml). The mixture was heated under reflux for 7 h and concentrated to dryness. The residue was dissolved in water, then the solution is made basic with nutrigenomics and were extracted with ethyl acetate. The extract was washed with water, dried and concentrated in vacuum. The obtained residue (1.4 g) was subjected to purification by column chromatography on silica gel (100 g), using for elution of a mixture of chloroform and methanol (10: 1), and the obtained crystals of 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl]pyrazole-3-Almati - lamina (1.0 g).

Melting point: 150-152aboutC.

IR-spectrum (nujol): 3380, 3300, 1600, 1510 cm-1.

The NMR spectrum (CDCl3, ): 1,85 (2H, s), of 3.07 (3H, s), 3,99 (2H, s), to 6.57 (1H, s), 7,0-7,5 (6N, m), 7,87 (2H, d, J 8 Hz).

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

1. Derivatives of pyrazole of the General formula

< / BR>
where R1phenyl, possibly substituted by 1-2 substituents selected from the group consisting of lower alkyl, halogen, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkyl, sulfonyloxy, hydroxy, nitro, amino, lower alkylamino, lower dialkylamino, lower alkanolamine, lower alkylsulfonyl, 1-3 halogen atoms or lower alkanoyloxy, carboxypropyl, lower alkoxycarbonyl, carbarnoyl, possibly substituted by 1 to 2 substituents, selected from the group consisting of lower alkyl, carboxy(lower)alkyl, cyclopropyl, phenyl and hydroxy, lower alkanoyl, possibly substituted lower alkoxygroup, pyrrolidinylcarbonyl, N-methyl-piperazinylcarbonyl, lower alkanolamine, lower alkoxycarbonyl, lower alkylsulfonyl, cyano, halogen, lower alkylthio, lower alkylsulfonyl or tetrazolyl;

R3phenyl, substituted lower alkyl and/or hydroxy, lower alkylthio, lower alkylsulfonyl, lower alkylsulfonyl, halogen, amino, lower alkylamino, lower alkanolamine, lower alkylsulfonyl, lower alkyl(lower alkanoyl)amino, lower alkoxy, cyano, lower alkanoyl, or thienyl, substituted lower alkylthio or lower alkylsulfonyl provided that when R2means carboxypropyl or lower alkoxycarbonyl or trihalomethyl, or R3means phenyl, substituted lower alkylthio, lower alkylsulfonyl, lower alkylsulfonyl, amino, lower alkylamino, lower alkanolamine, lower alkylsulfonyl, lower alkyl(lower alkanoyl)amino, hydroxy, € phenyl, possibly substituted lower alkylthio, lower alkylsulfonyl, hydroxy, lower alkylsulfonate, nitro, amino, lower alkylamino, lower dialkylamino, lower alkanolamine, lower alkylsulfonyl or lower alkyl(lower alkanoyl)amino,

or their pharmaceutically acceptable acid additive salt.

2. Connection on p. 1, where R2hydrogen, methyl, substituted amino, lower dialkylamino or lower alkanoyloxy group, carbarnoyl, possibly substituted by 1 to 2 substituents, selected from the group consisting of lower alkyl, cyclopropyl, phenyl and hydroxy, lower alkanoyl, possibly substituted lower alkoxygroup, pyrrolidinylcarbonyl, lower alkanolamine, N-methylpiperazine, lower alkoxycarbonyl, lower alkylsulfonyl, cyano, halogen, lower alkylthio, lower alkylsulfonyl, or tetrazolyl.

3. Connection on p. 2, where R3phenyl, substituted lower alkylthio, lower alkylsulfonyl or lower alkylsulfonyl, or thienyl, substituted lower alkylthio or lower alkylsulfonyl.

4. Connection on p. 3, where R3phenyl, substituted lower alkylthio, lower alkylsulfonyl or lower alkylsulfonyl.

5. Connection on p. 4, where Rthe th lower alkoxy, R2methyl substituted by 1-3 halogen atoms, R3phenyl, substituted lower alkylsulfonyl or lower alkylsulfonyl.

7. Connection on p. 1, which has anti-inflammatory, analgesic and antithrombotic action.

Priority signs:

22.09.89 when R1phenyl, substituted by halogen atom, R2is hydrogen, methyl, substituted lower dialkylamino, 3 halogen atoms, lower alkoxycarbonyl, carboxypropyl, carbarnoyl, di(lower alkyl)carbamoyl, cyano, lower alkanoyl, possibly substituted lower alkoxygroup, R3phenyl, substituted lower alkylthio or lower alkylsulfonyl.

12.04.90 when R1phenyl, possibly substituted by 1-2 two substituents selected from the group consisting of lower alkyl, halogen, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylsulfonate, hydroxy, nitro, amino, lower alkylamino, lower dialkylamino, R2hydrogen, methyl, substituted dialkylamino, 3 halogen atoms, carboxypropyl, lower alkoxycarbonyl, carbarnoyl, di(lower alkyl)carbarnoyl, cyano, lower alkanoyl, possibly substituted lower alkoxy, lower alkylsulfonyl, R3is phenyl, substituted by halogen, lower Alky the Chille alkylsulphonyl, or trihalomethyl, R3phenyl, substituted lower alkylthio, lower alkylsulfonyl or lower alkylsulfonyl.

 

Same patents:

The invention relates to a simple ester of (thio)-morpholinyl and piperazinil-alkyl phenols of the formula

(I) their salts accession acids and their stereochemical isomeric forms, while Het is a heterocycle of the formula

Ror< / BR>
R6is hydrogen, C1-C4-alkyl, halogen, actigraphy, trifluoromethyl, cyano, C1-4-alkyloxy-FROM1-4-alkylthiophene,1-4-alkylthio (alkylsulfonyl)1-4-alkylsulfonyl,1-4-allyloxycarbonyl,1-4-alkylcarboxylic or aryl;

R7and R8each independently is hydrogen or C1-4-alkyl;

R9is hydrogen, halogen, amino, C1-4-alkyl, trifluoromethyl or aryl;

R10is hydrogen, halogen, amino or nitro-group;

R11is hydrogen, C1-4-alkyl, C1-4-alkyloxyalkyl, WITH1-4the alkyl or aryl-C1-4-alkyl;

n is an integer from 1 to 4 inclusive;

R1and R2each independently is hydrogen, C1-4-alkyl or halogen;

R3is hydrogen, halogen, cyano-C1-4-alkyloxy, aryl or-СОOR4and R4is hydrogen, C1-4-alkyl, aryl-C1-4-alkyl, C3-6-cycloalkyl-C1-4-alkyl, C3-5-alkenyl,3-5-quinil or1-4-alkyloxy-C1-4-alkyl, or R3is a radical of the formula

or< / BR>
R12and R13each independently is hydrogen, C1-4the alkyl, aryl or aryl-C1-4-alkyl;

each aryl is phenyl, optionally substituted by one or two substituents, each independently selected from halogen, C1-4-alkyl, trifloromethyl,1-4-alkyloxy or actigraphy

The invention relates to new derivatives of 1-phenyl-3-azabicycloalkanes-2-ones, to a method for producing them, to pharmaceutical compositions containing them and to their use as therapeutic agents

The invention relates to new pyridazinyl, derivatives which have the General formula:

(1) where one or two carbon atoms of methylene groups in the residue-NX - can be substituted by alkyl WITH1-C4, alkoxygroup1-C4or two carbon atom of the methylene groups of the above-mentioned residue can be connected by bridge with alkane(C2-C4)delovym radical; X represents CH or a nitrogen atom; each of m and n, independently of one another, denotes 1, 2, 3, and the sum m+n is 3, 4 or 5; R1denotes a hydrogen atom, alkyl WITH1-C4the halogen atom; each of R2and R3independently denotes a hydrogen atom or alkyl WITH1-C4; Аlк denotes alkane(C1-C4)diyl, each of R4and R5independently denotes hydrogen atom or halogen atom, or WITH1-C4-alkyl, and Неt denotes the group of one of formulae

where R6denotes a hydrogen atom, alkyl (C1-C6), oxyalkyl(C1-C6), cycloalkyl(C3-C6), phenyl or amino; each of R7independently denotes a hydrogen atom, alkyl (C1-C6), cycloalkyl(C3-C6), phenyl or trifluoromethyl, and their salts or a stereochemical isomeric form

The invention relates to new biologically active compounds derived from 4-oxo-1,4-dihydropyrimidin having antiallergic activity, which can find application in pharmaceutical industry and medicine

The invention relates to the production of new proizvodnyh of thiazolidine that are used in pharmaceutical compositions

The invention relates to chemical-pharmaceutical industry, namely to new biologically active compounds on the basis of which can be created medicines that possess immunostimulating action

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The invention relates to organic chemistry, and in particular to methods obtain 1-ethyl-6-fluoro-7-(piperazinil-1)-4-oxo-1,4-dihydro-3-quinoline-carboxylic acid (norfloxacin) formula 1

which is a synthetic antibiotic with a broad spectrum of antibacterial activity, is among the five most active fluoroquinolones (ciprofloxacin, pefloxacin, norfloxacin, enoxacin, ofloxacin) and used as an antibiotic of the fourth generation

The invention relates to new indole derivative of General formula

I where R1hydrogen or C1-4-alkyl;

R2hydrogen or C1-4-alkyl;

R3hydrogen or C1-3-alkyl,

or their pharmaceutically acceptable salt, or solvate having NC1-like receptor antagonistic activity

The invention relates to new derivatives of azetidine General formula:

O-R7 (I) where a nitrogen atom or the group-CH-, or C-HaI, where HaI, a chlorine atom or fluorine;

R1lower alkyl or cycloalkyl, lower halogenated or phenyl substituted mono - or Diptera;

R2, R3and R5the same or different and signify hydrogen or lower alkyl;

R4hydroxyl, amino, aminoalkyl, alkylamino, dialkylamino, pyrrolyl-1 or pyrrolidinyl-1, acylaminoalkyl, trifurcated;

R6hydrogen or amino group,

or

A and R1together form a group-O-CH2-and in this case have a chiral center configuration R or S,

R7hydrogen or lower alkyl,

or their pharmaceutically acceptable salts

The invention relates to new derivatives of intellipedia General formula

where R1phenyl substituted by substituents selected from the group consisting of lower alkyl, hydroxyl, protected hydroxyl, halogen or lower alkoxy,

And lower alkylen,

In the lower albaniles, or their pharmaceutically acceptable salts which exhibit anti-allergic effect

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The invention relates to medicine, specifically to antisecretory and antiulcer drug
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