Derivatives of thiourea or their pharmaceutically acceptable salts, pharmaceutical composition and method for inhibition of reverse transcriptase of human immunodeficiency virus

 

(57) Abstract:

Usage: in medicine and biology. The invention is a derivative of thiourea of the formula I or their pharmaceutically acceptable salts (R5R6R8)C - CH(R9) - NH - C(=S) - OTHER1where R1- 5-6-membered heterocycles containing nitrogen, sulfur, unsubstituted or substituted alkyl (C1- C4, alkoxy, C1- C3, CN, OH, CH3S, NO2, CF3, halogen; R5- aryl, cycloalkyl, heterocycle; R6is hydrogen, methyl; R8and R9is independently hydrogen or methyl, or R8and R9together with the carbon atom to which they are attached, cyclopropyl or cyclobutyl, or R6and R8together with the carbon atom to which they are attached, cyclopropyl; a pharmaceutical composition having inhibitory activity against reverse transcriptase of human immunodeficiency virus, comprising as active principle an effective amount of the derivatives of formula I. 7 tab., 4 C. and 16 h.p. f-crystals.

The invention relates to the compounds and their pharmaceutically acceptable salts and methods for treating HIV infections and related viruses and/or treatment of syndrome acquired immuno is soedineniya, and to methods of using such compounds as such or in combination with other agents for the treatment and inhibition of AIDS virus infection from HIV.

Suppose that a retrovirus called human immunodeficiency virus (HIV) is the agent causing complex disease called acquired immunodeficiency syndrome (AIDS), and refers to members of lentiviruses family of retroviruses (M. A. Gonda, F. Wong-Staal. N. R. G. Gallo. Gomologichnosti sequences and morphological similarity of pathogenic lentiviruses: WLTC III (HTL V (III) and virus Vishnu. Science, 227, 173, 1985; P. Sonigo, N. Alizon and other Nucleotide sequence of lentivirus Vishnu, communication with the AIDS virus. Cell, 42, 369, 1985). The HIV virus, also called the AIDS virus, previously known under the names of AUTHORITIES (LAY), WLTC-III, ARV, and now referred to as HIV-I. Other closely related variants of HIV-I, including HIV-II and SIV (human immunodeficiency virus monkeys), their mutants.

Complex disease AIDS includes progressive destruction of the immune system and degeneration of the Central and peripheral nervous system. The HIV virus, probably mainly attacks the T-cells helper T-lymphocytes and OCT-bearing T-cells and other human cells, such as routename virus. T-cells helper quickly destroyed, their number in the human body is reduced to such an extent that B-cells, along with other T-cells, usually stimulated T-cells assistants, cease to function normally or to produce enough lymphokines and antibodies to destroy the virus-invader or other aggressive microbes.

Although the virus itself is not necessarily a cause of death, however, he holds to such severe damage of the immune system that the person ceases to resist other diseases, such as herpes, Pneumocistis carini, toxoplasmosis, cytomegalovirus disease, sarcoma Canesi, lymphomas associated with Epstein-Barr among others. These secondary infections, as usual, is subjected to a separate treatment with other medicines. In the early stages people affected by HIV live like no symptoms or minor their manifestation, but remain permanently infected. In the later stages of the disease the person is suffering from mild depression of the immune system with various symptoms such as weight loss, malaise, fever, and swelling of the lymph nodes. All these symptoms are called syndrome DCU.

In all cases infected with the AIDS virus are believed to remain stable infectious to others. In addition, AIDS and associated with AIDS complex after some time lead to death.

Description of the mechanism by which the virus infects the host, see (R. Yarchoan, and S. Broder. The advent of antiretroviral therapy of acquired immunodeficiency syndrome and related disorders. New England Journal of Medicine, 316, 557-564, February 26, 1987).

Significant efforts have been aimed at combating HIV through inhibition of HIV reverse transcriptase required for virus replication (y Merluzzi, etc. Inhibition of replication of HIV-I using non-nucleoside reverse transcriptase inhibitors, Science, 25, 1411, 1990). For example, the currently used this drug, as AZT, an inhibitor of viral reverse transcriptase (U.S. patent N 4724232). Unfortunately, many known compounds are toxic, lack of bioavailability or small resistance in vivo, viral resistance, or a combination of both.

Thus, the purpose of the invention is to provide compounds and their pharmaceutical acceptable salts for the inhibition and/or treatment of HIV is estimated at the value for the inhibition and/or treatment of infection by HIV and the treatment or inhibition of acquired immunodeficiency syndrome.

Another goal is to create methods of inhibiting and/or treating HIV infection and the resulting acquired immune deficiency syndrome.

Other aims, characteristics and advantages for professionals will become apparent from the following description and claims.

By the present invention are compounds applicable for the inhibition and/or treatment of HIV and AIDS either in pure form or in the form of pharmaceutically acceptable salts of the components of the pharmaceutical compositions in combination with other antiviral agents, immunomodulators, antibiotics or vaccines, and without them. In addition, the disclosed methods of treatment, methods of inhibiting HIV replication and methods of treating or inhibiting HIV in humans.

Compounds used in the methods of the present invention are derivatives of thiourea of General formula I

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where

R1- benzothiazole, benzimidazole, imidazole, pyrazine, pyrazolyl, pyridyl, pyridazinyl, chinoline, nitrosell, thiazolyl, thiadiazolyl or triazolyl, which may not necessarily be replaced by substituents selected from the following group: C1-C4- alkyl, C1-C3- alkoxy, the Lil, thienyl, benzothiazolyl, benzoxazolyl, naphthyl, indolyl, cyclohexenyl, some of which may be substituted up to five positions by substituents selected from the following groups: amino, azido, cyano, nitro, hydroxy, halogen, methyl, vinyl, ethinyl, trifluoromethyl, C1-C3- alkoxy, phenoxy, phenyl, methylenedioxy, a group of the formula-C(=0)R, where R represents a C1-C3- atsetamidometil, carboxamidates;

R8and R9independently represent hydrogen or methyl, or R8and R9together with the carbon atom to which they are attached, form cyclopropyl or cyclobutyl;

R6represents hydrogen or methyl, or R6and R8together with the carbon atom to which they are attached, form cyclopropyl,

or their pharmaceutically acceptable salts, provided that the compound of formula I is a compound of formula

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where

Rdrepresents hydrogen, halogen, hydroxy, alkyl or alkoxy,

or R1is not a group

< / BR>
where

Reand Rfrepresent lower alkyl,

or their salts.

Preferred derivatives of thiourea of General formula I are: the om)pyridyl]thiourea,

N-(2-CIS-vinylcyclopropyl)-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(CIS-2-pyridyl)cyclopropyl]-N'-[2-(5-bromo)Pirelli]thiourea,

N-[2-(CIS-2-pyridyl)cyclopropyl]-N'-[2-(5-chloro)Pirelli]thiourea,

N-{ 2-(CIS-2-(6-fluoro)pyridyl] cyclopropyl}-N'-[2-(5-bromo)pyridyl] thiourea,

N-{ 2-(CIS-2-(6-fluoro)pyridyl] cyclopropyl} -N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[CIS-2-(6-methoxy)pyridyl]cyclopropyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{ 2-(CIS-2-(6-methoxy)pyridyl]cyclopropyl}-N'-[2-(5-chloro)Pirelli] thiourea,

N-{ 2-[CIS-2-(6-ethoxy)pyridyl)cyclopropyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{ 2-[CIS-2-(6-ethoxy)pyridyl] cyclopropyl} -[2-(5-chloro)pyridyl] thiourea,

N-[2-(3-methoxyphenyl)ethyl]N'-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2-ethoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2-ethoxyphenyl)ethyl]-N'-[2-(5-[chloro)pyridyl]thiourea,

N -[2-(2,6-differenl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[2-(4-trifluoromethyl)N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[3-(6-[chloro)pyridazinyl]thiourea,

N-[2-(2-fluoro-6-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2-fluoro-6-methoxyphenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2-chlorophenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(2-chlorophenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea,

N-[2-(2-chlorophenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2-chlorophenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(3-chlorophenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(3-chlorophenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea,

N-[2-(3-chlorophenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(3-chlorophenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]Timofeevna,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[3-(6-chloro)pyridazinyl]thiourea,

N-[2-(2,5-acid)et-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-trifluoromethyl)pyridyl]thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-ethyl)pyridyl]thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-methyl)pyridyl]thiourea,

N-{2-[2-(6-methoxy)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(6-methoxy)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[2-(6-ethoxy)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(6-ethoxy)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(6-fluorine)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(6-fluorine)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[2-(3-fluorine)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(3-fluorine)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[2-(6-chloro)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(6-chloro)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{ 2-[2-(3-methoxy-6-fluoro)pyridyl] ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{ 2-[2-(3-methoxy-6-fluoro)pyridyl] ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{ 2-[2-(5-ethoxy-6-fluoro)pyridyl] ethyl} -N'-[2-(5-bromo)pyridyl]thiourea,

N-{ 2-[2-(5-ethoxy-6-fluoro)pyridyl] ethyl} -N'-[2-(5-chloro)pyridyl]thiourea,

N-{ 2-[2-(3-ethoxy-6-fluoro)pyridyl] ethyl} -N'-[2-(5-bromo)pyridyl is DIL]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(3,6-debtor)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2,6-debtor-3-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea

or their salts.

In addition, the invention relates to a pharmaceutical composition having inhibitory activity against reverse transcriptase of human immunodeficiency virus, comprising the active principle and targeted supplements, and as the active agent composition contains an effective amount of a derivative of thiourea of formula I or its pharmaceutically acceptable salt.

As mentioned above, the invention includes pharmaceutically acceptable salts of the compounds defined by the above formula I. Although generally neutral, specific compounds may possess a sufficiently acidic, a sufficiently basic, or both functional groups which could react with any of a number of non-toxic inorganic bases and non-toxic inorganic and organic acids with the formation of pharmaceutically acceptable salts. Acids commonly used for the formation of salts of the acid are inorganic acids such as hydrochloric acid, Hydrobromic acid, Jodi ursulaquelle, methansulfonate acid, oxalic acid, n - bromophenylacetate, carbonic acid, succinic acid, citric acid, benzoic acid, acetic acid, etc. are Examples of such pharmaceutically acceptable salts thus include sulfate, persulfate, bisulfate, sulfite, bisulfite, phosphate, monohydratefast, dihydrophosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, kaprilat, acrylate, formate, isobutyrate, caproate, heptanoate, propionate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, Butin-1, 4-diat, hexyne-1,6-diet, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, ecological, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, hydroxybutyrate, glycolate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate, etc. To the recommended pharmaceutically acceptable salts formed by addition of acids include salts with mineral acids such as hydrochloric acid and Hydrobromic acid, and organic acids, such as maleic acid and methanesulfonamide acid.

Salts formed DOB bicarbonates and the like, ammonium, alkali or alkaline earth metal. Thus, the base used to produce salts of the present invention include sodium hydroxide, potassium hydroxide, ammonium hydroxide, potassium bicarbonate, calcium hydroxide, calcium carbonate, etc.

Pharmaceutically acceptable salts of the invention are typically formed by reaction of the compound of the invention with an equimolar or excess amount of acid or base. The reagents are usually mixed in a common solvent such as diethyl ether or benzene for salts with acids and water or alcohols for salts with bases, resulting salts are precipitated from solution in the range from one hour to several days and can be isolated by filtration or other conventional method. Salts of the compounds of the invention after administration into the connection itself, which are predicatble. All predicate administered in a quantity sufficient for the formation of an effective amount of the compound in contact with the virus and interacting with them (e.g., by inhibiting its replication).

Compounds of the present invention, in addition, include the racemates, racemic mixture and the individual enantiomers or diastereomers, optically active diastereomers of compounds of formula I are considered as part of the present invention and such optically active isomers can be obtained from their optically active precursors of these methods or separation receices mixtures. Separation may be feasible in the presence of the separating means by chromatography, fractional crystallization, or a combination of these methods, well known to specialists. Additional details about the division can be found (Jaqgues and other Enantiomers, racemates, their separation. John Willy and sons, 1981).

Compounds of the present invention or their predecessors get methods known in the art. More specifically, the compounds of formula I are synthesized according to the procedures illustrated in the following schemes I, II and III and the subsequent explanation of the schemes.

According to scheme I, the derivative isothiocyanate (1) reacts with the amino group of (2) in a molar ratio of about 1:1 and an inert organic solvent such as N,N-dimethylformamide with stirring for 1-72 h in the temperature range 0-150oC. the Applicable time and temperature depend on the reaction of the individual reagents. The product of the shares, as scheme I.

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Scheme III illustrates the manner analogous to the method described in J. Org.Chem., so 49, 4123, 1984), given here as a reference.

Compounds used as initial products in the synthesis of compounds of the present invention, well-known, if they are not commodity products, and easily synthesized by standard methods commonly used by chemists organically.

Further notes on the synthesis of compounds of the invention can be found in the works (Organic Synthesis, 45, 69, 1965; Journal of the American Cremical Society, 79, 1236, 1957; Organic Synthesis, 20, 69, 1940; Synthesis, may 1983, S. 391), given here as a reference.

Tests of the above compounds of formula I showed their activity as inhibitors of HIV. Not wishing to be bound by theory, however, believe that the compounds act as inhibitors of reverse transcriptase, resulting inhibit viral replication.

Below is a description of the test systems used for analyzing the effectiveness of the compounds against HIV.

Tests A, B, C and D(HTT).

Cells MT-4 in the medium RPMI-1640. 5% PST (fetal calf serum), penicillin /streptomycin brought to concentration the cell, that makes 2 of 104cells on the cell. The test compound is prepared in the form of a mixture with a concentration of 10 mg/ml in DMSO and stored at -20oC. the Compound in DMSO is diluted with medium containing 10% DMSO, in series with a 10-fold dilution and obtain solutions with concentrations of 1, 10 and 100 mg/ml Further dilution to concentrations of 400, 40, 4, and 0.4 mg/ml is carried out in the environment contained in the microplate. 50 ml of solution with a concentration of 400, 40, 4, and 0.4 mg/ ml using a multichannel pipette, transferred into a containing cells microplates (final concentration of 100, 10 and 1 mg/ml). Finally, in each cell make 50 ml acetic suspension (with playback of multichannel pipettes Eppendorf). Each tablet has at least six cells with the following: test And HIV-6, test - HIV (II), the test of the C - virus SIV, test D - no virus, no drugs (control virus) and six cells without virus (control environment). The tablet is placed in a plastic bag and incubated for six days in an atmosphere of CO2. In each cell of the tablet make 50 ml of XTT - 2,3-bis-(2-methoxy-4-nitro-5-sulfonyl)-5-[(phenylamino)carbonyl] -2H-tetrazolium hydroxide(1 mg/ml 0.01-0.02 mm N-methylpentane of metasulfite. After 6 h incubation in almost the current density is determined at a wavelength of 450 nm and a reference wavelength of 650 nm. The percentage reduction of cytotoxicity caused by a viral infection, calculated according to the following equation:

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Test E, F, G, H: HIV-1RT, HIV-2RT, SIV-RT, no virus.

Cells MT-4/H9 lead lo a concentration of 2 to 105cells/ ml in medium (RPMI-1640, 5% PST, penicillin/streptomycin) and seeded in microplates (96 wells/plate) in the amount of 100 ml of cell suspension to a cell that gives 2 104cells/cell. The test compound is brought to a concentration of 10 mg/ml in DMSO (original solution, stored at -20oC). Dissolved in DMSO, the compound was diluted 25 times in an environment with obtaining a concentration of 400 mg/ml Further dilution is carried out in microplates up to concentrations of 40 and 4 mg/ml

Multichannel pipette in "containing cells in the microplate make 50 ml of dilutions 400, 40 and 4 mg/ml (final concentration of 100, 10 and 1 mg/ml).

Finally, in each cell make 50 ml of viral suspension (reproducing multichannel pipette Eppendorf): test E - HIV-1 test F-HIV-2, test G-SIV, test H-no virus.

Each tablet has at least four cells without drugs, but with the virus (virus control) and two cells without virus (control environment). the posadochkuju liquid (10 ml) from each cell in a multi-channel pipette is transferred to a new microplate in which each cell is added 40 ml of DVB (50 mm Tris-HCl with a pH of 7.6, 35 mm KCl, 4 mm DTT, 1 mm add 1.3% of Triton X-100). Add 50 ml of RT reaction mixture (10 ml of the supernatant liquid of the culture, 40 ml of DVB and 50 ml of the reaction mixture, which gives a final concentration of 100 mm Tris-HCl with a pH of 7.6, 100 mm KCl, 4 mm MgCl2, 4 mm DTT, 275 mg/ml ICA/ml, 5 mg (rA)n(dT)12-1/ml and 0.3 mm 3HdTTP (specific activity 18000 cpmpmol) gives a final volume of 100 ml per cell. After 60 min incubation fully analyzed volume is transferred through the cell collector filter on the pillow, pre-humidified 5% TCA. The filter was washed with 5% TCA and once rinsed with ethanol. After drying the filter bags (30 min at 60o(C) each filter element (96 on the pillow) is extracted, placed in vessels to count, add 2 ml of scintillation fluid and count (1 min) or filter the pillow entirely placed in a plastic bag, add 10 ml of scintillation fluid and count "Beckman, Metaplast" count for filter bags. The percentage reduction of RT activity is determined by comparison of the RT-activity for control of the virus with RT-activity specific to each dilution of the connection.

Test 1 [HIV-RT(rAdt)].

Connections have a direct ingibiruyushchee 200000 cpm).

100 mm Tris-HCl c pH of 7.6, 100 mM KCl, 4 mm MgCl2, 4 mm DTT, 275 mg/ml BSA, 0.5 mg (ha)n(dT)12-18and 0.3 mm H3=dTTR (specific activity 18000 cpm mol). After 60 min incubation with 40 ml of duplicates is applied in the form of spots on paper discs and washed with 5% TCA. After rinsing paper disk benchmark their dried and are counted in scintillation fluid.

Table. 1-6 illustrate the activity of the compounds in the above tests. Figures show the percentage of inhibition.

The features of the invention also include a method of introducing a person in need, compounds of the invention or their pharmaceutically acceptable salts for the treatment or inhibition of HIV/AIDS with inhibition of viral replication of HIV/AIDS in infected human cells and inhibition of the development of AIDS in humans infected with HIV/AIDS-virus, or antibodies to HIV/AIDS-virus.

The present invention also discloses compounds of the invention and their salts intended for use in the treatment of the above symptoms, and the use of such compounds for the preparation of pharmaceutical compositions for the treatment of these symptoms.

In General, for a given acceptable treatment effectne. The introduction can be performed by any acceptable means, including oral, rectal, Natalino, topically ( including boccalino and sublingual), vaginal or parenteral (including subcutaneous, intramuscularly, intravenously or intradermally). Of course, the preferred route of administration may vary depending on, for example, the condition, age and weight of the recipient.

Input components can be used as drugs in combination with other therapeutic agents (other antiviral, antibacterial compounds, and the compounds used for the prevention of emerging secondary or opportunistic diseases associated with HIV/AIDS), such as AZT, ddI, ddC, 9-{[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl}goatin, 9-(2-hydroxyethoxymethyl)guanine (acyclovir), 2-amino-9-(2-hydroxyethoxymethyl)purine, suramin, ribavirin, submenuarray (HPA-23), interferon, such as interferon, interleukin II, and phosphonoformate (foscarnet), or in combination with other immune modulators, including transplant of bone marrow or lymphocytes, or other drugs such as levamisole or thymosin able to increase the number of lymphocytes and/or their function.

To p the research against HIV-1 in CEM cells by the method of Prichard u Shipman (Anfiviral Researh, 14, 181-206, 1990). Peak synergism is observed at 0.5 mg/ml of the compounds of formulas and 0.005 μg/ml AZT.

Although the components used can be entered individually, however, we recommend that they view as part of a pharmaceutical composition. The compositions of the present invention include at least the input component defined above, in a mixture with one or more acceptable carriers and possibly other medical components. The carrier(s) must be "acceptable" in the sense of compatibility with other components and not for harmful actions on the recipient.

Such compositions exclude formulations suitable for oral, rectal, analnogo, local (including buckaloo and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous and intradermal) administration. The formulations may be presented in unit dosage forms such as tablets or capsules deferred action, which can be prepared with known pharmaceutical methods.

Such methods include the stage of mixing to be the introduction of components with a carrier consisting of one or more additional com is the teli or finely milled media or so, and others followed, if necessary, shaping the product.

The compositions of the present invention suitable for oral administration may be presented as discrete units such as capsules, starch wafers or tablets, each of which contains a defined amount of the active component, in the form of a powder or granules; as solution or suspension in an aqueous liquid or non-aqueous liquid or in the form of a liquid emulsion of the type oil-in-water type or water-in-oil, bolus, etc.

With regard to compositions for oral administration (e.g. tablets and capsules), the term "acceptable carrier" refers to the conventional excipients, such as binders such as syrup, gum acacia, gelatin, sorbitol, tragakant, polyvinylpyrrolidine (povidone), methylcellulose, ethylcellulose, sodium carboxymethyl cellulose, hypromellose, sucrose and starch, fillers and carriers, for example corn starch, gelatin, lactose, sucrose, microcrystalline cellulose, kaolin, mannitol, dicalcium phosphate, sodium chloride and alginic acid, disintegrators, such as microcrystalline cellulose, corn starch, nitroglycol starch, alginic sour is ALK, waxes, oils and colloidal silica. Can also be used flavouring agents such as peppermint, oil of Grushenka, cherry flavoring, etc., it May be desirable to add a dye to give a dosage form more pleasing aesthetic appearance and to facilitate the identification of the product.

Tablets can be manufactured by extrusion or molding, possibly with one or more additional components. Molded tablets can be obtained by compressing in a suitable machine the active ingredient in a free flowing condition, for example, in the form of powder or granules, possibly in a mixture with a binder agent, lubricant, inert diluent, preservative, surface-active agent or dispersing agent. Molded tablets can be obtained by molding in a suitable machine a mixture of the powdered compound moistened inert liquid diluent. The tablets may be coated or grooves, tablets can be prepared in such a way as to provide slow or controlled-release from the active component.

Formulations suitable for topical administration, include lozenges, cloudie active ingredient in an inert basis, such as gelatin and glycerin, sucrose, or gum acacia, as well as the compositions for rinsing of the mouth, including be the introduction of a component in an acceptable liquid carrier.

Formulations suitable for the local contribution in the skin, can be represented by ointments, creams, gels and pastes containing the active subject introduction component and a pharmaceutically acceptable carrier. An example of the system for the local introduction presents a transdermal patch containing subject to the introduction of a component.

Compositions for rectal injection can be represented by candles on an appropriate basis, for example cocoa butter or a salicylate.

Compositions for analnogo introduction, in which the carrier is a solid include a coarse powder with a particle size of, for example, in the range of 20-500 μm, administered by inhalation, for example by rapid inhalation through the nasal passage from a container of the powder when it is present close to the nose. Acceptable compositions in which the carrier is a liquid that presents, for example, naselenie aerosols or naselenie drops in the form of oil or aqueous solution of the active component.

Formulations suitable for vaginal administration, can be of the active ingredient such carriers, which are known to be suitable for such cases.

Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffering agents, bacteriostatic and soluble substances, which give the composition isotonicity with the blood of the intended recipient, and aqueous and non-aqueous sterile suspensions that can include suspendresume tools and thickeners. The formulations may be presented in a single dose or in the form of a container with multiple doses, for example in the form of sealed vials and vessels, and can be stored in dried by freezing (liofilizirovannom) condition requiring only the addition of sterile liquid carrier, for example water for injection immediately before use. Improvised solutions and suspensions for injection can be obtained from sterile powders, granules and tablets of the previously described type.

The recommended single dosage compositions include compositions containing the daily dose, a daily curioso according to the above definition or their appropriate share of the active component.

Antiviral compounds form protivovirusnogo connection can be effective for the purposes of disinfection. It is recommended that such solutions also contained a detergent or other bleaching agent. The solutions can be used to disinfect objects such as glass equipment, dental and surgical instruments and surfaces, such as walls, floors and tables, in those places, where it is important to maintain sterile conditions, for example in hospitals, places, cooking, etc.

In the implementation of the method of treating or inhibiting HIV and/or AIDS antiviral agent can be introduced in a single daily dose or as multiple doses per day. The treatment regimen may require the introduction for an extended period of time, for example within a few days, months or years. The number entered with the dose, or the total entered amount depends on such factors as the nature and severity of the infection, the age and General health of the patient, tolerant and patient, and the microorganism or microorganisms involved in the infection, the virus connection.

The following examples represent typical pharmaceutical compositions containing the compounds relating to the present method. The compositions of J. Sol. The examples are given only for illustrative purposes and in no way are intended to limit the scope of the invention.

Composition 1.

Hard gelatin capsules are prepared using the following components (mg/capsule:

The proposed connection - 1250

The dried starch - 200

Magnesium stearate - 10

These components are mixed and the mixture fill hard gelatin capsules in the amount of 460 mg.

Part 2.

Tableted composition of gain, using the above components, mg/tablet:

Connection - 250

Microcrystalline cellulose - 400

Silicon oxide, dust - 10

Stearic acid - 5

Magnesium stearate - 10

The components are mixed and pressed into tablets each weighing 675 mg.

Part 3.

Get a spray solution containing the following components:

Connection - 0,25

Ethanol - 29,75

The propellant 22 (Chlorodifluoromethane) - 70,00

The active compound is mixed with ethanol and the mixture added to a portion of the propellant 22, cooled to -30oC and transferred to a filling device. Then the stainless steel container filled with the required number and diluted with the remainder of the propellant. Poirit 60 mg of the active component, produced from the following components, mg:

Connection - 60

Starch - 45

Microcrystalline cellulose - 35

Polyvinylpyrrolidone (as 10% solution in water) - 4

Natrocarbonatite - 4,5

Magnesium stearate and 0.5

Talc - 1

The active ingredient, starch and cellulose are passed through sieve No. 45 mesh (Art. USA) and thoroughly mix. The solution of polyvinylpyrrolidone is mixed with the obtained powder and then passed through sieve No. 14 mesh (Art. USA). The resulting granules are dried at 40-60oC and sieved through sieve No. 18 mesh (Art. USA). To the pellet add natrocarbonatite, magnesium stearate and talc, previously passed through sieve # 60 mesh (Art. USA), and after mixing pressed into teletrauma machine to obtain tablets each weighing 150 mg

Part 5.

Capsules, each containing 80 mg of the drug is obtained from the following components, mg:

Connection - 80

Starch - 59

Microcrystalline cellulose - 59

Silicone fluid - 2

The active ingredient, cellulose, starch and magnesium stearate are blended, passed through sieve No. 45 mesh and the obtained mixture in an amount of 200 mg fill hard gelatin capsules.


Connection - 225

Glycerides of saturated fatty acids - 2

The active ingredient is sifted through sieve # 60 mesh (Art. USA) and suspended in the glycerides of saturated fatty acids, previously melted using the minimum number of required heat. The mixture is then poured into the form for candles nominal amount of 2 g and allowed to cool.

Part 7.

Composition for intravenous administration is obtained from the following components:

Connection, mg - 100

Isotonic saline solution, ml - 1000

The solution of these components is injected at a rate of 1 ml/min to a mammal in need of treatment.

You must specify that in addition to the above components, the compositions of the present invention can include other agents commonly used in these cases taking into account specific type of composition.

The following additional examples illustrate the compounds of the invention and methods of synthesis. Examples in no way limit the scope of the invention and should not be considered in this aspect.

The toxicity of the compounds of the present invention investigated, determining the concentration of compound that reduces zhiznesposobnoye presented in table. 7.

The data presented in the table.7, show that the compounds of the present invention are non-toxic.

Below are examples that illustrate how to obtain the proposed connections.

Example 1. N-(2-Phenethyl-N'[2-(1,3,4-thiadiazolyl]thiourea

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol) and 2-amino-1,3,4-thiadiazole (2,02 g, 20 mmol) in N, N-dimethylformamide (50 ml) is heated to 100oC. After 68 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution and water. The organic layer is filtered and washing the obtained solid (2.24 g) with ethyl acetate to obtain 1.9 g (36%) specified in the procurement connections, so pl. 210-211oC.

IR (KBr), cm-1: 3320, 2924, 2869, 2685, 1645, 1543, 1453, 1384, 1344, 1278, 762, 749, 700, 650.

1H-NMR (300 MHz, DMSO-d6), : 12,35 (ush.s, 1H), of 8.92 (s, 1H), 8,78 (ush. s, 1H), 7,38-to 7.18 (m, 5H), 3,84-and 3.72 (m, 2H), 2,92 (t, J=6 Hz, 2H).

MS (FD) m/e: 264/(M+).

UV (EtOH) nm: 277, 253, 205 nm.

Found,%: C 50,07; H Of 4.66; N 21,48.

C11H12N4S2< / BR>
Calculated,%: C 49,98; H 4,57, N 21, 19.

Example 2. N-(2-Phenethyl)-N'-[4,5-dimethyl-(2-thiazolyl)]timeonline and shaken with saturated sodium bicarbonate solution. The layers are separated and the aqueous layer washed with methylene chloride (2x). The combined organic phase is dried over magnesium sulfate, filtered and concentrated. To the obtained solid substance is added 2-geneticization (3,26 g, 20 mmol, 3 ml) and N,N-dimethylformamide (50 ml). The resulting solution was heated at 100oC. After 92,25 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution and with water (2x). The organic layer is filtered and recrystallization of the obtained solid product (3.9 g) from ethyl acetate to obtain 3.3 g of the compounds (57%), so pl. 186-187oC.

IR (KBr), cm-1: 3166, 3022, 1523, 1502, 1289, 1215, 737, 695.

1H-NMR (300 MHz, DMSO-d6), : 11,42 (ush.s, 1H), 9,83 (ush.s, 1H), was 7.36-7,16 (m, 5H), 3,86-to 3.73 (m, 2H), only 2.91 (t, J=7 Hz, 2H), 2,19 (s, 3H), of 2.08 (s, 3H).

MS (FD) m/e 291 (M+).

UV (EtOH): 298 nm ( = 17987), 257 nm ( = 9939), 204 nm ( = 20802).

Found,%: C 57,41; H Of 5.85; N 14,39.

C14H17N3S2< / BR>
Calculated,%: C 57,70; H 5,80; N 14,42.

Example 3. N-[2-(4-Methyl)-1-phenethyl]-N'-(2-thiazolyl)thiourea.

< / BR>
A solution of 2-(4-methylphenethyl)isothiocyanate (820 mg, 4.6 mmol) and 2-aminothiazole (565 mg, atoi temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), saturated sodium bicarbonate solution and brine. The organic layer is dried over magnesium sulfate, filtered and concentrated. The obtained solid product (1.1 g) clean pressure chromatography on silica gel (1% ethyl acetate in methylene chloride) and obtain 570 mg (45%) of the specified connection. A sample recrystallized from ethyl acetate, so pl. 132-133oC.

IR (KBr), cm-1: 3168, 2990, 1560, 1513, 1166, 808, 705.

1H-NMR (300 MHz, DMSO-d6), : are 11.62 (ush.s, 1H), RS 9.69 (ush.s, 1H), was 7.36 (d, J=4 Hz, 1H), 7,2-7,06 (m, 5H), 3,83-to 3.73 (m, 2H), 2,87 (t, J=7 Hz, 2H), 2,3 (s, 3H).

MS (FD) m/e: 277 (M+).

UV (EtOH): 288 nm ( = 18773), 257 nm ( = 11948), 215 nm ( = 14509).

Found,%: C 56,55; H 5,52; N 15,04.

C13H15N3S2< / BR>
Calculated,%: C 56,29; H The 5.45; N Br15.15.

Example 4. N-(2-Phenethyl)-N'-(2-pyridyl)thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-aminopyridine (1.9 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 4 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate, the organic solution washed with water (3x). The organic layer is dried over sodium sulfate, filtered and concentrated. Ne the CLASS="ptx2">

IR (KBr), cm-1: 3232, 1536, 1477, 1319, 775.

1H-NMR (300 MHz, CDCl3), : 11,72 (ush.s, 1H), 8,59 (ush.s, 1H), of 7.97 (d, J=4,2 Hz, 1H), to 7.64 (LW.t, J=1.7 and 8.2 Hz, 1H), 7,37-7,26 (m, 5H), 6,92 (LW. d, J=7.2 and 5.1 Hz, 1H), 6,74 (d, J=8,2 Hz, 1H), 4,06 (m, J=6,8 Hz, 2H), 3.04 from (t, J=6.9 Hz, 2H).

MS (FD) m/e 257 (M+).

UV (EtOH): 293 nm ( = 12040), 266 nm ( = 12961), 247 nm ( = 11912), 202 nm ( = 12963).

Found,%: C 65,45; H Of 5.82; N 16,24.

C14H15N3S

Calculated,%: C 65,35; H By 5.87; N 16,33.

Example 5. N-(2-Phenethyl)-N'-(4-pyridyl)thiourea.

< / BR>
A solution of 2-phenylisothiocyanate (3,26 g, 20 mmol, 3 ml) and 4-aminopyridine (1.92 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 4.5 hours the reaction mixture is cooled to room temperature and transferred to the ethyl acetate. The organic solution was washed with water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. The resulting oil purified pressure chromatography on silica gel (5% methanol in ethyl acetate to 10% methanol in ethyl acetate). By recrystallization of the resulting product from ethyl acetate to obtain 1.85 g (36%) of the specified connection, so pl. 154,5oC.

IR (KBr), cm-1: 3142, 1579, 1518, 1328, 1276, 750.

1H-NMR (300 MHz, CDCl3), : 8,42 (LW.d, J=1 and 5 Hz, 2H), 7,9 S="ptx2">

UV (EtOH): 281 nm ( =16486), 255 nm ( = 21182), 208 nm ( = 25744).

Found,%: C 65,43; H 5,97; N 16,17.

C14H15N3S

Calculated,%: C 65,34; H By 5.87; N 16,33.

Example 6. N-(2-Phenethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-6-perbenzoate (3,36 g, 20 mmol) in dimethylsulfoxide (10 ml) is heated at 150oC. After 5 h the reaction mixture was cooled to room temperature and filtered. The filtrate was poured into ethyl acetate, washed with water (5x) and brine (2x). The organic layer is concentrated and recrystallization from ethyl acetate receive 729,5 mg (11%) the specified connection, so pl. 212-213oC.

IR (KBr), cm-1: 3175, 3025, 1561, 1534, 1461, 1249, 1215.

1H-NMR (300 MHz, CDCl3), : 11,81 (ush.s, 1H), 9,83 (ush.s, 1H), to 7.77 (LW. d, J= 8.7 and 2.4 Hz, 1H), 7,52 (ush.s, 1H), 7,31-to 7.15 (m, 6H), with 3.79 (m, 2H), 2,9 (t, J=6.6 Hz, 2H).

MS (FD) m/e 331 (M+).

UV (EtOH, nm: 310, 289, 245, 208, 201.

Found,%: C 57,74; H 4,39; N 12,53.

C16H14N3S2F

Calculated,%: C 57,98; H 4.26 Deaths; N 12,68.

Example 7. N-(2-Phenethyl)-N'-[2-(4-phenyl-5-tetradecyl)thiazolyl] thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-4-phenyl-5-tetradec the support to room temperature and transferred to the ethyl acetate. The organic solution was washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer is dried over sodium sulfate, dried and concentrated. By recrystallization of the product once from ethyl acetate and once from hexane get is 4.93 g (46%) of the specified connection, so pl. to 108.5-109oC.

IR (KBr), cm-1: 3166, 3022, 2915, 1850, 1574, 1523, 1502, 1215, 695.

1H-NMR (300 MHz, CDCl3), : 10,87 (ush.s, 1H), 9.28 are (ush.s, 1H), 7,55-7,16 (m, 10H), 4-3,95 (m, 2H), 2,99 (t, J=7 Hz, 2H), and 2.79 (t, J=9 Hz, 2H), 1,65-1 (m, 24H), 0,86 (t, J=6 Hz, 3H).

MS (FD) m/e: 535 (M+).

UV (EtOH): 299 nm ( = 19199), 261 nm ( = 17809), 203 nm ( = 31542).

Found,%: C 71,93; H Is 8.75; N 7,92.

C32H45N3S2< / BR>
Calculated,%: C 71,73; H 8,46; N 7,84.

Example 8. N-[2-(3,4-Dimethoxy)phenethyl]-N'-(2-thiazolyl) thiourea.

< / BR>
A solution of 2-(3,4-dimethoxyphenethyl)isothiocyanate (0.52 g, of 2.33 mmol) and 2-aminothiazole (233 mg, of 2.33 mmol) in N,N-dimethylformamide (10 ml) is heated at 100oC. After 24 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic solution was washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer is dried over sulfate soda is so pl. 139oC.

IR (KBr), cm-1: 3168, 3112, 3013, 1572, 1550, 1516, 1461, 1263, 1237, 1183.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (ush.s,1H), 9,8-9,62 (ush.s, 1H), 7,35 (m, 1H), 7,15 (ush. s, 1H), 6,9-of 6.75 (m, 3H), of 3.8 to 3.7 (m, 2H), 3.72 points (c,6H), 2,84 (t, J = 6 Hz,2H).

MS (FD) m/e 323 (M+).

UV (EtOH): 287 nm ( = 21687), 258 nm ( = 11828), 228 nm ( = 11401), 205 nm ( = 36669).

Found, %: C 51,96; H 5,61; N 13,02.

C14H17N3S2< / BR>
Calculated, %: C 51,99; H And 5.30; N 12,99.

Example 9. N-(2-Phenethyl)-N'-{2-[4-(4-bromophenyl)thiazolyl]}thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-4-(4-bromophenyl)thiazole (5,15 g, 200 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 65 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic solution was washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. Contained in the solution, the solids filtered off. The filtrate is dried over sodium sulfate, filtered and concentrated, the residue is added to the previously filtered product. By recrystallization of the combined product from ethyl acetate receive 12,04 g (24%) the specified connection, so pl. 215,5-216,5oC.

IR (KBr), cm-1: 3166, 3022, 1574, ), 2,96 (t, J = 6 Hz, 2H).

MC (FD) m/e 419 (M+1).

UV (EtOH): 287 nm ( = 28740), 268 nm ( = 24574), 246 nm ( = 18009), 203 nm ( = 35813).

Found,%: C 51,39; H Of 3.77; N 9,77.

C18H16N3S2Br

Calculated, %: C 51,68; H 3,86; N 10,04.

Example 10. N-[2-(4-Chloro)phenethyl]-N,-(2-thiazolyl)thiourea.

< / BR>
A solution of 2-(4-chloro)geneticization (657 mg, 3.3 mmol) and 2-aminothiazole (335 mg, 3.3 mmol) in N, N - dimethylformamide (10 ml) is heated at 100oC. After 20.5 hours, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic solution was washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution and with water (3x). The organic layer is dried over sodium sulfate, filtered and concentrated. By recrystallization of the product from ethyl acetate (2x) obtain 136 mg (14%) the specified connection, so pl. 154-155oC.

IR (KBr), cm-1: 3090, 2991, 1561, 1515, 1490, 1176.

1H-NMR (300 MHz, DMSO-d6), : 11,58 (ush.s, 1H), 9,78-9,6(ush.s,1H), 7,4-7,28 (m,5H), 7,12 (ush.s, 1H), 3,81-and 3.72 (m, 2H), 2,92(t, J = 6 Hz, 2H).

MC (FD) m/e 297 (M+).

UV (EtOH): 289 nm ( = 19572), 257 nm ( = 12071), 220 nm( = 15393), 202 ( = 22079).

Found,%: C 48,17; H Was 4.02; N 13,83.

C12H12N3S2Cl

Calculated,%: C 48,40 nutrititional (1.63 g, 10 mmol, 1.5 ml) and 2-amino-4,5-dihydrothiazolo (1,02 g, 10 mmol) in dimethyl sulfoxide is heated at 100oC. After 2.5 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. By recrystallization of the obtained solid substance from ethyl acetate to obtain 1.48 g (56%) of the compounds in the form of white crystals. The product sample secondary recrystallized from ethyl acetate, so pl. 132-134oC.

IR (KBr), cm-1: 3161, 3027, 2945, 2862, 1630, 1574, 1552, 1221, 1033.

1H-NMR (300 MHz, CDCl3), : of 11.11 (ush. s, 1H), at 8.36 (c, 1H), 7,32-7,14 (m, 5H), 4,05-of 3.97 (m, 2H), 3.9 to a 3.83 (m, 2H), 3,3-up 3.22(m, 2H), equal to 2.94 (t, J = 7,1 Hz, 2H).

MC (EI), m/e 265 (M+).

UV (EtOH): 269 nm ( = 18349), 206 nm ( = 18745).

Found,%: C 54,36; H 5,66; N 15,78.

C12H15N3S2< / BR>
Calculated, %: C 54,31; H 5,70; N 15,83.

Example 12. N-(2-Phenethyl)-N'-[2-(4-methylthiazolyl)]thiourea.

< / BR>
A solution of 2-geneticization (1.63 g, 10 mmol, 1.5 ml), hydrochloride 2-amino-4-methylthiazole (1.51 g, 10 mmol) and N,N-diisopropylethylamine (1.29 g, 10 mmol, of 1.74 ml) in dimethyl sulfoxide (10 ml) is heated at 100ooC.

IR (KBr), cm-1: 3456, 3169, 3084, 3024, 1565, 1533, 1506, 1214.

1H-NMR (300 MHz, CDCl3), : 10,92 (c, 1H), 10,08 (c, 1H), 7,33 to 7.2 (m, 5H), of 6.31 (c, IH), 4.04 the-3,98 (m, 2H), 3,01 (t, J = 6.9 Hz, 2H) 2,17 (c, 3H).

MS(EI), m/e 277 (M+).

UV (EtOH): 293 nm ( = 18119), 258 nm ( = 10137), 204 nm ( = 18979).

Found, % : C 56,53; H Of 5.53; N 15,18.

C13H15N3S2< / BR>
Calculated,%: C 56,29; H The 5.45; N 15,18.

Example 13. N-(2-Phenethyl)-N'-[2-(4-ethylglycine)thiazolyl)]thiourea.

< / BR>
A solution of 2-geneticization (626 g, 20 mmol, 3 ml) and ethyl-2-amino-4-thiazoleacetate (4 g, 20 mmol) in dimethylsulfoxide (20 ml) is heated at 110oC. After 68 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, water (5x) and brine. The organic layer critografia on silica gel (10% ethyl acetate in dichloromethane) and after treatment decolorizing charcoal obtain 2.37 g(33%) of the indicated compound as a pale yellow substance. The product sample recrystallized from ethyl acetate, so pl. 168-169oC.

IR (KBr), cm-1: 3174, 3029, 1724, 1685, 1558, 1530, 1215, 1133, 1054.

1H-NMR (300 MHz, CDCl3), : 10,67 (s, 1H), 8,21 (c, 1H), 7,34, and 7.1 (m, 5H), 4,39 (K, J=7,17 Hz, 2H), 3.96 points-of 3.85 (m, 2H), 3,09-of 2.93 (m, 2H), 1,4 (t, J=7,1 Hz, 3H).

MC (FD) m/e 363 (M+).

UV (EtOH): 284 nm ( =18549), 255 nm ( =17141), 204 nm ( =23447).

Found,%: C 53,08; H 4,80; N 11,55-

C16H17N3O3S2< / BR>
Calculated,%: C 52,97; H 4,71; N To 11.56.

Example 14. N-(2-Phenethyl)-N'-[2-(5,6-dimethyl)benzothiazolyl)]thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-5,6-benzothiazole (3.57 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 24 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate with sediment. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (2x) and brine. The organic layer is filtered and finally obtained solid product (3 g), 20% ethanol in ethyl acetate receive only 2.91 g (43%) of the compounds in the form of a pale yellow substance, so pl. 226-228oC.

IR (KBr), cm-1: 3178, 3047, 1557, 1530, 1462, 1254, 1220.

1H-NMR (300 MHz, DMSO-d6<>.

UV (EtOH) nm: 307, 253, 204.

Found,%: C 63,15; H 5,63; N 12,14

C18H19N3S2< / BR>
Calculated, %: C 63,31; H 5,61; N 12,31.

Example 15. N-(2-Phenethyl)-N'-[2-(6-methoxybenzothiazole)]thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-6-methoxybenzothiazole (3.6 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 16 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. Filtration of the organic layer obtain 550 mg of the compounds. Concentration of the filtrate and recrystallization of the obtained solid residue from ethyl acetate get another 830 mg of the compounds. The total yield of 1.38 g (20%) of the compounds in the form of friable white matter, so pl. 217-218oC.

IR (KBr), cm-1: 3182, 3050, 1556, 1534, 1473, 1437, 1221, 1055.

1H-NMR (300 MHz, CDCl3), : 10,99 (c, 1H), 9,29 (c, 1H), 7,46-6,99 (m, 8H), 4,12-4,06 (m, 2H), 3,86 (c, 3H), is 3.08 (t, J=6,8 Hz, 2H).

MC (FD) m/e 343 (M+).

UV (EtOH): 312 nm ( =22725), 251 nm ( =11152), 204 nm ( =26183).

Found, %: C 59,21; H Equal To 4.97; N 12,19.

C17H17N3oC.

IR (KBr), cm-1: 3416, 3291, 3118, 2234, 1638, 1547, 1315, 1108.

1H-NMR (300 MHz, CDCl3), : of 7.23 (s, 1H), 5,19 (ush. s, 2H).

MS (FD) m/e: 125 (M+).

UV (EtOH): 278 nm ( =4359), 235 nm ( =4047), 210 nm ( =16728).

Found, %: C 38,65; H 2,46; N 33,24.

C4H3N3S

Calculated, %: C 38,39; H 2,42; N 33,57.

P, ,82 mmol) and 2-aminothiazole (300 mg, 3 mmol) in N,N-dimethylformamide (10 ml) is heated at 100oC. After 20 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. The obtained solid residue clean pressure chromatography on silica gel (1% ethyl acetate in dichloromethane) followed by recrystallization from ethyl acetate to obtain 129 mg of the compounds. By recrystallization of the second party from a mixture of ethyl acetate/hexane (1:1) to obtain 110 mg of the compounds. The overall yield of this compound in the form of snow-white matter 239 mg (30%). The product sample is again recrystallized from ethyl acetate, so pl. 126,5-127,5oC.

IR (KBr), cm-1: 3166, 3022, 1574, 1523, 1502, 1215, 1166.

1H-NMR (300 MHz, CDCl3), : 10,88 (c, 1H), 10,42 (c, 1H), 7,37-to 7.15 (m, 6H), PC 6.82 (d, J= 3.6 Hz, 1H), 3,82-3,71 (m, 2H), 2,74 (t, J=7.7 Hz, 2H), 2,12 is 2.01 (m, 2H).

MC (FD) m/e: 277 (M+).

UV (EtOH): 288 nm ( =19598), 256 nm ( =11329), 206 nm ( =19259).

Found, %: C 56,29; H 5,38; N 15,00.

C13H15N3S2< / BR>
Calculated, %: C 56,29; H The 5.45; N Br15.15.

Example 18. N-(2-Phenethyl)-N'-[2-(6-ecoxib is dibenzothiazyl (3.88 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 20 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. By recrystallization of the obtained solid residue from ethyl acetate receive 649 mg (9%) of the compounds in the form of substances tan so pl. 204-205oC.

IR (KBr), cm-1: 3166, 3022, 1523, 1502, 1435, 1215.

1H-NMR (300 MHz, CDCl3), : br11.01 (c, 1H), 9,77 (c, 1H), 7,43-to 6.95 (m, 8H), 4,08-4,01 (m, 4H), 3,06 (t, J=6.6 Hz, 2H), USD 1.43 (t, J=6.8 Hz, 3H).

MC (FD) m/e 357 (M+).

UV (EtOH): 312 nm ( =23035), 251 nm ( =11355), 204 nm ( =26891).

Found, %: C 60,21; H 5,10; N To 11.52.

C18H19N3OS2< / BR>
Calculated, %: C 60,48; H Are 5.36; N 11,75.

Example 19. N-(2-Phenethyl)-N'-[2-(4-tert-butylthiazole)]thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-4-tert-butylthiazole (3.13 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 64 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase ProMat over sodium sulfate, filter and concentrate. By recrystallization of the obtained solid residue from ethyl acetate receive 2,98 g (47%) of the compounds in the form of snow-white crystals, so pl. 173.5 metric - 175oC.

IR (KBr), cm-1: 3173, 2960, 1576, 1514, 1465, 1348, 1204, 1098.

1H - NMR (300 MHz, CDCl3), : 11,14 (s, 1H), 10,26 (c, 1H), 7,31-to 7.18 (m, 5H), 6,33 (s, 1H), 4,05-to 3.99 (m, 2H), 3.04 from (t, J = 7,1 Hz, 2H), 1.14 in (s, 9H).

MS (FD) m/e 319 (M+).

UV (EtOH): 292 nm ( = 20804), 257 nm ( = 10502), 203 nm ( = 19085).

Found,%: C 59,95; H 6,66; N 13,15.

C16H21N3S2< / BR>
Calculated,%: C 60,15; H 6,63; N 13,15.

Example 20. N-(2-Phenethyl)-N'-[2-(4-cryptomaterial)]thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-4-cryptomaterial (of 3.84 g, 20 mmol) in N, N-dimethylformamide (50 ml) is heated at 100oC. After 20 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. By recrystallization of the solid residue from a mixture of ethyl acetate hexane (1:1) receive 846 mg (13%) of the compounds in the form of a white substance, so pl. 162-163oC.

IR), 4,01-3,95 (m, 2H), to 3.02 (t, J = 6.9 Hz, 2H).

MS (FD) m/e 331 (M+).

UV (EtOH): 286 nm ( = 14352), 258 nm ( 14149), 205 nm ( = 24571).

Found,%: C 47,34; H Of 3.85; N 12,72.

C13H12F3N3S2< / BR>
Calculated,%: C 47,12; H 3,65; N 12,68.

Example 21. N-(2-Phenethyl)-N', N'-dimethylthiophene.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-5-chlorothiazole (2,69 g, 20 mmol) in N, N-dimethylformamide (50 ml) is heated at 100oC. After 20 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid and brine (3x). The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (1% ethyl acetate in dichloromethane) followed by double recrystallization from ethyl acetate receive 606 mg (14%) of the compounds in the form of snow-white crystals, so pl. 104,5-105,5oC.

IR (KBr), cm-1: 3284, 1536, 1452, 1347, 901.

1H-NMR (300 MHz, CDCl3), : 7,33-7,19 (m, 5H), lower than the 5.37 (ush.s, H1), 3,93-a 3.87 (m, 2H), and 3.16 (s, 6H), of 2.93 (t, J = 6,8 Hz, 2H).

MS (FD) m/e 208 (M+).

UV (EtOH): 242 nm ( = 12899), 210 nm ( = 21286).

Found,%: C 63,39; H 7,80;)-N'-[2-(4-zianoticnae)]thiourea.

< / BR>
A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-4-canadiate (2.5 g, 20 mmol) in N, N-dimethylformamide (50 ml) is heated at 100oC. After 20 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with saturated sodium bicarbonate solution, water (3x) and brine. Organizaci layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid product pressure chromatography on silica gel (1% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane (1:1) obtain 132 mg (2%) of the compounds in the form of a white substance, so pl. 169-170oC.

IR (KBr), cm-1: 3166, 3022, 1574, 1523, 1502, 1215, 1166.

1H-NMR (300 MHz, CDCl3), : 10,88 (s, 1H), to 10.09 (s, 1H), and 7.5 (s, 1H), 7,39-of 7.23 (m, 5H), 4,00-3,93 (m, 2H), to 3.02 (t, J = 6.9 Hz, 2H).

MS (FD) m/e 288 (M+).

UV (EtOH): 288 nm ( = 11104), 258 nm ( = 17433), 208 nm ( = 31355).

Found,%: C 54,04; H To 4.23; N 19,73.

C13H12N4S2< / BR>
Calculated,%: C 54,14; H 4,19; N 19,43.

Example 23. N-(2-Phenethyl)-N'-{2-[4-(4-pyridyl)thiazolyl]}thiourea.

< / BR>
In methylene chloride to form a suspension of 2-amino-4-(4-pyridyl)thiazole hydrobromide (1,2) and g is ilena and ethyl acetate. The combined organic layers are concentrated and to the resulting solid product (1 g, 5.6 mmol) is added 2-geneticization (0.9 g, 5.6 mmol, or 0.83 ml) in N, N-dimethylformamide (12.5 ml) and the resulting suspension heated at 100oC. After 20.5 hours, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. By recrystallization of the obtained solid residue from ethyl acetate (3x) get 133 mg (7%) the specified connection, so pl. 196oC.

IR (KBr), cm-1: 3250, 2939, 1723, 1604, 1506, 1223, 670, 664.

1H-NMR (300 MHz, DMSO-d6), : 11,72 (s, 1H), of 9.21 (ush.s, 1H), 8,54 (d, J = 6 Hz, 2H), 7,82 (s, 1H), 7,63 (d, J = 6 Hz, 2H), 7.3 to to 7.15 (m, 5H), 3,84-of 3.77 (m, 2H), 2,89 (t, J = 7 Hz, 2H).

MS (FD) m/e 340 (M+).

Msvr (FAB), m/e: (M+) calc. 341,0895, OBS. 341,0909.

UV (EtOH): 294 nm ( = 23935), 231 nm ( = 16356), 203 nm ( = 25793).

1. Nielsen, A. T., and Platt, E. N. Heterocyclic Chem., 1969, T. 6 S. 896.

2. Brown, Cowden, Grigg, Kavulak Aust. J. Chem. 1980, 33, 2291.

Example 24. N-(2-Phenethyl)-N'-{2-[4-(4-biphenyl)thiazolyl]}thiourea.

< / BR>
A solution of 2-phenetylisothiocyanate (of 0.82 g, 5 mmol, 0.75 ml) and 2-amino-4-(4-biphenyl)thiazole (1.26 g, 5 mmol) in N,N-dimethylformamid the Yat in ethyl acetate. The organic solution was washed with 1 N. hydrochloric acid, the mixture is filtered, the filtrate are separated and the organic phase is washed with saturated sodium bicarbonate solution, water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Cleaning product pressure chromatography on silica gel (1% ethyl acetate in dichloromethane to 2% ethyl acetate in dichloromethane) to obtain 372 mg (18%) of the specified connection. The yellow substance recrystallized from ethyl acetate, so pl. 208,5 - 209oC.

IR (KBr), cm-1: 3437, 3172, 30229, 1570, 1553, 1511, 1211, 1060, 738.

1H-NMR (300 MHz, DMSO-d6), : 11,72 (s, 1H), 9,54 (ush.s, 1H), 7,86 one-7.8 (m, 2H), 7,78-to 7.68 (m, 4H),7,58 (s, 1H), 7,52 - 7,44 (m, 2H), 7,41 - 7,35 (m, 1H), 7,34 - 7,29 (m, 4H), 7,27 to 7.2 (m, 1H), 3,92 - a-3.84 (m, 2H), 2,98 (t, J = 3 Hz, 2H).

MS (FD) m/e 415 (M+).

UV (EtOH) nm: 293, 212.

Found, %: C 69,08; H 5,10; N 9,99.

C24H21N3S2.

Calculated, %: C 69,36; H 5,09; N 10,11.

Example 25. N-(2-Phenethyl)-N'-{2-[4-(1-<1-etoxycarbonyl>-(3-tert - butoxycarbonylmethyl)imino)thiazolyl]}thiourea.

< / BR>
A mixture of 2-amino-4-[1-(1-etoxycarbonyl)-(3-tert-butoxycarbonylmethyl)imino] thiazole (2.64 g, 8 mmol) and 2-geneticization (1.31 g, 8 mmol, 1.2 ml) the temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Rinse the obtained solid residue with ethyl acetate receive 801 mg (20%) of the specified connection, so pl. 188,5oC.

IR (KBr), cm-1: 3293, 2975, 1749, 1594, 1543, 1453, 1382, 1231, 1154, 1054, 748, 698.

1H-NMR (300 MHz, DMSO-d6), : 11,85 (s, 1H), 8,46 (ush.s, 1H), 7,29 - 7,17 (m, 5H), 4,59 (s, 2H), or 4.31 - 4,24 (K, J = 7,1 Hz, 2H), 3,7 - to 3.64 (m, 2H), 2,82 (t, J = 7,1 Hz, 2H), of 1.36 (s, 9H), of 1.23 (t, J = 7,1 Hz, 3H).

MS (FD) m/e 492 (M+).

UV (EtOH) : 292, 257 nm ( = 16356), 203 nm.

Found,%: C 53,67; H Of 5.83; N 11,34.

C22H28N4O5S2< / BR>
Calculated, %: C 53,64; H 5,73; N 11,37.

Example 26. N-(2-Phenethyl)-N'-{2-[4-(tert-butyl-5-methyl)thiazolyl]} thiourea.

< / BR>
A mixture of 2-amino-2-tert-butyl-5-methylthiazole (1,87 g, 11 mmol) and 2-geneticization (1.8 g, 11 mmol) in N,N-dimethylformamide (25 ml) nagrevayut under 100oC. After 18.5 hours, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer is dried over a given link, so pl. 153 - 153,5oC.

IR (KBr), cm-1: 3171, 2966, 1474, 1534, 1510, 1455, 1346, 1221, 1186, 755, 704.

1H-NMR (300 MHz, DMSO-d6), : 11,28 (ush.s, 1H), 9,9 (ush. s, 1H), 7,28 - 7,14 (m, 5H), 3,78 - to 3.34 (m, 2H), 2,84 (t, J = 7 Hz, 2H), and 2.27 (c, 3H), 1,16 (c, 9H).

MS (FD) m/e: 333 (M+).

UV (EtOH): 297 nm ( = 19835), 257 nm ( = 9954), 202 nm ( = 21059).

Found, %: C 61,42; H 6,92; N 12,55.

C17H23N3S2< / BR>
Calculated,%: C 61,22; H 6,95; N 12,60.

Example 27. N-(2-Phenethyl)-N'-{ 5-methyl-[2-(1,3,4-thiadiazolyl)]}thiourea.

A solution of 2-amino-2-methyl-1,3,4-thiadiazole (2.3 g, 20 mmol) and 2-geneticization (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated for 18 h at 100oC.

The reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the obtained solid residue from ethyl acetate to obtain 1.86 g (33%) of the indicated compound as a white solid.

IR (KBr), cm-1: 3323, 3031, 1640, 1540, 1444, 1385, 781, 697, 652.

1H-NMR (300 MHz, DMSO-d6), : 12,4 (ush.s, 1H), 8,75 (ush.s, 1H), and 7.4 to 7.2 (m, 5H), 3,85 of 3.75 (m, 2H), 2,9 (t, J = 7 Hz, 2H), 2,54 (s, 3H).

MS (FD) m/e 278 (M+).

UV (EtOH): 280 nm ( = 10188), 253 nm ( = 11849), 205 nm ( = 19724).

Example 28. N-(2-Phenethyl)-N'-(2-pyrimidinyl)thiourea.

oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. By recrystallization of the obtained solid residue twice from ethyl acetate to obtain 0.9 g (17%) of the indicated compound as white needles.

IR (KBr), cm-1: 3325, 1588, 1524, 1434, 1415, 1333, 1228, 1154, 797.

1H-NMR (300 MHz, DMSO-d6), : 11,25 (ush.s, 1H), 10,65 (ush.s, 1H), and 8.6 (d, J = 5 Hz, 2H), and 7.4 to 7.2 (m, 6H), 3,85 of 3.75 (m, 2H), 2,9 (t, J = 7 Hz, 2H).

MS (FD) m/e 258 (M+).

UV (EtOH) : 286 nm ( = 17644), 267 nm ( = 15834), 244 nm ( = 12312), 205 nm ( = 21839).

Found, %: C 60,15; H 5,48; N 21,89.

C13H14N4S

Calculated,%: C 60,44; H 5,46; N 21,69.

Example 29. N-(2-Phenethyl)-N'-{2-[4-(4-chlorophenyl)thiazolyl]}thiourea.

A solution of 2-filatelistilor (0,77 g of 4.75 mmol) and 2-amino-4-(4-chlorophenyl)thiazole (1 g, of 4.75 mmol) in N,N-dimethylformamide (10 ml) is heated for 20 h at 120oC. the Solvent is removed in vacuo and recrystallization of the obtained solid residue from ethyl acetate to obtain 0.3 g (17%) of the indicated compound as a yellow solid.

IR (KBr), cm-1: 3176, 3029, 1579, 1515, 1231, 737, 698.

1H-NMR (300 MHz, DMSO-d6), : 11,7 (ush.s, 1H), 9,4 (ush.s, 1H) 7,74 - rate of 7.54 (m, 5H), was 7.36 - to 7.18 (m, 5H), from 3.9 to 3.8 (m, 2H), 2,96 (t, J = 6 Hz, 2H).

MC (FD), m/ex2">

C18H16N3S2Cl

Calculated, %: C 57,82; H Or 4.31; N 11,24.

Example 30. N-2-(Phenethyl)-N'-[2-(6-chloro)benzothiazolyl]thiourea.

A solution of 2-penetrateinto (3,26 g, 20 mmol) and 2-amino-2-chlorobenzothiazole (3,69 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated for 24 h at 120oC. the Solvent is removed in vacuo and recrystallization of the obtained solid residue from ethyl acetate receive 3,68 g (53%) of the indicated compound as a white solid.

IR (KBr), cm-1: 3165, 3021, 1574, 1522, 1501, 1289, 1215.

1H-NMR (300 MHz, DMSO-d6), : 12 (ush.s, 1H), 9,8 (ush.s,1H), 8,1-to 7.2 (m, 8H), 3,85 (m, 2H), 2.95 points (t, J= 7 Hz, 2H).

MS (FD) m/e 347 (M+).

UV (EtOH, nm: 304, 292, 248, 220, 205.

Example 31. N-(2-Phenethyl)-N'-{5-ethyl[2-(1,3,4-thiadiazolyl)]}thiourea.

A solution of 2-amino-5-ethyl-1,3,4-thiadiazole (2.58 g, 20 mmol) and 2-penicillinate (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated for 8 h at 120oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the obtained solid residue and ethyl acetate gain of 2.45 g (33%) of the indicated compound as a white solid.

IR (KBr), cm-1: 3317, 1645, 1536, 1448, 1384, 783, 693, 651.

MC (FD) m/e 292(M+).

UV (EtOH): 281 nm ( =13028), 253 nm ( = 13615), 206 nm ( = 23674).

Example 32. N-(2-Phenethyl)-N'-[4-(chlorophenyl)]thiourea.

A solution of 4-Chloroaniline (2.55 g, 20 mmol) and 2-phenylisocyanate (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated for 18 h at 120oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the obtained solid residue from ethyl acetate to obtain 2.5 g (26%) of the indicated compound as a yellow solid.

IR (KBr), cm-1: 3166, 3021, 1523, 1501, 1289, 1079, 802, 737, 695.

1H-NMR (200 MHz, DMSO-d6), : 9,6 (ush.s, 1H), 7,9 (ush.s, 1H), 7.5 to about 7.2 (m, 9H), 3,8-the 3.65 (m, 2H), 3-2,8 (t, J = 7 Hz, 2H).

MC (FD) m/e 290 (M+).

UV (EtOH): 270 nm ( = 14107), 247 nm ( = 18128), 206 nm ( = 27795).

Found,%: C 62,19; H 5,46; N 9,87.

C15H15N2SCl

Calculated, %: C Of 61.95; H 5,20; N 9,63.

Example 33. N-(2-Phenethyl)-N'-(3-chlorophenyl)thiourea.

A solution of 3-Chloroaniline (2.55 g, 20 mmol) and 2-geneticization (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated for 20 h at 120oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Purification of the obtained yellow oil using HPLC P>-1: 3310, 1591, 1542, 1495.

1H-NMR (300 MHz, DMSO-d6), : 9,85 (ush.s,1H), 7,9 (ush.s, 1H), 7,65 was 7.2 (m, 9H), 3,8-the 3.65 (m,2H), 3-2,8 (t, J = 7 Hz, 2H).

MC (FD) m/e 290 (M+).

UV (EtOH): 250 nm ( = 17296), 209 nm ( = 29630).

Found,%: C 61,65; H 5,44; N 9,84.

WITH15WITH15N2SCl

Calculated, %: C Of 61.95; H 5,20; N 9,63.

Example 34. N-(n-Propyl)-N'-(2-thiazolyl)thiourea.

A solution of 2-aminothiazole (2 g, 20 mmol) and n-propalestinian (2 g, 20 mmol) in N, N-dimethylformamide is heated for 20 h at 120oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Double recrystallization of the obtained yellow oil from ethyl acetate receive 0,42 g (10%) of the indicated compound as a white solid.

IR (KBr), cm-1: 3179, 1556, 1514, 1471, 680.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (ush.s, 1H), 9,7 (ush.s, 1H), and 7.4 (d, J = 5 Hz, 1H), and 7.1 (d, J = 5 Hz, 1H), 3,5 (m, 2H), 1,6 (m, 2H), of 0.95 (t, J = 7 Hz, 3H).

MC (FD) m/e 201 (M+).

UV (EtOH): 288 nm ( = 19469), 256 nm ( = 10151), 202 nm ( = 11550).

Found,%: C 42,02; H 5,61; N 20,93.

C7H11N3S2< / BR>
Calculated, %: C 41,77; H 5,51; N 20,87.

Example 35. N-(2-Phenethyl)-N'-[2-(4,5,6,7-tetrahydroindazole)]thiourea.

Rastede (25 ml) is heated for 48 h at 120oC. the Solvent is removed in vacuo and recrystallization of the obtained solid residue from ethyl acetate to obtain 0.32 g (11%) of the indicated compound as a white solid.

IR (KBr), cm-1: 3165, 3021, 2923, 1601, 1529, 1501, 1261, 1225.

1H-NMR (300 MHz, DMSO-d6), : 11,5 (ush.s, 1H), 10 (ush.s, 1H), and 7.4 to 7.2 (m, 5H), 3,85 (m, 2H), 2.95 points (t, J = 7 Hz, 2H), 2,6-2,4 (m, 4H), of 1.75 (m, 4H).

MC (FD) m/e 317 (M+).

UV (EtOH): 229 nm ( = 11400), 258 nm ( = 6011), 207 nm ( = 10579).

Example 36. N-(2-Phenylethyl)-N'-(2-benzothiazolyl)thiourea.

A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-aminobenzothiazole (3 g, 20 mmol) in toluene (50 ml) is heated to boiling. After 5 h the reaction mixture was cooled to room temperature, transferred into ethyl acetate, washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 1.8 g (29%) the specified connection, so pl. 203-207oC.

IR (KBr), cm-1: 3181, 3045, 1697, 1557, 1523, 1451, 1440, 1244, 749.

1H-NMR (300 MHz, CDCl3/DMSO-d6), : 11,7 (ush.s, 1 H), 10,6 (ush.s, 1H), 7,8-to 7.2 (m, 9H), 3,95 (m, 2H), 3,05 (t, J = 7 Hz, 2H).

MC (FD) m/e 313 (M+).

UV (EtOH): 300 nm ( = 24241), 207 nm ( = 28964).

Example 37. N-(2-Phenethyl)-N'-[2-(4-methyl)benzothiazolyl]thiourea.

A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-4-methylbenzothiazole (3.3 g, 20 mmol) in toluene (50 ml) is heated to boiling. After 5 h the reaction mixture was cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and precrystallization of the residue from ethyl acetate to obtain 1.68 g (26%) the specified connection, so pl. 185-188oC.

IR (KBr), cm-1: 3170, 3024, 1571, 1525, 1219, 767, 741, 698.

1H-NMR (300 MHz, CDCl3/DMSO-d6), : 11,4 (ush.s, 1H), 10,9 (ush.s, 1H), 7,6 to 7.1 (m, 8H), of 4.05 (m, 2H), 3,05 (t, J = 7 Hz, 2H), is 2.37 (s, 3H).

MC (FD) m/e 327 (M+).

UV (EtOH): 303 nm ( = 27416), 204 nm ( = 30294).

Found, %: C 62,56; H Lower Than The 5.37; N 12,77.

C17H17N3S2< / BR>
Calculated, %: C 62,35; H 5,23; N 12,83.

Example 38. N-(2-Phenethyl)-N'-[2-(4-methoxy)benzothiazolyl]thiourea.

A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-4-methoxybenzothiazole (3.2 g, 20 mmol) in N,N-dimethylformamide (20 ml) is heated for 24 h at 115oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and Prout and recrystallization of the residue from ethyl acetate to obtain 0.97 g (14%) of the specified connection so pl. 205-207oC.

IR (KBr), cm-1: 3165, 3021, 1574, 1522, 1215, 736, 695, 655.

1H-NMR (300 MHz, DMSO-d6), : 12,4 (ush.s, 1H), 9,9 (ush.s, 1H), 7,6-7 (m, 8H), at 3.9 (s, 3H), 3,85 (m, 2H), 2.95 points (t, J = 7 Hz, 2H).

MC (FD) m/e 343 (M+).

UV (EtOH): 293 nm( = 20046), 248 ( = 15731), 210 nm ( = 38172).

Example 39. N-(2-Phenethyl)-N'-[2-(4-chloro)benzothiazolyl]thiourea.

A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-4-chlorobenzothiazole (3.7 g, 20 mmol) in N,N-dimethylformamide (20 ml) is heated for 24 h at 115oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and paracrystalline of the residue from ethyl acetate gain of 2.56 g (37%) of the specified connection, so pl. 216 - 217oC.

IR (KBr), cm-1: 3166, 2940, 1568, 1527, 766, 733, 673.

1H-NMR (300 MHz, DMSO-d6), : 12,2 (ush. s, 1H), 9,3 (ush. s, 1H), 7,6 - 7 (m, 8H), 3,85 (m, 2H), 2.95 points (t, J = 7 Hz, 2 H).

MS (FD) m/e: 347 M+).

UV (EtOH): 301 nm ( = 20046), 248 nm ( = 15731), 210 nm ( = 38172).

Example 40. N-(2-Phenethyl)-N'-[3-(1,2,4-triazolyl)]thiourea.

A solution of 3-amino-1,2,4-triazole (1.7 g, 20 mmol) and 2-geneticization (3,26 g, 20 mmol, 3 ml) in N,arenasat in ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate receive 0,99 g (20%) of the specified connection, so pl. 160 - 162oC.

IR (KBr), cm-1: 3160, 3061, 2872, 1581, 1535, 1467, 1167, 977, 743, 681.

1H-NMR (300 MHz, DMSO-d6), : 13,9 ush. s, 1H), 10,85 (ush. s, 1H), 10 (ush. s, 1H), and 7.4 to 7.2 (m, 6H), 3,85 (m, 2H), 2, 96 (t, J = Hz, 2H).

MS (FD) m/e 247 (M+).

UV (EtOH): 261 nm ( = 21785), 229 nm ( = 11918), 206 nm ( = 17437).

Found,%: C 53,69; H 5,5; N 28,07.

C11H13N5S

Calculated,%: C 53,42; H 5,3; N Weighing 28.32.

Example 41. N-(2-Phenethyl)-N'-(3-chinoline)thiourea.

A solution of 3-aminoquinoline (2.9 g, 20 mmol) and 2-geneticization (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (20 ml) is heated for 72 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate receive 3,62 g (59%) of the specified connection, so pl. 162 - 164oC.

IR (KBr), cm-1: 3143, 1537, 1493, 1350, 1283, 1239, 749, 705.

1H-NMR (300 MHz, DMSO-d6), : 9,9 (ush. the m/e 308 (M+).

UV (EtOH): 331 nm ( = 5945), 257 nm ( = 27215), 247 nm ( = 37613).

Example 42. N-(2-Phenethyl)-N'-[2-(4-methyl)pyrimidinyl]thiourea.

A solution of 2-aminopyrimidine (1.9 g, 20 mmol) and 2-geneticization (of 33.26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (20 ml) is heated for 24 h at 115oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate get to 1.21 g (22%) the specified connection, so pl. 174 - 176oC.

IR (KBr), cm-1: 3184, 3034, 1561, 1409, 1344, 1291, 1165, 1030, 836, 792.

1H-NMR (300 MHz, DMSO-d6), : 11,3 (ush. s, 1H), 10,45 (ush. s, 1H), and 8.4 (d, J = 5Hz, 2H), and 7.4 to 7.2 (m, 5H), 7 (d, J = 5 Hz, 1H), 3,85 of 3.75 (m, 2H), 2,9 (t, J = 7 Hz, 2H), 2,3 (s, 3H).

MS (FD) m/e 272 (M+).

UV (EtOH): 274 nm ( = 25263), 248 nm ( = 15528), 203 nm ( = 17107).

Found,%: C 61,44; H 6,11; N 20,38.

C14H16N4S

Calculated,%: C 61,74; H Of 5.92; N 20,57.

Example 43. N-(2-Phenethyl)-N'-{2-[4-(4-forfinal)thiazolyl]}thiourea.

A solution of 2-geneticization (1.63 g, 10 mmol), triethylamine (1.01 g, 10 mmol) and hydroiodide 2-amino-4-(4-forfinal)thiazole (3.2 g, 10 mmol) in N, arenasat in ethyl acetate and washed with water, 1 N. HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 1.06 g (30%) the specified connection, so pl. 224 - 228oC.

IR (KBr), cm-1: 3178, 3030, 1553, 840, 737, 670.

1H-NMR (300 MHz, DMSO-d6), : 11,7 (ush. s, 1H), 9,5 (ush. s, 1H), 7,8 - to 7.2 (m, 10H), 3,9 - 3,81 (m, 2H), 2.95 points (t, J = 6 Hz, 2H).

MS (FD) m/e 357 (M+).

UV (EtOH): 282 nm ( = 15755), 264 nm ( = 17277, 239 nm ( = 13046), 209 nm ( = 18271).

Found,%: C 60,79; H 4,48; N 11,63.

C18H16N3S2F

Calculated,%: C 60,42; H 4,48; N 11,74.

Example 44. N-(2-Phenethyl)-N'-[2-(4-thiazolidone acid)]thiourea methyl ether.

A solution of 2-geneticization (of 0.82 g, 5 mmol) and methyl ester 2-aminothiazoline acid of 0.85 g, 5 mmol) in N,N-dimethylformamide (20 ml) is heated for 72 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 0.52 g (31%) the specified connection, so pl. 125 - 127oC.

IR (KBr), cm-1: 3168, 3085, 1740, 1557, 1524.

MS (FD) m/e 335 (M+).

UV (EtOH): 291 nm ( = 19133), 258 nm ( = 10917), 202 nm ( = 21433).

Found,%: C 53,96; H 5,16; N 12,79.

C15H17N3S2O2< / BR>
Calculated,%: C 53,71; H 5,11; N 12,53.

Example 45. N-(2-Phenethyl)-N'-(2-thiazolyl)thiourea.

A solution of 2-geneticization (7.5 g, at 45.9 mmol) and 2-aminothiazole (4.6 g, at 45.9 mmol) in N,N-dimethylformamide (100 ml) is heated for 12 h at 115oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue twice from ethyl acetate to obtain 5.7 g (47%) of the specified connection.

IR (KBr), cm-1: 3187, 3033, 2978, 1569, 1515, 1470, 1454, 1216, 1170, 1063.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (ush. s, 1H), 9,7 (ush. s, 1H), and 7.4 to 7.2 (m, 6H), and 7.1 (d, J = 3 Hz, 1H), and 3.8 (m, 2H), 2,9 (t, J = 7 Hz, 2H).

MS (FD) m/e 263 (M+).

UV (EtOH): 288 nm ( = 19656), 257 nm ( = 11658), 203 nm ( = 20054).

Found,%: C 54,63; H 5,02; N 15,85.

C12H13N3S2< / BR>
Calculated,%: C 54,72; H Equal To 4.97; N 15,95.

Example 46. N-[2-(1-Cyclohexenyl)ethyl]-N'-(2-thiazolyl)thiourea.

A solution of 2-(1-cyclohexenyl)EAC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 2.66 g (50%) of the specified connection, so pl. 147 - 148oC.

IR (KBr), cm-1: 3170, 3118, 2989, 1566, 1513, 1180, 706.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (ush. s, 1H), 9,7 (ush. s, 1H), 7,38 (d, J = 3 Hz, 1H), and 7.1 (d, J = 3 Hz, 1H), 5,45 (ush. s, 1H), 3,65 (m, 2H, in), 2.25 (t, J = 7 Hz, 2H), and 1.9 (m, 4H), 1,5 (m, 4H).

MS (FD) m/e 267 (M+).

UV(EtOH): 288 nm ( = 19663), 256 nm ( = 10534), 201 nm ( = 14819).

Found,%: C EUR 54.15; H Of 6.52; N 15,84.

C12H13N3S2< / BR>
Calculated,%: C 53,89; H 6,41; N 15,71.

Example 47. N-(2-Phenethyl)-N'-[2-(4-thiazolyl)acetic acid]thiourea ethyl ester.

A solution of 2-geneticization (3,62 g, 20 mmol) and ethyl ester of 2-aminothiazoline acid (and 3.72 g, 20 mmol) in N,N-dimethylformamide (20 ml) is heated 24 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue In, 730, 1580, 704.

1H-Yarm (300 MHz, DMSO-d6), : 11,6 (ush.s, 1H), 9,4 (ush.s, 1H), and 7.4 to 7.2 (m, 5H), 6,85 (c, 1H), 4,1 (K, J = 7 Hz, 2H), and 3.8 (m, 2H), 3,65 (c, 2H), 2,9 (t, J = 7 Hz, 2H), 1,2 (t, J = 7 Hz, 3H).

MC (FD) m/e 349 (M+).

UV (EtOH): 291 nm ( = 15025), 250 nm ( = 10893), 203 nm ( = 24071).

Found, %: C 55,24; H 5,62; N 11,96.

C16H19N3S2O2< / BR>
Calculated, %: C 54,99; H 5,48; N 12,02.

Example 48. N-(2-Phenethyl)-N'-[2-(4-thiazolyl)acetic acid]thiourea.

A solution of ethyl ester of N-(2-phenethyl)-N'-[2-(4-triazolyl)acetic acid] thiourea (0.7 g, 2 mmol) and 1 N. NaOH (2.5 ml, 2.5 mmol) in 50 ml of a mixture acetonitrile/water (1: 1) is stirred 24 h at room temperature. The reaction mixture is transferred into ethyl acetate and washed with saturated sodium bicarbonate solution. The aqueous solution acidified with 1 N. HCl to pH 2 and extracted with ethyl acetate. The organic extracts washed with brine and concentrated. By recrystallization of the residue from ethyl acetate receive 0,29 g (45%) of the specified connection, so pl. 188-190oC.

IR (KBr), cm-1: 3200-2800 (wide band), 1659, 1586, 1377, 671.

-1H-Yarm (300 MHz, DMSO-d6), : 12 (ush.s, 1H), 9,6 (ush. s, 1H), and 7.4 to 7.2 (m, 5H), 6,85 (c, 1H), and 3.8 (m, 2H), 3,65 (c, 2H), 2,9 (t, J = 7 Hz, 2H).

MC (FD) m/e 322 (M+).

UV (EtOH): 2O2< / BR>
Calculated, %: C 52,32; H 4,70; N 13,07.

Example 49. N-(Benzyl)-N'-(2-thiazolyl)thiourea.

The solution benzylisothiocyanate (1.5 g, 10 mmol) and 2-aminothiazole (1 g, 10 mmol) in N,N-dimethylformamide (25 ml) is heated for 12 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and double recrystallization of the residue from ethyl acetate get to 1.15 g (46%) of the specified connection, so pl. 165-167oC.

IR (KBr), cm-1: 3171, 3038, 1560, 1509, 1451, 1183, 972, 691.

1H-Yarm (300 MHz, DMSO-d6), : 11,7 (ush.s, 1H), 9,9 (ush.s, 1H), and 7.4 to 7.2 (m, 6H), 7,05 (d, J = 3 Hz, 1H), 4,8 (m, 2H).

MC (FD) m/e: 249 (M+).

UV (EtOH): 289 nm ( = 19103), 257 nm ( = 12196), 204 nm ( = 21328).

Found, %: C 53,09; H 4,50; N 16,77.

C11H11N3S2< / BR>
Calculated, %: C 52,99; H 4,47; N 16,85.

Example 50. N-(2-Phenethyl)-N'-(2-pyrazinyl)thiourea.

A solution of 2-aminopyrazine (1.9 g, 20 mmol) and 2-geneticization (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated for 17 h at 100oC. the Reaction mixture is cooled to room temperature, transferred to the ethyl acetate is concentrated and double recrystallization of the residue from ethyl acetate to obtain 0.95 g (18%) of the specified connection so pl. 142-143oC.

IR (KBr), cm1: 3181, 3049, 1606, 1533, 1472, 1314, 1221, 862, 725.

-1H-Yarm (300 MHz, DMSO-d6), : 11,02 (ush.s, 1H), 10,95 (ush.s, 1H), 8,5 (s, 1H), 8,18 (d, J = 2 Hz, 1H), with 8.05 (d, J = 2 Hz, 1H), and 7.4 to 7.2 (m, 5H), 3,85 of 3.75 (m,2H), 2,9 (t, J = 7 Hz, 2H).

MC (FD) m/e 258 (M+).

UV (EtOH): 318 nm ( = 10579), 263 nm ( = 17922), 202 nm ( = 15887).

Found, %: C 60,45; H 5,63; N 22,02.

C14H14N4S

Calculated, %: C 60,44; H 5,46; N 21,69.

Example 51. N-(2-Phenethyl)-N'-(3-pyrazolyl)thiourea.

A solution of 2-aminopyrazole (1.66 g, 20 mmol) and 2-geneticization (3,26 g, 200 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated for 18.5 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and double recrystallization of the residue from ethyl acetate to obtain 2.38 g (48%) of the specified connection, so pl. 142-144oC.

IR (KBr), cm-1: 3397, 3207, 3078, 1576, 1537, 1255, 1182, 751.

1H-Yarm (300 MHz, DMSO-d6), : 12,4 (ush.s, 1H), 10,35 (ush.s, 1H), 9,85 (ush.s,1H), and 7.6 (s,1H), and 7.4 to 7.2 (m, 5H), of 5.83(c, 1H, in), 3.75 (m,2H), 2,85 (t, J = 7 Hz, 2H).

MC (FD) m/e 246 (M+).

UV (EtOH): 264 nm ( = 21473), 204 nm ( = 17842).

A solution of aniline (1.86 g, 20 mmol) and 2-geneticization (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated for 18 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from a mixture of ethyl ether/hexane get 2,88 g (56%) of the specified connection, so pl. 102-104oC.

IR (KBr), cm-1: 3375, 1592, 1542, 1483, 1250, 1000, 695.

1H-Yarm (300 MHz, CDCl3), : a 7.85 (ush.s, 1H), 7.5 to 7 (m, 10H), 6 (ush.c, 1H), 3,9 (m,2H), 2,9 (t, J = 7 Hz, 2H).

MC (FD) m/e 256 (M+).

UV (EtOH): 248 nm ( = 15081), 206 nm ( = 25573).

Found, %: C 70,14; H 6,37; N 10,97.

C15H16N2S

Calculated, %: C 70,28; H 6,29; N Of 10.93.

Example 53. N-(Ethyl)-N'-(2-thiazolyl)thiourea.

The solution ethylisothiocyanate (1,74 g, 20 mmol) and 2-aminothiazole (2 g, 20 mmol) in N, N-dimethylformamide is heated for 23 hours at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. data connection so pl. 135-136oC.

IR (KBr), cm-1: 3165, 3021, 1574, 1501, 1435, 1366, 1215, 1179, 695.

1H-Yarm (300 MHz, DMSO-d6), : 10,4 (ush.s, 1H), and 7.4 (d, J = 3 Hz, 1H), 6,8 (d, J = 3 Hz, 1H), 3,7 (m,2H), 1,4 (t, J = 7 Hz, 3H).

MC (FD) m/e 187 (M+).

UV (EtOH): 287 nm ( = 19544), 256 nm ( = 10213), 202 nm ( = 11588).

Found, %: C 38,71; H To 4.92; N Cushion 22.66.

C6H9N3S2< / BR>
Calculated, %: C 38,48; H 4,84; N Of 22.44.

Example 54. N-(2-Phenethyl)-N'-(2-chlorophenyl)thiourea.

A solution of 2-Chloroaniline (2.55 g, 20 mmol) and 2-geneticization (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated for 17 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, aqueous 1 N. HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue HPLC on silica gel obtain 1.18 g (20%) of the indicated compound as a white solid.

IR (KBr), cm-1: 3378, 3167, 1540, 1499, 1470, 1250, 1060, 758, 685.

1H-Yarm (300 MHz, DMSO-d6), : 7,55 (ush.s, 1H), 7.5 to about 7.2(m, 9H), 5,9 (ush. s,1H), 3,9 (m,2H), 2,9 (t, J = 7 Hz, 2H).

MC (FD) m/e 290 (M+).

UV (EtOH): 245 nm ( = 16042), 209 nm ( = 29276).

Found, %: C 61,69; H 5,28; N 9,84.

C15H15N/P>The solution benzylisothiocyanate (3 g, 20 mmol) and 2-amino-5-chlorothiazole (2,69 g, 20 mmol) in N,N-dimethylformamide (25 ml) is heated for 20 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue HPLC on silica gel get 0,86 g (15%) the specified connection, so pl. 162-164oC.

IR (KBr), cm-1: 3154, 3003, 2958, 1588, 1515, 1421, 1231, 1192, 726.

1H-Yarm (300 MHz, DMSO-d6), : 8,8 (ush.s, 1H), 7,45 (s,1H), and 7.4 to 7.2 (m, 5H), 4,7 (m,2H).

MC (EI), m/e 283 (M+).

UV (EtOH): 295 nm ( = 6457), 259 nm ( = 5741), 208 nm ( = 11042).

Example 56. N-(3-Phenylpropyl)-N'[2-(5-chloro)thiazolyl]thiourea.

A solution of 3-phenylpropionylamino (of 3.54 g, 20 mmol) and 2-amino-5-chlorothiazole (2,69 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 18 h, the reaction mixture was cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue HPLC on silica gel get 0,29 g (5%) of the specified connection, so pl. 121-130oC.

And, ,3 (m, 5H), 3,5 (m, 2H), and 2.6 (t, J=7.7 Hz, 2H), 1.8 m (m, 2H).

MC (FD) m/e 311 (M+).

UV (EtOH): 295 nm ( =15069), 259 nm ( =12092), 205 nm ( =27316).

Found, %: C 50,17; H 4,51; N 13,42.

C13H14N3N3Cl

Calculated, %: C 50,07; H To 4.52; N 13,47.

Example 57. N-(2-Phenethyl)-N'-(5-tetrazolyl)thiourea.

The solution of the monohydrate of 5-aminotetrazole from 2.06 g, 20 mmol) and 2-phenylisothiocyanate (3,26 g, 20 mmol, 3 ml) in 50 ml of N,N-dimethylformamide is heated for 21 hours at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and double recrystallization of the residue from ethyl acetate receive 0,59 g (12%) the specified connection, so pl. 161-177oC.

IR (KBr), cm-1: 3451, 3235, 3148, 1547, 1511, 1169, 697.

1H-NMR (300 MHz, DMSO-d6), : 10,8 (c, 1H), 10,4 (m, 1H), 8,6 (ush. s, 1H), 7,2-7 (m, 5H), and 3.8 (m, 2H), and 2.8 (t, J=7 Hz, 2H).

MC (FD) m/e 248 (M+).

UV (EtOH): 258 nm ( =13630), 234 nm ( =15631), 204 nm ( =15594).

Example 58. N-(2-Phenethyl)-N'-[2-(4-methyl-5-acetyl)thiazolyl]thiourea.

A solution of 2-geneticization (1,14 g, 7 mmol) and 2-amino-4-methyl-5-acetylthiazole (1,09 g, 7 mmol) in N,N-dimethy in ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and double recrystallization of the residue from ethyl acetate to obtain 0.21 g (9%) the specified connection.

IR (KBr), cm-1: 3314, 3060, 1694, 1610, 1555, 1507, 1372, 1233, 980, 667.

1H-NMR (300 MHz, DMSO-d6), : 12,5 (ush. s, 1H), 8,8 (ush. s, 1H), and 7.4 to 7.2 (m, 5H), and 3.8 (m, 2H), 2,9 (t, J=7 Hz, 2H), and 2.4 (s, 3H), 2,3 (c, 3H).

MC (FD) m/e 319 (M+).

UV (EtOH): 319 nm ( =16944), 230 nm ( =13216), 201 nm ( =18476).

Example 59. N-(2-Phenethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea.

A solution of 2-amino-6-chloropyrazine (2,59 g, 20 mmol) and 2-geneticization (3,26 g, 20 mmol, 3 ml) in N,N-dimethylformamide (50 ml) is heated to 35 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue HPLC on silica gel get 0,23 g (4%) specified connection, so pl. 194-195oC.

IR (KBr), cm-1: 3171, 2932, 1575, 1517, 1465, 1359, 1270, 1169, 707.

1H-NMR (300 MHz, DMCO-d6), : 11,2 (c, 1H), 10,2 (ush. s, 1H), 8,5 (c, 1H), 8,3 (c, 1H), and 7.4 to 7.2 (m, 5H), 3,85 of 3.75 (m, 2H), 2,9 (t, J=7 Hz, 2H).

MS (FD) m/e 292 (+)

UV (EtOH): 328 the 2-finalisation (3.8 g, 20 mmol) and 2-aminothiazole (2 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated for 26 hours at 100o. The reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 2.3 g (39%) the specified connection, so pl. 105-107oC.

IR (KBr), cm-1: 3171, 2932, 1575, 1517, 1465, 1359, 1169, 1064, 707.

1H-NMR (300 MHz, DMSO-d6), : 11,5 (ush. s, 1H), 9,7 (ush. c, 1H), and 7.4 to 7.1 (m, 7H), 3,6 (m, 2H), and 2.6 (m, 2H), 1,6 (m, 4H).

MC (FD) m/e 291 (M+).

UV (EtOH): 288 nm ( =19013), 256 nm ( =10681), 203 nm ( =18908).

Found, %: C And 57.6; H Between 6.08; N 14,56.

C14H17N3S2< / BR>
Calculated, %: C 57,7; H 5,88; N 14,42.

Example 61. N-(2-Phenethyl)-N'-[2-(4-nitrophenyl)thiazolyl]thiourea.

A solution of 2-geneticization (0.74 g, 4.5 mmol) and 2-amino-4-[(3-nitro)phenyl] thiazole (1 g, 4.5 mmol) in 50 ml of N,N-dimethylformamide is heated for 120 hours at 100oC. the Reaction mixture was cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification is -1: 3165, 3023, 1571, 1517, 1352, 1217, 1166.

1H-NMR (300 MHz, DMSO-d6), : 11,7 (ush. s, 1H), 9 (ush. s, 1H), 8.6 out (c, 1H), and 8.2 (m, 2H), 7,75 (c, 1H), 7,66 (t, J=6 Hz, 1H), and 7.4 to 7.2 (m, 5H), and 3.8 (m, 2H), 2.95 points (t, J =6 Hz, 2H).

MC (FD) m/e 384 (M+).

UV (EtOH): 286 nm ( =21349), 264 nm ( =22766), 237 nm ( =19307), 202 nm ( =28514).

Found, %: C 56,12; N 4,24; N 14,47.

C18H16>N4S2O2< / BR>
Calculated, %: C 56,23; H 4,19; N Of 14.57.

Example 62. N-(n-Propyl)-N'-[2-(5-chlorothiazole)]thiourea.

A solution of 2-amino-5-chlorothiazole (2,69 g, 20 mmol) and n-propalestinian (2 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated for 18 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue HPLC on silica gel obtain 0.17 g (4%) specified connection, so pl. 128-133oC.

IR (KBr), cm-1: 3170, 2958, 1560, 1487, 1187, 691.

1H-NMR (300 MHz, DMSO-d6), : 11,5 (ush. s, 1H), 8.4V (ush. s, 1H), and 7.4 (c, 1H), 3,4 (m, 2H), 1,6 (m, 2H), of 0.95 (t, J=7 Hz, 3H).

MC (FD) m/e 235 (M+).

UV (EtOH): 294 nm ( =12928), 259 nm ( =10257), 204 nm ( =16979).

Found, %: C 35,85; H 4,19; N 19,78.

C7H10N3olil} thiourea.

A solution of 2-amino-[4-(2', 2'-diphenyl-2'-cyano)ethyl] thiazole (0,91 g, 3 mmol) and 2-geneticization (0,49 g, 3 mmol) in N,N-dimethylformamide (50 ml) is heated 91 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue HPLC on silica gel obtain 0.28 g (20%) of the specified connection.

IR (KBr), cm-1: 3179, 3024, 2238, 1562, 1250, 698.

1H-NMR (300 MHz, DMSO-d6), : 11,5 (c, 1H), 10,4 (ush. s, 1H), 7.5 to about 7.2 (m, 15H), 6,6 (c, 1H), 3,85 (c, 2H), and 3.8 (m, 2H), and 2.8 (t, J=7 Hz, 2H).

MC (FD) m/e 468 (M+).

UV (EtOH): 292 nm ( =12023), 259 nm ( =5862), 202 nm ( =25516).

Found,%: C 69,05; N 5,33; N 11,76.

C27H24N4S2< / BR>
Calculated, %: C 69,20; H 5,16; N 11,95.

Example 64. N-[2-(1-Cyclohexenyl)ethyl]-N'-(2-benzothiazolyl)thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (3.3 g, 20 mmol) and 2-aminobenzothiazole (3 g, 20 mmol) in 50 ml of N,N-dimethylformamide is heated for 17.5 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. water HCl, water, saturated sodium bicarbonate solution and races the aqueous compounds, so pl. 185-186oC.

IR (KBr), cm-1: 3179, 3044, 2921, 2830, 1556, 1523, 1441, 1196.

1H-NMR (300 MHz, DMSO-d6), : 11,8 (ush. s, 1H), 10,2 (ush. s, 1H), 8-7,2 (m, 4H), of 5.45 (s, 1H), 3,65 (m, 2H), 2,3 (t, J = 7 Hz, 2H), and 1.9 (m, 4H), 1,5 (m, 4H).

MS (FD) m/e 317 (M+).

UV (EtOH): 287 nm ( = 20679), 201 nm ( = 25939).

Found,%: C 60,29; H 5,94; N 13,49.

C16H19N3S2< / BR>
Calculated,%: C 60,53; H 6,03; N 143,24.

Example 65. N-(2-Phenethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea.

A solution of 2-geneticization (1.63 g, 10 mmol) and 2-amino-2-utilizou (1.28 g, 10 mmol) in N, N-dimethylformamide is heated for 23 hours at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 0.84 g (29%) the specified connection, so pl. 145-146oC.

IR (KBr), cm-1: 3199, 3049, 2962, 1591, 1275, 655.

1H-NMR (300 MHz, DMCO-d6), : 11,5 (ush.s, 1H), 9,8 (ush.s, 1H), and 7.4 to 7.2 (m, 5H), and 6.6 (s, 1H), and 3.8 (m, 2H), 2,9 (t, J = 7 Hz, 2H), 2,45 (K, J = 7 Hz, 2H), 1,1 (t, J = 7 Hz, 3H).

MS (FD) m/e 291 (M+).

UV (EtOH): 292 nm ( = 19382), 257 nm ( = 10362), 202 nm ( = 20282).

Found,%: 57,47; 1-[(2-Benzothiazolyl)thiocarbamoyl]imidazole.

A solution of 1,1'-thiocarbonyldiimidazole in (8.9 g, 50 mmol) and 2-aminobenzothiazole (7.5 g, 5 mmol) in acetonitrile (125 ml) is stirred for 20 h at room temperature. Filtration of the resulting precipitate receive 5.75 g (44%) of the specified connection.

IR (KBr), cm-1: 3199, 3049, 2962, 1628, 1461, 738.

1H-NMR (300 MHz, DMSO-d6), : cent to 8.85 (s, 1H), 8,1 (ush.s, 1H), 7,9-7 (m, 6H).

MS (FD) m/e 261 (M+).

UV (EtON) : 366 nm ( = 13072), 305 nm ( = 11556), 213 nm ( = 35893).

Found,%: C 50,50; H 3,02; N 21,49.

C11H8N4S2< / BR>
Calculated,%: C 50,75; H 3,10; N 21,52.

Example 67. N-[2-(2-Chlorophenyl)ethyl]-N'-(2-benzothiazolyl)thiourea.

A solution of 1-[(2-benzothiazolyl)thiocarbamoyl] imidazole (2.1 g, 8 mmol) and 2-(2-chlorophenyl)ethylamine (1.25 g, 8 mmol) in N, N-dimethylformamide (30 ml) is stirred for 1.5 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 1.6 g (57%) of the specified connection.

IR (KBr), cm-1: 3181, 3050, 1587, 1527, 1231, 753.

1H-NMR (300 MHz, DMSO-d6), : 11,9 (ush.s, 1H) 10 (ush.s, 1H), 7,8-to 7.2 (m, 8H), 3,95 (m, 2H), 3,1 (t, J = 7 Hz, 2H).

MS (FD) m/e 347 (M+).

UV (EtOH) : 301 nm ( = 23050), 202 nm ( = 30924).

email] imidazole (1.04 g, 4 mmol) and 2-(3-chlorophenyl)ethylamine (0,63 g, 4 mmol) in N, N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 0.88 g (63%) of the specified connection.

IR (KBr), cm-1: 3180, 2997, 1569, 1527, 1209, 755.

1H-NMR (300 MHz, DMSO-d6), : 11,9 (ush.s, 1H), 10,1 (ush.s, 1H), 7,8-to 7.2 (m, 8H), to 3.9 (m, 2H), 3 (t, J = 7 Hz, 2H).

MS (FD) m/e 347 (M+).

UV (EtOH): 301 nm ( = 25367), 202 nm ( = 31735).

Found,%: C 55,05; H Of 4.05; N A 12.03.

C16H14N3S2Cl

Calculated,%: C 55,24; H 4,06; N 12,08.

Example 69. N-[2-(4-Chlorophenyl)ethyl-N'-(2-benzothiazolyl)thiourea.

A solution of 1-[(2-benzothiazolyl)thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2-(4-chlorophenyl)ethylamine (0,63 g, 4 mmol) in N, N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate receive 0,89 g (64%) of the specified connection.

IR (KBr), cm-1: 3180, 2997, 1569, 1527, 1257, 755.

1H-NMR (300 MHz, DMSO-D6), : 12 (ush.s, 1H), 10 (ush.s, 1H), from 7.9 to 7.2 (m, 8H), 3,85 (m, 2H), 2.95 points (t, J = 7 Hz, 2H).

MS (FD) m/e 347 (MSUB>16
H14N3S2Cl

Calculated,%: C 55,24; H 4,06; N 12,08.

Example 70. N-[2-(2-Methoxyphenyl)ethyl]-N'-(2-benzothiazolyl)thiourea.

A solution of 1-[(2-benzothiazolyl)thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2-(2-methoxyphenyl)ethylamine (of 0.62 g, 4 mmol) in N, N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 0.9 g (66%) of the specified connection.

IR (KBr), cm-1: 3180, 1672, 1539, 1437, 1202, 1137, 783.

1H-NMR (300 MHz, DMSO-d6), : 12 (ush.s, 1H), 10 (ush.s, 1H), 7,9-7 (m, 8H), 3,85 (m, 2H, in), 3.75 (s, 3H), 2,9 (t, J = 7 Hz, 2H).

MS (FD) m/e 343 (M+).

UV (EtOH): 301 nm ( = 25894), 218 nm ( = 28357), 202 nm ( = 32552).

Found,%: C 59,70; H 5,01; N 11,99.

C17H17N3OS2< / BR>
Calculated,%: C 59,45; H 4,99; N 12,23.

Example 71. N-[2-(3-Methoxyphenyl)ethyl]-N'-(2-benzothiazolyl)thiourea.

A solution of 1-[(2-benzothiazolyl)thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2-(3-methoxyphenyl)ethylamine (of 0.62 g, 4 mmol) in N, N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization , 136, 718.

1H-NMR (300 MHz, DMSO-d6), : 11,9 (ush.s, 1H), of 10.05 (ush.s, 1H), 7,9-to 6.8 (m, 8H), a 3.87 (m, 2H, in), 3.75 (s, 3H), 2.95 points (t, J = 7 Hz, 2H).

MS (FD) m/e 343 (M+).

UV (EtOH): 301 nm ( = 24893), 216 nm ( = 28250), 203 nm ( = 33504).

Found,%: C 59,36; H 5,02; N 12,00.

C17H17N3OS2< / BR>
Calculated,%: C 59,45; H 4,99; N 12,23.

Example 72. N-[2-(4-Methoxyphenyl)ethyl]-N'-(2-benzothiazolyl)thiourea.

A solution of 1-[(2-benzothiazolyl)thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2-(4-methoxyphenyl)ethylamine (of 0.62 g, 4 mmol) in N, N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate receive 0,85 g (62%) of the specified connection.

IR (KBr), cm-1: 3162, 1610, 1572, 1255, 1208, 1106, 761.

1H-NMR (300 MHz, DMSO-d6), : 11,9 (ush.s, 1H), of 10.05 (ush.s, 1H), 7,9-to 6.8 (m, 8H), 3,85 (m, 2H, in), 3.75 (s, 3H), 2,9 (t, J = 7 Hz, 2H).

MS (FD) m/e 343 (M+).

UV (EtOH): 301 nm ( = 22113), 218 nm ( = 23878), 201 nm ( = 28098).

Found,%: C 59,33; H Is 5.06; N 12,04.

C17H17N3OS2< / BR>
Calculated,%: C 59,45; H 4,99; N 12,23.

Example 73. 1-{[2-(4,5-Dimethyl)thiazolyl]thiocarbamoyl}imidazole.

A solution of 1,1'-dicarbo is) in acetonitrile (40 ml) is stirred for 7 h at room temperature. Removal of solvent in vacuo receive raw the connection specified in the form of a yellow solid used in the next stage without purification.

Example 74. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(4,5-dimethyl)thiazolyl]thiourea.

A solution of 1-{[2-(4,5-dimethyl)thiazolyl]thiocarbamoyl}imidazole (10 mmol) and 2-(2-chlorophenyl)ethylamine (1.55 g, 10 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 2.1 g (65%) of the specified connection.

IR (KBr), cm-1: 3171, 3013, 1583, 1549, 1510, 1216, 759.

1H-NMR (300 MHz, DMSO-d6), : of 11.45 (ush.s, 1H), 9,75 (ush.s, 1H), 7.5 to about 7.2 (m, 4H), 3,85 (m, 2H), 3,05 (t, J = 7 Hz, 2H), 2,2 (s, 3H), of 2.05 (s, 3H).

MS (FD) m/e 325 (M+).

UV (EtOH): 297 nm ( = 9209), 257 nm ( = 5133), 201 nm ( = 14635).

Example 75. N-[2-(3-Chlorophenyl)ethyl]-N'-[2-(4,5-dimethyl)thiazolyl]thiourea.

A solution of 1-{[2-(4,5-dimethyl)thiazolyl]thiocarbamoyl}imidazole (10 mmol) and 2-(3-chlorophenyl)ethylamine (1.55 g, 10 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1 h at 90o

IR (KBr), cm-1: 3182, 3018, 1584, 1549, 1511, 1215, 788.

1H-NMR (300 MHz, DMSO-d6), : of 11.45 (ush.with.1H), 9,8 (ush. s, 1H) of 7.4 to 7.2 (m, 4H), 3,85 (m, 2H), 2,9 (t, J = 7 Hz, 2H), 2,2 (s, 3H), of 2.05 (s, 3H).

MS (FD) m/e 325 (M+).

UV (EtOH): 297 nm ( = 6543), 257 nm ( = 3650).

Found,%: C 51,73; H 4,99; N 13,16.

C14H16N3S2Cl

Calculated,%: C 51,60; H Of 4.95; N 12,89.

Example 76. N-[2-(2-Methoxyphenyl)ethyl-N'-[2-(4,5-dimethyl)thiazolyl]thiourea.

A solution of 1-{[2-(4,5-dimethyl)thiazolyl]thiocarbamoyl}imidazole (10 mmol) and 2-(3-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 1.9 g (65%) of the specified connection, so pl. 178-180oC.

IR (KBr), cm-1: 3175, 2998, 1598, 1495, 1213, 760, 707.

1H-NMR (300 MHz, DMSO-d6), : 11,4 P CLASS="ptx2">

UV (EtOH): 297 nm ( = 18573), 258 nm ( = 10587), 202 nm ( = 28862).

Found,%: C 56,29; H Is 6.19; N Of 13.27.

C15H18N3OS2< / BR>
Calculated,%: C 56,04; H 5,96; N To 13.09.

Example 77. N-[2-(3-Methoxyphenyl)ethyl-N'-[2-(4,5-dimethyl)thiazolyl]thiourea.

A solution of 1-{[2-(4,5-dimethyl)thiazolyl]thiocarbamoyl}imidazole (10 mmol) and 2-(3-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 2.2 g (69%) of the specified connection, so pl. 146-148oC.

IR (KBr), cm-1: 3179, 3035, 1587, 1551, 1214, 701, 682.

1H-NMR (300 MHz, DMSO-d6), : of 11.45 (ush.s, 1H), 9,8 (ush. s, 1H), 7,25 to 6.8 (m, 4H), and 3.8 (s, 2H, in), 3.75 (m, 3H), 2,85 (t, J = 7 Hz, 2H), 2,2 (s, 3H), of 2.05 (s, 3H).

MS (FD) m/e 321 (M+).

UV (EtOH): 297 nm ( = 16992), 258 nm ( = 9639), 202 nm ( = 27993).

Found,%: C 56,01; H 5,96; N 13,30.

C15H19N3S2< / BR>
Calculated,%: C 56,04; H 5,96; N To 13.09.

Example 78. N-[2-(4-Methoxyphenyl)ethyl-N'-[2-(4,5-dimethyl)thiazolyl]thiourea.

Rastilankallio (30 ml) is stirred for 1 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 2.2 g (69%) of the specified connection, so pl. 178-180oC.

IR (KBr), cm-1: 3174, 3024, 1590, 1552, 1214, 688.

1H-NMR (300 MHz, DMSO-d6), : of 11.45 (ush.s, 1H), 9,8 (ush. s, 1H), 7,2 (d, J = 8 Hz, 2H), 6,85 (d, J = 8 Hz, 2H), 3,78 (m, 2H, in), 3.75 (s, 3H), 2,85 (t, J = 7 Hz, 2H), 2,2 (s, 3H), of 1.05 (s, 3H).

Example 79. N-(2-Phenethyl)-N'-[5-(3-methyl)isothiazol]thiourea.

A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 5-amino-2-methylisothiazolone (3 g, 20 mmol) in N,N-dimethylformamide (30 ml) is heated 24 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 5.5 g (100%) specified connection, so pl. 213-216oC.

IR (KBr), cm-1: 3188, 2744, 1593, 1525, 1495, 1423, 1313, 1248, 829, 777, 752, 705, 670, 522.

1H-NMR (300 MHz, DMSO-d6), : 9,3 (ush.s, 1H), and 7.4 to 7.2 (m, 5H), 6,85 (ush.s, 1H), 3,7 (m, 2H), 2,9 (t, ptx2">

Example 80. 1-{[2-(6-Fluorine)benzothiazolyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (17.8 g, 100 mmol) and 2-amino-6-perbenzoate (16,8 g, 100 mmol) in acetonitrile (700 ml) is stirred for 20 h at room temperature and then for 6 h at 40oC. Filtering the resulting precipitate obtain 19.5 g (70%) of the specified connection.

IR (KBr), cm-1: 3200, 3050, 2558, 1595, 1560, 1461, 1331, 1216, 1088, 1040, 948, 740, 648, 627.

1H-NMR (300 MHz, DMSO-d6), : 12 (ush.s, 1H), cent to 8.85 (s, 1H), 8,1 (ush.s, 1H), 7,9-7 (m, 4H).

MS (FD) m/e 279 (M+-H).

UV (EtOH): 364 nm ( = 7372), 306 nm ( = 13593), 213 nm ( = 31325).

Found,%: C 47,72; H 2,66; N 20,09.

C11H7N4S2< / BR>
Calculated,%: C 47,47; H 2,54; N 20,13.

Example 81. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea.

A solution of 1-{[2-(6-fluoro)benzothiazolyl]thiocarbamoyl}imidazole (2,1, 8 mmol) and 2-(2-chlorophenyl)ethylamine (1.25 g, 8 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 1.6 g (57%) of the specified connection, so pl. 188-189oC.

IR (KBr), cm-1: 3166, 3014, 1560, 1538, 1460, 1217, 1198, 853.

+
).

UV (EtOH): 301 nm ( = 22535), 216 nm ( = 27344), 201 nm ( = 28624).

Found,%: C 52,79; H 3,72; N 11,76.

C16H13N3S2ClF

Calculated,%: C 52,53; H To 3.58; N 11,49.

Example 82. N-[2-(3-Chlorophenyl)ethyl]-N'-[2-(6 - fluoro)benzothiazolyl]thiourea.

A solution of 1-{ [2-(6-fluoro)benzothiazolyl] thiocarbamoyl} imidazole (2.1 g, 8 mmol) and 2-(3-chlorophenyl)ethylamine (1.25 g, 8 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1.5 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 1.6 g (57%) of the specified connection, so pl. 193-194oC.

IR (KBr), cm-1: 3171, 3015, 1557, 1526, 1460, 1229, 1201, 866.

1H-NMR (300 MHz, DMSO-d6), : 11,9 (ush. s, 1H), 9,9 (ush. s, 1H), from 7.9 to 7.2 (m, 7H), 3,85 (m, 2H), 3 (t, J = 7 Hz, 2H).

MC (FD) m/e 365 (M+).

UV (EtOH): 301 nm ( = 24232), 217 nm ( =30020), 201 nm ( =31875).

Found, %: C 52,50; H To 3.67; N 11,38.

C16H13N3S2ClF

Calculated, %: C 52,53; H To 3.58; N 11,49.

Example 83. N-[2-(4-Chlorophenyl)ethyl]-N'-[2-(6 - fluoro)benzothiazolyl]thiourea.

A solution of 1-{ [2-(6-fluoro)benzothiazolyl] thiocarbamoyl} imidazole (2.1 g, 8 mmol) and 2-(4-chlorophenethylamine) (1.25 g, 8 mmol) in N,N-dimethylformamide in vacuum. Crystallization of the residue from ethyl acetate to obtain 1.6 g (57%) of the specified connection, so pl. 217-218oC.

IR (KBr), cm-1: 3168, 3033, 1559, 1532, 1491, 1462, 1230, 1143, 809.

1H-NMR (300 MHz, DMSO-d6), : 11,85 (ush.s, 1H), 9,8 (ush.s, 1H), from 7.9 to 7.2 (m, 7H), 3,85 (m, 2H), 2.95 points (t, J = 7 Hz, 2H).

MC (FD) m/e 365 (M+).

UV (EtOH): 301 nm ( = 24527), 220 nm ( = 31031).

Found, %: C 52,80; H 3,70; N 11,34.

C16H13N3S2ClF

Calculated, %: C 52,53; H To 3.58; N 11,49.

Example 84. N-[2-(2-Methoxyphenyl)ethyl]-N'-[2-(6 - fluoro)benzothiazolyl]thiourea.

A solution of 1-{ [2-(6-fluoro)benzothiazolyl] thiocarbamoyl} imidazole (2.1 g, 8 mmol) and 2-(2-methoxyphenyl)ethylamine (1.25 g, 8 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1.5 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 1.6 g (57%) of the specified connection, so pl. 208-209oC.

IR (KBr), cm-1: 3168, 3034, 1561, 1536, 1462, 1242, 1198, 852.

1H-NMR (300 MHz, DMSO-d6), : 11,85 (ush.s, 1H), 9,8 (ush.s, 1H), 7,9-7 (m, 7H), 3,85 (m, 2H), and 3.8 (s, 3H), 2,9 (t, J = 7 Hz, 2H).

MC (FD) m/e 361 (M+).

UV (EtOH): 300 nm ( = 24273), 218 nm ( =28369), 201 nm ( =34036).

Found, %: C 56,56; H 5,59; N 11,66.

C-N'-[2-(6 - fluoro)benzothiazolyl]thiourea.

A solution of 1-{ [2-(6-fluoro)benzothiazolyl] thiocarbamoyl} imidazole (2.1 g, 8 mmol) and 2-(3-methoxyphenyl)ethylamine (1.25 g, 8 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1.5 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 1.6 g (57%) of the specified connection, so pl. 190-124oC.

IR (KBr), cm-1: 3050, 1536, 1460, 1302, 1221, 1060, 674.

1H-NMR (300 MHz, DMSO-d6), : 11,9 (ush.s, 1H), 9,9 (ush.s, 1H), 7,9-7 (m, 7H), 3,85 (m, 2H, in), 3.75 (s, 3H), 2.95 points (t, J=7 Hz, 2H).

MC (FD) m/e 361 (M+).

UV (EtOH): 301 nm ( = 24608), 218 nm ( = 28535), 201 nm ( = 37337).

Found, %: C 56,21; H Of 4.54; N 11,40.

C17H16N3OS2CF

Calculated, %: C 56,49; H 4,46; N 11,63.

Example 86. N-[2-(4-Methoxyphenyl)ethyl]-N'-[2-(6 - fluoro)benzothiazolyl]thiourea.

A solution of 1-{ [2-(6-fluoro)benzothiazolyl] thiocarbamoyl} imidazole (2.1 g, 8 mmol) and 2-(4-methoxyphenyl)ethylamine (1.25 g, 8 mmol) in N,N-dimethylformamide (30 ml) is stirred for 1.5 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 1.6 g (57%) of the specified connection, so pl. 203-204oC.

IR (KBr), cm-, H in), 3.75 (s, 3H), 2,9 (t, J = 7 Hz, 2H).

MC (FD) m/e 361 (M+).

UV (EtOH): 301 nm ( = 23562), 222 nm ( =28328).

Found, %: C 56,70; H 4,42; N To 11.79.

C17H16N3OS2CF

Calculated, %: C 56,49; H 4,46; N 11,63.

Example 87. 1-{[2-(5-Chlorine)thiazolyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (25 g, 140 mmol) in 2-amino-5-chlorothiazole (18,8 g, 140 mmol) in acetonitrile (300 ml) is stirred for 23 h at room temperature. Filtration of the resulting precipitate gain of 21.2 g (62%) of the specified connection.

1H-NMR (300 MHz, DMSO-d6), to 9.5 (s, 1H), and 8.2 (s, 1H), and 7.6 (s, 1H), and 7.5 (s, 1H).

MC (FD) m/e 361 (M+-C3H3N2).

Example 88. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(5-chloro)thiazolyl]thiourea.

A solution of 1-{[2-(5-chloro)thiazolyl]thiocarbamoyl}imidazole (0.68 g, 2.8 mmol) in N,N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 0.68 g (73%) of the specified connection, so pl. 172-174oC.

IR (KBr), cm-1m, 2H), 2,9 (t, J=7 Hz, 2H).

MC (FD) m/e 331 (M+).

UV (EtOH): 295 nm ( = 11804), 259 nm ( = 10397), 202 nm ( = 27067).

Found, %: C 43,61; H 3,57; N 12,57.

C12H11N3S2Cl2< / BR>
Calculated, %: C 43,38; H 3,34; N 12,65.

Example 89. N-[2-(3-Chlorophenyl)ethyl]-N'-[2-(5-chloro)thiazolyl]thiourea.

A solution of 1-{[2-(5-chloro)thiazolyl]thiocarbamoyl}imidazole (1.22 g, 5 mmol) and 2-(3-chlorophenyl)ethylamine (0,78 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 0.9 g (54%) of the specified connection, so pl. 154-155oC.

IR (KBr), cm-1: 3178, 3044, 1557, 1520, 1458, 1346, 1196, 784, 755.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (ush.s, 1H), 8.4V (ush.s, 1H), and 7.4 (s, 1H), and 7.4 to 7.2 (m, 4H), and 3.7 (m, 2H), and 2.8 (t, J=7 Hz, 2H).

MC (FD) m/e 331 (M+).

UV (EtOH): 296 nm ( =14281), 259 nm ( =12090), 205 nm ( = 29809).

Example 90. N-[2-(4-Chlorophenyl)ethyl]-N'-[2-(5-chloro)thiazolyl]thiourea.

A solution of 1-{[2-(5-chloro)thiazolyl]thiocarbamoyl}imidazole (1.22 g, 5 mmol) and 2-(4-chlorophenyl)atramentous temperature, transferred to the ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 1.1 g (66%) of the specified connection, so pl. 178-180oC.

IR (KBr), cm-1: 3180, 2927, 1610, 1536, 1492, 1325, 1256, 1181, 1088, 1014, 811, 747, 643, 508.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (ush.s, 1H), 8.4V (ush.s, 1H), and 7.4 (s, 1H), 7,32 (d, J=8 Hz, 2H), 7,22 (d, J=8 Hz, 2H), and 3.7 (m, 2H), and 2.8 (t, J=7 Hz, 2H).

MC (FD) m/e 331 (M+).

UV (EtOH): 195 nm ( = 13675), 259 nm ( = 12330), 202 nm ( = 27524).

Found, %: C 43,61; H Of 3.46; N 12,85.

C12H11N3S2Cl2< / BR>
Calculated, %: C 43,38; H 3,34; N 12,65.

Example 91. N-[2-(1-Methyl)-2-pyrrolidinyl]-N'-(2-thiazolyl)thiourea.

Isothiocyanate 2-(2-aminomethyl)-1-methylpyrrole synthesized according to the methods (Ann, 657, 104-107, 1962).

1H-NMR (CDCl3), : 2,95 (t, 2H), 3,55 (s, 1H), the 3.65 (t, 2H), 5.9 to 5,95 (m, 1H), equal to 6.05 (t, 1H), 6,55 (t, 1H). The resulting isothiocyanate dissolved in DMF (4 ml), to the solution was added 200 mg (2 mmol) of 2-aminothiazole and heated for approximately 16 h at 100oC. Add EtOAc and the organic phase is washed with a saturated solution of NH4Cl and brine. After drying (Na2SO4the product is purified on Colo is asanee connection. By recrystallization from a mixture of toluene/hexane receive 150 mg of the compounds, so pl. 183 - 184oC (decomposition).

1H-NMR (DMSO-d6), : of 2.86 (t, 2H), 3,55 (c, 3H), 3.75 to (K, 2H), 5,85 - 5,9 (m, 2H), 6,62 (s, 1H), to 7.09 (d, 1H), was 7.36 (d, 1H), 9,74 (broad s, 1H), 11,65 (broad s, 1H).

13C-NMR (DMSO-d6), : 25,03; 33,31; 43,92; 106,24; 106,31; 112,03; 121,55; 129,33; 136,71; 161,68; 178,25.

Example 92. N-[2-(1-Piperazinylmethyl)]-N'-(2-thiazolyl)thiourea.

To a solution of 1.29 g of 1-(2-amino-ethyl)piperazine (10 mmol) in 5 ml of methylene chloride at 0oC added 1.78 g of thiocarbonyldiimidazole. The reaction mixture is heated to room temperature and stirred for 30 minutes methylene Chloride is evaporated and to the residue is added 40 ml of dimethylformamide in a mixture from 10.01 g of 2-aminothiazole. The resulting product was then purified by chromatography on a column of silica gel with elution with mixtures of methanol and chloroform. Crystallization of salts with oxalic acid leads to a further purification of the product.

1H-NMR (oxalate in D2O): 2,8 - 3,7 ppm (m), to 6.75 ppm (d) and 7.1 ppm (d).

Example 93. N-[2-(2-Chloro)phenethyl]-N'-(2-thiazolyl)thiourea.

In 20 ml of methylene chloride is dissolved thiocarbonyldiimidazole (980 mg, 5.5 mmol) and the resulting solution at 0oC drop is to room temperature and concentrated in vacuo to a small volume. To the residue is added 20 ml of DMF and 2-aminothiazole (700 mg, 7 mmol). The mixture was incubated 3 h at 100oC. After cooling to room temperature, the mixture is transferred into a 1 HCl solution (100 ml) and extracted with ethyl acetate (2x100 ml), then the organic phase is washed with brine and dried over magnesium sulfate. The concentration of the solution in vacuo and separation column chromatography on silica gel obtain 440 mg (30%) of product.

1H-NMR (CDCl3), : 7,38 - 7,17 (m, 5H, ClPh, thiazole), for 6.81 (d, J = 3,7 Hz, 1H, thiazole), was 4.02 (t, J = 7 Hz, 2H, CH2NH), 3,17 (t, J = 7,1 Hz, CH2).

13C-NMR (CDCl3), : 177,5 (C=S), 161 (thiazole), 137,5 (thiazole), 136 (ClPh), 134,1 (ClPh), RB 131.1 (ClPh), 129,5 (ClPh), 128 (ClPh), A 126.7 (ClPh), 111,1 (thiazole), 44,8 (CH2), AND 32.3 (CH2). AP AF O M ] H t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ % m ° = M B M t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ M V n I j 6 t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ 6 t B L U E t t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t" g o ; } P X t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ X u t + h t 2 t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ 2 x M X b R t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ p in C ' m A In t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ F L K About t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ W e d and s 2

Example 94. N-[2-(2-Methoxy)phenethyl]-N'-(2-thiazolyl)thiourea.

To a solution of 1.8 g (10 mmol) of 1,1'-thiocarbonyldiimidazole in CH2Cl2at 0oC type of 1.46 ml (10 mmol) of 2-methoxyphenethylamine, pastorat in DMF (8 ml) and to the solution was added 1 g (10 mmol) of 2-aminothiazole (Merck). Then the reaction mixture is heated for approximately 16 h at 100oC. then add EtOAc and dilute aqueous HCl. The organic phase is separated and successively washed with diluted HCl solution, a saturated solution of NH4Cl and water (2x). After drying over Na2SO4the product was then purified column chromatography on silica gel with elution by the mixture hexane/EtOAc (2:1) and receipt of 0.77 g of crude product. By recrystallization from toluene gain of 0.54 g still contaminated specified connection. Final purification is carried out on a column of Al2O3with elution CHCl3(contains 0.5% EtOH). The result is 85 mg of the compounds, so pl. 126 - 127,5oC.

1H-NMR (CDCl3), : 3,03 (t, 2H), 3,82 (c, 3H), 3.96 points (K, 2H), 6,79 - 6,93 (m, 3H), 7,2 - 7,26 (m, 3H), 10,35 (broad s, 1H), of 10.73 (broad s, 1H).

13C-NMR (CDCl3), : 29,59; 45,69; 55,19; 110,22; 110,97; 120,4; 126,75; 127,96; 130,78; 137,72; 157,62; 161,58; 177,34.

Example 95. N-[2-(4-Fluoro)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method similar to the method of example 94, using 4-fortunetelling, so pl. 124,5 - 126oC.

Found, %: C 51; H 4,35; N 14,8.

Calculated, %: C 51,22; H 4,3; N 14,93.

1H-NMR (CDCl3), : 3 (is; 61,74 (d, 1C); 161,84; 177,52.

Example 96. N-[2-(4-Nitro)phenethyl]-N'-(2-thiazolyl)thiourea.

The specified connection was obtained using 4-nitroaniline by the method similar to the method of example 93.

1H-NMR (CDCl3), : 8,17 (d, J = 8.6 Hz, 2H, O2NPh), was 7.45 (d, J = 8.6 Hz, 2H, O2NPh), 7,21 (d, J = 3,7 Hz, 1H, thiazole), at 6.84 (d, J = 3,7 Hz, 1H, thiazole), 4,01 (K, J = 5.7 Hz, 2H, CH2NH) and 3.15 (t, J = 7.2 Hz, 2H, CH2).

13C-NMR (CDCl3+ CD3OD), : 179 (C=S), 161 (thiazole), 146,4 (O2NPh), 136,9 (thiazole), 129 (O2NPh), 123,4 (O2NPh), 111,1 (thiazole), 45,3 (CH2), 34,3 (CH2).

Example 97. N-[2-(4-Amino)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained by reduction of the product from example 96 with iron and hydrochloric acid according to the method (Vogel. Handbook of practical organic chemistry, 4th ed., S. 657, Longman, 1978).

1H-NMR (CDCl3), : of 7.23 (d, J = 3.8 Hz, 1H, thiazole), 7,07 (d, J = 8,3 Hz, 2H, H2NPh), 6,79 (d, J = 3,7 Hz, 1H, thiazole), of 6.65 (d, J = 8,3 Hz, 2H, N2NPh), 3,91 (K, 2H, CH2NH), only 2.91 (t, J = 7,1 Hz, 2H, CH2).

13C-NMR (CDCl3+ CD3OD), : 177 (C=S), 161 (thiazole), 144 (H2NPh), 137,3 (thiazole), 129,5 (H2NPh), of 128.6 (H2NPh), 115,4 (H2NPh), 110,9 (thiazole), to 46.7 (CH2), 33,6 (CH2).

Example 98. N-[2-(4-ylamine according to the method similar to the method of example 93.

1H-NMR (CDCl3), : 7,22 - to 7.18 (t, 3H, MeOPh and thiazole), 6,85 (d, J = 8.5 Hz, 2H, MeOPh), for 6.81 (d, J = 3,7 Hz, 1H, thiazole), 3,94 (K, J = 7,1 Hz, 2H, CH2NH), 3,79 (c, 3H, MeO), 2,96 (t, J = 7,1 Hz, 2H, CH2).

13C-NMR (CDCl3), : 177,3 (C=S), 161,6 (thiazole), 158,2 (MeOPh), 137,4 (thiazole), 130,4 (MeOPh), 129,7 (MeOPh), 113,8 (MeOPh), 111 (thiazole), 55,1 (MeO), 47 (CH2), AND 33.8 (CH2).

Example 99. N-[2-(4-Hydroxy)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained by treatment of the product from example 98 attributively in dichloromethane according to the method (H. Sakurai, Synthesis, S. 740, 1979) (example 97).

1H-NMR (CDCl3), : 7,22 (d, J = 3.6 Hz, 1H, thiazole), 7,14 (d, J = 8,4 Hz, 2H, HOPh), for 6.81 - 6,77 (t, 2H, thiazole, HOP), 3,94 (K, 2H, CH2NH2), to 2.94 (t, J = 7.2 Hz, 2H, CH2).

13C-NMR (CDCl3), : 177,4 (C=S), 161,4 (thiazole), 154,1 (HOPh), 137, 6mm (thiazole), 130,5 (HOPh), 129, 9mm (HOPh), 115,3 (HOPh), 110,9 (thiazole), 47,1 (CH2), 33,7 (CH2).

Example 100. N-[2-(4-Bromo)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound was synthesized by using 4-bromophenethylamine by the method similar to the method of example 93.

1H-NMR (CDCl3+ CD3OD), : the 7.43 (d, J = 6,4 Hz, 2H, BrPh), 7,22 (d, J = 3.6 Hz, 1H, thiazole), to 7.15 (d, J = 6.3 Hz, 2H, BrPh), 6,83 (d, J = 3,7 Hz, 1H, thiazole), of 3.95 (t, J = 7,1 Hz, 2H, CH22), 34 (CH2).

Example 101. N-[2-(1-Piperidyl)ethyl]-N'-(2-thiazolyl)thiourea.

This compound was obtained using 1-piperidinylidene by the method similar to the method of example 93.

1H-NMR (CDCl3), : to 7.32 (d, J = 3,7 Hz, 1H, thiazole), at 6.84 (d, J = 3,7 Hz, 1H, thiazole), and 3.8 (t, 2H, CH2NH), 2,62 (t, J = 6,4 Hz, 2H, CH2), 2,48 (m, 2H, PIP.), of 1.62 (m, 2H, PIP.), of 1.46 (m, 1H, PIP.).

13C-NMR (CDCl3+ CD3OD), : 177,3 (C=S), 161 (thiazole), 137,3 (thiazole), 111,1 (thiazole), 56,1 (CH2), 54,1 (PIP.), 42,2 (CH2), 25,6 (PIP.), 24 (PIP.).

Example 102. N-(2-Morpholinoethyl)-N'-(2-thiazolyl)thiourea.

This compound is obtained using morpholinoethyl by the method similar to the method of example 91.

1H-NMR (250 MHz, CDCl3), : 7,38 (d, 1H, CH=CH), 6,86 (d, 1H, CH=CH), 3,82 (K,2H, CH2NH), 3,86-3,71 (m, 4H, CH2-O-CH2), to 2.67 [t, 2H, CH2-N (cycle)] , 2,62-2,52 (m, 4H, CH2-N-CH2).

13C-NMR (250 MHz, CDCl3), : 178, 163, 138, 112, 67, 57, 53, 42.

So pl. 150,5-151,5oC.

Example 103. 1-(2-Aminothiazol)-1'-imidazoledicarbonitrile.

To 50 ml of acetonitrile add 8,9 g thiocarbonyldiimidazole (50 mmol) and 5 g of 2-aminothiazole (50 mmol). The mixture is heated to 40atroveht and washed with 300 ml of cold acetonitrile. The yield of pure product after drying is 9.7 g (46 mmol).

Found, %: C 39,3; H 2,8; N 26,2.

Calculated, %: C 40; H 2,87; N 26,6.

1H-NMR (250 MHz, DMSO), : 8,68 (s,1H, N=CH-N), of 7.97 (s,1H, N-CH=CH-N), 7,76 (d,1H, S-CH=CH-N), 7,33 (d,1H, S-CH=CH-N), was 7.08 (s,1H, N-CH=CH-N).

Example 104. N-(2-Phenethyl)-N'-[2-(6-hydroxy)pyridyl]thiourea.

Stir the solution geneticization (1.63 g, 10 mmol, 1.5 ml) and 2-amino-6-hydroxypyridine (1.1 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. Through 87,25 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solids pressure chromatography on silica gel (10% ethyl acetate in dichloromethane to 15% ethyl acetate) followed by rinsing with ethyl acetate get to 1.15 g of the compounds in the form of snow-white matter, so pl. 196-197oC.

IR (KBr), cm-1: 2937, 1668, 1595, 1475, 1428, 1365, 1219, 1158, 1023.

1H-NMR (300 MHz, DMSO-d6), : 11,49 (ush.s, 1H), was 10.82 (s,1H), 10,33 (s, 1H), 7,52 (t, J = 7.9 Hz, 1H), 7,25-7,14 (m, 5H), 6,53 (d, J = 7.9 Hz, 1H), to 6.19 (d, J = 8 Hz, 1H), 3,8-to 3.73 (m, 2H), 2,92 (t, J = 7.7 Hz, 2H).

MS (FD) m/e 2; N 15,57.

C14H15N3OS

Calculated,%: C 61,52; H Of 5.53; N Shed 15.37.

Example 105. N-[2-(2-Naphtalate]-N'-[2-thiazolyl]thiourea.

In 5 ml of DMF suspended 2-naphthalenemethylamine (256 mg, 1.5 mmol) and the product from example 103 (400 mg, 1.9 mmol). The reaction mixture is heated to 110oC, and within a few minutes it becomes transparent. After 1 h the reaction mixture was cooled to room temperature and add 20 ml of methylene chloride. The organic solution is washed successively with 0.5 N. HCl solution (70 ml), brine (50 ml) and water (50 ml). The organic solution is dried over magnesium sulfate and then dried in vacuum. Purification of the product column chromatography on silica gel (chloroform/cyclohexane, 1:1 vol./about.) received 324 mg (69%) of the connection.

1H-NMR (CDCl3), : 7,82-7,39 (m, 7H, naphthas.), 6,98 (t, J = 3,6 Hz, 1H, thiazole), was 6.73 (d, J = 3.1 Hz, 1H, thiazole), 4,07 (K, J= 7 Hz, 2H, CH2NH), or 3.28 (t, J= 7 Hz, 2H, CH2).

13C-NMR (CDCl3+CD3OD), : 177 (C=S), 161 (thiazole), 128,5 (naphthas.), 134,5 (naphthas. ), 133,6 (naphthas.), 131,7 (naphthas.), 128,5 (naphthas.), 125,2 (naphthas.), 123,6 (naphthas.), 110,9 (thiazole), with 45.8 (CH2), and 31.7 (CH).

Example 106. N-[1-(4-Pentenyl)-N'-(2-thiazolyl)thiourea.

A mixture of 4-pentenol (3.04 from g to 35.3 mmol), pyridine (2,79 g, 35,3 mmol) and 25 Orleanslindsay acid. The reaction mixture is slowly heated (30 min) to room temperature and the resulting salt is filtered off.

The filtrate is added dropwise at about -30oC is added to a mixture of 10 ml of diethyl ether and 30 ml of liquid ammonia. The ammonia is evaporated and the remaining solution was left to warm to room temperature. The ether solution is extracted with 10 ml of 10 M aqueous sodium hydroxide. By distillation at atmospheric pressure to obtain 4-pentylamine (2.35 g, 27.6 mmol).

According to the method of example 105 condense 0,85 g (10 mmol) of the obtained amine with 2.1 g of the product of example 103. Crystallization from a mixture of n-hexane to toluene obtain pure product.

1H-NMR (CDCl3), : of 1.85 ppm (m) and 2.2 ppm (m), which is 3.7 ppm (m), 5-5,15 ppm (m), 5,75-5,95 h/m (m), 6.85 h/m (d), and 7.3 ppm (d).

13C-NMR (CDCl3), : 177, 162, 137, 116, 111, 45, 31, 28 h/million

Example 107. N-[2-(3-Trifluoromethyl)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is synthesized according to the method similar to the method of example 106, using 1-trifluoromethyl-3-ethanolbased.

1H-NMR (CDCl3), : 3 (t, PhCH2, 2H), 4 (K, CH2N, 2H), 6,8 (d, thiazole, 1H), 7,4-7,6 (mult., o-, m - and n-, 4H).

Example 108. N-(CIS-3-Hexenyl)-N'-(2-thiazolyl)tibmachuni is canola.

1H-NMR (CDCl3), : 7,3 (d, J = 3,9 Hz, 1H, thiazole), 6,83 (d, J = 3.8 Hz, 1H, thiazole), 5.56mm and 5.4 (m, 2H, H-C=C-H), 3,75 (K, 2H, CH2NH), 2,47 (K, 2H, CH2), 2,09 (K,2H, CH2), of 0.95 (t, J = 5.4 Hz, 3H, CH3).

13C-NMR (CDCl3), : 177 (C=S), 161 (thiazole), 137,5 (thiazole), 134,8 (C= C), of 124.6 (C=C), 111 (thiazole), to 45.4 (CH2-NH), 26,3 (CH2), 20,6 (CH2), 14,1 (CH3).

Example 109. N-[2-(1-Naphthyl)ethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method similar to the method of example 106, using (1-naphthyl)-2-ethanol.

1H-NMR (CDCl3+CD3OD), : 8,24 to 7.4 (m, 7H, naphthas.), 7,16 (d, J = 3,7 Hz, 1H, thiazole), 6,8 (d, J= 3,7 Hz, 1H, thiazole), 4,1 (t, J= 7.5 Hz, 2H, CH2NH), 3,49 (t, J = 7.5 Hz, 2H, CH2).

Example 110. N-[2-(2-Fluoro)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method similar to the method of example 106, using 1-fluoro-2-ethanolbased.

1H-NMR (CDCl3), : 7,28-7,03 (m, 5H, thiazole, FPh), for 6.81 (d, J=3.8 Hz, 1H, thiazole), 3,99 (K, J = 7,1 Hz, 2H, CH2NH), is 3.08 (t, J=7 Hz, 2H, CH2).

13C-NMR (CDCl3), : 178 (C=S), 161 (thiazole), 137,4 (thiazole), 131 (d, C-F-bond, FPh), 128 (d, C-F-bond, FPh), 124 (FPh), 115,4 (FPh), 115 (FPh), 111 (thiazole), 45,3 (CH2), 28,1 (CH2).

Example 111. N-[2-(2-Trifluoromethyl)phenethyl]-N'-(2-thiazolane 1-trifluoromethyl-2-ethanolbased.

1H-NMR (CDCl3), : 7,66 (d,1H, TFMPh), 7,51 (m, 2H, TFMPh), 7,34 (m, 1H, TFMPh), 7,26 (d, J = 3.6 Hz, 1H, thiazole), at 6.84 (d, J= 3.8 Hz, 1H, thiazole), 3,99 (K, J= 6.3, in Hz, 2H, CH2NH), 3,23 (t, J=7,6 Hz, 2H, CH2).

13C-NMR (CDCl3), : 177,7 (C=S) 161,5 (thiazole), 137, 6mm (thiazole), 136,9 (TFMPh), 131,8 (TFMPh), 131, 6mm (TFMPh), 129 (C-F-bond, CF3), 126,6 (TFMPh), 125,9 (d, TFMPh), 111,1 (thiazole), 46,3 (CH2), OF 31.4 (CH2).

Example 112. N-(3-Pentenyl)-N'-(2-thiazolyl)thiourea.

The original 3-pentylamine was synthesized from 3-penten-1-ol.

3-Pentylamine. To a solution of 3-pentyn-1-ol (2 g, to 23.8 mmol) and pyridine (1,92 ml of 23.8 mmol) in diethyl ether (50 ml) is added at -45oC anhydride triftormetilfullerenov acid. The mixture is stirred for 15 min at the same temperature and with stirring, filtered cold diethyl ether (10 ml), saturated at -45oC NH3. The reaction mixture is stirred 3 h at room temperature and after evaporation obtain yellow crystals (2 g, 36%) as a salt of 3-pentylamine with triftormetilfullerenov acid.

1H-NMR (250 MHz, D2O), : of 3.12 (t, 2H, CH2- NH+3), to 2.55 (m, 2H, CH2- CC) 1,78 (t, 3H, CH3- CC).

13C-NMR (250 MHz, D2O), : 126, 83, 77, 41, 20, 5.

Then the method anals, CDCl3, : 7,33 (d, 1H, CH=CH), 6.87 in (d, 1H, CH=CH), 3,86 (K, 2H, CH2-NH), 2,56 (Tr. t, 2H, CH3-C C), is 1.81 (t, 3H, CH3-C C).

13C-NMR (250 MHz, CDCl3), : 178, 162, 138, 111, 45, 19, 4.

Example 113. 3-(2-Phenethyl)-2-thioxo-1,2,3,4-tetrahydroquinazolin.

In 200 ml of acetonitrile was dissolved 2-nitrobenzaldehyde (10 g, 66 mmol) and 2-phenethylamine (8,3 ml, 66 mmol) with pH 6 by adding acetic acid.

The largest portions add Lamborghini sodium. The solution is stirred for 40 min, diluted with water (400 ml) and extracted with ether.

Acid-base distribution (aq. HCl, in one. NH4OH) get oil that is suspended in water (200 ml), then added iron dust (10 g, 180 mmol). The mixture is heated to boiling and slowly add HCl (conc. aq.) and continue boiling for 40 minutes the Solution is cooled and alkalinized 40% sodium hydroxide to pH 14. The solution is stirred with toluene (700 Il) and filtered through a layer of celite.

Acid-base distribution (aq. HCl, aq. NH4OH) and evaporation receive the oil which is dissolved in acetonitrile (20 ml), then added N, N-thiocarbonyldiimidazole (0.7 g, 6.6 mmol). The solution is stirred for 72 h at room temperature, heated to 40 mi is Yu ethyl acetate hexane (1:3).

Product spontaneously crystallized from pure fractions with the formation of a long needle.

1H-NMR (CDCl3), : 3 (t, PhCH2, 2H), 4,1 (t, PCH2CH2N, 2H), 4,4 (s, PhCH2N, 2H), 6,7-7,5 (m, C6H5C6H4, 9H), and 8.7 (broad s, NH, 1H).

Example 114. N-(2-Phenethyl)-N'-[2-(3-methyl)pyridyl]thiourea.

Mix a solution of 2-geneticization (1.63 g, 10 mmol, 1.5 ml) and 2-amino-3-methylpyridine (1.08 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. After 16.5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (2% ethyl acetate in dichloromethane) to obtain 1.77 g (65%) of the specified compounds by recrystallization from a mixture of ethyl acetate/hexane receive 878 mg of the compounds in the form of pale yellow crystals, so pl. 82-84oC.

IR (KBr), cm-1: 3430, 2945, 1594, 1555, 1454, 1268, 1243, 1161.

1H-NMR (300 MHz, DMSO-d6), : are 11.62 (ush.s, 1H), 8,66 (s, 1H), 7,9 (d, J= 4,1 Hz, 1H), to 7.59 (d, J=7.2 Hz, 1H), 7,28-to 7.15 (m, 5H), of 6.96 (LW.d, J=7.4 and 5Hz, 1H), 3,84-of 3.78 (m, 2H), 2,89 (t, J=7 G4).

Found,%: C 66,66; N 6,32; N 15,73. C15H17N3S

Calculated,%: C 66,39; H6,31; N 15,48.

Example 115. N-[2-(2-Thienyl)ethyl]-N'-(2-thiazolyl)thiourea.

In 50 ml of diethyl ether are dissolved 6.4 g of 2-(2-thienyl)ethanol (50 mmol) and 3.95 g of pyridine (50 mmol). The mixture is cooled to -30oC and with stirring, added dropwise to 5.7 g methanesulfonanilide (950 mmol). Then the reaction mixture is heated and incubated for 30 minutes at boiling temperature. The mixture is cooled to room temperature and filtered. The filtrate is transferred into the autoclave together with 100 ml of a solution of ammonia in methanol (saturated at 0oC). The autoclave is sealed and heated for 17 hours at 150oC. the Solvent is removed by evaporation in vacuo and to the residue was added 100 ml of 5 M aqueous sodium hydroxide. The mixture was twice extracted with 100 ml methylene chloride to obtain a solution of 2-(2-thienyl)ethylamine mixed with the secondary amine.

Net primary amine receive fractional crystallization from methanol salts with oxalic acid, followed by addition of aqueous sodium hydroxide and extraction of methylene chloride.

To a solution of 800 mg of thiocarbonyldiimidazole (4.5 mmol) in 5 ml of methylene chloride added at 0oC 500 mg cell removed in vacuo and to the residue add 5 ml of dimethylformamide 500 mg 2-aminothiazole. The resulting mixture is heated for 17 h at 110oC. After evaporation of the solvent under vacuum was added 100 ml of ethyl acetate and the mixture is heated at 50oC. Warm the mixture was twice washed with 20 ml of 1 M HCl and once with 20 ml water. Evaporation of the solvent to get a small amount of crystals of the target product. Double recrystallization from ethyl acetate to obtain 340 mg of highly pure product.

13C-NMR (CDCl3+ DMSO-d6), : 178, 162, 141, 137, 127, 125, 124, 111, 46, 29 h/million

1H-NMR (CDCl3+ DMSO-d6), : 3.3V h/m (t), at 3.9 ppm (m), 6.85 h/m (d) and 6.9 ppm (m), to 7.2 ppm (d), to 7.25 ppm (d).

Example 116. N-[2-(2-Fluoro-6-chloro)phenethyl]-N'-(2-thiazolyl) thiourea.

In 30 ml of diethyl ether dissolve 2-chloro-6-perforaciones (2.5 g, 14.7 mmol) and the solution for 10 min in small portions add sociallyengaged (1.5 g). The mixture is then boiled for 15 min and after cooling to room temperature, slowly add 1.5 ml of water, 1.5 ml of aqueous sodium hydroxide and 4 ml of water. The ether solution containing the target 2-chloro-6-fortunetelling, decanted and the solvent is removed in vacuum.

The connection of the obtained amine with the product of example 103 according to the method of examples 104 and 105 receive after precrystallizer (d), 7,15 of 7.3 ppm (m), to 7.4 ppm (d).

Example 117. N-[2-(3-Methoxy)phenethyl]-N'-(2-thiazolyl) thiourea.

By the method similar to the method of example 105, conduct the reaction product of example 103 3-methoxyphenethylamine with obtaining the specified connection.

1H-NMR (DMSO - d6), : 2,9 (t, Ph, CH2, 2H, in), 3.75 (s, OCH3, 3H), 3,9 (CH2N, 2H), 6,8 (m, o - and n-, 4H), and 7.1 (d, thiazole, 1H), 7,2 (t, m, 1H), and 7.4 (d, thiazole, 1H).

Example 118. N-(2-Phenethyl)-N'-[2-(5-methyl)pyridyl]thiourea.

Mix a solution of 2-geneticization (1.63 g, 10 mmol, 1.5 ml) and 2-amine-5-methylpyridine (1.08 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 125oC. Through 16,54 the reaction mixture is cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. The obtained solid product was then purified pressure chromatography on silica gel (2% ethyl acetate in dichloromethane) to give a 2.01 g (74%) of the specified connection, by recrystallization from a mixture of ethyl acetate/hexane get 1,72 g of the compounds in the form of white crystals, so pl. 153-154oC.

IR (KBr), cm-1: 3235, 2939, 1613, 1559, 1534, 1493, 1300, 1188.

MS (FD) m/e 271 (M+).

UV (EtOH): 298 nm ( = 14080), 268 nm ( = 21638), 248 nm ( =15905).

Found,%: C 66,33; H Of 6.26; N 15,33.

C15H17N3S

Calculated,%: C 66,39; H Of 6.31; N 15,48.

Example 119. N-Methyl-N-(5-phenethyl)-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method similar to the method of example 105, the reaction product of example 103 N-methylphenethylamino.

1H-NMR (DMSO-d6), : 2,9 (t, PhCH2CH), 3,2 (s, NCH3, 3H), 4 (t, CH2N, 2H), 6,8 (t, thiazole, 1H), 7,2 (m, thiazole, 1H), and 7.3 (m, C6P5, 5H).

Example 120. N-(2-Indanyl)-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method similar to the method of example 105, the reaction product of example 103 2-indanamine.

1H-NMR (DMSO-d6), : 2,4 (K, CH2, 2H), 3,3 (CH2, 2H), 4,8 (K, CHN, 1H), 7 (d, thiazole, 1H), 7,1-7,3 (m, C6H4, 4H), and 7.4 (d, thiazole, 1H).

Example 121. N-[2-(2-Azido)phenethyl]-N'-(2-thiazolyl)thiourea.

In 15 ml of water at 0oC dissolved 2-aminopenicillanic alcohol (oliris, 0.8 g, 5.8 mmol) to the solution add triperoxonane acid (1.2 ml), then add sodium nitrite (0,41 g, 0.6 mmol), dissolved in Galicia (0,59 g, 12 mmol) in water (2 ml) and the solution is brought to room temperature. The solution is extracted with diethyl ether (3 x 50 ml), the organic phase is washed with 1 n aq. HCl (2 x 20 ml), dried over Na2SO4, filtered and evaporated.

The balance in the atmosphere of nitrogen dissolved in dichloromethane (20 ml), the solution is cooled to -10oC and to it add ethyldiethanolamine (1.1 ml, 6.4 mmol).

Added dropwise to the anhydride triftormetilfullerenov acid (0,87 ml, 5.17 mmol), the solution stirred for 20 min at 0oC, and then with vigorous stirring, a solution of ammonia (g) in methanol (50 ml, saturated at 0oC). The solution is stirred for 40 min at room temperature, diluted with water (100 ml) and extracted with dichloromethane (2 x 50 ml). Acid-base distribution (NH4OH, water, HCl, water) and evaporation receive 2-azidoaniline.

By the method similar to the method of examples 104 and 105, conduct the reaction product of example 103 2-azidoaniline and get the specified connection.

1H-NMR (DMSO-d6), : 2,9 (t, PhCH2, 2H), 3,8 (CH2N, 2H), 7 to 7.4 (m, Ph-O, m-, n-, triazole, 6H).

Example 122. N-[2-(3-Fluoro)phenethyl]-N'-(2-thiazolyl)thiourea.

This connection is received, the>/P>1H-NMR (DMSO-d6), : 2,9 (t, PhCH2, 2H), 3,8 (CH2N, 2H), 7 to 7.4 (m, Ph-O, n-, m-, thiazole, 6H).

Example 123. N-[2-(Benzosulfimide-4-ethyl]-N'-(2-thiazolyl) thiourea.

This compound is obtained according to the method similar to the method of example 105, the reaction product of example 103 4-(2-amino-ethyl)benzosulfimide.

1H-NMR (DMSO-d6), : 3 (t), 3,8 (m) and 7.1 (d), 7,35 (m), 7,45 (d), and 7.8 (d).

13C-NMR (DMSO-d6-CDCl3), : 178, 162, 143, 142, 137, 129, 126, 112, 45, 34.

Example 124. N-[2-(3,4-Dimethoxy)phenethyl]-N'-(2-thiazolyl) thiourea.

This compound is obtained according to the method similar to the method of example 105, the reaction product of example 103 from 3.4-dimethoxyphenethylamine.

1H-NMR (DMSO-d6-CDCl3), : 2,95 (t), 3,7 (t), 3,85 (s) of 3.9 (C), 6,8 (C) and 6.9 (C) and 7.4 (d).

Example 125. N-(Phenylpropane-1-ol-2-yl)-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method similar to the method of example 105, the reaction product of example 103 with norephedrine.

1H-NMR (DMSO-d6), : 0,95 (d), 4,25 (m) 4,95 (d) and 7.1 - 7.5 (m).

Example 126. N-[2-(2-Pyridyl)ethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained by reaction of the product from example 103 2-(2-amino-ethyl)pyridine (m, ,5 (d), 9,8 (C) to 11.7 (C).

Example 127. N-[2-(2,5-Dimethoxy)phenethyl]-N'-(2-thiazolyl) thiourea.

This compound is obtained by reaction of the product from example 103 with 2,6-dimethoxyphenethylamine by the method similar to the method of example 105.

1H-NMR (CDCl3), : 3 (t) of 3.73 (C) of 3.77 (s), 3,97 (m), 6,7 - 6,85 (m), 7,24 (d), and 10.8 (C).

13C-NMR (CDCl3), : 177, 162, 153, 152, 138, 128, 117, 112, 111, 111, 56, 56, 46, 30.

Example 128. N-[1-(2-Phenyl)propenyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained by reaction of the product from example 103 1-amino-2-phenylpropane by the method similar to the method of example 105.

1H-NMR (DMSO-d6), : 1,2 (d), 3,13 (K), 3,7 (t), to 7.09 (d), 7,2 - 7,5 (m). Broad peaks : 8,14; was 9.33; 9,75 and 10,57.

Example 129. N-[2-(3-Indolyl)ethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained by reaction of the product from example 103 with tryptamine by the method similar to the method of example 105.

1H-NMR (CDCl3+ CD3OD), : 7,68 - 7,06 (m, 6H, indole, thiazole), at 6.84 (d, J = 3,7 Hz, 1H, thiazole), was 4.02 (t, J = 7 Hz, 2H, CH2NH), 3,26 (t, J = 6.9 Hz, 2H, CH2).

13C-NMR (CDCl3+ CD3OD), : 177 (thiazole), 161 (thiazole), 137 (thiazole), 136 (indole), 127 (indole), 123 (indole), 121 (indole), 118 (indole), 117 (indole), 111 (thiazole), 110 (indole), 109 (S="ptx2">

This compound is obtained by reaction of the product from example 103 2-(2-aminoethoxy)ethanol according to the method similar to the method of example 105.

1H-NMR (CDCl3), : 7,34 (d, J = 3,4 Hz, 1H, thiazole), at 6.84 (d, J = 3,4 Hz, 1H, thiazole), of 3.95 (t, J = 4.9 Hz, 2H, CH2NH), 3,76 (m, 4H, CH2), 3,66 (t, J = 4.3 Hz, 2H, CH2).

13C-NMR (CDCl3), : 177,4 (C=S), 161,8 (thiazole), 137,5 (thiazole), 111,2 (thiazole), 72,1, 68,4, 61,5, 44,9.

Example 131. N-[2-(5-Nitrapyrin-2-yl)aminoethyl]-N'-(2-thiazolyl) thiourea.

This compound is obtained by reaction of the product from example 103 2-(2-ninetynine)-5-nitropyridine by the method similar to the method of example 105.

1H-NMR (CDCl3+ CD3OD), : of 8.95 (d, 1H, feast.), 8,12 (LW. d, 1H, feast.), 7,26 (d, J = 3.8 Hz, 1H, thiazole), 6,86 (d, J = 3.8 Hz, 1H, thiazole), of 6.52 (d, 1H, feast.), to 3.99 (t, 2H, CH2NH), of 3.78 (t, 2H, CH2).

Example 132. N-[2-(1-Methylpyrrole-2-yl)ethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained by reaction of the product from example 103 2-(2-amino-ethyl)-1-methylpyrrolidine by the method similar to the method of example 105.

1H-NMR (CDCl3), : to 7.32 (d, J = 4 Hz, 1H, thiazole), 6,83 (d, J = 3.6 Hz, 1H, thiazole), 3,78 (K, 2H, CH2NH), is 3.08 [m, 1H, NCH(CH2)2], was 2.34 (s, 3H, N-CH3), of 2.16 (m, 2H, NCH2), a 2.01 (m, 2H, CH2), and 1.7 (m,H2), TO 40.6 (CH2), 32,1 (PIR.), 30,3 (PIR.), 22,2 (PIR.).

Example 133. N-[2-(2,4-Dichloro)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained by reaction of the product from example 103 with 2,4-dichlorophenylamino by the method similar to the method of example 105.

1H-NMR (CDCl3+ CD3OD), : 7,4 (d, 1H, thiazole), 7,41 (s, 1H, Cl2Ph), from 7.24 (m, 2H, Cl2Ph), 6.87 in (d, 1H, thiazole), of 3.95 (t, 2H, CH2NH), 3,14 (t, 3H, CH2).

Example 134. N-[1,1-(2-n-Hydroxyphenyl)methoxycarbonylethyl] -N'-(2-thiazolyl)thiourea.

This compound is obtained by reaction of the product from example 103 with methyl ether of tyrosine by the method similar to the method of example 105.

1H-NMR (CDCl3), : to 7.25 (d, J = 3.3 Hz, 1H, thiazole), 7,02 (d, J = 8,2 Hz, 2H, Tyr. ), PC 6.82 (d, J = 3,4 Hz, 1H, thiazole), 6,74 (d, J = 8,2 Hz, 2H, Tyr.), of 5.29 (t, 1H, CH), to 3.73 (s, 3H, CH3), 3,19 (d, 2H, CH2).

13C-NMR (CDCl3), : 177,4 (C=S), WHICH IS 171,5 (CO2Me), 161,2 (thiazole), 155,4 (Tyr. ), 136,9 (thiazole), 130 (Tyr. ), 126,2 (Tyr. ), 115 (TIR.), 111,1 (thiazole), 59 (CH), with 51.9 (CH3), 36,4 (CH2).

Example 135. 1-(2-Thiazolyl)-4-(n-hydroxybenzyl-2-thiohydantoin.

This compound is obtained as a side product in the synthesis of the compound of example 134.

1H-NMR (CDCl3+ CD3OD), : 7,(2-TRANS-Vinylcyclopropyl)-N'-(2-thiazolyl) thiourea.

This compound is obtained by reaction of the product from example 103 with TRANS-2-phenylcyclopropane by the method similar to the method of example 105.

1H-NMR (CDCl3+ CD3OD), , 7,32 (d, J = 3.8 Hz, 1H, thiazole), of 7.23 (m, 5H, Ph) to 3.38 (m, 1H, CHNH), and 2.27 (m, 1H,CH), at 1.91 (m, 2H, CH2).

13C-NMR (CDCl3+CD3OD), : 179,2 (C=S), of 161.7 (thiazole), 139,8 (Ph), 137,3 (thiazole), 128,2 (Ph), 126,5 (Ph), 126 (Ph), 111,2 (thiazole), 36,1 (CH), 35,1 (CH), 16,1 (CH2).

Example 137. N-(4-Methyl-3-pentenyl)-N'-(2-thiazolyl)thiourea.

The original 4-methyl-3-pentylamine obtained from 5-bromo-2-methyl-2-pentene.

4-Methyl-3-pentylamine. To a solution of 5-bromo-2-methyl-2-pentene (1.63 g, 10 mmol ) in 5 ml of DMF add LiN3(1 g, 20 mmol) and the solution stirred for two days at room temperature. Then the reaction mixture is transferred into a mixture of hexane with a saturated solution of NH4Cl. The organic phase is washed with a saturated solution of NH4Cl, brine and water. After drying the solvent is removed and the crude azide is subjected to reaction with LiAlH4(380 mg, 10 mmol) in ether at 0oC. After 2 h, the reaction mixture is neutralized by adding 380 μl of water, 380 μl of 15% NaOH solution and 1.14 ml of water, in that order. After filtration the solvent is evaporated and the distillation residue in OCI with, 2H), and 1.6 (d, 3H), and 1.7 (d,3H), 2,68 (K, 2H), of 5.05-of 5.15 (m, 1H).

13C-NMR (CDCl3), : 17,7, 18,39, 25,66, 32,22, 42,03, 121,64, 133,5.

This compound is obtained by reaction of the product from example 103 4-methyl-3-pentylamine by the method similar to the method of example 105, so pl. is 87.5 88.5 inoC.

Found,%: C 49,35; H 6,2; N 17,15.

Calculated,%: C 49,76; H Of 6.26; N 17,41.

1H-NMR (CDCL3), : 1,65 (c,3H), 1,75 (c,3H), 2,4 (K,2H), to 3.73 (m,3H), 5,1-a 5.25 (m, 1H), 6,83 (d,1H), 7,29 (d, 1H).

13C-NMR (CDCl3), : 17,93, 25,88, 27,31, 45,54, 111,22, 120,4, 135,1, 137,51, 161,94, 177,21.

Example 138. N-(TRANS-3-Hexenyl)-N'-(2-thiazolyl)thiourea.

The original TRANS-hexanamine obtained from TRANS-3-HEXEN-1-ol.

TRANS-3-Hexanamine. To a stirred solution of TRANS-3-HEXEN-1-ol (5 g, 0.05 mol), Et3N (7.65 ml, by 0.055 mol) and CH2Cl2(70 ml) at -30oC add 4,33 ml (by 0.055 mol) of methanesulfonamide and the solution stirred for 2 h at -20oC. After addition of CH2Cl2the organic phase is washed with a saturated solution of NaHCO3, a saturated solution of NH4Cl and water, dried (Na2SO4) and concentrated in vacuo. The result is raw mesilate, which is dissolved in DMF (30 ml), then add LiN3(5 g, 100 mmol). The reaction is x) and dried (Na2SO4). The ether solution is concentrated to about 100 ml and cooled to 0oC, then added to 1.9 g (50 mmol) of LiAlH4. After 1 h, the reaction mixture is neutralized by the sequential addition of 1.9 ml of water, 1.9 ml of 15% NaOH solution and 5.7 ml of water. After filtration, evaporation of the solvent and distillation of the residue in vacuum to obtain 2.35 g of the specified amine, so Kip. 34oC/20 mm RT. Art.

1H-NMR (CDCl3), : 0,92,-1,05 (m, 3H), of 1.75 (broad s, 2H), 1,95-2,2 (m, 4H), 2,68 is 2.75 (m, 2H), 5,27-5,63 (m, 2H).

13C-NMR (CDCl3), : 13,8, 25,55, 36,62, 41,56, 126,1, 134,48.

Reaction of TRANS-3-hexanamine with the product from example 103 according to the method similar to the method of example 105, received the specified connection, so pl. 116-117oC.

Found,%: C Of 49.6; H 6,3; N 17,4.

Calculated,%: C 49,76; H Of 6.26; N 17,41.

1H-NMR (CDCl3), : and 0.98 (t,3H), 2-2,1 (m, 2H), 2,41 (K,2H), 3,76 (K, 2H), 5,4-5,7 (m, 2H), 6,83 (d, 1H), 7,29 (d, 1H), and 10.8 (broad s, 1H), 11,35 (broad s, 1H).

13C-NMR (CDCl3), : 13,72, 25,65, 45,42, 111,25, 124,97, 135,56, 137,5, 161,95, 177,14.

Example 139. N-[2-(Cyclo-2-penten-1-yl)ethyl]-N'-(2-thiazolyl)thiourea.

The original 2-(cyclo-2-penten-1-yl)ethylamine obtained from 2-cyclopenten-1-yl-acetic acid.

2-(Cyclo-2-penten-1-yl)ethylamine. the 0,063 mol). Upon completion of addition, the reaction mixture was stirred 2 h at room temperature. Then the reaction mixture is neutralized by the sequential addition of 2.4 g of water and 2.4 g of 15% aqueous NaOH solution and 7.2 ml of water. Filtration and evaporation receive of 4.45 g of crude 2-(cyclo-2-penten-1-yl)ethanol. The resulting alcohol is converted into the specified amine according to the method similar to the method of example 138.

1H-NMR (CDCl3), : 1,4-1,8 (m,4H), 2-2,15 (m, 1H), 2,2-2,4 (m,3H), 2,6-2,8 (m, 3H), 5,6-5,8 (m, 2H).

The reaction of 2-(cyclo-2-penten-1-yl) - ethylamine with the product of example 103 according to the method similar to the method of example 105, the received specified in the title compound, so pl. 139-140oC.

13C-NMR (CDCl3), : 29,68, 31,78, 40, 40,64, 42,97, 130,29, 134,61.

Found,%: C 52,2; H Equal To 6.05; N 16,35.

Calculated,%: C 52,14; H 5,97; N 16,58.

1H-NMR (CDCl3), : 1,42 is 1.58 (m, 1H), 1,62-of 1.92 (m, 2H), 2.06 to a 2.45 (m, 3H), 2,72-of 2.86 (m, 1H), 3,71-a-3.84 (m,2H), 5,7-5,8 (m,2H), 6,85(d, 1H), 7,32 (d, 1H), up 10.9(broad s, 1H), 10,96 (broad s, 1H).

13C-NMR (CDCl3), : 29,71; 32,01; 34,77; 43,23; 44,31; 111,15; 131,19; 134,13; 137,66; 161,99; 177,28.

Example 140. N-[2-(TRANS-3-Pentenyl)]-N'-(2-thiazolyl)thiourea.

The original TRANS-3-penten-1-ol obtained by reduction of 3-pentyn-1-ol by sociallyengaged in boiling tetrahydrofuran, H-NMR (250 MHz, CDCL3), : 7,28 (d,1H, CH=CH), 6,83 (d,1H, CH=CH), 5,66 is 5.38( m, 2H, TRANS-CH=CH), 3,67 (K, 2H, CH2-NH), 2,37 (K, 2H, CH2-CH= CH), 1,72 (LW.d,3H, CH=CH-CH3).

13C-NMR (250 MHz, CDCl3), : 177, 162, 138, 129, 127, 111, 46, 32, 18.

Found,%: C 47,9; H 5,8; N 17,8.

C9H13N3S2< / BR>
Calculated,%: C And 47.5; H 5,7; N 18,5.

Example 141. N-[2-(CIS-3-Pentenyl)]-N'-(2-thiazolyl)thiourea.

The original CIS-3-penten-1-ol obtained by reduction of 3-pentyn-1-ol with hydrogen in acetone at about 5 psi (0.35 kg/cm2in the presence as catalyst of palladium on calcium carbonate (Lindlar catalyst), then according to the methods of examples 106 and 112 received the specified connection, so pl. 76,5oC.

1H-NMR( 250 MHz, CDCl3), : 7,3 (d, 1H, CH=CH), 6,83 (d,1H, CH=CH), 5,73 -5,74 (m, 2H, CIS-CH=CH), 3,76 (K, 2H, CH2-NH), 2,48 (K, 2H, CH=CH-CH2), of 1.66 (d, 3H, CH=CH-CH3).

13C-NMR (250 MHz, CDCl3), : 177, 162, 138, 127, 126, 111, 45, 26.

Example 142. N-[2-(2-Methyl)phenethyl]-N'-(2-thiazolyl)thiourea.

Source 1-methylpentanol obtained by reduction of o-tolyloxy acid sociallyengaged in boiling tetrahydrofuran, then according to the methods of examples 106 and 112 synthesized the specified connection, so pl. 143-144oC.

In 70 ml of methanol is dissolved 3,4,5-trimethoxybenzoate (965 mg, 5 mmol) and cobalt chloride (2.37 g, 10 mmol) and the solution was added sodium borohydride (1.89 g, 50 mmol). After 3 h the reaction mixture was filtered through celite and concentrated to small volume. The residue is transferred into chloroform and extracted with 1 N. HCl (100 ml). The organic phase is discarded. The aqueous solution is alkalinized water ammonia and chloroform extracts. The organic phase is dried over magnesium sulfate and after drying in a vacuum get 427 mg of 2-(3,4,5-trimetoksi)phenethylamine.

1H-NMR (CDCl3), : to 6.58 (s,2H, h), 3,85 (m, 8H, 2x MeO, CH2), 3,82 (c, 3H, OMe), and 3.8(m, 2H, CH2).

Then by the method of example 105 received the specified connection.

1H-NMR (CDCl3), : 7,26 (d, 1H, thiazole), 6,85 (d, 1H, thiazole), only 6.64 (s, 2H, TMPh), 4,84 (d, J=5.7 Hz, 2H, CH2NH), 3,86 (m, 11H, CH2, MeO).

13C-NMR (CDCl3), : 177 (C=S), 161 (thiazole), 153 (TMPh), 138 (TMPh), 137 (thiazole), 132 (TMPh), 111 (thiazole), 104,8 (TMPh), 61 (MeO), 56,1 (MeO), 53 (CH2), 50 (CH2).

Example 144. N-[2-(2,4-Debtor)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method similar to the method of example 143, using 2,4-differentiational.

2).

Example 145. N-[2-(2,6-Debtor)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method similar to the method of example 143, using 2,6-differentiational.

1H-NMR (CDCl3), : of 7.23 (d, J=3.8 Hz, 1H, thiazole), 7,26 for 7.12 (m, 1H, h), 6,86 (m, 2H, h), for 6.81 (d, J = 3.6 Hz, 1H, thiazole), 3,96 (K, 2H, CH2NH), 3,11 (t, J=7 Hz, CH2).

13C-NMR (CDCl3), : 177 (C=S), 164 and 159 (LW.d, C-F-bond, Ph), 162 (thiazole), 137 (thiazole), 128 (m, C-F-bond, h), 111 (thiazole) and 110.8 (d, C-F-bond, h), 44.5cm (CH2), TO 21.6 (CH2).

Example 146. N-[2-(3,4-Methylendioxy)phenethyl]-N'-(2-thiazolyl)thiourea.

The specified connection is synthesized according to the method of example 143, using 3,4-methylenedioxyphenylacetone.

1H-NMR (CDCl3), : 7,24 (d, 1H, thiazole), 6,8 (m, 3H, Ph, thiazole), 6,74 (s, 1H, Ph), to 5.93 (s, 2H, OCH2O) 3,94 (K, 2H, CH2NH), with 2.93 (t, 2H, CH2).

13C-NMR (CDCl3), : 177,3 (C=S), 161,6 (thiazole), 148 (Ph), 146 (Ph), 137,4 (thiazole), 132,1 (Ph), 111,1 (thiazole), 109,2 (Ph), To 108.2 (Ph), to 100.7 (OCH2O), 47 (CH2), 34,4 (CH2).

Example 147. N-[2-(4-Trifluoromethyl)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound is obtained according to the method of example 143, using 4-triptoreline, 1H, thiazole), 6,83 (d, J=3,7 Hz, 1H, thiazole), of 3.95 (t, J=7.2 Hz, 2H, CH2NH), is 3.08 (t, 2H, CH2).

Example 148. (RS)-N-[2-Methyl-2-(2,6-debtor)phenethyl] -N'-(2 - thiazolyl)thiourea.

Within 2 h are the reaction between 2,6-diftorbenzofenonom (1,24 ml, 10 mmol) and sodium hydride (360 mg, 12 mmol) in THF (5 ml), and then to the reaction mixture add itmean. After 30 min the reaction mixture was treated and the product emit column chromatography on silica gel. Received 985 mg (59%) of product.

1H-NMR (CDCl3), : (mixture of two stereoisomers) 7,28 (m, 1H, h), 6,98 (m, 2H, h), 4.26 deaths (m, 1H, CH), 1,69, and of 1.66 (2 x s, 3H, CH3).

Using the method of example 143 2-methyl-2-(2,6 - debtor)phenethylamine received specified in the header of the connection.

1H-NMR (CDCl3), : (R - and S-stereotimes) for 7.12 (m, 2H, h, thiazole), 6,85 (t, 2H, h), 6,77, 6,76, 6,75, 6,74 (2D, J=3.6 Hz, 1H, thiazole), 4,11 (m, 1H, CH), 4,05-the 3.65 (m, 2H, CH2), 1,45, of 1.42 (2s, 3H, CH3).

Example 149. N-[2-(2-Bromo)phenethyl]-N'-(2-thiazolyl)thiourea.

The specified connection is obtained by the method of example 143, using 2-bromophenylacetonitrile.

1H-NMR (DMSO-d6), : 2,9 (t, PhCH2, 2H), 3,05 (t, PhCH2, 2H), 3,8 (CH2N, 2H), and 7.1 (d, thiazole, 1H), 7,15-7,6 (m, o-, m-, n-, thiazole, 5H) is constrained by the method of example 116 using 1-phenyl-1-cyclopropanecarbonitrile.

1H-NMR (CDCl3), : 1 (d), and 3.8 (d) and 6.9 (d), 7,2-7,4 (m), 7,9, 9,5 (NH).

Example 151. N-[2-(2,6-Dimethoxy)phenethyl]-N'-(2-thiazolyl)thiourea.

Source 2,6-dimethoxyphenethylamine obtained on the basis of 2,6-dimethoxybenzaldehyde. Reaction with nitromethane in methodology (described in the ed. Yogel. Handbook of practical organic chemistry, S. 176, Longman, 1978, 4th ed. receive 2,6-dimethoxy - nitrosothiol. The compound obtained (1.1 g, 5.3 mmol) dissolved in a mixture of diethyl ether-tetrahydrofuran (2:1, 200 ml) and to the solution in small portions add sociallyengaged (0.5 g, 13 mmol). The mixture is boiled for 120 min and then treated with 0.6 ml of water, 0.6 ml of 15% aqueous NaOH and 1.8 ml of water. The mixture is filtered, purified acid-base distribution (NH4OH water, dilute aqueous HCl and evaporated. Obtained as a crude product 2,6-dimethoxyphenethylamine sufficiently pure to be used directly in the next stage, where its reaction with the product of example 103 according to the method of example 105 receive the specified connection.

1H-NMR (DMSO-d6), : 2,9 (t, PhCH2, 2H), 3,7 (CH2N, 2H), and 3.8 (s, OCH3, 6H), 6,7 (d, o-, 2H), and 7.1 (d, thiazole, 1H), 7,2 (t, n, 1H), and 7.3 (d, thiazole, 1H).

Example 152. N-[2-(3,5-Dimethoxy)and from example 103 with a 3.5-dimethoxyphenethylamine, obtained from 3,5-dimethoxybenzaldehyde.

1H-NMR (DMSO-d6), : 2,8 (t, PhCH2, 2H), 3,65 (s, OCH3, 6H), 3,7 (CH2N, 2H), 6,3 (t, n, 1H), 6,4 (t, o-, 2H), and 7.1 (d, thiazole, 1H), and 7.3 (d, thiazole, 1H).

Example 153. N-[2-(3,5-Dichloro)phenethyl]-N'-(2-thiazolyl)thiourea.

This compound was synthesized according to the method of example 151 reaction product of example 103 with a 3.5-dichlorophenylamino obtained from 3,5-dichlorobenzaldehyde.

1H-NMR (DMSO-d6), : 2,9 (t, PhCH2, 2H), 3,8 (CH2N, 2H), and 7.1 (d, thiazole, 1H), and 7.3 (m, o and n, 3H), and 7.4 (d, thiazole, 1H).

Example 154. N-[2-(2,5-Dichloro-6-hydroxy)phenethyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 151 spend the reaction product of example 103 with 2,5-dichloro-6-hydroxyphenylethylamine obtained from 2,5-dichloro-6-hydroxybenzaldehyde.

1H-NMR (CDCl3), : 3 (t, PhCH2, 2H), 3,9 (CH2N, 2H), 6,9 (d, o-, 1H), and 7.1 (d, thiazole, 1H), 7,2 (d, n, 1H), and 7.3 (d, thiazole, 1H).

Example 155. N-[2,3,6-Trichloro)phenethyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 151 spend the reaction product of example 103 with 2,3,6-trichloroethylene derived from 2,3,6-trichlorobenzaldehyde.

1H-NMR (DMSO-d6), : 3,3 (t, PhCH2, 2H), 3,4 (K, CH2N, 2H), and 7.1 (d, thiazole, 1H),2">

According to the method of example 151 spend the reaction of 2,3,4-triptorelin obtained from 2,3,4-tripersonality, with the product of example 103.

1H-NMR (CDCl3), : 3 (t, PhCH2, 2H), 4 (K, CH2N, 2H), 6,8 (d, thiazole, 1H), 6,85 and 7.6 (m, m -, and o-, 2H), 7,2 (d, thiazole, 1H).

Example 157. N-[2-(2,3,4-Trichloro)phenethyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 151 spend the reaction product of example 103 with 2,3,5-trichloroethylene obtained from 2,3,5-trichlorobenzaldehyde.

1H-NMR (DMSO-d6), : 3,05 (t, PhCH2, 2H), 3,9 (CH2N, 2H), and 7.1 (d, thiazole, 1H), and 7.4 (d, thiazole, 1H), 7.5 (d, o-, 1H), 7.7 (d, n, 1H).

Example 158. N-[2-(2,4-Dimethoxy)phenethyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 151 spend the reaction product of example 103 with 2,4-dimethoxyphenethylamine obtained from 2,4-dimethoxybenzaldehyde.

1H-NMR (CDCl3+CD3OD), : of 7.23 (d, J=3.6 Hz, 1H, thiazole), and 7.1 (d, J=7.8 Hz, 1H, DMPh), for 6.81 (d, J=3.6 Hz, 1H, thiazole), 6,44 (s, 1H, DMPh), 6.42 per (d, 1H, MPh), a 3.87 (t, 2H, CH2N), and 3.8 (s, 3H, OMe), 3,79 (s, 3H, OMe), to 2.94 (t, 2H, CH2).

13C-NMR (CDCl3+ CD3OD), : 177, 3 (C=S), 161,6 (thiazole), 159,7 (MPh), To 158.4 (MPh), 137,5 (thiazole), 130,9 (MPh), 119,1 (MPh), 110,9 (thiazole), to 103.8 (MPh), 99,3 (MPh), At 55.3 (OMe), 55,1 (OMe), and 45.5 (CH2), OR 28.7 (CH2).

Prim is oduct from example 103 with 2,3-dimethoxyphenethylamine, obtained from 2,3-dimethoxybenzaldehyde.

1H-NMR (CDCl3), : of 7.23 (d, J = 3,7 Hz, 1H, thiazole), 7,02-6,83 (m, 3H, MPh), 6,79 (d, J = 3.6 Hz, 1H, thiazole), 3,99 (K, J = a 8.9 Hz, 2H, CH2N), a 3.87 (s, 3H, OMe), 3,86 (s, 3H, OMe), was 3.05 (t, 2H, CH2).

13C-NMR (CDCl3), : 177,3 (C=S), 161,6 (thiazole), 152,6 (MPh), 147,3 (MPh), 137,3 (thiazole), 132 (MPh), 123,7 (MPh), 122,2 (MPh), 110,9 (thiazole) and 110.8 (MPh), 60,6 (OMe), Of 55.5 (OMe), 45,8 (CH2), TO 28.9 (CH2).

Example 160. N-[2-(2,3,5,6-Titrator)phenethyl]-N'-(2-thiazolyl)urea.

According to the method of example 151 spend the reaction product of example 103 2, 3,5,6-tetrafluoroethylene obtained from 2,3, 5,6-terephthalaldehyde.

1H-NMR (CDCl3+ CD3OD), : 7,24 (d, J = 3 Hz, 1H, thiazole), 6,98 (m, C-F-bond, 1H, Ph), 6,83 (d, J = 3 Hz, 1H, thiazole), to 3.99 (t, J = 6,8 Hz, 2H, CH2N) 3,18 (t, J = 6.9 Hz, 2H, CH2).

13C-NMR (CDCl3), : 178,2 (C=S) 161,5 (thiazole), 147,6 (m, Ph), 143,6 (m, Ph), 137,3 (thiazole), 117,6 (t, Ph), 111,1 (thiazole), 104,3 (t, Ph), 53,3 (CH2), 43,7 (CH2).

Example 161. N-[2-(2-Methoxy-5-bromo)phenethyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 151 spend the reaction product of example 103 2-methoxy-5-bromophenethylamine obtained from 2-methoxy-5-bromobenzaldehyde.

1H-NMR (CDCl3), : 7,34 (m, 3H, Ph and thiazole), 6, Example 162. N-[2-(2-Ethoxy)phenethyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 151 spend the reaction product of example 103 2-ethoxyphenylurea obtained from 2-ethoxybenzaldehyde.

1H-NMR (250 MHz, CDCl3), : 7,37-7,16 (m, 2H, arene.). 7,22 (d, 1H, ), 6,91-of 6.78 (m, 2H, arene. ), is 6.78 (d, 1H, ), 4,07-3,93 (HK, HN, CH2-NH, CH2-O), totaling 3.04 (t, 2H, Ph-CH2), to 1.42 (t,3H, OCH2CH3).

13C-NMR (250 MHz, CDCl3), : 178, 162, 157, 138, 131, 128, 127, 120, 111, 111, 63, 46, 30, 15.

The compound obtained has so pl. 140oC.

Found,%: C To 54.4; H 5,6; N 13,3.

C14H17N3OS2< / BR>
Calculated,%: C 54,6; H 5,5; N 13,7.

Example 163. N-[2-(2,3-Dichloro)phenethyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 151 spend the reaction product of example 103 with 2,3-dichlorophenylamino obtained from 2,3-dichlorobenzaldehyde.

1H-NMR (250 MHz, DMSO-d6), : at 7.55 (d, 1H, CHCH), 7,42-to 7.32 (m, 3H, arene.), for 7.12 (d, 1H, C-CH, 3,86 (K, 2H, CH2NH), of 3.12 (t, 2H, Ph-CH2).

13C-NMR (250 MHz, DMSO-d6), : 178, 162, 138, 130, 129, 128, 112, 44, 33.

Example 164. N-[2-(4-Chlorophenyl)ethyl]-N'-[2-C4,5-dimethyl)thiazolyl]thiourea.

A solution of 1-{ [2-(4,5-dimethyl)thiazolyl]thiocarbonyl}imidazole (10 mmol) and 2-(4-chlorophenyl)ethylamine (1.55 g, 10 mperature, transferred to the ethyl acetate and washed with water, 1 N. aqueous HCl, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate receive 2,44 g (75%) of the specified connection.

IR (KBr), cm-1: 3170, 3024, 1550, 1260, 1212, 708.

1H-NMR (300 MHz, DMSO-d6), : of 11.45 (sh.s, 1H), 9,8 (sh.s, 1H), 7,35 (d, J = 8 Hz, 2H), and 7.3 (d, J = 8 Hz, 2H), and 3.8 (m, 2H), 2,85 (t, J = 7 Hz, 2H), 2,2 (s, 3H), of 2.05 (s, 3H).

MS (FD) m/e 326 (M+).

UV (EtOH): 297 nm ( = 17467), 257 nm ( = 10021), 219 nm ( = 16075), 201 nm ( = 22380).

Found,%: C Of 51.7; H 5,07; N 13,08.

C14H16N3S2Cl

Calculated,%: C Of 51.6; H Of 4.95; N 12,89.

Example 165. 1-[(2-Oil[1,2]thiazolyl)thiocarbamoyl]imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (1.8 g, 20 mmol) and 2-aminonaphthol[1,2]thiazole (2 g, 20 mmol) in acetonitrile (150 ml) is stirred for 24 h at 65oC. Filtering the resulting precipitate receive 1,69 g (46%) of the specified connection.

IR (KBr), cm-1: 3148, 2670, 1465, 736.

1H-NMR (300 MHz, DMSO-d6), : 9,2 (s, 1H), cent to 8.85 (c,1H), 8,65 (d, J = 8 Hz, 1H), 8,2 (sh.s, 1H), 8-7,3 (m, 5H).

MS (FD) m/e 309 (M+-H).

UV (EtOH) : 383 nm ( = 8297), 244 nm ( = 15160), 226 nm ( = 17126).

Found,%: C 58,13; H 3,21; N 18,03.

C15H

A solution of 1-[(2-oil[1,2] thiazolyl)thiocarbamoyl[imidazole (1,69 g, 5 mmol) and 2-phenethylamine (of 0.62 g, 5.2 mmol) in N, N-dimethylformamide (20 ml) is stirred for 1 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue and ethyl acetate to obtain 1.5 g (82%) of the specified connection.

IR (KBr), cm-1: 3171, 3027, 1581, 1521, 1213, 695.

1H-NMR (300 MHz, DMSO-d6), : 11,7 (sh.s, 1H), 9,9 (sh.s, 1H), 8,25 (d, J = 8 Hz, 1H), 8 (d, J = 8 Hz, 2H), 7,8 (d, J = 8 Hz, 1H), 7,6 to 7.2 (m, 7H), 3,95 (m, 2H), 3,05 (t, J = 7 Hz, 2H).

MS (FD) m/e 363 (M+).

UV (EtOH) : 340 nm ( = 23922), 325 nm ( = 19262), 313 nm ( = 20808), 245 nm ( = 39665), 209 nm ( = 36141).

Found,%: C 65,86; H 4,84; N 11,48.

C20H17N3S2< / BR>
Calculated,%: C 66,09; H 4,71; N To 11.56.

Example 167. 1-{[2-(4-Methyl)thiazolyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (13,37 g, 75 mmol) and 2-amino-4-methylthiazole (8,55 g, 75 mmol) in acetonitrile (150 ml) is stirred 24 h at room temperature. Filtration of the resulting precipitate receive 14,22 g (85%) of the specified connection.

IR (KBr), cm-1: 3179, 2558, 1455, 1217, 737.

1H-NMR (300 MHz, DMSO-d6), : 8,55 (s, 1H), and 7.9 (s, 1H), 7,05 (s, 1H), 6,9 (s, 1H), 2,3 (s, 3H).

MS (FD) ="ptx2">

C8H8N4S2< / BR>
Calculated,%: C 42,84; H 3,59; N 24,98.

Example 168. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

A solution of 1-{[2-(4-methyl)thiazolyl]thiocarbamoyl}imidazole (2.24 g, 10 mmol) and 2-(1-cyclohexenyl)ethylamine (1.25 g, 10 mmol) in N, N-dimethylformamide (25 ml) is stirred for 4 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization from ethyl acetate to obtain 2.4 g (86%) of the specified connection.

IR (KBr), cm-1: 3177, 2918, 1565, 1505, 1202, 717.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (sh.s, 1H), 9,85 (sh.s, 1H), 6,65 (c, 1H), the 5.45 (s, 1H), 3,65 (m, 2H, in), 2.25 (m, 5H), and 1.9 (m, 4H), of 1.55 (m, 4H).

MS (FD) m/e 281 (M+).

UV (EtOH): 291 nm ( = 19178), 257 nm ( = 9837), 201 nm ( = 16247).

Found, %: C 55,40; H 6,82; N 14,77.

C13H19N3S2< / BR>
Calculated, %: C 55,48; H To 6.80; N 14,93.

Example 169. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

A solution of 1-{[2-(4-methyl)thiazolyl]thiocarbamoyl}imidazole (2.24 g, 10 mmol) and 2-(2-chlorophenyl)ethylamine (1.56 g, 10 mmol) in N,N-dimethylformamide (25 ml) is stirred for 1.5 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystal, 1214, 754, 706.

1H-NMR (300 MHz, DMSO-d6) : 11,6 (sh.s, 1H), 9,8 (sh.s, 1H), 7.5 to about 7.2 (m, 4H), of 6.65 (s, 1H), 3,85 (m, 2H), 3,05 (t, J = 7 Hz, 2H), 2,2 (s, 3H).

MS (FD) m/e 311 (M+).

UV (EtOH): 292 nm ( = 18641), 257 nm ( = 10471), 202 nm ( = 24729).

Found, %: C 49,99; H 4,56; N 13,45.

C13H14N3S2Cl

Calculated, %: C 50,07; H To 4.52; N 13,47.

Example 170. N-[2-(3-Chlorophenyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

A solution of 1-{ [2-(4-methyl)thiazolyl] thiocarbamoyl} imidazole (2.24 g, 10 mmol) and 2-(3-chlorophenyl)ethylamine (1.56 g, 10 mmol) in N,N-dimethylformamide (25 ml) is stirred for 1.5 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 2.67 g (86%) of the specified connection.

IR (KBr), cm-1: 3171, 3016, 1581, 1214, 761, 713.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh.s,1H), 9,85 (sh.s, 1H), and 7.4 to 7.2 (m, 4H), of 6.65 (s, 1H), 3,85 (m, 2H), 2.95 points (t, J = 7 Hz, 2H), 2,2 (s, 3H).

MS (FD) m/e 311 (M+).

UV (EtOH): 293 nm ( = 18976), 257 nm ( = 10523), 202 nm ( = 27048).

Found, %: C 49,94; H 4,48; N 13,37.

C13H14N3S2Cl

Calculated, %: C 50,07; H To 4.52; N 13,47.

Example 171. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

Dimethylformamide (25 ml) is stirred for 1.5 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate receive 2,52 g (81%) of the specified connection.

IR (KBr), cm-1: 3170, 3022, 1562, 1215, 744, 709.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh.s,1H), 9,85 (sh.s, 1H), 7,38 (d, J = 8 Hz, 2H), and 7.3 (d, J = 8 Hz, 2H), 6,65 (s, 1H), and 3.8 (m, 2H), 2,9 (t, J = 7 Hz, 2H), 2,18 (s, 3H).

MS (FD) m/e 311 (M+).

UV (EtOH): 292 nm ( = 16470), 257 nm ( = 9506), 219 nm ( = 20563).

Found,%: C 49,94; H 4,55; N Of 13.58.

C13H14N3S2Cl

Calculated,%: C 50,07; H To 4.52; N 13,47.

Example 172. N-[2-(2-Methoxyphenyl)ethyl-N'-[2-(4-methyl)thiazolyl]thiourea.

A solution of 1-{[2-(4-methyl)thiazolyl]thiocarbamoyl}imidazole (2.25 g, 10 mmol) and 2-(2-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N-dimethylformamide (25 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate to obtain 2.2 g (73%) of the specified connection.

IR (KBr), cm-1: 3173, 3024, 1568, 1246, 1206, 750, 694.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (sh.s,1H), 9,85 (sh.s, 1H), 7,2-to 6.8 (m, 4H), of 6.65 (s, 1H, in), 3.75 (m, 5H), 2,9 (t, J = 7 Hz, 2H), 2,18 (s, 3H).

MS (FD) m/e 307 (M+).

UV (EtOH): 29SUB>2
< / BR>
Calculated,%: C 54,70; H To 5.57; N 13,67.

Example 173. N-[2-(3-Methoxyphenyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

A solution of 1-{[2-(4-methyl)thiazolyl]thiocarbamoyl}imidazole (2.24 g, 10 mmol) and 2-(3-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N-dimethylformamide (25 ml) is stirred for 3.5 hours at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate receive 2,73 g (89%) of the specified connection.

IR (KBr), cm-1: 3170, 3029, 1586, 1213, 749, 691.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (sh.s,1H), 9,9 (sh.s, 1H), 7,2-to 6.8 (m, 4H), of 6.65 (s, 1H), and 3.8 (m, 2H), and 3.72 (s, 3H), 2,85 (t, J = 7 Hz, 2H), 2,18 (s, 3H).

MS (FD) m/e 307 (M+).

UV (EtOH): 292 nm ( = 16935), 258 nm ( = 9604), 202 nm ( = 27197).

Found,%: C 54,97; H 5,58; N 13,60.

C14H17N3OS2< / BR>
Calculated,%: C 54,70; H To 5.57; N 13,67.

Example 174. N-[2-(2-Methoxyphenyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

A solution of 1-{[2-(4-methyl)thiazolyl]thiocarbamoyl}imidazole (2.24 g, 10 mmol) and 2-(4-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N-dimethylformamide (25 ml) is stirred for 3 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization OST 514.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (sh.s,1H), 9,9 (sh.s, 1H), 7,2 (d, J = 8 Hz, 2H), 6,9 (d, J = 8 Hz, 2H), 6,65 (s, 1H), and 3.8 (m, 2H, in), 3.75 (s, 3H), 2,85 (t, J = 7 Hz, 2H), 2,18 (s, 3H).

MS (FD) m/e 307 (M+).

UV (EtOH): 292 nm ( = 18700), 258 nm ( = 11165), 223 nm ( = 14043), 201 nm ( = 25520).

Found,%: C 54,62; H Of 5.55; N 13,69.

C14H17N3S2< / BR>
Calculated,%: C 54,70; H To 5.57; N 13,67.

Example 175. N-[2-(4-Were)ethyl] -N'-[2-(4-methyl)thiazolyl]thiourea.

A solution of 2-(4-were)ethylisothiocyanate (1 g, 5,64 mmol) and 2-amino-4-methylthiazole (0,44 g, 5,64 mmol) in N,N-dimethylformamide (20 ml) is heated 24 h at 90oC. the Solvent is removed in vacuo and recrystallization of the obtained solid residue gain of 0.67 g (41%) of the indicated compound as a white solid.

IR (KBr), cm-1: 3170, 3020, 1562, 1507, 1203, 986.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (sh.s,1H), 9,9 (sh.s, 1H), 7,18 (d, J = 8 Hz, 2H), 7,18 (d, J = 8 Hz, 1H), 6,65 (s, 1H), and 3.8 (m, 2H), 2,85 (t, J = 7 Hz, 2H), and 2.26 (s, 3H), of 2.18 (s, 3H).

MS (FD) m/e 291 (M+).

UV (EtOH): 292 nm ( = 18863), 257 nm ( = 10886), 202 nm ( = 21164).

Found,%: C 57,83; H 5,90; N 14,36.

C14H17N3S2< / BR>
Calculated,%: C 57,70; H 5,88; N 14,42.

Example 176. N-[2-(2-Methoxyphenyl)ethyl]-N'-[2-(5-chloro)thiazolyl]timoc is a (0,77 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate receive 0,86 g (53%) of the specified connection.

IR (KBr), cm-1: 3313, 2835, 1608, 1527, 1514, 1441, 1352, 1244, 1040.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (sh.s,1H), 8.4V (sh.s, 1H), and 7.4 (s, 1H), 7,2 - to 6.8 (m, 4H), 3,74 (s, 3H), 3,68 (m, 2H), and 2.8 (t, J = 7 Hz, 2H).

MS (FD) m/e 327 (M+).

UV (EtOH): 295 nm ( = 14366), 261 nm ( = 12558), 203 nm ( = 31267).

Example 177. N-[2-(3-Methoxyphenyl)ethyl]-N'-[2-(5-chloro) thiazolyl]thiourea.

A solution of 1-{[2-(5-chloro)thiazolyl]thiocarbamoyl}imidazole (1.22 g, 5 mmol) and 2-(3-medociprin)ethylamine (of 0.77 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the residue from ethyl acetate receive 0,86 g (53%) of the specified connection, so pl. 106 - 107oC.

IR (KBr), cm-1

MS (FD) m/e 327 (M+).

UV (EtOH): 295 nm ( = 13695), 260 nm ( = 11987), 203 nm ( = 32295).

Found, %: C 47,75; H To 4.41; N 12,65.

C13H14N3OS2Cl

Calculated, %: C 47,63; H 4,30; N 12,81.

Example 178. N-[2-(4-Methoxyphenyl)ethyl] -N'-[2-(5-chloro) thiazolyl]thiourea.

A solution of 1-{[2-(5-chloro)thiazolyl]thiazolyl]thiocarbamoyl}imidazole (1.22 g, 5 mmol) and 2-(4-methoxyphenyl)ethylamine (of 0.77 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate to obtain 1.2 g (74%) of the specified connection, so pl. 156 - 158oC.

IR (KBr), cm-1: 3315, 2934, 1601, 1511, 1320, 1243, 1180, 1034, 745.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh.s, 1H), 8.4V (sh.s, 1H), and 7.4 (s, 1H), and 7.1 (d, J = 8 Hz, 2H), 6,8 (d, J = 8 Hz, 2H), to 3.67 (s, 3H), 3,63 (m, 2H), and 2.7 (t, J = 7 Hz), 2H).

MS (FD) m/e 327 (M+).

UV (EtOH): 295 nm ( = 13569), 260 nm ( 12490), 223 nm ( = 18432), 202 nm ( = 28264).

Found, %: C 47,59; H 4,34; N 12,53.

C13H14N3OS2Cl

Calculated, %: C 47,6� 1-{[2-(5-chlorine)thiazolyl]thiocarbamoyl}imidazole (1.22 g, 5 mmol) and 2-(1-cyclohexenyl)ethylamine (to 0.645 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from methylene chloride receive 0,83 g (55%) of the specified connection, so pl. 145 - 147oC.

IR (KBr), cm-1: 3167, 2929, 1564, 1488, 1230, 1183, 1199, 1030, 685.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh.s, 1H), 8.4V (sh.s, 1H), and 7.4 (s, 1H), 5,4 (s, 1H), 3,5 (m, 2H), 2,15 (t, J = 7 Hz, 2H), and 1.9 (m, 4H), 1,5 (m, 4H).

MS (FD) m/e 301 (M+).

UV (EtOH): 295 nm ( = 14231), 259 nm ( = 11275), 204 nm ( = 20953).

Found, %: C 47,90; H Vs. 5.47; N 14,21.

C12H16N3S2Cl

Calculated, %: C 47,75; H 5,34; 13,92.

Example 180. 5-Benzyl-3-phenyl-2-thiohydantoin.

A solution of DL-phenylalanine (1.65 g, 10 mmol) methyl-N-phenyldiethanolamine (1.85 g, 10 mmol) and triethylamine (1.4 ml, 10 mmol) in ethanol (30 ml) is boiled for 5 hours the mixture is Then cooled to room temperature and the solvent is removed in vacuum. The residue is dissolved in ethyl acetate, washed with 1 N. aqueous HCl and water. The organic layer is concentrated and paracrystal is(M+).

Example 181. 1-{[2-(5-Bromine)thiazolyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (to 9.9 g, 50 mmol) and 2-amino-5-bromothiazole (of 8.95 g, 50 mmol) in acetonitrile (200 ml) is stirred for 24 h at 50oC. Filtering the resulting precipitate receive 5,38 g (37%) of the specified connection.

1H-NMR (300 MHz, DMSO-d6), : 9,3 (s, 1H), of 8.25 (s, 1H), 7,63 (s, 1H), 7,43 (s, 1H).

MS (FD) m/e: 288, 290 (M+).

Example 182. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(5-bromo)thiazolyl] thiourea.

A solution of 1-{[2-(5-bromo)thiazolyl]thiocarbamoyl}imidazole (0,72 g, 2.5 mmol) and 2-(2-chlorophenyl)ethylamine (0.4 g, 2.5 mmol) in N,N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue by chromatography on silica gel get 0.06 g (5%) of the specified connection.

IR (KBr), cm-1: 3318, 2926, 1562, 1512, 1257, 1177, 1052, 749, 687.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh.s, 1H), 8.4V (sh.s, 1H), 7,4 - 7 (m, 5H), and 3.8 (m, 2H), 2,9 (t, J = 7 Hz, 2H).

MS (FD) m/e: 375, 377 (M+).

UV (EtOH): 291 nm ( = 15522), 258 nm ( = 11594), 202 nm ( = 29572).

oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue by chromatography on silica gel obtain 0.36 g (38%) of the specified connection, so pl. 141 - 145oC.

IR (KBr), cm-1: 3168, 3019, 1568, 1514, 1331, 1251, 1189, 787, 686.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh.s, 1H), 8.4V (sh.s, 1H), 7,44 (s, 1H), and 7.4 to 7.2 (m, 4H), and 3.7 (m, 2H), and 2.8 (t, J = 7 Hz, 2H).

MS (FD) m/e: 377, 379 (M+).

UV (EtOH): 296 nm ( = 10140), 259 nm ( = 8392), 201 nm ( = 23984).

Example 184. N-[2-(4-Chlorophenyl)ethyl]-N'-[2-(5-bromo)thiazolyl] thiourea.

A solution of 1-{ [2-(5-bromo)thiazolyl] thiocarbamoyl} imidazole (0,72 g, 2.5 mmol) and 2-(4-chlorophenyl)ethylamine (0.4 g, 2.5 mmol) in N,N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue by chromatography on silica gel obtain 0.32 g (34%) ukazannoj the Mr (300 MHz, DMSO-d6), : 11,6 (sh.s, 1H), 8.4V (sh.s, 1H), 7,44 (s, 1H), and 7.3 (d, J = 8 Hz, 2H), 7,2 (d, J = 8 Hz, 2H), and 3.7 (m, 2H), and 2.8 (t, J = 7 Hz, 2H).

MS (FD) m/e: 377, 379 (M+).

UV (EtOH): 296 nm ( = 14604), 259 nm ( = 12656), 201 nm ( = 18845).

Example 185. N-[2-(2-Methoxyphenyl)ethyl] -N'-[2-(5-bromo) thiazolyl]thiourea.

A solution of 1-{[2-(5-bromo)thiazolyl]thiocarbamoyl}imidazole (0,72 g, 2.5 mmol) and 2-(2-methoxyphenyl)ethylamine (0,41 g, 2.5 mmol) in N,N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue by chromatography on silica gel get 0,38 g (41%) of the specified connection.

IR (KBr), cm-1: 3164, 2960, 1563, 1513, 1241, 1182, 1030, 757, 682.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh.s, 1H), 8.4V (sh.s, 1H), 7,43 (c, 1H), 7,4-7 (m, 4H), to 3.73 (c, 3H), and 3.7 (m, 2H), 2,9 (t, J=7 Hz, 2H).

MC (FD) m/e: 371, 373 (M+).

UV (EtOH): 291 nm ( =16746), 261 nm ( = 13112), 202 nm ( = 31492).

Example 186. N-[2-(3-Methoxyphenyl)ethyl]-N'-[2-(5-bromo)thiazolyl]thiourea.

A solution of 1-{[2-(5-bromo)thiazolyl]thiocarbamoyl}imidazole (0,72 g, 2.5 mmol) and 2-(3-methoxyphenyl)ethylamine (0,41 g, 2.5 mmol) in N,N-digitiform the ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue by chromatography on silica gel get 0,53 g (57%) of the specified connection.

IR (KBr), cm-1: 3174, 1558, 1510, 1339, 1238, 1175, 1041, 785, 688.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh. s, 1H), 8.4V (sh. s, 1H), 7,44 (c, 1H), and 7.3 to 6.8 (m, 4H), 3,7 (c, 3H), and 3.7 (m, 2H), 2,9 (t, J=7 Hz, 2H).

MC (FD) m/e: 371, 373 (M+).

UV (EtOH): 294 nm ( = 15068), 260 nm ( = 12248), 202 nm ( = 35594).

Example 187. N-[2-(4-Methoxyphenyl)ethyl]-N'-[2-(5-bromo)thiazolyl]thiourea.

A solution of 1-{[2-(5-bromo)thiazolyl]thiocarbamoyl}imidazole (0,72 g, 2.5 mmol) and 2-(4-bromophenyl)ethylamine (0,41 g, 2.5 mmol) in N,N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue by chromatography on silica gel get 0,42 g (45%) of the specified connection.

IR (KBr), cm-1: 3170, 1558, 2512, 1343, 1246, 1163, 1082, 824.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh. s, 1H), 8.4V (W, C. 1H), 7,44 (c, 1H) and 7.1 (d, J=8 Hz, 2H), 6,8 (d, J=8 Hz, 2H), 3,67 (c, 3H), 3,63 (m, 2H), 2,9 (t, J=7 Hz, 2H).

MC (FD), m/Astor 1-{[2-(5-bromo)thiazolyl]thiocarbamoyl]imidazole (0,72 g, 2.5 mmol) and 2-(1-cyclohexenyl)ethylamine (0.32 g, 2.5 mmol) in N,N-dimethylformamide (15 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from methylene chloride receive of) 0.157 g (18%) of the specified connection.

IR (KBr), cm-1: 3170, 2928, 1559, 1510, 1478, 1344, 1228, 1182, 1096, 834.

1H-NMR (300 MHz, DMCO-d6), : 11,6 (sh. s, 1H), 8.3 (the sh. s, 1H), and 7.4 (s, 1H), 5,4 (s, 1H), 3,5 (m, 2H), 2,15 (t, J=7 Hz, 2H), and 1.9 (m, 4H), 1,5 (m, 4H).

MS (FD) m/e 345, 347 (M+).

UV (EtOH): 295 nm ( = 15533), 259 nm ( = 11792), 201 nm ( = 21261).

Found, %: C 41,87; H 4,91; N 12,21.

C12H16N3S2Br

Calculated, %: C 41,62; H Of 4.66; N 12,13.

Example 189. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea.

Mix a solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-2-bromopyridine (1.73 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. After 17 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, vodago solid residue by recrystallization from ethyl acetate to obtain 1.08 g (32%) of the compounds in the form of snow-white matter, so pl. 166-167oC.

IR (KBr), cm-1: 3159, 2927, 1595, 1561, 1531, 1475, 1310, 1228, 1092.

1H-NMR (300 MHz, DMSO-d6), : 11,09 (sh. s, 1H), at 10.64 (s, 1H), and 8.2 (d, J= 2.4 Hz, 1H), 7,93 (LW.d, J=8,9 and 2.4 Hz, 1H), to 7.09 (d, J=9 Hz, 1H), vs. 5.47 (s, 1H), 3,62-to 3.58 (m, 2H), 2,19 (t, J=6,7 Hz, 2H), 2-1,9 (m, 4H), 1,55-of 1.44 (m, 4H).

MC (FD) m/e 339 (M+), 341 (M+2).

UV (EtOH): 305 nm ( = 14037), 274 nm ( = 25281).

Found, %: C 49,22; H 5,28; N 12,32.

C14H18BrN3S

Calculated, %: C 49,42; H 5,33; N 12,35.

Example 190. N-(2-Phenethyl)-N'-[2-(4-methyl)pyridyl]thiourea.

Mix a solution of 2-geneticization (1.63 g, 10 mmol) and 2-amino-4-methylpyridine (1.08 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. Through x 16.75 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue by recrystallization from a mixture of etelaat/hexane get 1,69 g (62%) of the compounds in the form of white crystals, so pl. 151-153oC.

IR (KBr), cm-1: 3225, 1616, 1534, 1486, 1313, 1192, 1037.

1H-NMR (300 MHz, DMSO-d6, : 11,72 (sh. s, 1H), 10,42 (c, 1H), 7,87 (d, LASS="ptx2">

UV (EtOH): 290 nm ( = 15080), 266 nm ( = 15528), 247 nm ( = 13132), 202 nm ( = 21819).

Found, %: C 66,09; H 6,34; N 15,71.

C15H17N3S

Calculated, %: C 66,38; H Of 6.31; N 15,48.

Example 191. N-(2-Phenethyl)-N'-[2-(4,6-dimethyl)pyridyl]thiourea.

Mix a solution of 2-geneticization (1.63 g, 10 mmol) and 2-amino-4,6-dimethylpyridine (1.22 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. After 16 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue by recrystallization from a mixture of ethyl acetate with hexane gain of 1.81 g (63%) of the compounds in the form of snow-white crystals, so pl. 165-167oC.

IR (KBr), cm-1: 3219, 1618, 1543, 1342, 1215.

1H-NMR (300 MHz, DMSO-d6), : 11,83 (sh. s, 1H), 10,35 (s, 1H), 7,25-7,16 (m, 5H), 6,69 (s, 1H), 6,63 (s, 1H), 3,88-3,82 (m, 2H), 2,89 (t, J=6,8 Hz, 2H), and 2.14 (s, 3H), of 2.09 (s, 3H).

MC (FD) m/e 285 (M+).

UV (EtOH): 294 nm ( = 17405), 266 nm ( = 15904), 247 nm ( = 14348), 203 nm ( = 23896).

Found, %: C 67,11; H 6,63; N 14,71.

C16H19N3S

Calculated, %: C 67,33; H of 6.71; N2-geneticization (1.63 g, 10 mmol) and 2-amino-2-hydroxypyridine (1.1 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. Through 65,5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. The obtained solid residue clean pressure chromatography on silica gel (5% ethyl acetate in dichloromethane to 10% ethyl acetate) to give 1.51 g (55%) of the specified compounds by recrystallization from ethyl acetate gain of 1.05 g of the compounds in the form of snow-white crystals, so pl. 168-169oC.

IR (KBr), cm-1: 3377, 1613, 1561, 1534, 1347, 1288, 1152.

1H-NMR (300 MHz, DMSO-d6), : 11,43 (sh.s, 1H), 10,94 (s, 1H), 8,32 (C. 1H), 7,54-7,52 (m, 1H), 7,28-7,14 (m,6H), 6,9-6,86 (m,1H), 3,84-of 3.77 (m, 2H), 2,9 (t, J = 7 Hz, 3H).

MC (FD) m/e 273 (M+).

UV (EtOH): 309 nm ( = 17349), 261 nm ( = 11851), 245 nm ( = 17252), 204 nm ( = 23596).

Example 193. N-[2-(2-Methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea.

Mix a solution of N-(diimidazole)-2-(2 - methoxyphenyl)ethylamine (2,61 g, 10 mmol) and 2-amino-5-bromopyridine (1.73 g, 10 mmol) in N,N-dimethylformamide (25 ml) is heated at 90oC. After 65 h reaktsii acid (2), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. By recrystallization of the obtained solid residue from ethyl acetate to obtain 1.78 g (49%) of the compounds in the form of snow-white crystals, so pl. 147-148oC.

IR (KBr), cm-1: 3224, 1596, 1530, 1492, 1459, 1229, 1191, 1038.

1H-NMR (300 MHz, DMSO-d6), : 11,1 (sh.s, 1H), 10,63 (s, 1H), 8,11 (d, J = 2.3 Hz, 1H), 7,9 (LW.d, J = 8,9 and 2.6 Hz, 1H), 7,21-7,16 (m,2H), 7,06 (d, J = 8,9 Hz, 1H), 6,94-6,83 (m, 2H), 3,78-to 3.73 (m,2H), and 3.72 (s, 3H), of 2.86 (t, J = 6,8 Hz, 2H).

MC (FD) m/e 365 (M+), 367 (M+2).

UV (EtOH): 305 nm ( = 13279), 274 nm ( = 26971), 202 nm ( = 28527).

Found, %: C 48, 97mm; H 4,36; N 11,66.

C15H16BrN3OS

Calculated, %: C 49,19; H 4,40; N 11,47.

Example 194. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea.

Mix a solution of N-(diimidazole)-2-(2-chlorophenyl)ethylamine (2.65 g, 10 mmol) and 2-amino-5-bromopyridine (1.73 g, 10 mmol) in N,N-dimethylformamide (20 ml) is heated at 90oC. Through 64,74 hours, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue Perachora, so PL, 160-161oC.

IR (KBr), cm-1: 3220, 1594, 1562, 1534, 1474, 1338, 1222, 1165, 1088.

-1H-NMR (300 MHz, DMSO-d6, : 11,16 (sh.s, 1H), 16,69 (c, 1H), 8,15 (d, J = 2.2 Hz, 1H), 7,93 (LW. d, J = 8,9 and 2.4 Hz, 1H), 7,41-7,38 (m,2H), 7,28-of 7.23 (m, 2H), was 7.08 (d, J =8,9 Hz, 1H), 3,86 to 3.8 (m,2H), 3.04 from (t, J = 6.9 Hz, 2H).

MC (FD) m/e 371 (M+2).

UV (EtOH): 306 nm ( = 14321), 275 nm ( = 24813), 257 nm ( = 16728), 201 nm ( = 27700).

Found, %: C 45,13; H Of 3.60; N 11,17.

C14H13BrClN3S

Calculated, %: C 45,36; H 3,53; N 11,33.

Example 195. N-(2-Phenethyl)-N'-[2-(n-propyl)thiazolyl]thiourea.

Mix a solution of 2-geneticization (1,38 g, 8,44 mmol, of 1.26 ml) and 2-amino-4-n-propitiate (1.2 g, 8,44 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. After 17 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue from a mixture of ethyl acetate/hexane obtain 1.39 g (54%) of the indicated compound as yellow crystals, so pl. 135-137oC.

IR (KBr), cm-1: 3175, 3027, 1562, 1529, 1507, 1216.

1H-Yarm (300 MHz, DMSO-d6), : 11.5cm (W.s, 1H), to 9.93 (sh.s, 1H), 7,29-7,1
).

UV (EtOH): 292 nm ( = 19216), 257 nm ( = 10283), 202 nm ( = 20314).

Found, %: C 59,17; H Between 6.08; N 13,55.

C15H19N3S2< / BR>
Calculated, %: C 58,98; H 6,27; N 13,76.

Example 196. N-(2-Phenethyl)-N'-[2-(3,5-dichloro)pyridyl]thiourea.

Mix a solution of 2-geneticization (1.63 g, 10 mmol, 1.5 ml) and 2-amino-3,5-dichloropyridine (3,26 g, 20 mmol) in N-methylpyrrolidinone (20 ml) is heated at 125oC. After 16.5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (5x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (20% hexane in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane receive 581 mg (18%) of the compounds in the form of white crystals, so pl. 102-104oC.

IR (KBr), cm-1: 3409, 3040, 1560, 1508, 1429, 1147, 1057.

1H-NMR (300 MHz, DMSO-d6), : 10,66 (s, 1H), 8,71 (s, 1H), 8,27 (d, J = 2.2 Hz, 1H), 8,12 (d, J = 2.2 Hz, 1H), 7,32 - 7,19 (m, 5H), 3,82 is 3.76 (m, 2H), 2,9 (t, J = 7,1 Hz, 2H).

MC (FD) m/e 325 (M+), 327 (M+2).

UV (EtOH): 311 nm ( = 8820), 276 nm ( = 16571), 257 nm ( = 13676), 203 nm ( = 19245).

Found,%: what measures 197. N-(2-Phenethyl)-N'-[2-(4-n-butyl)thiazolyl]thiourea.

Mix a solution of 2-geneticization (1.63 g, 10 mmol, 1.5 ml) and 2-amino-4-n-butylthiazole (1.56 g, 10 mmol) in N-pyrrolidinone (20 ml) is heated at 100oC. After 16.5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue from a mixture of ethyl acetate/hexane obtain 1.63 g (51%) of the indicated compound as yellow crystals, so pl. 100-102oC.

IR (KBr), cm-1: 3027, 1560, 1529, 1262, 1212.

1H-NMR (300 MHz, DMSO-d6), : to 11.52 (sh.s, 1H), 9,89 (sh.s, 1H), 7,29-to 7.15 (m, 5H), 6,59 (s, 1H), 3,79-to 3.73 (m, 3H), of 2.86 (t, J = 6.9 Hz, 2H), 2,45-2,4 (m, 2H), 1,5-1,4 (m,2H), 1,29-1,19 (m, 2H), from 0.84 (t, J = 7,3 Hz, 3H).

MC (FD) m/e 319 (M+).

UV (EtOH): 292 nm ( = 19193), 258 nm ( = 10262), 203 nm ( = 20024).

Found, %: C 59,86; H 6,62; N 12,99.

C16H21N3S2< / BR>
Calculated, %: C 60,15; H 6,62; N 13,15.

Example 198. N-[2-(1-Cyclohexenyl)ethyl] -N'-[2-(4-n - propyl)thiazolyl] thiourea.

Mix a solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino - 4-n-propertiesto room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue by recrystallization from a mixture of ethyl acetate/hexane obtain 1.26 g (41%) of the indicated compound as yellow crystals, so pl. 152-153oC.

IR (KBr), cm-1: 3175, 2930, 1561, 1529, 1507, 1203.

1H-NMR (300 MHz, DMSO-d6), : 11,49 (sh.s, 1H), 9,9 (sh.s, 1H), 6,63 (s, 1H), 5,42 (s, 1H), 3,6-of 3.54 (m, 2H), 2.49 USD at 2.45 (m, 2H), 2,16 (t, J=6.5 Hz, 2H), 1,95-of 1.88 (m, 4H), 1,6-of 1.43 (m, 6H), is 0.84 (t, J=7,3 Hz, 3H).

MC (FD) m/e 309 (M+).

UV (EtOH) nm: 292, 257, 201.

Found, %: C 58,29; H 7,58; N 13,37.

C12H23N3S2< / BR>
Calculated,%: C 58,21; H 7,49; N Of 13.58.

Example 199. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(4-n - butyl)thiazolyl]thiourea.

Mix a solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-4-n-butylthiazole (1.56 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. After 18 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. To clean the data connection in the form of yellow crystals, so pl. 92-94oC.

IR (KBr), cm-1: 3174, 2927, 1583, 1532, 1507, 1466, 1203.

1H-NMR (300 MHz, DMSO-d6), : 11,73 (sh.s, 1H), 10,14 (sh.s, 1H), 6,86 (s, 1H), 5,65 (s, 1H), 3,83-of 3.78 (m, 2H), 2,75 of 2.7 (m, 2H), 2,42-of 2.38 (m, 2H), 2,18-2,1 (m, 4H), 1,81-of 1.65 (m, 6H), 1,55 was 1.43 (m, 2H), only 1.08 (t, J=7,3 Hz, 3H).

MC (FD) m/e 323 (M+).

UV (EtOH): 292 nm ( = 19266), 257 nm ( = 9555), 201 nm ( = 15788).

Found, %: C 59,56; H Of 7.93; N 10,00.

C16H25N3S2< / BR>
Calculated,%: C 59,40; H 7,79; N 12,99.

Example 200. N-[2-(1-Cyclohexenyl)ethyl] -N'-[2-(4 - isopropylthiazole] thiourea.

Mix a solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-4-isopropylthiazole (1.42 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. Through of 15.75 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the residue by recrystallization from a mixture of ethyl acetate/hexane obtain 1.01 g (33%) of the compounds in the form of pale yellow crystals, so pl. 110-112oC.

IR (KBr), cm-1: 3164, 2936, 1562, 1525, 1463, 1321, 1214.

1H-NMR (300 MHz, DMSO-d6), : 11.5cm (W.s, 1H), P> MC (FD) m/e 309 (M+).

UV (EtOH): 291 nm ( = 20249), 256 nm ( = 9969), 201 nm ( = 15880).

Found, %: C 58,50; H 7,63; N 13,38.

C15H23N3S2< / BR>
Calculated,%: C 58,21; H 7,49; N Of 13.58.

Example 201. N-[2-(Phenethyl)-N'-[2-(4-isopropyl)thiazolyl]thiourea.

Mix a solution of 2-geneticization (1.63 g, 10 mmol, 1.5 ml) and 2-amino-4-isopropylthiazole (1.42 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. After 17 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 10 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue by recrystallization from a mixture of ethyl acetate/hexane obtain 1.42 g (46%) of the indicated compound as yellow crystals, so pl. 155-156oC.

IR (KBr), cm-1: 3172, 2962, 1581, 1525, 1467, 1350, 1290, 1210.

1H-NMR (300 MHz, DMSO-d6), : to 11.52 (sh.s, 1H), 9,89 (sh.s, 1H), 7,29-7,14 (m, 5H), to 6.58 (s, 1H), 3,8-3,74 (m, 2H), 2,87 (t, J=6.9 Hz, 2H), was 2.76-2.71 to (m, 1H), 1,07 (d, J=6.8 Hz, 6H).

MC (FD) m/e 305 (M+).

UV (EtOH): 292 nm ( = 19882), 257 nm ( = 10580), 203 nm ( = 20047).

Found, %: C 58,95; H To 6.39; N 13,72.

C15H19N3S2

A solution of N-(2-phenethyl)-N'-{ 2-[(4-ethylglycine)thiazolyl] } thiourea (1.3 g, 3.58 mmol) in ethanol (30 ml) is treated with 1 N. sodium hydroxide and heated to boiling. After 1 h the reaction mixture was cooled to room temperature, diluted with water and washed with ethyl acetate (2x). The aqueous layer was acidified with hydrochloric acid to pH 1 and extracted with dichloromethane (2x). The organic layers are combined, washed with brine, dried over sodium sulfate, filtered and concentrated. After the obtained solid residue by rinsing with ethyl acetate to obtain 390 mg (32%) of the indicated compound as a light brown substance, so pl. > 170oC (decomp.)

IR (KBr), cm-1: 3024, 1705, 1669, 1565, 1323, 1146.

1H-NMR (300 MHz, DMSO-d6), : 12,2 (sh.s, 1H), 9,07 (s, 1H), 8,01 (s, 1H), 7,28-7,14 (m, 5H), 3,71-to 3.64 (m, 2H), 2,84 (t, J=7,3 Hz, 2H).

MC (FD) m/e 336 (M+1).

MCBP (FAB), m/e: calc. 336,0477, detecting. 336,0474.

UV (EtOH): 284 nm ( =17301), 203 nm ( =18110).

Example 203. N-(2-Phenethyl)-N'-[2-(4-methoxybenzo)thiazolyl]thiourea.

A solution of 2-geneticization (3,26 g, 20 mmol) and 2-amino-4-methoxy-of-benzothiazole (3.6 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 64 h, the reaction mixture was cooled to room temperature and transferred to atjarocsalad. Directly from the organic layer receive a 3.87 g (56%) of the compounds in the form of a white substance, so pl. 209-211oC.

IR (KBr), cm-1: 3171, 2938, 1570, 1527, 1331, 1191, 1044.

1H-NMR (300 MHz, DMSO-d6), : 11,88 (s, 1H), 9,86 (s, 1H), 7,49-6,93 (m, 6H), 3,86 (s, 3H), of 3.77 to 3.7 (m, 2H), 2,89 (t, J=7,1 Hz, 2H).

MC (FD) m/e 343 (M+).

MCBP (FAB), m/e: calc. 344,0891, detecting. 344,0884.

UV (EtOH) nm: 290, 248, 210.

Example 204. N-(2-Phenethyl)-N'-{2-(5-trifluoromethyl)-1,3,4 - thiadiazolyl]}thiourea.

A solution of 2-geneticization (3,26 g, 20 mmol, 3 ml) and 2-amino-5-trifluoromethyl-1,3,4-thiadiazole (to 3.38 g, 20 mmol) in N,N-dimethylformamide (50 ml) is heated at 100oC. After 40 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (3x) and brine (2x). The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silicagel (5% ethyl acetate in dichloromethane) followed by recrystallization from ethyl acetate to obtain 171 mg (3%) of the compounds in the form of a white substance, so pl. 212-213oC.

IR (KBr), cm-1: 3336, 2788, 1629, 1534, 1494, 1398, 1327, 1148, 1038.

1H-NMR (300 MHz, DMSO-d6322 nm ( = 5240), 261 nm ( = 11025), 204 nm ( = 28776).

Example 205. N-(2-phenethyl)-N'-[2-(4-carboxylic acid)thiazolyl]thiourea.

A solution of N-(2-Phenethyl)-N'-[2-(4-cyano)thiazolyl]thiourea (250 mg, 0,867 mmol) in glacial acetic acid (10 ml) and 5 G. hydrochloric acid (10 ml) is heated to boiling. After 16 h, the reaction mixture was cooled to room temperature, diluted with acetonitrile and concentrated to dryness (2). The obtained solid residue clean pressure chromatography on silica gel (2% acetic acid in ethyl acetate) followed by recrystallization from methanol/ethyl acetate and obtain 13 mg of the compounds. By concentrating the mother liquor and rinsing the residue with ethyl acetate receive an additional 34 mg of the compounds, the total yield of which was 47 mg (18%), white matter, so pl. > 230oC.

IR (KBr), cm-1: 3276, 1603, 1531, 1394, 1268.

1H-NMR (300 MHz, DMSO-d6), : 7,26-7,14 (m, 6H), 3,71-the 3.65 (m, 2H), 2,87 (t, J = 7.2 Hz, 2H).

MC (FD) m/e 307 (M+).

MCBP (FAB), m/e: (M+1), calc. 309,0527, detecting. 309,0528

UV (EtOH) nm: 288, 260, 206.

Example 206. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(6-fermentational)]thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1.66 g, to 9.93 mmol the ion mixture is cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (1% ethyl acetate in dichloromethane) followed by recrystallization from ethyl acetate to obtain 1.04 g (31%) of the indicated compound as yellow crystals, so pl. 200-201oC.

IR (KBr), cm-1: 3451, 3177, 3044, 2924, 2832, 1560, 1255, 1462, 1215, 1198.

1H-NMR (300 MHz, CDCl3), : 10,83 (s, 1H), 10,33 (sh.s, 1H), to 7.61-7,56 (m, 1H), 7,41-7,37 (m, 1H), 7,17, and 7.1 (m, 1H), 5,65 (s, 1H), a 3.87-3,81 (m, 2H), of 2.38 (t, J = 6.5 Hz, 2H), 2,03-2 (m, 4H), 1,67-of 1.52 (m, 4H).

MC (FD) m/e 335 (M+).

UV (EtOH) nm: 301, 218, 201.

Found,%: C 57,58; H 5,44; N 12,42.

C16H18FN3S2< / BR>
Calculated,%: C 57,29; H 5,41; N 12,53.

Example 207. N-(2-Phenethyl)-N'-[-2-(5-chlorothiazole)]thiourea.

In dichloromethane to form a suspension of the hydrochloride of 2-amino-5-chlorothiazole, which is shaken with a slight excess of sodium hydroxide solution. The layers are separated and the aqueous layer washed with dichloromethane. The combined organic layers dried over sodium sulfate, filtered and concentrated. To the obtained solid product is added 2-penicillinate is C 20 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (2% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane obtain 187 mg of the compounds in the form of light brown crystals, so pl. 163-164oC.

IR (KBr), cm-1: 3312, 3028, 2925, 1607, 1527, 1513, 1438, 1377, 1348, 1314, 1026.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh.s, 1H), to 8.41 (s,1H), 7,39 (s,1H), 7.3 to to 7.15 (m,5H), 3,7-3,63 (m,2H), 2,82 (t, J= 7.2 Hz, 2H).

MC (FD) m/e 297 (M+), 299 (M+2).

UV (EtOH): 296 nm ( = 14487), 260 nm ( = 12442), 206 nm ( = 27427).

Found,%: C 48,4; H 4,16; N 13,85.

C12H12ClN3S2< / BR>
Calculated,%: C 48,4; H 4,06; N 14,11.

Example 208. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(4-triptorelin)thiazolyl] thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-4-cryptomaterial (1.68 g, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 125oC. After 20 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), who built the solid residue pressure chromatography on silica gel (1% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane (1: 1) obtain 139 mg (4%) of the compounds in the form of snow-white matter, so PL 153-154oC.

IR (KBr), cm-1: 3168, 2932, 1562, 1513, 1472, 1438, 1219, 1175, 1081.

1H-NMR (300 MHz, DMSO-d6), : 11,95 (s,1H), 8,21 (s,1H), 7,71 (s,1H), 5,41 (s, 1H), 3,55-to 3.49 (m, 2H), and 2.14 (t, J= 6,7 Hz, 2H), 1,33 of-1.83 (m, 4H), 1.56 to of 1.41 (m,4H).

MC (FD) m/e 335 (M+).

MCBP (FAB), m/e: (M+1), calc. 336,0816, detecting. 336,0842.

UV (EtOH): 285 nm ( = 15215), 258 nm ( = 12868), 203 nm ( = 20271).

Example 209. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea.

A solution of 2-(2-chlorophenyl)ethylamine (1.56 g, 10 mmol, 1,41 ml) and N-(diimidazole)-2-amino-4-cryptomaterial (3 g, the 10.8 mmol) in N,N-dimethylformamide (20 ml) is heated at 90-100oC. After 2 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (1% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane (1:1) obtain 870 mg (24%) of the compounds in the form of white crystals, so pl. 187-188oC.

IR (KBr), cm-1: 3169, 3018, 1569, 1512, 1245, 1220, 1154, 1133, 1080.

1H-NMR (300 MHz, DMSO-d

UV (EtOH): 285 nm ( = 13785), 257 nm ( = 14164), 202 nm ( = 30204).

Found,%: C 42,82; H 3,14; N 11,68.

C13H11F3ClN3S2< / BR>
Calculated,%: C 42,68; H 3,03; N 11,49.

Example 210. N-[2-(4-Chlorophenyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea.

A solution of 2-(4-chlorophenyl)ethylamine (1.56 g, 10 mmol, 1.4 ml) and N-(diimidazole)-2-amino-4-cryptomaterial (3 g, the 10.8 mmol) in N,N-dimethylformamide (20 ml) is heated at 90-100oC. After 2 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (1% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane (1: 1) obtain 570 mg (16%) of the compounds in the form of white crystals, so pl. 196-197oC.

IR (KBr), cm-1: 3167, 3021, 1562, 1516, 1469, 1445, 1184, 1173, 1126, 1083.

1H-NMR (300 MHz, DMSO-d6), : 11,91 (s,1H), of 8.27 (s,1H), 7,71 (s,1H), 7,32 (d, J=8,4 Hz, 2H), 7.23 percent (d, J=8,4 Hz, 2H), 3.72 points-of 3.65 (m, 2H), and 2.83 (t, J= 7 Hz, 2H).

MC (FD) m/e 365 (M+).

UV (EtOH): 286 nm ( = 11309), 257 nm ( = 11445), 202 nm ( = 2181 is,%: C 42,68; H 3,03; N 11,49.

Example 211. N-[2-(3-Chlorophenyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea.

A solution of 2-(3-chlorophenyl)ethylamine (1.56 g, 10 mmol, 1.4 ml) and N-(diimidazole)-2-amino-4-cryptomaterial (3 g, the 10.8 mmol) in N,N-dimethylformamide (20 ml) is heated at 90-100oC. After 2 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (1% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane get 407 mg (11%) of the compounds in the form of white crystals, so pl. 159-160oC.

IR (KBr), cm-1: 3176, 3017, 1567, 1517, 1224, 1133, 1080.

1H-NMR (300 MHz, DMSO-d6), : 11,93 (s, 1H), 8,28 (s, 1H), 7,72 (s, 1H), 7,33-7,17 (m, 4H), to 3.73-to 3.67 (m, 2H), 2,85 (t, J=7 Hz, 2H).

MC (FD) m/e 365 (M+), 367 (M+2).

UV (EtOH): 285 nm ( = 14175), 257 nm ( = 14293), 202 nm ( = 31514).

Found, %: C 42,72; H 3,09; N To 11.79.

C13H11F3ClN3S2< / BR>
Calculated, %: C 42,68; H 3,03; N 11,49.

Example 212. N-[2-(2-Methoxyphenyl)ethyl]-N'-[2-(4-thiazoyl)-2-amino-4-cryptomaterial (3 g, the 10.8 mmol) in N,N-dimethylformamide (20 ml) is heated at 90-100oC. After 2 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the obtained solid residue pressure chromatography on silica gel (2% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane (1:1) receive 872 mg (24%) of the compounds in the form of white crystals, so pl. 184-184,5oC.

IR (KBr), cm-1: 3168, 2973, 1571, 1514, 1244, 1221, 1168, 1127, 1077.

1H-NMR (300 MHz, DMSO-d6), : 11.87 per (s, 1H), 8,24 (s, 1H), 7,71 (s, 1H), 7,18 to 7.1 (m, 2H), 6,94-PC 6.82 (m, 2H), 3,74 (s, 3H), 3,68-3,61 (m, 2H), and 2.8 (t, J=7 Hz, 2H).

MC (FD) m/e 361 (M+).

UV (EtOH): 280 nm ( = 16781), 259 nm ( = 15202), 203 nm ( = 32863).

Found, %: C 46,52; H 3,94; N To 11.52.

C14H14F3N3OS2< / BR>
Calculated, %: C 46,53; H 3,90; N 11,63.

Example 213. N-[2-(3-Methoxyphenyl)ethyl]-N'-[2-(4 - trifluoromethyl)thiazolyl] thiourea.

A solution of 2-(3-methoxyphenyl)ethylamine (1.51 g, 10 mmol, 1,45 ml) and N-(diimidazole)-2-amino-4-cryptomaterial (3 g, the 10.8 mmol) in N,N-dimethylformamide (20 ml) neat. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the solid residue pressure chromatography on silica gel (2% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane (1: 1) gain of 1.32 g (36%) of the compounds in the form of a white substance, so pl. 139-140oC.

IR (KBr), cm-1: 3215, 3018, 1598, 1582, 1544, 1490, 1299, 1242, 1180, 1081.

1H-NMR (300 MHz, DMSO-d6), : 11,93 (s, 1H), compared to 8.26 (s, 1H), 7,71 (s, 1H), 7,18(t, J= 8 Hz, 1H), 6,79-6,74 (m, 3H), of 3.73-3,66 (m, 2H), 3,69 (s, 3H), and 2.8 (t, J=7 Hz, 2H).

MC (FD) m/e 361 (M+).

UV (EtOH): 281 nm ( = 15384), 258 nm ( = 14389), 202 nm ( = 35020).

Found, %: C 46,76; H 3,91; N To 11.52.

C14H14F3N3OS2< / BR>
Calculated, %: C 46,53; H 3,90; N 11,63.

Example 214. N-[2-(4-Methoxyphenyl)ethyl]-N'-[2-(4 - trifluoromethyl)thiazolyl] thiourea.

A solution of 2-(4-methoxyphenyl)ethylamine (1.51 g, 10 mmol, 1,46 ml) and N-(imidazol)-2-amino-4-cryptomaterial (3 g, the 10.8 mmol) in N,N-dimethylformamide (20 ml) is heated at 90-100oC. After 2 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1N. salt cyclotouriste pressure chromatography on silica gel (2% ethyl acetate in dichloromethane) followed by recrystallization from a mixture of ethyl acetate/hexane (1:1) get 879 mg (25%) of the compounds in the form of white crystals, so pl. 169-170oC.

IR (KBr), cm-1: 3173, 3025, 1565, 1515, 1240, 1181, 1127, 1083.

1H-NMR (300 MHz, DMSO-d6), : 11,9 (s, 1H), compared to 8.26 (s, 1H), 7,71 (s, 1H), 7,12 (d, J=8.5 Hz, 2H), 6,83 (d, J=8.5 Hz, 2H), to 3.67 (s, 3H), 3,67-3,61 (m, 2H), was 2.76 (t, J=7,1 Hz, 2H).

MC (FD) m/e 361 (M+).

UV (EtOH): 284 nm ( = 15865), 258 nm ( = 14872), 224 nm ( = 16821).

Found, %: C 46,70; H To 3.89; N 11,50.

C14H14F3N3OS2< / BR>
Calculated, %: C 46,53; H 3,90; N 11,63.

Example 215. N-[2-(1-Cyclohexenyl)ethyl] -N'-[2-(4,5 - dimethyl)thiazolyl] thiourea.

In dichloromethane to form a suspension of the hydrochloride of 2-amino-4,5-dimethylthiazole (1.65 g, 10 mmol) and shaken with a mixture of sodium hydroxide and a saturated solution of sodium bicarbonate. The organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated. To the resulting solid residue is added 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and N-(methylpyrrolidinone (20 ml) and the resulting solution was heated at 105oC. After 20 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Cleaning solid Oslo-yellow crystals, so pl. 162-164oC.

IR (KBr), cm-1: 3170, 2917, 1583, 1554, 1514, 1433, 1325, 1255, 1215.

1H-NMR (300 MHz, DMSO-d6), : 11,35 (s, 1H), 9,83 (sh.s, 1H), 5,43 (s, 1H), to 3.58-to 3.52 (m, 2H), 2,17-2,11 (m, 5H), 2,07 (s, 3H), 1,94-1,89 (m, 4H), 1,57-of 1.44 (m, 4H).

MC (FD) m/e 295 (M+).

UV (EtOH): 297 nm ( = 18557), 256 nm ( = 9443), 201 nm ( = 16880).

Found, %: C 57,10; H 7,28; N 14,36.

C14H21N3S2< / BR>
Calculated, %: C 56,91; H 7,16; N 14,22.

Example 216. N-[2-(3-Ethoxy-4-methoxyphenyl)ethyl]-N'-(2 - thiazolyl)thiourea.

A solution of 2-(3-ethoxy-4-methoxyphenyl)ethylamine (1 g, 5,12 mmol) and N-(diimidazole)-2-aminothiazole (1.08 g, 5,12 mmol) in N,N-dimethylformamide (20 ml) is heated at 90-100oC. After 16 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the solid residue from a mixture of dichloromethane/ethyl acetate receive 471 mg (27%) of the compounds in the form of snow-white matter, so pl. 150-152oC.

IR (KBr), cm-1: 3176, 3112, 3040, 1575, 1514, 1469, 1261, 1235, 1140, 1042.

1H-NMR (300 MHz, DMSO-d6), : 11,51 (s, 1H), 9,73 (sh.s, 1H), 7,28 (d, J= 3.8 Hz, 1H), 7,07 (s, 1H), 6,9-of 6.78 (m, 2H), 6,72 (d): 287 nm ( = 21828), 259 nm ( = 11770), 205 nm ( = 35881).

Found, %: C 53,10; H 5,64; N 12,22.

C15H19N3O2S2< / BR>
Calculated, %: C 53,39; H 5,67; N 12,45.

Example 217. N-[2-(3-Methoxy-4-isopropoxyphenyl)ethyl] -N'-(2 - thiazolyl)thiourea.

A solution of 2-(3-methoxy-4-isopropoxyphenyl)ethylamine (1 g, 4,78 mmol) and N-(diimidazole)-2-aminothiazole (1 g, 4,78 mmol) in N,N-dimethylformamide (20 ml) is heated at 90-95oC. After 24 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the solid residue from ethylacetate receive 891 mg (53%) of the indicated compound as yellowish needles. Secondary recrystallization of the product from ethyl acetate, the obtained sample so pl. 140-141oC.

IR (KBr), cm-1: 3165, 2971, 1560, 1516, 1466, 1266, 1182, 1144.

1H-NMR (300 MHz, DMSO-d6), : 11,53 (s, 1H), 9,71 (sh.s, 1H), 7,28 (d, J=3.6 Hz, 1H), 7,06 (s, 1H), 6,84-for 6.81 (m, 5H), of 6.71 of 6.68 (m, 1H), 4,45-4,37 (m, 1H), 3,74-3,66 (m, 5H), 2,77 (t, J=7 Hz, 2H), 1,17 (d, J=6 Hz, 6H).

MS (FD) m/e 351 (M+).

UV (EtOH) nm: 286, 258, 204.

Found, %: C 54,79; H 6,11; N 12,21.

C16H21N3O2on.

In dichloromethane to form a suspension of the hydrochloride of 2-(3,4-dichlorophenyl)ethylamine (1 g, to 4.41 mmol), which is shaken with a slight excess of sodium hydroxide solution. The layers are separated and the organic layer dried over sodium sulfate, filtered and concentrated. To the resulting oil is added N-(diimidazole)-2-aminothiazole (928 mg, to 4.41 mmol) and N,N-dimethylformamide (20 ml) and the resulting solution is heated at 90-100oC. After 18 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the residue pressure chromatography on silica gel (2% ethyl acetate in dichloromethane) to obtain 1 g (68%) of product as a white solid, recrystallization of which from ethyl acetate to obtain 700 mg of the compounds in the form of white crystals, so pl. 159,5-160oC.

IR (KBr), cm-1: 3175, 1577, 1515, 1472, 1328, 1190, 1029.

1H-NMR (300 MHz, DMSO-d6), : for 11.55 (s, 1H), 9,63 (sh.s, 1H), 7,54-of 7.48 (m, 2H), 7.3 to 7,21 (m, 2H), 7,06 (s, 1H), of 3.77 to 3.7 (m, 2H), 2,87 (t, J=6.9 Hz, 2H).

MS (FD) m/e 331 (M+).

UV (EtOH): 289 nm ( = 19623), 265 nm ( = 11818), 204 nm ( = 36059).

Found, %: C 43/P> Example 219. N-[2-(2-Methyl-3-triptoreline)ethyl] -N'-(2 - thiazolyl)thiourea.

In dichloromethane to form a suspension of the hydrochloride of 2-(2-methyl-3-triptoreline)ethylamine (1 g, to 4.17 mmol) and shaken with a slight excess of sodium hydroxide solution. The layers are separated and the organic layer is dried over magnesium sulfate, filtered and concentrated. To the resulting oil is added N-(diimidazole)-2-aminothiazole (877 mg, of 4.17 mmol) and N,N-dimethylformamide (20 ml) and the solution heated at 90-100oC. After 65 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the residue pressure chromatography on silica gel (2% ethyl acetate in dichloromethane) followed by recrystallization from ethyl acetate (first party) or a mixture of ethyl acetate/hexane (1: 1) (the second party) receive 581 mg (40%) of the compounds in the form of a white substance, so pl. 158-159oC.

IR (KBr), cm-1: 3178, 3130, 2994, 1566, 1514, 1473, 1321, 1161, 1120.

1H-NMR (300 MHz, DMSO-d6), : the 11.6 (s, 1H), 9,76 (sh.s, 1H), 7,52-7,47 (m, 2H), 7,33-7,28 (m, 2H), 7,07 (s, 1H), 3.75 to 3,68 (m, 2H), 2,98 (t, J=7.4 Hz, 2H), and 2.4 (s, 3H).

MS (FDLASS="ptx2">

C14H14F3N3S2< / BR>
Calculated, %: C 48,68; H 4,08, N 12,16.

Example 220. N-{ 2-[3-(3,3,3-Cryptor)propylphenyl] ethyl} -N'-(2 - thiazolyl)thiourea.

In dichloromethane to form a suspension tosilata 2-[3-(3,3,3-Cryptor)propylphenyl] ethylamine (1 g, 2.57 mmol), which is shaken with a slight excess of sodium hydroxide solution. The layers are separated and the aqueous layer was extracted with dichloromethane. The combined organic phase is dried over magnesium sulfate, filtered and concentrated. To the resulting oil is added N-(diimidazole)-2-aminothiazole (540 mg, 2.57 mmol) and N,N-dimethylformamide (20 ml) and the solution heated at 90-95oC. After 1 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the residue from a mixture of 40% ethyl acetate in hexane get 508 mg (55%) of the compounds in the form of snow-white crystals, so pl. 138-139oC.

IR (CHCl3), cm-1: 3192, 3058, 2979, 1567, 1514, 1259, 1139.

1H-NMR (300 MHz, DMSO-d6), : 11,53 (s, 1H), 9,73 (sh.s, 1H), 7,29-7,06 (m, 6H), 3.75 to at 3.69 (m, 2H), and 2.83 (t, J=7 Hz, 2H), 2.77-to a 2.71 (m, 2H), 2.57 m at 2.45 (m, 2H).

MS (FD) m/e: 3">

C15H16F3N3S2< / BR>
Calculated, %: C 50,13; H 4,49; N Of 11.69.

Example 221. N-[2-(1-Cyclohexenyl)ethyl]-N'-(2-pyridyl)thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-aminopyridine (941 mg, 10 mmol) in N-methylpyrrolidinone (20 ml) is heated at 100oC. After 16.5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the residue by recrystallization from ethyl acetate to obtain 1.31 g (50%) of the compounds in the form of white crystals, so pl. 153 to 155oC.

IR (KBr), cm-1: 3219, 2921, 1605, 1569, 1537, 1481, 1319, 1235, 1181, 1092.

1H-NMR (300 MHz, DMSO-d6), : for 11.55 (s, 1H), 10,47 (s, 1H), of 8.09 (d, J= 3,9 Hz, 1H), 7,74-to 7.68 (m, 1H), to 7.09 (d, J=8,3 Hz, 1H), 7-6,96 (m, 1H), vs. 5.47 (s, 1H), 3,65-3,59 (m, 2H), 2,19 (t, J=6.6 Hz, 2H), 1,94-1,9 (m, 4H), 1,55 was 1.43 (m, 4H).

MS (FD) m/e 261 (M+).

UV (EtOH): 292 nm ( = 15926), 265 nm ( = 17724), 247 nm ( = 15198).

Found, %: C 64,12; H 7,33; N 15,89.

C14H19N3S

Calculated, %: C 64,33; H 7,33; N 16,08.

Example 222. N-(2-Phenethyl)-N'-[2-(5-bromo)pyridyl]thiourea.

A solution of 2-geneticization (1.63 g is C 22 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid (2x), water (2x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the residue by recrystallization from a mixture of ethyl acetate with hexane obtain 1.2 g (36%) of the compounds in the form of white crystals, so pl. 160-162oC.

IR (KBr), cm-1: 3028, 1595, 1559, 1531, 1475, 1311, 1228, 1092.

1H-NMR (300 MHz, DMSO-d6), : 11,16 (s, 1H), 10,65 (s, 1H), 8,11 (d, J= 2.1 Hz, 1H), 7,93 to 7.9 (m, 1H), 7,29-to 7.18 (m, 5H), 7,05 (d, J=8,8 Hz, 1H), 3,82-of 3.77 (m, 2H), 2,88 (t, J=7 Hz, 2H).

MS (FD) m/e 335 (M+), 337 (M+2).

UV (EtOH): 305 nm ( = 14171), 275 nm ( = 24881), 201 nm ( = 21601).

Found, %: C 49,93; H 4,19; N To 12.52.

C14H14BrN3< / BR>
Calculated, %: C Repossessed A 50.01; H 4,20; N 12,50.

Example 223. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5 - cyano)pyridyl]thiourea.

Mix a solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,36 g, 8,14 mmol) and 2-amino-5-cyanopyridine (0.97 g, 8,14 mmol) in N-methylpyrrolidinone (20 ml) is heated to 100oC. After 5 days the reaction mixture is cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (4x) and brine. The organic layer is dried over Na2SO4filter and concentrate. Cleaning solid mod from a mixture of EtOAc/hexane obtain 78 mg (3%) of the compounds in the form of snow-white matter, so pl. 195-197oC.

IR (KBr), cm-1: 2927, 2224, 1605, 1570, 1533, 1487, 1369, 1228, 1165.

1H-NMR (300 MHz, DMSO-d6), : 11,17 (sh. s, 1H), 10,96 (s, 1H), to 8.57 (d, J=1.8 Hz, 1H), 8,12 (LW. d, J=8.8 and 2.1 Hz, 1H), 7,2 (d, J=8,8 Hz, 1H), vs. 5.47 (s, 1H), 3,66-3,59 (m, 2H), 2,2 (t, J=6.6 Hz, 2H), 1,94-1,89 (m, 4H), 1,54 was 1.43 (m, 4H).

MS (FD) m/e 286 (M+).

UV (EtOH) nm: 308, 202.

Found, %: C 62,70; H 6.42 Per; N 19,42.

C15H18N4S

Calculated, %: C 62,91; H 6,34; N 19,56.

Example 224. N-(2-Phenethyl)-N'-{2-[4-(4-biphenyl)thiazolyl]}thiourea.

A solution of 2-geneticization (of 0.82 g, 5 mmol, 0.75 ml) and 2-amino-4-(4-biphenyl)thiazole (1.26 g, 5 mmol) in N,N-dimethylformamide (12.5 ml) is heated at 100oC. Through a 19.5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid. The mixture is filtered, the filtrate are separated and the organic phase is washed with saturated sodium bicarbonate solution, water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Cleaning product pressure chromatography on silica gel (1% ethyl acetate in dichloromethane to 2% ethyl acetate in dichloromethane) to obtain 372 mg (18%) of the specified connection. The yellow substance paracrystal is 2">

1H-NMR (300 MHz, DMSO-d6), : 11,72 (s, 1H), 9,54 (sh. s, 1H), 7,86 one-7.8 (m, 2H), 7,78-to 7.68 (m, 4H), 7,58 (s, 1H), 7,52-7,44 (m, 2H), 7,41-7,35 (m, 1H), 7,34-7,29 (m, 4H), 7,27 to 7.2 (m, 1H), 3,92-a-3.84 (m, 2H), 2,98 (t, J=3 Hz, 2H).

MS (FD) m/e 415 (M+).

UV (EtOH) nm: 293, 212.

Found, %: C 69,08; H 5,10; N 9,99.

C24H21N3S2< / BR>
Calculated, %: C 69,36; H 5,09, N 10,11.

Example 225. N-(2-Phenethyl)-N'-{2-[4-pyridyl)thiazolyl]}thiourea.

In methylene chloride to form a suspension of the hydrobromide of 2-amino-4-(4-pyridyl)thiazole and shaken with saturated sodium bicarbonate solution. The layers are separated and the aqueous layer washed with methylene chloride and ethyl acetate. The combined organic layers are concentrated. The solid residue (1 g, 5.6 mmol) is added 2-geneticization (0,91 g, 5.6 mmol, or 0.83 ml) in N,N-dimethylformamide (12.5 ml) and the resulting suspension heated at 100oC. Through 20,5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed phase was washed with water (4x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. By recrystallization of the obtained solid residue from ethyl acetate (3x) get 133 mg (7%) the specified connection, so pl. 196,5oC.

MS (FD) m/e 340 (M+).

Msvr (FAB), m/e: (M+) calc. 341,0895; detecting. 341,0909.

UV (EtOH): 294 nm ( = 23935), 231 nm ( = 16356), 203 nm ( = 25793).

Example 226. N-(2-Phenethyl)-N'-(2-{ 4-[1-(1-etoxycarbonyl)-(3-tert - butoxycarbonylmethyl)imino]thiazolyl}thiourea.

2-Amino-4-[1-(1-etoxycarbonyl)-(3-tert - butoxycarbonylmethyl)imino] thiazole (2.64 g, 8 mmol) and 2-geneticization (1.31 g, 8 mmol, 1.2 ml) in N, N-dimethylformamide (20 ml) is heated at 100oC. After 24 h the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. The rinsing of the solid residue with ethyl acetate receive 801 mg (20%) of the specified connection, so pl. 188,5oC.

IR (KBr), cm-1: 3293, 2975, 1749, 1594, 1543, 1453, 1382, 1231, 1154, 1054, 748, 698.

1H-NMR (300 MHz, DMSO-d6), : 11,85 (s, 1H), 8,46 (sh. s, 1H), 7,29-7,17 (m, 5H), 4,59 (s, 2H), or 4.31-5,24 (K, J=7,1 Hz, 2H), 3,7-to 3.64 (m, 2H), 2,82 (t, J=7,1 Hz, 2H), of 1.36 (s, 9H), of 1.23 (t, J=7,1 Hz, 3H).

MS (FD) m/e 492 (M+).

UV (EtOH): 292, 257 nm ( = 16356), 203 nm.

,37.

Example 227. N-(2-Phenethyl)-N'-2-(4-tert-butyl-5 - methylthiazolyl)thiourea.

2-Amino-4-tert-butyl-5-methylthiazole (1,87 g, 11 mmol) and 2-geneticization (1.8 g, 11 mmol, of 1.64 ml) in N,N-dimethylformamide (25 ml) is heated at 100oC. After 18.5 hours, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. The rinsing of the solid residue with ether get 1,02 g (28%) the specified connection, so pl. 153-153,5oC.

IR (KBr), cm-1: 3171, 2966, 1474, 1534, 1510, 1455, 1346, 1221, 1186, 755, 704.

1H-NMR (300 MHz, DMSO-d6), : 11,28 (sh. s, 1H), 9,9 (sh. s, 1H), 7,28-7,14 (m, 5H), 3,78-to 3.34 (m, 2H), 2,84 (t, J=7 Hz, 2H), and 2.27 (s, 3H), of 1.16 (s, 9H).

MS (FD) m/e: 333 (M+).

UV (EtOH): 297 nm ( = 19835), 257 nm ( = 9954), 202 nm ( = 21059).

Found, %: C 61,42; H 6,92; N 12,55.

C17H23N3S2< / BR>
Calculated,%: C 61,22; H 6,95; N 12,60.

Example 228. N-(2-Phenethyl)-N'-2-[4-(4-bromophenyl-5 - atillasoy]thiourea.

2-Amino-4-(4-bromophenyl)-5-utiltity (848 mg, 3 mmol) and 2-geneticization (490 mg, 3 mmol, 0.45 ml) in N,N-dimethylformamide (7.5 ml) negrevergne phase was washed with 1 N. hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. By recrystallization of the solid residue from ethyl acetate and toluene obtain 146 mg (11%) the specified connection, so pl. 169-170oC.

IR (KBr), cm-1: 3169, 3025, 2969, 2930, 1581, 1558, 1520, 1234, 1168, 1009.

1H-NMR (300 MHz, DMSO-d6), : 11,54 (s, 1H), 9,4 (sh. s, 1H), EUR 7.57 (d, J=8,3 Hz, 2H), was 7.36 (d, J=8,3 Hz, 2H), 7,21-7,14 (m, 5H), 3.75 to to 3.73 (m, 2H), 2,87-2,82 (m, 2H), 2,8 (K, J=7.8 Hz, 2H) 1,17 (t, J=7.8 Hz, 2H).

MS (FD) m/e 445 (M+), 447 (M+2).

UV (EtOH, nm: 291, 263, 237, 203.

Found, %: C 53,71; H Br4.61; N 9,39.

C20H20BrN3S2< / BR>
Calculated,%: C 53,81; H To 4.52; N 9,41.

Example 229. N-(2-Phenethyl)-N'-pyridine[2,3-a]thiazolyl)thiourea.

A solution of 2-geneticization (1,33 g, 8,13 mmol, 1,21 ml) and 2-aminopyridine[2,3-d] thiazole (1,23 g, 8,13 mmol) in N,N-dimethylformamide (15 ml) is heated at 105oC. Through 46,5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic solution was washed with water (6x) and brine. The organic layer is dried over sodium sulfate, filtered and concentrated. Purification of the residue pressure chromatography on silica gel IDA white powder, recrystallized from ethyl acetate, so pl. 202-202,5oC.

IR (KBr), cm-1: 3445, 3171, 3025, 1565, 1551, 1510, 1382, 1201, 1150.

1H-NMR (300 MHz, DMSO-d6), : 11,91 (sh.s, 1H), 9,76 (sh.s, 1H), of 8.37 (m, 1H), 7,88 (m, 1H), 7,43 (LW.d, J = 3 and 6 Hz, 1H), 7,33 to 7.2 (m, 5H), 3,82-with 3.79 (m, 2H), 2,89 (t, J = 7,0 Hz, 2H).

MS (FAB) m/e 315 (M+1).

UV (EtOH): 312 nm ( = 22468), 211 nm ( = 19194).

Found,%: C 57,2; H 4,49; N 17,66.

C15H14N4S2< / BR>
Calculated,%: C 57,3; H Of 4.49; N, 17,82.

Example 230. N-(2-Phenethyl)-N'-[2-(3-ethyl)pyridyl]thiourea.

A. 2-tert-Butoxycarbonylamino-3-ethylpyridine.

In 80 ml of tetrahydrofuran was dissolved 2-tert-butoxycarbonylamino (10 g, 51,5 mmol) and cooled to -78oC. for 1 hour and added dropwise n-utility (80 ml 1,49 M solution in hexane, 120 mmol). After stirring for 15 min at -78oC and then 2.5 h at -10oC the solution is again cooled to -78oC and for 15 min with a syringe and added dropwise Iodate (77.2 mmol, 6,18 ml). The solution is allowed to warm to room temperature. The reaction mixture was neutralized with a saturated solution of ammonium chloride (100 ml) and extracted with ethyl acetate (3x). The organic extracts are combined, dried over magnesium sulfate and the end of the g (43%) of the indicated compound as a light brown substance, so pl. 101-102oC.

IR (KBr), cm-1: 3174, 2968, 1725, 1594, 1519, 1442, 1278, 1249, 1156.

1H-NMR (300 MHz, DMSO-d6), : 8,98 (s, 1H), 8,17 (m, 1H), to 7.61 (m, 1H), 7,15 (m, 1H), 2,52 (K, J = 7.5 Hz, 2H), 1.39 in (s, 9H), of 1.08 (t, J = 7.5 Hz, 3H).

MS (FD) m/e 222 (M+).

UV (EtOH): 270 nm ( = 4398), 223 nm ( = 6745).

Found,%: C 64,91; H A 8.34; N 12,42.

C12H18N2O2< / BR>
Calculated,%: C 64,84; H 8,16; N 12,60.

B. Obtain 3-ethyl-2-aminopyridine.

In 90 ml of a mixture of 3 N. HCl with acetic acid dissolve 2-tert-butoxycarbonylamino-3-ethylpyridine (4.9 g, and 19.8 mmol) and stirred for 2 hours, the Solution is neutralized 2 N. NaOH to pH 7 and then extracted with ethyl acetate (2 x 400 ml). The organic phase is dried over magnesium sulfate, and after concentrating obtain 2.3 g (95%) of a yellowish solid product used in subsequent reactions without further purification.

C. N-(2-Phenethyl)-N'-[2-(3-ethyl)pyridyl]thiourea.

A solution of 2-geneticization (3,61 g of 18.8 mmol, 3.3 ml) and 2-amino-3-ethylpyridine (2.3 g, 18,8 mmol) in N,N-dimethylformamide (20 ml) is stirred for 3 h at 90-95oC. the Solution is cooled to room temperature, transferred into ethyl acetate (150 ml) and washed with 0.1 G. of hydrochloric acid (2x), water (3x) and brine. The organic phase sushi is on silica gel (1.5% ethyl acetate in dichloromethane) followed by recrystallization (30% ethyl acetate in hexane) to obtain 1.1 g (21%) of the compounds in the form of a white substance, so pl. 57-58oC.

IR (KBr), cm-1: 3433, 2932, 1561, 1516, 1452, 1433, 1328, 1237, 760.

1H-NMR (300 MHz, DMSO-d6), : 11,58 (sh.s, 1H), 8,66 (sh.s, 1H), 7,92 to 7.9 (m, 1H), 7,6-7,58 (m, 1H), 7.3 to to 7.15 (m, 5H), 7,02-6,98 (m, 1H), 3,83-of 3.77 (m, 2H), 2,89 (t, J = 6 Hz, 2H), 2,64 (K, J = 7.5 Hz, 2H), 1,09 (t, J = 7.5 Hz, 3H).

MS (FD) m/e 285 (M+).

UV (EtOH): 293 nm ( = 16632), 265 nm ( = 14930), 244 nm ( = 16594), 202 nm ( = 21127).

Found,%: C 67,17; H 6,88; N 14,51.

C16H19N3S

Calculated,%: C 67,33; H Of 6.71; N 14,72.

Example 231. N-(2-Phenethyl)-N-[2-(3-bromo)pyridyl]thiourea.

A. 2-tert-Butoxycarbonylamino-3-bromopyridin.

In 80 ml of tetrahydrofuran was dissolved 2-tert-butoxycarbonylamino (10 g, 51,5 mmol), cooled to -78oC for 1 h are added dropwise n-utility (120 mmol, 80 ml 1,49 M solution in hexane). After stirring for a further 15 min at -78oC and 2.5 h at -10oC the solution is again cooled to -78oC and to it for 15 min with a syringe and added dropwise 1,2-dibromethane (77.2 mmol, 6,65 ml). The solution is allowed to warm to room temperature. The reaction mixture was neutralized with 100 ml of saturated solution of ammonium chloride and extracted with ethyl acetate (3x). The organic layers are combined, dried over magnesium sulfate, filtrex) are obtained 4.5 g (32%) of the indicated compound as a light brown substance, so pl. 120-121oC.

IR (KBr), cm-1: 3191, 2980, 1729, 1521, 1442, 1365, 1272, 1166, 1032.

1H-NMR (300 MHz, DMSO-d6), : 9.28 are (s, 1H), 8.34 per (m, 1H), with 8.05 (m, 1H), 7,15 (m, 1H), of 1.39 (s, 9H).

MS (FD) m/e 272 (M+), 274 (M+2).

UV (EtOH): 280 nm ( = 4047), 230 nm ( = 9067), 204 nm ( = 16385).

B. Obtain 3-bromo-2-aminopyridine.

In 70 ml of a mixture of 3 N. HCl with acetic acid dissolve 3-bromo-2-tert-butoxycarbonylamino (3.8 g, a 13.9 mmol) and stirred for 2 hours, the Solution is neutralized 2 N. NaOH to pH 7 and then extracted with ethyl acetate (3 x 300 ml). The organic phase is dried over magnesium sulfate and after preconcentration get a brown oil. The oil about a night stand in a vacuum and obtain 2.4 g (100%) of crystalline product used in the subsequent stage without further purification, so pl. 57-59oC.

1H-NMR (300 MHz, DMSO-d6), : 7,9 (m, 1H), 7,65 (m, 1H), 6.4 (m, 1H), 6,2-or 6.1 (s, 2H).

C. N-(2-Phenethyl)-N'-[2-(3-bromo)pyridyl]thiourea.

A solution of 2-geneticization (1.89 g, 11.6 mmol, 1.73 ml) and 2-amino-3-bromopyridine (2 g, 11.6 mmol) in N,N-dimethylformamide is stirred for 3 h at 90-95oC. the Solution is cooled to room temperature, transferred into ethyl acetate and washed with 0.1 G. of hydrochloric acid (2x), water (3x) Alnoy chromatography, on silica gel (30% ethyl acetate in hexane) and obtain 0.5 g (13%) of the compounds in the form of a white substance, so pl. 95-96oC.

1H-NMR (300 MHz, DMSO-d6), : 11,2 (m, 1H), 8,45 (s, 1H), 8,13-of 8.06 (m, 2H), 7,29-to 7.18 (m, 5H),? 7.04 baby mortality-7 (m, 1H), 3,86 to 3.8 (m, 2H), only 2.91 (t, J = 6 Hz, 2H).

MS (FD) m/e 335 (M+), 337 (M+2).

UV (EtOH): 298 nm ( = 13404), 272 nm ( = 16029), 250 nm ( = 17186), 203 nm ( = 22974).

Found,%: C 49,77; H 4,21; N 12,37.

C14H14N4S2Br

Calculated,%: C Repossessed A 50.01; H 4,20; N 12,50.

Example 232. N-(4-Bromophenetole)-N'-[2-(4-ethyl)thiazolyl]thiourea.

In dichloromethane with water to form a suspension of the hydrochloride of 4-bromophenethylamine (1 g, 4,22 mmol), obtained suspension add aqueous sodium hydroxide (0.17 g, 4,22 mmol) and stirred. The organic portion was separated, washed with brine, dried over sodium sulfate, filtered and concentrated. The obtained solid product is added to N-(diimidazole)-2-amino-4-atillasoy (1 g, 4,22 mmol) in 20 ml of N,N-dimethylformamide and stirred for 3 h at 90-95oC. the Solution is cooled to room temperature, add 150 ml of ethyl acetate and washed with 0.1 G. of hydrochloric acid (2x), water (3x) and brine. The organic phase is dried over sodium sulfate, filtered and concentrated. Precrystallization>o
C.

IR (KBr), cm-1: 2963, 1560, 1527, 1259, 1212, 1011, 802, 743.

1H-NMR (300 MHz, CDCl3), : 10,94 (sh.s, 1H), 9,77 (sh.s, 1H), 7,41 (d, J = 8,3 Hz, 2H), 7,24 (d, J = 8,2 Hz, 2H), 6,33 (s, 1H), 4,03-of 3.97 (m, 2H), 2,97 (t, J = 6,8 Hz, 2H), 2.49 USD (K, J = 7.5 Hz, 2H), 1,13 (t, J = 7.5 Hz, 3H).

MS (FD) m/e 369 (M+), 371 (M+2).

UV (EtOH): 292 nm ( = 10803), 257 nm ( = 6300).

Found,%: C 45,53; H 4,42; N 11,49.

C14H16N3SBr

Calculated,%: C 45,41; H 4,35; N 11,35.

Example 233. N-(3-Phenoxyphenyl)-N'-[2-(4-ethyl)thiazolyl] thiourea.

In dichloromethane with water to form a suspension of the hydrochloride of 3-renoxification (1 g, 4 mmol), suspended solids add aqueous sodium hydroxide (0.16 g, 4 mmol) and stirred. The organic portion was separated, washed with brine, dried over sodium sulfate, filtered and concentrated. To the resulting solid residue is added N-(diimidazole)-2-amino-4-utiltity (1 g, 4,22 mmol) and N,N-dimethylformamide (20 ml) and stirred for 3 h at 90-95oC. the Solution is cooled to room temperature, added to 150 ml of ethyl acetate and washed with 0.1 G. of hydrochloric acid (2x), water (3x) and brine. The organic phase is dried over sodium sulfate, filtered and concentrated. Oil for about a day placed under vacuum and recrystallization (5tx2">

IR (KBr), cm-1: 3177, 2966, 1563, 1534, 1509, 1491, 1446, 1349, 1287, 1218, 1158, 773.

1H-NMR (300 MHz, CCl3), : 10,99 (sh.s, 1H), 9,87 (sh.s, 1H), 7,31-of 7.23 (m, 3H), 7,09-6,84 (m, 6H), 6,32 (s, 1H), 4,03-of 3.97 (m, 2H), 2,99 (t, J = 6,8 Hz, 2H), 2,53 (K, J = 7.5 Hz, 2H), 1.14 in (t, J = 7.5 Hz, 3H).

MS (FD) m/e 383 (M+).

UV (EtOH): 293 nm ( = 19262), 258 nm ( = 11356), 205 nm ( = 37212).

Found,%: C 62,69; H 5,61; N 11,06.

C20H21N3OS2< / BR>
Calculated,%: C 62,63; H 5,52; N 10,96.

Example 234. In dichloromethane with water to form a suspension tosilata 2-nitroaniline (0.97 g, 3 mmol), suspended solids add aqueous sodium hydroxide (0.12 g, 3 mmol) and stirred. The organic portion was separated, washed with brine, dried over sodium sulfate, filtered and concentrated. The obtained solid residue is added to N-(diimidazole)-2-amino-4-atillasoy (VK8-T-074) (0.71 g, 3 mmol) in 20 ml of N,N-dimethylformamide and stirred for 3 h at 90-95oC. the Solution is allowed to cool to room temperature, then added to 150 ml of ethyl acetate and washed with 0.1 G. of hydrochloric acid (2x), water (3x) and brine. The organic phase is dried over sodium sulfate, filtered and concentrated. By recrystallization (50% ethyl acetate in hexane) of the solid residue receive 0.5 g (54%) of the indicated compound as a white bi, CDCl3), : 11,06 (sh.s, 1H), 9,76 (sh.s, 1H), 7,88 (d, J = 8,1 Hz, 1H), 7,56-7,35 (m, 3H), 6.35mm (s, 1H), 4,13-was 4.02 (m, 2H), 3.33 and (t, J = 7,0 Hz, 2H), 2,56 (K, J = 7,4 Hz, 2H), 1,16 (t, J = 7.4 Hz, 3H).

MS (FD) m/e 336 (M+).

UV (EtOH): 292 nm ( = 20546), 258 nm ( = 14748), 203 nm ( = 24932).

Found,%: C 49,95; H A 4.86; N 16,59.

C14H16N4O2S2< / BR>
Calculated,%: C 49,98; H 4,79; N 16,65.

Example 235. N-[6-(2-Phenylbenzoxazole)ethyl] -N'-(2-atillasoy) thiourea.

In dichloromethane with water to form a suspension of the hydrochloride of 2-[6-(2-phenylbenzoxazole)] ethylamine, add aqueous sodium hydroxide (0,13 g, 3.2 mmol) and stirred. The organic portion was separated, washed with brine, dried over sodium sulfate, filtered and concentrated. The remainder is added to N-(diimidazole)-2-amino-4-atillasoy (0.71 g, 3 mmol) in N,N-dimethylformamide (20 ml) and stirred for 3 h at 90-95oC. the Solution is cooled to room temperature, added to 150 ml of ethyl acetate and washed with 0.1 G. of hydrochloric acid (2x), water (3x) and brine. The organic phase is dried over sodium sulfate, filtered and concentrated. By recrystallization (50% ethyl acetate in hexane) of the solid residue receive 0.64 g (49%) of the compounds in the form of a white substance, so pl. 183oC.

IR (KBr), cm-1= 8,1 Hz, 1H), 7,53-of 7.48 (m, 4H), 7,29 (m, 1H), 6,28 (s, 1H), 4,13-4,06 (m, 2H), 3,17 (t, J = 6.6 Hz, 2H), 2,39 (K, J = 7.5 Hz, 2H), 1 (t, J = 7.5 Hz, 3H).

MS (FD) m/e 408 (M+).

UV (EtOH): 294 nm ( = 12603), 201 nm ( = 14517).

Found,%: C 61,99; H 5,18; N 13,85.

C21H20N4OS2< / BR>
Calculated,%: C 61,74; H Is 4.93; N 13,71.

Example 236. N-(2-Phenoxyphenyl)-N'-[2-(ethyl)thiazolyl)]thiourea.

In dichloromethane with water to form a suspension of the hydrochloride of 2-renoxification (0.97 g, 3.9 mmol), add aqueous sodium hydroxide (0,13 g, 3.9 mmol) and stirred. The organic portion was separated, washed with brine, dried over sodium sulfate, filtered and concentrated. The obtained solid product is added to N-(diimidazole)-2-amino-4-atillasoy (0,929 g, 3.9 mmol) in N,N-dimethylformamide (20 ml) and stirred for 3 h at 90-95oC. the Solution is cooled to room temperature, added to 150 ml of ethyl acetate and washed with 0.1 G. of hydrochloric acid (2x), water (3x) and brine. The organic phase is dried over sodium sulfate, filtered and concentrated. By recrystallization of the solid residue from 50% ethyl acetate in hexane obtain 0.73 g (49%) of the compounds in the form of a white substance, so pl. 168oC.

IR (KBr), cm-1: 3168, 3013, 1581, 1532, 1487, 1237, 1209, 753.

1

MS (FD) m/e 383 (M+).

UV (EtOH): 292 nm ( = 19052), 258 nm ( = 11450), 204 nm ( = 38534).

Found,%: C 62,91; H 5,67; N 11,22.

C20H21N3OS2< / BR>
Calculated,%: C 62,63; H 5,52; N 10,96.

Example 237. N-{[(4-Methyl-2-thiazolyl)amino]taxometer}-DL - phenylalanine, methyl ester.

A solution of 1-{[2-(4-methyl)thiazolyl]thiocarbamoyl}imidazole (0.45 g, 5 mmol) and methyl ester hydrochloride DL-phenylalanine (of 0.43 g, 2 mmol) in N,N-dimethylformamide (50 ml) is heated for 12 h at 110oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ethyl ether and hexane obtain 118 mg (18%) the specified connection, so pl. 131-132oC.

IR (KBr), cm-1: 3179, 3027, 1578, 1579, 1533, 1224.

1H-NMR (300 MHz, DMSO-d6), : 11,8 (sh. s, 1H), 10,2 (sh. s, 1H), 7,2-7,38 (m, 5H), 6,63 (s, 1H), 5,1 (, 1H), 3,63 (s, 3H), 3,03-up 3.22 (m, 2H), 2,12 (s, 3H).

MS (FD) m/e 335 (M+).

UV (EtOH): 294 nm ( = 18428), 257 nm ( = 9852), 202 nm ( = 21796).

Found,%: C 53.47 USD; H 5,11; N Was 12.75.

C15H17N3O2S2< / BR>
Calculated,%: C 53,71; H 5,11; N 12,53.

Example 238. ()-3-(4-Methyl-2-thiazolyl)-5-phenylmethyl-2-Toccoa (0,94 g, 2.8 mmol) and hydrate p-toluenesulfonic acid (0.2 g, 1.05 mmol) in toluene (80 ml) is boiled for 24 hours with a trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and concentrated. By recrystallization of the resulting product from a mixture of ethyl acetate/hexane get 216,1 mg (25%) of the specified connection, so pl. 169-171oC.

IR (KBr), cm-1: 3153, 1776, 1539, 1280, 1195, 744, 303.

1H-NMR (300 MHz, DMSO-d6), : 10,85 (s, 1H), and 7.4 (d, 1H), and 7.3 (m, 3H), 7,11 (m, 2H), a 4.83 (t, 1H), 3,5 (d, 2H), 2,35 (s, 3H).

MS (FD) m/e 303 (M+).

UV (EtOH): 265 nm ( = 16902), 203 nm ( = 17971).

Found,%: C 55,63; H Of 4.45; N 13,91.

C14H13N3OS2< / BR>
Calculated, %: C To 55.42; H 4,32; N 13,85. Hell/ AC R _ & n t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ A U S g C t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ z b 1 Z b c and 8 t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ 8 q > O f t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ [ th d l z t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ z J R d Sch . t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ . r t T R o o f ( c l t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ l ( o n 9 a B t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ B 9 ~ E M t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ Z j S u

Example 239. N-[(2-Thiazolylazo)taxameter]-DL-phenylalanine, methyl ester.

oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ether/hexane get 3,26 g (51%) of the specified connection.

IR (KBr), cm-1: 3184, 3029, 1735, 1569, 1510, 1223, 1189.

1H-NMR (300 MHz, DMSO-d6), : 11,9 (s, 1H), and 7.4 (d, 1H), 7,2-7,38 (m, 5H), 7,17 (d, 1H), 5,3 (K, 1H), 3,63 (s, 3H), 3,02-up 3.22 (m, 2H).

MS (FD) m/e 321 (M+).

UV (EtOH): 291 nm ( = 18235), 255 nm ( = 10773), 202 nm ( = 20575).

Found,%: C 52,24; H Br4.61; N Of 13.18.

C14H15N3O2S2< / BR>
Calculated,%: C 52,31; H 4,70; N 13,07.

Example 240. DL-5-(Phenylmethyl)-3-(2-thiazolyl-2-thioxo-4 - thiazolidinone.

A solution of methyl ester of N-[(2-thiazolylazo)taxameter]-DL-phenylalanine (0,47 g of 2.23 mmol) and hydrate p-toluenesulfonic acid (0.2 g, 1.05 mmol) in toluene (50 ml) is boiled for 12 h with trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and concentrate under reduced pressure. By recrystallization obtained), cm-1: 3099, 2985, 2873, 1775, 1532, 1440, 1398, 1329, 1251, 1208, 737.

1H-NMR (300 MHz, DMSO-d6), : 10,9 (s, 1H), 7,83 (d, 1H), and 7.8 (d, 1H), 7.5 (m, 3H), 7,2 (m, 2H), 4,9 (t, 1H), 3,17 (d, 2H).

MS (FD) m/e 289 (M+).

UV (EtOH): 264 nm ( = 16108), 202 nm ( = 17275).

Found,%: C 54,22; H 3,96; N 14,30.

C13H11N3OS2< / BR>
Calculated,%: C 53,96; H 3,83; N 14,52.

Example 241. N-[(2-Benzothiazolylthio)taxameter]-DL - phenylalanine, methyl ester.

A solution of 1-[(2-benzothiazolyl)thiocarbamoyl] imidazole (1.3 g, 5 mmol) and methyl ester hydrochloride DL-phenylalanine (1.08 g, 5 mmol) in N,N-dimethylformamide (50 ml) was heated 3 h at 90oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ether/hexane get 1,31 g (70%) of the specified connection, so pl. 168-169oC.

IR (KBr), cm-1: 3168, 3030, 1732, 1548, 1525, 1206, 1193.

1H-NMR (300 MHz, DMSO-d6), :10,3 (sh.s, 1H), 7,88 (d, 1H), 7.62mm (d, 1H), 7,32 (m, 1H), 7,2-7,29 (m, 6H), 5,18 (K, 1H), and 3.7 (s, 3H), up 3.22 (m, 2H).

MS (FD) m/e 371 (M+).

UV (EtOH): 303 nm ( = 25329), 247 nm ( = 12095), 203 nm ( = 28990).

Found,%: C 58,19; H 4,70; N 11,30.

C13H11N3OS2< / BR>
Calculated,%: C 58,20; H Br4.61; N 11,31.

oC.

IR (KBr), cm-1: 3250, 1766, 1522, 1489.

1H-NMR (300 MHz, DMSO-d6), : 11 (s, 1H), 8,18 (d, 1H), 8,02 (d, 1H), 7,08-8 (m, 2H), 7,37 (m, 3H), of 7.23 (d, 2H), equal to 4.97 (t, 1H), 3,18 (d, 2H).

MS (FD) m/e 339 (M+).

UV (EtOH): 300 nm ( = message 7355), 265 nm ( = 19454), 217 nm ( = 26558), 203 nm ( = 31150).

Found,%: C 60,33; H 4,14; N 12,25.

C17H13N3OS2< / BR>
Calculated,%: C 60,16; H 3,86; N 12,38.

Example 243. N-{[(6-fluoro-2-benzothiazolyl)amino]taxometer}-DL - phenylalanine, methyl ester.

A solution of 1-{ [2-(6-fluoro)benzothiazolyl] thiocarbamoyl} imidazole (1.4 g, 5 mmol) and methyl ester hydrochloride DL - phenylalanine (1.08 g, 5 mmol) in N, N-dimethylformamide (175 ml) was heated 3 h at 90oC. what estanlizania from a mixture of ether/ethyl acetate receive 900 mg (46%) of the specified connection.

1H-NMR (300 MHz, DMSO-d6), : there is a 10.03 (sh.s, 1H), 7,82 (K, 1H), 7,6 (m, 1H), 7,2-to 7.32 (m, 6H), 5,1 (, 1H), 3,63 (s, 3H), 3,2 (t, 2H).

MS (FD) m/e 389 (M+).

Example 244. DL-3-(6-fluoro-2-benzothiazolyl)-5-(phenylmethyl)-2 - thioxo-4-imidazolidinone.

A solution of methyl ester of N-{[(6-fluoro-2-benzothiazolyl)amino] taxometer} -DL-phenylalanine (0.9 g, 2,31 mmol) and hydrate n-toluenesulfonic acid (0.2 g, 1.05 mmol) in toluene (80 ml) is boiled for 48 h with trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and concentrate under reduced pressure. By recrystallization of the resulting product from a mixture of ether/hexane obtain 251 mg (31%) the specified connection, so pl. p.223-224oC.

IR (KBr), cm-1: 3173, 1767, 1538, 1453, 1388, 1267.

1H-NMR (300 MHz, DMSO-d6), : 11,02 (s, 1H), 8-8,12 (m, 2H), and 7.4-7.5 (m, 1H), 7,2-7,39 (m, 5H), equal to 4.97 (t, 1H), 3,2 (d, 2H).

MS (FD) m/e 357 (M+).

UV (EtOH): 265 nm ( = 15680), 223 nm ( = 19505), 201 nm ( = 23665).

Found,%: C 56,89; H 3,43; N 11,60.

C17H12FN3OS2< / BR>
Calculated,%: C 57,13; H 3,38; N 11,76.

Example 245. N-{[(4,5 the Lil]thiocarbamoyl}imidazole (1.8 g, 7.5 mmol) and methyl ester hydrochloride DL-phenylalanine (1.6 g, 7.5 mmol) in N, N-dimethylformamide (50 ml) is heated 4 hours at 90oC. the Reaction mass is then cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ether/hexane get 1,91 g (72%) of the specified connection.

IR (KBr), cm-1: 3178, 3079, 1756, 1552, 1505, 1219.

1H-NMR (300 MHz, DMSO-d6), : 11,65 (s, 3H), 7,2-7,38 (m, 5H), 5,1 (, 1H), the 3.65 (s, 3H), 3,05-is 3.21 (m, 2H), 2,2 (s, 3H), 2,08 (t, 3H).

MS (FD) m/e 349 (M+).

UV (EtOH): 300 nm ( = 17248), 257 nm ( = 9202), 203 nm ( = 22444).

Found,%: C 55,16; H To 5.57; N 12,01.

C16H19N3O2S2< / BR>
Calculated,%: C 54,99; H 5,48; N 12,02.

Example 246. DL-(4,5-Dimethyl-2-thiazolyl)-5-(phenylmethyl)-2 - thioxo-4-imidazolidinone.

A solution of N-{[(4,5-dimethyl-2-thiazolyl)amino]taxometer}-DL - phenylalanine (1 g, of 2.86 mmol) and hydrate n-toluenesulfonic acid (0.2 g, 1.05 mmol) in toluene (50 ml) is boiled for 48 h with trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and concentrate the (60%) of the specified connection so pl. 205-207oC.

IR (KBr), cm-1: 3161, 1783, 1527, 1287, 1164.

1H-NMR (300 MHz, DMSO-d6), : 10,8 (s, 1H), and 7.3 (m, 3H), 7,2 (m, 2H), a 4.83 (t, 1H), 3,1 (d, 2H), 2,32 (s, 3H), of 2.21 (s, 3H).

MS (FD) m/e 317 (M+).

UV (EtOH): 266 nm ( = 16921), 201 nm ( = 17995).

Found,%: C 56,53; H 4,94; N 13,49.

C15H15N3OS2< / BR>
Calculated,%: C 56,76; H Amounts To 4.76; N 13,24.

Example 247. N-{[(4-Cyano-2-thiazolyl)amino]taxometer}-DL - phenylalanine, methyl ester.

A solution of 1-{[2-(4-cyano)thiazolyl]thiocarbamoyl}imidazole (1,76 g, 7.5 mmol) and methyl ester hydrochloride DL-phenylalanine (1,62 g, 7.5 mmol) in N, N-dimethylformamide (50 ml) is heated 5 h at 90oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ethyl ether and hexane obtain 1.42 g (55%) of the specified connection.

IR (KBr), cm-1: 3011, 2220, 1742, 1672, 1586, 1455, 1372.

1H-NMR (300 MHz, DMSO-d6), : 7,12-7,38 (m, 5H), and 7.4 (s, 1H), of 5.05 (K, 1H), 3,63 (s, 3H), 3,03-up 3.22 (m, 2H).

MS (FD) m/e 346 (M+).

UV (EtOH): 287 nm ( = 7404), 257 nm ( = 12260), 206 nm ( = 30014).

Example 248. DL-3-(4-Cyano-2-thiazolyl)-5-(phenylmethyl)-2-thioxo-4 - imidazolidinone.

A solution of methyl EF, ,05 mmol) in toluene (80 ml) is boiled for 24 hours with a trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and concentrate under reduced pressure. By recrystallization of the resulting product from a mixture of ethyl ether/hexane receive USD 170.1 mg (10%) of the specified connection, so pl. 214-216oC.

IR (KBr), cm-1: 3294, 3092, 2246, 1781, 1505, 1381, 1325, 1244.

1H-NMR (300 MHz, DMSO-d6), : 11,08 (s, 1H), 8,9 (s, 1H), 7,22-7,8 (m, 3H), 7,2-7,22 (m, 2H), a 4.83 (t, 1H), 3,17 (d, 1H).

MS (FD) m/e 314 (M+).

UV (EtOH): 259 nm ( = 15097), 205 nm ( = 26419).

Found,%: C 53,75; H 3,43; N 17,62.

C14H10N4OS2< / BR>
Calculated,%: C 53,49; H Is 3.21; N, 17,82.

Example 249. N-{ [(4-Trifluoromethyl-2-thiazolyl)amino]taxometer}- DL-phenylalanine, methyl ester.

A solution of 1-{ [2-(4-trifluoromethyl)thiazolyl] thiocarbamoyl}imidazole (1.6 g, 5.8 mmol) and methyl ester hydrochloride DL-phenylalanine (1.24 g, 5.8 mmol) in N,N-dimethylformamide (50 ml) is heated 5 h at 90oC. the Reaction mixture is cooled to room temperature, the solvent is removed at Pont is.

IR (KBr), cm-1: 3000, 1744, 1672, 1554, 1523, 1226.

1H-NMR (300 MHz, DMSO-d6), : 8,64 (d, 1H), 7,82 (s, 1H), 7,21-7,38 (m, 3H), 7,19-7,21 (d, 2H), of 5.05 (K, 1H), 3,63 (s, 3H), 3,02-up 3.22 (m, 2H).

MS (FD) m/e 389 (M+).

UV (EtOH): 287 nm ( = 11327), 256 nm ( = 11674), 203 nm ( = 24532).

Found,%: C 46,55; H 3,57; N 11,06.

C15H14F3N3O2S2< / BR>
Calculated,%: C 46,27; H 3,62; N 10,79.

Example 250. DL3-(4-Trifluoromethyl-2-thiazolyl)-5-(phenylmethyl)-2 - thioxo-4-imidazolidinone.

A solution of N-{ [(4-trifluoromethyl-2-thiazolyl)amino] taxometer}- DL-phenylalanine, methyl ester (2,09 g, 5,38 mmol) and hydrate p-toluenesulfonic acid (0.2 g, 1.05 mmol) in toluene (80 ml) is boiled for 48 h with trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and concentrate under reduced pressure. By recrystallization of the resulting product from a mixture of ethyl ether/hexane obtain 1.01 g (53%) of the specified connection, so pl. 187-189oC.

IR (KBr), cm-1: 3431, 3008, 1782, 1495, 1369, 1328, 1242, 1178, 1149, 1085.

1H-NMR (300 MHz, DMSO-d6), : 11,02 (s, 1H), 8,59 (C ( = 19355).

Found,%: C 47,33; H 2,86; N 11,67.

C14H10F3N3OS2< / BR>
Calculated,%: C 47,05; H 2,82; N 11,76.

Example 251. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(6-bromo)pyridinyl]thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-6-bromopyridine (1.73 g, 10 mmol) in N,N-dimethylformamide (100 ml) is heated for 96 hours at 100oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with 1 N. HCl. The organic layer is concentrated and purification of the residue HPLC (elution with hexane/EtOAc) get 70.1 mg (2.1 per cent) specified connection, so pl. 174-175oC.

IR (CHCl3), cm-1: 2936, 1592, 1512, 1448, 1203.

1H-NMR (300 MHz, DMSO-d6), : 10,79 (s, 1H), 10,65 (m, 1H), and 7.7 (t, 1H), 7,28 (d, 1H), 7,19 (d, 1H), 5,6 (s, 1H), 3,7 (K, 2H), 2,23 (t, 2H), 1,95 (s, 4H), 1,62-of 1.42 (m, 4H).

MS (FD) m/e 341 (M+).

UV (EtOH): 303 nm ( = 19786, 269 nm ( = 18279), 252 nm ( = 18006), 201 nm ( = 17992).

Found,%: C 49,69; H Are 5.36; N 12,09.

C14H18BrN3S

Calculated,%: C 49,42; H 5,33; N 12,35.

Example 252. N-[2-(1-Cyclohexenyl)ethyl] -N'-[(4-isopropyl) pyridinyl] thiourea.

A solution of 2-(1-cyclohexenyl)utilizationof (0.36 g, 2.2 mmol) is Y. the mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate and washed with 1 N. aqueous HCl. The organic layer is concentrated and purification of the residue HPLC (elution with hexane/EtOAc) to obtain 169 mg (5.6 percent) specified connection, so pl. 105-106oC.

IR (KBr), cm-1: 3215, 2931, 1614, 1556, 1534, 1487, 1199.

1H-NMR (300 MHz, DMSO-d6), : 11,65 (t, 1H), 10,4 (s, 1H), 8.3 (l, 1H), 7,2 (s, 1H), 6,93 (d, 1H), 5,52 (s, 1H), 3,63 (K, 2H), 2,8 (m, 1H), 2,22 (t, 2H), 1,95 (m, 4H), 1,62-of 1.42 (m, 4H), of 1.18 (d, 6H).

Example 253. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(6-methylthio) benzothiazole]thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-aminobenzothiazole (a 1.96 g, 10 mmol) in N,N-dimethylformamide (20 ml) is heated for 96 hours at 100oC. the Reaction mixture is cooled to room temperature, the precipitate is collected and washing with ethyl acetate, to obtain 1.22 g (54%) of the specified connection, so pl. 186-187oC.

IR (KBr), cm-1: 3171, 3036, 2918, 1548, 1522, 1251, 1214.

1H-NMR (300 MHz, DMSO-d6), : 11,82 (sh. s, 1H), 10,2 (sh. s, 1H), 7,88 (s, 1H), and 7.6-7.5 (m, 1H), 7,4-7,3 (K, 1H), of 5.55 (s, 1H), 3,67 (K, 1H), and 2.4 (s, 3H), of 2.25 (t, 2H), 1,95 (s, 4H), 1,62-of 1.42 (m, 4H).

MS (FD) m/e 363 (M+).

UV (EtOH): 318 nm ( = 14538), 256 nm ( = 6742), 224 nm ( = 13749), 201 nm ( = 11940).

Found,%: C 56,40; H 5,2-(1-Cyclohexenyl)ethyl]-N'-{2-[4-(4-bromo)phenyl]}thiazolidinedione.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-4-(4-bromophenyl)thiazole (2.55 g, 10 mmol) in N,N-dimethylformamide (20 ml) is heated for 72 h at 100oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ethyl acetate/hexane obtain 455 mg (11%) the specified connection, so pl. 219-220oC.

IR (KBr), cm-1: 3171, 2927, 1566, 1516, 1301, 1211, 1110, 1071.

1H-NMR (300 MHz, DMSO-d6), : 11,7 (s, 1H), 9,3 (sh.s, 1H), and 7.8 (d, 2H), 7,6 (m, 3H), 5,43 (s, 1H), 3,67 (K, 2H, in), 2.25 (t, 2H), 1,95 (s, 4H), 1,62-of 1.42 (m, 4H).

MS (FD) m/e 421 (M+).

UV (EtOH): 285 nm ( = 27781), 245 nm ( = 17426), 202 nm ( = 31192).

Found,%: C 51,08; H 4,47; N To 9.91.

C18H20BrN3S2< / BR>
Calculated,%: C 51,18; H Of 4.77; N 9,95.

Example 255. N-[2-(1-Cyclohexenyl)ethyl] -N'-{ 2-[4-(2- hexadecenoic)phenyl]thiazolyl}thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (840 mg, 5 mmol) and 2-amino-4-[(2-hexadecenoic)phenyl] thiazole (2.1 g, 5 mmol) in N,N-dimethylformamide (20 ml) is heated for 72 h at 100oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization from a mixture of ethyl acetate/hexane get the 91H-NMR (300 MHz, DMSO-d6), : are 11.62 (s, 1H), 9,62 (sh.s, 1H), 7,95 (d, 1H), 7,56 (s, 1H), and 7.3 (t, 1H), 7,12 (d, 1H), 7 (t, 1H), 5,43 (s, 1H), 4,1 (t, 2H), 3,65 (K, 2H, in), 2.25 (t, 2H), 1,95 (sh.s, 2H) and 1.83 (t, 3H), 1,94-of 1.73 (m, 4H), 1,4-of 1.38 (m, 2H), 1,23 (s, 28H).

MS (FD) m/e 583 (M+).

UV (EtOH): 299 nm ( = 21244), 263 nm ( = 21549), 202 nm ( = 30773).

Found,%: C 69,70; H 8,99; N 7,28.

C34H53N3OS2< / BR>
Calculated,%: C 69,93; H 9,15; N 7,19.

Example 256. N-[(2-Thiazolyl)amino]taxometer-DL-2-forfinally, methyl ester.

A solution of 1-[(2-thiazolyl)thiocarbamoyl] imidazole (3,15 g, 15 mmol) and the hydrochloride of the methyl ester of DL-2-pertanyaannya (3.51 g, 15 mmol) in N, N-dimethylformamide (100 ml) is heated for 8 h at 80oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ethyl ether/hexane get 1,89 g (37%) of the specified connection.

IR (KBr), cm-1: 3187, 3122, 3090, 3037, 2950, 1739, 1566, 1495, 1209, 1182.

1H-NMR (300 MHz, DMSO-d6), : 11,81 (sh.s, 1H), 7,39 (d, 1H), 7,26 (m, 2H), 7,18 (m, 3H), 5,16 (K, 1H), to 3.64 (s, 3H), of 3.28 (m, 2H).

MS (FD) m/e 339 (M+).

UV (EtOH): 290 nm ( = 18548), 256 nm ( = 10899), 203 nm ( = 19927).

Found,%: C 49,45; H 4,07; N 12,40.

C14H14FN3O2S2

A solution of methyl ester of N-[(2-thiazolyl)amino]taxometer-DL-2 - pertanyaannya (1 g, 2,95 mmol) and hydrate p-toluenesulfonic acid (0.2 g, 1.05 mmol) in toluene (100 ml) is boiled for 48 h with trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and concentrate under reduced pressure. By recrystallization of the resulting product from a mixture of ethyl acetate/hexane obtain 305 mg (23%) of the specified connection.

IR (KBr), cm-1: 3104, 2870, 1781, 1531, 1438, 1330, 1255, 1204.

1H-NMR (300 MHZ, DMSO-d6), : 10,95 (sh.s, 1H), a 7.85 (d, 1H), 7,78 (d, 1H), and 7.3 (m, 2H), 7,18 (m, 2H), a 4.83 (t, 1H), 3,18 (d, 2H).

MS (FD) m/e 307 (M+).

UV (EtOH): 397 nm ( = 586), 263 nm ( = 16615), 201 nm ( = 15980).

Found,%: C 50,84; H To 3.33; N 13,38.

C13H10N2FOS2< / BR>
Calculated,%: C 50,80; H 3,28; N 13,67.

Example 258. N-[(2-Thiazolyl)amino]taxometer-DL-3,5-bis(trifluoromethyl)phenylalanine, methyl ester.

A solution of 1-[2-thiazolyl)thiocarbamoyl] imidazole (0,46 g, 2,19 mmol) and methyl ester hydrochloride DL-3,5-dateformatpattern (0,77 g, 2,19 mmol) in N,N-doretel removed under reduced pressure and recrystallization of the residue from a mixture of ethyl ether/hexane obtain 203 mg (20%) of the specified connection.

IR (KBr), cm-1: 3179, 3022, 1745, 1568, 1379, 1291, 1212.

1H-NMR (300 MHZ, DMSO-d6), : 11,82 (sh. s, 1H), 7,98 (s, 3H), and 7.1 (m, 1H), 5,12 (m, 1H), and 3.31 (s, 3H), is 3.08 (m, 2H).

MS (FD) m/e 457 (M+).

UV (EtOH): 291 nm ( = 18895), 255 nm ( = 10490), 202 nm ( = 19571).

Found,%: C 41,90; H 2,74; N 9,36.

C16H13F6N3O2S2< / BR>
Calculated,%: C 42,01; H 2,86; N 9,19.

Example 259. DL-3-(2-Thiazolyl)-5-[(3,5-bis-(trifluoromethyl) phenylmethyl]-2-thioxo-4-imidazolidinone.

A solution of N-[(2-Thiazolyl)amino] taxometer-DL-3,5-bis-triftormetilfullerenov, methyl ester (0.15 g, 0.32 mmol) and hydrate p-toluenesulfonic acid (0.1 g, of 0.53 mmol) in toluene (65 ml) is boiled for 48 h with trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and after concentration under reduced pressure to obtain 39 mg (29%) of the specified connection.

IR (KBr), cm-1: 3105, 1771, 1535, 1500, 1444, 1380, 1278, 1217.

1H-NMR (300 MHz, DMSO-d6), : of 10.93 (sh.s, 1H), 8,03 (s, 1H), of 7.96 (s, 2H), 7,89 (d, 1H), and 7.8 (d, 1H), free 5.01 (t, 1H), 3,37 (d, 2H).

MS (FD) m/e 425 (M+).

UV (EB>2
< / BR>
Calculated,%: C 42,35; H 2,13; N 9,88.

Example 260. N-[(2-Thiazolyl)amino]taxometer-DL-2 - chlorophenylalanine, methyl ester.

A solution of 1-[(2-thiazolyl)thiocarbamoyl]imidazole (1.5 g, 7.1 mmol) and the hydrochloride of the methyl ester of DL-2-chlorophenylalanine (1.78 g, 7.1 mmol) in N,N-dimethylformamide (65 ml) is heated for 7 h at 80oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ethyl ether/hexane get 280 mg (12%) the specified connection.

1H-NMR (300 MHz, DMSO-d6), : 7,38 (m, 3H), of 7.23 (m, 2H), 7,08 (sh.s, 1H), 5,17 (K, 1H), 3,62 (s, 3H), 3,21 (m, 2H).

MS (FD) m/e 355 (M+).

Example 261. N-[(2-Thiazolyl)amino] taxometer-DL-4 - chlorophenylalanine, methyl ester.

A solution of 1-[(2-thiazolyl)thiocarbamoyl]imidazole (1.5 g, 7.1 mmol) and methyl ester hydrochloride DL-4-chlorophenylalanine (1.78 g, 7.1 mmol) in N,N-dimethylformamide (65 ml) is heated for 6 h at 80oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ethyl ether/hexane obtain 840 mg (20%) of the specified connection.

IR (KBr), cm-1: 3176, 3025, 1735, 1562, 1510, 1493, 1467, 1452, 1387, 1353, 3,18 (m, 2H).

MS (FD) m/e 355 (M+).

UV (EtOH): 291 nm ( = 18545), 255 nm ( = 11222), 220 nm ( = 16171), 201 nm ( = 18545).

Found,%: C 47,28; H 3,94; N 11,88.

C12H14ClN3O2S2< / BR>
Calculated,%: C 47,25; H 3,96; N 11,81.

Example 262. DL-3-(2-Thiazolyl)-5-[(4-chloro)phenylmethyl] -2-thioxo-4 - imidazolidinone.

A solution of methyl ester of N-[(2-thiazolyl)amino]taxometer-DL-4 - chlorophenylalanine (0.84 g, 2.36 mmol) and hydrate p-toluenesulfonic acid (0.2 g, 1.05 mmol) in toluene (100 ml) is boiled for 48 h with trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and concentrate under reduced pressure. By recrystallization of the resulting product from a mixture of ethyl acetate/hexane obtain 176 mg (23%) of the specified connection.

1H-NMR (300 MHz, DMSO-d6), : 7,83 (d, 1H), 7,78 (d, 1H), 7,38 (d, 2H), 7,22 (d, 2H), around 4.85 (t, 1H), 3,11 (d, 2H).

MS (FD) m/e 323 (M+).

Example 263. N-[(2-Thiazolyl)amino]taxometer-DL-4 - cryptomaterial, methyl ester.

A solution of 1-[(2-thiazolyl)thiocarbamoyl] imidazole (1,03 g, 4.1 mmol) and the Hydra is h at 80oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ethyl ether/hexane receive 389 mg (24%) of the specified connection.

IR (KBr), cm-1: 3178, 3020, 1747, 1577, 1509, 1325, 1278, 1185.

1H-NMR (300 MHz, DMSO-d6), : 11,82 (sh. s, 1H), 9,82 (sh. s, 1H), 7,63 (d, 2H), 7,39 (d, 2H), 7,35 (d, 1H), 7,13 (s, 1H), 5,18 (K, 1H), 3,62 (s, 3H), and 3.31 (m, 2H).

MS (FD) m/e 389 (M+).

UV (EtOH): 291 nm ( = 18127), 255 nm ( = 10867), 201 nm ( = 20712).

Found,%: C 46,21; H 3,69; N 11,00.

C15H14N3F3O2S2< / BR>
Calculated,%: C 46,26; H 3,62; N 10,79.

Example 264. DL-3-(2-Thiazolyl)-5-[(4-trifluoromethyl)phenylmethyl] -2 - thioxo-4-imidazolidinone.

A solution of N-[(2-thiazolyl)amino]taxometer-DL-4 - cryptomaterial, methyl ester (0.34 g, 0.87 mmol) and hydrate p-toluenesulfonic acid (0.2 g, 0,106 mmol) in toluene (100 ml) is boiled for 48 h with trap Dean-stark. The reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate, washed with saturated solutions of sodium bicarbonate and sodium chloride, dried over magnesium sulfate and after concentration under reduced pressure produces is SUP>1H-NMR (300 MHz, DMSO-d6), : 10,9 (sh. s, 1H), 7,83 (d, 1H), 7,79 (d, 1H), 7,65 (d, 2H), 7,41 (d, 2H), 4,88 (t, 1H), up 3.22 (d, 2H).

MS (FD) m/e 357 (M+).

UV (EtOH): 264 nm ( = 15626), 201 nm ( = 16341).

Found,%: C 47,17; H 2,82; N 11,53.

C14H10F3N3OS

Calculated,%: C 47,05; H 2,82; N 11,76.

Example 265. N-[(2-Thiazolyl)amino]taxometer-DL-2,6 - dipertanyakan, methyl ester.

A solution of 1-[(2-thiazolyl)thiocarbamoyl] imidazole (0.65 g, is 3.08 mmol) and methyl ester hydrochloride DL-2,6-diferencialnye (0,78 g is 3.08 mmol) in N, N-dimethylformamide (75 ml) is heated for 7 h at 80oC. the Reaction mass is then cooled to room temperature, the solvent is removed under reduced pressure and recrystallization of the residue from a mixture of ethyl ether/hexane receive 413 mg (38%) of the specified connection.

IR (KBr), cm-1: 3205, 3036, 1737, 1625, 1554, 1511, 1468, 1442, 1388, 1265.

1H-NMR (300 MHz, DMSO-d6), : 11,83 (sh. s, 1H), 7,37 (K, 2H), was 7.08 (m, 2H), total of 5.21 (K, 1H), 3,62 (s, 3H), and 3.31 (m, 2H).

MS (FD) m/e 357 (M+).

UV (EtOH): 291 nm ( = 18495), 256 nm ( = 10699), 202 nm ( = 20082).

Found,%: C 47,08; H 3,76; N 11,93.

C14H13F2N3O2S2< / BR>
Calculated,%: C 47,05; H To 3.67; N 11,76.

Example 266. N-[2-(1-Cyclohexenyl)ethyl] - mmol) and 2-amino-4,5,6,7-tetrahydroindazole (1.54 g, 10 mmol) in N,N-dimethylformamide (100 ml) is heated to 120 h at 100oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate and washed with 1 N. HCl. The organic layer is concentrated and recrystallization of the residue from a mixture of ethyl acetate/hexane receive 426 mg (13%) the specified connection.

IR (KBr), cm-1: 3169, 3031, 2931, 1580, 1258, 1198.

1H-NMR (300 MHz, DMSO-d6), : 11,41 (sh.s, 1H), 10,85 (sh.s, 1H), 5,43 (s, 1H), to 3.58 (m, 2H), 2,6-1,9 (m, 10H), to 1.7 (m, 4H), 1,5 (m, 4H).

MS (FD) m/e 321 (M+).

UV (EtOH): 298 nm ( = 12157), 257 nm ( = 6569), 201 nm ( = 12172).

Found,%: C 60,06; H 6,95; N 12,82.

C16H23N3S2< / BR>
Calculated,%: C 59,97; H 7,21; N 13,07.

Example 267. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5-chloro) pyrazinyl]thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (2.3 g, 13.7 mmol) and 2-amino-5-chloropyrazine (1.75 g, 13.7 mmol) in N,N-dimethylformamide (40 ml) is heated to 192 h at 100oC. the Reaction mixture was cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate and washed with 1 N. aqueous HCl. The organic layer is concentrated and recrystallization of the resulting product from a mixture of a, 1153.

1H-NMR (300 MHz, DMSO-d6), : br11.01 (sh.s, 1H), 10,45 (t, 1H), scored 8.38 (d, 1H), 8,29 (d, 1H), 5,5 (sh.s, 1H), 3,63 (K, 2H), of 2.21 (t, 2H), 1,95 (m, 4H), of 1.52 (m, 4H).

MS (FD) m/e 296 (M+).

UV (EtOH): 330 nm ( = 9176), 273 nm ( = 21432), 201 nm ( = 10972).

Found,%: C 67,55; N 8,48; N 13,94.

C13H17N4SCl

Calculated,%: C 67,28; 8,30 H; N 13,85.

Example 268. N-[2-(1-Cyclohexenyl)ethyl]-N'-{2-[4-(3,4-dichloro) phenyl]thiazolyl}thiourea.

A solution of 4-(3,4-dichlorophenyl)-2-thiazoline (of 2.45 g, 10 mmol) and 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) in N,N-dimethylformamide (50 ml) is heated to 120 h at 100oC. the Reaction mixture is cooled to room temperature, the solvent is removed under reduced pressure, the residue is transferred into ethyl acetate and washed with 1 N. HCl. The organic layer is concentrated and recrystallization of the residue from a mixture of ethyl acetate/hexane receive 933 mg (2,3%) the specified connection.

IR (KBr), cm-1: 3169, 2927, 1573, 1558, 1523, 1460, 1393, 1295, 1214.

1H-NMR (300 MHz, DMSO-d6), : 11,72 (sh.s, 1H), 9,11 (sh.s, 1H), 8,07 (d, 1H), 7,83 (m, 1H), 7.62mm (m, 2H), of 5.45 (m, 1H), 3,6 (m, 2H), of 2.21 (m, 2H), of 1.85 (m, 4H), USD 1.43 (m, 4H).

MS (FD) m/e 411 (M+).

UV (MeOH): 287 nm ( = 25040), 241 nm ( = 16142), 205 nm ( = 29362).

Found,%: C 52,63; H 4,48; N Of 10.21.

C18

A solution of 1,1'-thiocarbonyldiimidazole (1.78 g, 10 mmol) and 2-methoxyphenethylamine (1.51 g, 10 mmol) in acetonitrile (25 ml) is stirred for 20 h at room temperature. Filtration of the resulting precipitate obtain 1.4 g (53%) of the specified connection.

IR (KBr), cm-1: 2944, 1563, 1493, 1409, 1282, 1246, 1031, 755.

1H-NMR (300 MHz, DMSO-d6), : 12 (sh.s, 1H), 7,65 (s, 1H), 7,25 (m, 2H), 7,05-6,9 (m, 4H), and 3.8 (m, 2H), and 3.8 (s, 3H), 2.95 points (t, J = 7 Hz, 2H).

MS (FD) m/e 261 (M+).

UV (EtOH): 278 nm ( = 7083), 216 nm ( = 12683), 203 nm ( = 22221).

Example 270. N-[2-(2-Methoxy)ethyl]-N'-(2-pyridyl)thiourea.

A solution of 1-[2-(2-methoxyphenyl)ethyl]thiocarbonyldiimidazole (0.52 g, 2 mmol) and 2-aminopyridine (0,19 g, 2 mmol) in N,N-dimethylformamide (5 ml) is stirred for 4 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. By recrystallization of the residue from ethyl acetate to obtain 0.25 g (44%) of the specified connection.

IR (KBr), cm-1: 3219, 3048, 1607, 1557, 1236, 1036, 756.

1H-NMR (300 MHz, DMSO-d6), : 11,65 (m, 1H), 10,55 (sh. s, 1H), 8,1 (m, 1H), to 7.75 (m, 1H), 7,3 or 6.9 (m, 6H), and 3.8 (m, 2H), of 3.78 (s, 3H), 2,9 (t, J = 7 Hz, 2H).

MS (FD) m/e 287 (M+).

UV (EtOH): 290 nm ( = 10141), 267 nm ( = 13121), 247 nm ( = 10959), 202 nm ( = 24078).

Example 271. N-[2-(1-Cyclohexen) and 2-amino-6-methylpyridine (1.08 g, 10 mmol) in N,N-dimethylformamide (25 ml) is heated for 20 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure. By recrystallization of the resulting product from a mixture of ethyl acetate/hexane obtain 1.04 g (38%) of the specified connection.

IR (KBr), cm-1: 3230, 2920, 1608, 1572, 1540, 1457, 1378, 1317, 1235, 1164.

1H-NMR (300 MHz, DMSO-d6), : 11,7 (sh. t, 1H), 10,45 (s, 1H), 7.62mm (t, 1H), 6,95 (d, 1H), 6,9 (d, 1H), 5,5 (sh. s, 1H), 3,7 (K, 2H), and 2.4 (s, 3H), of 2.25 (t, 2H), 1,95 (m, 4H), of 1.55 (m, 4H).

MS (FD) m/e 275 (M+).

UV (EtOH): 296 nm ( = 17669), 265 nm ( = 16667), 247 nm ( = 15266).

Found,%: C, 65.42 Per; H Of 7.75; N 15,20.

C15H21N3S

Calculated,%: C, 65.42 Per; H Of 7.69; N 15,26.

Example 272. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5-methyl)pyridyl] thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-5-methylpyridine (1.08 g, 10 mmol) in N,N-dimethylformamide (25 ml) is heated for 20 h at 100oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. By recrystallization of the resulting residue from a mixture of ethyl acetate/hexane obtain 1.06 g (39%) of the specified connection.

IR (KBr), cm-1: 3225, 2933, 1586, 1569, 1532, 1494, 1344, 1311, 1232, 827.

1H-NMR (3.

MS (FD) m/e 275 (M+).

UV (EtOH): 298 nm ( = 13663), 268 nm ( = 21631), 249 nm ( = 14893).

Found,%: C 65,15; H 7,75; 15,33.

C15H21N3S

Calculated,%: C, 65.42 Per; H Of 7.69; N 15,26.

Example 273. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(4-methyl)pyridyl]thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-4-methylpyridine (1.08 g, 10 mmol) in N,N-dimethylformamide (25 ml) is heated for 16 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure. Purification of the product by HPLC receive 1,67 g (61%) of the specified connection.

IR(KBr), cm-1: 3220, 2935, 1617, 1535, 1487, 1322, 1188, 866.

1H-NMR (300 MHz, DMSO-d6), : 11,65 (sh.t, 1H), 10,45 (s,1H), 8 (d, 1H), 6,95 (s,1H), 6,85 (d,1H), 5,5 (sh.s, 1H), 3,65 (K,2H), 2,3 (m, 5H), of 1.95 (m, 4H), of 1.55 (m,4H).

MS (FD) m/e 275 (M+).

UV (EtOH): 289 nm ( = 16865), 266 nm ( = 17870), 247 nm ( = 14179), 202 nm ( = 20105).

Found, %: C 65,16; H Of 7.55; N 15,30.

C15H21N3S

Calculated, %: C, 65.42 Per; H Of 7.69; N 15,26.

Example 274. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(3-methyl)pyridyl]thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-3-methylpyridine (1.08 g, 10 mmol) in N,N-dimethylformamide (2 is under reduced pressure. Purification of the product by HPLC obtain 1.8 g (65%) of the specified connection.

IR (KBr), cm-1: 3220, 2931, 1589, 1513, 1462, 1325, 1164.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh. t, 1H), 8,65 (c, 1H), with 8.05 (d, 1H), 7,65 (d, 1H), 7,05 (LW, d, 1H), 5,5 (sh. s, 1H), 3,65 (K, 2H), 2,3 (s, 3H), of 2.25 (t, 2H), 1,95 (m, 4H), of 1.55 (m,4H).

MS (FD) m/e 275 (M+).

UV (EtOH): 293 nm ( = 16693), 264 nm ( = 14464), 244 nm ( = 14762), 201 nm ( = 16723).

Example 275. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(6-ethyl)pyridyl]thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-6-ethylpyridine (1.22 g, 10 mmol) in N,N-dimethylformamide (25 ml) is heated for 20 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure. Purification of the product by HPLC obtain 1.55 g (54%) of the specified connection.

IR (KBr), cm-1: 3230, 2930, 1604, 1533, 1450, 1211, 1157.

1H-NMR (300 MHz, DMSO-d6), : 11,8 (sh. t, 1H), 10,45 (s, 1H), 7.62mm (t, 1H), 6,95 (d, 1H), 6,9 (d,1H), 5,45 (sh. c, 1H), 3,7 (K, 2H), 2,7 (K,2H, in), 2.25 (t,2H), 1,95 (m, 4H), of 1.55 (m,4H), 1,2 (t,3H).

MS (FD) m/e 289 (M+).

UV (EtOH): 296 nm ( = 17903), 265 nm ( = 16556), 247 nm ( = 14932), 201 nm ( = 14174).

Found, %: C To 66.4; H 8,00; N 14,75.

C16H23N3S

Calculated, %: C To 66.4; H 8,01; N 14,52.

Primatologica (1,67 g, 10 mmol) and 2-amino-4-ethylpyridine (1.22 g, 10 mmol) in N,N-dimethylformamide (25 ml) is heated for 16 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure. Purification of the product by HPLC obtain 1.2 g (42%) of the specified connection.

IR (KBr), cm-1: 3215, 2931, 1615, 1535, 1407, 1334, 1198, 843.

1H-NMR (300 MHz, DMSO-d6), : 11,68 (sh.t, 1H), 10,45 (s, 1H), 8, (d, 1H), 7 (s, 1H), 6,9 (d, 1H), 5,5 (sh. s,1H), 3,65 (K, 2H), 2,6 (K, 2H, in), 2.25 (t,2H), 1,95 (m,4H), of 1.55 (m, 4 H), 1,2 (t,3H).

MS (FD) m/e 290 (M+-H).

UV (EtOH): 289 nm ( = 17378), 266 nm ( = 18654), 247 nm ( = 14847), 202 nm ( = 23101).

Found, %: C 66,45; H 7,99; N 14,26.

C16H23N3S

Calculated, %: C 66,40; H 8,01; N 14,52.

Example 277. N-[2-(1-Cyclohexenyl)ethyl]-N1-[2-(5-trifluoromethyl)pyridyl] thiourea.

A solution of 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) and 2-amino-5-triptoreline (of 1.62 g, 10 mmol) in N,N-dimethylformamide (25 ml) is heated for 72 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure. Purification of the product by HPLC obtain 0.33 g (10%) of the specified connection.

IR (KBr), cm-1: 3220, 2929, 1618, 1551, 1500, 1324, 1238, 1132, 1078, 828.

4H), of 1.55 (m, 4H).

MS (FD) m/e 329 (M+).

UV (EtOH): 296 nm ( = 17058), 255 nm ( = 14250).

Found, %: C 54,98; H 5,67; N 12,59.

C15H18N3F3S

Calculated, %: C 54,70; H 5,51; N 12,76.

Example 278. N-[(1-Cyclohexenyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

A solution of 1- {[2-(4-methyl)thiazolyl]thiocarbamoyl}imidazole (1 g, of 4.46 mmol) and 2-cyclohexylethylamine (0,567 g of 4.46 mmol) in N,N-dimethylformamide (25 ml) is stirred for 16 h at 90oC. the Reaction mass is then cooled to room temperature and the solvent is removed in vacuum. By recrystallization of the residue from ethyl acetate get to 0.72 g (57%) of the specified connection.

IR (KBr), cm-1: 3220, 2922, 1565, 1505, 1227, 1168.

1H-NMR (300 MHz, DMSO-d6), : 11.5cm (W.s, 1H), 9,9 (sh.s, 1H), 6,65 (s, 1H), 3,55 (m, 2H, in), 2.25 (s, 3H), 1,8-0,8 (m, 13H).

MS (FD) m/e 283 (M+).

UV (EtOH): 291 nm ( = 5315), 257 nm ( = 2711).

Found, %: C 55,29; H 7,60; N 14,64.

C13H21N3S2< / BR>
Calculated, %: C 55,09; H 7,47; N 14,82.

Example 279. N-[2-(2-Methoxyphenyl)ethyl]-N'-[2-(5-methyl)pyridyl]thiourea.

A solution of 1-[2-(2-methoxyphenyl)ethyl] thiocarbonyldiimidazole (0.7 g, 2.68 mmol) and 2-amino-5-methylpyridine (0,29 g, 2.68 mmol) in N,N-dimethylformamide (5 ml) stirred the recrystallization of the residue from ethyl acetate gain of 0.62 g (77%) of the specified connection.

IR (KBr), cm-1: 3227, 2932, 1612, 1534, 1493, 1273, 1037.

1H-NMR (300 MHz, DMSO-d6), : 11,55 (sh.t, 1H), 10,45 (s, 1H), 7,9 (sh.s, 1H), 7,6 (m, 1H), 7,2-6,9 (m, 5H), and 3.8 (m, 5H), 2,9 (t, J= 7 Hz, 2H), 2,2 (s, 3H).

MS (FAB), m/e 302 (M+-H).

UV (EtOH): 298 nm ( = 13316), 268 nm ( = 23132), 249 nm ( = 15574).

Found, %: C 63,71; H 6,34; N 13,79.

C16H19N3OS

Calculated, %: C 63,76; H 6,35; N 13,94.

Example 280. 1-[2-(2-Chlorophenyl)ethyl]thiocarbonyldiimidazole.

A solution of 1,1'-thiocarbonyldiimidazole (1.8 g, 10 mmol) and 2-(2-chlorophenyl)ethylamine (1.56 g, 10 mmol) in acetonitrile (100 ml) is stirred for 3 h at room temperature. The solution is concentrated to approximately 50 ml and placed for 4 days in the refrigerator. Filtration of the formed crystals get 2,37 g (89%) of crude specified connection, so pl. 74-78oC.

IR (KBr), cm-1: 3134, 2924, 1564, 1529, 1474, 1448, 1411, 1353, 1287, 1215.

MS (FD) m/e 266 (M+).

UV (EtOH): 278 nm ( = 5421), 247 nm ( = 5655), 202 nm ( = 22240).

Example 281. N-[2-(2-Chlorophenyl)ethyl]-N1-[2-(5-methyl)pyridyl] thiourea.

A solution of 1-[2-(2-chlorophenyl)ethyl]thiocarbonyldiimidazole (1 g, 3,76 mmol) and 2-amino-5-methylpyridine (0,41 g, 3,76 mmol) in N,N-dimethylformamide (10 ml) is stirred for 16 h at 90oC. the Reaction mixture ahmadiyyat of 0.82 g (80%) of the specified connection.

IR (KBr), cm-1: 3226, 1597, 1532, 1491, 1273, 1050.

1H-NMR (300 MHz, DMSO-d6), : 11,6 (sh. s, 1H), and 10.5 (s, 1H), 7,9 (sh.s, 1H), 7,6-7 (m, 6H), 3,9 (K, 2H), 3,1 (t, J= 7 Hz, 2H), 2,2 (s, 3H).

MS (FD) m/e 305 (M+).

UV (EtOH): 298 nm ( = 14145), 268 nm ( = 21034), 249 nm ( = 23053).

Found, %: C 58,65; H 5,39; N 13,77.

C15H16N3ClS

Calculated, %: C 58,91; H 5,27; N 13,74.

Example 282. 1-{[2-(4-Ethyl)thiazolyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (11.9 g, 60 mmol) and 2-amino-4-utilizou (8 g, 60 mmol) in acetonitrile (250 ml) is stirred for about 5 h at room temperature. Filtration of the resulting precipitate obtain 12 g (85%) of the specified connection, so pl. 198-200oC.

IR(KBr), cm-1: 2970, 2637, 1609, 1529, 1461, 1398, 1357, 1226, 1262.

1H-NMR (300 MHz, DMSO-d6), : 8,6 (s, 1H), and 7.9 (s, 1H), 7 (s, 1 H) and 6.9 (s, 1 H), 2,6 (K, J = 7 Hz, 2H), 1,2 (t, J = 7.0 Hz, 3H).

MS (FD) m/e : 238 (M+).

UV (EtOH) : 361 nm ( = 11223), 290 nm ( = 8828), 203 nm ( = 20303).

Found, %: C 45,51; H 4,20; N 23,53.

C9H10N4S2< / BR>
Calculated, %: C 45,36; H To 4.23; N 23,51.

Example 283. N-[2-(2-Pyridyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea.

A solution of 1-{[2-(4-ethyl)thiazolyl]thiocarbamoyl}imidazole (1 g, 4.2 mmol) and 2-(2-amhlaidh to room temperature and the solvent is removed vacuum. By recrystallization of the residue from ethyl acetate to obtain 0.75 g (61%) of the specified connection.

IR (KBr), cm-1: 3163, 1557, 1524, 1222, 757.

1H-NMR (300 MHz, DMSO-d6), : 11,3 (sh.s, 1H), 10 (sh.s, 1H), 8,5 (m, 1H), and 7.7 (m, 1H), 7,25 (m, 2H), and 6.6 (s, 1H), 3,9 (m, 2H), 3,05 (m, 2H), 2,45 (K, J = 7 Hz, 2H), of 1.05 (t, J = 7 Hz, 3H).

MS (FD) m/e 292 (M+).

UV (EtOH) : 292 nm ( = 17803), 261 nm ( = 12919), 201 nm ( = 17809).

Found, %: C 53,64; H 5,51; N 19,02.

C13H16N4S2< / BR>
Calculated, %: C 53,40; H 5,51; N 19,16.

Example 284. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl] thiourea.

A solution of 1-{[2-(4-ethyl)thiazolyl]thiocarbamoyl}imidazole (0.75 g, a 3.15 mmol) and 2-(1-cyclohexenyl)ethylamine (0.39 g, a 3.15 mmol) in N,N-dimethylformamide (15 ml) is stirred for 4 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. By recrystallization of the residue from ethyl acetate receive 0,77 g (83%) of the specified connection, so pl. 155-156oC.

IR (KBr), cm-1: 3172, 2914, 1560, 1507, 1202, 710.

1H-NMR (300 MHz, DMSO-d6), : 11.5cm (W.s, 1H), 9,8 (sh.s, 1H), and 6.6 (s, 1H), 5,42 (s, 1H), 3,56 (K, J = 7 Hz, 2H), 2,45 (m, 2H), 2,16 (m, 2H), and 1.9 (m, 4H), 1,5 (m, 4H), of 1.12 (t, J = 7 Hz, 3 H).

MS (FD) m/e 295 (M+).

UV (EtOH) : 291 nm ( = 19227), 257 nm ( = 9628), 201 nm ( =91; H 7,16; N 14,22.

Example 285. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl] thiourea.

A solution of 1-{ [2-(4-ethyl)thiazolyl] thiocarbamoyl] imidazole} (0.75 g, a 3.15 mmol) and 2-(2-chlorophenyl)ethylamine (0,49 g and 3.15 mmol) in N,N-dimethylformamide (15 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate receive 0,85 g (83%) of the specified connection, so pl. 153 to 155oC.

IR (KBr), cm-1: 3167, 3018, 1570, 1505, 1215, 749, 699.

1H-NMR (300 MHz, DMSO-d6), : 11,65 (sh.s, 1H), 9,85 (sh.s, 1H), 7.5 to about 7.2 (m, 4H), of 6.65 (s, 1H), 3,85 (m, 2H), 3,05 (t, J = 7 Hz, 2H), 2,55 (K, J = 7 Hz, 2H), 1,1 (t, J = 7 Hz, 3H).

UV (EtOH) : 292 nm ( = 19154), 257 nm ( = 10451), 202 nm ( = 24308).

Found, %: C Won With 51.75; H To 4.98; N 12,79.

C14H16N3S2Cl

Calculated, %: C 51,60; H Of 4.95; N 12,87.

Example 286. N-[2-(2-Methoxyphenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea.

A solution of 1-{[2-(4-ethyl)thiazolyl]thiocarbamoyl}imidazole (0.7 g, to 2.94 mmol) and 2-(2-methoxyphenyl)ethylamine (0,44 g, to 2.94 mmol) in N,N-dimethylformamide (15 ml) is stirred for 2 h at 95oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. By recrystallization of the residue from ethyl acetate floor is CLASS="ptx2">

1H-NMR (300 MHz, DMSO-d6), : 11.5cm (W.s, 1H), 9,85 (sh.s, 1H), 7,2-to 6.8 (m, 4H), to 6.57 (s, 1H), 3,7 (m, 5H), 2,82 (t, J = 7 Hz, 2H), 2,04 (K, J = 7 Hz; 2H), 1.06 a (t, J = 7.0 Hz, 3H).

MS (FD) m/e 321 (M+).

UV (EtOH) : 291 nm ( = 12114), 259 nm ( = 6792), 201 nm ( = 18914.

Found, %: C 55,83; H 6,00; N 13,08.

C15H19N3OS2< / BR>
Calculated,%: C 56,04; H 5,96; N 13,07.

Example 287. N-[2-(3-Methoxyphenyl)ethyl] -N'-[2-(4-ethyl)thiazolyl] thiourea.

A solution of 1-{[2-(4-ethyl)thiazolyl]thiocarbamoyl}imidazole (0.7 g, to 2.94 mmol) and 2-(3-methoxyphenyl)ethylamine (0,44 g, to 2.94 mmol) in N,N-dimethylformamide (15 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature and the solvent is removed in vacuum. Crystallization of the residue from ethyl acetate receive 0,76 g (80%) of the specified connection, so pl. 123-125oC.

IR (KBr), cm-1: 3167, 3027, 1587, 1207, 699.

1H-NMR (300 MHz, DMSO-d6), : 11.5cm (W. s, 1H), 9,9 (sh. s, 1H), 7,2-to 6.8 (m, 4H), to 6.58 (s, 1H, in), 3.75 (m, 2H), to 3.67 (s, 3H), 2,84 (t, J = 7 Hz, 2H), 2,45 (K, J = 7,0 Hz, 2H), of 1.05 (t, J = 7 Hz, 3H).

MS (FD) m/e 321 (M+).

UV (EtOH) : 292 nm ( = 19113), 258 nm ( = 10607), 202 nm ( = 29289).

Found, %: C 56,08; H 5,96; N 13,16.

C15H19N3OS2< / BR>
Calculated, %: C 56,04; H 5,96; N 13,07.

Example 288. 1-{[2-(4-Canadiate (2 g, 16 mmol) in acetonitrile is stirred for 72 h at room temperature and heated for 24 h at 60oC. Filtering the resulting precipitate receive 2,74 g (73%) of the specified connection.

IR (KBr), cm-1: 3097, 2230.

1H-NMR (300 MHz, DMSO-d6), : 11,99 (sh. s, 1H), 8,76 (s, 1H), 8,67 (s, 1H), 8,07 (s, 1H), 7,92 (s, 1H).

MS (FAB), m/e 236 (M+-H).

Example 289. N-[2-(2-Chlorophenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea.

A solution of 1-{[2-(4-cyano)thiazolyl]thiocarbamoyl}imidazole (0.66 g, 2.8 mmol) and 2-(2-chlorophenyl)ethylamine (0.45 g, 2.8 mmol) in N,N-diethylformamide (15 ml) is stirred for 2 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue by chromatography on silica gel obtain 0.24 g (26%) the specified connection, so pl. 165-168oC.

IR (KBr), cm-1: 3119, 2955, 2232, 1577, 1505, 1461, 1328, 1299, 1221, 1053, 826.

1H-NMR (300 MHz, DMSO-d6), : 11,8 (sh.s, 1H), 8,5 (sh.s, 1H) and 8.1 (s, 1H), 7,2-7,4 (m, 4H), 3,74 (m, 2H), 2,98 (t, J = 7 Hz, 2H).

MS (FD) m/e 322 (M+).

UV (EtOH) : 287 nm ( = 10082), 258 nm ( = 15462), 205 nm ( = 31601).

Example 290. N-[2-(3-Chlorophenyl)ethyl]-N l) and 2-(3-chlorophenyl)ethylamine (0,44 g, 2.8 mmol) in N,N-dimethylformamide (15 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from methylene chloride obtain 0.21 g (23%) of the compounds in the form of substances tan, T. pl. 180-185oC.

IR (KBr), cm-1: 2955, 2239, 1559, 1522, 1331, 1251, 106, 1168, 823.

1H-NMR (300 MHz, DMSO-d6), : 11,8 (sh.s, 1H), 8.4V (sh.s, 1H) and 8.1 (s, 1H), 7,1-7,3 (m, 4H), 3,71 (m, 2H), 2,86 (t, J = 7 Hz, 2H).

MS (FD) m/e 322 (M+), 324.

UV (EtOH) : 287 nm ( = 10684), 258 nm ( = 16406), 207 nm ( = 33113).

Example 291. N-[2-(2-Methoxyphenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea.

A solution of 1-{[2-(4-cyano)thiazolyl]thiocarbamoyl}imidazole (0.66 g, 2.8 mmol) and 2-(2-methoxyphenyl)ethylamine (and 0.46 g, 2.8 mmol) in N, N-dimethylformamide (15 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of residue by chromatography on silica gel obtain 0.21 g (23%) 301, 1243, 1208, 1173, 754.

1H-NMR (300 MHz, DMSO - d6), : 11,8 (sh.s, 1H), 8.4V (sh. s, 1H) and 8.1 (s, 1H), 6,8-7,2 (m, 4H), to 3.73 (s, 3H), 3,66 (m, 2H), of 2.81 (t, J=7 Hz, 2H).

UV (EtOH): 279 nm ( = 12102), 259 nm ( = 16281), 203 nm ( = 33347).

MS (FD) m/e 318 (M+).

Example 292. N-[2-(3-Methoxyphenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea.

A solution of 1-{[2-(4-cyano)thiazolyl]thiocarbamoyl}imidazole (0.66 g, 2.8 mmol) and 2-(3-methoxyphenyl)ethylamine (0,44 g, 2.8 mmol) in N,N-dimethylformamide (15 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residue by chromatography on silica gel obtain 0.21 g (23%) of the compounds in the form of a yellow substance, so pl. 151-153oC.

IR (KBr), cm-1: 3065, 2235, 1564, 1515, 1295, 1250, 1209, 1155, 1058, 874, 768, 748, 684.

1H-NMR (300 MHz, DMSO - d6), : 11,8 (sh. s, 1H), 8.4V (sh. s, 1H) and 8.1 (s, 1H), 7,18 (m, 1H), 6,77 (m, 3H), 3,68 (m, 5H), and 2.8 (t, J=7,0 Hz, 2H).

MS (FD) m/e 318 (M+).

UV (EtOH): 280 nm ( = 11770), 258 nm ( = 16613), 204 nm ( = 34785).

Example 293. N-[2-(1-Cyclohexenyl)ethyl]-N1-[2-(4-cyano)thiazolyl]thiourea.

A solution of 1-{[2-(4-cyano)thiazole is l) is stirred for 1.5 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the solid residue by chromatography on silica gel obtain 0.27 g (26%) of the compounds in the form of a pale yellow substance, so pl. 176-178oC.

IR (KBr), cm-1: 3169, 3075, 2924, 2233, 1556, 1513, 1330, 1298, 1260, 1217, 1200, 1167, 1145, 983, 922.

1H-NMR (300 MHz, DMSO - d6), :11.87 per (W. s, 1H), 8.4V (sh. s, 1H), 8,11 (s, 1H), 5,42 (sh.s, 1H), 3,52 (m, 2H), and 2.14 (t, J=7 Hz, 2H), and 1.9 (m, 4H), for 1.49 (m, 4H).

MS (FD) m/e 292 (M+).

UV (EtOH): 288 nm ( = 11250), 258 nm ( = 16113), 206 nm ( = 25473).

Found,%: C 53,1; H of 5.55; N 18,96;

C13H16N4S2< / BR>
Calculated,%: C 53,4; H 5,22; N 19,16.

Example 294. 1-{2-[4-(3-Chlorophenyl)thiazolyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (2,52 g, 12 mmol) and 4-(3-chlorophenyl)-2-thiazoline (2.14 g, 12 mmol) in acetonitrile (35 ml) is stirred for 30 h at room temperature. Filtration of the resulting precipitate receive 2,77 g (72%) of the specified connection.

MS (FAB) m/e 321 (M+-H).

Example 295. N-[2-(2-Chlorophenyl)ethyl]-N'-{2-[4-(3-chlorophenyl)]}thiazolidinedione.

Rai) in N, N-dimethylformamide (15 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue in EtOAc get 1 g (86%) of the indicated compound as yellow needles, so pl. 193-195oC.

IR (KBr), cm-1: 3018, 1560, 1515, 1470, 1291, 1210, 1065, 935, 785, 757, 716.

1H-NMR (300 MHz, DMSO - d6), : 11,65 (sh. s, 1H), 9,29 (sh. s, 1H), 7,79 (s, 1H), 7,63 (m, 2H), 7,35 (m, 4H), of 7.23 (m, 2H), 3,83 (m, 2H), to 3.02 (t, J= 7 Hz, 2H).

MS (FD) m/e 407 (M+), 409 (M+2).

UV (EtOH): 295 nm ( = 22709), 266 nm ( = 20608), 202 nm ( = 37861).

Found,%: C 52,96; H 3,74; N 10,49.

C18H15N3SCl2< / BR>
Calculated,%: C 52, 94; H 3,70; N 10,29.

Example 296. N-[2-(3-Methoxyphenyl)ethyl]-N'-{2-[4-(3-chlorophenyl)]}thiazolyl thiourea.

The solution 1-{ 2-[4-(3-chlorophenyl)thiazolyl] thiocarbamoyl}imidazole (0,92 g of 2.86 mmol) and 2-(3-methoxyphenyl)ethylamine (0.45 g, of 2.86 mmol) in N,N-dimethylformamide (15 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated solution bicarbonate%) of the compounds in the form of a white substance, so pl. 183-185oC.

IR (KBr), cm-1: 3172, 3024, 1569, 1515, 1466, 1319, 1287, 1260, 1220, 1067, 996, 775, 728, 604.

1H-NMR (300 MHz, DMSO - d6), : 11,66 (sh. s, 1H), 9,2 (sh. s, 1H), 7,81 (s, 1H), 7,63 (m, 2H), 7,35 (m, 2H), 7,16 (m, 1H), 6.73 x (m, 3H), of 3.77 (m, 2H), to 3.64 (s, 3H), of 2.86 (t, J=7 Hz, 2H).

MS (FD) m/e 403 (M+), 405 (M+2).

UV (EtOH): 280 nm ( = 23880), 202 nm ( = 42912).

Found,%: C 56,62; H 4,50; N Of 10.58.

C19H18N3OS2Cl2< / BR>
Calculated,%: C 56,49; H 4,49; N The 10.40.

Example 297. N-[2-(1-Cyclohexenyl)ethyl]-N'-{2-[4-(3-chlorophenyl)]}thiazolidinedione.

The solution 1-{ 2-[4-(3-chlorophenyl)thiazolyl] thiocarbamoyl}imidazole (0,92 g of 2.86 mmol) and 2-(1-cyclohexenyl)ethylamine (0,37 g of 2.86 mmol) in N,N-dimethylformamide (15 ml) is stirred for 0.5 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc obtain 0.7 g (65%) of the compounds in the form of a white substance, so pl. 196-197oC.

IR (KBr), cm-1: 2939, 1557, 1514, 1469, 1287, 1202, 1062, 881, 784, 719, 661.

1H-NMR (300 MHz, DMSO - d6), : 11,66 (sh. s, 1H), 9,17 (sh. s, 1H), a 7.85 (s, 1H), 7,76 (m, 1H), to 7.61 (s, 1H), 7,37

UV (EtOH): 285 nm ( = 23385), 232 nm ( = 18756), 202 nm ( = 31779).

Found,%: C 57,04; H 5,32; N 11,09.

C18H20N3S2Cl

Calculated,%: C 57,20; H 5,33; N 11,12.

Example 298. 1-{2-[4-(3-Nitrophenyl)thiazolyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (0,41 g, 2.3 mmol) and 4-(3-nitrophenyl)-2-thiazoline (0.5 g, 2.3 mmol) in acetonitrile (25 ml) is stirred for 72 h at room temperature and heated for 72 h at 60oC. Filtering the resulting precipitate obtain 0.51 g (68%) of the specified connection.

MS (FAB) m/e 332 (M+-H).

Found,%: C 47,35; H 2,69; N 21,03.

C13H9N5O2S2< / BR>
Calculated,%: C 47,12; H 2,73; N 21,13.

Example 299. N-[2-(1-Cyclohexenyl)ethyl]-N'-{2-[4-(3-nitrophenyl)]}thiazolidinedione.

The solution 1-{ 2-[4-(3-nitrophenyl)thiazolyl] thiocarbamoyl}imidazole (0.5 g, 1.5 mmol) and 2-(1-cyclohexenyl)ethylamine (0,19 g, 1.5 mmol) in N, N-dimethylformamide is stirred for 0.75 hours at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc get 0,37 g (63%) UK, 1465, 1352, 1265, 1216, 1065, 877, 788, 713, 676.

1H-NMR (300 MHz, DMSO-d6), : 11,76 (s, 1H), cent to 8.85 (sh.s, 1H), 8,61 (s, 1H), 8,25 (d, J = 8.0 Hz, 1H), 8,11 (d, J = Hz, 1H), to 7.77 (s, 1H), to 7.67 (m, 1H), 5,42 (sh.s, 1H), to 3.58 (m, 2H), 2,2 (t, J = 7 Hz, 2H), 1,89 (m, 4H), of 1.46 (m, 4H).

MS (FD) m/e 388 (M+).

UV (EtOH): 286 nm ( = 22903), 265 nm ( = 23582), 237 nm ( = 17806), 202 nm ( = 24107).

Found, %: C 55,45; H 5,14; N 14,51.

C18H20N4O2S2.

Calculated, %: C 55,65; H 5,19; N 14,42.

Example 300. N-[2-(4-Chlorophenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea.

A solution of 1-{[2-(4-cyano)thiazolyl]thiocarbamoyl}imidazole (0.71 g, 3 mmol) and 2-(4-chlorophenyl)ethylamine (0,48 g, 3 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc obtain 0.4 g (41%) of the compounds in the form of substances tan, T. pl. 188 - 190oC.

IR (KBr), cm-1: 3396, 3110, 2226, 1586, 1518, 1490, 1353, 1248, 1087, 808, 766, 649, 517.

1H-NMR (300 MHz, DMSO-d6), : to 11.8 (s, 1H), 8,43 (sh.s, 1H), 8,12 (s, 1H), 7,33 (d, J = 8 Hz, 2H), 7,24 (d, J = 8 Hz, 2H), 3,69 (m, 2H), 2,84 (t, J = 7,0 Hz, 2H).

A solution of 1-{[2-(4-cyano)thiazolyl]thiocarbamoyl}imidazole (0.9 g, 3.8 mmol) and 2-(4-methoxyphenyl)ethylamine (0,59 g, 3.8 mmol) in N,N-dimethylformamide (25 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc obtain 0.66 g (55%) of the compounds in the form of a yellow substance, so pl. 185 - 190oC.

IR (KBr), cm-1: 3208, 3064, 2236, 1547, 1514, 1259, 1201, 1164, 1033, 886, 775, 748, 680.

1H-NMR (300 MHz, DMSO-d6), : 11,8 (sh.s, 1H), 8.4V (sh.s, 1H) and 8.1 (s, 1H), 7,13 (d, J = 8 Hz, 2H), 6,83 (d, J = 9 Hz, 2H), 3,68 (s, 3H), of 3.64 (m, 2H), 2,77 (t, J = 7 Hz, 2H).

MS (FD) m/e 318 (M+).

UV (EtOH): 284 nm ( = 12158), 258 nm ( = 17248), 204 nm ( = 30994).

Example 302. 1-[(2-(Benzimidazolyl)thiocarbamoyl]imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (8,91 g, 50 mmol) and 2-aminobenzimidazole (of 6.66 g, 50 mmol) in acetonitrile (50 ml) is stirred for 19 h at room temperature. Filtration of the resulting precipitate receive of 8.92 g (73%) of the specified connection.

IR (KBr), cm-1: 3058, 2621, 1623, 1580, 1509, 1469, 1445, 1355, 1290, 1252, 1212, 1153, 1099, 1081, 1048, 925, 898, 746, 659.

+1).

UV (EtOH): 351 nm ( = 18204), 283 nm ( = 13099), 227 nm ( = 17339), 204 nm ( = 31915).

Example 303. N-[2-(2-Chlorophenyl)ethyl]-N'-(2-benzimidazolyl)thiourea.

A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5 mmol) and 2-(2-chlorophenyl)ethylamine (0,81 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc gain of 0.67 g (40%) of the compounds in the form of a white substance, so pl. 166 - 169oC.

IR (KBr), cm-1: 3235, 1656, 1554, 1459, 1248, 1224, 1192, 754, 737, 629.

1H-NMR (300 MHz, DMSO-d6), : 11,95 (sh.s, 1H), 1082 (W.s, 1H), 7,42 (m, 5H), 7,25 (m, 2H), 7,12 (m, 2H), 3,83 (m, 2H), 3,05 (t, J = 7 Hz, 2H).

MS (FD) m/e 330 (M+).

UV (EtOH): 301 nm ( = 18044), 293 nm ( = 18559), 266 nm ( = 11113), 260 nm ( = 10441), 239 nm ( = 8428), 206 nm ( = 27620).

Example 304. N-[2-(3-Chlorophenyl)ethyl]-N'-(2-benzimidazolyl)thiourea.

A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5 mmol) and 2-(3-chlorophenyl)ethylamine (0,79 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is a sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc obtain 0.24 g (14%) of the compounds in the form of a white substance, so pl. 171 - 177oC.

IR (KBr), cm-1: 3387, 1574, 1539, 1461, 1426, 1237, 1175, 734, 699, 477.

1H-NMR (300 MHz, DMSO-d6), : 11.8 in (m, 2H), 7,28 (m, 2H), 7,06 (m, 1H), 3,83 (m, 2H), equal to 2.94 (t, J = 7 Hz, 2H).

MS (FD) m/e 330 (M+).

UV (EtOH): 293 nm ( = 17219), 266 nm ( = 9969), 260 nm ( = 8196), 203 nm ( = 27483).

Example 305. N-[2-(4-Chlorophenyl)ethyl]-N'-(2-benzimidazolyl)thiourea.

A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5 mmol) and 2-(4-chlorophenyl)ethylamine (0,79 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc get 1,31 g (79%) of the compounds in the form of a white substance, so pl. 173 - 182oC.

IR (KBr), cm-1: 3168, 3031, 1668, 1562, 1494, 1470, 1327, 1221, 1174, 1090, 817, 777, 742, 657, 526, 457.

1H-NMR (300 MHz, DMSO-d6), : 12,18 (sh.s, 1H), 10,36 (sh.s, 1H), 7,52 (m, 2H), 7,22 - 7,38 (m, 7H), 3,76 (m, 2H), 2,89 (t, J = 7 Hz, 2H).

MS (FD) m/e 330 (M+

A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5 mmol) and 2-(2-methoxyphenyl)ethylamine (of 0.82 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc gain of 0.62 g (38%) of the compounds in the form of a white substance, so pl. 176 - 184oC.

IR (KBr), cm-1: 3035, 1644, 1539, 1495, 1463, 1331, 1246, 1203, 1025, 750, 454.

1H-NMR (300 MHz, DMSO-d6), : 11,95 (sh.s, 1H), 10,32 (sh.s, 1H), 7,52 (m, 2H), 7,2 (m, 5H), to 6.88 (m, 2H, in), 3.75 (s, 3H), and 3.7 (m, 2H), 2,88 (t, J = 7 Hz, 2H).

MS (FD) m/e 326 (M+).

UV (EtOH): 301 nm ( = 20950), 293 nm ( = 21508), 265 nm ( = 14212), 239 nm ( = 9552), 204 nm ( = 30277).

Example 307. N-[2-(3-Methoxyphenyl)ethyl]-N'-(2-benzimidazolyl)thiourea.

A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5 mmol) and 2-(3-methoxyphenyl)ethylamine (0,78 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water purification of the solid residue by chromatography on silica gel get 1.2 g (73%) of the compounds in the form of a white substance, so pl. 161 - 167oC.

IR (KBr), cm-1: 2932, 1574, 1541, 1460, 1230, 1152, 1016, 737, 694, 577, 461.

1H-NMR (300 MHz, DMSO-d6), : 11,14 (sh.with. 1H), 10,95 (sh. s, 1H), and 7.3 (m, 2H), 7,16 (m, 1H), 7,06 (m, 2H), 6.87 in (m, 2H), 6.75 in (m, 2H), 3,83 (m, 2H), and 3.8 (s, 3H), 2,89 (t, J = 7 Hz, 2H).

MS (FD) m/e 326 (M+).

UV (EtOH): 301 nm ( = 23757), 293 nm ( = 24495), 265 nm ( = 16086), 260 nm ( = 14682), 239 nm ( = 11477), 204 nm ( = 36963).

Example 308. N-[2-Methoxyphenyl)ethyl]-N1-(2-benzimidazolyl)thiourea.

A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5 mmol ) and 2-(4-methoxyphenyl)ethylamine (of 0.77 g, 5 mmol) in N, N - dimethylformamide (20 ml) is stirred for 1 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the solid residue by chromatography on silica gel obtain 1.1 g (67%) of the compounds in the form of a white substance, so pl. 166-172oC.

IR (KBr), cm-1: 3416, 3195, 3065, 1575, 1543, 1511, 1464, 1243, 1176, 1037, 747, 442.

1H-NMR (300 MHz, DMSO-d6), : of 11.11 (sh.s, 1H), 10,95 (sh.s, 1H), was 7.36 (m, 2H), 7,2 (d, = J= 8 Hz, 2H), was 7.08 (m, 3H), PC 6.82 (d, J 8 Hz, 2H), of 3.78 (s, 3H), to 3.67 (s, 3H), 2,85 (t, J = 7 Hz, 2H).

MS (FD) m/e 326 (M+).

Y is-N'-(2-benzimidazolyl)thiourea.

A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5 mmol) and 2-(1-cyclohexenyl)ethylamine (0.64 g, 5 mmol) in N, N-dimethylformamide (20 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc get 0,82 g (55%) of the indicated compound as yellow needles, so pl. 178-180oC.

IR (KBr), cm-1: 3182, 2922, 1576, 1540, 1421, 1271, 1232, 1033, 740, 450.

1H-NMR (300 MHz, DMSO-d6), : 11,08 (sh.s, 1H), 11,07 (sh.s, 1H), 11,02 (sh. s, 1H), was 7.36 (m, 2H), 7,06 (m, 2H), 5,51 (c, 1H), 3,66 (m, 2H), of 2.21 (t, J= 7 Hz, 2H), 1.93 and (m, 4H) and 1.51 (m, 4H).

MS (FD) m/e 300 (M+).

UV (EtOH): 301 nm ( = 25279), 292 nm ( = 26214), 265 nm ( = 15965), 259 nm ( = 14734), 239 nm ( = 11012), 206 nm ( =30007).

Found, %: C 64,25; H 6,99; N 18,63.

C16H20N4S

Calculated, %: C 63,97; H Of 6.71; N 18,65.

Example 310. 1-[(2-Pyridyl)thiocarbamoyl]imidazole.

A solution of 1,1' - thiocarbonyldiimidazole (to 9.9 g, 50 mmol) and 2-aminopyridine (4,75 g, 50 mmol) in acetonitrile (50 ml) is stirred for 72 h at room temperature. The resulting solution is evaporated to a black oil and rinse hexachordal substances.

1H-NMR (300 MHz, DMSO-d6), : 8,89 (sh.with. 1H), 8,58 (m, 1H), 8,35 (m, 1H), 7,8 (m, 2H), and 7.4 (m, 1H), 7,15 (m, 1H), 6,95 (m, 1H).

MS (FAB) m/e 204 (M+weak).

Example 311. N-[2-(2-Chlorophenyl)ethyl]-N'-(2-pyridyl)thiourea.

A solution of 1-[(2-pyridyl)thiocarbamoyl]imidazole (1,02 g, 5 mmol) and 2-(2-chlorophenyl)ethylamine (0,81 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 24 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the residual oil by chromatography on silica gel obtain 0.21 g (14%) of the compounds in the form of a yellow substance, so pl. 116-122oC.

IR (KBr), cm-1: 3235, 1606, 1592, 1558, 1437, 1477, 1439, 1332, 1259, 1234, 1212, 1185, 1150, 1088, 1057, 861.

1H-NMR (300 MHz, DMSO-d6), : 11,63 (m, 1H), 10,53 (s, 1H), 8,03 (m, 1H), 7,68 (m, 1H), 7,41 (m, 2H), and 7.3 (m, 2H), 7,07 (m, 1H), of 6.96 (m, 1H), 3,84 (m, 2H), 3.04 from (t, J = 7 Hz, 2H).

MS (FD) m/e 291 (M+).

UV (EtOH): 293 nm ( = 14959), 266 nm ( =15723), 246 nm ( = 15174), 201 nm ( = 23340).

Example 312. 2-(2,6-Differenl)ethylamine.

In 75 ml of tetrahydrofuran at room temperature dissolve 2,6-differentiational (to 15.8 g, 100 mmol), the solution onIy the addition of borane mixture is stirred for 23 h at room temperature and under nitrogen atmosphere. For 30 min with stirring, added dropwise a saturated aqueous solution of ammonium chloride (20 ml). The reaction mixture is filtered through diatomaceous earth, concentrated to oil, re-dissolved in a mixture of ethyl acetate/water and concentrated hydrochloric acid to establish a pH of 1. The mixture is filtered through diatomaceous earth and an ethyl acetate layer is extracted with 1 N. hydrochloric acid (4 x 10 ml). The combined aqueous acid extracts washed with ethyl acetate (2 x 50 ml). To the acidic aqueous extracts add solid sodium chloride, by the addition of solid sodium bicarbonate and 5 n sodium hydroxide solution set pH 9 and the mixture is extracted with methylene chloride (7 x 50 ml). The combined extracts methylene chloride washed with brine, dried over anhydrous sodium sulfate, filtered and after concentrating obtain 10.6 g (68%) of the compounds in the form of almost colorless oil.

IR (KBr), cm-1: 2967, 2876, 1626, 1590, 1469, 1265, 1236, 1213, 1157, 1128, 1085, 1051, 1016, 956, 843.

1H - NMR (300 MHz, CDCl3), : 7,13 (m, 1H) 6,83 (m, 2H), 2,89 (m, 2H), and 2.8 (t, J = 7 Hz, 2H), 1,19 (s, 2H).

MS (FD) m/e: 157 (M+weak).

UV (EtOH): 265 nm ( = 650), 260 nm ( = 674), 204 nm ( = 7922).

Titration (66% DMF - H2O): pKa 9,06.

N-[2-(2,6-Differenl)ethyl]-N'- [2-(4-ethyl)thiazolyl]thiourea.

A solution of 2-(2,6-differenl)ethylamine (0.16 g, 1 mmol) and 1-{[2-(4-ethyl)thiazolyl] thiocarbamoyl} imidazole (0.24 g, 1 mmol) in N,N-dimethylformamide (15 ml) is stirred for 2 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc get to 0.29 g (89%) of the compounds in the form of a pale yellow substance, so pl. 157-158oC.

IR (KBr), cm-1: 178, 2972, 1584, 1502, 1469, 1340, 1351, 1293, 1267, 1212, 1075, 1014, 953, 787, 726, 672.

1H-NMR (300 MHz, DMSO-d6), : 11,54 (sh. s, 1H), 9,75 (sh. s, 1H), 7,29 (m, 1H), 7,01 (m, 2H), return of 6.58 (s, 1H), of 3.77 (m, 2H), 2,92 (t, J= 7 Hz, 2H), 2,45 (K, J = 8 Hz, 2H), of 1.05 (t, J = 8 Hz, 3H).

MS (FD) m/e 327 (M+).

UV (EtOH): 292 nm ( = 18786), 257 nm ( = 10109), 202 nm ( = 19042).

Found, %: C 51,60; H 4,78; N 13,08.

C14H15F2N3S2< / BR>
Calculated, % : C 51,36; H To 4.62; N 12,83.

Example 314. N-[2-(2,6-Differenl)ethyl]-N'-(2-pyridyl)thiourea.

A solution of 2-(2,6-differenl)ethylamine (0,43 g, 2.7 mmol) and 1-[(2-Pirelli)thiocarbamoyl] imidazole (0.55 g, 2.7 mmol) in N,N-dimethylformamide (20 ml) is stirred for 27 h at 90oC. the Reaction mixture OHL what tworoom sodium bicarbonate and brine. The organic layer is concentrated and purification of the resulting oil by chromatography on silica gel get 0.08 g (10%) of the compounds in the form of a pale yellow substance, so pl. 157-160oC.

IR (KBr), cm-1: 3226, 1605, 1539, 1466, 1332, 1260, 1236, 1188, 1100, 874, 899, 861, 774, 725, 635, 516.

1H-NMR (300 MHz, DMSO-d6), : 11,68 (sh.s, 1H), 10,53 (sh.s, 1H), 7,99 (m, 1H), and 7.7 (m, 1H), 7,28 (m, 1H),? 7.04 baby mortality (m, 4H), 3,82 (m, 2H), 2,97 (t, J = 7 Hz, 2H).

MS (FD) m/e 293 (M+).

UV (EtOH): 292 nm ( = 15506), 266 nm ( = 16020), 245 nm ( = 14709).

Example 315. 1-{[2-(2,6-Differenl)ethyl]thiocarbamoyl} imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (9.5 g, 48 mmol) and 2-(2,6-differenl)ethylamine (rate of 7.54 g, 48 mmol) in acetonitrile (100 ml) is stirred for 20 h at room temperature. The solution is concentrated under reduced pressure, the precipitate is filtered off and rinsed with hexane obtain 16 g of crude specified connection in the form of a brown solid.

IR (KBr), cm-1: 3129, 1565, 1468, 1355, 1259, 1203, 1120, 1065, 1031, 937, 900, 827, 787, 751, 664, 621, 499.

1H-NMR (300 MHz, DMSO-d6), to 10.5 (W.with. 1H), 8,29 (s, 1H), 7,71 (s, 1H), 7,35 (m, 1H),? 7.04 baby mortality (m, 3H), 3,85 (m, 2H), 3 (m, 2H).

MS (FAB), m/e 268 (M+-H).

UV (EtOH): 280 nm ( = 4068), 250 nm ( = 4341), 201 nm ( = 15062).

Example mmol) and 2-(1-cyclohexenyl)ethylisothiocyanate (3,34 g, 20 mmol) in N, N - dimethylformamide (25 ml) is stirred for 27 h at 95oC. the Reaction mixture is cooled at room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the solid residue by chromatography on silica gel gain of 0.44 g (7%) of the indicated compound as white needles, so pl. 170-171oC.

IR (KBr), cm-1: 3207, 2926, 1584, 1514, 1414, 1295, 1161, 1005, 866, 714, 459.

1H-NMR (300 MHz, DMSO-d6), : 11,08 (sh.s, 1H), 10,02 (sh.s, 1H), 8,49 (s, 1H), 8,29 (s, 1H), 5,48 (sh.s, 1H), to 3.64 (m, 2H), of 2.21 (t, J=7 Hz, 2H), and 1.9 (m, 4H), for 1.49 (m, 4H).

MS (FD) m/e 296 (M+), 298 (M+2).

UV (EtOH): 327 nm ( = 12429), 266 nm ( = 17577).

Found,%: C 52,89; H Of 5.89; N 19,11.

C13H17N4SCl

Calculated,%: C 52,60; H 5,77; N 18,87.

Example 317. N-[2-(2.6-Differenl)ethyl]-N'-[2-(6-methyl)pyridyl]thiourea.

A solution of 1-{ [2-(2,6-difieren)ethyl] thiocarbamoyl}imidazole (of 0.53 g, 2 mmol) and 2-amino-6-methylpyridine (0,22 g, 2 mmol) in N, N - dimethylformamide (20 ml) is stirred for 3 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated bicarbonate solution(23%) of the compounds in the form of almost colorless prisms, so pl. 187-189oC.

IR (KBr), cm-1: 3195, 1612, 1544, 1468, 1451, 1380, 1293, 1269, 1230, 1192, 1160, 1072, 950, 788, 722, 635, 501.

1H-NMR (300 MHz, DMSO-d6), : 11,83 (sh.s, 1H), 10,44 (sh.s, 1H), 7,56 (t, J=8 Hz, 1H), 7,26 (m, 1H), 6,98 (m, 2H), 6.87 in (d, J=8 Hz, 1H), 6,79 (d, J=8 Hz, 1H), a 3.87 (m, 2H), equal to 2.94 (t, J=7 Hz, 2 H), 2,11 (s, 3H).

MS (FD) m/e 307 (M+).

UV (EtOH): 296 nm ( = 12052), 265 nm ( = 10578), 246 nm ( = 10257).

Found,%: C 58,35; H To 4.98; N 13,39.

C15H15F2N3S

Calculated,%: C 58,62; H To 4.92; N 13,67.

Example 318. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(3,5-dimethyl)pyrazinyl] thiourea.

A solution of 2-amino-3,5-dimethylpyrazine (of 0.62 g, 5 mmol) and 2-(1-cyclohexenyl)ethylisothiocyanate (0.84 g, 5 mmol) in N, N - dimethylformamide (20 ml) is stirred for 24 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate, water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the resulting oil by chromatography on silica gel obtain 0.27 g (19%) of the compounds in the form of snow-white matter, so pl. 100-103oC.

IR (KBr), cm-1: 3387, 2929, 1515, 1329, 1214, 1164, 1014, 966, 907.

1H-NMR (300 MHz, DMSO-d6), :10,57 (sh. s, 1H), 9,12 (sh. s, 1H), to $ 7.91 (s, 1H), 5,44 (sh. s, 1H), 3,61( = 11659), 265 nm ( = 16153), 201 nm ( = 11795).

Found,%: C 62,06; H 7,65; N 18,58.

C15H22N4S

Calculated,%: C 62,03; H 7,63; N 18,29.

Example 319. N-[2-(2,6-Differenl)ethyl]-N'-[2-(5-trifluoromethyl)pyridyl] thiourea.

A solution of 1-{ [2-(2,6-differenl)ethyl] thiocarbamoyl}imidazole (1.07 g, 4 mmol) and 2-amino-5-triptoreline (0.65 g, 4 mmol) in N, N - dimethylformamide (20 ml) is stirred for 25 h at 95oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the solid residue by chromatography on silica gel obtain 0.26 g (18%) of the compounds in the form of a white substance, so pl. 148 - 152oC.

IR (KBr), cm-1: 3165, 3033, 1619, 1600, 1548, 1470, 1332, 1248, 1189, 1160, 1138, 1106, 1079, 964, 886, 776, 669, 603, 435.

1H-NMR (300 MHz, DMSO-d6), : 11,42 (sh. s, 1H), 10,94 (sh. s, 1 H), at 8.36 (s, 1H), 8,08 (m, 1H), 7,28 (m, 2H), 7,02 (m, 2H), 3,82 (m, 2H), 2,98 (t, J= 7 Hz, 2H).

MS (FD) m/e 361 (M+).

UV (EtOH): 297 nm ( = 18455), 253 nm ( = 14782), 201 nm ( = 15765).

Found,%: C 49,59; H 3,28; N 11,35.

C15H12F5N3S

Calculated.%: C 49,86; H 3,35; N 11,63.

Example 320. N-[2-(2,6-Differenl) Is, mmol) and 2-amino-5-chloropyridine (0,53 g, 4 mmol) in N, N - dimethylformamide (20 ml) is stirred for 22 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtAc obtain 0.65 g (50%) of the compounds in the form of substances tan, T. pl. 172-175oC.

IR (KBr), cm-1: 3233, 1597, 1557, 1529, 1468, 1340, 1308, 1265, 1231, 1190, 1112, 1072, 950, 857, 834.

1H-NMR (300 MHz, DMSO-d6), : 11,19 (m, 1H), 10,67 (s, 1H), 8,03 (c, 1H), 7,82 (m, 1H), and 7.3 (m, 1H), 7,13 (m, 1H), 7,03 (m, 2H), 3,79 (m, 2H), 2,96 (t, J=7 Hz, 2H).

MS (FD) m/e 327 (M+), 329 (M+2).

UV (EtOH): 304 nm ( = 13180), 274 nm ( = 23154), 253 nm ( = 15998), 201 nm ( = 19019).

Example 321. N-[2-(2,6-Differenl)ethyl]-N'-[2-(5-methyl)pyridyl]thiourea.

A solution of 1-{ [2-(2,6-differenl)ethyl] thiocarbamoyl}imidazole (1,33 g, 5 mmol) and 2-amino-5-methylpyridine (0.54 g, 5 mmol) in N, N - dimethylformamide (20 ml) is stirred for 7 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer of Kontsedalov, so pl. 195-196oC.

IR (KBr), cm-1: 3230, 1611, 1535, 1492, 1468, 1334, 1274, 1236, 1190, 1111, 1065, 957, 821, 777, 716, 657, 608, 513.

1H-NMR (300 MHz, DMSO-d6), : 11,59 (sh. s, 1H), 10,44 (sh. s, 1H), 7,83 (sh. s, 1H), 7,53 (d, J=8 Hz, 1H), and 7.3 (m, 1H), 7,02 (m, 3H), and 3.8 (m, 2H), 2,96 (t, J=7 Hz, 2H), 2,16 (s, 3H).

MS (FD) m/e 307 (M+).

UV (EtOH): 297 nm ( = 5129), 268 nm ( = 7508), 247 nm ( = 5383).

Found, %: C 58,36; H To 4.98; N 13,73.

C15H15F2N3S

Calculated,%: C 58,62; H To 4.92; N 13,67.

Example 322. N-[2-(2,6-Differenl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea.

A solution of 1-{ [2-(2,6-differenl)ethyl] thiocarbamoyl}imidazole (1,33 g, 5 mmol) and 2-amino-5-bromopyrazine (0.87 g, 5 mmol) in N, N - dimethylformamide is stirred for 26 h at 95oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the solid residue by chromatography on silica gel obtain 0.31 g (17%) of the compounds in the form of a white substance, so pl. 175-178oC.

IR (KBr), cm-1: 3200, 1596, 1560, 1526, 1469, 1441, 1324, 1259, 1179, 1161, 1114, 1012, 962, 899, 874, 788, 780, 667, 601.

1H-NMR (300 MHz, DMSO-d6), : 10,98 (sh.s, 1H), 10,51 (sh.s, 1H), with 8.33 (s, 1H), 8,24 ( 333 nm ( = 10125), 275 nm ( = 22570), 201 nm ( = 16801).

Found, %: C 42,10; H 3,12; N 14,73.

C13H11BrF2N4S

Calculated, %: C 41,84; H 2,97; N 15,01.

Example 323. N-[2-(2,6-Differenl)ethyl]-N'-[2-(6-ethyl)pyridyl]thiourea.

A solution of 1-{ [2-(2,6-differenl)ethyl] thiocarbamoyl}imidazole (1,33 g, 5 mmol) and 2-amino-6-ethylpyridine (and 0.61 g, 5 mmol) in N,N-dimethylformamide is stirred for 21 h at 95oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue receive 0,63 g (39%) of the compounds in the form of a thick yellow crystals, so pl. 147 - 148oC.

IR (KBr), cm-1: 2972, 1609, 1541, 1468, 1344, 1292, 1265, 1225, 1155, 1073, 951, 804, 786, 727, 692, 635, 501.

1H-NMR (300 MHz, DMSO-d6), : of $ 11.97 (m, 1H), 10,48 (sh.s, 1H), to 7.59 (t, J = 8 Hz, 1H), 7,27 (m, 1H), 6,98 (m, 2H), 6.89 in (d, J = 8 Hz, 1H), 6,8 (d, J = 8 Hz, 1H), a 3.87 (m, 2H), 2.95 points (t, J = 7 Hz, 2H), 2,44 (K, J = 8.0 Hz, 2H), of 0.93 (t, J = 8 Hz, 3H).

MS (FD) m/e 321 (M+).

UV (EtOH): 296 nm ( = 17512), 266 nm ( = 15047), 246 nm ( = 14627), 201 nm ( = 16211).

Found,%: C 60,04; H 5,38; N 12,22.

C16H17F2N3S

Calculated,%: C 59,80; H 5,33; N 13,07.

oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the solid residue by chromatography on silica gel obtain 0.7 g (14%) of the indicated compound as a pale yellow substance, so pl. 175 - 180oC.

IR (KBr), cm-1: 3232, 1588, 1512, 1468, 1414, 1296, 1240, 1163, 1097, 1004, 981, 869, 777, 714, 659, 459.

1H-NMR (300 MHz, DMSO-d6), : 11,07 (sh.s, 1H), 10,07 (sh.s, 1H), 8,5 (s, 1H), 8,28 (s, 1H), 7,28 (m, 1H), 7 (m, 2H), 3,85 (m, 2H), 2.95 points (t, J = 7 Hz, 2H).

MS (FD) m/e 328 (M+), 330 (M+2).

UV (EtOH): 327 nm ( = 10851), 265 nm ( = 14817), 201 nm ( = 16442).

Example 325. N-[2-(2-Pyridyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea.

A solution of 1-{ [2-(4-cyano)thiazolyl] thiocarbamoyl} imidazole (2.35 g, 10 mmol) and 2-(2-pyridyl)ethylamine (1.29 g, 10 mmol) in N,N-dimethylformamide (25 ml) is stirred for 2 h at 95oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purified mod is>.

IR (KBr), cm-1: 3165, 3100, 2996, 2234, 1540, 1489, 1433, 1305, 1266, 1219, 1159, 1132, 999, 904, 817, 758, 574, 435.

1H-NMR (300 MHz, DMSO-d6), : 11,88 (sh.s, 1H), 8,67 (sh.s, 1H), 8,49 (d, J = 4 Hz, 1H), 8,11 (s, 1H), 7,69 (m, 1H), 7.23 percent (m, 2H), a 3.87 (m, 2H), 3,01 (t, J = 7 Hz, 2H).

MS (FD) m/e 289 (M+).

UV (EtOAc): 288 nm ( = 10826), 257 nm ( = 19925), 205 nm ( = 28658).

Example 326. N-[2-(2,6-Differenl)ethyl]-N'-[2-(4-methyl)pyridyl]thiourea.

A solution of 1-{ [2-(2,6-differenl)ethyl] thiocarbamoyl}imidazole (1,33 g, 5 mmol) and 2-amino-4-methylpyridine (0.54 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 3 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc get 0,49 g (32%) of the indicated compound as yellow needles, so pl. 168 - 170oC.

IR (KBr), cm-1: 3233, 1616, 1536, 1465, 1335, 1262, 1181, 1104, 959, 815, 783, 719, 653, 442.

1H-NMR (300 MHz, DMSO-d6), : 11,74 (sh.s, 1H), 10,44 (sh.s, 1H), a 7.85 (d, J = 5 Hz, 1H), 7,27 (m, 1H), 7,02 (m, 2H), to 6.88 (s, 1H), 6,8 (d, J = 5 Hz, 1H), and 3.8 (m, 2H), 2,96 (t, J = 7 Hz, 2H), 2,2 (s, 3H).

MS (FD) m/e 307 (M+).

UV (EtOH): 290 nm ( = 16210), 266 nm ( = 15920), 246 nm ( = 13211), 202 nm ( = 13211).

oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the solid residue from EtOAc obtain 0.32 g (20%) of the indicated compound as a light brown substance, so pl. 140 - 142oC.

IR (KBr), cm-1: 2939, 1616, 1590, 1536, 1469, 1341, 1267, 1189, 1104, 1064, 960, 868, 826, 781, 759, 721, 668, 652.

1H-NMR (300 MHz, DMSO-d6), : 11,74 (sh.s, 1H), 10,42 (sh.s, 1H), 7,87 (d, J = 5 Hz, 1H), 7,29 (m, 1H), 6,99 (m, 2H), 6,85 (s, 1H), at 6.84 (d, J = 5 Hz, 1H), 3,81 (m, 2H), 2.95 points (t, J = 7 Hz, 2H), 2.49 USD (K, J = 8 Hz, 2H), 1,09 (t, J = 8 Hz, 3H).

MS (FD) m/e 321 (M+).

UV (EtOH): 290 nm ( = 18247), 266 nm ( = 18045), 246 nm ( = 15212), 202 nm ( = 27817).

Found,%: C 59,50; H 5,31; N 12,87.

C16H17F2N3S

Calculated,%: C 59,79; H 5,33; N 13,07.

Example 328. 1-{[2-(2-pyridyl)ethyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (to 9.9 g, 50 mmol) and 2-(2-pyridyl)ethylamine (to 6.43 g, 50 mmol) in acetonitrile (120 ml) is stirred 24 h at room temperature. The solution is concentrated under reduced pressure and the obtained max the data connection in the form of a black solid.

IR (KBr), cm-1: 3125, 2930, 2098, 1548, 1477, 1437, 1363, 1329, 1284, 1221, 1098, 1063, 1030, 925, 828, 750, 661, 620.

1H-NMR (300 MHz, DMSO-d6), : 10,35 (sh. s, 1H), 8,48 (m, 1H), with 8.33 (s, 1H), 7,76 (s, 1H), 7,72 (m, 2H), 7,25 (m, 2H), 3,95 (m, 2H), 3,1 (m, 2H).

MS (FAB) m/e 233 (M+-H).

UV (EtOH): 267 nm ( = 5516), 261 nm ( = 6306), 256 nm ( = 6220), 203 nm ( = 14929).

Example 329. N-[2-(2-Pyridyl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea.

A solution of 1-{[2-(2-pyridyl)ethyl]thiocarbamoyl}imidazole (of 1.16 g, 5 mmol) and 2-amino-5-bromopyrazine (0.87 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 27 h at 95oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purified composition by chromatography on silica gel and crystallization from EtOAc gain of 0.13 g (7%) of the compounds in a solid tan, T. pl. 185 - 190oC.

IR (KBr), cm-1: 3186, 1588, 1558, 1517, 1479, 1439, 1356, 1325, 1289, 1268, 1220, 1185, 1156, 1100, 1083, 1013, 996, 900, 876, 800, 760, 716, 569, 511, 431.

1H-NMR (300 MHz, DMSO-d6), : of 10.93 (sh.s, 1H), a 10.74 (sh.s, 1H), 8,54 (d, J = 5 Hz, 1H), 8,31 (s, 1H), 8,28 (s, 1H), 7,69 (m, 1H), 7,28 (m, 1H), 7,21 (m, 1H), 3.96 points (m, 2H), 3,05 (t, J = 7 Hz, 2H).

MS (FD) m/e 337 (M+), 339 nm (M+2).

UV>Calculated, %: C 42,61; H To 3.58; N 20,71.

Example 330. N-[2-(2,6-Differenl)ethyl]-N'-[2-(5-chloro)pyrazinyl]thiourea.

A solution of 1-{ [2-(2,6-differenl)ethyl] thiocarbamoyl}imidazole (1,33 g, 5 mmol) and 2-amino-5-chloropyrazine (0.65 g, 5 mmol) in N, N-dimethylformamide (20 ml) is stirred for 24 h at 95oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and purification of the solid residue by chromatography on silica gel and crystallization from EtOAc receive 0.1 g (6%) of the compounds in the form of a white substance, so pl. 170-171oC.

IR (KBr), cm-1: 3199, 3070, 1593, 1563, 1529, 1468, 1443, 1418, 1327, 1263, 1184, 1166, 1128, 1016, 779.

1H-NMR (300 MHz, DMSO - d6), :11 (sh.s, 1H), 10,53 (sh. s, 1H), with 8.33 (s, 1H), 8,19 (s, 1H), and 7.3 (m, 1H),? 7.04 baby mortality (m, 2H), 3,81 (m, 2H), 2,96 (t, J=7 Hz, 2H).

MS (FD) m/e 328 (M+), 330 (M+2).

UV (EtOH): 332 nm ( = 10097), 274 nm ( = 22879).

Found,%: C 47,54; H Of 3.45; N 17,19.

C13H11ClF2N4< / BR>
Calculated,%: C 47,49; H 3,37; N 17,04.

Example 331. 1-{[2-(5-Etoxycarbonyl)thiazolyl]thiocarbonyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole in (8.9 g, 50 mmol) and 2-amino-5-etxegana sediment obtain 6.5 g (40%) of the specified connection so pl. 208-210oC.

IR (KBr), cm-1: 3205, 3176, 3146, 3115, 1708, 1557, 1470, 1352, 1298, 1244, 1225.

1H-NMR (300 MHz, DMSO - d6), : 13,2 (sh.s, 1H) and 8.1 (s, 1H), and 7.9 (s, 1H), and 7.6 (s, 1H), and 7.1 (s, 1H), 4,2 (K, 2H), 1,3 (t, 3H).

MS (FD) m/e: lack of the right peak (M+).

UV (EtOH): 349 nm ( = 4746), 269 nm ( = 8713), 209 nm ( = 21033).

Found,%: C 42,37; H 3,55; N 19,59.

C10H10N4O2S2< / BR>
Calculated,%: C 42,54; H 3,57; N 19,84.

Example 332. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5-etoxycarbonyl) thiazolyl]thiourea.

A solution of 1-{[2-(5-etoxycarbonyl)thiazolyl]thiocarbamoyl}imidazole (1.12 g, 4 mmol) and 2-(1-cyclohexyl)ethylamine (0.5 g, 4 mmol) N,N-dimethylformamide (40 ml) is stirred for 1 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and recrystallization of the residue from ethyl acetate receive 0,79 g (56%) of the specified connection, so pl. 197-198oC.

IR (KBr), cm-1: 3243, 3121, 3044, 2991, 2925, 1707, 1582, 1543, 1458, 1190.

1H-NMR (300 MHz, DMSO - d6), : 12 (sh. s, 1H), 8,5 (sh. s, 1H), and 7.9 (s, 1H), 5,5 (s, 1H), 4,3 (K, 2H), 3,6 (m, 2H), 2,2 (t, J = 7 Hz, 2H), and 1.9 (m, 4H), 1,5 (m, 4H), 1,3 (t, J = 7 G is 4; N 12,42.

C15H21N3O2S2< / BR>
Calculated,%: C 53,07; H 6,23; N 12,38.

Example 333. N-(2-Phenethyl)-N'-[2-(5-etoxycarbonyl)thiazolyl]thiourea.

A solution of 1-{[2-(5-etoxycarbonyl))thiazolyl]thiocarbamoyl}imidazole (1.1 g, 4 mmol) and 2-(1-phenyl)ethylamine (0.6 g, 4 mmol) in N,N-dimethylformamide (40 ml) is stirred for 1 h at 90oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, 1 N. aqueous HCl, water, saturated sodium bicarbonate solution and brine. The organic layer is concentrated and crystallization of the residue from ethyl acetate to obtain 1.07 g (80%) of the specified compounds, vol square 174-175oC.

IR (KBr), cm-1: 3340, 3253, 3124, 3056, 1707, 1682, 1579, 1537, 1454, 1252, 1222.

1H-NMR (300 MHz, DMSO - d6), : 12 (sh. s, 1H), 8,7 (sh.s, 1H), and 7.9 (s, 1H), and 7.3 (m, 5H), 4,3 (K, 2H), and 3.8 (m, 2H), 2,9 (t, J = 7 Hz, 2H), 1,3 (t, J = 7 Hz, 3H).

MS (FD) m/e 335 (M+).

UV (EtOH), 262 nm ( = 19184), 206 nm ( 26117).

Found,%: C 53,48; H 5,10; N 12,68.

C15H17N3O2S2< / BR>
Calculated,%: C 53,71; H 5,11; N 12,53.

Example 334. N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea.

A solution of 2-amino-5-chloropyridine (1.28 g, 20 mmol) and 2-(1-cyclohexenyl)utilization room temperature, concentrate under vacuum to remove solvent and purification of the residue by HPLC obtain 0.56 g (19%) the specified connection, so pl. 166-167oC.

IR (KBr), cm-1: 3455, 3159, 1599, 1555, 1534, 1476.

1H-NMR (300 MHz, DMSO - d6), : 11,1 (sh.s, 1H) and 10.7 (s, 1H), and 8.2 (d, 1H), 7,9 (m, 1H), 7,2 (d, 1H), 5,5 (s, 1H), 3,6 (m, 2H), 2,2 (t, J=7 Hz, 2H), and 1.9 (m, 4H), 1,5 (m, 4H).

MS (FD) m/e 295 (M+).

UV (EtOH): 305 nm ( = 12139), 273 nm ( = 15905), 244 nm ( = 25052).

Found,%: C 56,59; H 6,00; N 14,09.

C14H18N3SCl

Calculated,%: C 56,84; H 6,13; N 14,20.

Example 335. N-[2-(2 - Chlorophenyl)ethyl]-N1-[2-(5-chloro)pyridyl]thiourea.

A solution of N-[2-(2-chlorophenyl)ethyl] -N'-thiocarbonyldiimidazole (1.3 g, 5 mmol) and 2-amino-5-chloropyridine (0.65 g, 5 mmol) in N,N-dimethylformamide (25 ml) is stirred for 1 h at 100oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, brine. The organic layer is concentrated and apalachiana residue with hexane get 0,83 g (55%) of the specified connection, so pl. 178-179oC.

1H-NMR (300 MHz, DMSO - d6), : 11,2 (m, 1H) and 10.7 (s, 1H), 8,1 (m, 1H), 7.5 (m, 1H) 7,4 (m, 2H), 7,2 (m, 2H), and 7.1 (d, 1H), and 3.8 (m, 2H), 3,1 (t, J = 7 Hz, 2H).

MS (FD) m/e 325 (M+).

UV (EtOH): 35 nm ( = 12931), 273 nm ( Calculated,%: C 51,54; H WAS 4.02; N 12,88.

Example 336. N-[2-(1-Cyclohexenyl)ethyl]-N'-[3-(6-chloro)pyridazinyl]thiourea.

A solution of 3-amino-6-chloropyridazine (1.3 g, 10 mmol) and 2-(1-cyclohexenyl)ethylisothiocyanate (1,67 g, 10 mmol) in N, N-dimethylformamide (20 ml) is stirred for 1.5 h at 90oC. the Reaction mixture is cooled to room temperature and concentrate under vacuum to remove solvent. The residue is purified by HPLC and get 0,22 g (7,5%) specified connection, so pl. 149-153oC.

pKa (66% DMF): 12,8.

IR (KBr), cm-1: 3203, 3072, 2935, 1599, 1565, 1520, 1424, 1351, 1308, 1280, 1184, 1147, 1073.

1H-NMR (300 MHz, DMSO-d6), : 11,1 (m, 1H), up 10.9 (s, 1H), and 7.8 (d, 1H), and 7.6 (d, 1H), 5,5 (s, 1H), 3,7 (m, 2H), 2,2 (t, J = 7 Hz, 2H), and 1.9 (m, 4H), 1,5 (m, 4H).

MS (FD) m/e 296 (M+).

UV (EtOH): 275 nm ( = 23066).

Found,%: C 52,85; H Of 5.84; N 19,15.

C13H17N4SCl

Calculated,%: C 52,60; H 5,77; N 18,87.

Example 337. N-[2-(2,6-Differenl)ethyl]-N'-[3-(6-chloro)pyridazinyl]thiourea.

A solution of N-[2-(2,6-differenl)ethyl] -N'-thiocarbonyldiimidazole (1,33 g, 5 mmol) and 3-amino-6-chloropyridazine (0.65 g, 5 mmol) in N, N-dimethylformamide (20 ml) is stirred for 19 h at 80oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed the data connection, so pl. 187-189oC.

IR (KBr), cm-1: 3199, 3055, 1626, 1593, 1555, 1522, 1469, 1425, 1348, 1313, 1263.

1H-NMR (300 MHz, DMSO - d6), : 11,2 (m, 1H), up 10.9 (s, 1H), 7,9 (d, 1H), and 7.6 (d, 1H), and 7.3 (m, 1H), and 7.1 (m, 2H), 3,9 (m, 2H), 3 (t, J = 7 Hz, 2H).

MS (FD) m/e 328 (M+).

pKa (66% DMF): of 12.73.

UV (EtOH): 277 nm ( = 20141), 252 nm ( = 12935), 201 nm ( = 17891).

Example 338. N-[2-(2,6-Differenl)ethyl]- N'-[3-(6-methoxy)pyridazinyl] thiourea.

A solution of N-[2-(2,6-differenl)ethyl] -N'-thiocarbonyldiimidazole (0.8 g, 3 mmol) and 3-amino-6-methoxypyridazine (0.4 g, 3 mmol) in N, N-dimethylformamide (20 ml) is stirred for 19 h at 70oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water and brine. The organic layer is concentrated and the precipitation of the residue from diethyl ether get 0,235 g (24%) the specified connection, so pl. 193-196oC.

IR (KBr), cm-1: 3222, 3084, 1628, 1586, 1560, 1531, 1468, 1423, 1356, 1310, 1266.

1H-NMR (300 MHz, DMSO-d6), : of 11.45 (m, 1H) and 10.7 (s, 1H), 7,42 (d, J = 10 Hz, 1H), 7,28 (m, 1H), 7,21 (d, J = 10 Hz, 1H), 7 (t, J = 8 Hz, 2H), 3,9 (s, 3H), 3,85 (m, 2H), 3 (t, J = Hz, 2H).

MS (FD) m/e 324 (M+).

UV (EtOH) : 269 nm ( = 18845), 235 nm ( = 10636), 201 nm ( = 16622).

Example 339. N-[2-(2-Pyridyl)ethyl]-N'-[3-(6-(chloro)pyridazinyl]thiourea.

IR (KBr), cm-1: 3172, 3045, 1583, 1562, 1511, 1478, 1428, 1345, 1313, 1280.

1H-NMR (300 MHz, DMSO-d6), : 11,3 (m, 1H), up 10.9 (s, 1H), and 8.6 (d, J = 5 Hz, 1 H), and 7.8 (d, J = 10 Hz, 1H), and 7.7 (m, 1H), 7,55 (d, J = 10 Hz, 1H), and 7.3 (d, J = 8 Hz, 1H), 7,2 (m, 1H), 4 (m, 2H), 3,1 (t, J = 7 Hz, 2H).

MS (FD) m/e 293 (M+).

RCA (66% DMF): 4,17; 12,32.

UV (EtOH) : 275 nm ( = 21715), 270 nm ( = 21836), 221 nm ( = 9867).

Found, %: C 48,91; H 4,14; N 23,76.

C12H12N5SCl2< / BR>
Calculated, %: C 49,06; H 4,12; N 23,84.

Example 340. N-[2-(2,6-Differenl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea.

Mix a solution of N-(diimidazole)-2-(2,6 - differenl)ethylamine (2.67 g, 10 mol) and 2-amino-5-bromopyridine (1.73 g, 10 mmol) in 1-methyl-2-pyrrolidinone (20 ml) is heated at 90oC. After 16.5 h, the reaction mixture was cooled to room temperature and transferred to the ethyl acetate. The organic phase is washed with water (2x), 1 N. HCl, water and brine. The organic layer is dried over Na2SO4filter and concentrate. Polietilene. Repeated recrystallization from 70% EtOAc in hexane gain of 1.16 g of the title compound as light brown crystals, so pl. 174-175oC.

IR (KBr), cm-1: 3229, 1593, 1558, 1529, 1468, 1265, 1188, 1071, 832.

1H-NMR (300 MHz, DMSO-d6), : and 11.2 (s, 1H), is 10.68 (c, 1H), 8,11 (s, 1H), 7.95 is-to $ 7.91 (m, 1H), 7,33-7,28 (m, 1H), 7,09-7,01 (m, 3H), 3,83-of 3.77 (m, 1H), 2,98-to 2.94 (m, 2H).

MS (FD) m/e 371 (M+), 373 (M+2).

UV (EtOH) : 306 nm ( = 12790), 275 nm ( = 22096), 257 nm ( = 14120), 201 nm ( = 17270).

Found, %: C 44,96; H 3,29; N 11,21.

C14H12BrF2N3S

Calculated, %: C 45,17; H 3,25; N 11,29.

Example 341. 2-Cyanomethyl-3-ethoxypyridine.

To a solution of 2-ethoxy-3-hydroxymethylbilane (3 g, a 19.6 mmol) in CH2Cl2(20 ml) at 0oC and stirring, added dropwise a solution of thionyl chloride (3,26 g, a 27.4 mmol, 2 ml) in CH2Cl2. Bath ice is removed and the reaction mixture was stirred 2 h at room temperature. The reaction mixture was concentrated in vacuo and re-dissolved in MeOH (30 ml). In 10 ml of water is dissolved potassium cyanide (3,82 g of 58.7 mmol) and one portion is added to the reaction mixture. The mixture is heated to boiling and stirred for 66 h, then neutralized with saturated solution of Na2CO3. The reaction mixture R is hell Na2SO4filter and after preconcentration get 2,84 g (89%) of the indicated compound as a brownish oil. Additional cleaning small sample displacement chromatography (40% EtOAc in hexane) to obtain colorless transparent oil.

IR (KBr), cm-1: 3020, 2988, 2936, 1579, 1450, 1397, 1282, 1122, 1041.

1H-NMR (300 MHz, CDCl3), : 8,17-of 8.15 (m, 1H), 7,25-to 7.15 (m, 2H), 4.09 to (K, J = 7 Hz, 2H), 3,9 (s, 2H), 1,47 (t, J = 7.0 Hz, 3H).

MS (FD) m/e : 162 (M+).

UV (EtOH) : 278 nm ( = 5241), 220 nm ( = 7490). AB at 5 t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ 7 2 t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ q t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ & m t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ f t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ U t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ D t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ H t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ u t t@ t@ t@ t@ t@ t@ t@ t@ t@ t@ x +

Example 342. N-[2-(3-Ethoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea.

A solution of 2-cyanomethyl-3-ethoxypyridine (22,03 g, 136 mmol) in EtOH (475 ml) and 5 N. HCl (3 ml) is treated with PtO2(4.5 g) as a catalyst under pressure of H260 psi (4.2 kg/cm2). The reaction mixture is stirred for about a day at room temperature and then filtered. The crude reaction mixture was concentrated and re-dissolved in water and EtOAc. The aqueous layer was alkalinized 5 N. NaOH and extracted what do 16,89 g yellow oil. The resulting crude product is dissolved in 1-methyl-2-pyrrolidinone (175 ml) and to the solution was added N-(diimidazole)-2-amino-5-bromopyridin (36 g, 127 mmol). The reaction mixture is heated to 100oC and stirred for 68 hours the Crude reaction mixture is cooled to room temperature and transferred into EtOAc. The organic layer was washed with water (4x) and brine, dried over Na2SO4filter and concentrate. The obtained solid residue is again dissolved in EtOAc and extracted with 1 N. HCl (3x). The acid extracts are mixed with CH2CH2, alkalinized 5 N. NaOH and extracted with CH2Cl2(2x). Extracts in CH2CH2unite, washed with brine, dried over MgSO4filter and concentrate. The crude product is distilled pressure chromatography (10% EtOAc in CH2Cl2) and then rinse with a mixture of EtOAc/hexane (1:1) and receiving 3,76 g (7%) of the compounds in the form of white crystals, so pl. 170-172oC.

1H-NMR (300 MHz, DMSO-d6), : is 11.39 (s, 1H), 10,59 (s, 1H), 8,13-8,11 (m, 2H), 7,92-7,87 (m, 1H), and 7.3 (d, J = 8,1 Hz, 1H), 7,22-to 7.18 (m, 1H), 7,05 (d, J = 8,9 Hz, 1H), 4,05-3,95 (m, 4H), 3 (t, J = 6.3 Hz, 2H), 1,29 (t, J = 6.9 Hz, 3H).

MS (FD) m/e 380 (M+), 382 (M+2).

UV (EtOH) : 305 nm ( = 16291), 276 nm ( = 36829).

Example 343. N-[2-(3-Ethoxyphenyl)ethyl is tworay N-[2-(3-ethoxyphenyl)ethyl] -N'-[2-(5-bromo)pyridyl] thiourea (of 5.17 g, 13.5 mmol). After complete dissolution of the precipitate begins to form. The solution with stirring pour in Et2O (400 ml) and the resulting white substance is filtered off. By washing the crude product with a mixture of MeOH-EtOAc get 5,47 g (97%) of the compounds in the form of a white substance, so pl. 203-205oC (decomposition).

IR (KBr, cm-1) : 3226, 3007, 2306, 1596, 1565, 1530, 1472, 1290, 1197, 1172.

1H-NMR (300 MHz, DMSO-d6), : 11,24 to 11.2 (m, 1H), 10,65 (s, 1H), 8,29 (d, J = 5.3 Hz, 1H), 8,17 (d, J = 2.3 Hz, 1H), of 7.96-7,88 (m, 2H), 7,73-to 7.68 (m, 2H), was 7.08 (d, J = 8,9 Hz, 1H), 4.1 and a 4.03 (m, 4H), 3,24 (t, J = 6 Hz, 2H), 1.27mm (t, J = 6.9 Hz, 3H).

MS (FD) m/e 380 (M+), 382 (M+2).

UV (EtOH) : 304 nm ( = 13635), 276 nm ( = 28876).

Found, %: C 42,90; H 4,36; N 13,11.

C15H18BrClN4OS

Calculated, %: C 43,13; H 4,34; N 13,41.

Example 344. 1-[(2-Amino-5-bromopyridin)thiocarbamoyl]imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (17.8 g, 0.1 mol) and 2-amino-5-bromopyridine (17.3 g, 0.1 mol) in acetonitrile (150 ml) was stirred at room temperature for 2 hours To the resulting suspension add the following product.

Example 345. N-[2-(2-Pyridyl)ethyl] -N'-[(2-amino-5-bromo)pyridyl) thiourea.

To a solution of 1-[(2-amino-5-bromopyridin)thiocarbamoyl] imidazole from vicepresidente 50oC. the Reaction mixture is cooled to room temperature, filtered and washed with acetonitrile. The obtained solid is dissolved in methanol, filtered through the solution while cooling propulsive gaseous hydrogen chloride. The solvents are removed under reduced pressure and recrystallization of the residue from a mixture of methanol with ethyl ether to obtain 24.8 g (76%) of the compounds in the form of a white substance, so pl. 215-216oC.

IR (KBr), cm-1: 3015, 2576, 1634, multiple peaks in the interval 1633-400.

1H-NMR (300 MHz, DMSO-d6), : to 11.3 (s, 1H), 10,75 (s, 1H), 10,78 (s, 1H), and 8.8 (d, 1H), 8.4V (t, 1H), they were 8.22 (s, 1H), 7,97-8 (K, 1H), 7,82 to 7.9 (d, 1H), and 7.8 (t, 1H), and 7.1 (d, 1H), 4,1 (K, 1H), 3,35 (t, 2H).

MS (FD) m/e 338 (M+).

UV (EtOH) : 305 nm ( = 13565), 274 nm ( = 24201), 201 nm ( = 17628).

Found, %: C 42,02; H 3,86; N 15,16.

C13H14N4BrClS

Calculated, %: C 41,78; H Of 3.78; N 14,99.

Example 346. N-{ 2-[(3-Methoxy)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea, hydrochloride.

A. Obtaining 2-hydroxymethyl-3-methoxypyridine.

In the atmosphere of nitrogen crushed potassium hydroxide (41,66 g, 0,744 mol) and stirred for 20 min with DMSO (130 ml, anhydrous). Then add the hydrochloride of 3-hydroxy-2-hydroxymethylpropane (Aldrich) (ml) in DMSO (20 ml) and stirred for about a day at room temperature. Add 5 N. HCl to pH 1 and the solution extracted with dichloromethane (I ml). The aqueous phase is alkalinized 5 N. NaOH to pH 14 and extracted with dichloromethane (I ml). The organic phase (washing with alkali), dried over sodium sulfate and after preconcentration get a tan crystals, recrystallization of which (50% ethyl acetate in hexane) to obtain 10.8 g (32%) of the compounds in the form of crystals color light tan, T. pl. 72oC.

IR (KBr), cm-1: 3080, 1575, 1459, 1424, 1278, 1218, 1066, 809.

1H-NMR (300 MHz, DMSO-d6), : 8,5 (d, J=4.5 Hz, 1H), and 7.3 (d, J=8,3 Hz, 1H), 7,25 (LW.d, J=8,2 and 4.6 Hz, 1H), 4,77 (t, J=5,74 Hz, 1H), 4,48 (d, J= 5.6 Hz, 2H), of 3.77 (s, 3H).

MS (FD) m/e: 139 (M+).

UV (EtOH): 278 nm ( = 4909), 220 nm ( = 6984).

Found, %: C 60,32; H Is 6.54; N 10,23.

C7H9NO2< / BR>
Calculated, %: C 60,42; H Of 6.52; N 10,07.

B. Obtain 2-[(3-methoxy)pyridyl]acetonitrile.

To a cooled in a bath with ice 2-hydroxy-3-methoxypyridine (to 13.9 g, 0.1 mol) was added with stirring thionyl chloride (100 ml). After the termination of the initial foaming thionyl chloride added more quickly. After this, the solution is boiled for 2 hours After cooling, thionyl chloride is removed under reduced pressure to obtain brown crystals, the 8 mol), dissolved in 80 ml of water. The resulting solution was heated to boiling and boil for about a day. The solution is cooled, add 150 ml of saturated sodium carbonate solution and transferred into diethyl ether (500 ml). The solution is still 3 times extracted with 500 ml of diethyl ether. The combined organic solutions are dried over sodium sulfate and after concentration gain of 12.1 g (81,7%) of brown crystals, so pl. 71oC used in the subsequent reaction recovery without additional purification.

IR (KBr), cm-1: 3074, 2949, 2253, 1578, 1459, 1286, 1017, 821.

1H-NMR (300 MHz, DMSO-d6), : 8,07 (m, 1H), 7,43 (m,1H), 7,35 (m, 1H), 4 (s, 2H), and 3.8 (s, 3H).

MS (FD) m/e: 148 (M+).

UV (EtOH): 278 nm ( =5407), 219 nm ( = 7435).

Found, %: C 64,62; H 5,50; N 19,00.

C8H8N2O

Calculated, %: C 64,85; H 5,44; N 18,91.

C. Obtaining 2-ethylamine-3-methoxypyridine.

2-[3-Methoxy)pyridyl]acetonitrile (2 g, 13 mmol) in 25 ml of ethanol restore 24 at room temperature under a pressure of 60 psi (4.2 kg/cm2in the presence as catalyst of platinum oxide (0.5 g) and 5 N. HCl (0.2 ml). Organic part of concentrate, and then transferred to the ethyl acetate with water. Add 1 N. NaOH to pH and amine extracted e is over sodium sulfate. The solution is filtered and after concentrating obtain 1.5 g of oily product, used without further purification.

D. Obtain N-{ 2-[(3-methoxy)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]urea.

Thiocarbonyldiimidazole (5 g, 28 mmol) is transferred in acetonitrile (50 ml, anhydrous) and stirred. To the solution was added 2-amino-5-bromopyridine (Aldrich) (4,85 g 27 mmol) and 30 ml of acetonitrile and stirred for about a day with sediment. Solid cream-colored product is filtered off and used in the next stage without additional purification (6,89 g, 87%).

A solid cream color (2,88 g of 10.3 mmol) is transferred into a 1-methyl-2-pyrrolidinone (Aldrich), add 2-ethyl-3-methoxypyridine and the solution is heated to about the day when 100oC. Then the solution is transferred into ethyl acetate and washed with water and saturated sodium bicarbonate solution (g ml). Purification of the crude product pressure chromatography on silica gel (40% ethyl acetate in hexane) to obtain 100 mg (3%) of needle-like crystals, so pl. 178oC.

IR (KBr), cm-1: 3157, 3037, 1595, 1562, 1434, 1314, 1275, 1178, 1023, 825.

1H-NMR (300 MHz, DMSO-d6), : 11,53 (s, 1H), 8,5 (c, 1H), 8.17-a to 8.12 (m, 2H), 7.68 per-7,65 (LW.d, J=8,75 and 8,73 Hz, 1H), 4,24-4,18 (m, 2H), and 3.8 (s, 3H), 3,2-3-17 (t, J=6,63 LASS="ptx2">

Found, %: C 45,85; H 4,12; N 15,12.

C14H15N4OSBr

Calculated, %: C 45,78; H 4,12; N 15,25.

E. Obtain N-{2-[(3-methoxy)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl}thiourea, hydrochloride.

In a solution of methanol saturated with HCl, transferred to N-{2-[(3-methoxy)pyridyl] ethyl} -N'-[2-(5-bromo)pyridyl] thiourea (70 mg, 0.02 mmol). Solid immediately goes into solution, and then reappears in the form of a white precipitate, most of which crushed diethyl ether. Filtering sediment obtain 65 mg (84%) of the hydrochloride.

Example 347. N-[2-Fluoro-6-methoxy)phenethyl]-N'-(2-thiazolyl)thiourea.

In 200 ml of THF was dissolved 3-Floransa (10 ml, 88 mmol), the solution is cooled to -75oC and to it is slowly added n-BuLi (52 ml, 105 mmol). The pale yellow solution is stirred 10 min at -70oC add DMF (20 ml) and the solution warmed to room temperature. Add 200 ml of toluene, the solution is washed with water and evaporated to dryness with the formation of crystalline product. The aldehyde is transformed into the corresponding specified titlelocation by the method of example 151.

1H-NMR (CDCl3), : 2,9-3 (2H, t), of 3.7-3.9 (2H, t), 6,7-6,9 (2H, m), 7-7,1 (1H, d), 7,15-7,3 (1H, K), and 7.4 (1H, d).

Example 348. CIS-(DL)-2-Paneltitle remaut to a boil. Within 30 min add ethyl diazo acetate (50 ml, 475 mmol) in styrene (100 ml, 873 mmol) and the solution is boiled for another 5 minutes the Solution is cooled and filtered through a short column of alumina with elution with a mixture of ethyl acetate/hexane (1:9). Solvents, including styrene, evaporated. The residual oil is a mixture of CIS - and TRANS-isomers (3: 7). The oil was dissolved in methanol (200 ml) and to the solution was added potassium hydroxide (30 g, 535 mmol) in water (50 ml). The solution is boiled for 2 h, cooled and diluted with toluene (100 ml) and water (100 ml).

The aqueous phase is separated and acidified with hydrochloric acid. The solution is extracted with toluene, the organic phase is dried over sodium sulfate, filtered and after evaporation obtain a pale brown solid product (70 g, 430 mmol) is dissolved under mechanical stirring and in an atmosphere of N2in acetone (400 ml). The solution is cooled to 5oC for 20 min add ethylchloride (41 ml, 430 mmol). The solution is stirred for further 5 minutes add sodium azide (30 g, 460 mmol) in water (100 ml) and stirred for 30 minutes After adding toluene (400 ml) produces a dense white precipitate. The solution is decanted from the sludge separation and dried over sodium sulfate (50 g). The solution is evaporated to 1/4 of the original volume is make a mixture of 100 ml of hydrochloric acid (concentrated water), 100 ml of water and 200 ml of dioxane. The solution is boiled for 3 hours with gaseous CO2. The solution was diluted with water (200 ml), the aqueous phase is separated, washed with 1,2-dichloroethane, alkalinized with ammonia (concentrated water) and extracted with dichloromethane (3 x 100 ml). The organic phase is washed with water (100 ml), dried over sodium sulfate, filtered and evaporated.

The residual oil (50 g) is divided into 1000 ml of silica gel with elution by ethyl acetate, and the target product (CIS-) is more quickly eluruumis component. Evaporation of the pure CIS-factions get 14 g butter.

1H-NMR (CDCl3), , ppm: 0,8-0,9 (1H, CH2, m), 1.1 to 1.2 (1H, CH2, m), 2-2,1 (1H, PhCH,), 2,6-2,7 (1H, CHNH2, m) and 7.1 to 7.4 (5H, Ph).

Example 349. N-[CIS-(DL)-2-Vinylcyclopropyl]-N'-(2-thiazolyl)thiourea.

Obtained as the product in example 348 CIS-(DL)-phenylcyclopropane by the method of example 151 converted into the specified connection.

1H-NMR (CDCl3), , ppm: 1,2-1,3 (1H, CH2, m), a 1.5-1.6 (1H, m), 2,4-2,5 (1H, PhCH), up 3.6-3.7 (1H, m), and 6.6 and 6.7 (1H, d), 6.8 or 6.9 (1H, d), of 7.2 to 7.4 (5H, m).

Example 350. N-[CIS-(DL)-2-Phenylcyclohexyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 105 carry out the reaction of CIS-TRANS mixture of 2-phenylcyclohexylamine (C. Bea is rectally filtered off and washed on the filter CH3CN. The stereochemistry was determined by NOE-differentiated NMR, whereby the crystals are pure CIS-isomer.

1H-NMR (CDCl3), , ppm: 2,2-2,4 (3H, m), 2,6-2,7 (1H, m), 3.9 to 4 (1H, K), 5,1-5,2 (1H, K), and 6.6 and 6.7 (1H, d, thiazole), 6.8 or 6.9 (1H, d, thiazole), 7,3-7,5 (5H, m, Ph).

Example 351. N-[CIS-(DL)-2-Methyl-2-vinylcyclopropyl] -N'-(4-chlorophenyl)thiourea.

According to the method of example 348 - methylsterol (Aldrich) is converted into the corresponding amine in the form of CIS-/TRANS - mixture. Amine (300 mg, 2.04 mmol) and 4-chlorophenothiazine boil for 60 min in CH3CN (5 ml). The solution is evaporated and the final cleaning implement pressure chromatography on silica gel and elution with a mixture of ethyl acetate/hexane (1: 4). The collected fractions contain according NOE-differentiated NMR pure CIS-isomer.

1H-NMR (CDCl3, , ppm: 1.1 to 1.2 (2H,m, CH2), 1,4-1,5 (3H, c, CH3), a 3.2 and 3.4 (1H, m, CHN), 6,4-6,5 (1H, sh.s, NH), 7-7,1 (2H, Ph), 7,3-7,5 (7H, s + m, Ph), of 7.9 and 8.1 (1H, sh.s, NH).

Example 352. N-[2-(2,6-Differenl)ethyl]- N'-(2-pyrazinyl)thiourea.

According to the method of example 93 conduct the reaction between 2,6-differentiation (1 g, 6.4 mmol), 2-aminopyrazine (0,61 g, 6.4 mmol) and N, N-thiocarbonyldiimidazole (1.13 g, 6.4 mol) to obtain the specified connection in the form of crystals.

Example 353. N-[2-(2,6-Debtor-3-carboxyethylidene)ethyl]-N'-[2-(5-bromo) pyridyl]thiourea.

A mixture of 2,6-diferentialglea (10 g, of 70.4 mmol), ethylene glycol (20 ml), triethylorthoformate (10 ml), n-toluenesulfonic acid in 1,2-dichloroethane is heated for 2 hours at 80oC. the Solution is neutralized with sodium bicarbonate, washed with water, dried over sodium sulfate, filtered and evaporated. Residual oil in an atmosphere of nitrogen dissolved in tetrahydrofuran (700 ml), the solution with stirring, cooled to -70oC and to it is slowly added n-BuLi (48 ml of 1.6 M). The solution is stirred for 20 min and to it as soon as possible add dry ice (20 g, 455 mmol), foaming is observed.

The solution is slowly brought to room temperature, water is added and the solution washed with ethyl acetate, acidified with acetic acid and extracted with ethyl acetate.

The organic phase is dried over sodium sulfate, filtered and evaporated. In 50 ml of dichloromethane is dissolved 1 g of residual solid product (4.35 mmol) and N, N-Diisopropylamine (2 ml) and cooled to 0oC.

Add thionyl chloride (0.5 ml, 6,9 mmol) and the solution slowly warmed to room temperature. CLASS="ptx2">

The residue is dissolved in a mixture of water with dioxane (1:2, 20 ml) and add n-toluensulfonate (0.5 g, 2,63 mmol). The solution is heated and stirred for 2 h at 60oC. the Solution is neutralized with sodium bicarbonate, extracted with ethyl acetate, dried over sodium sulfate, filtered and evaporated.

The residue is dissolved in toluene and to the solution add benzyloxycarbonylglycine (1.5 g, 3.7 mol). The solution is stirred for 30 min at 50oC, and then transferred to a column of silica gel. Column elute with a mixture of ethyl acetate/hexane (1:2) and the collected fractions evaporated. The residue (0.15 g) hydronaut in methanol (50 ml) and acetic acid (5 ml) in the presence of Pd/C (10%, 100 mg) and hydrogen gas in a Parr apparatus (1.5 bar, 1 h).

The solution is filtered through celite and evaporated. Part of the residue (50 mg, 0.26 mmol) is dissolved at 0oC in acetone.

Add triethylamine (50 ml, 0.36 mmol) followed by addition of ethylchloride (30 ml, 0.32 mmol). Solution mixing for 15 minutes, then add sodium azide (30 mg, 0.46 mmol) in water (2 ml). The solution is stirred for 15 min, diluted with ethyl acetate, washed with water, dried over sodium sulfate, filtered and evaporated.

The residue is dissolved in toluene (20 ml) and paramesh the data of water (1: 3: 1). The solution is stirred for 20 min at room temperature. The solution is evaporated and the obtained residue hydrochloride 2-(2,6-debtor-3-carboxyethylidene)ethylamine by the procedure of example 94 condensed with 1-(2-amino-5-bromopyridin)-1'-(imidazolyl)thiocarbonyl.

The reaction mixture is evaporated and the residue purified pressure chromatography on silica gel with elution with a mixture of ethyl acetate/hexane (1:1). Evaporation of the collected fractions receive the specified connection.

1H-NMR (CDCl3), , ppm: 2,9-3 (3H, s, CH3), 3,1-3,2 (2H, m, PhCH2), 4-4,1 (2H, t, CH2N), 6.8 or 6.9 (1H, d), 6,9-7 (2H, t), 7,7-7,8 (2H, m), 8-8,1 (1H, s).

Example 354. N-[2-(3-Atsetamidometil-2,6-differenl)ethyl]-N'- [2-(5-bromo)pyridyl]thiourea.

In 200 ml of tetrahydrofuran in a nitrogen atmosphere under stirring to dissolve 2,4-diferential (Aldrich) (4.6 g, 33 mmol). The solution is cooled to -75oC and to it add sitedisability (25 ml, 1.5 M solution). The solution is stirred for 15 min and then add dimethylformamide (10 ml). The cooling is removed, the solution was diluted with toluene, washed with water, dried over sodium sulfate, filtered and evaporated. The residue (4,76 g, 28.5 mmol) was dissolved in 250 ml of toluene and to the solution add benzyloxycarbonylglycine then transferred to a column of silica gel. Column elute with a mixture of ethyl acetate/hexane (1: 4) and the collected fractions evaporated. A small portion of the residue (0.5 g) dissolved in methanol (50 ml) and acetic acid (6 ml), add 5% Pd/C and the mixture hydronaut 1 h in a Parr apparatus at 1.5 bar.

The solution is filtered through celite and evaporated. The residue is dissolved in acetic anhydride and the solution stirred for 20 min at 50oC. the Excess reagent is evaporated, and the residue is dissolved in water. The solution is heated with stirring 20 min at 60oC. the Residue (0.29 grams, to 1.14 mmol) is dissolved at 0oC in acetone.

Add triethylamine (0,315 ml, 2.3 mmol) followed by addition of ethylchloride (0.16 ml, 1.7 mmol). The solution is stirred for 15 minutes, then add sodium azide (220 mg, 3.3 mmol) in water (2 ml). The solution is stirred for 15 min, diluted with ethyl acetate, washed with water, dried over sodium sulfate, filtered and evaporated.

The residue is dissolved in toluene (20 ml) and stirred for 1 h at 90oC. the Solution is evaporated and re-dissolved in a mixture of dioxane/water/concentrated hydrochloric acid water (50:10:1). The mixture is stirred for 20 min at room temperature and then evaporated. Received in the remainder of aminogidrohlorid by the method of example 94 condensed with 1-(2-amino-5-broneerimistasuta on silica gel with elution with a mixture of ethyl acetate/hexane (1:1). Evaporation of the collected fractions obtained as crystals the specified connection.

1H-NMR (CDCl3), , ppm: 1,9-2 (3H, s, CH3CON), 3-3,1 (2H, sh, s, PhCH2CH2N), 3,9-4,1 (2H, s, W, PhCH2CH2N), a 4.3 and 4.4 (2H, s, PhCH2N), 6.8 or 6.9 (2H, m), 7,2-7,4 (1H, m), 7,7-7,8 (1H, d), of 8.1 to 8.2 (1H, s).

Example 355. N-(4-Methyl-3-pentenyl)-N'-(4-methyl-2-thiazolyl)thiourea.

This connection receive according to the method of example 105 reaction of 4-methyl-3-pentylamine activated derivative of 2-amino-4-methylthiazole, for example 1-(2-amino-4-methylthiazole)-1'-imidazoledicarbonitrile, so pl. 164,5 - 165,5oC.

Found, %: C 52,00; H 6,90; N 16,70.

Calculated, %: C 51,73; H Of 6.71; N 16,45.

1H-NMR (CDCl3), : of 1.65 (s, 3H), at 1.73 (d, 3H), to 2.29 (d, 3H), 2,4 (K, 2H), 3,7 - of 3.78 (m, 2H), 5,16 with 5.22 (m, 1H), 6,36 (K, 1H), 10,14 (sh.s, 1H), 10,9 (sh.s, 1H).

13C-NMR (CDCl3), : 17,16; 17,93; 25,83; 27,28; 45,69; 105,04; 120,53; 134,84; 147; 99; 160,79; 177,28.

Example 356. N-[2-(2,6-Debtor)phenethyl]-N'-(2-benzimidazolyl)thiourea.

This compound is synthesized according to the method of examples 93 and 94 by the reaction of 2,6-differentiationin and 2-aminobenzimidazole using 2-aminobenzimidazole instead of 2-aminothiazole, so pl. 195 - 197oC (decomposition).

1H-NMR (DMSO-d6), : and 3.16 (t, 2H), was 4.02 (K, 2H), 7,14 - 7,24 wine.

This compound is obtained according to the methods of examples 93 and 94 in the reaction of 3-hydroxyphenylethylamine and 5-bromo-2-aminopyridine using instead 2-aminothiazole 5-bromo-2-aminopyridine, so pl. 176,5 - 178oC (yield 35%).

1H-NMR (DMSO-d6), : 2,95 (t, 2H), 3,9 (K, 2H), 6.73 x - 6,85 (m, 3H), 7,2 - 7,27 (m, 2H), 8,08 (LW.D. 1H), 8,32 (d, 1H), 9,49 (s, 1H), 10,84 (s, H), 11,33 (t, 1H).

13C-NMR (DMSO-d6), : 34,01; 46,3; 111,7; 113,26; 114,41; 115,7; 119,32; 129,35; 140,41; 141,29; 145,79; 152,29; 157,34; 179,07.

Example 358. N-[2-(1-Methyl)-2-pyrrolidinyl] -N'-(5-chloro-2-pyridinyl)thiourea.

This connection to the outlet 78% obtained by the method of example 105 reaction of 2-(aminoethyl)-1-methylpyrrole with 5-chloro-2-aminopyridine, I. 169, 5mm square - 170oC.

1H-NMR (DMSO-d6), : a 3.01 (t, 2H), to 3.67 (s, 3H), 3,93 (K, 2H), 6 - of 6.02 (m, 2H), 6,74 (s, 1H), 7,32 (d, 1H), 7,97 (LW.D. 1H), 8,27 (d, 1H), of 10.76 (s, 1H), 11,36 (sh.s, 1H).

13C-NMR (DMSO-d6), : 24,97; 33,19; 44,37; 106,22; 106,39; 114,02; 121,58; 123,7; 129,32; 138,7; 143,61; 152,05; 179,31.

Example 359. N-[2-(3-Methyl)phenethyl]-N'-(2-thiazolyl)thiourea.

(3-Were)acetic acid restores in boiling tetrahydrofuran by sociallyengaged 2-(3-were)ethanol, which is then by the method of example 106 converted into 2-(3-were)ethylamine. The reaction of the amine obtained by the method of example the>
, 250 MHz), : 178, 162, 132, 137, 137, 130, 128, 127, 126, 102, 47, 35, 22.

Example 360. N-[2-(2-Ethoxy)phenethyl]-N'-[2-(4-methyl)thiazolyl)thiourea.

This connection (so pl. 188 - 189oC) obtained by the method of example 105 reaction of 2-(2-ethoxyphenyl)ethylamine 1-(2-amino-4-methylthiazolyl)-1'-imidazoledicarbonitrile synthesized according to the method of example 105.

1H-NMR (250 MHz, DMSO), : 7,32 - of 6.73 (m, 5H, phenyl, thiazole), 4.09 to (K, 2H, OCH2CH3), 3,86 (K, 2H, CH2NH), of 2.97 (t, 2H, Ph-CH2in ), 2.25 (s, 3H, thiazole-CH3), was 1.43 (t, 3H, OCH2-CH3).

13C-NMR (250 MHz, DMSO), : 176, 162, 157, 130, 128, 127, 120, 112, 107, 106, 63, 44, 29, 17, 15.

Example 361. N-[2-(3-Ethoxy)phenethyl]-N'-(2-thiazolyl)thiourea.

A mixture of 3-hydroxybenzaldehyde (3 g, 24.6 mmol), ethyliodide (5,9 ml, 73.8 mmol) and K2CO3(3.4 g, 24.6 mmol) in 50 ml of acetone is stirred for 6 h at 40oC and about a day at room temperature. The mixture is filtered and evaporated. The product was then purified column chromatography on silica gel (EtOAc/petroleum ether, 15:100) and receive only 2.91 g (79%) 3-ethoxybenzaldehyde.

1H-NMR (250 MHz, CDCl3), : becomes 9.97 (s, 1H, CHO), 7,45 - 7,14 (m, 4H, phenyl), 4,1 (, 2H, CH2CH3), the 1.44 (t, 3H, CH2CH3).

According to the method of example 151 3-ethoxybenzaldehyde prirastaniem specified connection, T. p. 169 - 170oC.

1H-NMR (250 MHz, DMSO), : to 7.6 (d, 1H, thiazole), 7,3 - 6,93 (m, 4H, phenyl), 4,08 (K, 2H, OCH2CH3), a 3.87 (K, 2H, CH2NH), 2,96 (t, 2H, phenyl-CH2), to 1.42 (t, 3H, OCH2CH3).

Example 362. N-[2-(2-Ethoxy-6-fluoro)phenethyl]-N'-(2-thiazolyl)thiourea.

1. A mixture of 3-terfenol (20 g, to 178.4 mmol), ethyliodide (83,5 g, 535,2 mmol) and K2CO3(49,3 g, 356,8 mmol) in 250 ml of acetone is stirred for approximately day 50oC. the Mixture is filtered and after evaporation receive 19,84 g (79%) 1 ethoxy-3-fervently.

1H-NMR (250 MHz, CDCl3), : 7.2V (K, 1H, phenyl), 6,69 - to 6.57 (m, 3H, phenyl), 4 (K, 2H, CH2CH3), and 1.4 (t, 3H, CH2CH3).

2. To a solution of 1-ethoxy-3-fervently (5 g, to 35.7 mmol) in 100 ml dry THF at -65oC in nitrogen atmosphere slowly (0.5 h) was added a 1.6 M solution of Buli in hexane (24 ml, 38.4 mmol). The solution is stirred for 25 min at -65oC and to it are added dropwise DMF (5,22 g, and 71.4 mmol). The mixture is left to warm to room temperature. To the mixture is added 300 ml of ice water and extracted with diethyl ether. A solution of diethyl ether, washed with brine, dried over Na2SO4and evaporated. Purification of the product column chromatography on silica gel (EtOAc/ petroleum ether, 10:100) get 3, H, CH2CH3), and 1.5 (t, 3H, CH2CH3).

13C-NMR (250 MHz, CDCl3), : 188, 165, 161. 136, 109, 108, 65, 14.

3. According to the method of example 151 obtained aldehyde converted into 2-(2-ethoxy-6-forfinal)ethylamine according to the procedure of example 105 is introduced into reaction with the product of example 103 with the formation of the specified connection.

1H-NMR (250 MHz, DMSO), : 7,32 - 6,72 (m, 5H, phenyl, thiazole), 4 (K, 2H, CH2CH3), 3,78 (K, 2H, CH2-NH), 2,92 (t, phenyl-CH2), of 1.33 (t, 3H, CH2CH3).

Example 363. N-[2-(3-Isopropoxy)phenethyl]-N'-(2-thiazolyl)thiourea.

According to the method of example 361 of 3-hydroxybenzaldehyde and isopropylated get 3-isopropoxybenzonitrile. The resulting aldehyde by the method of example 151 converted into 2-(3-isopropoxyphenyl)ethylamine according to the procedure of example 105 is introduced into reaction with the product of example 103 with the formation of the specified connection.

1H-NMR (250 MHz, DMSO), : 7,44 - 6,84 (m, 6H, phenyl, thiazole), 4,69 with 4.64 (m, 1H, isopropoxy-CH), a 3.87 (K, 2H, CH2-NH), 2,96 (t, 2H, phenyl-CH2), 1,36 - of 1.32 (m, 6H, 2CH3).

Example 364. N-[2-(5-Bromo-2-ethoxy)phenethyl]-N'-(2-thiazolyl)thiourea.

1. A mixture of (5-bromo-2-hydroxybenzoato alcohol (5 g, 24.6 mmol), ethyliodide (11,5 g, 73.8 mmol) and K2

1H-NMR (250 MHz, CDCl3), : 7,42 - 7,31 (m, 2H, phenyl), was 6.73 (d, 1H, phenyl), of 4.67 (d, 2H, CH2OH), 4,07 (K, 2H, CH2CH3), 1,6 (c, 1H, OH), was 1.43 (t, 3H, CH2CH3).

2. A mixture of 5-bromo-2-ethoxybenzyl alcohol (2,78 g, 12 mmol) and pyridinediamine (4,51 g, 12 mmol) in 120 ml of CH2Cl2stirred for 6 h at room temperature. The mixture is filtered, washed with water, 0,5 N. HCl and brine and dried on Na2SO4. Purification of the product column chromatography on silica gel (EtOAc/petroleum ether, 10:100) gain of 2.33 g (85%) of 5-bromo-2-ethoxybenzaldehyde.

1H-NMR (250 MHz, CDCl3), : 10,4 (s, 1H, CHO), to $ 7.91 (d, 1H, phenyl), 7,6 (LW. d, 1H, phenyl), to 6.88 (d, 1H, phenyl), 4,14 (K, 2H, CH2CH3) and 1.51 (t, 3H, CH2CH3).

3. According to the method of example 151 aldehyde converted into 2-(5-bromo-2-ethoxyphenyl)ethylamine, a reaction which according to the method of example 105 with the product from example 103 receive the specified connection.

1H-NMR (250 MHz, DMSO), : 7,1 - 6,62 (m, 5H, phenyl, thiazole), to 3.73 (K, 2H, CH2CH3), 3,52 (K, 2H, CH2NH), 2,62 (t, 2H, phenyl-CH2), with 1.07 (t, 3H, CH2CH3).

Example mol) 7 DMF at 0oC add 2,5-dimethoxyphenethylamine (0.36 g, 2 mmol) in 7 ml of DMF and after 5 min add at 0oC 2-aminopyridine (0,19 g, 2 mmol) in 7 ml DMF.

The resulting mixture was boiled for 4 h at 150oC. After cooling at room temperature the mixture is transferred into ice-cold water, extracted with diethyl ether, dried over Na2SO4and the solvent evaporated. Purification of the product column chromatography on silica gel (EtOAc/petroleum ether, 15:100) to obtain 0.24 g (39%) of the specified connection.

1H-NMR (250 MHz. CDCl3), : to 8.41 (sh.s, 1H, 11H), of 8.04 (d, 1H, pyridine), to 7.61 (t, 1H, pyridine), 6,94 is 6.67 (m, 5H, phenyl, pyridine), a 4.03 (2H K., CH2NH), 3,78 (c, 3H, CH3O) to 3.73 (s, 3H, CH3O), 3 (t, 2H, phenyl-CH2).

Example 366. N-[2-(2-Ethoxy)phenethyl]-N'-[2-(5-bromo)pyridyl] thiourea.

According to the method of example 151 2-ethoxybenzaldehyde get 2-amoxifillin.

To a mixture of 1,1'-thiocarbonyldiimidazole (1,32 g 7.4 mmol) and 20 ml of acetonitrile at 0oC is slowly added 2-detoxification (1.1 g, 6.7 mmol) in 20 ml of acetonitrile. The mixture is heated to room temperature and evaporated. Add 2-amino-5-bromopyridin (1.63 g, 9.4 mmol) and the resulting crude reaction mixture is boiled for 6 h at 140oC in 30 ml of DMF. After cooling down to to the2SO4and the solvent evaporated. The product was then purified column chromatography on silica gel (EtOAc/petroleum ether, 15:100).

1H-NMR (250 MHz, CDCl3), : 8,73 (sh.s, 1H, 11H), 8 (d, 1H, pyridine), 7,68 (LW. d, 1H, pyridine), 7,26-7,16 (m, 2H, phenyl), of 6.96-PC 6.82 (m, 2H, phenyl), of 6.68 (d, 1H, pyridine), a 4.03 (K, 2H, CH2CH3), a 4.03 (K, 2H, CH2NH), to 3.02 (t, 2H, phenyl-CH2), to 1.42 (t, 3H, CH2CH3).

13C-NMR (250 MHz, CDCl3), : 179, 157, 152, 146, 141, 131, 128, 127, 120, 113, 112, 111, 63, 46, 30, 15.

Example 367. N-[2-(2-Ethoxy-6-fluoro)phenethyl]-N'-(2-pyridyl)thiourea.

The original 2-(2-ethoxy-6-forfinal)ethylamine was synthesized according to the method of example 362. This compound is obtained according to the method the condensation reaction described in example 366, using 2-aminopyridine instead of 2-amino-5-bromopyridine.

1H-NMR (250 MHz, CDCl3), : 8 (d, 1H, pyridine), 7,58 (t, 1H, pyridine), 7,14 (K, 1H, pyridine), 6,91-6,59 (m, 4H, phenyl, pyridine), 3,95 (K, 2H, CH2-NH), 3,95 (K, 2H, CH2CH3), to 3.09 (t, 2H, phenyl-CH2), of 1.39 (t, 3H, CH2CH3).

13C-NMR (250 MHz, CDCl3), : 179, 164, 153, 145, 138, 128, 128, 117, 112, 108, 107, 107, 64, 45, 22, 15.

Example 368. N-2-(2-Methoxy)phenethyl-N'-(2-thiazolyl)methyl thioether.

To a solution of N-[2-(2-methoxy)phenethyl]-N'-(2-thiazolyl)thiourea temperature. Methyliodide evaporated, the mixture is transferred on ice, extracted with methylene chloride, dried over Na2SO4and evaporated. The product was then purified column chromatography on silica gel (EtOAc/petroleum ether, 10:100).

1H-NMR (250 MHz, CDCl3), : to 7.25 (d, 1H, thiazole), 7,24 - 7,16 (m, 2H, phenyl), 6,92-for 6.81 (m, 2H, phenyl), and 6.7 (d, 1H, thiazole), 3,79 (s, 3H, CH3O) 3,57 (K, 2H, CH2NH), 2,95 (t, 2H, phenyl-CH2), 2,46 (c, 3H, SCH3).

13C-NMR (250 MHz, CDCl3), : 173, 162, 157, 137, 130, 127, 126, 120, 111, 110, 55, 43, 30, 13.

Example 369. N-[2-(2-Ethoxy-6-fluoro)phenethyl]-N'-[2-(5-methyl)pyridyl]thiourea.

The original 2-(2-ethoxy-6-forfinal)ethylamine obtained by the method of example 362. By the method of the condensation reaction described in example 366, using 2-amino-5-methylpyridine instead of 2-amino-5-bromopyridine synthesized the specified connection.

1H-NMR (250 MHz, CDCl3), : 8,65 (sh.s, 1H, NH), 7,83 (c, 1H, pyridine), 7,41 (d, 1H, pyridine), 7,22-7,05 (K, 1H, phenyl), 6.73 x-to 6.58 (m, 3H, phenyl, pyridine), 3,98 (K, 2H, CH2NH), 3,98 (K, 2H, CH2CH3), of 3.07 (t, 2H, phenyl-CH2in ), 2.25 (s, 3H, CH3), and 1.4 (t, 3H, CH2CH3).

13C-NMR (250 MHz, CDCl3), : 179, 168, 152, 145, 139, 127, 127, 126, 111, 108, 108, 107, 63, 44, 22, 17, 14.

Example 370. N-Phenethyl-N'-[2-(5-chloro)pyridyl]thiourea.< the 0.5 h at room temperature. The mixture is filtered, the precipitate is dried and is recrystallized from acetonitrile, so pl. 152-153oC.

1H-NMR (250 MHz, DMSO), : 8,2 (d, 1H, pyridine), 7,98 (LW. d, 1H, pyridine), 7,45 to 7.4 (m, 5H, phenyl), 7,27 (d, 1H, pyridine), 3,94 (K, 2H, CH2NH), 3.04 from (t, 2H, phenyl-CH2).

13C-NMR (250 MHz, DMSO), : 179, 152, 143, 139, 139, 129, 128, 126, 124, 114, 46, 34.

Example 371. N-[CIS-(DL)-2-Vinylcyclopropyl]-N'-(2-pyridyl)thiourea.

This compound is obtained according to the methods of examples 93 and 94 by the reaction of CIS-(DL)-2-phenylcyclopropane and 2-aminopyridine, which is used instead of 2-aminothiazole.

1H-NMR: 1,19-of 1.27 (m, 1H), 1,45-1,55 (m, 1H), 2,5 (K, 1H), 3,67-of 3.78 (m, 1H), 6.73 x-is 6.78 (m, 2H), 7,27-7,34 (m, 5H), 7,41-7,53 (m, 2H), 10,08 (sh.s, 1H).

13C-NMR: 12,4; 21,9; 34,6; 111,8; 117,3; 126,5; 128,2; 129,1; 136,5; 138,2; 145,1; 153, 180,3.

So pl. 184,5-186oC.

Example 372. N-(5-Chloro-2-pyridyl)-N'-[CIS-(DL)-2-vinylcyclopropyl]thiourea.

This connection (so pl. 194-195,5oC) obtained by the method of example 105 reaction of CIS-(DL)-2-phenylcyclopropane (example 148) with an activated derivative of 2-amino-5-chloropyridine, for example 1-(2-amino-5-chloropyridin)-1'-imidazoledicarbonitrile.

1H-NMR (CDCl3) : 1,19-of 1.26 (m, 1H), 1,46-of 1.55 (m, 1H), of 2.51 (K, 1H), 3,64-3,74 (m, 1H), 6,74 (LW. d, 1H), 7.3 to 7.4 (m, 6H), 7,47 (LW. d, 1H), 9,2 (sh. s, 1H), 1 373. N-(5-Bromo-2-pyridyl)-N'-[CIS-(DL)-2-vinylcyclopropyl]thiourea.

This compound is obtained according to the method of examples 93 and 94 by the reaction of CIS-(DL)-2-phenylcyclopropane (example 148) and 2-amino-5-bromopyridine, which is used instead of 2-aminothiazole.

1H-NMR (CDCl3): 1,19 - of 1.26 (m, 1H), 1,47 - of 1.55 (m, 1H), 2,52 (K, 1H), 3,66 of 3.75 (m, 1H), 6,66 (LW.d, 1H), 7,27 - 7,41 (m, 5H), 7,47 (d, 1H), 7,6 (LW.d, 1H), 8,98 (sh.s, 1H), 10,88 (sh.s, 1H).

13C-NMR (CDCl3): 12,4; 22; 34,7; 112,3; 113,1; 126,8; 128,4; 129,2; 136,5; 140,9; 146,2; 151,3; 180,2.

Found, %: C 51,5; H 4,00; N 12,00.

C15H14BrN3S

Calculated, %: C Of 51.7; H Of 4.05; N 12,07.

Example 374. 5-Chloropyridin-2-yl-isothiocyanate.

To a solution of thiocarbonyldiimidazole (14,26 g) in acetonitrile (100 ml) at room temperature and stirring for 25 min servings add 2-amino-5-chloropyridin (10,28 g). Stirring is continued and the solution-suspension is left for several hours at the same temperature. The precipitate is filtered and washed with acetonitrile (3 x 25 ml). The solid residue is dissolved in hot acetone and filtered. The acetone solution is evaporated in vacuum, the residue is dissolved in hot ethyl acetate and filtered through a layer of silica (size: 3 x 7 cm). The silica was washed with another portion of asanoha connection.

1H-NMR (DMSO): rate of 7.54 (d, J=8.7 Hz, 1H), 8,17 (LW.d, J=2.7 and 8.7 Hz, 1H), 8,63 (d, J=2.7 Hz, 1H).

13C-NMR (DMSO): 121,4; 130,1; 139,4; 140,7; 143,9; 148,6.

Example 375. N-CIS-(DL)-[2-(3-Methoxy)vinylcyclopropyl] -N'- (2-thiazolyl)thiourea.

The original 3-mitoxantron obtained in the following way. To the mixture 26,2 g (73.4 mmol) of methyltriphenylphosphonium and 200 ml of THF, cooled to 0oC, for 30 min add 42 ml of sitedisability (2 M in THF, 82 mmol). The mixture is stirred for a further 2 hours, then added dropwise over 25 min add 10 g (73.4 mmol) of 3-methoxybenzaldehyde. The reaction mixture was stirred 1 h at room temperature and then boiled for 14 hours After cooling, the solvent is evaporated in vacuo, the residue diluted with 200 ml diethyl ether and the precipitate filtered off. The ether solution is washed with water, dried over Na2SO4and evaporated in vacuum. The product was then purified column chromatography on silica gel (diethyl ether/cyclohexane), yield 2.83 g (29%).

1H-NMR (CDCl3), : 7,24 (t, J=8,1 Hz, 1H, Ph), 7,21-6,98 (m, 1H, Ph), to 6.95 (t, J=2.3 Hz, 1H, Ph), for 6.81 (two DV. d, J=8,1 Hz, 2.3 Hz, 0.9 Hz, 1H, Ph), 6,69 (LW. d, J=17,6 and 10.8 Hz, 1H, CH), 5,74 (LW. d, J=17,6 and 0.9 Hz, 1H, CH2in ), 5.25 (LW. d, J=10,8 and 0.9 Hz, 1H, CH2), 3,81 (s, 3H, CH3).

13C-NMR (CDCl3

1H-NMR (CDCl3), : 7,26-7,19 (t and d, 2H, o-, p-, thiazole), 6,9 - 6,69 (m, 4H, o-, m-, p-, thiazole), 3,76 (s, 3H, OMe), 3,65 (sh. s, 1H, NH-CH-), 2,5 (K, 1H, Ph-CH-), 1,22 (m, 2H, cyclopropyl).

13C-NMR (CDCl3), : 178,6 (C = S), 161,3 (thiazole), 159,8 (C-OMe), 137,8 (Ph), 137,7 (thiazole), of 129.5 (Ph), To 121.6 (Ph), 114,5 (Ph) 112,8 (Ph), 111 (thiazole), 55,2 (O-CH3), 44 (CH-H), 22 (CH-Ph), 12,1 (CH2).

Example 376. N-CIS-((DL)-[2-(2-Forfinal)cyclopropyl]-N'-(2-thiazolyl) thiourea.

This compound is synthesized according to the methods described in examples 348 and 349, using a 2-torterolo instead of styrene.

1H-NMR (CDCl3), : 7,32 - 7,05 (m, 4H), 6,91 - only 6.64 (m, 2H), 3,68 (sh.s, 1H, CH-NH), 2.57 m (K, 1H, CH-Ph), 1,7 - 1,4 (m, 3H), 1,31 - of 1.18 (m, 1H).

13C-NMR (CDCl3), : 178,8 (C = S), 162,5 and 160,5 (C - F, Ph), 161,2 (thiazole), 137,4 (thiazole), 129, 9mm (Ph), 128,5 and 128,4 (m - F, Ph), 124 (n-F, Ph), 115,4 and or 115.1 (F, Ph), 111,8 (thiazole), and 33.8 (CH-NH), and 16.4 (CH-Ph), and 12.2 (CH2).

Example 377. N-{2-[3-(6-Chloro-3-methoxy)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea.

The original 3-(2-amino-ethyl)-6-chloro-2-methoxypyridine obtained in the following way. To a solution of 1 g (7 mmol) of 2-chloro-6-methoxypyridine in 20 ml of dry THF under nitrogen atmosphere and while cooling on -178oC added 10.9 ml n-BuLi (of 1.6 M in hexane, to 17.4 mmol). Before adding 4 ml of ethylene oxide in 6 ml of ether temperatury layer is separated and extracted with EtOAc (2x 100 ml). The organic extracts are combined, washed once with water, dried over Na2SO4and concentrated in vacuo. The crude product is purified dry pressure column chromatography (hexane/EtOAc) to obtain 0,22 g of 3-(2-hydroxyethyl)-6-chloro-3-methoxypyridine in the form of a yellowish oil.

To cooled at -50oC to a solution of 0.2 g (0.8 mmol) of 3-(2-hydroxyethyl)-6-chloro-2-methoxypyridine in 10 ml of dry CH2Cl2in nitrogen atmosphere add to 0.18 ml (0.8 ml) anhydride triftormetilfullerenov acid. The mixture is stirred for 30 min at the same temperature and 10 min at -78oC before the addition of cold (-78oC) NH3(W). The mixture is stirred for 15 min at room temperature, followed by concentration in vacuum to obtain 1 g of crude 3-(2-amino-ethyl)-6-chloro-2-methoxypyridine in the form of a salt with triftormetilfullerenov acid.

1H-NMR (CD3OD), : 7,66 (d, 1H, Py), 7,03 (d, 1H, Py), Android 4.04 (s, 3H, CH3-O), 3,24 (t, 2H, CH2-N), 3,03 (t, 2H, CH2-Py).

Crude 3-(2-amino-ethyl)-6-chloro-2-methoxypyridine by the method of example 103 condensed with N-[2-(5-bromo)pyridyl]-N'-[1-imidazolyl]urea with the formation of the specified connection.

1H-NMR (CD3OD), : 11,25 (sh.s, 1H, N-H) 10,82 (sh. s, 1H, N-H), 8,31 (C,UP>13C-NMR (CD3OD), : 179,45 (C = S), 161,43 (Cl-C Py), 152,41 (Br-C Py), 145,92 (Cl-Py), 145,14 (MeO-C-Py), 141,89 (Br-Py), 141,51 (Br-Py), 120,32 (Cl-Py), 116,48 (Cl-Py), 114,6 (Br-Py), 111,95 (Br-Py), with 55.1 (CH3O), 43,76 (CH2-NH), 27,89 (CH2-Ph).

Example 378. N-{2-[3-(2-Fluorine)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea.

The original 3-(2-amino-ethyl)-2-herperidin obtained in the following way. To a cooled to -78oC to a solution of 2 g (to 20.6 mmol) of 2-herperidin in 25 ml dry THF under nitrogen atmosphere add 25 ml of BuLi solution (a 1.6 M in hexane, to 41.6 mmol). Before adding 4 ml of ethylene oxide in 7 ml of ether, the mixture is stirred for 2 h at the same temperature. The mixture is heated to room temperature and to it was added 150 ml of ether and 25 ml of acetone. The precipitate is filtered off and the filtrate concentrated in vacuum to 1.3 of its volume. The residue is washed once with brine, dried over Na2SO4and concentrated in vacuo. Purification of the crude product dry pressure column chromatography (hexane/EtOAc) gain of 0.42 g of 3-(2-hydroxyethyl)-2-herperidin in the form of a brown oil.

To a cooled to -40oC to a solution of 0.2 g (of 1.42 mmol) of 3-(2-hydroxyethyl)-2-herperidin in 8 ml of dry CH2Cl2in nitrogen atmosphere add to 0.18 ml (0.8 mmol) of anhydride triftormetilfullerenov acid. After Peta 30 min at -40oC and after concentration in vacuo gain of 1.03 g of dry salt by washing twice with 20 ml diethyl ether gain of 0.82 g of 3-(2-amino-ethyl)-2-herperidin in the form of a salt with triftormetilfullerenov acid.

1H-NMR (CD3OD), : 8,23 (d, 1H, Py), 7,98 (t, 1H, Py), and 7.4 (m, 1H, Py), and 3.3 (t, 2H, CH2-N) of 3.12 (t, 2H, CH2-Py).

Crude 3-(2-amino-ethyl)-2-herperidin by the method of example 103 is introduced into reaction with N-[2-(5-bromo)pyridyl]-N'-(1-imidazolyl)thiourea with the formation of the specified connection.

1H-NMR (CD3OD), : 8,31 (d, 1H, Br-Py), 8,23 (m, 1H, F-Py), of 8.06 (m, 2H, Br and F-Py), was 7.45 (m, 1H, F-Py), of 7.23 (d, 1H, Br - Py), 4 (K, 2H, CH2-N), 3,14 (m, 2H, CH2-Py).

13C-NMR (CD3OD), : 179,59 (C = S), 163,53 and 159,78 (F-C Py), 152,39 (Br-Py), 145,87 (F-Py), 145,63 and 142,38 (F-Py), 142,28 (Br-Py), 141,54 (Br-Py), 122,31 and 122,26 (F-Py), 120,94 and 120,45 (F-Py), 114,59 (Br-Py), 111,97 (Br-Py), 44,29 (CH2-N), 27,32 (CH2-Ph).

Example 379. N-[2-(2,6-Debtor)phenethyl]-N'-(2-benzothiazolyl)thiourea.

According to the method of example 105 carry out the reaction between 2,6-differentiation and 1-(2-aminobenzothiazole)-1'-imidazoledicarbonitrile synthesized according to the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3+ CD3OD): to 7.64 (m, 2H, benzo), 7,38 (m, 3H, h, benzo), 7, is alil]thiourea.

According to the method of example 105 carry out the reaction between 2,6-differentiation and 1-(2-amino-4,5-dimethylthiazol)-1'-imidazoledicarbonitrile synthesized according to the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3), : 7,21 (m, 1H, h), to 7.15 (t, 2H, h), 4 (K, 2H, CH2), to 3.09 (t, 2H, CH2), 2,22 (d, J = 0.5 Hz, 3H, Me), 2,08 (d, J = 0.6 Hz, Me).

Example 381. N-[2-(2-Fluoro)phenethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea.

According to the method of example 105 2-fortunetelling condensed with 1-(2-amino-6-fermentation)-1'-imidazoledicarbonitrile obtained by the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3+ CD3OD), : 7,53 - 7,06 (m, 7H, benzo, h), Android 4.04 (t, 2H, CH2), 3,1 (t, 2H, CH2).

Example 382. N-[2-(2,6-Debtor)phenethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea.

According to the method of example 105 2,6-differentiatin condensed with 1-(2-amino-6-fermentation)-1'-imidazoledicarbonitrile obtained by the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3+ CD3OD), : 7,52 (m, 1H, benzo), and 7.4 (m, 1H, benzo), 7,14 (m, 2H, h, benzo), to 6.88 (m, 2H, h), was 4.02 (t, 2H, CH2), 3,14 (t, 2H, CH is RA 105 2-fortunetelling condensed with 1-(2-aminobenzothiazole)-1-imidazoledicarbonitrile, obtained by the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3+ CD3OD), : 7,63 (K, 2H, benzo), 7,32 (m, 4H, benzo, h), 7,1 (, 2H, h), 4,06 (t, 2H, CH2), the 3.11 (t, 2H, CH2).

Example 384. N-[2-(2-Fluoro)phenethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

According to the method of example 105 2-fortunetelling condensed with 1-(2-amino-4-methylthiazole)-1-imidazoledicarbonitrile obtained by the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3+ CD3OD), : of 7.23 (m, 2H, h), 7,06 (m, 2H, h), 6,34 (d, J = 1 Hz, 1H, thiazole), to 3.99 (t, 2H, CH2), was 3.05 (m, 2H, CH2), 2,2 (d, J = 0.9 Hz, 3H, Me).

Example 385. N-[2-(2,5-Debtor)phenethyl]-N'-[2-(4-methyl)thiazolyl]thiourea.

According to the method of example 105 2,6-differentiatin condensed with 1-(2-amino-4-methylthiazole)-1-imidazoledicarbonitrile obtained by the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3+ CD3OD), : 7,19 (m, 1H, h), 6.87 in (t, 2H, h), 6.35mm (s, 1H, thiazole), 3,98 (t, 2H, CH2), to 3.09 (t, 2H, CH2), 2,22 (s, 3H, Me).

Example 386. N-[2,2-Dimethyl-2-(2-chloro-6-fluoro)phenethyl] -N'- (2-thiazolyl)thiourea.

To the cooled alamid (the 5.25 ml, 10.5 mmol). After 30 min to the reaction mixture add methyliodide (0.68 ml, 11 mmol), the mixture is slowly heated to 0oC and incubated for 1 h at the same temperature. Then again cooled to -60oC and adds extra sitedisability (6 ml, 12 mmol). After 30 minutes add methyliodide (of 1.87 ml, 30 mmol). The reaction mixture was left to warm to room temperature, kept at this temperature for 2 h and then transferred into a solution of sodium bicarbonate and extracted with chloroform. The organic phase is washed with water, dried and the solvent evaporated in vacuum. Obtained as a product of 2,2-dimethyl-2-(2-chloro-6-fluoro)acetonitrile allocate column chromatography on silica gel.

1H-NMR (CDCl3), : 7,25 (m, 2H, Ph), 7,03 (m, 1H, Ph) to 1.98 (s, 3H, Me), a 1.96 (s, 3H, Me).

2,2-Dimethyl-2-(2-chloro-6-forfinal)ethylamine obtained by reduction of 2,2-dimethyl-2-(2-fluoro-6-forfinal)acetonitrile cobalt chloride and sodium borohydride according to the method (described in: L. S. Heizman. J. Am. Chem. Soc. , 104, 6801 S., 1980). Then, the resulting amine condensate according to the method of example 105 1-(2-aminothiazol)-1'-imidazoledicarbonitrile. The specified connection is highlighted column chromatography on silica gel.

1H-NMR of 2-(5-Bromo-2-methoxy)phenethyl] -N'-[2-(4-methyl) thiazolyl] thiourea.

According to the method of example 105 5-bromo-2-methoxyphenethylamine condensed with 1-(2-amino-4-methylthiazole)-1'-imidazoledicarbonitrile obtained by the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3+ CD3OD), : 7,31 (d, 1H, Ph), 7,29 (s, 1H, Ph), 6,72 (d, 1H, Ph), 6,34 (s, 1H, thiazole), of 3.95 (t, 2H, CH2), 3,79 (s, 3H, MeO), 2,96 (t, 2H, CH2), of 2.23 (s, 3H, Me).

Example 388. N-[2-(5-Bromo-2-methoxy)phenethyl] -N'-[2-(4-cyano) thiazolyl] thiourea.

According to the method of example 105 5-bromo-2-methoxyphenethylamine condensed with 1-(2-amino-4-cenotesa)-1-imidazoledicarbonitrile obtained by the method of example 103. The specified connection purified column chromatography on silica gel.

1H-NMR (CDCl3+ CD3OD), : 7,51 (thiazole), 7,32 (d, 1H, Ph), 7,27 (s, 1H, Ph) 6,76 (d, 1H, Ph) of 3.9 (t, 2H, CH2), 3,83 (s, 3H, MeO), of 2.97 (t, 2H, CH2).

Example 389. N-[2-(2,6-Debtor(phenethyl] -N'-[2-(4-cyano)thiazolyl] thiourea.

According to the method of example 105 2,6-differentiatin condensed with 1-(2-amino-4-cenotesa)-1'-imidazoledicarbonitrile obtained by the method of example 103. The specified connection crystallized from methylene chloride.

1H-NMR (CDCl3+ CD3OD), : 7,51 (s, 1H, thiazole), 7,22 (m, 1H, h) and 6.9 (t, 2H, h),CLASS="ptx2">

This compound is obtained according to the method of example 93 using 2,6-differentiating and 2-aminoimidazole.

1H-NMR (DMSO + D2O): 7,28 (m, 1H, h), 7,02 (t, 2H, h), 6,78 (sh. band, 1H, imidazole), 6,62 (sh. band, 1H, imidazole), with 3.79 (t, 2H, CH2), of 2.97 (t, 2H, CH2).

Example 391. N-[1-1-Amino-2-(5-imidazolyl)ethyl]-N'-[2-(5-methyl) thiazolyl] thiourea.

1-[2-(5-Methyl)aminothiazol] -1'-imidazoledicarbonitrile (obtained by the method of example 103 using 2-amino-5-methylthiazole instead of 2-aminothiazole) (910 mg, 4,06 mol) and histamine (450 mg, of 4.05 mmol) in dimethylformamide (10 ml) was heated 3 h at 50oC. the Mixture is concentrated and distributed between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer is dried over MgSO4and after concentrating receive 463 mg (43%) of the specified connection.

1H-NMR (250 MHz, DMSO-d6), : to 2.18 (s, 3H), 2,8 (m, 2H), to 6.57 (s, 1H), 6,9 (s, 1H), and 7.6 (s, 1H).

Example 392. 1-(2-Amido-5-bromopyridin)-1-(imidazolyl) thiocarbonyl.

A mixture of 2-amino-5-bromopyridine, 97% (25 g, 140 mmol) and 1,1'-thiocarbonyldiimidazole, 90% (27,72 g, 140 mmol) in 300 ml of acetonitrile is stirred for about a day at room temperature and then filtered. Drying the precipitate in vacuo receive 37.5 gcii with a variety of phenethylamine.

Example 393. 1-(5-Chloropyrid-2-yl-thiocarbamoyl)imidazole.

In the reaction flask 500 ml when moving and 50oC in 400 ml of acetonitrile was dissolved N, N-thiocarbonyldiimidazole (60 g, 337 mmol) and the solution after cooling to 20oC add 2-amino-5-chloropyridin (43 g, 337 mmol).

The solution is stirred for 35 min and kept for about a day at room temperature. The solution is filtered to obtain a crystalline mass consisting of granules and needles. Granules are mechanically separated and purified by fluidization using blowers and obtaining the specified connection.

1H-NMR (DMSO-d6), : 7,1-7,2 (2H, s, imide), a 7.5 and 7.6 (1H, d, ortho-relationship FIC.), 7,9-8 (1H, s, imide.), of 8.1 to 8.2 (1H, DV. D., feast.), 8.6 out of 8.7 (1H, d, meta-communication, the feast.).

Example 394. N-2-(2,5-Dimethoxyphenethyl)-N'-2- (6-fermentational)thiourea.

A mixture of 450 mg of 2,5-dimethoxyphenethylamine (2.5 mmol) and 740 mg of 1-{[2-(6-fluoro)benzothiazolyl]thiocarbamoyl}imidazole (2.5 mmol) (see example 80) in 5 ml of acetonitrile is boiled for half an hour. The mixture is cooled and the crystals filtered off. By recrystallization from ethanol-dimethylformamide obtain 640 mg of the pure product as fine needles, so pl. 196oC.

1H-NMR: 3 (2H, t), of 3.77 (3H, s), of 3.84 (3H, s), 3,91 (2H, m), 6,91-7,03 (3H,>N3O2S2< / BR>
Calculated,%: C 55,22; H 4,63; N Of 10.73.

Example 395. N-2-(2,5-Dimethoxyphenethyl)-N'-[2-(4-methyl)thiazolyl] thiourea.

A mixture of 1000 mg (4,46 mmol) 1-[2-(4-methylthiazolyl)thiocarbamoyl] imidazole (obtained analogously to 1-[(2-thiazolyl)thiocarbamoyl]imidazole of example 103) and 800 mg of 2,5-dimethoxyphenethylamine (4,42 mmol) in 7 ml of acetonitrile is boiled for half an hour. The mixture is cooled to 0oC, the crystals are filtered, rinsed with acetonitrile and dried. By recrystallization from a mixture of ethanol/dimethylformamide obtain 1.42 g of pure product, so pl. 210oC.

1H-NMR (DMSO-d6): of 2.27 (3H, s), 2,96 (2H, t), of 3.78 (3H, s), 3,83 (3H, s), a-3.84 (2H, m), of 6.73 (1H, s), 6,85? 7.04 baby mortality (3H, m).

Found, %: C 53,1; H 5,65; N 12,35.

C15H19N3O2S2< / BR>
Calculated, %: C 53,39; H 5,67; N 12,45.

Example 396. N-2-(2,5-Dimethoxyphenethyl)-N'-(2-benzothiazolyl) thiourea.

The mixture 556 mg of 1-(2-benzothiazolyl)thiocarbamoyl]imidazole (2 mmol) (example 66) and 2,5-dimethoxyphenethylamine (2 mmol) in 5 ml of acetonitrile is boiled for half an hour. By recrystallization from a mixture of ethanol/dimethylformamide receive 565 mg of pure product.

1H-NMR (DMSO-d6): to 3.02 (2H, t), of 3.77 (3H, s), 3,85 (3H, s), 3,93 (2H, m), 6,92? 7.04 baby mortality (3H, m), 7,38 (1H, m), 7,53 (1H, m), and 7.7 (1H, m), keno, %: C 57,88; H 5,13; N 11,25.

Example 397. N-2-(2,6-Dichloroethyl)-N'-(2-thiazolyl)thiourea.

To a mixture of 5 g of sociallyengaged and 200 ml of ether are added dropwise 9.3 g of 2,6-dichlorobenzonitrile in 50 ml of diethyl ether. The mixture is heated to boiling and boil 2 hours the Mixture is cooled to room temperature, added dropwise 5 ml of water and then 5 ml of 25% aqueous sodium hydroxide. After addition of 10 ml water the mixture is filtered and mixed with the filtrate quickly add 10 ml of acetic acid. Usageprice 2,6-differentelements filtered and dried.

In 5 ml of acetonitrile is mixed with 500 mg of 2,6-dichlorophenylisocyanate (2 mmol), 0,42 g of 1-(2-aminothiazol)-1'-imidazoledicarbonitrile (example 103) and 0.5 g of Diisopropylamine and the mixture is boiled for 30 minutes the Mixture was incubated for 17 h at 0oC and the crystals filtered off. By recrystallization from acetonitrile obtain 265 mg of the compounds.

1H-NMR (DMSO-d6): 3,3 (2H, t), 3,9 (2H, m), 7,2 (1H, d), 7,35 and 7.6 (4H, m).

Example 398. N-2-(2,6-Dichlorophenyl)-N'-[2-(4-methyl)thiazolyl]thiourea.

In 5 ml of acetonitrile is mixed with 500 mg of 2,6-dichlorophenylisocyanate (2 mmol) (see example 397), of 0.48 g of 1-[2-4-methylthiazolyl)thiocarbamoyl]imidazole (obtained analogously to 1-[(2 the crystallization from acetonitrile receive 598 mg specified connection.

1H-NMR (DMSO-d6): 2,2 (3H, s), 3,3 (2H, t), 4 (2H, m), 6,7 (1H, s), and 7.4 (1H, m), and 7.5 (2H, m), and 9.8 (1H, sh.C) to 11.7 (1H, sh.C).

Found, %: C 45,45; H 3,9; N 12,55.

C13H13Cl2N3S2< / BR>
Calculated, %: C 45,09; H Of 3.78; N 12,13.

Example 399. N-[2-(2,6-Dichlorophenyl)ethyl]-N'-(2-benzothiazolyl)thiourea.

In 5 ml of acetonitrile is mixed with 500 mg of 2,6-dichlorophenylisocyanate (2 mmol) (see example 397), 0.55 g of 1-[2-benzothiazolyl)thiocarbamoyl]imidazole (2 mmol) (see example 66) and 0.5 g of diisopropylethylamine and the mixture is boiled for 30 minutes the Mixture is cooled and the crystals filtered off. By recrystallization from acetonitrile receive 497 mg of the compounds.

1H-NMR (DMSO-d6): 3,3 (2H, t), 4 (2H, m), and 7.3 to 7.7 (6H, m), 8 (1H, d), 10 (1H, broad peak), compared to 12.1 (broad peak).

Found, %: C 50,3; H Of 3.45; N 11,1.

C16H13Cl2N3S2< / BR>
Calculated, %: C 50,26; H 3,43; N 10,99.

Example 400. N-[2-(2,6-Dichlorophenyl)ethyl]-N'-[2-(6-fermentational)]thiourea.

In 5 ml of acetonitrile is mixed with 500 mg of 2,6-dichlorophenylisocyanate (2 mmol) (see example 397), of 0.59 g of 1-{[2-(6-fluoro)benzothiazolyl]thiocarbamoyl} imidazole (2 mmol) (see example 80) and 0.5 g of diisopropylethylamine and the mixture is boiled for 30 minutes the Mixture is cooled and the crystals otfit the DMSO-d6): 3,4 (2H, t), 4 (2H, m), 7.3 to 7.4 (2H, m), of 7.5 to 7.7 (2H, m), 8 (1H, m), and 9.8 (1H, broad peak), 12 (1H, broad peak).

Found, %: C 48,25; H 3,1; N 10,6.

C16H12Cl2FN3S2< / BR>
Calculated,%: C 48; H 3,02; N 10,5.

Example 401. N-[2-(2,6-Debtor-3-methoxyphenyl)ethyl]-N'-(2-thiazolyl)thiourea.

To a solution of 10 mmol of 2,4-diferently in 30 ml of diethyl ether are added dropwise at 6.25 ml of a 1.6 M solution of n-utility in hexane. The temperature of the mixture during the addition of support at -65oC. Then add 3 ml of dimethylformamide and the mixture is left slowly (1 h) to warm to room temperature. The mixture is transferred into a separating funnel containing 50 ml of ice water. The ether layer is separated, washed with 50 ml of water and dried over Na2SO4. The solvent is evaporated and the residue is again dissolved in 50 ml of ethanol. Add 2 g of ammonium acetate and 3 ml of nitromethane and the mixture is boiled for 3 hours the Solvent is evaporated and the residue partitioned between 50 ml of dichloromethane and 50 ml of water. The organic layer is dried and the solvent evaporated. Crystallization from cold ethanol 480 mg of brown crystals of 1-nitro-2-(2,6-debtor-3-methoxyphenyl)Atena.

1H-NMR (CDCl3): of 3.9 (3H, s), 6,9-7,1 (2H, m), and 7.8 (1H, d) and 8.1 (1H, d).

In 50 ml of TII added to a solution of 2 g of sociallyengaged in 50 ml of tetrahydrofuran. The mixture is boiled for 3 hours Obtained amine is treated with dropwise addition of 2 ml of water followed by addition of 2 ml of 25% aqueous sodium hydroxide and then 4 ml of water.

The mixture is filtered and the filtrate is extracted with 1 M HCl ( 2 x 20 ml). The aqueous layer was alkalinized by adding 50 ml of 45% sodium hydroxide solution, then extracted with dichloromethane (3 x 50 ml). Obtained by evaporation of the solvent 2-(2,6-debtor-3-methoxyphenyl)ethylamine sufficiently pure for use in the next stage.

1H-NMR: 1,2 (2H, sh.C), and 2.6 (2H, m), 2,7 (2H, m), the 3.65 (3H, s), 6,4-6,6 (2H, m).

A mixture of 172 mg of 2-(2,6-debtor-3-methoxyphenyl)ethylamine (1 mmol) and 210 mg of 1-(2-aminothiazol)-1'-imidazoledicarbonitrile (1 mmol) in 5 ml of acetonitrile is boiled for 1 hour the Solution is cooled and left overnight for crystallization. Solids filtered off and recrystallization from acetonitrile obtain 138 mg of the compounds.

1H-NMR (DMSO-d6): 3,1 (2H, t), 3,8-4 (5H, m), 6,9-7,2 (3H, m), and 7.4 (1H, d), and 9.8 (1H, broad peak), an 11.7 (1H, broad peak).

Found, %: C 47,6; H 4,1; N Was 12.75.

C13H13F2N3OS2< / BR>
Calculated, %: C To 47.4; H 3,98; N 12,76.

Example 402. N-[2-(2-Benzothiazolyl)ethyl]-N'-(2-thiazolyl)thiourea.

700 ml demetillo add drops of 73.5 g (0.6 mol) of ethylchloride. Stir the mixture slowly heated to 40oC and kept at this temperature for 17 hours, the Solvent evaporated and the residue extracted with ethyl acetate. GC showed the formation of one dominant and one smaller product. Resulting in fewer ethyl ester 2-(2-benzotriazolyl)acetic acid selected fractional crystallization from cold ethanol-ethyl acetate.

50 ml of a mixture of diethyl ether/tetrahydrofuran (1:1) dissolved 7,1 (40 mmol) of the obtained ether, then add 1.5 g of lithium borohydride and the reaction mixture stirred for 17 h at room temperature. The solvent is removed and replaced with 50 ml of butanol. Add 5 ml of water and the temperature is slowly increased to approximately the 50oC. After 4 h of incubation at this temperature, the solvent is removed, the residue is partitioned between dichloromethane and water. The organic layer is dried and the resulting 2-(2-benzotriazolyl)produce ethanol by crystallization from cold ethanol.

In 200 ml of diethyl ether dissolving 4.7 g of 2-(2-benzotriazolyl)ethanol (28.8 mmol) and the solution was added 2.28 g of pyridine (28.8 mmol). The mixture is cooled to -50oC and to it was added 8,18 g Trifonova anhydride (29 mmol). The mixture is extracted from ohla is cooled to -40oC the solution approximately 150 ml of ammonia in 50 ml of diethyl ether. The resulting mixture was left to warm to room temperature and the ether removed. Add 50 ml of 2 M HCl and the resulting mixture is washed with methylene chloride. The aqueous phase is alkalinized by addition of 25% aqueous sodium hydroxide solution and extracted with methylene chloride (3 x 25 ml). Evaporation of the solvent to obtain 2.1 g of 2-(2-benzothiazolyl)ethylamine used in the next stage without additional purification.

In 3 ml of acetonitrile is mixed 324 mg (2 mmol) of 2-(2-benzothiazolyl)ethylamine and 420 mg of 1-(2-aminothiazol)-1'-imidazoledicarbonitrile, the mixture is slowly heated to boiling and then cooled for crystallization. Re-crystallization from acetonitrile obtain 234 mg of pure N-[2-(2-benzothiazolyl)ethyl]-N'-(2-thiazolyl)thiourea.

1H-NMR (DMSO-d6): 4,5 (2H, m), 5,1 (2H, m), of 6.75 (1H, d), 7,05 (1H, d), and 7.4 (2H, m), 7,9 (2H, m).

13C-NMR: 47, 56, 112, 119, 127, 145, 180.

Found, %: C 47,3; H 3,95; N 27,2.

C12H12N6S2< / BR>
Calculated, %: C 47,35; H Of 3.97; N 27,61.

Example 403. CIS-/TRANS-N-[2-(2-Ethoxybenzylidene)]-N'-(2-pyridyl)thiourea.

The solution 28,56 g methyltriphenylphosphonium (80 mmol) in 500 ml of tet is IMEMO 1.6 M, 80 mmol). The mixture is slowly warmed to room temperature and kept at this temperature for 2 hours Then the mixture is cooled to -30oC and add 12 g (80 mmol) of 2-ethoxybenzaldehyde. The mixture is heated to room temperature, most of the solvent removed, the residue is mixed with 400 ml of ether and filtered. The solvent is removed and to the residue is added ethyl acetate. The solution is passed through a layer of silica gel. Crude 2-atoxicity dissolved in 50 ml dichloromethane and used in this form in the next stage of the reaction.

Add 0.1 g of CuI and the mixture heated to boiling. Then for 1 hour and added dropwise 8.8 g of ethyl diazo acetate in 30 ml of dichloromethane. GC analysis showed the formation of two products in the approximate ratio 1:2. Two isomeric product is separated from the other reaction products column chromatography (silica gel, mixture of hexane/ethyl acetate). The result obtained 3.1 g of CIS-/TRANS-mixture of 2-(2-ethoxyphenyl)-1-carboximetilcelulosa. The resulting mixture was hydrolized in a boiling mixture of 50 ml ethanol and 10 ml of water and 4 g of sodium hydroxide (2 hours). The solvent is evaporated, the residue acidified with 100 ml of 2M hydrochloric acid and extracted with dichloromethane (2 x 50 ml). The organic phase is dried and the solvent evaporated. Add 50 m are removed. Add acetone (100 ml), the solution is cooled in a bath with ice, add 4 g of sodium azide in 20 ml of water and 100 ml of toluene, after which the mixture is washed with water (3 x 50 ml). The organic layer is dried over Na2SO4the solvent is evaporated, the residue is dissolved in 100 ml of dioxane. Dioxane solution was slowly heated to boiling and boil for 30 minutes Add 25 ml of concentrated hydrochloric acid and the mixture is boiled for 2 hours the Solvent is removed and the residue is partitioned between 50 ml of dichloromethane and 50 ml of 2M hydrochloric acid. The aqueous layer was alkalinized by addition of 50 ml of 25% aqueous sodium hydroxide solution and extracted with dichloromethane (3 x 50 ml). Dichloromethane is evaporated and the residue is purified column chromatography (silica gel, ethanol-ethyl acetate) to give the CIS-/TRANS-mixture (approximately 1:1) 2-(2-ethoxyphenyl)cyclopropylamine.

In 5 ml of acetonitrile is stirred for 2 h 0.24 g (2.6 mmol) of 2-aminopyridine and 0.46 g (2.6 mmol) of thiocarbonyldiimidazole. Then add 0,41 g (2.6 mmol) of cyclopropylamine, the temperature of the mixture is slowly increased to 70oC and stirred at this temperature for 17 hours, the Solvent evaporated, and the connection specified allocate column chromatography (silica gel, mixture of hexane/ethyl acetate).

1H-NMR : 1,15-1,2 is)] thiourea.

In 15 ml of acetonitrile is stirred for 2 h 1.73 g (10 mmol) 2-amino-5-chloropyridine and 1.78 g (10 mmol) of thiocarbonyldiimidazole. Added 1.47 g (12 mmol) of 2-(2-amino-ethyl)pyridine and the mixture is stirred for 2 h at room temperature. Then the reaction mixture is heated to 50oC and stirred for 17 hours, After cooling the mixture, the crystals are filtered. By recrystallization from acetonitrile get clean the specified connection.

1H-NMR (DMSO-d6): 3,2 (2H, t), 4,1 (2H, m), 7,2-7,5 (3H, m), 7,8-8 (2H, m), and 8.2 (2H, d), and 8.7 (1H, m), 18 (1H, s), and 11.5 (1H, s).

Example 405. N-[2-(2-Pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea.

In 15 ml of acetonitrile is stirred for 2 h 1.28 g (10 mmol) 2-amino-5-bromopyridine and 1.78 g (10 mmol) of thiocarbonyldiimidazole. Then added 1.47 g (12 mmol) of 2-(2-amino-ethyl)pyridine and the mixture is stirred for 2 h at room temperature. The reaction mixture is heated to 50oC and stirred for 17 hours, After cooling the mixture, the crystals are filtered. By recrystallization from acetonitrile get clean the specified connection.

1H-NMR (DMSO-d6): 3,5 (2H, t), is 4.2 (2H, m), 7,2 (2H, d), of 7.9 to 8.1 (3H, m), and 8.3 (1H, d), and 8.6 (1H, m), 8,9 (1H, d), or 10.9 (1H, s), and 11.4 (1H, t).

Example 406. N-[2-(2-Pyridyl)ethyl]-N'-[2-(5-nitro)pyridyl] thiourea.

20 ª, the mixture is heated to 50oC and stirred for 30 minutes the Mixture is cooled and most of the liquid decanted from the resulting red precipitate. The precipitate is transferred into 20 ml of acetonitrile, then added 1.78 g of thiocarbonyldiimidazole in 10 ml of acetonitrile. The resulting mixture was stirred for 10 min at room temperature, added 1.22 g of 2-(2-amino-ethyl)pyridine and the mixture is stirred for 1 h was Added 1 ml of acetic acid and the solvent is evaporated. The residue is washed with water and repeated crystallization from acetonitrile obtain 1.28 g of the compounds in the form of yellow crystals.

1H-NMR (DMSO-d6): 3,1 (2H, t), and 3.2 (2H, t), 7,2 (1H, m), and 7.3 (3H, m), and 7.7 (1H, m), and 8.4 (1H, m), and 8.5 (1H, m), 8,9 (1H, d).

Example 407. N-[2-(2-Pyridyl)ethyl]-N'-[2-(5-methyl)pyridyl]thiourea.

A mixture of 1.78 g of thiocarbonyldiimidazole (10 mmol) and 1.58 g of 2-amino-5-methylpyridine (10 mmol) in 15 ml of acetonitrile is stirred for 1 h at room temperature. Added 1.22 g of 2-(2-amino-ethyl)pyridine and the mixture is stirred for 1 h at room temperature, and then 17 hours at 50oC. the Mixture is cooled and the crystals filtered off. By recrystallization from acetonitrile obtain 1.3 g of pure specified connection.

1H-NMR (DMSO-d6): 2,2 (3H, s), 3,1 (3H, t), 4 (2H, m), 7 (1H, is 9,2; to 151.8; 159; 179,2.

Example 408. N-[2-(2-Pyridyl)ethyl] -N'-[2-(5-bromo)pyridyl] thiourea, HCl-salt.

Approximately 10 ml of water is suspended 100 mg of N-[2-(2 - pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl] thiourea (see example 405), the suspension is heated to approximately 90oC and adding hydrochloric acid to establish a pH of about 3. The specified connection allocate freeze-drying.

1H-NMR (DMSO-d6) : 3,6 (2H, t), is 4.2 (2H, m), 7,2 (2H, d), of 7.9 to 8.1 (3H, m), and 8.3 (1H, d), and 8.6 (1H, m), 8,9 (1H, d), or 10.9 (1H, s), and 11.4 (1H, t).

Example 409. N-[2-(2-Pyridyl)ethyl] -N'-[2-(5-chloro)pyridyl] thiourea, HCl-salt.

About 10 ml of water was added 100 mg of N-[2-(2-pyridyl)ethyl]- N'-[2-(5-chloro)pyridyl] thiourea (about 404), the suspension is heated to approximately 90oC and adding hydrochloric acid to establish a pH of about 3. The specified connection allocate freeze-drying.

1H-NMR (DMSO-d6): 3,6 (2H, t), is 4.2 (2H, m), and 7.3 (1H, d), 8-8,2 (3H, m), and 8.3 (1H, m), and 8.6 (1H, m), 9 (1H, m), or 10.9 (1H, s), and 11.4 (1H, t).

Example 410. N-[2-(2-Benzothiazolyl)ethyl]-N'-[2-(5-bromo)pyridyl] thiourea.

A mixture of 356 mg (2 mmol) of thiocarbonyldiimidazole and 346 mg (2 mmol) 2-amino-5-bromopyridine in 2 ml of acetonitrile is stirred for 1 h at room temperature. Add 324 mg (2 mmol) of 2-(2-benzothiazolyl)ethylamine is 3 ml of dimethylformamide with the formation of a transparent solution. The solution is cooled and the resulting precipitate is centrifuged. By recrystallization from a mixture of acetonitrile/dimethylformamide obtain 310 mg of pure specified connection.

1H-NMR (DMSO-d6): of 4.44 (2H, m), 5,15 (2H, m), 7,18 (1H, d), 7,56 (2H, m), and 7.9 (1H, d), of 8.04 (3H, m), of 10.93 (1H, s), 11,41 (1H, s).

13C-NMR, ppm: 44, 55, 114, 118, 118, 127, 142, 144, 146, 152, 180.

Example 411. N-[2-(2,6-Debtor-3-methoxyphenyl)ethyl]-N'-[2-(5-bromo) pyridyl]thiourea.

In 3 ml of acetonitrile is mixed 334 mg (2 mmol) of 2-(2,6-debtor-3-methoxyphenyl)ethylamine (see example 401), of 167.2 MB, and 566 mg (2 mmol) 1-{2-[5-bromo)pyridyl] thiocarbamoyl} imidazole (see example 392), MB 283,15. The mixture is slowly heated to boiling, then cooled for crystallization. Repeated recrystallization from acetonitrile get 238 mg of pure specified connection.

1H-NMR (DMSO): of 3.12 (2H, t), 3,86 (3H, s), 4 (2H, m), PC 6.82 (3H, m), 7.68 per-7,72 (1H, m) to 8.12 (1H, d), 9,16 (1H, s), 11,35 (1H, s).

Example 412. N-(3,4,5-Trimethoxybenzyl)-N'-(2-thiazolyl) thiourea.

Source 3,4,5-trimethoxybenzylamine obtained by reduction of 3,4,5-trimethoxybenzoyl cobalt chloride and sodium borohydride according to the General method described in: L. S. Heinzman, J. Am.Chem.Soc., 104, 6801 S., 1980).

In 70 ml of methanol is dissolved 3,4,5-TRIG, 50 mmol). After 3 h the reaction mixture was filtered through celite and concentrated to small volume. The residue is transferred into ethyl acetate and extracted with 1 N. HCl (100 ml). The organic phase is discarded. The aqueous phase is alkalinized water ammonia and extracted with chloroform. The organic phase is dried over magnesium sulfate and after evaporation of getting 427 mg of 3,4,5-trimethoxybenzylamine.

1H-NMR (CDCl3), : to 6.58 (s, 2H, TMPh), 3,85 (m, 6H, 2 x MeO), 3,82 (s, 3H, MeO), and 3.8 (m, 2H, CH2).

Specified in the header of the compound obtained by the method of example 105.

1H-NMR (CDCl3), : 7,26 (d, 1H, thiazole), 6,85 (d, 1H, thiazole), only 6.64 (s, 2H, TMPh), 4,84 (d, J = 5.7 Hz, 2H, CH2), 3,86 (m, 6H, MeO), 3,85 (s, 3H, MeO).

13C-NMR (CDCl3), : 177 (C=S), 161 (thiazole), 153, (TMPh), 138 (TMPh), 137 (thiazole), 132 (TMPh), 111 (thiazole), 104 (TMPh), 61 (MeO), 56 (MeO), 50 (CH2).

Example 413. 2-Formyl-3-herperidin.

Into a flask of 1 l in a stream of dry nitrogen at -60oC load dry ethyl ether (500 ml), n-BuLi (of 1.6 M in hexane, 62.5 ml, 0.1 mol) and dry 1,4-diazabicyclo[2,2,2] octane (DABCO) (to 11.56 g, 0.1 mol) and the resulting cloudy solution is stirred for 1 h at -20oC. the Mixture is cooled to -75oC added dropwise a solution of 3-herperidin (9.81 g, 0.1 mol) in ethyl ether and stirring properformance (charged 8.52 ml, 0.11 mol) in ethyl ether (50 ml) and the mixture is stirred for 2 h at -75oC. At -10oC slowly add water (175 ml), the aqueous layer was extracted with ethyl acetate (CH ml) and the combined extracts dried over anhydrous sodium sulfate. After removal of the solvent to obtain a dark brown oil, from which vacuum distillation and purification by chromatography on silica gel get 4.4 g (35%) of the compounds in the form of snow-white crystals, so pl. 48-49oC.

IR (CHCl3), cm-1: 3071, 3020, 2873, 2842, 1720, 1588, 1461, 1441.

1H-Yarm (300 MHz, CDCl3), : of 10.21 (s, 1H), to 8.62 (m, 1H), EUR 7.57 (m, 2H).

MS (FD) m/e: 125 (M+).

UV (EtOH): 263 nm ( = 1551), 201 nm ( = 2188).

Example 414. 2-Hydroxymethyl-3-herperidin.

A solution of 2-formyl-3-herperidin (4 g, 32 mmol) and sodium borohydride (309 mg, 8 mmol) in absolute ethanol (40 ml) is stirred 15 min at 0oC and 1 h at room temperature. The reaction mixture was neutralized with a saturated aqueous solution of ammonium chloride (5 ml) and filtered through diatomaceous earth to remove solids. The filtrate is evaporated and the resulting white solid was dissolved in ethyl acetate with water. The aqueous layer was extracted with ethyl acetate (5 x 30 ml) and dried over anhydrous sulfate">

IR (CHCl3), cm-1: 3607, 3439, 3019, 1607, 1576, 1451, 1416, 1312, 1257, 1218, 1209, 1167, 1105, 1053, 857, 803.

1H-Yarm (300 MHz, CDCl3), : scored 8.38 (m, 1H), 7,39 (m, 1H), 7,26 (m, 1H), a 4.83 (s, 2H), of 3.73 (sh.s, 1H).

MS (FD) m/e: 127 (M+).

UV (EtOH): 263 nm ( = 2796), 201 nm ( = 3651).

Found, %: C 56,45; H Equal To 4.97; N 10,89.

C6H6FNO

Calculated, %: C 56,69; H Amounts To 4.76; N 11,02.

Example 415. 2-Chloromethyl-3-herperidin, hydrochloride.

To a cooled to -10oC to a solution of 2-hydroxymethyl-6-herperidin (3,43 g, 27 mmol) in dichloromethane (30 ml) dropwise over 5 min add undiluted thionyl chloride (4.4 ml, 60 mmol) and the resulting pale green solution was stirred for 3 h at -10oC. followed by evaporation to dryness receive of 4.66 g (95%) of the compounds in the form of snow-white crystals.

IR (CHCl3), cm-1: 2984, 1732, 1551, 1470, 1452, 1333, 1286, 1273, 1237, 1219, 1208, 1193, 1094, 905, 863, 806.

1H-Yarm (300 MHz, CDCl3), : 8,69 (m, 1H), of 8.06 (m, 1H), 7,89 (m, 1H), 5,09 (s, 2H).

MS (FD) m/e: 145 (M+, free base), 147 (M+2, free base).

Example 416. 2-Cyanomethyl-3-herperidin.

A solution of the hydrochloride of 2-chloromethyl-3-herperidin (4,85 g, to 26.7 mmol) and potassium cyanide (3,47 g, with 53.4 mmol) in 50 ml of methane and 20 ml of water pesla, which is dissolved in ethyl acetate with water and adding dry sodium carbonate establish a pH of 11.5. The aqueous layer was podsalivayut sodium chloride, extracted with ethyl acetate (7 x 40 ml), the combined extracts dried over anhydrous sodium sulfate. Removal of solvent obtain 3.6 g (99%) of the indicated compound as a black solid.

IR (CHCl3), cm-1: 3019, 3011, 2977, 1708, 1603, 1578, 1454, 1412, 1259, 1222, 1219, 1215, 1161, 1097, 1047, 804.

1H-Yarm (300 MHz, CDCl3), : 8,43 (m, 1H), 7,42 (m, 1H), 7,33 (m, 1H), 3,97 (s, 1H), 3.96 points (s, 1H).

MS (FD) m/e : 136 (M+).

UV (EtOH) : 263 nm ( = 3719), 203 nm ( = 3707).

Example 417. 2-amino-ethyl-3-herperidin.

To a solution of 2-cyanomethyl-3-herperidin in absolute ethanol (75 ml) and 5 G. hydrochloric acid (0.3 ml) is added as a catalyst of platinum oxide (0.64 g) and the mixture hydronaut 1 h under a pressure of 60 psi (4.2 kg/cm2in the apparatus for hydrogenation Parra. The catalyst is filtered off, the filtrate is concentrated under reduced pressure to a brown oil, the oil dissolved in water (40 ml) and ethyl acetate (10 ml) and added with concentrated hydrochloric acid to establish a pH of 0.9. The layers are separated, an ethyl acetate layer is extracted with 1 N. HCl (1 x 10 ml), the aqueous acid extracts merge the combined extracts dried over anhydrous sodium sulfate. Removal of solvent receive 1,58 g (70%) of the indicated compound as a brown oil.

IR (CHCl3), cm-1: 2969, 2873, 1632, 1602, 1575, 1550, 1450, 1414, 1359, 1246, 1219, 1203, 1169, 1093.

1H-Yarm (300 MHz, CDCl3), : 8,31 (m, 1H), 7,29 (m, 1H), 7,13 (m, 1H), 3,03 (m, 4H), 1.8 m (sh.s, 2H).

MS (FD) m/e: 140 (M+).

Titration (66% DMF/H2O).

Example 418. 1-{[2-(5-Chloro)pyridyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (4,95 g, 25 mmol) and 2-amino-5-chloropyridine (3.28 g, 25 mmol) in acetonitrile (75 ml) is stirred for 23 h at room temperature. Filtration of the resulting precipitate obtain 3.42 g (57%) of the specified connection.

IR (KBr), cm-1: 3218, 3090, 1599, 1572, 1551, 1529, 1471, 1455, 1390, 1375, 1340, 1310, 1228, 1183, 1109, 1053, 939, 831.

1H-Yarm (300 MHz, DMSO-d6), : 8,58 (m, 1H), 8,25 (m, 1H), 8,05 (sh.s, 1H), 8,03 (m, 1H), 7,65 (m, 1H), 7,15 (d, J = 8 Hz, 1H), 6,8 (s, 1H).

MS (FAB) m/e 239 (M+1).

UV (EtOH): 305 nm ( = 15141), 273 nm ( = 14730), 226 nm ( = 11407), 203 nm ( = 16456).

Example 419. 1-{[2-(5-Bromo)pyridyl]thiocarbamoyl}imidazole.

A solution of 1,1'-thiocarbonyldiimidazole (4,95 g, 25 mmol) and 2-amino-5-bromopyridine (4,46 g, 25 mmol) in acetonitrile (75 ml) is stirred for 23 h at room temperature. Filtering the resulting osedc, 1182, 1096, 1053, 938, 828.

1H-Yarm (300 MHz, DMSO-d6), : to 8.57 (m, 1H), 8,3 (m, 1H), 8,15 (m, 1H), 8,03 (sh.s, 1H), to 7.75 (m, 1H), 7,15 (d, J= 8 Hz, 1H), 6,8 (s, 1H).

MS (FAB) m/e 284 (M+1).

UV (EtOH): 304 nm ( = 13932), 274 nm ( = 13051), 230 nm ( = 11098), 204 nm ( = 17821).

Example 420. N-{2-[2-(3-Fluorine)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea.

A solution of 1-{[2-(5-bromo)pyridyl]thiocarbamoyl}imidazole (1.42 g, 5 mmol) and 2-amino-ethyl-3-herperidin (0.7 g, 5 mmol) in N,N-dimethylformamide (20 ml) is stirred for 3 h at 95oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, saturated aqueous sodium bicarbonate and brine. The organic layer is dried over anhydrous sodium sulfate, concentrated and purification of the solid residue by chromatography on silica gel obtain 0.33 g (19%) of the compounds in the form of a white substance, so pl. 184-187oC.

IR (KBr), cm-1: 3161, 3023, 1597, 1579, 1555, 1524, 1488, 1473, 1447, 1364, 1342, 1315, 1236, 1221, 1172, 1142, 1087, 833.

1H-Yarm (300 MHz, DMSO-d6), : 11, 38 (m, 1H), at 10.64 (s, 1H), to 8.41 (m, 1H), 8,14 (d, J= 2 Hz, 1H), to $ 7.91 (m, 1H), 7,63 (m, 1H), 7,33 (m, 1H), 7,06 (d, J= 9.0 Hz, 1H), 4,01 (m, 2H), 3,1 (t, J= Hz, 2H).

MS (FD) m/e 355 (M+), 357 (M+2).

UV (EtOH): 305 nm ( = 13169), 273 nm ( = 25811), 201 nm ( = 17493).

Example 421. N-is desola (2,39 g, 10 mmol) and 2-amino-ethyl-3-herperidin (1.4 g, 10 mmol) in N,N dimethylformamide (25 ml) is stirred for 3 h at 95oC. the Reaction mixture is cooled to room temperature, transferred into ethyl acetate and washed with water, saturated aqueous sodium bicarbonate and brine. The organic layer is dried over anhydrous sodium sulfate, concentrated and purification of the solid residue by chromatography on silica gel get 0.96 g (31%) of the compounds in the form of snow-white matter, so pl. 170-173oC.

IR (KBr), cm-1: 3167, 3022, 1603, 1583, 1554, 1524, 1492, 1474, 1449, 1367, 1342, 1317, 1238, 1222, 1173, 1142, 1087, 835, 803.

1H-Yarm (300 MHz, DMSO-d6), : is 11.39 (m, 1H), 10,65 (s, 1H), 8,42 (m, 1H), 8,07 (d, J = 2 Hz, 1H), 7,81 (m,1H), 7,63 (m, 1H), 7,33 (m, 1H), 7,11 (d, J = 9 Hz, 1H), 4,01 (m, 2H), 3,1 (t, J = 6 Hz, 2H).

MS (FD) m/e 310 (M+), 312 (M+2).

UV (EtOH): 305 nm ( = 11338), 272 nm ( = 23394).

Example 422. (+) and (-) N-(CIS-2-Vinylcyclopropyl)-S- -methoxyphenylacetamide.

In 100 ml of dichloromethane is dissolved S- -methoxyphenylalanine acid (2 g, 12 mmol) and the solution add oxalicacid (1,36 ml, 16 mmol) together with 2 drops of N,N-dimethylformamide. The solution is stirred under nitrogen atmosphere and at room temperature for 120 minutes, the Solvent and excess reagent is removed in a rotary esprits. example 202) (2 g, 15 mmol) in pyridine (5 ml). The solution is stirred for 15 min and then add diethyl ether (200 ml). The residue is filtered off and the solution evaporated. The residual crystalline diastereomer mixture cleanse pressure chromatography with elution with a mixture of ethyl acetate/toluene/dichloromethane (1:2:2). Evaporation of fractions containing more quickly eluruumist product, get product A. Evaporation slower eluruumiks factions receive the product B.

A.1H-Yarm (35 mg in 0.6 ml CDCl3, 294K): 0,99 was 1.06 (1H,m), 1,29-to 1.38 (1H, m), 2,29-of 2.38 (1H, K), 3 (3H, s), 3,07-3,17 (m) to 4.41 (1H, s), and 6.3 (1H), 7,16-to 7.32 (10H,m).

13C-NMR: 11,18; 21,83; 27,82; 57,11; 83,68; 126,34; 126,43; 128,08; 128,18; 128,26; 128,78; 136,15; 136,85; 171,75; 171,75.

Calculated for C18H19N, %: C 76,84; H 6,8; N 4,99, so pl. 136,7-137,1oC.

B.1H-NMR (same conditions as for (A): 1,09-of 1.16 (1H, K), 1,32-of 1.41 (1H, K), 2,24-of 2.38 (1H, K), 3,1-3,2 (4H, m), of 4.45 (1H, s) of 6.4 (1H), 6,95-6,99 (2H, m), 7,15-7,27 (7H, m).

13C-NMR: 10,69; 21,82; 27,85; 56,87; 83,63; 126,35; 126,87; 128; 128,13; 128,19; 128,83; 135,88; 136,54; 171,55.

Calculated for C18H19N, %: C 76,84; H 6,8; N 4,9, so pl. 143,6-144,7oC.

Example 423. (-)-CIS-2-Phenylcyclopropane.

Compound a (1.2 g) is boiled for 4 h in a mixture of water/dioxane (concentrated water)/hydrochloric acid (1:1:1). Rast is extracted with dichloromethane, dried over sodium sulfate, filtered and after evaporation receive the specified connection in the form of butter.

1H-NMR (CDCl3), []D20, ppm: 0,8-0,9 (1H, CH2, m), 1.1 to 1.2 (1H, CH2, m), 2-2,1 (1H,PhCH,), 2,6-2,7 (1H, CHNH2, m) and 7.1 to 7.4 (5H, Ph).

Example 424. (+)-CIS-2-Phenylcyclopropane.

Compound B (1.2 g) is boiled for 4 h in a mixture of water/dioxane (concentrated water)/hydrochloric acid (1:1:1). The solution was diluted with water, washed with dichloromethane, alkalinized with ammonium hydroxide (concentrated water), extracted with dichloromethane, dried over sodium sulfate, filtered and after concentration obtained as oils the specified connection.

1H-NMR (CDCl3), , ppm: 0,8-0,9 (1H, CH2, m), 1.1 to 1.2 (1H, CH2, m), 2-2,1 (1H, PhCH,), 2,6-2,7 (1H, CHNH2, m) and 7.1 to 7.4 (5H, Ph).

[]D20= +62,7o(c = 1, CHCl3).

Example 425. (-)-N-(CIS-2-Vinylcyclopropyl)-N'-(5-chloropyrid-2-yl) thiourea.

(+)-N-CIS-2-Phenylcyclopropane (0,23 g, 1.7 mmol) from example 424 condense according to the method of example 372 1-(5-chloropyrid-2-yl-thiocarbamoyl)imidazole with the formation of the compounds in the form of crystals, so pl. 189,6-191,3oC.

1H-NMR (CDCl3), , h/NH).

[]D20= 62,7 million tonso(c = 1, CHCl3).

Example 426. (+)-N-(CIS-2-Vinylcyclopropyl)-N'-(5-chloropyrid-2-yl) thiourea.

(-)-N-CIS-2-Phenylcyclopropane (0,23 g, 1.7 mmol) from example 423 condense according to the method of example 372 1-(5-chloropyrid-2-yl-thiocarbamoyl)imidazole with the formation of the compounds in the form of crystals, so pl. 189,2-191,8oC.

1H-NMR (CDCl3), []20, ppm: 1,2-1,3 (1H, m, CH2), a 1.5-1.6 (1H, m, CH2), 2,5-2,6 (1H, PhCH), of 3.7-3.8 (CHN), and 6.6 and 6.7 (1H, d, feast.), a 7.2 to 7.5 (7H, Ph, feast.), 8,9-9 (1H, NH), 10,8-10,9 (1H, 11H).

[]20= +59,3o(c = 1, CHCl3).

Example 427. (-)-N-(CIS-2-Vinylcyclopropyl)-N'-(5-pampered-2-yl) thiourea.

Carry out a reaction between (+)-N-CIS-2-phenylcyclopropane of example 424 2-amino-5-bromopyridine according to the methods of examples 93 and 94, using 2-amino-5-bromopyridine instead of 2-aminothiazole and get the connection specified in the form of crystals, so pl. 192-193oC.

1H-NMR (CDCl3): 1,19-of 1.26 (m, 1H), 1,47-of 1.55 (m, 1H), 2,52 (K, 1H), 3,66 of 3.75 (m, 1H), 6,66 (LW. d, 1H), 7,27-7,41 (m, 5H), 7,47 (d, 1H), 7,6 (LW. d, 1H), 8,98 (sh.s, 1H), 10,88 (sh.s, 1H).

= -52,8o(c = 1, CHCl3).

Example 428. (+)-N-(CIS-2-Vinylcyclopropyl)-N'-(5-pampered-2-yl) thiourea.

On metodom, which is used instead of 2-aminothiazole, and get the connection specified in the form of crystals, so pl. 195,5-196,5oC.

1H-NMR (CDCl3): 1,19-of 1.26 (m, 1H), 1,47-of 1.55 (m, 1H), 2,52 (K, 1H), 3,66 of 3.75 (m, 1H), 6,66 (LW. d, 1H), 7,27-7,41 (m, 5H), 7,47 (d, 1H), 7,6 (LW. d, 1H), 8,98 (sh.s, 1H), 10,88 (sh.s, 1H).

[]20= +50o(c = 1, CHCl3).

Example 429. N-(2-Vinylphenol)-N'-(5-pampered-2-yl) thiourea.

A solution of 2-methoxybenzylamine (10 g, 66 mmol, Janssen) is heated in 50 ml of 47% HBr to 120oC for 12 hours the reaction mixture was added a solution of NaOH and washed with simple ether. Bring the pH to 8 and extracted with simple ether, obtaining 2.1 g of 2-hydroxyphenylethylamine. The amine was dissolved in dichloromethane (50 ml) and added to 2.8 ml of triethylamine. To the solution was added to 2.85 ml of benzylchloride at the 5oC. After reaction for 1 h at room temperature, the reaction mixture was poured into dichloromethane and brine. The organic layer is dried (sodium sulfate) and evaporated, obtaining the crude product, which was further purified on silikagelevye column, elwira with ethyl acetate 3 and hexane 7, obtaining 2.0 g of Cbz-protected 2-hydroxyphenylethylamine. The compound obtained (271 g) is dissolved in dichloromethane and subjected to interaction with angeredet - dichloromethane) 251 mg of Cbz-protected 2-triglyceridemia. This compound is subjected to interaction with tri-n-butylaniline in the presence of Pd (II) and lithium chloride according to the method described in J. Am.Chem.Soc., p. 5478-5486, 1987. After removing the protection of TMS-1 obtained 2-vinylephenylamino converted into the target compound using the procedure described in example 345.

1H-NMR (250 MHz, CDCl3): 1,21 (t, 2H), 3,97 (K, 2H), 5,32 (LW. d, 1H), of 6.71 (d, 1H), 7,10 (LW. d, 1H), 7.23 percent-of 7.55 (m, 1H), 7,70 DV. d, 1H), 8,04 (d, 1H), 8,86 (broad s, 1H), 11,21 (broad s, 1H).

Example 430. N-(3-Ethynylphenyl)-N'-(5-pampered-2-yl) thiourea.

Cbz-protected 3-triglyceridemic obtained from 3-methoxyphenethylamine (Janssen) according to the method described in example 429, is subjected to reaction with TMS-acetylene in the presence of Pd (II) according to the method described in Tetrahedron Letters, p. 6403-6406, 1993), receiving Cbz-protected 3-ethynylphenyl. After removal of the protective group (NaOH) were obtained 3-ethynylphenyl converted into the target compound by the method described in example 345, so pl. 162,5-163,5oC.

1H-NMR (250 MHz, CDCl3): 1,98 (t, 2H), 3,09 (s, 1H), 4.00 points (K, 2H), 6,77 (d, 1H), 7,26-7,42 (m, 4H), to 7.67 DV. d, 1H), 8,12 (d, 1H), 9,20 (broad s, 1H), of 11.26 (broad s, 1H).

Example 431. N-(3-Cyanophenyl)-N'-(5-pampered-2-yl) thiourea.vannoy in example 429, subjected to reaction with KCN in the presence of Ni (II) and Zn according to the method described in J. Chem. Soc. Perkin Trans 1, p. 1365-1366, 1986). After removal of the protective group TMS-1 obtained 3-cianfanelli converted into the target compound by the method described in example 345, so pl. 173.5 metric-of 174.5oC.

1H-NMR (250 MHz, CDCl3): is 3.08 (t, 2H), 4,01 (K, 2H), 6,79 (d, 1H), 7,41-to 7.59 (m, 4H), 7,73 (LW. d, 1H), 8,10 (d, 1H), 9,14 (broad s, 1H), 11,32 (broad s, 1H).

Example 432. N-(3-Acetylphenyl)-N'-(5-pampered-2-yl) thiourea.

Cbz-protected 3-triplification obtained from 3-methoxyphenethylamine (Janssenn) according to the method described in example 429, is subjected to interaction with CO in the presence of Pd (II) with 1,3-bis(diphenylphosphino)propane, triallylamine and methanol according to the method described in J. Chem. Soc. Chem. Commun., p. 904-905). Received Cbz-protected 3-methoxycarbonylmethylene hydrolyzing aqueous LiOH and transformed into the acid chloride by reaction with thionyl chloride. Received Cbz-protected 3-chlororespiration subjected to interaction with dimethylcarbinol (I) lithium according to the method described in J. am. Chem., p. 5106-5108). After removing the protective group (TMS-1) obtained 3-acetylpenicillamine converted into the target compound by the method described in example 345, so pl. 133,0-135,0oC.

1H-NMR (250 Hiroki with, 1H).

Example 433. N-(2-Phenyl-1-methylethyl)-N'-(thiazol-2-yl)thiourea.

2-Phenyl-1-methylethanol converted into the corresponding amine by the method described in example 106. Amin condense with the product from example 103 under the reaction conditions described in example 105, receiving the target connection, so pl. 118,5oC.

1H-NMR (CDCl3): of 1.27 (3H), 2,80 (LW. D. 1H), 3,18 (LW. d, 1H), and 4.75 (m, 1H), 6,79 (D. 1H), 7.23 percent-7,29 (m, 6H).

Found, %: H The 5.45; C 56,02; N 15,30.

C13H15N3S2< / BR>
Calculated, %: H The 5.45; C 56,29; N Br15.15.1

1. Derivatives of thiourea of General formula I

< / BR>
where R1- benzothiazole, benzimidazole, imidazole, pyrazinyl, pyrazolyl, pyridyl, pyridazinyl, chinoline, tetrazolyl, thiazolyl, thiadiazolyl, pyridyl, pyridazinyl, chinoline, tetrazolyl, thiazolyl, thiadiazolyl or triazolyl, which may not necessarily be replaced by substituents selected from the following group:1- C4-alkyl, C1- C3-alkoxy-, hydroxy-, methylthio-, nitro-group, halogen, trifluoromethyl;

R5represents phenyl, pyridyl, pyrrolyl, thienyl, benzothiazolyl, benzoxazolyl, naphthyl, indolyl, cyclohexenyl, any of which may be substituted up to five Polozheniye, ethinyl, trifluoromethyl, C1- C3-alkoxy, phenoxy-, phenyl, methylendioxy, a group of the formula-C(=O)R, where R represents a C1- C3-alkyl, atsetamidometil, carboxamidates;

R8and R9independently represent hydrogen or methyl, or R8and R9together with the carbon atoms to which they are attached, form cyclopropyl or cyclobutyl;

R6represents hydrogen or methyl, or R6and R8together with the carbon atom to which they are attached, form cyclopropyl;

or their pharmaceutically acceptable salts, provided that the compound of formula I is a compound of formula

< / BR>
where Rdrepresents hydrogen, halogen, hydroxy, alkyl or alkoxygroup, or R1is not a group

< / BR>
where Reand Rfrepresent lower alkyl, or their salts.

2. Derivatives of thiourea of formula I under item 1, wherein R1is thiazolyl, substituted thiazolyl, pyridyl, substituted pyridyl, pyridazinyl, substituted pyridazinyl, pyrazinyl or substituted pyrazinyl;

R5represents pyridyl, substituted pyridyl, phenyl or substituted phenyl;

R8the Noah thiourea under item 1, characterized in that it is a (N-(2-CIS-vinylcyclopropyl) N'-(2-thiazolyl) thiourea.

4. Derivatives of thiourea under item 1, characterized in that they are selected from the group

N-(2-CIS-vinylcyclopropyl)-N'-[2-(5-bromo)pyridyl]thiourea,

N-(2-CIS-vinylcyclopropyl) N'-[2-(5-chloro)pyridyl]thiourea,

N-(2-CIS-pyridylcarbonyl)-N'-(2-(5-bromo)pyridyl]thiourea,

N-[2-(CIS-2-pyridyl)cyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[CIS-2-(6-fluoro)pyridyl]cyclopropyl}-N'-[2-(5-bromo)pyridyl]timeonline,

N-{2-[CIS-2-(6-fluoro)pyridyl]cyclopropyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[CIS-2-(6-methoxy)pyridyl]cyclopropyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{ 2-[CIS-2-(6-methoxy)pyridyl)]cyclopropyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[CIS-2-(6-ethoxy)pyridyl]cyclopropyl}-N'-[2-(5-bromo)pyridyl]timeonline,

N-{ 2-[CIS-2-(6-ethoxy)pyridyl]cyclopropyl}-N'-[2-(5-chloro)pyridyl]thiourea

or their salts.

5. Derivatives of thiourea under item 1, wherein R6, R8and R9all represent hydrogen.

6. Derivatives of thiourea under item 1, wherein R5is phenyl, substituted phenyl, pyridyl, substituted pyridyl or cyclohexenyl.

7. Triazolyl, substituted thiazolyl, benzothiazolyl, substituted benzothiazolyl, thiadiazolyl, substituted thiadiazolyl, pyrazinyl, substituted pyrazinyl, pyridazinyl or substituted pyridazinyl.

8. Derivatives of thiourea under item 1, wherein R1represents pyridyl, herperidin, chloropyridin, bromperidol, methylpyridyl, ethylpyridine, cryptomaterial, dimethylpyridin, thiazolyl, tortezais, chlorothiazole, bromothiazole, methylthiazolyl, atillasoy, cryptomaterial, dimethylthiazole, zianoticnae, forpersonal, bromperidol, cyanopyridyl, methylpyrazine, ethylpyrazine, dimethylpyrazine, cryptomaterial, pyridazinyl, herperidin, bromopyridine, chloropyridinyl, cyanopyridine, methylpyridazine, ethylpyridine, cryptomaterial, dimethylpyridine;

R5represents cyclohexenyl, phenyl or phenyl substituted 1 to 4 times a methoxy group, ethoxypropane, bromine, stands, fluorine, chlorine and their combinations;

R8and R9independently represent hydrogen or methyl or their salts.

9. Derivatives of thiourea under item 1 selected from the group

N-[2-methoxyphenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-2-methoxyphenyl)e is R> N-[2-(2-methoxyphenyl)ethyl]- N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2-methoxyphenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2(4-cyano)thiazolyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(3-methoxyphenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2-ethoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2-ethoxyphenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2,6-differenl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[2-(5-bromo)pyridinyl]thiourea,

N-[2-(2,6-differenl)ethyl]-N'-[3-(6-chloro)pyridazinyl]thiourea,

N-[2-(2-fluoro-6-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2-fluoro-6-methoxyphenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2-chlorophenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(2-chlorine[2-(2-chlorophenyl)ethyl]- N'-[2-(5-chloro)Pirelli]thiourea,

N-[2-(3-chlorophenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(3-chlorophenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea,

N-[2-(3-chlorophenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(3-chlorophenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea,

N-[2-(1-cyclohexenyl) ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(1-cyclohexenyl)ethyl]-N'-[3-(6-chloro)pyridazinyl]thiourea,

N-[2-(2,5-acid)ethyl]-N'-[2-(5-chloro)pyrazinyl]thiourea,

N-[2-(2,5-acid)ethyl] N'-[2-(5-bromo)pyrazinyl] thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-tricorner)pyridyl]thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-ethyl)pyridyl]thiourea,

N-[2-(2-pyridyl)ethyl]-N'-[2-(5-methyl)pyridyl]thiourea,

N-{2-[2-(6-methoxy)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(6-methoxy)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{-[2-(6-ethoxy)pyridyl]ethyl}-N'-[2-who Ridel]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-(6-fluoro)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[2-(3-fluorine)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(3-fluorine)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl}thiourea,

N-{2-[2-(6-chloro)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(6-chloro)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-[2-(3-methoxy-6-fluoro)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N - {2-[2-(3-methoxy-6-fluoro)pyridyl]ethyl-N'-[2-(5-chloro)pyridyl]thiourea,

N-{ 2-[2-(5-ethoxy-6-fluoro)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{ 2-[2-(5-ethoxy-6 fluorine)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{ 2-[2-(3-ethoxy-6-fluoro)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(3-ethoxy-6-fluoro)pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-{2-(3,6-debtor)pyridyl]ethyl}-N'-[2-(5-bromo)pyridyl]thiourea,

N-{2-[2-(3,6-debtor) pyridyl]ethyl}-N'-[2-(5-chloro)pyridyl]thiourea,

N-[2-(2,6-debtor-3-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea,

or their salts.

10. N-[2-(2-Pyridyl)ethyl] N'-[2-(5-bromo) pyridyl]thiourea.

11. Pharmaceutical composition having inhibitory activity against reverse transcriptase of the virus immunodeficita person, comprising the active principle and target doba is Icewine formula I under item 1 or its pharmaceutically acceptable salt.

12. The pharmaceutical composition according to p. 11, characterized in that it additionally contains at least one active compound selected from the group comprising 2', 3'-dideoxyinosine, 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidin.

13. The pharmaceutical composition according to p. 11, characterized in that it contains a derivative of thiourea under item 5.

14. The pharmaceutical composition according to p. 13, characterized in that it additionally contains at least one active compound selected from the group comprising 2', 3'-dideoxyinosine, 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidin.

15. The method of inhibition of reverse transcriptase of human immunodeficiency virus through exposure to infected virus cell active compound, characterized in that active compound using an effective amount of a derivative of thiourea of formula I under item 1 or its pharmaceutically acceptable salt.

16. The method according to p. 15, characterized in that use is derived thiourea under item 5.

17. The method according to p. 15, characterized in that use is derived thiourea under item 6.

18. The method according to p. 15, characterized in that the use of a derivative of thiourea on the acidic salt.

20. The method according to p. 15, characterized in that it further uses at least one active compound selected from the group comprising 2', 3'-dideoxyinosine, 2',3'-dideoxycytidine, 3'-azido-3-'-deoxythymidin.

 

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